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Abstract Background A stent with characteristics of a hybrid design may have advantages in improving the patency of symptomatic iliofemoral vein obstruction. This study assessed the safety and effectiveness of the V-Mixtent Venous Stent in treating symptomatic iliofemoral outflow obstruction. Methods Eligible patients had a Clinical-Etiologic-Anatomic-Physiologic (CEAP) C classification of ≥ 3 or a Venous Clinical Severity Score (VCSS) pain score of ≥ 2. The primary safety endpoint was the rate of major adverse events within 30 days. The primary effectiveness endpoint was the 12-month primary patency rate. Secondary endpoints included changes in VCSS from baseline to 6 and 12 months, alterations in CEAP C classification, Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-14) scores at 12 months, and stent durability measures. Results Between December 2020 and November 2021, 171 patients were enrolled across 15 institutions. A total of 185 endovenous stents were placed, with 91.81% of subjects receiving one stent and 8.19% receiving 2 stents. Within 30 days, only two major adverse events occurred (1.17%; 95% confidence interval [CI], 0.14–4.16%), below the literature-defined performance goal of 11% (P

Abstract Background Triple-negative breast cancer (TNBC) represents a highly aggressive subset of breast malignancies characterized by its challenging clinical management and unfavorable prognosis. While TFAP2A, a member of the AP-2 transcription factor family, has been implicated in maintaining the basal phenotype of breast cancer, its precise regulatory role in TNBC remains undefined. Methods In vitro assessments of TNBC cell growth and migratory potential were conducted using MTS, colony formation, and EdU assays. Quantitative PCR was employed to analyze mRNA expression levels, while Western blot was utilized to evaluate protein expression and phosphorylation status of AKT and ERK. The post-transcriptional regulation of TFAP2A by miR-8072 and the transcriptional activation of SNAI1 by TFAP2A were investigated through luciferase reporter assays. A xenograft mouse model was employed to assess the in vivo growth capacity of TNBC cells. Results Selective silencing of TFAP2A significantly impeded the proliferation and migration of TNBC cells, with elevated TFAP2A expression observed in breast cancer tissues. Notably, TNBC patients exhibiting heightened TFAP2A levels experienced abbreviated overall survival. Mechanistically, TFAP2A was identified as a transcriptional activator of SNAI1, a crucial regulator of epithelial-mesenchymal transition (EMT) and cellular proliferation, thereby augmenting the oncogenic properties of TFAP2A in TNBC. Moreover, miR-8072 was unveiled as a negative regulator of TFAP2A, exerting potent inhibitory effects on TNBC cell growth and migration. Importantly, the tumor-suppressive actions mediated by the miR-8072/TFAP2A axis were intricately associated with the attenuation of AKT/ERK signaling cascades and the blockade of EMT processes. Conclusions Our findings unravel the role and underlying molecular mechanism of TFAP2A in driving tumorigenesis of TNBC. Targeting the TFAP2A/SNAI1 pathway and utilizing miR-8072 as a suppressor represent promising therapeutic strategies for treating TNBC.

Abstract Random bit generators are critical for information security, cryptography, stochastic modeling, and simulations. Speed and scalability are key challenges faced by current physical random bit generation. Herein, we propose a massively parallel scheme for ultrafast random bit generation towards rates of order 100 terabit per second based on a single micro-ring resonator. A modulation-instability-driven chaotic comb in a micro-ring resonator enables the simultaneous generation of hundreds of independent and unbiased random bit streams. A proof-of-concept experiment demonstrates that using our method, random bit streams beyond 2 terabit per second can be successfully generated with only 7 comb lines. This bit rate can be easily enhanced by further increasing the number of comb lines used. Our approach provides a chip-scale solution to random bit generation for secure communication and high-performance computation, and offers superhigh speed and large scalability.

Introduction: Chronic ankle instability (CAI) carries a high risk of progression to talar osteochondral lesions and post-traumatic osteoarthritis. It has been clinically hypothesized the progression is associated with abnormal joint motion and ligament elongation, but there is a lack of scientific evidence.Methods: A total of 12 patients with CAI were assessed during level walking with the use of dynamic biplane radiography (DBR) which can reproduce the in vivo positions of each bone. We evaluated the uninjured and CAI side of the tibiotalar and subtalar joint for three-dimensional kinematics differences. Elongation of the anterior talofibular ligament (ATFL), calcaneofibular ligament (CFL), and posterior talofibular ligament (PTFL) were also calculated bilaterally.Results: For patients with CAI, the dorsiflexion of the tibiotalar joint had reduced (21.73° ± 3.90° to 17.21° ± 4.35°), displacement of the talus increased (2.54 ± 0.64 mm to 3.12 ± 0.55 mm), and the inversion of subtalar joint increased (8.09° ± 2.21° to 11.80° ± 3.41°). Mean ATFL elongation was inversely related to mean dorsiflexion angle (CAI: rho = −0.82, P < 0.001; Control: rho = −0.92, P < 0.001), mean ATFL elongation was related to mean anterior translation (CAI: rho = 0.82, P < 0.001; Control: rho = 0.92, P < 0.001), mean CFL elongation was related to mean dorsiflexion angle (CAI: rho = 0.84, P < 0.001; Control: rho = 0.70, P < 0.001), and mean CFL elongation was inversely related to mean anterior translation (CAI: rho = −0.83, P < 0.001; Control: rho = −0.71, P < 0.001). Furthermore, ATFL elongation was significantly (CAI: rho = −0.82, P < 0.001; Control: rho = −0.78, P < 0.001) inversely correlated with CFL elongation.Discussion: Patients with CAI have significant changes in joint kinematics relative to the contralateral side. Throughout the stance phase of walking, ATFL increases in length during plantarflexion and talar anterior translation whereas the elongation trend of CFL was the opposite. This understanding can inform the development of targeted therapeutic exercises aimed at balancing ligament tension during different phases of gait. The interrelationship between two ligaments is that when one ligament shortens, the other lengthens. The occurrence of CAI didn’t change this trend. Surgeons might consider positioning the ankle in a neutral sagittal plane to ensure optimal outcomes during ATFL and CFL repair.

BackgroundMyopia is a significant public health problem across the globe. This study aimed to examine the regional disparity in prevalence and correlated factors of myopia in children and adolescents in two typical regions, Gannan Tibetan Autonomous Prefecture (Gannan Prefecture for short, a Tibetan residential area) and Wuwei City (a Han residential area) in Gansu Province, China, and to provide a reference for the prevention and control of regional myopia.MethodsThe study was a cross-sectional study of children and adolescents in Gansu Province, China. A total of 6,187 (Wuwei City: 3,266, Gannan Tibetan Autonomous Prefecture: 2,921) students were selected by stratified cluster sampling. Eye examinations and questionnaires were administered to the participants. Myopia is defined as a condition in which the spherical equivalent refractive error of an eye is less than or equal to −0.50 D when ocular accommodation is relaxed. The χ2 test and multivariate logistic regression analysis were used to analyze the correlated factors of myopia.ResultsThe myopia rate of 6,187 students was 71.4%, and students had a higher rate of myopia (77.5%) in Wuwei City compared to Gannan Prefecture (64.6%) (p

Environmental heterogeneity partly drives microbial succession in arthropods, while the microbial assembly mechanisms during environmental changes remain largely unknown. Here, we explored the temporal dynamics and assembly mechanisms within both bacterial and fungal communities in Liriomyza huidobrensis (Blanchard) during the transition from field to laboratory conditions. We observed a decrease in bacterial diversity and complexity of bacterial-fungal co-occurrence networks in leaf miners transitioning from wild to captive environments. Both neutral and null models revealed that stochastic processes, particularly drift (contributing over 70%), play a crucial role in governing bacterial and fungal community assembly. The relative contribution of ecological processes such as dispersal, drift, and selection varied among leaf miners transitioning from wild to captive states. Furthermore, we propose a hypothetical scenario for the assembly and succession of microbial communities in the leaf miner during the short- and long-term transition from the wild to captivity. Our findings suggest that environmental heterogeneity determines the ecological processes governing bacterial and fungal community assembly in leaf miners, offering new insights into microbiome and mycobiome assembly mechanisms in invasive pests amidst environmental change.

Addressing the threats of climate change, pollution, and overfishing to marine ecosystems necessitates a deeper understanding of coastal and oceanic fluid dynamics. Within this context, Lagrangian Coherent Structures (LCS) emerge as essential tools for elucidating the complexities of marine fluid dynamics. Methods used to detect LCS include geometric, probabilistic, cluster-based and braid-based approaches. Advancements have been made to employ Finite-time Lyapunov Exponents (FTLE) to detect LCS due to its high efficacy, reliability and simplicity. It has been proven that the FTLE approach has provided invaluable insights into complex oceanic phenomena like shear, confluence, eddy formations, and oceanic fronts, which also enhanced the understanding of tidal-/wind-driven processes. Additionally, FTLE-based LCS were crucial in identifying barriers to contaminant dispersion and assessing pollutant distribution, aiding environmental protection and marine pollution management. FTLE-based LCS has also contributed significantly to understanding ecological interactions and biodiversity in response to environmental issues. This review identifies pressing challenges and future directions of FTLE-based LCS. Among these are the influences of external factors such as river discharges, ice formations, and human activities on ocean currents, which complicate the analysis of ocean fluid dynamics. While 2D FTLE methods have proven effective, their limitations in capturing the full scope of oceanic phenomena, especially in 3D environments, are evident. The advent of 3D LCS analysis has marked progress, yet computational demands and data quality requirements pose significant hurdles. Moreover, LCS extracted from FTLE fields involves establishing an empirical threshold that introduces considerable variability due to human judgement. Future efforts should focus on enhancing computational techniques for 3D analyses, integrating FTLE and LCS into broader environmental models, and leveraging machine learning to standardize LCS detection.

Summary: Sunitinib, a primary treatment for clear cell renal cell carcinoma (ccRCC), frequently encounters the challenge of resistance development. Metabolic reprogramming, a characteristic change in ccRCC, is likely linked to this resistance. Our research revealed a notable decrease in the expression of the key metabolic gene ABAT in ccRCC, which contributed to diminished sensitivity to sunitinib. Downregulation of ABAT led to an increase in the intracellular level of gamma-aminobutyric acid (GABA), triggering abnormal activation of the G-protein-coupled receptor GABA-B. This activation resulted in increased transactivation of the tyrosine kinase receptors SYK and LYN, thereby reducing the antitumor and antiangiogenic properties of sunitinib. However, the application of SYK and LYN inhibitors successfully inhibited this effect. The transactivation of SYK and LYN caused resistance to the antiangiogenic effects of sunitinib through the upregulation of PGF protein levels. Furthermore, the combined application of an LYN inhibitor with sunitinib has been shown to enhance therapeutic efficacy.

Last-mile delivery plays a crucial role in improving the service level of express delivery, as it involves direct contact with customers. Providing personalized last-mile delivery services is an important means of improving customer satisfaction. Massive consumer data makes it possible to mine customers’ personalized logistics preferences. The paper studies the vehicle routing problem in last-mile delivery considering customers' preferences. The paper first quantifies customers' preferences for delivery time, location, and mode, and obtains preference probabilities based on historical data. Then, an optimization considering customer satisfaction and enterprise delivery costs is established, and a vehicle routing problem model considering customer preferences is proposed. To solve the problem, we designed an adaptive large neighborhood search (ALNS) algorithm with virtual delivery points to solve the problem and proposed specific destroy and repair operators. Through the case analysis of an express delivery company, this article provides the optimal routs and analyzes the customer preferences on each route. In addition, this article explores the impact of the customer preference constraint and complaint constraint on cost and gives the appropriate customer preference constraint and complaint rate constraint from the perspective of cost-saving.

Abstract Background Prostate cancer is a common solid tumor that affects a significant number of men worldwide. Conventional androgen deprivation therapy (ADT) increases the risk of developing castration-resistant prostate cancer (CRPC). Effective clinical management of patients with CRPC is challenging due to the limited understanding. Methods In this study, transcriptomic and metabolomic profiles of androgen-dependent prostate cancer cell line LNCaP and the androgen-independent cells developed from LNCaP cells (LNCaP-ADR) were investigated using RNA-sequencing and LC-MS/MS, respectively. The differentially expressed genes and metabolites were analyzed, and integrative analysis of transcriptomic and metabolomic data was further conducted to obtain a comprehensive understanding of the metabolic characteristics in LNCaP-ADR cells. Quantitative real-time PCR (QPCR) was employed to ascertain the mRNA expression levels of the selected differentially expressed genes. Results The arginine and proline metabolism pathway was identified as a commonly altered pathway at both the transcriptional and metabolic levels. In the LNCaP-ADR cells, significant upregulation was observed for metabolites including 5-Aminopentanoic acid, L-Arginine, L-Glutamic acid, N-Acetyl-L-alanine, and Pyrrole-2-carboxylic acid at the metabolic level. At the transcriptional level, MAOA, ALDH3A2, ALDH2, ARG1, CKMT2, and CNDP1 were found to be significantly upregulated in the LNCaP-ADR cells. Gene set enrichment analysis (GSEA) identified various enriched gene sets in the LNCaP-ADR cells, encompassing inflammatory response, 9plus2 motile cilium, motile cilium, ciliary plasm, cilium or flagellum-dependent cell motility, cilium movement, cilium, response to endoplasmic reticulum stress, PTEN DN.V1 DN, SRC UP.V1 UP, IL15 UP.V1 DN, RB DN.V1 DN, AKT UP MTOR DN.V1 UP, VEGF A UP.V1 UP, and KRAS.LUNG.BREAST UP.V1 UP. Conclusions These findings highlight the substantial association between the arginine and proline metabolism pathway and CRPC, emphasizing the need to prioritize strategies that target dysregulated metabolites and differentially expressed genes as essential interventions in the clinical management of CRPC.

BackgroundThis study aimed to employ plasma proteomics to investigate the molecular changes, pathway alterations, and potential novel biochemical markers associated with balloon pulmonary angioplasty (BPA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH).MethodsPre- and post-BPA plasma samples from five CTEPH patients in the PRACTICE study were analyzed to identify differentially expressed proteins. Proteomic and bioinformatics analyses were conducted, and the identified proteins were further validated using ELISA assays in a separate cohort of the same study. Correlation and multivariate regression analyses were performed to investigate the associations between these differentially expressed proteins and clinical parameters.ResultsSignificantly higher serum levels of asialoglycoprotein receptor 2 (ASGR2) were detected in 5 CTEPH patients compared to those in healthy individuals but decreased significantly after successful BPA procedures. The decrease in serum levels of ASGR2 after the completion of BPA procedures was further validated in a separate cohort of 48 patients with CTEPH [0.70 (0.51, 1.11) ng/mL vs. 0.38 (0.27, 0.59) ng/mL, P < 0.001]. Significant associations were found between the pre-BPA ASGR2 level and clinical parameters, including neutrophil percentage (R = 0.285, P < 0.05), platelet (PLT) count (R = 0.386, P < 0.05), and high-density lipoprotein cholesterol (HDL-C) before BPA (R = -0.285, P < 0.05). Significant associations were detected between post-BPA serum ASGR2 levels and lymphocyte percentage (LYM%) (R = 0.306, P < 0.05), neutrophil-to-lymphocyte ratio (R = -0.294, P < 0.05), and pulmonary vascular resistance after BPA (R = -0.35, P < 0.05). Multivariate stepwise regression analysis revealed that pre-BPA ASGR2 levels were associated with HDL-C and PLT count (both P < 0.001), while post-BPA ASGR2 levels were associated with LYM% (P < 0.05).ConclusionSerum levels of ASGR2 may be a biomarker for the effectiveness of BPA treatment in CTEPH patients. The pre-BPA serum level of ASGR2 in CTEPH patients was associated with HDL-C and the PLT count. The post-BPA serum level of ASGR2 was correlated with the LYM%, which may reflect aspects of immune and inflammatory status.

Efficient obstacle-avoidance path planning is critical for orchards with numerous irregular obstacles. This paper presents a continuous bidirectional Quick-RRT* (CBQ-RRT*) algorithm based on the bidirectional RRT (Bi-RRT) and Quick-RRT* algorithms and proposes an expansion cost function that evaluates path smoothness and length to overcome the limitations of the Quick-RRT* algorithm for non-holonomic mobile robot applications. To improve the zigzag between dual trees caused by the dual-tree expansion of the Bi-RRT algorithm, CBQ-RRT* proposes the CreateConnectNode optimization method, which effectively solves the path smoothness problem at the junction of dual trees. Simulations conducted on the ROS platform showed that the CBQ-RRT* outperformed the unidirectional Quick-RRT* in terms of efficiency for various orchard layouts and terrain conditions. Compared to Bi-RRT*, CBQ-RRT* reduced the average path length and maximum heading angle by 8.5% and 21.7%, respectively. In addition, field tests confirmed the superior performance of the CBQ-RRT*, as evidenced by an average maximum path lateral error of 0.334 m, a significant improvement over Bi-RRT* and Quick-RRT*. These improvements demonstrate the effectiveness of the CBQ-RRT* in complex orchard environments.

Abstract To analyze the clinical significance of MATN1-AS1 as ceRNA of Mir-200b in the tissues and serum of cervical cancer patients. A total of 50 patients with cervical cancer admitted to our hospital from March 2018 to March 2019 were selected as the research objects. All patients underwent surgical resection of cancer tissues in our hospital, and cervical cancer tissues and adjacent tissues more than 2 cm away from the edge of cancer tissues were retained. Patients with cervical cancer were selected as the research group, and 50 patients with benign uterine lesions were selected as the control group. The expressions of MATN1-AS1 and Mir-200b in cervical cancer tissues and serum were detected by real-time PCR, and the correlation between MATN1-AS1 and Mir-200b was analyzed. The relationship between MATN1-AS1, Mir-200b and clinical features was analyzed, and the 3-year survival rate of cervical cancer patients was analyzed. Compared with adjacent tissues, the relative expression levels of MATN1-AS1 and Mir-200b in cancer tissues were significantly increased (P

Lithium-ion battery energy storage systems are rapidly gaining widespread adoption in power systems across the globe. This trend is primarily driven by their recognition as a key enabler for reducing carbon emissions, advancing digitalization, and making electricity grids more accessible to a broader population. In the present study, we investigated the dynamic behavior of lithium-ion batteries during the charging and discharging processes, with a focus on the impact of terminal voltages and rate parameters on the state of charge (SOC). Through modeling and simulations, the results show that higher terminal charging voltages lead to a faster SOC increase, making them advantageous for applications requiring rapid charging. However, large values of voltage-sensitive coefficients and energy transfer coefficients were found to have drawbacks, including increased battery degradation, overheating, and wasted energy. Moreover, practical considerations highlighted the trade-off between fast charging and time efficiency, with charging times ranging from 8 to 16 min for different rates and SOC levels. On the discharging side, we found that varying the terminal discharging voltage allowed for controlled discharging rates and adjustments to SOC levels. Lower sensitivity coefficients resulted in more stable voltage during discharging, which is beneficial for applications requiring a steady power supply. However, high discharging rates and sensitivity coefficients led to over-discharging, reducing battery life and causing damage. These new findings could provide valuable insights for optimizing the performance of lithium-ion batteries in various applications.

IntroductionThe type VI secretion system (T6SS) is a crucial virulence factor in the nosocomial pathogen Acinetobacter baumannii. However, its association with drug resistance is less well known. Notably, the roles that different T6SS components play in the process of antimicrobial resistance, as well as in virulence, have not been systematically revealed.MethodsThe importance of three representative T6SS core genes involved in the drug resistance and virulence of A. baumannii, namely, tssB, tssD (hcp), and tssM was elucidated.ResultsA higher ratio of the three core genes was detected in drug-resistant strains than in susceptible strains among our 114 A. baumannii clinical isolates. Upon deletion of tssB in AB795639, increased antimicrobial resistance to cefuroxime and ceftriaxone was observed, alongside reduced resistance to gentamicin. The ΔtssD mutant showed decreased resistance to ciprofloxacin, norfloxacin, ofloxacin, tetracycline, and doxycycline, but increased resistance to tobramycin and streptomycin. The tssM-lacking mutant showed an increased sensitivity to ofloxacin, polymyxin B, and furazolidone. In addition, a significant reduction in biofilm formation was observed only with the ΔtssM mutant. Moreover, the ΔtssM strain, followed by the ΔtssD mutant, showed decreased survival in human serum, with attenuated competition with Escherichia coli and impaired lethality in Galleria mellonella.DiscussionThe above results suggest that T6SS plays an important role, participating in the antibiotic resistance of A. baumannii, especially in terms of intrinsic resistance. Meanwhile, tssM and tssD contribute to bacterial virulence to a greater degree, with tssM being associated with greater importance.

Objectives: To determine the clinical significance of Ro52 protein/tripartite motif-containing 21 antibody and specific antinuclear antibody patterns using indirect immunofluorescence technique. Method: The retrospective study was conducted at the clinical laboratory of the First Affiliated Hospital of Chongqing Medical University, China, and comprised data from January 2017 to December 2021 of patients who underwent antinuclear antibody and anti-extractable nuclear antigen antibody detection. Inpatients with Ro52 antibody-positive status were taken as the cases, while anti-Ro52 negative patients with clear clinical diagnosis were taken as the controls. Data was analysed using SPSS 19. Results: There were 1802 cases and 1211 controls. Positive Ro52 showed significantly greater frequency in patients with primary Sjogren’s syndrome, systemic lupus erythematosus, inflammatory myositis, dry eyes and interstitial lung disease (p

The integrated Vegetation-Activated Sludge Process (V-ASP) has emerged as a promising solution for decentralized wastewater treatment, offering a unique combination of landscape vegetation with the traditional Anaerobic-Anoxic-Oxic process (AAO). The experiments displayed that V-ASP consistently demonstrated remarkable treatment performance, maintaining stable removal efficiency exceeding 90 % for COD, NH4+-N, and TP. The vegetation growth is helpful for the removal of pollutants and the microbial community in the allocated vegetation root, while the bulk suspended sludge was changed significantly by using PCR test. To comprehensively evaluate the environmental footprint of V-ASP, a Life Cycle Assessment (LCA) was conducted. The mass balance calculation containing wastewater treatment performance, energy consumption, vegetation growth behavior, greenhouse gas (GHG) emissions, treated water, and sludge discharge was carried out to establish the life cycle inventories (LCI). SimaPro 9.0 software and the ReCiPe (H) midpoint impact assessment method were employed, which revealed that the V-ASP system boasts low GHG emissions and freshwater eutrophication potential compared to the traditional AAO process. In essence, this study provides a comprehensive understanding of the V-ASP system, especially the environmental impacts, guiding its potential for sustainable decentralized sewage treatment applications.

Gradient nanostructure was introduced to enhance the strength and ductility via deformation incompatibility accommodated by geometrical necessary dislocations for most metallic materials recently. However, few intensive researches were carried out to investigate the effect of gradient structure on the deformation twin evolution and resulting performance improvements. In the present paper, we produced gradient-structured AZ31 Mg alloy with fine-grain layers, parallel twin laminates and a coarse-grain core from two upmost surfaces to the center of plate. Surprisingly, this architected Mg alloy exhibited simultaneous enhancement of strength and ductility. Subsequent microstructural observations demonstrated that abundant twin-twin interactions resulting from higher strength and multi-axial stress state could make great contributions to the increase of work-hardening capability. This was further proved by the measurement of full-field strain evolution during the plastic deformation. Such a design strategy may provide a new path for producing advanced structure materials in which the deformation twinning works as one of the dominant plasticity mechanisms.

Abstract A patented strain of Bacillus amyloliquefaciens C-1 in our laboratory could produce functional sodium selenite (Na2SeO3) under optimized fermentation conditions. With the strong stress resistance and abundant secondary metabolites, C-1 showed potential to be developed as selenium-enriched postbiotics. C-1 has the ability to synthesize SeNPs when incubated with 100 μg/ml Na2SeO3 for 30 h at 30 °C aerobically with 10% seeds-culture. The transformation rate from Na2SeO3 into SeNPs reached to 55.51%. After selenium enrichment, there were no significant morphology changes in C-1 cells but obvious SeNPs accumulated inside of cells, observed by scanning electron microscope and transmission electron microscope, verified by energy dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy. SeNPs had antioxidant activity in radical scavenge of superoxide (O2 −), Hydroxyl radical (OH−) and 1,1-diphenyl-2-picryl-hydrazine (DPPH), where scavenging ability of OH− is the highest. Selenium-enriched C-1 had obvious anti-inflammatory effect in protecting integrity of Caco-2 cell membrane destroyed by S. typhimurium; it could preventing inflammatory damage in Caco-2 stressed by 200 μM H2O2 for 4 h, with significantly reduced expression of IL-8 (1.687 vs. 3.487, P = 0.01), IL-1β (1.031 vs. 5.000, P

A grid blackout is an intractable problem with serious economic consequences in many developing countries. Although it has been proven that microgrids (MGs) are capable of solving this problem, the uncertainties regarding when and for how long blackouts occur lead to extreme difficulties in the design and operation of the related MGs. This paper addresses the optimal design problem of the MGs considering the uncertainties of the blackout starting time and duration utilizing the kernel density estimator method. Additionally, uncertainties in solar irradiance and ambient temperature are also considered. For that, chance-constrained optimization is employed to design residential and industrial PV-based MGs. The proposed approach aims to minimize the expected value of the levelized cost of energy (LCOE), where the restriction of the annual total loss of power supply (TLPS) is addressed as a chance constraint. The results show that blackout uncertainties have a considerable effect on calculating the size of the MG’s components, especially the battery bank size. Additionally, it is proven that considering the uncertainties of the input parameters leads to an accurate estimation for the LCOE and increases the MG reliability level.

Sandwich structures are often used as protective structures on ships. To further improve the energy-absorbing characteristics of traditional honeycomb sandwich structures, an energy-absorbing mechanism is proposed based on the gradient folding deformation of lotus root nodes and a leafy stem vein homogenizing load mechanism. A honeycomb sandwich structure is then designed that combines lotus root nodes and leafy stem veins. Four types of peak-nest structures, traditional cellular structure (TCS), lotus root honeycomb structure (LRHS), leaf vein honeycomb structure (LVHS), and lotus root vein combined honeycomb structure (LRVHS), were prepared using 3D printing technology. The deformation modes and energy absorption characteristics of the four honeycomb structures under quasistatic action were investigated using a combination of experimental and simulation methods. It was found that the coupling design improved the energy absorption in the structural platform region of the LRHS by 51.4% compared to that of the TCS due to its mechanical mechanism of helical twisting and deformation. The leaf vein design was found to enhance the peak stress of the structure, resulting in a 4.84% increase in the peak stress of the LVHS compared to that of the TCS. The effects of the number, thickness, and position of the leaf vein plates on the honeycomb structure were further explored. The greatest structural SEA effect of 1.28 J/g was observed when the number of leaf vein plates was four. The highest SEA of 1.36 J/g was achieved with a leaf vein plate thickness of 0.6 mm, representing a 7.3% improvement compared to that of the 0.2 mm thickness. These findings may provide valuable insights into the design of lightweight honeycomb sandwich structures with high specific energy absorption.

Abstract Background The incidence of pediatric inflammatory bowel disease (PIBD) has been steadily increasing globally. Delayed diagnosis of PIBD increases the risk of complications and contributes to growth retardation. To improve long-term outcomes, there is a pressing need to identify novel markers for early diagnosis of PIBD. Methods The candidate biomarkers for PIBD were identified from the GSE117993 dataset by two machine learning algorithms, namely LASSO and mSVM-RFE, and externally validated in the GSE126124 dataset and our PIBD cohort. The role of ficolin-1 (FCN1) in PIBD and its association with macrophage infiltration was investigated using the CIBERSORT method and enrichment analysis of the single-cell dataset GSE121380, and further validated using immunoblotting, qRT-PCR, and immunostaining in colon biopsies from PIBD patients, a juvenile murine DSS-induced colitis model, and THP-1-derived macrophages. Results FCN1 showed great diagnostic performance for PIBD in an independent clinical cohort with the AUC of 0.986. FCN1 expression was upregulated in both colorectal biopsies and blood samples from PIBD patients. Functionally, FCN1 was associated with immune-related processes in the colonic mucosa of PIBD patients, and correlated with increased proinflammatory M1 macrophage infiltration. Furthermore, single-cell transcriptome analysis and immunostaining revealed that FCN1 was almost exclusively expressed in macrophages infiltrating the colonic mucosa of PIBD patients, and these FCN1+ macrophages were related to hyper-inflammation. Notably, proinflammatory M1 macrophages derived from THP-1 expressed high levels of FCN1 and IL-1β, and FCN1 overexpression in THP-1-derived macrophages strongly promoted LPS-induced activation of the proinflammatory cytokine IL-1β via the NLRP3-caspase-1 axis. Conclusions FCN1 is a novel and promising diagnostic biomarker for PIBD. FCN1+ macrophages enriched in the colonic mucosa of PIBD exhibit proinflammatory phenotypes, and FCN1 promotes IL-1β maturation in macrophages via the NLRP3-caspase-1 axis.

IntroductionAn extended-spectrum beta-lactamase (ESBL)-hypervirulent Klebsiella pneumoniae (HvKP) strain HKE9 was isolated from the blood in an outpatient.MethodsThe effect of the global regulatory factor RpoS on antimicrobial resistance, pathogenicity, and environmental adaptability was elucidated.ResultsHKE9 is a novel ST3355 (K20/O2a) hypervirulent strain with a positive string test and resistant to cephems except cefotetan. It has a genome size of 5.6M, including two plasmids. CTX-M-15 was found in plasmid 2, and only ompk37 was found in the chromosome. HKE9 could produce bacterial siderophores, and genes of enterobactin, yersiniabactin, aerobactin, and salmochelin have been retrieved in the genome. As a global regulatory factor, knockout of rpoS did not change antimicrobial resistance or hemolytic phenotype while increasing the virulence to Galleria mellonella larvae and showing higher viscosity. Moreover, rpoS knockout can increase bacterial competitiveness and cell adhesion ability. Interestingly, HKE9-M-rpoS decreased resistance to acidic pH, high osmotic pressure, heat shock, and ultraviolet and became sensitive to disinfectants (H2O2, alcohol, and sodium hypochlorite). Although there were 13 Type 6 secretion system (T6SS) core genes divided into two segments with tle1 between segments in the chromosome, transcriptomic analysis showed that rpoS negatively regulated T4SS located on plasmid 2, type 1, and type 3 fimbriae and positively regulate genes responsible for acidic response, hyperosmotic pressure, heat shock, oxidative stress, alcohol and hypochlorous acid metabolism, and quorum sensing.DiscussionHere, this novel ST3355 ESBL-HvKP strain HKE9 may spread via various clonal types. The important regulation effect of rpoS is the enhanced tolerance and resistance to environmental stress and disinfectants, which may be at the cost of reducing virulence and regulated by T4SS.

Abstract Sepsis‐induced muscle atrophy often increases morbidity and mortality in intensive care unit (ICU) patients, yet neither therapeutic target nor optimal animal model is available for this disease. Here, by modifying the surgical strategy of cecal ligation and puncture (CLP), a novel sepsis pig model is created that for the first time recapitulates the whole course of sepsis in humans. With this model and sepsis patients, increased levels of the transcription factor zinc finger BED‐type containing 6 (ZBED6) in skeletal muscle are shown. Protection against sepsis‐induced muscle wasting in ZBED6‐deficient pigs is further demonstrated. Mechanistically, integrated analysis of RNA‐seq and ChIP‐seq reveals dedicator of cytokinesis 3 (DOCK3) as the direct target of ZBED6. In septic ZBED6‐deficient pigs, DOCK3 expression is increased in skeletal muscle and myocytes, activating the RAC1/PI3K/AKT pathway and protecting against sepsis‐induced muscle wasting. Conversely, opposite gene expression patterns and exacerbated muscle wasting are observed in septic ZBED6‐overexpressing myotubes. Notably, sepsis patients show increased ZBED6 expression along with reduced DOCK3 and downregulated RAC1/PI3K/AKT pathway. These findings suggest that ZBED6 is a potential therapeutic target for sepsis‐induced muscle atrophy, and the established sepsis pig model is a valuable tool for understanding sepsis pathogenesis and developing its therapeutics.

BackgroundDifferences exist between high- and low-risk endometrial cancer (EC) in terms of whether lymph node dissection is performed. Factors such as tumor grade, myometrial invasion (MDI), and lymphovascular space invasion (LVSI) in the European Society for Medical Oncology (ESMO), European SocieTy for Radiotherapy & Oncology (ESTRO) and European Society of Gynaecological Oncology (ESGO) guidelines risk classification can often only be accurately assessed postoperatively. The aim of our study was to estimate the risk classification of patients with endometrial endometrioid adenocarcinoma before surgery and offer individualized treatment plans based on their risk classification.MethodsClinical information and last preoperative pelvic magnetic resonance imaging (MRI) of patients with postoperative pathologically determined endometrial endometrioid adenocarcinoma were collected retrospectively. The region of interest (ROI) was subsequently plotted in T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and diffusion-weighted imaging (DWI) MRI scans, and the traditional radiomics features and deep-learning image features were extracted. A final radiomics nomogram model integrating traditional radiomics features, deep learning image features, and clinical information was constructed to distinguish between low- and high-risk patients (based on the 2020 ESMO-ESGO-ESTRO guidelines). The efficacy of the model was evaluated in the training and validation sets of the model.ResultsWe finally included 168 patients from January 1, 2020 to July 29, 2021, of which 95 patients in 2021 were classified as the training set and 73 patients in 2020 were classified as the validation set. In the training set, the area under the curve (AUC) of the radiomics nomogram was 0.923 (95%CI: 0.865–0.980) and in the validation set, the AUC of the radiomics nomogram was 0.842 (95%CI: 0.762–0.923). The nomogram had better predictions than both the traditional radiomics model and the deep-learning radiomics model.ConclusionMRI-based radiomics models can be useful for preoperative risk classification of patients with endometrial endometrioid adenocarcinoma.

Traditional binary combinational logic circuits are generally obtained by cascading multiple basic logic gate circuits, using more components and complicated wiring. In contrast to the binary logic circuit design in this method, ternary combinational logic circuit implementation is more complicated. In this paper, a ternary circuit design method that does not require cascading basic ternary logic gates is proposed based on a tri-valued memristor, which can directly realize specific logic functions through a series connection of memristors. The ternary encoder, ternary decoder, ternary comparator, and ternary data selector are implemented by this method, and the effectiveness of the circuits is verified by LTspice simulations.