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In the emerging 5G and beyond 5G (B5G) era, the spotlight is sharply focused on the power amplifier, a critical component with stringent specification requirements that dictates the performance of the transmitter. The gallium nitride (GaN) device, with its superior inherent properties, is surfacing as a front-runner for power amplifier applications. The increasing demand for high frequency, high linearity, and cost-effective GaN power amplifiers is driven by anticipated traffic surges and the need for extensive 5G deployment. This paper offers a thorough review and future perspective on research developments in RF GaN device technology. It encompasses critical issues in advanced device and circuit technology, with a focus on high frequency, high linearity, cost-effective GaN-on-Si high electron mobility transistors (HEMTs), and compact modeling. This work aims to serve as a guide for the utilization of GaN HEMTs in 5G communication applications.

Abstract We investigated the correlation between Triglyceride-glucose (TyG) index and cardiovascular disease (CVD) mortality in type 2 diabetes mellitus (T2DM) population across different obesity classications using a cohort study. We analyzed 7867 T2DM participants from the National Health and Nutrition Examination Survey 1999–2018, categorizing them into obese or non-obese group by body mass index (BMI) and waist circumference (WC). Cox regression models were used to estimate the correlation between TyG index and CVD mortality risk, comparing the results across the two obesity classifications. Over a 9.1-year follow-up, 691 CVD deaths occurred. Among non-obese T2DM participants (BMI-defined), the hazard ration for CVD mortality was 1.73 in the fourth quartile group of TyG index compared with the first quartile group. Conversely, among obese T2DM participants (WC-defined), the fourth quartile group of TyG index held a 1.51-fold risk of CVD mortality compared with the first quartile group. The association between obesity and higher CVD risk was observed in WC-defined obesity but not in BMI-defined obesity. A totally opposite relationship appeared between TyG index and CVD mortality based on how obesity was defined using BMI or WC in the T2DM participants, suggesting a reevaluation of BMI’s accuracy in predicting mortality risk.

Abstract Iron alloys, including steels and magnetic functional materials, are widely used in capital construction, manufacturing, electromagnetic technology, etc. However, they face the long-standing challenge of high coefficient of thermal expansion (CTE), limiting the applications in high-precision fields. This work proposes a strategy involving the in-situ formation of a nano-scale lamellar/labyrinthine negative thermal expansion (NTE) phase within the iron matrix to tackle this problem. For example, a model alloy, Fe-Zr10-Nb6, was synthesized and its CTE is reduced to approximately half of the iron matrix. Meanwhile, the alloy possesses a strength-plasticity combination of 1.5 GPa (compressive strength) and 17.5% (ultimate strain), which outperforms other low thermal expansion (LTE) metallic materials. The magnetovolume effect of the NTE phase is deemed to counteract the positive thermal expansion in iron. The high stress-carrying hard NTE phase and the tough matrix synergistically contribute to the high mechanical properties. The interaction between the slip of lamellar microstructure and the slip-hindering of labyrinthine microstructure further enhances the strength-plasticity combination. This work shows the promise of offering a method to produce LTE iron alloys with high mechanical properties.

Abstract Objective Researchers have proposed a novel surgical treatment for moderate diabetic foot ulcer: tibial periosteal distraction (TPD) which could improve affected limb microcirculation. We aimed to describe the method and therapeutic effects of this technique. Methods We provided a technical guide to perform TPD surgery for the treatment of moderate diabetic foot ulcer of who had been treated in our department. The demographic information had been collected at the time of their admission. The patients were followed up at 3, 6, and 12 months after the operation with the ulcer area, skin temperature of the medial malleolus, transcutaneous oxygen pressure of the medial malleolus, ankle brachial index, dorsalis pedis artery pulsation, 12 item short form survey quality of life scale score, and visual analogue scale. Results A total of 35 patients with type 2 diabetes were included in this study, including 19 males and 16 females, with an average age of 62.49 ± 10.34 years and a maximum age of 87 years. The ulcers of all patients were cured, and the average healing time of ulcers was 8.09 ± 2.28 weeks, with no associated complications. The microcirculation indexes of the affected foot were significantly improved (p

Abstract Background The traditional classification for lateral malleolus fracture has its limitations. In this study, we introduced a three-dimensional (3D) fracture mapping technique using computed tomography (CT) data to assess fracture line distributions and their impact on patient outcomes, offering a refined classification approach. Methods Retrospectively, we analysed 97 patients who underwent lateral malleolus fracture surgeries (2014–2019), using CT Digital Imaging and Communications in Medicine data to create 3D models and fracture maps. This methodology refined the Danis–Weber classification and enabled the assessment of fracture severity and syndesmotic stability through clinical scoring. Results Danis–Weber type B fractures were predominant (83.5%), showing a distinct pattern. Subtypes were identified based on the bone fragments that are clinically associated with increased injury severity but did not significantly affect syndesmotic stability or prognostic scores. Conclusion The 3D fracture map provides a detailed view of fracture characteristics, enabling precise classification. In type B fractures, bone fragments indicating higher trauma do not predict clinical outcomes, thereby supporting personalised surgical planning.

In this study, toughening of WC-Co composite prepared by amorphous-crystallization method was investigated. Co-rich nanoparticles, a Co(W,C) solid solution, were incorporated into the WC matrix through the process integrating crystallization of amorphous Co2W4C powder and its in-situ reaction with carbon. The microstructural evolution of the ceramic-metal composite during fabrication was studied in detail. Owing to the interactions between Co-rich nanoparticles coherent with the WC matrix and the dislocations and stacking faults inside WC grains, the composite exhibited high hardness and strength combined with exceptional fracture toughness. The mechanisms for the synergistic improvement of mechanical properties of the composite were disclosed.

After metallographic etching, unetched white bright bands (WBB) are evident in the SA508-3/52(M) dissimilar metal weld joints. The WBBs in both joint without a buttering layer (JWOBL) and joint with a buttering layer (JWBL) are composed of austenite, with no presence of martensite. A pronounced elemental gradient is present within the WBB. The width of the WBB in JWOBL exceeds that in JWBL. Owing to differences in the welding thermal cycling process, precipitates are present in the WBB of JWOBL, whereas JWBL lacks such precipitates. These precipitates hinder dislocation movement and assist in the nucleation and growth of helium bubbles. Consequently, the nanoindentation hardness and helium bubble number density of the WBB in JWOBL are significantly higher than those in JWBL. Irradiation damage, including helium bubbles, induces irradiation hardening of the joints. At elevated irradiation temperatures, however, the extent of irradiation hardening diminishes.

Laser scribing effectively reduces the energy loss of grain-oriented silicon steel in alternating and pulsating magnetic fields. This study focuses on the 27Q120 material, analyzes the macroscopic surface morphology and iron loss variations of grain-oriented silicon steel under the influence of two types of laser spots (circular spots without the application of a diffractive optical element (DOE) and rectangular spots formed by a DOE), laser power (600 W–2400 W), and scribing spacing (3.5 mm–7.5 mm) as process parameters. The relationship between magnetic domain width, stress, and iron loss was analyzed. The result shows that the iron loss improvement rates (β) achieved with circular and rectangular spot scribing were 16.054% and 17.116%, respectively. Corresponding magnetic domain widths were 0.17754 mm and 0.1636 mm, with hysteresis losses of 0.5114 W/kg and 0.5033 W/kg, respectively. Under the same laser power and scribing spacing, a lower energy density significantly reduced the damage to the surface macroscopic morphology by the laser, leading to improved iron loss. Furthermore, the iron loss of grain-oriented steel is positively correlated with the width of magnetic domains and negatively correlated with compressive stress.

Controlled-release urea (CRU) releases nitrogen (N) at the same pace that rice takes it up, which can effectively improve N use efficiency, increase rice yield and improve rice quality. However, few studies have described the effects of CRU application on the photosynthetic rate and endogenous enzyme activities of rice. Accordingly, a two-year field trial was conducted with a total of seven treatments: CK, no N fertilizer; BBF, regular blended fertilizer; RBBF, 20% N-reduced regular blended fertilizer; CRF1, 70% CRU+30% regular urea one-time base application; CRF2, 60% CRU+40% regular urea one-time base application; RCRF1, CRF1 treatment with 20% N reduction; and RCRF2, CRF2 treatment with 20% N reduction. Each treatment was conducted in triplicate. The results showed that the N recovery efficiency (NRE) of the controlled-release bulk blending fertilizer (CRBBF) treatments was significantly greater over the two years. There were significant yield increases of 4.1–5.9% under the CRF1 treatment and 5.6–7.6% under the CRF2 treatment compared to the BBF treatment, but the differences between the reduced-N treatments RBBF and RCRF2 were not significant. Photosynthetic rates under the CRF1 and CRF2 treatments were significantly higher than under the other treatments, and they had significantly greater RuBPCase, RuBisCO, glutamate synthase (GOGAT) and glutamine synthetase (GS) enzyme activities. Additionally, the soil NH4+-N and NO3−-N contents under the CRBBF treatments were significantly higher at the late growth stage of rice, which was more in-line with the fertilizer requirements of rice throughout the reproductive period. CRBBF also led to some improvement in rice quality. Compared with the BBF and RBBF treatments, the protein contents under the CRBBF treatments were reduced but the milling, appearance, eating and cooking qualities of the rice were improved. These results showed that the application of CRBBF can improve the NRE, photosynthetic rate and endogenous enzyme activities of rice, ensuring sufficient N nutrition and photosynthetic material production during rice growth and thereby achieving improved rice yield and quality.

Abstract The effect of particle packing height (10, 30, 50, 70 mm) on the yield and composition of oil shale pyrolysis products is investigated. The results show that the oil yield could decrease 1.0% and the noncondensable gases yield could increase 0.5% as the oil shale packing height increased from 10 to 70 mm. The main hydrocarbon gases are C1–C6 gases, and the increase of packing bed height could decrease the relative content ratio of alkanes to alkenes in hydrocarbon gases. The primary components of the derived oil are aliphatic compounds, aromatic compounds, and compounds containing heteroatoms in the carbon atoms range of C6–C28. And the hydrogen type of shale oil is mainly composed of methylene groups (about 70%) with longer alkyl chains, and CH3 in aromatics, cycloalkanes, and alkanes. The chemical composition and hydrogen type have certain regularity changes with the changing of packing height, attributing to the effect of temperature gradients between surface and center of packing bed, and the diffusing time of products through the packing bed.

Abstract Background Blood–brain barrier (BBB) dysfunction has been viewed as a potential underlying mechanism of neurodegenerative disorders, possibly involved in the pathogenesis and progression of Alzheimer’s disease (AD). However, a relation between BBB dysfunction and dementia with Lewy bodies (DLB) has yet to be systematically investigated. Given the overlapping clinical features and neuropathology of AD and DLB, we sought to evaluate BBB permeability in the context of DLB and determine its association with plasma amyloid-β (Aβ) using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Methods For this prospective study, we examined healthy controls (n = 24, HC group) and patients diagnosed with AD (n = 29) or DLB (n = 20) between December 2020 and April 2022. Based on DCE-MRI studies, mean rates of contrast agent transfer from intra- to extravascular spaces (K trans) were calculated within regions of interest. Spearman’s correlation and multivariate linear regression were applied to analyze associations between K trans and specific clinical characteristics. Results In members of the DLB (vs HC) group, K trans values of cerebral cortex (p = 0.024), parietal lobe (p = 0.007), and occipital lobe (p = 0.014) were significantly higher; and K trans values of cerebral cortex (p = 0.041) and occipital lobe (p = 0.018) in the DLB group were significantly increased, relative to those of the AD group. All participants also showed increased K trans values of parietal ( $$\upbeta$$ β = 0.391; p = 0.001) and occipital ( $$\upbeta$$ β = 0.357; p = 0.002) lobes that were significantly associated with higher scores of the Clinical Dementia Rating, once adjusted for age and sex. Similarly, increased K trans values of cerebral cortex ( $$\upbeta$$ β = 0.285; p = 0.015), frontal lobe ( $$\upbeta$$ β = 0.237; p = 0.043), and parietal lobe ( $$\upbeta$$ β = 0.265; p = 0.024) were significantly linked to higher plasma Aβ1-42/Aβ1-40 ratios, after above adjustments. Conclusion BBB leakage is a common feature of DLB and possibly is even more severe than in the setting of AD for certain regions of the brain. BBB leakage appears to correlate with plasma Aβ1-42/Aβ1-40 ratio and dementia severity.

In this study, manganese oxide supported biochar (MBC) was used as a catalyst of periodate (PI) for the oxidative degradation of sulfonamide antibiotic sulfamethazine (SMZ). The degradation rate of 10 mg/L SMZ reached 99 % in 60 min in the MBC/PI system, and the optimal condition was pH 3.5, 0.12 g/L of MBC, and 0.17 mM of PI. Combined with quenching experiment and electron paramagnetic resonance (EPR) characterization, it was determined that the reactive oxygen species (ROS) participating in the reaction include iodate radical (IO3∙), singlet oxygen (1O2), and hydroxyl radical (∙OH). ROS, Mn(III) and electron transfer are three crucial SMZ removal mechanisms in MBC activated PI system, and the conversion process of reactive species was deduced. The manganese redox cycles, oxygen-containing functional groups on MBC surface, and BC-O-Mn(II) complex participated in reactive species production. The loading of manganese oxide increases the number of oxygen-containing functional group on the surface of BC, and BC-O-Mn(II) complex formation resulted in the higher catalytic activity compared with BC. Ten SMZ oxidative products and four transformation pathways was identified. This study provided an efficient and practical method to remove sulfonamide antibiotics and revealed its theoretical mechanism.

Abstract Solid bubbles have expanded the SERS assay toolbox, but their detection performance in biofluids is still hampered by the irrational design of the plasmonic sensing interface. A plasmonic bubble aggregate‐driven DNA‐encoded SERS assay is reported here that enables simultaneous, ultrasensitive, and specific detection of multiple miRNAs in blood samples for accurate cancer diagnosis. In this assay, the buoyancy of plasmonic bubbles allows them to self‐aggregate at a droplet apex for SERS reconfiguration, form single‐layer bubble aggregates with plasmonic nanogaps, and prevent the coffee ring effect during evaporation assembly. Furthermore, DNA‐encoded plasmonic bubbles seamlessly couple with dual‐color catalytic hybridization assembly to amplify the specific miRNA‐responsive Raman signal, and function as both an analyte concentrator and a Raman signal aggregator without external forces. Using these merits, this magnet‐free, portable assay achieves femtomolar dual‐miRNA quantitation with single‐base resolution, simultaneous miRNA detection across four cell lines, and accurate cancer diagnosis (AUC = 1) via analyzing 40 blood samples with machine learning, thus providing a promising tool for clinical diagnosis.

ABSTRACTConvex and concave hulls originating from computational geometry are widely applied in practice. For instance, to determine the boundaries of a geographical area within a group of cities, convex hulls can represent the approximate boundaries of the areas. Concave hulls can accurately describe the shape of the area. The traditional methods for solving two-dimensional convex hull problems include the Jarvis March algorithm and the Graham scanning algorithm. The K-nearest neighbours and alpha-shape methods are designed for solving the concave hull problem. Other than traditional algorithms, we consider using deep neural networks to handle the convex and concave hull problems. General neural networks cannot deal with the problem whose output is a variable-length sequence. Our study provides a machine-learning approach for solving the convex hull and concave hull problems. We combine the Pointer network (Ptr-Net) with the Transformer model and propose the DeepHullNet. The trained DeepHullNet can provide a feasible solution in the majority of cases. The experimental results show that DeepHullNet outperforms the original Ptr-Net regarding accuracy. Compared with traditional methods, DeepHullNet can generate a good solution quickly, and the running time is shortened by nearly 100 times based on GPU.

Abstract We aimed to build a deep learning-based pathomics model to predict the early recurrence of non-muscle-infiltrating bladder cancer (NMIBC) in this work. A total of 147 patients from Xuzhou Central Hospital were enrolled as the training cohort, and 63 patients from Suqian Affiliated Hospital of Xuzhou Medical University were enrolled as the test cohort. Based on two consecutive phases of patch level prediction and WSI-level predictione, we built a pathomics model, with the initial model developed in the training cohort and subjected to transfer learning, and then the test cohort was validated for generalization. The features extracted from the visualization model were used for model interpretation. After migration learning, the area under the receiver operating characteristic curve for the deep learning-based pathomics model in the test cohort was 0.860 (95% CI 0.752–0.969), with good agreement between the migration training cohort and the test cohort in predicting recurrence, and the predicted values matched well with the observed values, with p values of 0.667766 and 0.140233 for the Hosmer–Lemeshow test, respectively. The good clinical application was observed using a decision curve analysis method. We developed a deep learning-based pathomics model showed promising performance in predicting recurrence within one year in NMIBC patients. Including 10 state prediction NMIBC recurrence group pathology features be visualized, which may be used to facilitate personalized management of NMIBC patients to avoid ineffective or unnecessary treatment for the benefit of patients.

Abstract The cross beam of a mining linear vibrating screen is prone to cracking under long-term cyclic load. In order to accurately predict the fatigue life of the cracked cross beam, a coupled analysis method of vibration and crack propagation is proposed. A 2D dynamic model of the vibrating screen is established based on the finite element method, which is verified by the vibration test platform. The cracked Euler beam element is used to model the cracked cross beam. The effects of crack depth, amplitude of excitation force, frequency of excitation force, and crack location on the crack-tip stress intensity factor of the cracked cross beam are investigated in detail. In addition, an iterative method is proposed on the basis of the Paris model. The residual service life of the beam under different frequencies of excitation force, amplitudes of excitation force, spring stiffness, crack positions, and degrees of stiffness imbalance are discussed. The results demonstrate that the fatigue life of the beam increases as the frequency of excitation force and spring stiffness increase. The increase of the amplitude of excitation force and spring permanent deformation reduces the fatigue life. The conclusion obtained provide some theoretical guidance for the design and routine maintenance of mining linear vibrating screens.

Abstract Background Emerging evidence indicates the pivotal involvement of circular RNAs (circRNAs) in cancer initiation and progression. Understanding the functions and underlying mechanisms of circRNAs in tumor development holds promise for uncovering novel diagnostic indicators and therapeutic targets. In this study, our focus was to elucidate the function and regulatory mechanism of hsa-circ-0003764 in hepatocellular carcinoma (HCC). Methods A newly discovered hsa-circ-0003764 (circPTPN12) was identified from the circbase database. QRT-PCR analysis was utilized to assess the expression levels of hsa-circ-0003764 in both HCC tissues and cells. We conducted in vitro and in vivo experiments to examine the impact of circPTPN12 on the proliferation and apoptosis of HCC cells. Additionally, RNA-sequencing, RNA immunoprecipitation, biotin-coupled probe pull-down assays, and FISH were employed to confirm and establish the relationship between hsa-circ-0003764, PDLIM2, OTUD6B, P65, and ESRP1. Results In HCC, the downregulation of circPTPN12 was associated with an unfavorable prognosis. CircPTPN12 exhibited suppressive effects on the proliferation of HCC cells both in vitro and in vivo. Mechanistically, RNA sequencing assays unveiled the NF-κB signaling pathway as a targeted pathway of circPTPN12. Functionally, circPTPN12 was found to interact with the PDZ domain of PDLIM2, facilitating the ubiquitination of P65. Furthermore, circPTPN12 bolstered the assembly of the PDLIM2/OTUD6B complex by promoting the deubiquitination of PDLIM2. ESRP1 was identified to bind to pre-PTPN12, thereby fostering the generation of circPTPN12. Conclusions Collectively, our findings indicate the involvement of circPTPN12 in modulating PDLIM2 function, influencing HCC progression. The identified ESRP1/circPTPN12/PDLIM2/NF-κB axis shows promise as a novel therapeutic target in the context of HCC. Graphical Abstract

Abstract A dual-arm nursing robot can gently lift patients and transfer them between a bed and a wheelchair. With its lightweight design, high load-bearing capacity, and smooth surface, the coupled-drive joint is particularly well suited for these robots. However, the coupled nature of the joint disrupts the direct linear relationship between the input and output torques, posing challenges for dynamic modeling and practical applications. This study investigated the transmission mechanism of this joint and employed the Lagrangian method to construct a dynamic model of its internal dynamics. Building on this foundation, the Newton-Euler method was used to develop a dynamic model for the entire robotic arm. A continuously differentiable friction model was incorporated to reduce the vibrations caused by speed transitions to zero. An experimental method was designed to compensate for gravity, inertia, and modeling errors to identify the parameters of the friction model. This method establishes a mapping relationship between the friction force and motor current. In addition, a Fourier series-based excitation trajectory was developed to facilitate the identification of the dynamic model parameters of the robotic arm. Trajectory tracking experiments were conducted during the experimental validation phase, demonstrating the high accuracy of the dynamic model and the parameter identification method for the robotic arm. This study presents a dynamic modeling and parameter identification method for coupled-drive joint robotic arms, thereby establishing a foundation for motion control in humanoid nursing robots.

Bedding-parallel lamellated fractures are widely developed in shale in the 7th member of Triassic Yanchang Formation (hereinafter referred to as Chang 7) in the southwestern Ordos Basin, which holds significant importance for sweet spot selection, fracturing operations, and development planning. In this paper, based on the surface outcrop and core observations in the Qingcheng to Huachi region of the southwestern basin, combined with analysis and testing of organic matter content, mineral composition and fabric characteristics, the developmental characteristics of bedding-parallel lamellated fractures in different lithologies in the Chang 7 shale were identified, and the main controlling factors of fracture development were analyzed. Results show that the morphology and distribution of the bedding-parallel lamellated fractures are mainly controlled by the laminates, exhibiting characteristics such as continuous flatness, wavy bending and branching due to the different characteristics of the laminae. Sandstone bedding-parallel lamellated fractures are mostly distributed along the biotite laminae, with good continuity and large aperture, and are generally unfilled. Shale bedding-parallel lamellated fractures are most developed in black shale, mostly distributed along the bedding laminates composed of organic matter layers, with a few partially or completely filled by calcite and organic matter. The aperture is smaller than that of sandstone, but the density is higher. Bedding-parallel lamellated fractures are also controlled by organic matter content, lithology, mineral composition, and laminate structure. The sandstone bedding-parallel lamellated fractures are mainly controlled by the content of biotite and the laminates formed by it. When sandstone sorting is good and biotite content is high with a layered distribution, the degree of fracture development is high. As the density of the laminates increases, the degree of development of bedding-parallel lamellated fractures also increases. Shale bedding-parallel lamellated fractures mainly develop in organic matter laminates and tuffaceous laminates, and are controlled by organic matter content and mineral components. Fracture density increases first and then decreases with the density of the layers. Fracture density in thin laminates is higher than that in thick laminates.

Abstract Purpose To evaluate the difference in the diagnostic efficacy of 18F-PSMA-1007 PET/CT and pelvic MRI in primary prostate cancer, as well as the correlation between the two methods and histopathological parameters and serum PSA levels. Methods A total of 41 patients with suspected prostate cancer who underwent 18F-PSMA-1007 PET/CT imaging in our department from 2018 to 2023 were retrospectively collected. All patients underwent 18F-PSMA-1007 PET/CT and MRI scans. The sensitivity, PPV and diagnostic accuracy of MRI and 18F-PSMA-1007 PET/CT in the diagnosis of prostate cancer were calculated after comparing the results of MRI and 18F-PSMA-1007 PET/CT with biopsy. The Spearman test was used to calculate the correlation between 18F-PSMA-1007 PET/CT, MRI parameters, histopathological indicators, and serum PSA levels. Results Compared with histopathological results, the sensitivity, PPV and diagnostic accuracy of 18F-PSMA-1007 PET/CT in the diagnosis of prostate cancer were 95.1%, 100.0% and 95.1%, respectively. The sensitivity, PPV and diagnostic accuracy of MRI in the diagnosis of prostate cancer were 82.9%, 100.0% and 82.9%, respectively. There was a mild to moderately positive correlation between Gleason (Gs) score, Ki-67 index, serum PSA level and 18F-PSMA-1007 PET/CT parameters (p 0.05). Conclusion Compared with MRI, 18F-PSMA-1007 PET/CT has higher sensitivity and diagnostic accuracy in the detection of malignant prostate tumors. In addition, the Ki-67 index and AMACR (P504S) expression were only correlated with 18F-PSMA-1007 PET/CT parameters. Gs score and serum PSA level were correlated with 18F-PSMA-1007 PET/CT and MRI parameters. 18F-PSMA-1007 PET/CT examination can provide certain reference values for the clinical diagnosis, evaluation, and treatment of malignant prostate tumors.

This study investigates the correlation between insulin resistance and obesity indicators with sarcopenic obesity (SO) and develops diagnostic models. Utilizing the 1999–2006 National Health and Nutrition Examination Survey (NHANES) database, the research included 5,574 adults. Sarcopenic obesity was defined following the 2022 consensus by ESPEN and EASO. The study analyzed indicators such as the triglyceride-glucose index (TyG), homeostasis model assessment of insulin resistance (HOMA-IR), body roundness index (BRI), and lipid accumulation product (LAP). Results indicated a significant positive correlation between these indicators and SO, with the strongest association observed for TyG-WHtR. Predictor variables were identified through logistic and Lasso regression, including age, sex, weight-height ratio (WHtR), and TyG-WCR. The diagnostic model demonstrated good predictive performance with AUC values of 0.897 for internal validation and 0.853 for external validation. The study underscores the importance of early identification of SO patients and provides a theoretical foundation for future prevention and management strategies. Limitations include the cross-sectional study design and the potential limited generalizability of the model based on the American population.

Background: Chronic total occlusion (CTO) is the most challenging subset in percutaneous coronary intervention (PCI), but the optimal selection of patients and indication for such procedures remain a subject of debate. We sought to investigate the role of physiological function in treatment decisions of CTO PCI by measuring fractional flow reserve (FFR) and Dynamic SPECT imaging in this study. Methods: All the FFR of CTO vessel were measured before and immediately after CTO revascularization, and Dynamic SPECT imaging were detected before PCI in patients with an identified CTO. Results: A total of 53 patients with single-vessel CTO lesions were included in this cohort study. The mean FFR value was 0.34 ± 0.09 at baseline. Immediately after successful CTO PCI, the FFR value significantly increased to 0.79 ± 0.11. The regional coronary flow reserve (CFR) of CTO vessels was 1.62 ± 0.64, which was significantly and positively correlated with the baseline FFR value (r = 0.607, p = 0.005). The area under the ROC curve of the baseline FFR for the detection of ischemia was 0.923 (p

Epidemiological studies have suggested a positive association between environmental cadmium (Cd) exposure and type 2 diabetes mellitus (T2DM). Skeletal muscle insulin resistance (IR) plays a critical role in the pathogenesis of T2DM. This study aimed to investigate the effects of chronic low-level Cd exposure on skeletal muscle IR and its potential mechanism. Rats were exposed to drinking water containing 2 or 10 mg/L Cd for 24 weeks. Differentiated L6 myotubes were treated with Cd for 72 h. Immunofluorescence, flow cytometry assay, RNA-sequencing, and Seahorse analysis were conducted to determine the effects of Cd and its underlying mechanism on relevant parameters, including insulin sensitivity, glucose uptake, oxidative stress, mitophagy, and mitochondrial function in skeletal muscle and L6 myotubes. N-acetyl-cysteine (NAC), a scavenger of reactive oxygen species (ROS), and mitophagy inhibitor Cyclosporin A (CsA) were used to confirm the role of oxidative stress in mitophagy and mitochondrial dysfunction caused by Cd. We found that rats exposed to 10 mg/L Cd exhibited hyperglycemia and skeletal muscle IR. Cd markedly increased IRS-1 phosphorylation at Ser612, while decreased levels of phosphorylated PI3K, Akt, AS160, inhibited GLUT4 translocation and glucose uptake. Mechanistically, Cd increased the intracellular ROS, hydrogen peroxide, and malondialdehyde levels and decreased antioxidase activity in L6 myotubes. Furthermore, Cd upregulated the mRNA and protein levels of LC3II/I, PINK1, and Parkin. In addition, Cd induced the formation of mitophagosomes, reduced the mitochondrial membrane potential, decreased the adenosine triphosphate content, and impaired the mitochondrial respiratory capacity. Strikingly, NAC ameliorated oxidative stress, excessive mitophagy, and the associated reduction in myotube insulin sensitivity, while inhibition of mitophagy by CsA alleviated skeletal muscle IR. In conclusion, this study reveals a previously unrecognized mechanism that chronic low-level Cd exposure may induce mitophagy by activating the PINK1/Parkin signal pathway by increasing ROS, thus causing skeletal muscle IR and elevated blood glucose.

In this era of Transformers enjoying remarkable success, Convolutional Neural Networks (CNNs) remain highly relevant and useful. Indeed, hybrid Transformer-CNN network architectures, which combine the benefits of both approaches, have achieved impressive results. Vision Transformer (ViT) is a significant neural network architecture that features a convolutional layer as its first layer, primarily built on the transformer framework. However, owing to the distinct computation patterns inherent in attention and convolution, existing hardware accelerators for these two models are typically designed separately and lack a unified approach toward accelerating both models efficiently. In this paper, we present a dedicated accelerator on a field-programmable gate array (FPGA) platform. The accelerator, which integrates a configurable three-dimensional systolic array, is specifically designed to accelerate the inferential capabilities of hybrid Transformer-CNN networks. The Convolution and Transformer computations can be mapped to a systolic array by unifying these operations for matrix multiplication. Softmax and LayerNorm which are frequently used in hybrid Transformer-CNN networks were also implemented on FPGA boards. The accelerator achieved high performance with a peak throughput of 722 GOP/s at an average energy efficiency of 53 GOPS/W. Its respective computation latencies were 51.3 ms, 18.1 ms, and 6.8 ms for ViT-Base, ViT-Small, and ViT-Tiny. The accelerator provided a 12× improvement in energy efficiency compared to the CPU, a 2.3× improvement compared to the GPU, and a 1.5× to 2× improvement compared to existing accelerators regarding speed and energy efficiency.

Cyclin-dependent kinase 2 (CDK2) is a critical regulator of cell division and has emerged as a promising target for anticancer treatment. In this article, we summarize the structural features of CDK2 inhibitors and corresponding binding modes, in particular the noncompetitive binding modes that offer unique advantages for the development of highly selective inhibitors. In addition, we present an overview of the latest advancements in the development of CDK2 inhibitors and discuss the trend in the field. This review provides valuable insights into the structure–activity relationships of the reported CDK2 inhibitors, inspiring the development of potent and selective CDK2 inhibitors in the future.

Background: Post-ischemic angiogenesis is crucial for reestablishing blood flow in conditions such as peripheral artery disease (PAD). The role of insulin-like growth factor-2 mRNA-binding protein 2 (IGF2BP2) in post-transcriptional RNA metabolism and its involvement in post-ischemic angiogenesis remains unclear. Methods: Using a human GEO database and a hind-limb ischemia (HLI) mouse model, the predominant isoform IGF2BP2 in ischemic gastrocnemius tissue was identified. Adeno-associated virus with the Tie1 promoter induced IGF2BP2 overexpression in the HLI model, evaluating the expression of vascular structural proteins (CD31 and α-SMA) and blood flow recovery after HLI. In vitro experiments with human umbilical vein endothelial cells (HUVECs) demonstrated that lentivirus-mediated IGF2BP2 overexpression upregulates cell proliferation, migration, and tube formation. GeneCards, RNAct databases, and subsequent reverse transcription quantitative polymerase chain reaction (RT-qPCR) predicted IGF2BP2 interactions with fibroblast growth factor 2 (FGF2) mRNA, and actinomycin D treatment, binding site predictions and CLIP-seq data further confirmed this interaction. Furthermore, western blotting, enzyme-linked immunosorbent assay, and RNA immunoprecipitation followed by RT-qPCR were performed to validate IGF2BP2's interaction with FGF2 mRNA and to assess its role in stabilizing FGF2 mRNA, as well as its impact on FGF2 protein expression. Results: HLI reduced IGF2BP2 expression in the gastrocnemius tissue, which gradually increased during blood flow recovery. IGF2BP2 overexpression in HLI mice accelerated blood flow recovery and increased capillary and small artery densities. The overexpression of IGF2BP2 in HUVECs stimulated proliferation, migration, and tube formation by interacting with FGF2 mRNA to increase its stability. This interaction resulted in increased levels of FGF2 protein and secretion, ultimately promoting angiogenesis. Conclusions: IGF2BP2 contributes to blood flow restoration post-ischemia in vivo and promotes angiogenesis in HUVECs by enhancing FGF2 mRNA stability and FGF2 protein expression and secretion. These findings underscore IGF2BP2's therapeutic potential in ischemic conditions, such as PAD.

Abstract The dry reforming of methane provides an attractive route to convert greenhouse gases (CH4 and CO2) into valuable syngas, so as to resolve the carbon cycle and environmental issues. However, the development of high-performance catalysts remains a huge challenge. Herein, we report a 0.6% Ir/CeO2−x catalyst with a metal-support interface structure which exhibits high CH4 (~72%) and CO2 (~82%) conversion and a CH4 reaction rate of ~973 μmolCH4 gcat −1 s−1 which is stable over 100 h at 700 °C. The performance of the catalyst is close to the state-of-the-art in this area of research. A combination of in situ spectroscopic characterization and theoretical calculations highlight the importance of the interfacial structure as an intrinsic active center to facilitate the CH4 dissociation (the rate-determining step) and the CH2* oxidation to CH2O* without coke formation, which accounts for the long-term stability. The catalyst in this work has a potential application prospect in the field of high-value utilization of carbon resources.

Purposes It is of great significance for the storage and utilization of solar energy to develop high-efficiency non-precious metal oxygen evolution reaction (OER) catalysts that can be used in water splitting under near-neutral conditions. Methods FeOOH@Ni-Bi/NF electrocatalyst was constructed in two steps by electro-oxidation treatment and electro-deposition of Ni(OH)2/NF that obtained by hydrothermal method. Findings The large number of active sites provided by nickel foam (NF) substrate and three-dimensional nanosheet array structure of the catalyst facilitate the mass transfer process of OER. In addition, the electrochemical activity of catalyst is greatly enhanced by modulating the electro-oxidation degree of Ni-Bi and the amount of deposited FeOOH. Catalytic performance of the optimized FeOOH@Ni-Bi/NF is tested in near-neutral medium (0.1 mmol/L K2B4O7) with an overpotential of 394 mV and a Tafel slope of 54.2 mV/dec at 20 mA/cm2, showing excellent catalytic activity and long-term stability for OER.

Abstract Background Perihematomal edema (PHE) after post-intracerebral hemorrhage (ICH) has complex pathophysiological mechanisms that are poorly understood. The complicated immune response in the post-ICH brain constitutes a crucial component of PHE pathophysiology. In this study, we aimed to characterize the transcriptional profiles of immune cell populations in human PHE tissue and explore the microscopic differences between different types of immune cells. Methods 9 patients with basal ganglia intracerebral hemorrhage (hematoma volume 50-100 ml) were enrolled in this study. A multi-stage profile was developed, comprising Group1 (n = 3, 0–6 h post-ICH, G1), Group2 (n = 3, 6–24 h post-ICH, G2), and Group3 (n = 3, 24–48 h post-ICH, G3). A minimal quantity of edematous tissue surrounding the hematoma was preserved during hematoma evacuation. Single cell RNA sequencing (scRNA-seq) was used to map immune cell populations within comprehensively resected PHE samples collected from patients at different stages after ICH. Results We established, for the first time, a comprehensive landscape of diverse immune cell populations in human PHE tissue at a single-cell level. Our study identified 12 microglia subsets and 5 neutrophil subsets in human PHE tissue. What’s more, we discovered that the secreted phosphoprotein-1 (SPP1) pathway served as the basis for self-communication between microglia subclusters during the progression of PHE. Additionally, we traced the trajectory branches of different neutrophil subtypes. Finally, we also demonstrated that microglia-produced osteopontin (OPN) could regulate the immune environment in PHE tissue by interacting with CD44-positive cells. Conclusions As a result of our research, we have gained valuable insight into the immune-microenvironment within PHE tissue, which could potentially be used to develop novel treatment modalities for ICH.

Blasting operations, which are crucial to open-pit mine production due to their simplicity and efficiency, require precise control through accurate vibration velocity calculations. The conventional Sadowski formula mainly focuses on blast center distance but neglects the amplification effect of blasting vibration waves by terraced terrain, from which the calculated blasting vibration velocities are smaller than the actual values, affecting the safety of the project. To address this issue, our model introduces the influences of slope and time into Sadowski formula to measure safety through blast vibration displacement. In the northern section of the open-pit quartz mine in Jinchang City, Gansu Province, China, the data of a continuous blasting slope project are referred to. Our findings reveal a noticeable vibration amplification effect during blasting when a multi-stage slope platform undergoes a sudden cross-sectional change near the upper overhanging surface. The amplification vibration coefficient increases with height, while vibration waves within rocks decrease from bottom to top. Conversely, platforms without distinct cross-sectional changes exhibit no pronounced amplification during blasting. In addition, the vibration intensity decreases with distance as the rock height difference change propagates. The results obtained by the proposed blast vibration displacement equation incorporating slope shape influence closely agree with real-world scenarios. According to Pearson correlation coefficient (PPMCC) analysis, the average accuracy rate of our model is 88.84%, which exceeds the conventional Sadowski formula (46.92%).

Abstract Background Although physician-pharmacist collaborative clinics for diabetes management have been shown to be effective and cost-effective worldwide, there is limited understanding of the factors that influence their sustainable implementation. This study aims to identify the associated factors and provide sustainability strategy to better implement physician-pharmacist collaborative clinics for diabetes management in primary healthcare centers in China. Methods A sample of 43 participants were participated in face-to-face, in-depth, semi-structured interviews. Consolidated Framework for Implementation Research was used to identify facilitators and barriers to implementing physician-pharmacist collaborative clinics for diabetes management in primary healthcare centers, and to explore discriminating factors between low and high implementation units. A sustainable strategy repository based on dynamic sustainability framework was established to inform further implementation. Results This study demonstrated that clear recognition of intervention benefits, urgent needs of patients, adaptive and tailored plan, highly collaborative teamwork and leadership support were the major facilitators, while the major barriers included process complexity, large number and poor health literacy of patients in primary areas, inappropriate staffing arrangements, weak financial incentives and inadequate staff competencies. Six constructs were identified to distinguish between high and low implementation units. Sixteen strategies were developed to foster the implementation of physician-pharmacist collaborative clinics, targeting Intervention, Practice setting, and Ecological system. Conclusion This qualitative study demonstrated facilitators and barriers to implementing physician-pharmacist collaborative clinics for diabetes management in primary healthcare centers and developed theory-based strategies for further promotion, which has the potential to improve the management of diabetes and other chronic diseases in under-resourced areas.

Abstract Background Indobufen is widely used in patients with aspirin intolerance in East Asia. The OPTION trial launched by our cardiac center examined the performance of indobufen based dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). However, the vast majority of patients with acute coronary syndrome (ACS) and aspirin intolerance were excluded. We aimed to explore this question in a real-world population. Methods Patients enrolled in the ASPIRATION registry were grouped according to the DAPT strategy that they received after PCI. The primary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE) and Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. Propensity score matching (PSM) was adopted for confounder adjustment. Results A total of 7135 patients were reviewed. After one-year follow-up, the indobufen group was associated with the same risk of MACCE versus the aspirin group after PSM (6.5% vs. 6.5%, hazard ratio [HR] = 0.99, 95% confidence interval [CI] = 0.65 to 1.52, P = 0.978). However, BARC type 2, 3, or 5 bleeding was significantly reduced (3.0% vs. 11.9%, HR = 0.24, 95% CI = 0.15 to 0.40, P

Abstract Bio-based coating materials have received increased attention because of their low-cost, environmentally friendly, and sustainable properties. In this paper, a novel coating material was developed to coat ureas using bio-based coating material derived from liquefied eggplant branches to form controlled-release ureas (CRUs). Also, the optimum proportion of liquefier was studied. Furthermore, dimethyl siloxane was used to modify liquified eggplant branches to make them hydrophobic, resulting in hydrophobic controlled-release ureas (SCRUs). This hydrophobic-enabled coating is environmentally friendly and highly efficient. The products were characterized by specific scanning electron microscopy, energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, and differential scanning calorimetry, and the water contact angles of CRUs and SCRUs were determined. The nutrient-release characteristics of the SCRUs in water were determined at 25 °C and compared with those of CRUs. The results showed that the modification with dimethyl siloxane reduced the N release rate and increased the longevity of the fertilizer coated with hydrophobic bio-based coating material. In addition, organosilicon atoms on the SCRU surface also block the micro-holes on the coating and thus reduce the entry of water onto the coating. The results suggest that the new coating technology can create a hydrophobic surface on bio-based coating material and thus improve their controlled-release characteristics.

To accurately and quantitatively reveal the physical mechanism underlying the formation of microstructure during coaxial powder-fed laser cladding, a three-dimensional comprehensive model, coupling laser-powder interaction, temperature field, and flow field, is developed to identify the effects of multiphysics on microstructure characteristics. The high-speed camera and numerical simulation are employed to characterize the powder distribution, which is converted into the corresponding cladding layer growth rate and applied to solve the temperature rise and flow behavior of the molten pool. The energy conservation equation and the Navier-Stokes equation are applied to describe the physical field government, and the free surface motion of metallic liquid is tracked utilizing the Level Set method. The comprehensive model accurately visualizes the molten pool hydrodynamic behavior and temperature field distribution during laser cladding. In addition, the experimental results are combined to analyze the formation mechanism of microstructure. The direction and magnitude of forces acting on the metallic liquid in the flow field (such as surface tension, Marangoni force, recoil pressure) intuitively explain the formation of circulation in the molten pool, ultimately reflected in the grain growth direction. The evolution of cooling rates in the molten pool indicates that the specific location and varied temperature field dominates the grain type and size of the cladding layer, which contributes to the planar crystal, cellular crystal, columnar dendrite, equiaxed dendrite and equiaxed crystal from bottom to top.

Shot peening post-treatment was conducted at SUS304 austenite steel bar-plate rotary friction welding joint with fatigue property deterioration from welding flash. along the shotting intensity increasing, non-synchronous deformation of the plate and flash resulted in non-monotonically evolution of local microstructure, residual stresses, and make the fatigue life increased to flash-removed joint level.

Abstract Enhancing the device electroluminescence quantum efficiency (EQE EL ) is a critical factor in mitigating non-radiative voltage losses (V NR ) and further improving the performance of organic solar cells (OSCs). While the common understanding attributes EQE EL in OSCs to the dynamics of charge transfer (CT) states, persistent efforts to manipulate these decay dynamics have yielded limited results, with the EQE EL of high-efficiency OSCs typically remaining below 10−2%. This value is considerably lower than that observed in high efficiency inorganic photovoltaic devices. Here, we report that EQE EL is also influenced by the dissociation rate constant of singlet states (k DS ). Importantly, in contrast to the traditional belief that advocates maximizing k DS for superior photovoltaic quantum efficiency (EQE PV ), a controlled reduction in k DS is shown to enhance EQE EL without compromising EQE PV . Consequently, a promising experimental approach to address the V NR challenge is proposed, resulting in a significant improvement in the performance of OSCs.

In this paper, AlGaN/GaN high electron mobility transistors (HEMTs) with different thicknesses of unintentional doping GaN (UID-GaN) channels were compared and discussed. In order to discuss the effect of different thicknesses of the UID-GaN layer on iron-doped tails, both AlGaN/GaN HEMTs share the same 200 nm GaN buffer layer with an Fe-doped concentration of 8 × 1017 cm−3. Due to the different thicknesses of the UID-GaN layer, the concentration of Fe trails reaching the two-dimensional electron gas (2DEG) varies. The breakdown voltage (Vbr) increases with the high concentration of Fe-doped in GaN buffer layer. However, the mobility of the low concentration of the Fe-doped tail is higher than that of the high concentration of the Fe-doped tail. Therefore, the effect of different thicknesses of UID-GaN on the DC and radio frequency (RF) performance of the device needs to be verified. It provides a reference to the epitaxial design for high-performance GaN HEMTs.

Optically pumped magnetometer magnetoencephalography (OPM-MEG) represents a novel method for recording neural signals in the brain, offering the potential to measure critical neuroimaging characteristics such as effective brain networks. Effective brain networks describe the causal relationships and information flow between brain regions. In constructing effective brain networks using Granger causality, the noise in the multivariate autoregressive model (MVAR) is typically assumed to follow a Gaussian distribution. However, in experimental measurements, the statistical characteristics of noise are difficult to ascertain. In this paper, a Granger causality method based on a cost-reference particle filter (CRPF) is proposed for constructing effective brain networks under unknown noise conditions. Simulation results show that the average estimation errors of the MVAR model coefficients using the CRPF method are reduced by 53.4% and 82.4% compared to the Kalman filter (KF) and maximum correntropy filter (MCF) under Gaussian noise, respectively. The CRPF method reduces the average estimation errors by 88.1% and 85.8% compared to the MCF under alpha-stable distribution noise and the KF method under pink noise conditions, respectively. In an experiment, the CRPF method recoversthe latent characteristics of effective connectivity of benchmark somatosensory stimulation data in rats, human finger movement, and auditory oddball paradigms measured using OPM-MEG, which is in excellent agreement with known physiology. The simulation and experimental results demonstrate the effectiveness of the proposed algorithm and OPM-MEG for measuring effective brain networks.

Cross beam fracture is one of the common failures of vibrating screens, and crack is the early manifestation of fracture, which is hard to detect. In order to meet the screening requirement of the vibrating screen and improve the service life of the cracked beam, the cracked Euler-Bernoulli beam model is established to investigate the dynamics of the cross beam with a straight crack under different weights of eccentric block, processing capacities, and Rayleigh damping coefficients based on the finite element method in this paper. The local flexibility coefficients are derived from the principles of fracture mechanics and strain release energy and solved by the adaptive five-point Gaussian Legende algorithm. The stiffness matrix of the cracked beam element is calculated through the inverse method of total flexibility. The four order Runge-Kutta algorithm and MATLAB tools are used to solve the dynamic equation of the cracked cross beam. The relationship between the vibration amplitude of the cracked cross beam and the weight of the eccentric block is studied by fitting formulas using the least squares method. The influence of different weights of eccentric block, processing capacities, and Rayleigh damping coefficients on the vibration amplitude and service life of the cracked beam are discussed. The results show that the greater the weight of the eccentric block, the shorter service life of the beam. When the damping is greater, the service life of the cracked beam is longer.

IntroductionThis study introduces the Supervised Magnitude-Altitude Scoring (SMAS) methodology, a novel machine learning-based approach for analyzing gene expression data from non-human primates (NHPs) infected with Ebola virus (EBOV). By focusing on host-pathogen interactions, this research aims to enhance the understanding and identification of critical biomarkers for Ebola infection.MethodsWe utilized a comprehensive dataset of NanoString gene expression profiles from Ebola-infected NHPs. The SMAS system combines gene selection based on both statistical significance and expression changes. Employing linear classifiers such as logistic regression, the method facilitates precise differentiation between RT-qPCR positive and negative NHP samples.ResultsThe application of SMAS led to the identification of IFI6 and IFI27 as key biomarkers, which demonstrated perfect predictive performance with 100% accuracy and optimal Area Under the Curve (AUC) metrics in classifying various stages of Ebola infection. Additionally, genes including MX1, OAS1, and ISG15 were significantly upregulated, underscoring their vital roles in the immune response to EBOV.DiscussionGene Ontology (GO) analysis further elucidated the involvement of these genes in critical biological processes and immune response pathways, reinforcing their significance in Ebola pathogenesis. Our findings highlight the efficacy of the SMAS methodology in revealing complex genetic interactions and response mechanisms, which are essential for advancing the development of diagnostic tools and therapeutic strategies.ConclusionThis study provides valuable insights into EBOV pathogenesis, demonstrating the potential of SMAS to enhance the precision of diagnostics and interventions for Ebola and other viral infections.

Tight sandstone reservoirs have extremely low porosity and permeability. Bedding-parallel fractures (BPFs) contribute prominently to the storage and seepage capability. However, the distribution of BPFs is remarkably heterogeneous, impeding the prediction and modeling of sweet spots. BPFs are controlled fundamentally by laminations, which are widely distributed in lacustrine tight reservoirs and provide most weakness planes. Based on core and thin section data, BPFs of the upper Triassic Chang 7 tight oil reservoir are characterized microscopically. The lamination combination unit, which is defined by distinctive lamination assemblage and relatively stable lamination thickness and space, is utilized as a homogeneous unit to measure the density of lamination and related BPFs. The influence of laminations on BPFs is discussed further. Results show that most bedding-parallel fractures are unfilled, with apertures generally

Pyrrolizidine alkaloids (PAs) are a group of naturally occurring alkaloids widely present in plants. PAs are highly hepatotoxic and have been documented to cause many incidents of human and animal poisoning. Retrorsine (RTS) is a pyrrolizidine alkaloid (PA) derived from the Compositae Senecio, which has been shown to cause hepatotoxicity. Human liver poisoning occurs through the consumption of RTS-contaminated food, and animals can also be poisoned by ingesting RTS-containing toxic plants. The mechanism of RTS-induced liver toxicity is not fully understood. In this study, we demonstrated that RTS-induced oxidative stress plays a pivotal role in RTS-induced liver toxicity involving apoptosis and autophagy. The results showed that RTS treatment in the cultured Primary rat hepatocytes caused cytotoxicity and release of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in a time- and dose-dependent manner. Our study showed that treatment of RTS induced ROS and MDA (malondialdehyde, a lipid peroxidation marker) in the hepatocytes, and reduced antioxidant capacity (GSH content, SOD activity), suggesting RTS treatment caused oxidative stress response in the hepatocytes. Furthermore, we found that RTS induced apoptosis and autophagy in the hepatocytes, and RTS-induced apoptosis and autophagy could be alleviated by ROS scavenger N-acetylcysteine (NAC) and the MAPK pathway inhibitors suggesting ROS/MAPK signaling pathway plays a role in RTS induced apoptosis and autophagy. Collectively, this study reveals the regulatory mechanism of oxidative stress in RTS-induced apoptosis and autophagy in the hepatocytes, providing important insights of molecular mechanisms of hepatotoxicity induced by RTS and related pyrrolizidine alkaloids in liver. This mechanism provides a basis for the prevention and treatment of PA poisoning in humans and animals.

Carbonate reservoirs are characterized by abundant reserves and are currently focal points for development in oil and gas producing regions such as the Ahdab oilfield, Tarim Basin, Sichuan Basin, and Ordos Basin. The primary method for exploiting carbonate reservoirs is waterflooding. However, due to the complex pore structure and pronounced heterogeneity of carbonate rocks, the waterflooding process often leads to an unclear distribution of remaining oil and low waterflooding recovery efficiency, significantly impacting the stable and high production of carbonate reservoirs. This paper presents a two-phase flow model of oil and water in distinct pore structures by integrating fluid flow equations and interface tracking equations. It visually represents the waterflooding process at the pore scale, elucidates the distribution and formation mechanism of remaining oil, and discusses the mechanism of microscopic displacement efficiency change. The study reveals that: 1) After waterflooding, the distribution patterns of remaining oil can be categorized into dead-end remaining oil, pressure balance remaining oil, wall-bound remaining oil, Jamin effect remaining oil, and water-encapsulating remaining oil, which are governed by microscopic pore structure, wettability, and preferential flow paths; 2) From the perspective of actual reservoir displacement efficiency, intergranular pores > intergranular dissolved pores > visceral foramen > mould pore, with this trend being more pronounced under hydrophilic wetting conditions; 3) Given the oil-wet to strong oil-wet wettability characteristics of these carbonate rocks, capillary forces pose significant resistance during waterflooding. The conclusion underscores the importance of leveraging the reservoir’s microscopic pore structure and wettability characteristics for actual oil wells, elucidating the evolutionary law of the mechanical mechanism of oil-water interface advancement, clarifying oil-water percolation characteristics at the pore scale, and understanding the microscopic displacement physical mechanism, all of which are crucial for guiding the design of schemes aimed at enhancing reservoir recovery efficiency.

This study established a numerical model that considers elevation conditions and slope shape factors by the modified Sadovsky formula to analyze the vibration attenuation law of open-pit slopes under blasting vibration conditions. The blasting excavation of a slope in a certain open-pit mine in Yunfu, Guangdong, is selected as an example. Using a numerical model that considers elevation conditions and slope shape factors by the modified Sadovsky formula, a triangular pulse load was utilized to approximate the time-history characteristics of explosion vibration with FLAC3D software. The simulation results showed the radiation range of the blasting vibration seismic wave. By comparison with field monitoring data, the numerical model that considers the slope shape factor had a relative error of ∼10%, while the numerical model that disregards the slope shape factor had a relative error of ∼15%. The relative accuracy of the calculation results of the new numerical model is higher and closer to the actual attenuation law of blasting particle vibration speed, providing more reliable results for slope stability assessment. The peak particle velocities obtained from the numerical simulation results were generally higher than the field monitoring data. These discrepancies might be attributed to the use of simplified models that disregard the discontinuous structural planes within the rock mass. This study provides an important reference for the stability assessment of open-pit slopes under blasting vibration conditions, offering guidance for improving slope stability assessment and related engineering practices.

Summary: Background: High prices of anticancer drugs have raised concerns due to their financial impact on patients and healthcare systems. This study aimed to assess the initial and latest list prices and clinical value of reimbursed anticancer drugs in China, Japan, and South Korea. Methods: We identified anticancer drugs newly approved by the National Medical Products Administration of China from January 2012 to June 2022, and by the Pharmaceuticals and Medical Devices Agency of Japan and the Ministry of Food and Drug Safety of South Korea up until June 2022. We compared initial and latest treatment prices between countries and assessed clinical value using patients’ survival, quality of life (QoL), and European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). We calculated Spearman rank correlation coefficients of treatment prices with clinical value for individual countries and employed regression analyses to investigate whether the relationship between prices and clinical value was modified by the country setting. Findings: Our cohort included 91 anticancer drug indications, with 60 listed for reimbursement in China, 91 in Japan, and 87 in South Korea. Median treatment prices were highest in Japan, followed by South Korea, and lowest in China, both for initial prices (US$64082 vs. US$45529 vs. US$19144, p