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Oral squamous cell carcinoma (OSCC) is notorious for its low survival rates, due to the advanced stage at which it is commonly diagnosed. To enhance early detection and improve prognostic assessments, our study harnesses the power of machine learning (ML) to dissect and interpret complex patterns within mRNA-sequencing (RNA-seq) data and clinical-histopathological features. 206 retrospective Vietnamese OSCC formalin-fixed paraffin-embedded (FFPE) tumor samples, of which 101 were subjected to RNA-seq for classification based on gene expression. Then, learning models were built based on clinical-histopathological data to predict OSCC subtypes and propose potential biomarkers for the remaining 105 samples. 2 distinct groups of OSCC with different clinical-histopathological characteristics and gene expression. Subgroup 1 was characterized by severe histopathologic features with immune response and apoptosis signatures while subgroup 2 was denoted by more clinical/pathological features, cell division and malignant signatures. XGBoost and SVM (Support Vector Machine) models showed the best performance in predicting subtype OSCC. The study also proposed 12 candidate genes as potential biomarkers for OSCC subtypes (6/group). The study identified characteristics of Vietnamese OSCC patients through a combination of mRNA sequencing and clinical-histopathological analysis. It contributes to the insight into the tumor microenvironment of OSCC and provides accurate ML models for biomarker prediction using clinical-histopathological features. [ABSTRACT FROM AUTHOR]

The research team has developed an information system based on clinical blood cell analysis and designed and implemented highly innovative algorithms. A neural network model was created based on these feature data of the blood cell population. Artificial intelligence algorithms can label susceptible populations for digestive tract cancer with an accuracy rate of over 80 %. A multi universe optimized BP neural network model was implemented based on TCGA data of common immune antigens in clinical laboratories. The working mechanism of this model is to assign values to the parameters of the BP neural network by using the process of searching for the best fitness in multiple universes. This model can predict the five-year survival rate of patients based on immunohistochemical data. Based on these data, an AI algorithm was used to develop a clinical prognostic model with an accuracy rate of over 99 %. The research team used single-cell sequencing data to locate cell subtypes in the features of immunohistochemical data, providing a biological basis for artificial intelligence models. The research team explored the potential biological mechanisms of cancer progression and occurrence based on gastrointestinal neuroendocrine products, and these algorithms have contributed to the prediction of cancer survival and incidence,team invented a simple and efficient algorithm. [ABSTRACT FROM AUTHOR]

The importance of statistical distributions in accurately representing real-world scenarios and aiding in educated decision-making is well recognized. Nonetheless, it is also true that the limitations of these distributions can hinder optimal fitting in certain situations. This awareness has led researchers to seek out improved and more optimal probability distributions. Based on factual motivation, this paper introduces a new probability distribution called the weighted sine generalized inverse Weibull (WSGI-Weibull) distribution. This model emerges from the amalgamation of the generalized inverse Weibull distribution and a sine-inspired probabilistic framework. Certain statistical properties, particularly those based on quantiles, of the newly introduced WSGI-Weibull distribution have been derived. An established estimation method is applied to calculate the point estimators of the WSGI-Weibull distribution, and subsequently, a simulation study is conducted. To highlight the benefits of the WSGI-Weibull distribution, two data sets sourced from the reliability and hydrology sectors are analyzed. The empirical fitting of the WSGI-Weibull distribution is evaluated against specific adversarial distributions, utilizing the two data sets as a basis for comparison. Utilizing specific evaluation tools, it has been noted that the WSGI-Weibull distribution delivers the best and most optimal fit for the reliability and hydrological data sets. [ABSTRACT FROM AUTHOR]

A new furanoditerpene, saurufuranol (1) along with a flavonoid, 3,5,7,3′,4′-pentamethoxyflavone (2), and eight lignans including macelignan (3), 5-((2 R ,3 R)-4-(3,4-dimethoxyphenyl)-2,3-dimethylbutyl)benzo[ d ][1,3]dioxole (4), dihydroguaiaretic acid (5), (+)- zuonin A (6), sauchinone (7), saucerneol A (8), manassantin A (9) and saucerneol C (10). Their structures were determined by extensive spectroscopic studies using NMR spectroscopy and mass spectrometry in combination with literature. These compounds were evaluated cytotoxicity on PC-9 and HT-29 cancer cell line. Compound 8 showed significant activity on both of cancer cell lines with IC 50 values of 1.33±0.23 and 1.18±0.27 µM, respectively. [Display omitted] • A new furanoditerpene compound, saurufuranol (1), was isolated from Saururus chinensis. • Nine known compounds, including a flavonoid (2) and eight lignans (3 - 10), were also isolated. • Their structures were successfully determined by spectroscopic evidence. • Compounds 3–6, 8 and 10 showed the cytotoxic effects. [ABSTRACT FROM AUTHOR]

[Display omitted] • Salidroside could protect the blood brain barrier from leakage during CSVD. • Salidroside could rescue the memory dysfuction in CSVD model. • Salidroside promote the pro-angiogenesis through Notch/ITGB1 signal pathway to act the above mentioned functions. • Salidroside activates Notch signal pathway first, then to promote the ITGB1 signal pathway. Salidroside (SAL), extracted from Rhodiola rosea , has been widely used in coronary heart disease and myocardial ischemia for decades. Previous studies have demonstrated that SAL could reduce arteriosclerosis, and thus combat ischemic brain damage. However, the in-depth function of the salidroside in Cerebral Small Vascular Disease (CSVD) has not been discovered, and related molecular mechanism is still unclear. The present study aims to explore the effects of salidroside in angiogenesis as well as repair of blood brain barrier (BBB) and its possible mechanisms. We established a rat model of SHR via 2-vessel gradual occlusion (SHR-2VGO) to mimic the CSVD. Subsequently, the MRI, pathomorphism, as well as Morriss water maze test were conducted to determine CSVD-related indicators. 8 weeks post-surgery, animals were randomly administered SAL, DAPT, ATN161 or saline.The aim was to explore the protective effects of SAL in CSVD as well as its possible mechanism. Here we found that SAL could attenuate cerebral hypoperfusion-induced BBB disruption, promote the pro-angiogenesis through enhancing the cell budding. Further investigations demonstrated that SAL could significantly increase the expression of Notch1, Hes1, Hes5, and ITGB1. In addition, we confirmed that SAL could activate Notch signal path, and then up-regulate ITGB1 to promote pro-angiogenesis and thus protect BBB from disruption. The aforementioned findings demonstrated that SAL could protect BBB integrity through Notch-ITGB1 signaling path in CSVD, which indicated that SAL could be a potential medicine candidate for CSVD treatment. [ABSTRACT FROM AUTHOR]

Osteosarcoma tissues demonstrated elevated expression of proteins (FDX1 and DLAT) integral to cuproptosis in our preliminary study, indicating the potential effectiveness of anti-tumor strategies predicated on this process. Nevertheless, the overexpression of copper export proteins and the challenge of copper ion penetration may contribute to insufficient local copper ion concentration for inducing cuproptosis. Herein, we engineered a biomimetic copper-elesclomol-polyphenol network for the efficient delivery of copper ions and the copper ionophore elesclomol. Simultaneously, we integrated catalase (CAT) to alleviate tumor hypoxia, thereby inducing a greater reliance of tumor cells on aerobic respiration and enhancing cuproptosis sensitivity. In vitro analyses revealed that the nanocomplex exhibited potent cytotoxicity and displayed hallmark characteristics of cuproptosis. In vivo trials further validated targeted tumor accumulation, resulting in the suppression of tumor growth and lung metastasis. An augmentation in the proportion of activated immune cells in both tumor and draining lymph nodes was observed. The improvement of immunosuppressive microenvironment facilitated a synergistic antitumor effect with cuproptosis. The therapeutic efficacy was further evidenced in two osteosarcoma models, highlighting the potential as a safe and effective strategy against osteosarcoma and lung metastasis. Osteosarcoma tissues exhibit a marked increase in the expression of proteins FDX1 and DLAT, which are crucial for cuproptosis. Moreover, cells that depend on mitochondrial respiration are more susceptible to cuproptosis. Here we developed a biomimetic copper-based nanocomplex to trigger cuproptosis against osteosarcoma and lung metastases. The nanocomplex demonstrated excellent biocompatibility and tumor targeting. Catalase incorporating facilitated oxygen generation within tumor microenvironment and alleviated hypoxia, thereby inducing a greater reliance of tumor cells on aerobic respiration and enhancing cuproptosis sensitivity. Simultaneously, the released Cu-elesclomol complexes induced proteotoxic stress responses and efficiently elicited cuproptosis, leading to increased release of proinflammatory factors and triggering anti-tumor immune activation. Our strategy holds promise for osteosarcoma treatment by inducing cuproptosis and achieving potent tumor suppression. [Display omitted] [ABSTRACT FROM AUTHOR]

Recent progress in additive manufacturing (AM) has transformed how complex bioinspired engineering structures are designed and produced. Nonetheless, these structures present substantial difficulties in mathematical modeling and computational analysis. The main goal of this paper is to develop an effective computational method to predict the dynamic response of graphene platelets (GPLs)-reinforced functionally graded triply periodic minimal surface (FG-TPMS) plates (referred to as GPLR-FG-TPMS plates) supported by PF. To achieve this, we employ TrSDT within the IGA framework for efficiency and accuracy. The study establishes advanced plate models by combining three sheet-based TPMS configurations with three porosity distributions and three GPL distribution variations through the plate thickness. Then, we consider the effects of geometrical parameters, material properties, and BCs on free vibration and the dynamic response of GPLR-FG-TPMS plates supported by PF. The findings greatly improve our understanding of the complex dynamic responses of GPLR-FG-TPMS plates, paving the way for applications in various fields in the future. [ABSTRACT FROM AUTHOR]

While angioembolization is occasionally required for craniofacial fracture patients who experience massive maxillofacial hemorrhage, complications such as headache, temporal-facial pain, soft tissue necrosis, and embolic material migration leading to stroke or blindness can arise. Few studies have explored delayed or progressive intracerebral hemorrhage (ICH) following angioembolization for craniofacial fractures. A retrospective review of craniofacial fracture patients from January 1, 2015, to December 31, 2022 at our institution was conducted. We applied univariate and multivariable logistic regression (MLR) analyses to assess whether angioembolization served as an independent factor for delayed or progressive ICH. Propensity score matching (PSM) was used to balance the groups of patients who underwent angioembolization with those who did not. Outcome measurements included delayed or progressive ICH occurring within 72 hours, the need for additional neurosurgical interventions, and the length of stay (LOS) in the intensive care unit (ICU) and hospital. Of the 2,519 craniofacial fracture patients studied over an 8-year period, 21 (0.8%) underwent angioembolization for maxillofacial hemorrhage. MLR analysis revealed that angioembolization was an independent factor for delayed or progressive ICH (odds ratio=5.71, p = 0.028). After 1:2 PSM, patients who underwent angioembolization had greater rates of delayed or progressive ICH (28.6% vs. 7.1%, p = 0.023), an extended hospital LOS (17.0 vs. 15.0 days, p = 0.009) and a longer ICU LOS (10.0 vs. 4.0 days, p = 0.004). A greater probability of delayed or progressive ICH was observed in craniofacial fracture patients who underwent angioembolization for maxillofacial hemostasis. [ABSTRACT FROM AUTHOR]

Macrophage-mediated inflammation plays a pivotal role in cardiovascular disease pathogenesis. However, current cell-based models lack a comprehensive understanding of crosstalk between macrophages and cardiomyocytes, hindering the discovery of effective therapeutic interventions. Here, a microfluidic model has been developed to facilitate the coculture of macrophages and cardiomyocytes, allowing for mapping key signaling pathways and screening potential therapeutic agents against inflammation-induced dynamic myocardial injury. Through metabolic profiling and bioinformatic enrichment analysis, the microchip model with dynamic cell-cell crosstalk reveals robust activation of inflammatory and oxidative stress-associated metabolic pathways, closely resembling metabolic profiles of myocardial infarction in both humans and rodents. Furthermore, an integrative screening strategy has been established to screen bioactive natural products precisely, identifying ginsenoside Rb 1 and protocatechualdehyde as promising cardioprotective candidates in vitro and in vivo. Taken together, the microfluidic coculture model advances mechanistic insight into macrophage-mediated cardio-immunology and may accelerate the discovery of therapeutics for myocardial injury. A microfluidic model that recapitulates macrophage-mediated myocardial injury reveals activated inflammatory and oxidative pathways mirroring patient metabolic profiles. Ginsenoside Rb 1 and protocatechualdehyde are identified to prevent myocardial injury. [Display omitted] [ABSTRACT FROM AUTHOR]

Global climate change and its subsequent impact on energy demand present pressing issues for policymakers. Existing literature presents various determinants of energy demand, but the intricate relationship between energy demand and climate policy uncertainty (CPU) remains underexplored. Utilizing the Fourier-augmented ARDL (FA-ARDL) model and drawing from monthly data spanning March 1995 to August 2022, we investigate the impact of CPU on energy demand in China. Our study finds a significant long-run co-integration between climate policy uncertainty (CPU) and renewable energy demand. The FA-ARDL analysis shows that CPU negatively impacts renewable energy demand in both the short and long term, as it leads to higher renewable energy prices. These increased prices deter stakeholders from investing in or adopting renewable technologies, making renewables less competitive compared to traditional energy sources. Our findings are helpful for policymakers to communicate the climate objectives since mitigating climate-related uncertainties would substantially drive renewable energy consumption. [ABSTRACT FROM AUTHOR]

The beneficial effects of ultrasonic vibration-assisted arc welding on the performance of welded joints have been experimentally confirmed. However, the mechanism of the influence of ultrasonic vibration on the temperature and flow fields of the welding pool is still not clear, which also limits further application prospects of this technology. The present study established a three-dimensional molten pool model for ultrasonic vibration-assisted gas tungsten arc (UV-GTA) welding of low-alloy high-strength steel, considering free deformation of the molten pool surface and different ultrasonic vibration amplitudes. The temperature field evolution and the molten pool flow behavior under various ultrasonic vibration amplitudes were systematically analyzed. Compared with GTA welding, the ultrasonic vibration in UV-GTA welding enhanced uniformity of the temperature distribution in molten pool. Moreover, the larger the ultrasonic amplitude in UV-GTA welding, the smaller the depth of the molten pool and the time required for the molten pool to reach a quasi-steady state, but the larger the maximum flow rate at the surface as well as at the center of the molten pool. At an ultrasonic vibration amplitude of 40 µm, the molten pool depth in UV-GTA welding decreased by 34.8 % compared with GTA molten pool depth. The time for this UV-GTA molten pool to reach a quasi-steady state was just 0.57 s, and the maximum velocity at its center increased by 88.1 % over that of the GTA molten pool. Comparative analysis of the UV-GTA molten pool and the GTA molten pool revealed a shorter circulating flow field on the upper surface and periodic variations in the internal flow field motion. The simulation outcomes closely align with the experimental findings, confirming both the validity of the model and the accuracy of the pertinent conclusions. This research may lay a solid theoretical foundation for further systematic exploration of the wider application prospects of ultrasonic vibration-assisted arc welding. [ABSTRACT FROM AUTHOR]

Despite the significant advancements in piezoelectric materials for sonodynamic therapy (SDT), the suppression of orthotopic glioma remains challenging, primarily due to the unclear mechanism and the restriction of blood-brain barrier (BBB). Herein, we proposed that layered piezoelectric SrBi 2 Ta 2 O 9 nanoparticles (SBTO NPs) could effectively depolarize the mitochondrial membrane potential (ΔΨ m) of glioma cells under ultrasound (US) exposure. The US-induced band bending in SBTO NPs enhanced redox ability, promoting an increase in reactive oxygen species (ROS) generation. The in vitro results proved that SBTO NPs selectively accumulated in mitochondria under US and induced apoptosis in a mitochondrial depolarization manner mediated by the generation of ROS and free charges. Furthermore, SBTO NPs could cross the BBB and then accumulate in gliomas through US/microbubbles (MBs) procedure and protein-mediated transport. The therapeutic effect of piezoelectric SBTO NPs mediated SDT was proved in the orthotopic glioma mouse model. As validated by the histopathological observation and the long-term evaluation, the good biocompatibility and biosafety of SBTO NPs make it possible for deep tumor therapy, and worthy for further preclinical study. Employing piezoelectric sonosensitizers for sonodynamic therapy (SDT) has emerged as a promising strategy for cancer treatment; however, the unclear mechanism and blood-brain barrier (BBB) limit the effectiveness of SDT in glioma. Herein, we developed piezoelectric SrBi 2 Ta 2 O 9 nanoparticles (SBTO NPs) with a built-in electric field for glioma treatment and explored the underlying therapeutic mechanism. Notably, SBTO NPs selectively accumulated in mitochondria under ultrasound (US) and induced apoptosis in a mitochondrial depolarization manner, which is mediated by the generation of reactive oxygen species (ROS) and free charges. In an orthotopic glioma mouse model, SBTO NPs were delivered into the glioma through US/microbubbles and transferrin-mediated transport pathways, inhibiting tumor growth. This work provides a new paradigm for the treatment of orthotopic glioma and other tumor types. [Display omitted] [ABSTRACT FROM AUTHOR]

There are no clinical trials with a head-to-head comparison between the 2 most commonly used oral anticoagulants (apixaban and rivaroxaban) in patients with atrial fibrillation (AF). The comparative efficacy and safety between these drugs remain unclear, especially in older patients who are at the highest risk for stroke and bleeding. The purpose of this study was to compare the risk of major bleeding and thromboembolic events between apixaban and rivaroxaban in older patients with AF. We conducted a population-based retrospective cohort study of all adult patients (66 years or older) with AF in Ontario, Canada, who were treated with apixaban or rivaroxaban between April 1, 2011, and March 31, 2020. The primary safety outcome was major bleeding, and the primary efficacy outcome was thromboembolic events. Secondary outcomes included any bleeding. Rates and hazard ratios (HRs) were adjusted for baseline comorbidities with inverse probability of treatment weighting. This study included 42,617 patients with AF treated with apixaban and 30,725 patients treated with rivaroxaban. After inverse probability of treatment weighting using the propensity score, patients in the apixaban and rivaroxaban groups were well balanced for baseline values of demographic characteristics, comorbidities, and medications; both groups had a similar mean age of 77.4 years, and 49.9% were female. At 1 year, the apixaban group had a lower risk for both major bleeding with an absolute risk reduction at 1 year of 1.1% (2.1% vs 3.2%; HR 0.65; 95% confidence interval [CI] 0.59–0.71]) and any bleeding (8.1% vs 10.9%; HR 0.73; 95% CI 0.69–0.77), with no difference in the risk for thromboembolic events (2.2% vs 2.2%; HR 1.02; 95% CI 0.92–1.13). In patients with AF, 66 years or older, treatment with apixaban was associated with lower risk for major bleeding, with no difference in the risk for thromboembolic events compared with rivaroxaban. [ABSTRACT FROM AUTHOR]

Deep vein thrombosis (DVT) is a common medical condition that is associated with clinically significant sequelae, including postthrombotic syndrome (PTS). Anticoagulation alone remains the guideline-recommended treatment for many patients with iliofemoral DVT. Recent technological advances have led to an increase in the use of mechanical thrombectomy for DVT, but mechanical thrombectomy-based procedures have not yet been compared with standard-of-care anticoagulation therapy in randomized studies. The DEFIANCE study (ClinicalTrials.gov: NCT05701917) is an international and actively enrolling randomized controlled trial (RCT) in lower extremity DVT assessing an interventional strategy that includes mechanical thrombectomy with the ClotTriever System (Inari Medical, Irvine, CA) versus anticoagulation alone. Approximately 300 patients with unilateral iliofemoral DVT and symptom duration ≤ 12 weeks will be randomized 1:1. Study conduct includes an independent core laboratory for duplex ultrasound assessment, an independent medical monitor for safety adjudication, and evaluation of PTS severity on the Villalta scale using best clinical practices. The primary endpoint is a composite outcome structured as a hierarchal win ratio of 1) the occurrence of treatment failure or therapy escalation as adjudicated by the medical monitor, with failure defined as amputation or gangrene of the target leg or venous thromboembolism-related mortality, and 2) the assessment of PTS severity at the 6-month follow-up visit. In addition to being a component of the primary endpoint, the severity of PTS at 6 months is also evaluated as a stand-alone secondary endpoint. An additional secondary endpoint is a composite of outcomes at the 10-day visit and is structured as a hierarchal win ratio of 1) vessel compressibility on duplex ultrasound, 2) patient-reported pain, and 3) improvement of edema. The safety endpoints are access site complications requiring endovascular or surgical repair and the occurrence through the 30-day visit of mortality, major bleeding, or new symptomatic pulmonary embolism. DEFIANCE will be the first RCT to evaluate a mechanical thrombectomy-based interventional approach versus anticoagulation therapy alone for DVT. The results will inform the treatment of patients with iliofemoral DVT and the prevention of PTS-associated morbidity. DEFIANCE: RCT of ClotTriever System Versus Anticoagulation In Deep Vein Thrombosis (DEFIANCE), ClinicalTrials.gov: NCT05701917, URL: https://clinicaltrials.gov/study/NCT05701917?cond=Deep%20Vein%20Thrombosis&term=defiance&rank=1 [Display omitted] [ABSTRACT FROM AUTHOR]

This study examines a cooperative non-orthogonal multiple access (NOMA) network utilizing an energy-constrained unmanned aerial vehicle (UAV) relay (UAVR) to expand coverage and improve network throughput. In order to provide energy to the UAVR, we consider the hybrid simultaneous wireless information and power transmission (SWIPT) method, which allows the UAVR to harvest energy from the source (i.e., sink node) signal. Herein, a hybrid time switching (TS)-based and power splitting (PS)-based relaying scheme is applied to improve the UAVR's energy harvesting (EH) efficiency and the system performance. Given this context, we derive the closed-form expression of the outage probability (OP) for the sensors to evaluate the network performance. Based on the achieved analytical results, we apply the bat algorithm optimization (BAO) method to determine the optimal working point (as a fraction of received power and power allocation coefficients, and the 3-D positions of the UAVR) for the system such that the OP is minimized. The numerical analysis indicates that BAO is effective in both exploring and exploiting solutions, making it a suitable choice for similar non-convex optimization problems in continuous search spaces for cooperative NOMA IoT networks. [ABSTRACT FROM AUTHOR]

Asthma is a common chronic respiratory disease in childhood, requiring effective management strategies. This study aims to evaluate the effectiveness of a nurse-led WeChat Mini Program in managing asthma among children aged 6 to 11 years. This randomized controlled trial adhered to the CONSORT checklist and was conducted at a tertiary hospital in China from January 2023 to August 2023. One hundred and eight children with asthma were randomly assigned to two groups, and 81 children completed the 6-month follow-up. All participants received asthma management from specialist nurses, including routine treatments such as inhaled corticosteroids. The experimental group also utilized the WeChat Mini Program for asthma management. Both groups underwent follow-up assessments at 3 and 6 months post-enrollment, which included the Childhood Asthma Control Test (C-ACT), asthma control levels, frequency of exacerbations, and lung function. At 3 and 6 months, the experimental group showed significantly higher C-ACT scores and a lower exacerbation frequency compared to the control group (p < 0.05). While Peak Expiratory Flow improved, Forced Expiratory Volume in 1 Second Percentage Predicted (FEV1%) and FEV1/FVC did not change significantly. The WeChat Mini Program significantly improved asthma control and reduced exacerbations but did not substantially enhance all lung function parameters. Further research is required to confirm its long-term effects. Incorporating a specialist nurse-led digital management tool, such as the WeChat Mini Program, into standard pediatric asthma care may offer an effective management strategy. • WeChat Program Management improved asthma control and lung function in children. • Asthma specialist nurses played an essential role in the management of asthma. • Effective asthma management reduced the frequency of acute exacerbations. [ABSTRACT FROM AUTHOR]

Six novel compounds, comprising three quinolones (1a , 1b , and 2) and three flavanones (3 – 5), along with seven known analogs (6 – 13), were isolated from the 95% EtOH extract of the stems and leaves of Glycosmis craibii var. glabra. The structures of the new compounds were elucidated using HR-ESI-MS, UV, and 1D and 2D nuclear magnetic resonance (NMR) data analysis. The absolute configurations were determined through Mosher ester and electronic circular dichroism (ECD) spectral analysis. Compounds 2, 6, 9 , and 10 demonstrated inhibition of nitric oxide (NO) production stimulated by lipopolysaccharide in BV-2 microglial cells, with IC 50 values ranging from 13.5 to 20.1 μmol·L−1, comparable to the positive control, dexamethasone. [ABSTRACT FROM AUTHOR]

The association of coronary computed tomography angiography (CTA) and left ventricular (LV) myocardium measurements with cancer therapy–related cardiac dysfunction (CTRCD) is limited. In this study, the authors sought to evaluate the changes in coronary arteries and LV myocardium in patients with left breast cancer (BC) receiving anthracycline with or without radiotherapy, with the use of coronary CTA. Participants with left BC receiving anthracycline with or without radiotherapy were prospectively included. All participants underwent coronary CTA before and after treatment, including nonenhanced calcium-scoring scan, computed tomography angiography, and dual-energy late enhancement scan. Computed tomographic fractional flow reserve (CT-FFR), pericoronary adipose tissue (PCAT) CT attenuation, and LV segments' extracellular volume (ECV) before and after treatment were compared. Logistic regression analysis was used to assess the association between baseline coronary CTA parameters and CTRCD. Eighty participants receiving anthracycline and 59 participants receiving anthracycline with radiotherapy were included. CT-FFR decreased and PCAT CT attenuation and LV global and segments' ECV increased after treatment (all P < 0.05). After chemoradiotherapy, CT-FFR was lower and PCAT CT attenuation and LV myocardial ECV were higher than after chemotherapy. Twenty-four participants developed CTRCD. After adjustment by Heart Failure Association–International Cardio-Oncology Society risk in multivariable logistic regression analysis, baseline stenosis of the left anterior descending artery (LAD) (OR: 1.987 [95% CI: 1.322-2.768]; P = 0.021), left circumflex artery (LCX) (OR: 1.895 [95% CI: 1.281-2.802]; P = 0.031), and right coronary artery (RCA) (OR: 1.920 [95% CI: 1.405-2.811]; P = 0.028), and baseline CT-FFR of the LAD (OR: 3.425 [95% CI: 1.621-9.434]; P < 0.001), LCX (OR: 2.058 [95% CI: 1.030-5.076]; P = 0.006), and RCA (OR: 2.469 [95% CI: 1.232-6.944]; P = 0.004) were associated with CTRCD. Multiparameter coronary CTA contributes to comprehensive assessment of the coronary arteries and myocardium in patients with left BC receiving anthracycline with or without radiotherapy. Baseline coronary artery stenosis and CT-FFR might be imaging markers for predicting CTRCD in these patients. [Display omitted] [ABSTRACT FROM AUTHOR]

Robot assembly skill learning has gradually become a research focus in the field of industrial robots. To improve the learning efficiency and adaptability of robot peg-in-hole assembly strategy, a deep reinforcement learning (DRL) method combining PD force controller is proposed in this paper. Firstly, the twin delayed deep deterministic policy gradient (TD3) algorithm based on prioritized experience replay (PER) is used to perceive the environment and make assembly skill decisions. Then, according to the PD force controller, the action output of the DRL policy network is adjusted to modify the robot's trajectory. Finally, the curriculum learning strategy is adopted to gradually increase the task difficulty in the process of algorithm training, thus improving the convergence speed and generalization ability of the model. The proposed method is verified in two different peg-in-hole assembly tasks, which realizes the autonomous acquisition of robot assembly skills, and effectively improves the learning efficiency and adaptability of assembly strategy. [ABSTRACT FROM AUTHOR]

Immunotherapy can enhance primary tumor efficacy, restrict distant growth, and combat lung metastasis. Unfortunately, it remains challenging to effectively activate the immune response. Here, tertiary butyl, methoxy, and triphenylamine (TPA) were utilized as electron donors to develop multifunctional photosensitizers (PSs). CNTPA-TPA, featuring TPA as the donor (D) and cyano as the acceptor (A), excelled in reactive oxygen species (ROS) generation due to its smaller singlet-triplet energy gap (ΔE S-T) and larger spin-orbit coupling constant (SOC). Additionally, cyano groups reacted with glutamate (Glu) and glutathione (GSH), reducing intracellular GSH levels. This not only enhanced PDT efficacy but also triggered redox dyshomeostasis-mediated ferroptosis. The positive effects of photodynamic therapy (PDT) and ferroptosis promoted immunogenic cell death (ICD) and immune activation. By further combining anti-programmed cell death protein ligand-1 (anti-PD-L1) antibody, the powerful treatments of ferroptosis-assisted photodynamic immunotherapy significantly eradicated the primary tumors, inhibited the growth of distant tumors, and suppressed lung metastasis. In this study, a three-pronged approach was realized by single-component CNTPA-TPA, which simultaneously served as metal-free ferroptosis inducers, type-I photosensitizers, and immunologic adjuvants for near-infrared fluorescence imaging (NIR FLI)-guided multimodal phototheranostics of tumor. (1) CNTPA-TPA shared the smallest singlet-triplet energy gap and the largest spin-orbit coupling constant, which boosted intersystem crossing for efficient type-I photodynamic therapy (PDT); (2) Special reactions between cyano groups with glutamate and glutathione in mild conditions restricted the biosynthesis of intracellular GSH. GSH-depletion efficiently induced glutathione peroxidase 4 inactivation and lipid peroxide, resulting in ferroptosis of tumor cells; (3) The combination treatments of ferroptosis-assisted photodynamic immunotherapy induced by single-component CNTPA-TPA with the participation of anti-PD-L1 antibody resulted in increased T-cell infiltration and profound suppression of both primary and distant tumor growth, as well as lung metastasis. [Display omitted] [ABSTRACT FROM AUTHOR]

• We conducted a meta-analysis of twenty-two trials involving 1074 adults with mild cognitive impairment and Alzheimer's disease. • The effects of transcranial direct current stimulation (tDCS) on various on global cognitions were assessed. • The tDCS can ameliorate global cognition of patients with MCI and AD, and it has a better rehabilitation effect than non-tDCS or sham-tDCS. To systematically assess the effectiveness of transcranial direct current stimulation (tDCS) on global cognition in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Ten databases were retrieved for pertinent Chinese and English studies published up until February 2023. Two researchers independently selected the literature, extracted the data, evaluated using the Cochrane Collaboration's quality criteria, and then cross-checked. Meta-analysis was performed using RevMan 5.4. 22 studies involving 1074 patients were included. Compared with the control group received the interventions such as pharmacotherapy, cognitive stimulation, et al., with/without sham-tDCS, while the experiment group received tDCS added to the interventions of the control group. The meta-analysis found that tDCS increased MMSE, MoCA, MODA scores and reduced the P300 latency scores (all P < 0.05). The tDCS can ameliorate the global cognition of patients with MCI and AD, and it has a better rehabilitation effect than non-tDCS or sham-tDCS. [ABSTRACT FROM AUTHOR]

Although serving as the workhorse, MS/MS cannot fully satisfy the analytical requirements of quantitative sub-metabolome characterization. Because more information intrinsically correlates to more structural and concentration clues, here, efforts were devoted to comprehensively tracing and deciphering MS/MS behaviors through constructing triple three-dimensional (3×3D)-MS/MS spectrum. Ginsenosides-targeted metabolomics of notoginseng, one of the most famous edible medicinal plants, was employed as a proof-of-concept. Serial authentic ginsenosides were deployed to build the correlations between 3×3D-MS/MS spectra and structure/concentration features. Through assaying ginsenosides with progressive concentrations using QTOF-MS to configure 1st 3D spectrum, the generations of MS1 spectral signals, particularly multi-charged multimer anions, e.g. , [2M–2H]2– and [2M+2HCOO]2– ions, relied on both concentration and the amount of sugar chains. By programming progressive collision energies to the front collision cell of Qtrap-MS device to gain 2nd 3D spectrum, optimal collision energy (OCE) corresponding to the glycosidic bond fission was primarily correlated with the masses of precursor and fragment ions and partially governed by the glycosidation site. The quantitative relationships between OCEs and masses of precursor and fragment ions were utilized to build large-scale quantitative program for ginsenosides. After applying progressive exciting energies to the back collision chamber to build 3rd 3D spectrum, the fragment ion and the decomposition product anion exhibited identical dissociation trajectories when they shared the same molecular geometry. After ginsenosides-focused quantitative metabolomics, significant differences occurred for sub-metabolome amongst different parts of notoginseng. The differential ginsenosides were confirmatively identified by applying the correlations between 3×3D-MS/MS spectra and structures. Together, 3×3D-MS/MS spectrum covers all MS/MS behaviors and dramatically facilitates sub-metabolome characterization from both quantitative program development and structural identification. 3×3D-MS/MS spectrum, consisting of full concentration ramp-MS1, FCER-MS2, and FEER-MS3 spectra, dramatically facilitates confirmative structural identification and quantitative sub-metabolome characterization. [Display omitted] [ABSTRACT FROM AUTHOR]

Due to the unhealthy principal-agent relationships prevalent in state-owned enterprises (SOEs), these enterprises often lack transparency in financial reporting and other critical information. Drawing on signaling theory, this study examines the impact of mixed-ownership reform (MOR) on financial constraints in Chinese SOEs. Using data from listed manufacturing SOEs between 2009 and 2019, we find that every 0.1 increase in the proportion of non-state shareholders, a proxy for MOR intensity, is associated with an average 2.34 ‰ reduction in financial constraints. This mitigation in constraints primarily arises from decreased information asymmetry between enterprises and the external capital market. Specifically, MOR promotes corporate information disclosure, which sends quality signals to investors, while simultaneously reinforcing corporate governance, which projects intention signals to capital markets. Notably, the effectiveness of MOR in alleviating financial constraints is more significant in capital-intensive and information-sensitive industries, as well as in central SOEs. These findings not only highlight the critical role of MOR in alleviating information asymmetry within SOEs, but also provide valuable insights for similar reforms aimed at advancing sustainable development of SOEs in other countries. [ABSTRACT FROM AUTHOR]

Clavicular hook plates are extensively used in the treatment of acromioclavicular dislocation. Subacromial osteolysis is a typical complication following hook plate fixation. We performed a systematic review and meta-analysis to determine the incidence of subacromial osteolysis and analyzed the associated characteristics of subacromial osteolysis to guide surgeons. PubMed, EMBASE, and Cochrane Library databases were comprehensively searched for relevant literature. We screened the literature based on the eligibility criteria, extracted relevant data, and assessed the quality of the included studies. Pooled odds ratios or mean differences with 95% confidence intervals (CIs) were calculated by a fixed-effects or random-effects model. Heterogeneity was evaluated by the chi-squared test and I2 statistics. A meta-regression analysis was performed to explore the potential source of heterogeneity. Thirty-two studies met the inclusion criteria. The total pooled incidence of subacromial osteolysis was 29% and the only covariate that could influence the incidence of subacromial osteolysis was the radiological measurement method (P =.017). Patients in the hook plate fixation with coracoclavicular ligament reconstruction group had lower odds of subacromial osteolysis (odds ratio, 2.54, 95% CI 1.54-4.18; P <.001). There were no significant differences in the Constant-Murley scores at the final follow-up between patients with and without subacromial osteolysis (standardized mean difference, −0.17; 95% CI, −0.50 to 0.15; P =.294). Subacromial osteolysis has a relatively high and variable incidence, and the primary factor influencing the reported incidence is the radiological assessment method. The current analysis suggests coracoclavicular ligament reconstruction as an effective surgical approach for decreasing the incidence of subacromial osteolysis. The presence or absence of subacromial osteolysis did not significantly impact the functional outcomes observed during the final follow-up period. [ABSTRACT FROM AUTHOR]

Our goal was to assess the impact of childhood/adolescent cancer history on overall survival (OS) and disease-specific survival (DSS) in patients with parotid mucoepidermoid carcinoma (MEC). Patients who underwent surgical treatment for primary parotid MEC and those with a second malignancy of parotid MEC were retrospectively identified from the Surveillance, Epidemiology, and End Results (SEER) database. The primary outcome variables were OS and DSS. The hazard ratios (HRs) of these survival rates associated with cancer history were analysed using Cox regression models. In total, 2681 patients were included, 263 of whom had a second malignancy. The 10-year OS rates in the primary (72%) and second malignancy groups (59%) were significantly different. Cox regression confirmed that a history of cancer tended to decrease OS (p = 0.062, HR: 1.28, 95% confidence interval: 0.99 to 1.64). Subgroup analyses showed that a history of solid tumour as opposed to haematological cancer predicted worse OS, with central nervous system tumours exhibiting a more significant influence than others (p = 0.030 vs p = 0.088). Cancer history was not related to DSS. A history of childhood/adolescent cancer negatively influenced the prognosis of patients with parotid MEC, and this effect was primarily driven by a history of solid malignancy. [ABSTRACT FROM AUTHOR]

Previous studies have established the existence of the mesogastrium, dividing it into 6 sections. The mesogastrium is identified during surgery and used in surgical practice. The aim of the present study was to further investigate its role in gastric cancer prognosis. Between January 2014 and January 2018, patients from the Tongji Hospital were included in this post hoc analysis, including data from a randomized clinical study (DCGC01; http://www.clinicaltrials.gov , NCT01978444). Mesogastria containing metastatic lymph nodes were referred to as metastatic mesogastria. Pathology reports were examined to assess metastases in the mesogastrium. Survival was assessed using Kaplan–Meier curves and multivariable Cox models. Among the 479 patients, 230 (48.0%) had no lymph node metastasis, 34 (7.1%) had 1 metastatic mesogastrium, and 215 (44.9%) had 2 to 6 metastatic mesogastria. Multivariate analysis showed that the number of metastatic mesogastria and N stages were independent risk factors for patient prognosis. In general, a higher metastatic mesogastrium number is positively correlated with a worse prognosis. For identical N stages, 5-year survival rates for patients with 2 to 6 metastatic mesogastria were significantly lower than those for patients with 1 metastatic mesogastrium. The number of metastatic mesogastria serves as an independent prognostic factor from the N stage. [ABSTRACT FROM AUTHOR]

The current scores used to help diagnose acute appendicitis have a "gray" zone in which the diagnosis is usually inconclusive. Furthermore, the universal use of CT scanning is limited because of the radiation hazards and/or limited resources. Hence, it is imperative to have an accurate diagnostic tool to avoid unnecessary, negative appendectomies. This was an international, multicenter, retrospective cohort study. The diagnostic accuracy of the artificial intelligence platform was assessed by sensitivity, specificity, negative predictive value, the area under the receiver curve, precision curve, F1 score, and Matthews correlation coefficient. Moreover, calibration curve, decision curve analysis, and clinical impact curve analysis were used to assess the clinical utility of the artificial intelligence platform. The accuracy of the artificial intelligence platform was also compared to that of CT scanning. Two data sets were used to assess the artificial intelligence platform: a multicenter real data set (n = 2,579) and a well-qualified synthetic data set (n = 9736). The platform showed a sensitivity of 92.2%, specificity of 97.2%, and negative predictive value of 98.7%. The artificial intelligence had good area under the receiver curve, precision, F1 score, and Matthews correlation coefficient (0.97, 86.7, 0.89, 0.88, respectively). Compared to CT scanning, the artificial intelligence platform had a better area under the receiver curve (0.92 vs 0.76), specificity (90.9 vs 53.3), precision (99.8 vs 98.9), and Matthews correlation coefficient (0.77 vs 0.72), comparable sensitivity (99.2 vs 100), and lower negative predictive value (67.6 vs 99.5). Decision curve analysis and clinical impact curve analysis intuitively revealed that the platform had a substantial net benefit within a realistic probability range from 6% to 96%. The current artificial intelligence platform had excellent sensitivity, specificity, and accuracy exceeding 90% and may help clinicians in decision making on patients with suspected acute appendicitis, particularly when access to CT scanning is limited. [Display omitted] [ABSTRACT FROM AUTHOR]

Multidisciplinary collaborative care has been widely recommended as an effective strategy for managing diabetes; however, the cardiovascular risk factors of patients with diabetes are often inadequately managed in primary care settings. This study aimed to assess the effect of multidisciplinary collaboration on cardiovascular risk factors among patients with diabetes in primary care settings. Five databases (i.e., Medline, Embase, CINAHL, SCOPUS and CENTRAL) were systematically searched to retrieve randomised controlled trials. Studies were eligible for inclusion if the interventions included a multidisciplinary team with professionals from at least three health disciplines and focused on patients with diabetes in primary care settings. A random-effects model was used to calculate the pooled effects. In total, 19 studies comprising 6538 patients were included in the meta-analysis. The results showed that compared with usual care, multidisciplinary collaborative care significantly reduced cardiovascular risk factors, including mean systolic blood pressure (–3.27 mm Hg, 95 % confidence interval [CI]: –4.72 to –1.82, p < 0.01), diastolic blood pressure (–1.4 mm Hg, 95 % CI: –2.32 to –0.47, p < 0.01), glycated haemoglobin (–0.42 %, 95 % CI: –0.59 to –0.25, p < 0.01), low-density lipoprotein (–0.16 mmol/L, 95 % CI: –0.26 to –0.06, p < 0.01) and high-density lipoprotein (0.06 mmol/L, 95 % CI: 0.00–0.12, p < 0.05). The subgroup analysis showed multidisciplinary collaboration was more effective in reducing cardiovascular risk factors when it comprised team members from a number of different disciplines, combined pharmacological and non-pharmacological components, included both face-to-face and remote interactions and was implemented in high-income countries. Multidisciplinary collaborative care is associated with reduced cardiovascular risk factors among patients with diabetes in primary care. Further studies need to be conducted to determine the optimal team composition. • Multidisciplinary team reduces cardiovascular risk factors in adults with diabetes. • Multidisciplinary collaboration is an integral component of primary care. • Digital health is beneficial in improving the effects of team collaboration. • Multidisciplinary team is predominantly available in high-income countries. [ABSTRACT FROM AUTHOR]

This population-based cohort study aimed to examine the association with childhood attention deficit/hyperactivity disorder (ADHD) and bullying experiences during adolescence among Digital Generation individuals, exploring both traditional and cyberbullying. This study included data from 15,240 participants, collected from the Taiwan Adolescent to Adult Longitudinal Study project. Participants, initially in seventh and 10th grade in 2015, were selected through a multistage stratified sampling approach. Self-report questionnaires assessed traditional and cyberbullying victimization experiences during adolescence, with 5-year longitudinal follow-up. Childhood ADHD diagnoses were identified by linking data to Taiwan's National Health Insurance Research Database from 2000 to 2015. Logistic regression models were employed to examine the relationship between childhood ADHD and bullying victimization while controlling for relevant covariates. Individuals diagnosed with childhood ADHD exhibited a significantly higher likelihood of experiencing bullying during adolescence (adjusted odds ratio (aOR) = 1.52, 95% confidence interval (CI): 1.28–1.80). This association extended to various forms of bullying, including physical (aOR = 1.42, 95% CI: 1.20–1.68), verbal (aOR = 1.42, 95% CI: 1.20–1.67), relational (aOR = 1.45, 95% CI: 1.22–1.71), and cyber (aOR = 1.35, 95% CI: 1.14–1.61). Additional factors positively associated with bullying victimization included male, binge drinking, and depression, while a positive campus atmosphere was protective against bullying. However, there is no evidence for interactions between these factors and ADHD in their associations with bullying. Childhood ADHD increases the risk of both traditional and cyberbullying during adolescence. Recognizing this risk is essential for targeted interventions and further research on underlying mechanisms. [ABSTRACT FROM AUTHOR]

Hepatic sinusoidal obstruction syndrome induced by pyrrolizidine alkaloids (PA-HSOS) is a complication of drug-induced liver damage. Few studies have examined the relationship between pathological changes and clinical circumstances in PA-HSOS. The Drum Tower Severity Scoring System (DTSS) was developed using prognostic indicators from clinical treatment outcomes. We hypothesized that the severity of pathological damage is consistent with DTSS. We aimed to improve our understanding and assessment of vascular liver injury disease histopathology by studying larger sample sizes of human histopathological samples. We also wanted to confirm the link between histopathological findings and DTSS. The study included 62 patients with PA-HSOS who underwent transjugular liver biopsy. Their hepatic pathological tissues were evaluated. Analyses of linear regression and Spearman's correlation were employed to examine the relationship between DTSS and pathological characteristics. Clinical performance and the DTSS score were used to determine histopathological severity. The sinusoidal congestion area (SCA), central venous endothelial injury (CVEI), and fibrinoid exudation in congestion foci (FECF) were significant indicators. SCA was linearly related to the DTSS score. Our findings show that hepatic pathological characteristics correlate with DTSS scores in PA-HSOS. SCA, CVEI, and FECF may be helpful for determining PA-HSOS severity. [ABSTRACT FROM AUTHOR]

Abdominal wall reconstruction requires extensive dissection of the abdominal wall, exposure of the retroperitoneum, and aggressive chemoprophylaxis to reduce the risk of thromboembolic complications. The need for early anticoagulation puts patients at risk for bleeding. We aimed to quantify postoperative blood loss, incidence of transfusion and reoperation, and associated risk factors in patients undergoing complex abdominal wall reconstruction. All patients underwent a posterior component separation with transversus abdominis release and placement of retromuscular mesh for ventral hernias <20 cm wide and were enrolled in a clinical trial assessing the utility of trans-fascial mesh fixation. A post hoc analysis was performed to quantify postoperative hemoglobin drop, blood transfusions, and procedural interventions for ongoing bleeding during the first 30 postoperative days. Multivariate logistic regression was used to identify predictors of transfusion. In 325 patients, hemoglobin decreased by 3.61 (±1.58) g/dL postoperatively. Transfusion incidence was 9.5% (n = 31), and 3.1% (n = 10) required a surgical intervention for bleeding. Initiation of therapeutic anticoagulation postoperatively resulted in a higher likelihood of requiring surgical intervention for bleeding (odds ratio 10.4 [95% confidence interval 2.75–43.8], P <.01). Use of perioperative therapeutic anticoagulation was associated with higher rates of transfusion (odds ratio 3.51 [95% confidence interval 1.34–8.53], P <.01). Neither intraoperative blood loss nor operative times were associated with an increased transfusion requirement or need for operative intervention. Patients undergoing transversus abdominis release are at a high risk of postoperative bleeding that can require transfusion and reoperation. Patients requiring postoperative therapeutic anticoagulation are at particularly high risk. [ABSTRACT FROM AUTHOR]

Insufficient therapeutic strategies for acute kidney injury (AKI) necessitate precision therapy targeting its pathogenesis. This study reveals the new mechanism of the marine-derived anti-AKI agent, piericidin glycoside S14, targeting peroxiredoxin 1 (PRDX1). By binding to Cys83 of PRDX1 and augmenting its peroxidase activity, S14 alleviates kidney injury efficiently in Prdx1 -overexpression (Prdx1 -OE) mice. Besides, S14 also increases PRDX1 nuclear translocation and directly activates the Nrf2/HO-1/NQO1 pathway to inhibit ROS production. Due to the limited druggability of S14 with low bioavailability (2.6%) and poor renal distribution, a pH-sensitive kidney-targeting dodecanamine-chitosan nanoparticle system is constructed to load S14 for precise treatment of AKI. l -Serine conjugation to chitosan imparts specificity to kidney injury molecule-1 (Kim-1)-overexpressed cells. The developed S14-nanodrug exhibits higher therapeutic efficiency by improving the in vivo behavior of S14 significantly. By encapsulation with micelles, the AUC 0‒ t , half-life time, and renal distribution of S14 increase 2.5-, 1.8-, and 3.1-fold, respectively. The main factors contributing to the improved druggability of S14 nanodrugs include the lower metabolic elimination rate and UDP-glycosyltransferase (UGT)-mediated biotransformation. In summary, this study identifies a new therapeutic target for the marine-derived anti-AKI agent while enhancing its ADME properties and druggability through nanotechnology, thereby driving advancements in marine drug development for AKI. Marine-derived S14 targets PRDX1 and regulates PRDX1/Nrf2 to mitigate AKI-induced reactive oxygen species. A S14-loaded Kim-1-targeted nanodelivery system was established to enhance renal biodistribution and pharmacokinetics properties for AKI therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Reducing plaque lipid content and enhancing plaque stability without causing extensive apoptosis of foam cells are ideal requirements for developing a safe and effective treatment of atherosclerosis. In this study, we synthesized IR780-Gd-OPN nanomicelles by conjugating osteopontin (OPN) and loading a gadolinium-macrocyclic ligand (Gd-DOTA) onto near-infrared dye IR780-polyethylene glycol polymer. The nanomicelles were employed for mild phototherapy of atherosclerotic plaques and dual-mode imaging with near-infrared fluorescence and magnetic resonance. In vitro results reveal that the mild phototherapy mediated by IR780-Gd-OPN nanomicelles not only activates heat shock protein (HSP) 27 to protect foam cells against apoptosis but also inhibits the nuclear factor kappa-B (NF-κB) pathway to regulate lipid metabolism and macrophage polarization, thereby diminishing the inflammatory response. In vivo results further validate that mild phototherapy effectively reduces plaque lipid content and size while simultaneously enhancing plaque stability by regulating the ratio of M1 and M2-type macrophages. In summary, this study presents a promising approach for developing a safe and highly efficient method for the precise therapeutic visualization of atherosclerosis. The rupture of unstable atherosclerotic plaques is a major cause of high mortality rates in cardiovascular diseases. Therefore, the ideal outcome of atherosclerosis treatment is to reduce plaque size while enhancing plaque stability. To address this challenge, we designed IR780-Gd-OPN nanomicelles for mild phototherapy of atherosclerosis. This treatment can effectively reduce plaque size while significantly improving plaque stability by increasing collagen fiber content and elevating the ratio of M2/M1 macrophages, which is mainly attributed to the inhibition of the NF-κB signaling pathway by mild phototherapy-activated HSP27. In summary, our proposed mild phototherapy strategy provides a promising approach for safe and effective treatment of atherosclerosis. [Display omitted] [ABSTRACT FROM AUTHOR]

T cells require second immune checkpoint molecules for activation and immune memory after antigen presentation. We found that inducible co-stimulator (ICOS) has been a favorable prognostic factor amongst B7 immune checkpoint co-stimulators (ICSs) families in head and neck squamous cell carcinoma (HNSCC) and oral SCC (OSCC). This study analyzed the expression of non-B7 tumor necrosis factor (TNF) superfamily ICSs in the Cancer Genome Atlas (TCGA) HNSCC cohort, our OSCC cohort, and TCGA pan-cancer datasets. The correlation in expression, prognosis, and immune status was assessed. The higher expression of CD27, CD30, CD40L, death domain 3 (DR3), and OX40, presumably on the T cell surface, defined better overall survival of HNSCC patients. Besides, CD27, CD30, CD40L, and OX40 were highly correlated with ICOS expression in tumors. CD27, CD40L, and DR3 expression are higher in HPV+ HNSCC tumors than in HPV- tumors. The combined expression level of CD27/OX40 or CD27/CD40L/OX40 enables the potent survival prediction of small, less nodal involvement, early stage, and HPV + tumor subsets. Tumors expressing high CD27, CD30, CD40L, ICOS, and OX40 exhibited enhanced immune cell infiltration. The high correlation in the expression of these ICSs was also noted in the vast majority of tumor types in TCGA datasets. The findings of this study not only confirm the potential of the concordant stimulation of CD27, CD30, CD40L, ICOS, and OX40 as a crucial strategy in cancer immunotherapy but also inspire further exploration into the field, highlighting the promising future of cancer treatment. [ABSTRACT FROM AUTHOR]

Dental anxiety is prevalent and may result in the avoidance of periodontal therapy and maintenance. This study aimed to explore the impact of non-surgical periodontal treatment (NSPT) on dental anxiety among patients with periodontitis. In this study, 122 patients with periodontitis participated. The Chinese version of the Modified Dental Anxiety Scale (MDAS) gauged baseline dental anxiety during the initial appointment. Patients receiving non-surgical periodontal treatment (NSPT) in subsequent appointments formed the NSPT group, while those with a delayed NSPT of at least two months constituted the delayed group. In the NSPT group, the second termination questionnaire was administered one month post the last NSPT visit, just before the periodontal re-evaluation. In the delayed group, the second questionnaire was completed before the delayed NSPT initiation. Baseline MDAS scores were comparable between the delay and NSPT groups. However, the NSPT group exhibited lower total scores and scores for each of the five MDAS items at termination compared with the delay group. At baseline, MDAS total scores were inversely associated with age and were lower in males. A reduction in MDAS total scores between observation points was correlated with NSPT, sex, and age after adjustment. Regarding MDAS item 4 (teeth scaled/polished), score reduction consistently correlated with NSPT and age. Participation in NSPT may alleviate dental anxiety, and consequently enhance the patients' conceptiveness to undergo periodontal maintenance or surgery. [ABSTRACT FROM AUTHOR]

A patent design around based on extension innovative method is proposed to address the problem of limited solution process for patent design. This method mainly includes three basic strategies—firstly, extension transformations are used to transform existing patented technical solutions; secondly, conduction analysis and transformations are introduced to transform infringing part of the solutions; and thirdly, reverse rhombus thinking is proposed to expand the protection scope of the design solution. In the end of the paper, the cutting room products are taken as an example to verify the feasibility of the method. [ABSTRACT FROM AUTHOR]

The rapid development of information technology and various information terminals has contributed to the advancement of online learning platforms, and the "Internet + education" has greatly contributed to the development of online learning platforms, which have become a new way for people to receive education. However, many online learning platforms also suffer from low user satisfaction, high dropout rates and low willingness to continue using them. This paper presents an in-depth analysis of both the platform and user perceptions to explore the factors that influence users' willingness to use. This paper uses a combination of exploratory and validation analyses to verify the factors influencing users' intention to continue using online learning platforms, construct an Interpretative Structural Model, further analyze the mechanism of the influencing factors and clarify the relationship between them, which is of great significance for improving the service experience of users' online learning platforms and promoting the sustainable development of online learning platforms. [ABSTRACT FROM AUTHOR]

Neurologic impairments are a significant concern for survivors after pediatric cardiac surgery with cardiopulmonary bypass (CPB). We have previously shown that mesenchymal stromal cell (MSC) delivery through CPB has the potential to mitigate the effects of CPB on neural stem/progenitor cells. This study assessed the dose effects of MSCs. Piglets (n = 20) were randomly assigned to 1 of 4 groups: control, CPB, or CPB followed by MSC administration with low and high doses (10 × 106 and 100 × 106 cells per kilogram). We assessed acute dose effect on cell distribution, multiorgan functions, systemic inflammation, microglia activation, and neural stem/progenitor cell activities. By magnetic resonance imaging, approximately 10 times more MSCs were detected within the entire brain after high-dose delivery than after low-dose delivery. No adverse events affecting hemodynamics, various biomarkers, and neuroimaging were detected after high-dose MSC delivery. High-dose MSCs significantly increased circulating levels of interleukin 4 after CPB. Both MSC groups normalized microglia activation after CPB, demonstrating MSC-induced reduction in cerebral inflammation. There was a significant increase in neuroblasts in the subventricular zone in both treatment groups. The thickness of the most active neurogenic area within the subventricular zone was significantly increased after high-dose treatment compared with CPB and low-dose MSCs, suggesting dose-dependent effects on the neurogenic niche. MSC delivery through CPB is feasible up to 100 × 106 cells per kilogram. MSC treatment during cardiac surgery has the potential to reduce systemic and cerebral inflammation and to modulate responses of an active neurogenic niche to CPB. Further investigation is necessary to assess the long-term effects and to develop a more complete dose-response curve. [ABSTRACT FROM AUTHOR]

[Display omitted] • HMGB1/STAT3/p65 axis mediated microglial activation and autophagy in mPFC correlated with MDD were first identified, and HMGB1 was found to be a potential biomarker for MDD. • Increased HMGB1 expression was mainly observed in microglia from the medial prefrontal cortex of MDD model mice. • Specific knockdown of HMGB1 rescues chronic stress-induced depressive-related phenotypes, microglial activation, and autophagy in mice. • The effects induced by chronic stress were mimicked by exogenous administration of recombinant HMGB1 or specific overexpression of HMGB1, while blocked by STAT3 specific inhibitor or p65 knockdown. • Inhibition of HMGB1/STAT3/p65 axis prevented LPS-induced microglial activation and autophagy in vitro , which was reversed by recombinant HMGB1 protein overexpression. • Microglial HMGB1/STAT3/p65 axis within the mPFC is a novel therapeutic target in the treatment of MDD associated with stress. Neuroinflammation and autophagy are implicated in stress-related major depressive disorder (MDD), but the underlying molecular mechanisms remain largely unknown. Here, we identified that MDD regulated by HMGB1/STAT3/p65 axis mediated microglial activation and autophagy for the first time. Further investigations were performed to uncover the effects of this axis on MDD in vivo and in vitro. Bioinformatics analyses were used to re-analysis the transcriptome data from the dorsolateral prefrontal cortex (dlPFC) of post-mortem male MDD patients. The expression level of HMGB1 and its correlation with depression symptoms were explored in MDD clinical patients and chronic social defeat stress (CSDS)-induced depression model mice. Specific adeno-associated virus and recombinant (r)HMGB1 injection into the medial PFC (mPFC) of mice, and pharmacological inhibitors with rHMGB1 in two microglial cell lines exposed to lipopolysaccharide were used to analyze the effects of HMGB1/STAT3/p65 axis on MDD. The differential expression of genes from MDD patients implicated in microglial activation and autophagy regulated by HMGB1/STAT3/p65 axis. Serum HMGB1 level was elevated in MDD patients and positively correlated with symptom severity. CSDS not only induced depression-like states in mice, but also enhanced microglial reactivity, autophagy as well as activation of the HMGB1/STAT3/p65 axis in mPFC. The expression level of HMGB1 was mainly increased in the microglial cells of CSDS-susceptible mice, which also correlated with depressive-like behaviors. Specific HMGB1 knockdown produced a depression-resilient phenotype and suppressed the associated microglial activation and autophagy effects of CSDS-induced. The effects induced by CSDS were mimicked by exogenous administration of rHMGB1 or specific overexpression of HMGB1, while blocked by STAT3 inhibitor or p65 knockdown. In vitro , inhibition of HMGB1/STAT3/p65 axis prevented lipopolysaccharide-induced microglial activation and autophagy, while rHMGB1 reversed these changes. Our study established the role of microglial HMGB1/STAT3/p65 axis in mPFC in mediating microglial activation and autophagy in MDD. [ABSTRACT FROM AUTHOR]

Enzymatic malonylation of natural glycosides provides a promising alternative method for drug-like malonylated glycosides supply. However, the catalytic potential and structural basis of plant malonyltransferase are far from being fully elucidated. This work identified a new malonyltransferase CtMaT1 from Cistanche tubulosa. It displayed unprecedented mono- and/or di-malonylation activity toward diverse glucosides with different aglycons. A "one-pot" system by CtMaT1 and a malonyl-CoA synthetase was established to biosynthesize nine new malonylated glucosides. Structural investigations revealed that CtMaT1 possesses an adequately spacious acyl-acceptor pocket capable of accommodating diverse glucosides. Additionally, it recognizes malonyl-CoA through strong electrotactic and hydrogen interactions. QM/MM calculation revealed the H167-mediated S N 2 reaction mechanism of CtMaT1, while dynamic simulations detected the formation of stable hydrogen bonds between the glucose-6-OH group and H167, resulting in its high malonylation regiospecificity. Calculated energy profiles of two isomeric glycosides highlighted lower reaction energy barriers towards glucoside substrates, emphasizing CtMaT1's preference for glucosides. Furthermore, a mutant CtMaT1 H36A with notably increased di-malonylation activity was obtained. The underlying molecular mechanism was illuminated through MM/GBSA binding free energy calculation. This study significantly advances the understanding of plant acyltransferases from both functional and protein structural perspectives, while also providing a versatile tool for enzymatic malonylation applications in pharmacology. CtMaT1, a plant malonyltransferase with both unprecedented substrate promiscuity and malonylation regiospecificity, was functionally and structurally identified, and employed in universal enzymatic synthesis of diverse malonylated glycosides with potential druggabilities. [Display omitted] [ABSTRACT FROM AUTHOR]