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Background: Exosomes produced by mesenchymal stem cells (MSCs) have vascular generative properties and are considered new effective candidates for the treatment of bone defects as alternatives to cell therapy. Improving the pro-regenerative function and efficacy of exosomes has been a popular research topic in the field of orthopaedics. Methods: We prepared mesoporous bioactive glass (mBG) microspheres via the template method. The ionic products of mBGs used to treat MSCs were extracted, and the effects of exosomes secreted by MSCs on osteoblast (OB) and macrophage (MP) behaviour and bone defect repair were observed in vivo (Micro-CT, H&E, Masson, and immunofluorescence staining for BMP2, COL1, VEGF, CD31, CD163, and iNOS). Results: The mBG spheres were successfully prepared, and the Exo-mBG were isolated and extracted. Compared with those in the blank and Exo-Con groups, the proliferation and osteogenic differentiation of OBs in the Exo-mBG group were significantly greater. For example, on Day 7, OPN gene expression in the Ctrl-Exo group was 3.97 and 2.83 times greater than that in the blank and Exo-mBG groups, respectively. In a cranial defect rat model, Exo-mBG promoted bone tissue healing and angiogenesis, increased M2 macrophage polarisation and inhibited M1 macrophage polarisation, as verified by micro-CT, H&E staining, Masson staining and immunofluorescence staining. These effects may be due to the combination of a higher silicon concentration and a higher calcium-to-phosphorus ratio in the mBG ionic products. Conclusion: This study provides insights for the application of exosomes in cell-free therapy and a new scientific basis and technical approach for the utilisation of MSC-derived exosomes in bone defect repair. The translational potential of this article: Our study demonstrated that exosomes produced by mBG-stimulated MSCs have excellent in vitro and in vivo bone-enabling and immunomodulatory functions and provides insights into the use of exosomes in clinical cell-free therapies.

Abstract Questions of unfairness and inequity pose critical challenges to the successful deployment of artificial intelligence (AI) in healthcare settings. In AI models, unequal performance across protected groups may be partially attributable to the learning of spurious or otherwise undesirable correlations between sensitive attributes and disease-related information. Here, we introduce the Attribute Neutral Framework, designed to disentangle biased attributes from disease-relevant information and subsequently neutralize them to improve representation across diverse subgroups. Within the framework, we develop the Attribute Neutralizer (AttrNzr) to generate neutralized data, for which protected attributes can no longer be easily predicted by humans or by machine learning classifiers. We then utilize these data to train the disease diagnosis model (DDM). Comparative analysis with other unfairness mitigation algorithms demonstrates that AttrNzr outperforms in reducing the unfairness of the DDM while maintaining DDM’s overall disease diagnosis performance. Furthermore, AttrNzr supports the simultaneous neutralization of multiple attributes and demonstrates utility even when applied solely during the training phase, without being used in the test phase. Moreover, instead of introducing additional constraints to the DDM, the AttrNzr directly addresses a root cause of unfairness, providing a model-independent solution. Our results with AttrNzr highlight the potential of data-centered and model-independent solutions for fairness challenges in AI-enabled medical systems.

Objective:. This study aims to investigate the impact of tricuspid regurgitation (TR) severity on the accuracy of echocardiographic estimation of systolic pulmonary arterial pressure (sPAP) in patients with pulmonary arterial hypertension (PAH). Methods:. Patients who were diagnosed with PAH and had a right heart catheterization (RHC) and echocardiography examination were selected retrospectively from May 2018 to December 2021. sPAP measured by RHC is used as the gold standard. A difference in sPAP of less than 10 mmHg between echocardiographic estimation by peak TR velocity and RHC measurement was defined as accurate, with a difference ≥10 mmHg considered inaccurate. The factors affecting the accuracy of echocardiographic sPAP estimation were analyzed by univariate and multivariate analysis. Results:. A total of 138 patients aged (45.57 ± 15.97) years with PAH were enrolled. sPAP measured by echocardiography and RHC were (80.83 ± 23.46) and (81.62 ± 30.05) mmHg, respectively. The values of the 2 methods were highly correlated (r = 0.809, P < 0.01) and Bland-Altman plots showed good consistency. The accuracy rate of sPAP estimation by echocardiography was 42.03% (58/138). In the 57.97% (80/138) of patients where echocardiography was inaccurate, sPAP was overestimated in 28.26% (39/138) and underestimated in 29.71% (41/138). Univariate analysis showed that there was a statistically significant difference between the accurate and inaccurate groups in World Health Organization-Function Class, N-terminal pro-B-type natriuretic peptide, severity of TR, tricuspid annular plane systolic excursion (TAPSE), sPAP-RHC, mean pulmonary artery pressure, pulmonary vascular resistance (P < 0.05). Multivariate logistic regression analyses identified the TR severity (odds ratio = 2.292, 95% confidence interval: 1.126–4.667, P = 0.022) and TAPSE (odds ratio = 0.733, 95% confidence interval: 0.621–0.865, P < 0.001) as independent predictors for the accuracy of echocardiographic sPAP estimation. Conclusion:. Higher TR severity and lower TAPSE values reduce the accuracy of sPAP estimated by echocardiography. Therefore, TR severity and right heart function should be considered when echocardiography is used to estimate sPAP by the TR velocity.

Abstract The cycling stability of O3‐type NaNi1/3Fe1/3Mn1/3O2 (NFM) as a commercial cathode material for sodium ion batteries (SIBs) is still a challenge. In this study, the Ni/Fe/Mn elements are replaced successfully with tantalum (Ta) in the NFM lattice, which generated additional delocalized electrons and enhanced the binding ability between the transition metal and oxygen, resulting in suppressed lattice distortion during charging and discharging. This caused significant mitigation of voltage decay and improved cycle stability within the potential range of 2.0–4.2 V. The optimized Na(Ni1/3Fe1/3Mn1/3)0.97Ta0.03O2 sample achieved a reversible capacity of 162.6 mAh g−1 at a current rate of 0.1 C and 73.2 mAh g−1 at a high rate of 10 C. Additionally, the average charge/discharge potential retention reached 98% after 100 cycles, significantly mitigating the voltage decay. This work demonstrates a significant contribution towards the practical utilization of NFM cathodes in the SIBs energy storage field.

The microstructure, phase transformation behavior, heat treatment effects, and their impacts on the mechanical properties and high-temperature oxidation resistance of IN718 nickel-based superalloy processed by selective laser melting (SLM) both before and after heat treatment was systematically investigated. The heat treatment process involved a two-step aging at 720 °C for 8 h plus 620 °C for 10 h with a controlled slow cooling rate of 10 °C/min. Through the comprehensive use of scanning electron microscopy (SEM), X-ray diffraction (XRD), electron backscattering diffraction (EBSD), and transmission electron microscopy (TEM), the evolution of the microstructure and its mechanism of influence on material properties were revealed. The study identified the formation of γ phase, γ′ phase, γ'' phase, δ phase, and Laves phase during the SLM forming process. Heat treatment played a key role in improving the microstructure and properties of the SLM-processed alloy, with experimental results showing that the mechanical performance and high-temperature oxidation resistance were significantly enhanced after heat treatment. Specifically, the material after heat treatment exhibited a yield strength of 1472 MPa, a tensile strength of 1608 MPa, and an elongation of 9.2%, which represented increases of 76.5%, 38.4%, and 16.5% respectively, compared to the as-printed alloy. Moreover, the oxidation resistance at 1000 °C of the heat-treated samples improved significantly, with weight loss reduced from −0.17 mg/cm2 before heat treatment to −0.15 mg/cm2. Microstructural analysis further indicated that heat treatment optimized the crystal orientation, promoted the formation of more precipitated phases and reduced defects, thereby enhancing the overall performance of the material. This work provides significant scientific insights into understanding and optimizing the IN718 nickel-based superalloy processed by SLM, demonstrating the crucial role of heat treatment in improving its microstructure and properties.

Abstract Accurate differentiation between angina with no obstructive coronary arteries (ANOCA) and mental stress-induced myocardial ischemia (MSIMI) is crucial for tailored treatment strategies, yet public data scarcity hampers understanding. Given the higher incidence of both conditions in women, this study prospectively enrolled 80 female ANOCA and 39 age-matched female controls, subjecting them to three types of mental stress tasks. ECGs were continuously monitored across Rest, Stress, and Recover stages of the mental stress tasks, with PET/CT imaging during the Stress stage to evaluate myocardial perfusion. With PET/CT serving as the gold standard for MSIMI diagnosis, 35 of the 80 ANOCA patients were diagnosed as MSIMI. Using ECG variables from different stages of mental stress tasks, we developed five machine learning models to diagnose MSIMI. The results showed that ECG data from different stages provide valuable information for MSIMI classification. Additionally, the dataset encompassed demographic details, physiological, and blood sample test results of the patients. We anticipate this new dataset will significantly push further progress in ANOCA and MSIMI research.

Abstract Excited‐state intramolecular proton transfer (ESIPT) has attracted great attention in fluorescent sensors and luminescent materials due to its unique photobiological and photochemical features. However, the current structures are far from meeting the specific demands for ESIPT molecules in different scenarios; the try‐and‐error development method is labor‐intensive and costly. Therefore, it is imperative to devise novel approaches for the exploration of promising ESIPT fluorophores. This research proposes an artificial intelligence approach aiming at exploring ESIPT molecules efficiently. The first high‐quality ESIPT dataset and a multi‐level prediction system are constructed that realized accurate identification of ESIPT molecules from a large number of compounds under a stepwise distinguishing from conventional molecules to fluorescent molecules and then to ESIPT molecules. Furthermore, key structural features that contributed to ESIPT are revealed by using the SHapley Additive exPlanations (SHAP) method. Then three strategies are proposed to ensure the ESIPT process while keeping good safety, pharmacokinetic properties, and novel structures. With these strategies, >700 previously unreported ESIPT molecules are screened from a large pool of 570 000 compounds. The ESIPT process and biosafety of optimal molecules are successfully validated by quantitative calculation and experiment. This novel approach is expected to bring a new paradigm for exploring ideal ESIPT molecules.

The Bypass Dual-Throat Nozzle (BDTN) has garnered growing attention due to its remarkable thrust vectoring capabilities. This type of nozzle boasts broad application prospects as it achieves deflection control of the jet stream merely through regulating the opening and closing of bypass channels. Our comprehensive study delves deeply into the intricate parameterization of the bypass channel within the BDTN. Research has demonstrated that utilizing Fluent software in conjunction with the Realizable k-epsilon turbulence model, standard wall functions, and the Sutherland formula for viscosity coefficient approximation can yield a relatively accurate representation of the vector flow field structure within the BDTN. Following the validation of the numerical computation methodology employed in this study, we have investigated the influence of factors such as bypass channel radius, precise valve positioning, and actuation direction on the nozzle's vectoring performance. Key findings indicate that, due to the relatively small proportion of secondary flow, the radius of the bypass channel has minimal impact on the thrust vector angle. The positioning of the valve and its opening direction are critical in determining the thrust vector angle, requiring careful consideration during the design and optimization process. Fully opening the bypass channel does not necessarily yield the maximum thrust vector angle. Moreover, the total pressure, velocity, position, and direction of the secondary flow within the bypass channel exert a more profound influence on the nozzle's vector performance compared to the mere presence of the secondary flow itself. Notably, the forward opening method of the valve emerges as the preferred choice, as it facilitates more precise later vector control.

In Northeast China, permafrost is controlled by a combination of biotic, climatic, physiographic, and anthropogenic factors. Due to the complexity of these governing or influencing factors, it is challenging to exactly describe the features of the Xing’an permafrost in Northeast China. By integrating remote sensing (RS) and geographic information system (GIS) technologies, we have quantified these influencing factors of permafrost changes as an important approach to understanding the nature of latitudinal and mountain permafrost in Northeast China at the mid-latitudes in the Northern Hemisphere. In this study, we combine Geographical Detector (Geodetector) model, trend analysis, and multi-source RS data to quantify the controlling or influencing factors of permafrost thermal state and of permafrost changes, and explain the interactions among permafrost, environment, and climate. The results indicate that, at the regional scale, changes in the thermal state of permafrost are primarily governed or influenced by mean annual land surface temperature (MALST), precipitation, and snow cover duration (SCD). Topographic factors also affect the spatial patterns of permafrost development. Additionally, in the context of climate warming, the insulation effect of snow cover on the permafrost is weakened, or has been weakening. Moreover, the interactive effects among various factors significantly enhance their explanatory power for changes in the thermal state of permafrost. The study emphasizes the complexity of the interactions among permafrost, climate, and the environment, and highlights the significance of understanding these interactions for regional socio-economic development, ecological management, carbon pool stabilization, and research on future climate change in Northeast China.

The divertor must simultaneously withstand unprecedented high heat fluxes of up to 20 MW/m2 and high-energy neutron irradiation of 14-MeV during fusion reactor operation. Accordingly, it is necessary to simultaneously meet the excellent heat dissipation capacity of the divertor and maintain good material performance in harsh neutron irradiation environments. The flat-type divertor demonstrates better heat transfer performance compared to monoblock divertor. Nevertheless, under the condition of a heat flux of 20 MW/m2, the heat transfer and thermal fatigue performance of flat-type divertor using advanced materials are still unidentified. In this study, we conducted a thorough analysis of the heat transfer capabilities and thermal fatigue characteristics of potassium-doped tungsten (KW)/Cu/Oxide dispersion strengthened copper (ODS-Cu)/reduced activation ferritic/martensitic (RAFM) divertor mockup adopts hypervaportron (HV) structure by numerical simulations combined with experiments. The numerical results indicate that the flat-type KW/Cu/ODS-Cu/RAFM divertor mockup expresses excellent heat transfer capacity. The contact area between the edge of the fins and the bottom surface of the ODS-Cu heat sink induces a significant increase in water flow velocity to ∼15 m/s. The peak temperature of loaded KW surface is only ∼985 °C under the flow rate of 5 t/h and inlet temperature of 20 °C. During the high heat flux tests, the prepared flat-type divertor mockup successful endured 1000 cycles of 20 MW/m2 with the peak temperature of 883 °C, and the surface temperature experienced a fluctuation of 2.4 % during the thermal fatigue tests. This study can provide a strong data reference and technical support for the development of fusion reactors, and is of great significance in advancing the commercialization of fusion energy.

This paper presents an experimental and numerical investigation into the bending behaviour of reinforced concrete (RC) T-beams damaged by overheight vehicle impact strengthened with ultra-high performance concrete (UHPC). Four-point bending tests were conducted on one RC T-beam and six UHPC-strengthened RC T-beams, and the primary parameters included the length and thickness of the UHPC strengthening layer, as well as the filling area of UHPC for the damaged region. The test results demonstrated that the UHPC strengthening layer effectively delayed the development of concrete cracks, improved the bending stiffness, cracking load, and resistance of the T-beams. The UHPC-strengthened T-beams exhibited an increase in cracking and ultimate loads by 39–339 % and 26–113 %, respectively, compared to the RC T-beam. Subsequently, a finite element (FE) model of the UHPC-strengthened T-beams was developed and validated using the experimental results. A parametric study using the validated FE model was conducted, revealing that insufficient strengthened length or excessive strengthened thickness of the UHPC layer increased the risk of debonding failure. Furthermore, for T-beams experiencing bending failure, increasing the thickness and height of the UHPC layer, as well as the UHPC filling area for the damaged region, significantly improved the bending resistance, while the UHPC layer length had little effect on the bending resistance. Finally, based on the calculation theory of RC beams under bending loads and considering the strain-hardening behaviour of UHPC in tension, a design method for the bending resistance of damaged RC T-beams strengthened with UHPC was proposed and verified using the experimental and numerical results.

Background: Prevention of high-risk HPV (HR-HPV) infection and effective medical intervention of persistent HPV infection and precancerous lesions are critical for the prevention of cervical cancer. Aims: The aim of this retrospective comparative study was to evaluate the outcomes of ALA PDT and observation only in the management of low-grade squamous intraepithelial lesions (LSIL). Methods: In PDT Group (n = 138), ALA PDT was applied to patients with colposcopic biopsy confirmed cervical LSIL accompanied with HR-HPV infection longer than 1 year or HPV 16/18 subtype infection. Cervical LSIL only patients received 3 times of ALA PDT and those with concurrent cervical canal or vaginal lesions received 6 times ALA PDT. Control Group (n = 69) received observation only. Colposcopy, TCT and HPV typing were performed before and after treatment. Patients were followed up for up to two years. Result: The observation group showed 26.1%, 34.8% and 53.6% HR-HPV negative conversion at 3-6, 12 and 24 months, respectively. LSIL regression rate of the observation group was 33.33%, 36.23% and 65.22% at 3-6, 12 and 24 months, respectively. There was 62.32%, 80.56% and 89.22% patients achieved HPV clearance at 3-6, 12 and 24 months after PDT treatment, respectively. The LSIL remission rate was 89.86%, 94.40% and 96.08% at 3-6, 12 and 24 months after ALA PDT, respectively. The abnormal TCT (≧ ASCUS) was reduced from 92% to 10.1%, 4.6% and 3.9% at 3-6, 12 and 24 months after ALA PDT, respectively. The patient age was not a factor affecting the clearance of HPV infection and the LSIL regression rate of PDT treatment. Conclusions: This study demonstrates that the application of multiple ALA PDT treatments has added value in achieving both short-term and long-term HPV and lesion clearance.

To improve the flexural performance of damaged reinforced concrete T-beams, a method of filling ultra-high performance concrete (UHPC) in the damaged area was adopted. Experimental studies were conducted on two UHPC-reinforced concrete T-beams with different lengths of damaged areas and one undamaged concrete T-beam as a reference. Crack distribution, failure modes, cracking loads, flexural capacities, and strain variation of the specimens were analyzed. Subsequently, a nonlinear finite element (FE) model of the UHPC-reinforced T-beam was developed using ABAQUS, and the FE model results were compared with the experimental results to validate the accuracy of the FE simulation method. The results indicated that the two UHPC-reinforced T-beams exhibited a similar flexural failure process to the undamaged T-beam. The longitudinal tensile strain distribution at the mid-span section showed that the composite section formed by the filling of UHPC in the damaged region still adhered the assumption of the planar section. Owing to the excellent bond performance between UHPC and the existing concrete, the main cracks of the UHPC-reinforced T-beams appeared in the chiseled area, and the crack widths of the UHPC-reinforced T-beams under the same load were smaller than those of the reference T-beam. Overall, the reinforcing method of filling UHPC in the damaged region can restore or even enhance the flexural performance of the damaged reinforced concrete T-beams.

Abstract Early detection is critical to achieving improved treatment outcomes for child patients with congenital heart diseases (CHDs). Therefore, developing effective CHD detection techniques using low-cost and non-invasive pediatric electrocardiogram are highly desirable. We propose a deep learning approach for CHD detection, CHDdECG, which automatically extracts features from pediatric electrocardiogram and wavelet transformation characteristics, and integrates them with key human-concept features. Developed on 65,869 cases, CHDdECG achieved ROC-AUC of 0.915 and specificity of 0.881 on a real-world test set covering 12,000 cases. Additionally, on two external test sets with 7137 and 8121 cases, the overall ROC-AUC were 0.917 and 0.907 while specificities were 0.937 and 0.907. Notably, CHDdECG surpassed cardiologists in CHD detection performance comparison, and feature importance scores suggested greater influence of automatically extracted electrocardiogram features on CHD detection compared with human-concept features, implying that CHDdECG may grasp some knowledge beyond human cognition. Our study directly impacts CHD detection with pediatric electrocardiogram and demonstrates the potential of pediatric electrocardiogram for broader benefits.

Shared autonomous electric vehicle systems (SAEVS) combine autonomous driving technology with shared electric vehicle services to provide advantages over traditional shared vehicle systems, including autonomous vehicle relocation and rapid response to user needs. In this study, we seek to enhance the operational efficiency and profitability of SAEVS by considering trip selection and the potential opportunity cost associated with unmet user demands. An integer linear programming (ILP) model is developed using a spatio-temporal state network to optimize the system design planning (e.g., charging facility, vehicle fleet sizing and distribution) and operational decisions (e.g., vehicle operational relocation and trip selection strategy). To handle the computational complexities of this model, we propose a Lagrangian relaxation (LR) algorithm. The performance of the LR algorithm is evaluated through a case study. The results, along with a parameter sensitivity analysis, reveal several key findings: (ⅰ) Allocating vehicles to stations with concentrated early peak demand, distributing charging facilities to stations with high total demand throughout the day and implementing vehicle relocation after the early demand peak can mitigate uneven vehicle distribution; (ⅱ) Implementing trip selection enhances SAEVS profitability; (ⅲ) Increasing opportunity cost meets user demands but at the expense of reduced profit; (ⅳ) It is recommended that SAEVS be equipped with charging facilities of suitable charging power based on operational conditions.

Abstract Halving nitrogen pollution is crucial for achieving Sustainable Development Goals (SDGs). However, how to reduce nitrogen pollution from multiple sources remains challenging. Here we show that reactive nitrogen (Nr) pollution could be roughly halved by managed urban development in China by 2050, with NH3, NOx and N2O atmospheric emissions declining by 44%, 30% and 33%, respectively, and Nr to water bodies by 53%. While rural-urban migration increases point-source nitrogen emissions in metropolitan areas, it promotes large-scale farming, reducing rural sewage and agricultural non-point-source pollution, potentially improving national air and water quality. An investment of approximately US$ 61 billion in waste treatment, land consolidation, and livestock relocation yields an overall benefit of US$ 245 billion. This underscores the feasibility and cost-effectiveness of halving Nr pollution through urbanization, contributing significantly to SDG1 (No poverty), SDG2 (Zero hunger), SDG6 (Clean water), SDG12 (Responsible consumption and production), SDG14 (Climate Action), and so on.

Abstract This study was to probe the protective effects and mechanisms of salvianolic acid A (SAA) on cerebral ischemia–reperfusion injury (CIRI). The middle cerebral artery occlusion model (MCAO) was established in rats. Rats' behavior, neurological deficits, brain injury, inflammation, and apoptosis in the brain tissue were evaluated. The inflammatory response and apoptosis of PC12 cells induced by oxygen glucose deprivation/reperfusion (OGD/R) were detected. SAA‐mediated changes in miR‐212‐3p, SOX7, and Wnt/β‐catenin pathway were determined, and the targeting relationship between miR‐212‐3p and SOX7 was clarified. SAA alleviated the neurological deficits and brain injury of MCAO rats and inhibited the inflammatory response and apoptosis of OGD/R‐conditioned PC‐12 cells. SAA upregulated miR‐212‐3p, Wnt3a, and β‐catenin, whereas inhibited SOX7 levels. Silencing miR‐212‐3p counteracted the protective effect of SAA in the context of CIRI. SOX7 was a target protein of miR‐212‐3p. Silencing SOX7 based on SAA and miR‐212‐3p knockdown suppressed OGD/R‐induced inflammation and apoptosis and increased Wnt3a and β‐catenin levels in PC12 cells. SAA can improve the brain and nervous system injury caused by cerebral ischemia–reperfusion by upregulating miR‐212‐3p, thereby inhibiting SOX7 and activating the Wnt/βcatenin signaling pathway.

Developing an efficient power system is an important way for icebreakers to respond to high maneuverability and strong fluctuation loads under icebreaking conditions. The performance of power systems under short-period, regularly fluctuating load-sea conditions has been intensively studied. However, the performance of the power system in the face of a long-period, stochastic multi-frequency fluctuation icebreaking process has not been fully explored, especially the parameter uncertainty and battery cycle life. In this study, an integrated electric propulsion system with an optimal control strategy is suggested for improving the power system’s dynamic performance and battery cycle life. First, an energy flow model with a diesel–electric unit as the main body and coupled energy storage system/hybrid energy storage system has been constructed. A comparative analysis of rule-based and optimization-based energy management strategies has been performed, and an optimized strategy with dynamic programming as global regulation at the upper level and model predictive control at the lower level is suggested to integrate the slow and fast dynamic powers and achieve adaptability to strong fluctuation loads. In this control strategy, the uncertainties of energy storage system/hybrid energy storage system parameters have been introduced to eliminate their impact on the system performance. Then, the icebreaking process with multi-frequency fluctuation has been simulated, and the hybrid energy storage system with battery and supercapacitor is recommended to reach multi-objective with the lowest power fluctuation of diesel–electric unit, highest efficiency, and the minimum battery degradation. Finally, the fuel oil consumption and emissions of the hybrid energy storage system have been discussed, and the optimized strategy can save fuel oil by up to 5.33% and reduce the CO2 emission by 22% during the icebreaking process, exhibiting great potential in the environmental friendliness and significant advantages in terms of low fuel oil consumption.

On-orbit geometric calibration is key to improving the geometric positioning accuracy of high-resolution optical remote sensing satellite data. Grouped calibration with geometric consistency (GCGC) is proposed in this paper for the Jilin1-KF01B satellite, which is the world’s first satellite capable of providing 150-km swath width and 0.5-m resolution data. To ensure the geometric accuracy of high-resolution image data, the GCGC method conducts grouped calibration of the time delay integration charge-coupled device (TDI CCD). Each group independently calibrates the exterior orientation elements to address the multi-time synchronization issues between imaging processing system (IPS). An additional inter-chip geometric positioning consistency constraint is used to enhance geometric positioning consistency in the overlapping areas between adjacent CCDs. By combining image simulation techniques associated with spectral bands, the calibrated panchromatic data are used to generate simulated multispectral reference band image as control data, thereby enhancing the geometric alignment consistency between panchromatic and multispectral data. Experimental results show that the average seamless stitching accuracy of the basic products after calibration is better than 0.6 pixels, the positioning accuracy without ground control points(GCPs) is better than 20 m, the band-to-band registration accuracy is better than 0.3 pixels, the average geometric alignment consistency between panchromatic and multispectral data are better than 0.25 multispectral pixels, the geometric accuracy with GCPs is better than 2.1 m, and the geometric alignment consistency accuracy of multi-temporal data are better than 2 m. The GCGC method significantly improves the quality of image data from the Jilin1-KF01B satellite and provide important references and practical experience for the geometric calibration of other large-swath high-resolution remote sensing satellites.

To enhance the static and dynamic performance of the grinding wheel spindle system, with the gear grinding machine (YKF2060) as the research object, a static mechanics model of the spindle system was established based on Castigliano’s theorem, taking into account the equivalent effect of the triple-point contact ball bearing at the front end of the spindle. Meanwhile, based on the overall transfer matrix method, a dynamic model of the main spindle–eccentric shaft dual-rotor system was established, taking into account the effects of shear deformation and gyroscopic moments. On this basis, the effect of the spindle span, the front and rear overhang of the eccentric shaft, and the bearing stiffness on the static stiffness and first-order critical speed of the system was analyzed. Finally, static stiffness experiments, modal tests, and finite element simulation models were conducted to verify the static and dynamic models. The results show that the stiffness of the front outer bearing has the greatest influence on the static and dynamic performance of the system, while the stiffness of the rear inner bearing has the least influence. The relative errors of the static stiffness and the first two natural frequencies between static stiffness experiments, modal tests, and finite element simulation models are less than 10%, and the mode shapes match well. The established static and dynamic model can effectively reflect both the static and dynamic characteristics of the spindle system.

In this work, a novel heterogeneous catalyst consisting of peroxophosphotungstate, microporous MOF-808, and mesoporous SBA-15 was synthesized, characterized, and used to remove sulfides from model fuel. The prepared material, PW4@MOF-808@SBA-15, exhibits excellent catalytic activity with a desulfurization efficiency of 99.8% in 60 min for multicomponent simulated fuel, and the desulfurization rate can reach more than 90% after ten consecutive cycles. The excellent catalytic activity and reusability are attributed to the hierarchically porous hybrid material MOF-808@SBA-15, which can effectively encapsulate PW4 and provide a site for the oxidation of sulfides.

Background: Estrogen-containing hormonal contraception (HC) is a well-established risk factor for venous thromboembolism (VTE). Women with sickle cell disease (SCD) also have an increased risk of VTE. However, it is unknown if exposure to HC exacerbates the risk of VTE in women with SCD. Objectives: Assess the impact of HC on VTE risk in women with SCD and explore additional risk factors contributing to VTE development. Methods: We analyzed a retrospective cohort of women of reproductive age (15-49 years) with SCD at the University of North Carolina from 2010 to 2022. Results: We identified 370 women with SCD, and 93 (25.1%) had a history of VTE. Among 219 women exposed to HC, 38 of 184 (20.6%) had a VTE while actively using HC, whereas 20 of 151 (13.2%) women never exposed to HC had a VTE. Of the patients exposed to HC, 64 of 184 (34.7%) were on estrogen-containing HC, with 120 of 184 (65.3%) using progestin-only formulations. Cox regression analysis found that progestin-only formulations increased VTE risk (hazard ratio: 2.03; 95% CI: 1.107-3.726, P < .05). However, when accounting for disease severity, the association between progestin-only treatment and VTE risk was not significant. Indeed, a nuanced analysis revealed that both severe (odds ratio: 11.79; 95% CI: 5.14-27.06; P < .001) and moderate (odds ratio: 4.37; 95% CI: 1.77-10.76; P = .001) disease increased risk compared with mild disease. Neither genotype nor hydroxyurea use influenced VTE risk. Conclusion: Overall, we found that increased thrombotic risk is more likely influenced by disease status than HC exposure and should play a role in shared decision-making with patients.

With the increase of extreme weather events such as cold waves, power transmission line icing has become more and more severe, affecting the safe and stable operation of power systems. Thus, icing prediction has become crucial for power grids. In this study, we collect multi-source data including the historical observations of meteorological elements and transmission line icing in Sichuan during 2017–2019, and develop an artificial intelligence (artificial intelligence)-based integrated model to achieve icing thickness prediction according to meteorological elements. Using the Weather Research and Forecasting model and the three-dimensional variational data assimilation method, we analyze the weather conditions in Sichuan of China during the 2020 winter, and obtain the high-precision meteorological element fields that are related to icing prediction. The forecasted meteorological elements are then combined with the AI-based integrated model to predict icing conditions, assisting in the warning of transmission line icing. The results indicate that the AI-based integrated model displays superior performance on the accurate prediction of icing thickness in the test set, with only two samples having prediction errors of more than 3 mm. Data assimilation can effectively improve the forecast accuracy of meteorological elements near icing observation stations and thus enhance the accuracy of icing thickness prediction. In particular, icing thickness prediction is remarkably improved at Gaoqiao, Laolinkou and Erlangshan stations.

Fresh ginseng has a high moisture content and is easy to be deteriorated, thus an effective drying method is needed. Infrared drying is known as low energy consumption, and high heat transfer, thus the far infrared (FIR) and near infrared (NIR) drying characteristics of ginseng were investigated and compared. Influences of infrared temperature, radiation distance, and slice thickness on the drying kinetics, specific energy consumption, color change and rehydration ratio were analyzed. Results indicated that the drying rate of ginseng increased with increasing infrared temperature and decreasing radiation distance and slice thickness. The drying time under FIR was shortened by 33.3%, 25% and 20% at 40 °C, 50 °C, 60 °C compared to that under NIR, indicating that the drying efficiency of FIR was superior to that of NIR and with the decrease of temperature, this improvement became more obvious. The specific energy consumption can be reduced by up to 40% under FIR and the infrared drying was much more energy-efficient than hot air drying, with an energy reduction by up to 51.1%. Optimization of FIR drying showed that the optimal conditions were at a drying temperature of 50 °C, a slice thickness of 2 mm and a radiation distance of the 4th layer.

Reducing the secondary inflammatory response, which is partly mediated by microglia, is a key focus in the treatment of spinal cord injury. Src homology 2-containing protein tyrosine phosphatase 2 (SHP2), encoded by PTPN11, is widely expressed in the human body and plays a role in inflammation through various mechanisms. Therefore, SHP2 is considered a potential target for the treatment of inflammation-related diseases. However, its role in secondary inflammation after spinal cord injury remains unclear. In this study, SHP2 was found to be abundantly expressed in microglia at the site of spinal cord injury. Inhibition of SHP2 expression using siRNA and SHP2 inhibitors attenuated the microglial inflammatory response in an in vitro lipopolysaccharide-induced model of inflammation. Notably, after treatment with SHP2 inhibitors, mice with spinal cord injury exhibited significantly improved hind limb locomotor function and reduced residual urine volume in the bladder. Subsequent in vitro experiments showed that, in microglia stimulated with lipopolysaccharide, inhibiting SHP2 expression promoted M2 polarization and inhibited M1 polarization. Finally, a co-culture experiment was conducted to assess the effect of microglia treated with SHP2 inhibitors on neuronal cells. The results demonstrated that inflammatory factors produced by microglia promoted neuronal apoptosis, while inhibiting SHP2 expression mitigated these effects. Collectively, our findings suggest that SHP2 enhances secondary inflammation and neuronal damage subsequent to spinal cord injury by modulating microglial phenotype. Therefore, inhibiting SHP2 alleviates the inflammatory response in mice with spinal cord injury and promotes functional recovery postinjury.

Abstract Hepatocellular carcinoma (HCC) is a lethal malignancy worldwide with an increasing number of new cases each year. Apolipoprotein (APOL) isoforms have been explored for their associations with HCC.The GSE14520 cohort was used for training data; The Cancer Genome Atlas (TCGA) database was used for validated data. Diagnostic, prognostic significance and mechanisms were explored using these cohorts. Risk score models and nomograms were constructed using prognosis-related isoforms and clinical factors for survival prediction. Oncomine and HCCDB databases were further used for validation of diagnostic, prognostic significance. APOL1, 3, and 6 were differentially expressed in two cohorts (all P ≤ 0.05). APOL1 and APOL6 had diagnostic capacity whereas APOL3 and APOL6 had prognostic capacity in two cohorts (areas under curves [AUCs] > 0.7, P ≤ 0.05). Mechanism studies demonstrated that APOL3 and APOL6 might be involved in humoral chemokine signaling pathways (all P ≤ 0.05). Risk score models and nomograms were constructed and validated for survival prediction of HCC. Moreover, diagnostic values of APOL1 and weak APOL6 were validated in Oncomine database (AUC > 0.700, 0.694); prognostic values of APOL3 and APOL6 were validated in HCCDB database (all P

Large quantity of observational data from ground and sounding meteorological observation data, ocean station observation data, ERA reanalysis data are used to count the sea fog process that occurred during April to July in Rizhao City from 1988 to 2019 altogether 32 years in this paper. The synoptic characteristics of the sea fog and their formation mechanism are statistically analyzed, and furthermore the main meteorological elements affecting the formation of sea fog in Rizhao area and their combined effects are put forward. The results indicate that sea fog occur in Rizhao area is most likely under the control of several weather conditions, such as the west of transition high to sea, the Pacific subtropical high ridge or the front of low or trough of the eastern China in spring and summer. Under the control of these synoptic characteristics, the direction and speed of wind, dew-point temperature, atmospheric temperature, SST, stratification stability of these hydrometeorological elements play an important role in the formation of sea fog. On these basis, the method of discriminance analysis is used to establish of discriminant equation for sea fog forecast. Through the forecast testing, the statistical forecasting method of sea fog has a great application, the forecast accuracy is between 88% and 94%. It can be used for short-term forecast of sea fog characteristics in Rizhao City, providing services for industry, agriculture, fishery production, sea and land transportation.

Abstract Background In this study, we investigated the coping mechanisms and stress perceptions of adolescent patients with Crohn's disease. Methods Using semi-structured face-to-face interviews, we conducted an extensive qualitative study of the disease perceptions, stress experiences, and corresponding coping mechanisms in adolescent patients with Crohn's disease. We used Colaizzi content analysis to synthesize the themes. Results The two main themes in this study were inappropriate coping mechanisms and physical and psychological stress. The primary initiators of physical and psychological stress in adolescents with Crohn's disease were weak disease perception, symptom distress, negative emotions, lack of support, and multiple stressors. The decrease in self-management and self-control induced by the initiators led to changes in cognition, emotions, and attitudes, which subsequently led to poor coping behavior. Conclusion Adolescents with Crohn's disease can better combat the condition by implementing appropriate coping strategies. Their mental health should be given attention, and a multidisciplinary team should be assembled to provide them with supportive care.

Abstract Worldwide, cancer is a huge burden, and each year sees an increase in its incidence. RAB (Ras-related in brain) 13 is crucial for a number of tumor types. But more research on RAB13's tumor-related mechanism is still required. This study's goal was to investigate RAB13's function in human pan-cancer, and we have also preliminarily explored the relevant mechanisms. To investigate the differential expression, survival prognosis, immunological checkpoints, and pathological stage of RAB13 in human pan-cancer, respectively, databases of TIMER2.0, GEPIA 2, and UALCAN were employed. CBioPortal database was used to analyze the mutation level, meanwhile, PPI network was constructed based on STRING website. The putative functions of RAB13 in immunological infiltration were investigated using single sample gene set enrichment analysis (ssGSEA). The mechanism of RAB13 in hepatocellular cancer was also briefly investigated by us using gene set enrichment analysis (GSEA). RAB13 was differentially expressed in a number of different cancers, including liver hepatocellular carcinoma (LIHC), stomach adenocarcinoma (STAD), etc. Additionally, RAB13 overexpression in LGG and LIHC is associated with a worse prognosis, including overall survival (OS) and disease-free survival (DFS). Then, we observed that early in BLCA, BRAC, CHOL, ESCA, HNSC, KICH, KIRC, LIHC, LUAD, LUSC, and STAD, the level of RAB13 expression was raised. Next, we found that “amplification” was the most common mutation in RAB13. The expression of SLC39A1, JTB, SSR2, SNAPIN, and RHOC was strongly positively linked with RAB13, according to a correlation study. RAB13 favorably regulated B cell, CD8 + T cell, CD4 + T cell, macrophage, neutrophil, and dendritic cell in LIHC, according to immune infiltration analysis. Immune checkpoint study revealed a positive correlation between RAB13 expression and PD1, PDL1, and CTLA4 in LIHC. According to GSEA, RAB13 is involved in a number of processes in LIHC, including MTORC1 signaling, MYC targets v1, G2M checkpoint, MITOTIC spindle, DNA repair, P53 pathway, glycolysis, PI3K-AKT-MTOR signaling, etc. RAB13 is a possible therapeutic target in LIHC and can be used as a prognostic marker.

Substantial proteolysis occurs and free amino acids can be degraded to biogenic amines by decarboxylation during stylo (Stylosanthes guianensis) ensiling. High biogenic amine concentrations in silage are harmful to the health of ruminant animals. The purposes of this work were to (1) analyze the biogenic amines and amino acids concentrations, bacterial composition, and fermentation profile of spontaneously fermented stylo silage, (2) explore the effect of formic acid or sugar additive on these silage parameters, and (3) further reveal the correlations between silage amines and fermentation parameters, amino acids, and bacteria. Freshly chopped stylo was treated with distilled water (control), formic acid (4 mL/kg), and sugar (20 g/kg) and fermented for 28 days. The results indicated that putrescine (321 mg/kg dry matter), cadaverine (384 mg/kg dry matter), and tyramine (127 mg/kg dry matter) rapidly increased in concentration and become predominant in the control silage after 28 days of fermentation. Applying formic acid and sugar at ensiling, especially the acidifier, significantly decreased putrescine, cadaverine, tyramine, and total biogenic amine concentrations compared with the control treatment (p < 0.0001). Clostridium pabulibutyricum, Weissella cibaria and W. paramesenteroides were the predominant bacteria in the control silage, and the application of both additives remarkably lowered their relative abundance in comparison with the control treatment (p < 0.001). Correlation analysis showed that putrescine, cadaverine, and tyramine were positively related to pH, butyric acid, non-protein nitrogen, and ammonia nitrogen (p < 0.01). These amines also had significant correlations with C. pabulibutyricum, W. cibaria and W. paramesenteroides (p < 0.001). Putrescine, cadaverine, and tyramine were the main biogenic amines and C. pabulibutyricum was the predominant undesirable bacterium in naturally fermented stylo silage. C. pabulibutyricum, W. cibaria and W. paramesenteroides were positively related to putrescine, cadaverine, and tyramine formation. The application of formic acid or sugar significantly reduced the undesirable bacterial population and improved the fermentation and hygienic quality of the stylo silage. These findings lay the foundation for further elucidating the microbial mechanism underlying the main biogenic amine formation during fermentation of stylo silage.

The China–Russia crude oil pipeline (CRCOP) operates at a temperature that continuously thaws the surrounding permafrost, leading to secondary periglacial phenomena along the route. However, the evolution and formation mechanisms of these phenomena are still largely unknown. We used multi-temporal airborne light detection and ranging (LiDAR), geophysical, and field observation data to quantify the scale of ponding and icing, capture their dynamic development process, and reveal their development mechanisms. The results show that the average depth of ponding within 5 m on both sides of the pipeline was about 31 cm. The volumes of three icings (A–C) above the pipeline were 133 m3, 440 m3, and 186 m3, respectively. Icing development can be divided into six stages: pipe trench settlement, water accumulation in the pipe trench, ponding pressure caused by water surface freezing, the formation of ice cracks, water overflow, and icing. This study revealed the advantages of airborne LiDAR in monitoring the evolution of periglacial phenomena and provided a new insight on the development mechanisms of the phenomena by combining LiDAR with geophysics and field observation. The results of our study are of great significance for developing disaster countermeasures and ensuring the safe operation of buried pipelines.

Mulberry sclerotiniose is a devastating fungal disease of mulberry fruit and has been a limitation for the utility of mulberry fruits and the diversified development of sericulture. In the present study, we presented a workflow for screening candidate sclerotiniose-resistance genes and small secreted peptides (SSPs) based on a genome-wide annotation of SSPs and comparative transcriptome analysis of different mulberry varieties. A total of 1088 SSPs with expression evidence were identified and annotated in mulberry. A comprehensive analysis of the sclerotiniose-related RNA sequencing datasets showed that photosynthesis, plant hormone signaling, and metabolic pathways were the main pathways involved in the response to sclerotiniose. Fifty-two candidate sclerotiniose-response genes (SRGs), including 15 SSPs, were identified based on comparative transcriptome analysis. These SRGs are mainly involved in the hormone signaling pathway and cell wall biogenesis. Transient overexpression in tobacco and the knock-down of five SRGs affected the resistance against Ciboria shiraiana. MaMYB29, MaMES17, and MaSSP15 were primarily determined as negative regulators of plant resistance to C. shiraiana infection. Our results provide a foundation for controlling sclerotiniose in mulberry using genetic engineering and biological approaches such as spraying antifungal peptides.

Abstract Background Autophagy is a critical self-eating pathway involved in numerous physiological and pathological processes. Lysosomal degradation of dysfunctional organelles and invading microorganisms is central to the autophagy mechanism and essential for combating disease-related conditions. Therefore, monitoring fluctuations in the lysosomal microenvironment is vital for tracking the dynamic process of autophagy. Although much effort has been put into designing probes for measuring lysosomal viscosity or pH separately, there is a need to validate the concurrent imaging of the two elements to enhance the understanding of the dynamic progression of autophagy. Methods Probe HFI was synthesized in three steps and was developed to visualize changes in viscosity and pH within lysosomes for real-time autophagy tracking. Then, the spectrometric determination was carried out. Next, the probe was applied to image autophagy in cells under nutrient-deprivation or external stress. Additionally, the performance of HFI to monitor autophagy was employed to evaluate acetaminophen-induced liver injury. Results We constructed a ratiometric dual-responsive probe, HFI, with a large Stokes shift over 200 nm, dual-wavelength emission, and small background interference. The ratiometric fluorescent signal (R = I 610/I 460) of HFI had an excellent correlation with both viscosity and pH. More importantly, high viscosity and low pH had a synergistic promotion effect on the emission intensity of HFI, which enabled it to specially lit lysosomes without disturbing the inherent microenvironment. We then successfully used HFI to monitor intracellular autophagy induced by starvation or drugs in real-time. Interestingly, HFI also enabled us to visualize the occurrence of autophagy in the liver tissue of a DILI model, as well as the reversible effect of hepatoprotective drugs on this event. Conclusions In this study, we developed the first ratiometric dual-responsive fluorescent probe, HFI, for real-time revealing autophagic details. It could image lysosomes with minimal perturbation to their inherent pH, allowing us to track changes in lysosomal viscosity and pH in living cells. Ultimately, HFI has great potential to serve as a useful indicator for autophagic changes in viscosity and pH in complex biological samples and can also be used to assess drug safety.

Abstract Background Hepatocellular carcinoma (HCC) is a long-term malignancy that causes high morbidities and mortalities worldwide. Notably, long non-coding RNAs (LncRNAs) have been identified as candidate targets for malignancy treatments. Methods LncRNA LINC01116 and its Pearson-correlated genes (PCGs) were identified and analyzed in HCC patients. The diagnostic and prognostic value of the lncRNA was evaluated using data from The Cancer Genome Atlas (TCGA). Further, we explored the target drugs of LINC01116 for clinical application. Relationships between immune infiltration and PCGs, methylation and PCGs were explored. The diagnostic potentials were then validated by Oncomine cohorts. Results LINC01116 and the PCG OLFML2B are differentially and highly expressed in tumor tissues (both P ≤ 0.050). We found that LINC01116, TMSB15A, PLAU, OLFML2B, and MRC2 have diagnostic potentials (all AUC ≥ 0.700, all P ≤ 0.050) while LINC01116 and TMSB15A have prognostic significance (both adjusted P ≤ 0.050). LINC01116 was enriched in the vascular endothelial growth factor (VEGF) receptor signaling pathway, mesenchyme morphogenesis, etc. After that, candidate target drugs with potential clinical significance were identified: Thiamine, Cromolyn, Rilmenidine, Chlorhexidine, Sulindac_sulfone, Chloropyrazine, and Meprylcaine. Analysis of immune infiltration revealed that MRC2, OLFML2B, PLAU, and TMSB15A are negatively associated with the purity but positively associated with the specific cell types (all P 0.700). Conclusions Differentially expressed LINC01116 could be a candidate diagnostic and an independent prognostic signature in HCC. Besides, its target drugs may work for HCC therapy via the VEGF receptor signaling pathway. Differentially expressed OLFML2B could be a diagnostic signature involved in HCC via immune infiltrates.

In recent years, it has been gradually recognized that efficient scheduling of automated guided vehicles (AGVs) can help companies find the balance between energy consumption and workstation satisfaction. Therefore, the energy consumption of AGVs for the manufacturing environment and the AGV energy efficient scheduling problem with customer satisfaction (AGVEESC) in a flexible manufacturing system are investigated. A new multi-objective non-linear programming model is developed to minimize energy consumption while maximizing workstation satisfaction by optimizing the pick-up and delivery processes of the AGV for material handling. Through the introduction of auxiliary variables, the model is linearized. Then, an interactive fuzzy programming approach is developed to obtain a compromise solution by constructing a membership function for two conflicting objectives. The experimental results show that a good level of energy consumption and workstation satisfaction can be achieved through the proposed model and algorithm.

Abstract Background Yolk sac tumour (YST) is the second most common ovarian germ cell tumour and usually presents in children and young women. However, tumours rarely occur as malignant gynaecological tumours with YST components. Case presentation We present one case of endometrioid carcinoma and clear cell carcinoma with YST components and two other cases of YSTs associated with high-grade serous carcinoma of the ovary in females. After surgery and adjuvant chemotherapy, the patient with endometrioid carcinoma had progressive disease and died 20 months later, and the other two were still alive at the last follow-up. Conclusions To our knowledge, these mixed neoplasm associations are unusual, and these cases illustrate the diagnosis and prognosis of YST associated with malignant gynaecological tumours, emphasizing early recognition and aggressive treatment.

Following a loss of coolant accident (LOCA), prestressing concrete containment vessels (PCCVs) may experience high thermal load as well as internal pressure. The high temperature stress would increase the risk of premature damage to the containment, which reduces the safety margin during the increasing internal pressure. However, current investigations cannot clearly address the issues of thermal-pressure coupling effect on damage propagation and thus safety of the containment. Thus, this paper offers three simple and powerful damage parameters to differentiate the severity of damage of the containment. Moreover, despite of the temperature action severely threatening the pressure performance of the containment, the research regarding the improvement of the resistant performance of the containment is quite scarce. Therefore, in this paper, a comprehensive comparison of damage propagation and mechanism between conventional and fiber-reinforced concrete (FRC) containments is performed. The effects of fiber characteristics parameters on damage propagation of structures following the LOCA are also specifically revealed. It is found that the proposed damage indices can properly indicate state of damage in the containment body and the addition of fiber can be used to obviously mitigate the damage propagation in PCCV considering the thermal-pressure coupling.

Bile acids (BAs) constitute essential components of cholesterol metabolites that are synthesized in the liver, stored in the gallbladder, and excreted into the intestine through the biliary system. They play a crucial role in nutrient absorption, lipid and glucose regulation, and the maintenance of metabolic homeostasis. In additional, BAs have demonstrated the ability to attenuate disease progression such as diabetes, metabolic disorders, heart disease, and respiratory ailments. Intriguingly, recent research has offered exciting evidence to unveil their potential antitumor properties against various cancer cell types including tamoxifen-resistant breast cancer, oral squamous cell carcinoma, cholangiocarcinoma, gastric cancer, colon cancer, hepatocellular carcinoma, prostate cancer, gallbladder cancer, neuroblastoma, and others. Up to date, multiple laboratories have synthesized novel BA derivatives to develop potential drug candidates. These derivatives have exhibited the capacity to induce cell death in individual cancer cell types and display promising anti-tumor activities. This review extensively elucidates the anticancer activity of natural BAs and synthetic derivatives in cancer cells, their associated signaling pathways, and therapeutic strategies. Understanding of BAs and their derivatives activities and action mechanisms will evidently assist anticancer drug discovery and devise novel treatment.

Mycotoxin aflatoxin B1 (AFB1) is a threat to food safety and human health because it is present in animal feed and is metabolized into aflatoxin M1 (AFM1), a more toxic form, during lactation. The aim of this study was to quantify AFM1 concentrations in raw milk of buffalos, cows, sheep, and goats sampled randomly from four regions within Baghdad ‎Province, Iraq, and to compare these levels with the maximum allowable levels set forth by the ‎European Commission (EC), the Iraqi Standard Specification (IQS), and the food and Drug Administration (FDA). The carry-over of AFB1 from feed to AFM1 in milk were also calculated for each of the ‎studied species. A total of 200 random samples, including 50 each from cows, buffaloes, ‎sheep, and goats, were collected from farms located in Zu'afraniya, Nahrawan, Abu Ghraib, and ‎Fedhalia regions. AFM1 and AFB1 concentrations were determined using the ‎enzyme-linked immunosorbent assay (ELISA). Raw milk samples from cows, sheep, buffaloes, and goats were all found to have AFM1 concentrations that were below the limits set by the EC, IQS, and FDA. Animal feed samples, on the other hand, had AFB1 concentrations of 10.08, 5.95, 4.27, and 7.10 ppb for ‎buffaloes, cows, sheep, and goats, respectively. The observed carry-over rates ranged from 0.36% ‎in goats to 0.78% in buffaloes to 0.66% in cows. Multiple factors, including animal species, ‎are considered, and it is determined that a universal carry-over equation cannot be applied to all cases. ‎Therefore, it is essential to regularly monitor AFM1 levels in milk from various animal species in order to ‎lessen potential health risks. Furthermore, the study suggests enhancing agricultural and veterinary ‎practices to better regulate feed quality for dairy animals‎‎‎‎.

The stability of underground entry-type excavations will directly affect the working environment and the safety of staff. Empirical critical span graphs and traditional statistics learning methods can not meet the requirements of high accuracy for stability assessment of entry-type excavations. Therefore, this study proposes a new prediction method based on machine learning to scientifically adjust the critical span graph. Accordingly, the particle swarm optimization (PSO) algorithm is used to optimize the core parameters of the gradient boosting decision tree (GBDT), abbreviated as PSO-GBDT. Moreover, the classification performance of eight other classifiers including GDBT, k-nearest neighbors (KNN), two kinds of support vector machines (SVM), Gaussian naive Bayes (GNB), logistic regression (LR) and linear discriminant analysis (LDA) are also applied to compare with the proposed model. Findings revealed that compared with the other eight models, the prediction performance of PSO-GBDT is undoubtedly the most reliable, and its classification accuracy is up to 0.93. Therefore, this model has great potential to provide a more scientific and accurate choice for the stability prediction of underground excavations. In addition, each classification model is used to predict the stability category of several grid points divided by the critical span graph, and the updated critical span graph of each model is discussed in combination with previous studies. The results show that the PSO-GBDT model has the advantages of being scientific, accurate and efficient in updating the critical span graph, and its output decision boundary has strict theoretical support, which can help mine operators make favorable economic decisions.

With the rapid development of asphalt pavement technology, it has attracted considerable attention to improving the durability of asphalt pavement. An effective action is to use modified asphalt with high performance and durability. Polyurethane (PU) has been used in asphalt pavement engineering to enhance the durability and service life of asphalt pavement because of its excellent high-temperature performance, toughness, wear resistance, aging resistance and oil resistance. However, PU modified asphalt technology is still in the exploratory stage. The preparation, modification mechanism and working performances of PU modified asphalt need to be further clarified. Therefore, this paper summarized the research progress of PU modified asphalt and its mixture. The composition of PU modified asphalt was introduced. The addition methods of PU materials and preparation process parameters of the PU modified asphalt were determined. The modification mechanism of PU on asphalt was discussed. The effects of polyurethane on asphalt were analyzed and the road performances of its mixture were evaluated. Finally, the development tendency towards PU modified asphalt and its mixture were forecasted.

A decentralized supply chain network under uncertain cost is studied to obtain the optimal decisions of the enterprises in a situation in which the cost is uncertain. The supply chain network members adopt a chance-constrained approach to make decisions. The second-order cone-constrained variational inequality problem is used to construct the chance-constrained supply chain network equilibrium model. Then, the existence and uniqueness properties of the proposed equilibrium model are discussed under some mild assumptions. For the discontinuous functions in the feasible region of the model, the proposed model is converted to a second-order cone complementarity problem. The numerical results show that the uncertainty and risk attitude of retailers and manufacturers have different effects on supply chain network members. When the risk attitude is high, a small change in the risk attitude will significantly change all decisions of supply chain members. If the supply chain member is affected by the uncertainty positively, its profit will increase as its risk attitude increases. Moreover, it is appropriate to adopt a chance-constrained approach when the supply chain members can estimate the distributions of the competitor's strategies.

Abstract Background Macroautophagy is an essential cellular self-protection mechanism, and defective autophagy has been considered to contribute to a variety of diseases. During the process, cytoplasmic components are transported via autophagosomes to acidic lysosomes for metabolism and recycling, which represents application niches for lysosome-targeted fluorescent probes. Additionally, in view of the complexity of the autophagy pathway, it entails more stringent requirements for probes suitable for monitoring autophagy. Meanwhile, aggregation-induced emission (AIE) fluorescent probes have been impressively demonstrated in the biomedical field, which bring fascinating possibilities to the autophagy visualization. Methods We reported a generalizable de novo design of a novel pH-sensitive AIE probe ASMP-AP tailored to lysosome targeting for the interpretation of autophagy. Firstly, the theoretical calculation was carried out followed by the investigation of optical properties. Then, the performance of ASMP-AP in visualizing autophagy was corroborated by starvation or drugs treatments. Furthermore, the capability of ASMP-AP to monitor autophagy was demonstrated in ex vivo liver tissue and zebrafish in vivo. Results ASMP-AP displays a large stokes shift, great cell permeability and good biocompatibility. More importantly, ASMP-AP enables a good linear response to pH, which derives from the fact that its aggregation state can be manipulated by the acidity. It was successfully applied for imaging autophagy in living cells and was proved capable of monitoring mitophagy. Moreover, this novel molecular tool was validated by ex vivo visualization of activated autophagy in drug-induced liver injury model. Interestingly, it provided a meaningful pharmacological insight that the melanin inhibitor 1-phenyl-2-thiourea (PTU)-induced autophagy was clearly presented in wild-type zebrafish. Conclusions ASMP-AP offers a simple yet effective tool for studying lysosome and autophagy. This is the first instance to visualize autophagy in zebrafish using a small-molecule probe with AIE characters, accurate lysosome targeting and simultaneous pH sensitivity. Ultimately, this novel fluorescent system has great potential for in vivo translation to fuel autophagy research. Graphical Abstract

The precise editing of genes mediated by CRISPR-Cas9 necessitates the application of donor DNA with appropriate lengths of homologous arms and fragment sizes. Our previous development, SSB/CRISPR-Cas9, has demonstrated high efficiency in homologous recombination and non-homologous end joining gene editing within bacteria. In this study, we optimized the lengths and sizes of homologous arms of the donor DNA within this system. Two sets of donor DNA constructs were generated: one set comprised donors with only 10–100 bp homologous arms, while the other set included donors with homologous arms ranging from 10–100 bp, between which was a tetracycline resistance expression cassette (1439 bp). These donor constructs were transformed into Escherichia coli MG1655 cells alongside pCas-SSB/pTargetF-lacZ. Notably, when the homologous arms ranged from 10 to 70 bp, the transformation efficiency of non-selectable donors was significantly higher than that of selectable donors. However, within the range of 10–100 bp homologous arm lengths, the homologous recombination rate of selectable donors was significantly higher than that of non-selectable donors, with the gap narrowing as the homologous arm length increased. For selectable donor DNA with homologous arm lengths of 10–60 bp, the homologous recombination rate increased linearly, reaching a plateau when the homologous arm length was between 60–100 bp. Conversely, for non-selectable donor DNA, the homologous recombination rate increased linearly with homologous arm lengths of 10–90 bp, plateauing at 90–100 bp. Editing two loci simultaneously with 100 bp homologous arms, whether selectable or non-selectable, showed no difference in transformation or homologous recombination rates. Editing three loci simultaneously with 100 bp non-selectable homologous arms resulted in a 45% homologous recombination rate. These results suggest that efficient homologous recombination gene editing mediated by SSB/CRISPR-Cas9 can be achieved using donor DNA with 90–100 bp non-selectable homologous arms or 60–100 bp selectable homologous arms.

The application potential of additive manufacturing nickel-based superalloys in aeroengines and gas turbines is extensive, and evaluating their mechanical properties is crucial for promoting the engineering application in load-bearing components. In this study, Hastelloy X alloy was prepared using the laser powder bed fusion process combined with solution heat treatment. The tensile and high cycle fatigue properties were experimentally investigated at room temperature as well as two typical elevated temperatures, 650 °C and 815 °C. It was found that, during elevated-temperature tensile deformation, the alloy exhibits significant serrated flow behavior, primarily observed during the initial stage of plastic deformation at 650 °C but occurring throughout the entire plastic deformation process at 815 °C. Notably, when deformation is small, sawtooth fluctuations are significantly higher at 815 °C compared to 650 °C. Irregular subsurface lack of fusion defects serve as primary sources for fatigue crack initiation in this alloy including both single-source and multi-source initiation mechanisms; moreover, oxidation on fracture surfaces is more prone to occur at elevated temperatures, particularly at 815 °C.

Despite the deployment of specific breast cancer screening strategies, breast cancer incidence rates have escalated significantly over recent decades. In a bid to reverse this trend, scientists have engaged in extensive epidemiological research into breast cancer prevalence, identifying numerous individual risk factors and promoting population-wide health education. Coupled with advances in genetic testing, risk prediction models based on breast cancer genes have been developed, albeit with inherent limitations. In the new millennium, the emergence of artificial intelligence (AI) as a dominant technological force suggests that breast cancer prediction models developed with AI may represent the next frontier in research.

Adequate vascularization is crucial for the repair of bone defects. Platelet-derived growth factor-BB (PDGF-BB) has been shown to promote H-type vessel formation, a specialized blood vessel, strongly positive for CD31 and endomucin, coupling angiogenesis and osteogenesis. However, the lack of a controllable growth factor delivery limits its clinical application, causing certain complications associated with PDGF-BB administration. This study developed an injectable heparin-conjugated hydrogel (GHH) for controlled delivery to facilitate the effective binding of PDGF-BB and rapid vascularized bone regeneration. Herein, in vitro experiments involving the controlled release of PDGF-BB showed that the PDGF-BB-loaded GHH (GHHP) hydrogel demonstrated excellent cytocompatibility and osteogenic properties. The subcutaneous implantation model in rats revealed that the GHHP hydrogel has the potential to induce the formation of H-type blood vessels in vivo. Furthermore, the healing of distal femoral condyle defects in rat models in vivo demonstrated that GHHP could substantially promote H-type angiogenesis and effectively repair bone defects. Our injectable heparin-conjugated sustained-release PDGF-BB hydrogel has excellent angiogenic and osteogenic properties, thus providing a novel and promising solution for bone defect repair.

Regulation of cell mortality for disease treatment has been the focus of research. Ferroptosis is an iron-dependent regulated cell death whose mechanism has been extensively studied since its discovery. A large number of studies have shown that regulation of ferroptosis brings new strategies for the treatment of various benign and malignant diseases. Iron excess and lipid peroxidation are its primary metabolic features. Therefore, genes involved in iron metabolism and lipid metabolism can regulate iron overload and lipid peroxidation through direct or indirect pathways, thereby regulating ferroptosis. In addition, glutathione (GSH) is the body’s primary non-enzymatic antioxidants and plays a pivotal role in the struggle against lipid peroxidation. GSH functions as an auxiliary substance for glutathione peroxidase 4 (GPX4) to convert toxic lipid peroxides to their corresponding alcohols. Here, we reviewed the researches on the mechanism of ferroptosis in recent years, and comprehensively analyzed the mechanism and regulatory process of ferroptosis from iron metabolism and lipid metabolism, and then described in detail the metabolism of GPX4 and the main non-enzymatic antioxidant GSH in vivo.

Abstract Background Anterior colporrhaphy (AC) is a conventional surgical repair technique for cystocele but with high recurrence rate. We present a novel technique: Cable-suspended structure (CSS) by non-absorbable suture combined with "bridge" formation in surgical treatment of cystocele. This study aimed to evaluate and compare the long-term outcome of CSS technique for anterior vaginal wall repair with AC. Methods A retrospective review was performed on patients who underwent anterior vaginal wall repair between January 2012 and March 2017 at our center. All the patients were under a follow-up survey. The primary outcomes were objective cure (anterior prolapse POP-Q ≤ stage 1) and subjective cure (no symptoms of bulge or retreatment for prolapse). Secondary outcomes included quality of life (QOL) and patients’ satisfaction, outcomes of site-specific POP-Q points Aa, Ba and C, as well as postoperative complications. Results Of 91 included participants, 43 underwent AC and 48 underwent CSS. The proportion of sarcrospinous ligament fixation in the CSS group was higher than in the AC group (81.4% vs. 77.1%, P

Abstract Short‐term traffic flow prediction is particularly important for urban traffic control and congestion management. To improve the accuracy of traffic flow prediction, a new traffic flow prediction approach is proposed from the perspective of vehicle functions by using Radio Frequency Identification (RFID) electronic license plate (ELP) data. First, the improved Wavelet Neural Network (WNN) is introduced by adding three momentum terms to avoid local minimum and overfitting. The Long Short‐Term Memory Neural Network (LSTM) is constructed to train the time series with long time lags. Second, a novel short‐term traffic flow prediction method is developed by combining the improved WNN and LSTM in an urban road section. The proposed method performs a weighted combination to obtain a new prediction value according to whether the difference between the prediction values of the two methods satisfy the defined threshold, and then selects the one with the smallest error among the three prediction values as the final prediction result. Third, the experiments explore the prediction performance of the weekdays and weekends with 5 min‐interval, 15 min‐interval and 30 min‐interval via using RFID‐ELP data from Chongqing, China. Compared with existing prediction methods, the proposed approach can promote prediction performance and meet real‐time requirements.