[Danshenxinkun B protects human umbilical vein endothelial cells against ox-LDL-induced injury by inhibiting pyroptosis and the NF-κB/NLRP3 pathway].

OBJECTIVE: To investigate the protective effect of Danshenxinkun B against oxidized low-density lipoprotein (ox-LDL)- induced human umbilical vein endothelial cell (HUVEC) injury and explore the underlying mechanism. METHODS: HUVECs cultured in the presence of 10% fetal bovine serum were treated with ox-LDL (100 µg/mL), ox-LDL+0.1% dimethyl sulfoxide (DMSO), or ox-LDL+Danshenxinkun B (100 ng/mL, dissolved in DMSO) for 24 h. The changes in lactate dehydrogenase (LDH) release was detected, and qRT-PCR was used to detect the mRNA expressions of nuclear factor-κB1 (NF-κB1), nucleotide binding oligomerization domain-like receptor family pyrin domain protein 3 (NLRP3), gasdermin D (GSDMD) and interleukin- 1ß (IL-1ß). The protein expressions of NF-κB1, NLRP3, caspase-1, IL-1ß and GSDMD-N were detected with Western blotting. Immunofluorescence assay was performed to examine the changes in GSDMD expression in the cells. RESULTS: Compared with the normal control cells, the cells treated with ox-LDL alone or in combination with DMSO exhibited significantly increased LDH release, mRNA expressions of NF-κB1, NLRP3, GSDMD, and IL- 1ß and the protein levels of NF-κB1, NLRP3, IL- 1ß, GSDMD-N and caspase-1 (P<0.01), which were all significantly lowered by treatment with Danshenxinkun B (P<0.05 or 0.01). Danshenxinkun B treatment significantly inhibited GSDMD expression on the cell membrane and restricted its entry into the cell nucleus. CONCLUSION: Danshenxinkun B alleviates ox-LDL-induced HUVEC injury possibly by suppressing pyroptosis mediated by NLRP3 inflammatory bodies and inhibiting the NF-κB/NLRP3 signaling pathway.

[Advances of hydrogel in early protection of exposed intra-abdominal organs after open abdomen].

The protection of open abdomen (OA) wound is a significant subject in the field of trauma surgery. The key technical challenge in the early stage of OA wound management involves promoting granulation tissue filling between intestinal segments, reducing intestinal wall abrasion, and preventing the development of enteroatmospheric fistulas (EAF). Hydrogels, characterized by their high water content and exceptional biocompatibility, serve as extracellular matrix-mimicking materials, and are extensively employed in various medical and healthcare applications. In this review, we discuss the application of hydrogel developed by natural biomaterials in OA wounds protection, taking into consideration the unique pathophysiological characteristics of the OA wounds. This review aims to provide valuable insights for the development of hydrogel materials for early-stage OA wound protection in future research.

Probing size-dependent defects in zinc oxide using synchrotron techniques: impact on photocatalytic efficiency.

In the present study, synchrotron-based X-ray diffraction (XRD), X-ray absorption spectroscopy (XAS) and X-ray excited optical luminescence (XEOL) have been used to investigate the induced defect states in metal oxide nanomaterials. Specifically, two synthesis approaches have been followed to develop unique nano-sized peanut-shaped (N-ZnO) nanostructures and micron-sized hexagonal rods (M-ZnO). XANES analysis at the Zn K-edge revealed the presence of defect states with a divalent oxidation state of zinc (Zn2+) in a tetrahedral structure. Furthermore, XAS measurements performed at the Zn L3,2-edge and O K-edge confirm higher oxygen-related defects in M-ZnO, while N-ZnO appeared to have a higher concentration of surface defects due to size confinement. Moreover, the in-line XEOL and time dependent-XEOL measurements exposed the radiative excitonic recombination phenomena occurring in the band-tailing region as a function of absorption length, X-ray energy excitation, and time. Based on the chronology developed in the defect state improvement, a possible energy band diagram is proposed to accurately locate the defect states in the two systems. Furthermore, the increased absorption intensity at the Zn L3,2-edge and the O K-edge under the UV lamp suggests delayed recombination of electrons and holes, highlighting their potential use as photo catalysts. The photocatalytic activity degrading the rhodamine B dye established M-ZnO as a superior catalyst with a rapid degradation rate and significant mineralization. Overall, this work provides valuable insights into ZnO defect states and provides a foundation for efficient advanced materials for environmental or other optoelectronic applications.

Causal effects of diabetic retinopathy on depression, anxiety and bipolar disorder in the European population: a Mendelian randomization study.

PURPOSE: To verify the causal effects of diabetic retinopathy (DR) on depression, anxiety and bipolar disorder (BD). METHODS: Mendelian randomization (MR) analysis was performed to identify the causal relationships between DR and depression or anxiety or BD via using DR-related GWAS data (14,584 cases and 176,010 controls), depression-related GWAS data (59,851 cases and 113,154 controls), anxiety-related GWAS data (7016 cases and 14,745 controls) and BD-related GWAS data (41,917 cases and 371,549 controls). The inverse-variance weighted (IVW) model was adopted to estimate the causal relationship. The outcome was expressed as odds ratio (OR) with 95% confidence intervals (CI). RESULTS: The MR analysis results presented that DR was causally associated with a significantly increased risk of BD in the European population (IVW, OR = 1.06, 95%CI [1.03, 1.08], P = 2.44 × 10-6), while DR was unable to causally influence the risk of depression (IVW, OR = 1.01, 95%CI [0.99, 1.04], P = 0.32) and anxiety (IVW, OR = 0.97, 95%CI [0.89, 1.06], P = 0.48) in the European population. Subgroup analysis based on BD identified DR causally increased the risk of bipolar I disorder (BD I) but not bipolar II disorder (BD II). Sensitivity analysis results did not show any pleiotropy and heterogeneity in both groups of analyses, indicating that the results were stable and reliable. CONCLUSIONS: The results of the current MR analysis indicated a causal relationship between DR and BD in the European population, while there was no causal connection between DR and depression or anxiety. However, further research is needed to confirm these conclusions.

[Clinical significance of intersphincteric resection related anatomy effect on surgical safety].

The anatomical studies of intersphincteric resection (ISR) have made remarkable progress in recent years. The anatomy of internal, external sphincter and hiatal ligament has been further understood. In this paper, the generation and functional mechanism of ISR related anatomy are described from the embryonic development process, and then the influence of hiatal ligament and internal sphincter on ISR surgery is analyzed respectively according to the anatomical characteristics. Finally, the correlation analysis of anatomical factors on the common problems of mucosal bleeding and instrument anastomosis in ISR is carried out. The objective of this paper is to improve the safety of ISR surgery by providing detailed anatomical explanations.

Low-Income Caregiver Perspectives on a State Education Savings Program and Receptivity to Clinic-Based Financial Counseling.

BACKGROUND AND OBJECTIVE: In 2019, Pennsylvania launched a Children's Development Account (CDA) program that invests $100 in an education savings account for every child born in the state. However, as of 2021, only 10.6% of families claimed the investment. Low-income communities may stand to benefit most from educational investments, but few studies have assessed barriers and facilitators of uptake in these communities. We sought to examine low-income caregivers' perceptions of and barriers and facilitators to participation in a statewide CDA program and their receptivity to clinic-based financial counseling through a medical financial partnership. METHODS: We surveyed 100 caregivers of Medicaid-insured children from 2 primary care practices serving a predominantly low-income community. From these 100, we purposively sampled 30 caregivers for follow-up interviews. RESULTS: The 100 survey participants were predominantly female (83%), Black or African American (92%), and non-Hispanic or Latino (93%). Twenty-nine percent of survey participants were aware of the CDA program, 4% had enrolled, and 64% were interested in clinic-based financial counseling. In interviews, caregivers identified several barriers to and facilitators of engagement in the CDA program. They also identified several strategies to boost engagement, including simplifying registration, providing additional and personalized program information, expanding the investment amount, and providing clinic- and community-based outreach. CONCLUSIONS: Low-income caregivers identified several barriers to enrollment in a statewide CDA program and strategies to boost enrollment, including clinic-based financial counseling. Future research should examine the effectiveness, cost-effectiveness, and long-term financial and health consequences of clinic-based financial services for low-income families.

[Clinical presentation and prognosis in children over 10-year-old with primary nephrotic syndrome].

Objective: To summary the clinical presentation and prognosis of primary nephrotic syndrome (PNS) in teenagers. Methods: The clinical data, renal pathological types and prognosis of 118 children over 10-year-old with PNS treated in the Department of Nephrology of the Children's Hospital Affiliated to Capital Institute of Pediatrics from January 2010 to December 2020 were retrospectively analyzed, with 408 children ≤10-year-old as control group synchronously. Chi-square test was used to compare the difference of clinical types, pathologic types, response to steroids and tubulointerstitial changes between the groups. The teenagers with steroid resistant nephrotic syndrome (SRNS) were divided into initial non-responder group and late non-responder group. Kaplan-Meier method was used to compare the difference of persistent proteinuria, and Fisher's exact test for the histological types. Results: There were 118 children >10-year-old, including 74 males and 44 females, with the onset age of 12.1 (10.8, 13.4) years; and 408 children ≤10-year-old with the onset age of 4.5 (3.2, 6.8) years. The proportion of SRNS was significantly higher in patients >10-year-old than those ≤10-year-old (24.6% (29/118) vs. 15.9% (65/408), χ2=4.66, P=0.031). There was no statistical difference in the pathological types between >10-year-old and ≤10-year-old (P>0.05), with minimal change disease the most common type (56.0% (14/25) vs. 60.5% (26/43)). The percentage of cases with renal tubulointerstitial lesions was significantly higher in children >10-year-old compared to those ≤10-year-old (60.0% (15/25) vs. 23.3% (10/43), χ2=9.18, P=0.002). There were 29 cases presented with SRNS in PNS over 10-year-old, including 19 initial non-responders and 10 late non-responders. Analyzed by Kaplan-Meier curve, it was shown that the percentage of persistent proteinuria after 6 months of immunosuppressive treatments was significantly higher in initial non-responders than those of the late non-responders ((22±10)% vs. 0, χ2=14.68, P<0.001); the percentage of minimal change disease was significantly higher in patients of late non-responders than those of the initial non-responders (5/6 vs. 3/13, P=0.041). Of the 63 >10-year-old with steroid-sensitive nephrotic syndrome followed up more than one year, 38 cases (60.3%) had relapse, and 14 cases (22.2%) were frequent relapse nephrotic syndrome and steroid dependent nephrotic syndrome. Among the 45 patients followed up over 18-year-old, 22 cases (48.9%) had recurrent proteinuria continued to adulthood, 3 cases of SRNS progressed to kidney insufficiency, and one of them developed into end stage kidney disease and was administrated with hemodialysis. Conclusions: Cases over 10-year-old with PNS tend to present with SRNS and renal tubulointerstitial lesions. They have a favorable prognosis, but are liable to relapse in adulthood.

iBT-Net: an incremental broad transformer network for cancer drug response prediction.

In modern precision medicine, it is an important research topic to predict cancer drug response. Due to incomplete chemical structures and complex gene features, however, it is an ongoing work to design efficient data-driven methods for predicting drug response. Moreover, since the clinical data cannot be easily obtained all at once, the data-driven methods may require relearning when new data are available, resulting in increased time consumption and cost. To address these issues, an incremental broad Transformer network (iBT-Net) is proposed for cancer drug response prediction. Different from the gene expression features learning from cancer cell lines, structural features are further extracted from drugs by Transformer. Broad learning system is then designed to integrate the learned gene features and structural features of drugs to predict the response. With the capability of incremental learning, the proposed method can further use new data to improve its prediction performance without retraining totally. Experiments and comparison studies demonstrate the effectiveness and superiority of iBT-Net under different experimental configurations and continuous data learning.

[Structural changes of the frontal cortex in depressed mice are associated with decreased expression of brain-derived neurotrophic factor].

OBJECTIVE: To investigate the changes in gray matter volume in depressive-like mice and explore the possible mechanism. METHODS: Twenty-four 6-week-old C57 mice were randomized equally into control group and model group, and the mice in the model group were subjected to chronic unpredictable mild stimulation (CUMS) for 35 days. Magnetic resonance imaging was performed to examine structural changes of the grey matter volume in depressive-like mice. The expression of brain-derived neurotrophic factor (BDNF) in the grey matter of the mice was detected using Western blotting and immunofluorescence staining. RESULTS: Compared with the control mice, the mice with CUMS showed significantly decreased central walking distance in the open field test (P < 0.05) and increased immobile time in forced swimming test (P < 0.05). Magnetic resonance imaging showed that the volume of the frontal cortex was significantly decreased in CUMS mice (P < 0.001, when the mass level was greater than or equal to 10 756, the FDRc was corrected with P=0.05). Western blotting showed that the expression of mature BDNF in the frontal cortex was significantly decreased in CUMS mice (P < 0.05), and its expression began to decrease after the exposure to CUMS as shown by immunofluorescence staining. The volume of different clusters obtained by voxel-based morphometry (VBM) analysis was correlated with the expression level of mature BDNF detected by Western blotting (P < 0.05). CONCLUSION: The decrease of frontal cortex volume after CUMS is related with the reduction of mature BDNF expression in the frontal cortex.

Measurement of Direct-Photon Cross Section and Double-Helicity Asymmetry at sqrt[s]=510 GeV in p[over →]+p[over →] Collisions.

We present measurements of the cross section and double-helicity asymmetry A_{LL} of direct-photon production in p[over →]+p[over →] collisions at sqrt[s]=510 GeV. The measurements have been performed at midrapidity (|η|<0.25) with the PHENIX detector at the Relativistic Heavy Ion Collider. At relativistic energies, direct photons are dominantly produced from the initial quark-gluon hard scattering and do not interact via the strong force at leading order. Therefore, at sqrt[s]=510 GeV, where leading-order-effects dominate, these measurements provide clean and direct access to the gluon helicity in the polarized proton in the gluon-momentum-fraction range 0.02

First Study of Reaction Ξ

Using (1.0087±0.0044)×10^{10} J/ψ events collected with the BESIII detector at the BEPCII storage ring, the process Ξ^{0}n→Ξ^{-}p is studied, where the Ξ^{0} baryon is produced in the process J/ψ→Ξ^{0}Ξ[over ¯]^{0} and the neutron is a component of the ^{9}Be, ^{12}C, and ^{197}Au nuclei in the beam pipe. A clear signal is observed with a statistical significance of 7.1σ. The cross section of the reaction Ξ^{0}+^{9}Be→Ξ^{-}+p+^{8}Be is determined to be σ(Ξ^{0}+^{9}Be→Ξ^{-}+p+^{8}Be)=(22.1±5.3_{stat}±4.5_{sys}) mb at the Ξ^{0} momentum of 0.818 GeV/c, where the first uncertainty is statistical and the second is systematic. No significant H-dibaryon signal is observed in the Ξ^{-}p final state. This is the first study of hyperon-nucleon interactions in electron-positron collisions and opens up a new direction for such research.

Cardiovascular capacity in adults with obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea (OSA) patients have a decreased exercise capacity. Potential cardiovascular capacity in patients with OSA with different severity without known cardiovascular disease has not been described.OBJECTIVE: To evaluate impaired potential exercise cardiovascular capacity during cardiopulmonary exercise testing (CPET) in OSA patients and to compare cardiovascular performance reaction with different severity during graded exercise stages.DESIGN: All participants were accompanied without cardiovascular disease, especially hypertension and arrhythmia. Parameters of different stages were compared between subjects with and without OSA, and among OSA patients with varied severity.RESULTS: Despite having significantly higher peak exercise diastolic blood pressure (DBP) and ventilatory equivalent for CO2 (EQCO2), patients with OSA had a lower peak oxygen uptake (VO2), heart rate (HR), heart rate recovery (HRR) and respiratory reserve (BR) than normal subjects. Furthermore, significant correlations were found between VO2, DBP, EQCO2, HRR, BR and the apnoea-hypopnea index. In severe OSA, there was a greater difference in HR and HRR during the anaerobic threshold stages.CONCLUSIONS: OSA patients demonstrate reduced potential cardiovascular capacity, even without documented cardiovascular disease. Patients with severe OSA develop impaired exercise capacity at early stage during exercise. These data point to exaggerated haemodynamic response to graded exercise and delayed post-exercise cardiovascular response recovery in OSA patients. CPET can be a supplement for assessment of OSA severity.

Flexible Label-Induced Manifold Broad Learning System for Multiclass Recognition.

Broad learning system (BLS), which emerges as a lightweight network paradigm, has recently attracted great attention for recognition problems due to its good balance between efficiency and accuracy. However, the supervision mechanism in BLS and its variants generally relies on the strict binary label matrix, which imposes limitations on approximation and fails to adequately align with the data distribution. To address this issue, in this article, two novel flexible label-induced BLS models with the manifold manner are proposed, whose notable characteristics are as follows. First, two proposed label relaxation strategies can both enlarge the margins between different categories and simultaneously enhance the diversity within labels. Second, the integration of manifold geometrical criterion enables the models to capture local feature structures, ensuring the obtained flexible labels align better with the similarity between samples. Third, the proposed models can be optimized efficiently with the alternating direction method of multipliers. Each iteration benefits from a closed-form solution, facilitating the optimization process. Extensive experiments and thorough theoretical analysis are intended to show the advantages of our proposed models compared to other state-of-the-art recognition algorithms.

[MiR-30e-5p overexpression promotes proliferation and migration of colorectal cancer cells by activating the CXCL12 axis via downregulating PTEN].

OBJECTIVE: To investigate the regulatory effects of miR-30e-5p on biological behaviors of colorectal cancer cells and the role of PTEN/CXCL12 axis in mediating these effects. METHODS: Bioinformatic analysis was performed to explore the differential expression of miR-30e-5p between colorectal cancer tissues and normal tissues. RT-qPCR was used to detect the differential expression of miR-30e-5p in intestinal epithelial cells and colorectal cancer cells. Bioinformatics and dual luciferase assay were used to predict and validate the targeting relationship between miR-30e-5p and PTEN. Human and murine colorectal cancer cell lines were transfected with miR-30e-5p mimics, miR-30e-5p inhibitor, miR-30e-5p mimics+LV-PTEN, or miR-30e-5p inhibitor + si-PTEN. The changes in biological behaviors of the cells were detected using plate clone formation assay, CCK-8 assay, flow cytometry, scratch healing and Transwell assays. PTEN and CXCL12 expressions in the cancer cells were detected by Western blotting. The effects of miR-30e-5p inhibitor on colorectal carcinogenesis and development were observed in nude mice. RESULTS: Bioinformatic analysis showed that miR-30e-5p expression was significantly elevated in colorectal cancer tissues compared with the adjacent tissue (P < 0.01). Higher miR-30e-5p expression was detected in colorectal cancer cell lines than in intestinal epithelial cells (P < 0.01). Dual luciferase assay confirmed the targeting relationship between miR-30e-5p and PTEN (P < 0.05). Transfection with miR-30e-5p mimics significantly enhanced proliferation and metastasis and inhibited apoptosis of the colorectal cancer cells (P < 0.05), and co-transfection with LV-PTEN obviously reversed these changes (P < 0.05). MiR-30e-5p mimics significantly inhibited PTEN expression and enhanced CXCL12 expression in the cancer cells (P < 0.01), and miR-30e-5p inhibitor produced the opposite effect. Transfection with miR-30e-5p inhibitor caused cell cycle arrest in the cancer cells, which was reversed by co-transfection with si-PTEN (P < 0.05). In the in vivo experiments, the colorectal cancer cells transfected with miR-30e-5p inhibitor showed significantly lowered tumorigenesis. CONCLUSION: Overexpression of miR-30e-5p promotes the malignant behaviors of colorectal cancer cells by downregulating PTEN to activate the CXCL12 axis.

Development and validation of a deep-broad ensemble model for early detection of Alzheimer's disease.

Introduction: Alzheimer's disease (AD) is a chronic neurodegenerative disease of the brain that has attracted wide attention in the world. The diagnosis of Alzheimer's disease is faced with the difficulties of insufficient manpower and great difficulty. With the intervention of artificial intelligence, deep learning methods are widely used to assist clinicians in the early recognition of Alzheimer's disease. And a series of methods based on data input with different dimensions have been proposed. However, traditional deep learning models rely on expensive hardware resources and consume a lot of training time, and may fall into the dilemma of local optima. Methods: In recent years, broad learning system (BLS) has provided researchers with new research ideas. Based on the three-dimensional residual convolution module and BLS, a novel broad-deep ensemble model based on BLS is proposed for the early detection of Alzheimer's disease. The Alzheimer's Disease Neuroimaging Initiative (ADNI) MRI image dataset is used to train the model and then we compare the performance of proposed model with previous work and clinicians' diagnosis. Results: The result of experiments demonstrate that the broad-deep ensemble model is superior to previously proposed related works, including 3D-ResNet and VoxCNN, in accuracy, sensitivity, specificity and F1. Discussion: The proposed broad-deep ensemble model is effective for early detection of Alzheimer's disease. In addition, the proposed model does not need the pre-training process of its depth module, which greatly reduces the training time and hardware dependence.

Reinforcement Learning-Based Adaptive Optimal Control for Nonlinear Systems With Asymmetric Hysteresis.

This article investigates the adaptive optimal tracking problem for a class of nonlinear affine systems with asymmetric Prandtl-Ishlinskii (PI) hysteresis nonlinearities based on actor-critic (A-C) learning mechanisms. Considering the huge obstacles arising from the uncertainty of hysteresis nonlinearity in actuators, we develop a scheme for the conflict between the construction of Hamilton functions and hysteresis nonlinearity. The actuator hysteresis forces the input into a hysteresis delay, thus preventing the Hamilton function from getting the current moment's input instantly and thus making optimization impossible. In the first step, an inverse model is constructed to compensate for the hysteresis model with a shift factor. In the second step, we compensate for the control input by designing a feedback controller and incorporating the estimation and approximation errors into the Hamilton error. Optimal control, the other part of the actual control input, is obtained by taking partial derivatives of the Hamiltonian function after the nonlinearities have been circumvented. At the end, a simulation is given to validate the developed solution.

[Outcomes of laryngotracheal reconstruction with anterior and posterior costal cartilage grafts in severe pediatric subglottic stenosis or laryngeal web].

Objective: To investigate outcomes of laryngotracheal reconstruction (LTR)with anterior and posterior costal cartilage grafts in severe pediatric subglottic stenosis (SGS) or laryngeal web (LW). Methods: A review of patients with severe subglottic stenosis or laryngeal web between January 2020 and January 2022 was performed. Demographic features including gender, age at diagnosis, age at surgery, etiology, airway support, and other comorbidities were collected preoperatively. Patients were evaluated in surgical site, breathing, swallowing, phonation and complications postoperatively.Descriptive analysis was used in this research. Results: Eight patients were included: six with grade Ⅲ SGS following Cotton-Myer grading scale, and two with type Ⅲ LW following Cohen's classification. All patients underwent LTR with anterior and posterior costal cartilage grafts. Five patients underwent single-stage LTR (ssLTR), and three patients underwent double-stage LTR (dsLTR). Seven out of eight patients were able to successfully extubate or decannulate with normal swallowing function; four patients had mild hoarseness, and three had moderate hoarseness. One patient failed in extubation, and underwent tracheotomy. Conclusions: LTR with anterior and posterior costal cartilage grafts is an effective and safe treatment for severe SGS or LW. Careful preoperative assessment of disease severity and overall medical status will help selection between ssLTR and dsLTR, thereby maximizing patient outcomes for both modalities.

Dynamic Event-Driven Finite-Horizon Optimal Consensus Control for Constrained Multiagent Systems.

This article investigates the event-driven finite-horizon optimal consensus control problem for multiagent systems with symmetric or asymmetric input constraints. Initially, in order to overcome the difficulty that the Hamilton-Jacobi-Bellman equation is time-varying in finite-horizon optimal control, a single critic neural network (NN) with time-varying activation function is applied to obtain the approximate optimal control. Meanwhile, for minimizing the terminal error to satisfy the terminal constraint of the value function, an augmented error vector containing the Bellman residual and the terminal error is constructed to update the weight of the NN. Furthermore, an improved learning law is proposed, which relaxes the tricky persistence excitation condition and eliminates the requirement of initial stability control. Moreover, a specific algorithm is designed to update the historical dataset, which can effectively accelerate the convergence rate of network weight. In addition, to improve the utilization rate of the communication resource, an effective dynamic event-triggering mechanism (DETM) composed of dynamic threshold parameters (DTPs) and auxiliary dynamic variables (ADVs) is designed, which is more flexible compared with the ADV-based DETM or DTP-based DETM. Finally, to support the effectiveness of the proposed method and the superiority of the designed DETM, a simulation example is provided.