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The interfacial behaviors between protective coatings and substrate single-crystal superalloys significantly impact their service performances. This work focuses on the elements interdiffusion and microstructural evolution at the interface between a NiCrAlY coating and a series of high-Mo Ni3Al-based single-crystal superalloys, through the coupled phase-field simulations and DICTRA kinetics calculations of their model systems. The critical roles of Al and Cr played in the microstructural evolution at coating/superalloy interface have been confirmed, which requires the appropriate content decreases of Al and Cr in the coating at 1100 °C. However, the addition of Mo reduces the driving force of element diffusion from coating to substrate by increasing the activities of Al and Cr in superalloy. Moreover, increasing the Mo content in superalloy from 8 wt% to 10 wt% could also counteract the promoting effect of Al on Ni mobility and mitigate the γ′ coarsening and detrimental TCP precipitation. Therefore, the effects of Mo enable the reasonable increase of Al content in coating to better balance the interfacial stability and oxidation resistance of coated superalloy, besides its advantage in reducing the anisotropy of TCP precipitate. The obtained interfacial evolution mechanisms resulting from the phase transformation thermodynamics and element interdiffusion kinetics are expected to aid the coating design for advanced single-crystal superalloys servicing at ultra-high temperature.

Progranulin (PGRN), a multifunctional growth factor-like protein expressed by a variety of cell types, serves an important function in the physiologic and pathologic processes of fibrotic diseases, including wound healing and the inflammatory response. PGRN was discovered to inhibit pro-inflammation effect by competing with tumor necrosis factor-alpha (TNF-α) binding to TNF receptors. Notably, excessive tissue repair in the development of inflammation causes tissue fibrosis. Previous investigations have indicated the significance of PGRN in regulating inflammatory responses. Recently, multiple studies have shown that PGRN was linked to fibrogenesis, and was considered to monitor the formation of fibrosis in multiple organs, including liver, cardiovascular, lung and skin. This paper is a comprehensive review summarizing our current knowledge of PGRN, from its discovery to the role in fibrosis. This is followed by an in-depth look at the characteristics of PGRN, consisting of its structure, basic function and intracellular signaling. Finally, we will discuss the potential of PGRN in the diagnosis and treatment of fibrosis.

To explore the structural dynamic characteristics of the impeller and shaft system of the axial flow pump as turbine, the variation law of impeller transient equivalent stress, deformation, and the impeller and shaft system mode are analyzed by the transient fluid-structure interaction method. Findings indicate that the equivalent stress is centralized at the blade root around the hub and tends to decrease as it moves towards the shroud. The maximum equivalent stress at 1.0Qbep and 1.1Qbep is 1.26 times and 2.0 times higher than that at 0.8Qbep. Blade deformation is significantly influenced by flow rate. The maximum deformation of the blade at 1.0Qbep and 1.1Qbep is 1.6 times and 3.6 times higher than that at 0.8Qbep. The impeller and shaft system with prestress in dry mode has an average natural frequency of the first 10 orders that is 16.7 Hz higher than without prestress. However, with the fluid adding mass and flow damping, the average natural frequency of the first 10 orders of the impeller and shaft system in wet mode is reduced by 278.08 Hz compared with dry mode. In fact, the impeller and shaft system of the axial flow pump as turbine is not prone to vibration.

Ultra-fine grained magnesium alloys are usually prepared by severe deformation and medium-low temperature deformation. In this work, it has been found that the binary Mg-1.2Ce alloy with the uniform distributed Mg12Ce precipitates smaller than 3 μm is a good candidate to obtain ultra-fine grains by conventional one-step extrusion at high temperatures. All the three Mg-1.2Ce samples extruded at 300 °C, 350 °C and 400 °C show a bimodal microstructure with high-density dislocations, whose average grain sizes are 1.19 ± 0.92 μm, 1.32 ± 1.30 μm, and 1.44 ± 1.33 μm, respectively. A linear relation of ln(d) = -0.05ln(Z)+1.27 was determined relating the average grain size (d) to the Zener-Hollomon parameter (Z). The alloy extruded at 300 °C exhibits an exceptionally high ultimate tensile strength (UTS) of 412.3 ± 5.3 MPa and yield strength (TYS) of 387.6 ± 3.2 MPa, but a low elongation after fracture (El) of 4.9 ± 0.8 %. With the extrusion temperature increasing, the tensile strength gradually decreases. For the 1.2E-400 sample, the TYS and the UTS drop to 347.2 ± 2.1 MPa and 349.4 ± 2.8 MPa, while the El increases to a more acceptable value of 12.6 ± 1.4 %. The microstructure analysis reveals that Ce atoms segregate along grain boundaries and dislocations in the Mg-1.2Ce alloy, which can limit the gliding of GBs or the slipping and climbing of dislocations. Additionally, dislocations can be pinned by Mg12Ce precipitates, thereby also restricting dislocation and grain boundary mobility. Consequently, the dynamic recrystallization (DRX) process is delayed, leading to the formation of a bimodal microstructure.

20CrMnTi steel is widely used in the gear manufacturing field of engineering machinery. The addition of Ti element to steel can effectively improve its low-temperature impact toughness and enhance its mechanical properties. However, during the smelting process of 20CrMnTi, large-sized TiN inclusions are inevitably formed in the steel, which affects its service performance improvement. This paper focuses on the directional modification behaviors of TiN inclusions in 20CrMnTi gear steel by rare earth Ce under deoxygenation conditions of Si–Ca–Ba alloy. The results show that under the deoxygenation conditions of Si–Ca–Ba alone, there are composite inclusions in 20CrMnTi steel with CaAl12O19 as the core and TiN wrapped around the periphery, all of which have sizes greater than 2 μm. This type of inclusion is square or diamond shaped, and the addition of Si–Ca–Ba deoxygenation alone has poor TiN modification effect on gear steel 20CrMnTi. Adding Ce element can effectively improve the nucleation core of inclusions. The CeAlO3–TiN and (CaAl12O19–Ba–Ce)–TiN composite inclusions are formed, and the TiN inclusions are modified in terms of morphology and size. The average size of inclusions decreases from 4.1 to 3.0 μm, which prevented the excessive growth of pure TiN inclusions to some extent.

The Gross Domestic Product (GDP) per capita is one of the most widely used socioeconomic indicators, serving as an integral component for climate change impact analysis. However, a national scale assessment may induce considerable bias because it conceals any internal variations within a country. The lack of a long-term sub-national scale GDP data is a substantive hinderance. Leveraging the close relationship between nighttime lights and GDP, we address this gap by developing a novel methodological framework in two steps. First, under the modeling philosophy of spatial statistics, we developed a novel approach based on deep and machine learning techniques to establish a complex mapping between two inconsistent nighttime lights (NTL) datasets: the Defense Meteorological Satellite Program’s Operational Linescan System (DMSP) and the National Polar-Orbiting Partnership’s Visible Infrared Imaging Radiometer Suite (VIIRS). The models achieve accuracies ranging from 0.945 to 0.980 (correlation coefficients). By taking the estimations ensemble of the two techniques, the time series of DMSP data was extended to 2021. Next, a novel modeling strategy based on multi-layer perceptron was developed to derive the non-linear relationship between NTL and GDP per capita at sub-national scale to alleviate scale effects at this granularity, while explicitly capturing regional heterogeneity effect. The trained models achieve average accuracies of 0.967, 0.959, and 0.959 on the training, validation, and test sets, respectively. We evaluate the developed dataset at the global, national, and sub-national scales from various perspective, and the results offer solid evidence on the reliability of the estimated economic data. By linking to historical global climate change data, we quantify global economic losses attributed to extreme heat to demonstrate how the estimated GDP data can be useful in the climate change impact analysis.

Artificial light at night (ALAN) is a common form of light pollution worldwide, and the intensity, timing, duration, and wavelength of light exposure can affect biological rhythms, which can lead to metabolic, reproductive, and immune dysfunctions and consequently, host–pathogen interactions. Insect vector-borne diseases are a global problem that needs to be addressed, and ALAN plays an important role in disease transmission by affecting the habits and physiological functions of vector organisms. In this work, we describe the mechanisms by which ALAN affects host physiology and biochemistry, host–parasite interactions, and vector-borne viruses and propose preventive measures for related infectious diseases to minimize the effects of artificial light on vector-borne diseases.

Summary: Background: In order to address the low compliance and dissatisfied specificity of low-dose computed tomography (LDCT), efficient and non-invasive approaches are needed to complement its limitations for lung cancer screening and management. The ASCEND-LUNG study is a prospective two-stage case–control study designed to evaluate the performance of a liquid biopsy-based comprehensive lung cancer screening and post-screening pulmonary nodules management system. Methods: We aimed to develop a comprehensive lung cancer system called Peking University Lung Cancer Screening and Management System (PKU-LCSMS) which comprises a lung cancer screening model to identify specific populations requiring LDCT and an artificial intelligence-aided (AI-aided) pulmonary nodules diagnostic model to classify pulmonary nodules following LDCT. A dataset of 465 participants (216 cancer, 47 benign, 202 non-cancer control) were used for the two models’ development phase. For the lung cancer screening model development, cancer participants were randomly split at a ratio of 1:1 into the train and validation cohorts, and then non-cancer controls were age-matched to the cancer cases in a 1:1 ratio. Similarly, for the AI-aided pulmonary nodules model, cancer and benign participants were also randomly divided at a ratio of 2:1 into the train and validation cohorts. Subsequently, during the model validation phase, sensitivity and specificity were validated using an independent validation cohort consisting of 291 participants (140 cancer, 25 benign, 126 non-cancer control). Prospectively collected blood samples were analyzed for multi-omics including cell-free DNA (cfDNA) methylation, mutation, and serum protein. Computerized tomography (CT) images data was also obtained. Paired tissue samples were additionally analyzed for DNA methylation, DNA mutation, and messenger RNA (mRNA) expression to further explore the potential biological mechanisms. This study is registered with ClinicalTrials.gov, NCT04817046. Findings: Baseline blood samples were evaluated for the whole screening and diagnostic process. The cfDNA methylation-based lung cancer screening model exhibited the highest area under the curve (AUC) of 0.910 (95% CI, 0.869–0.950), followed by the protein model (0.891 [95% CI, 0.845–0.938]) and lastly the mutation model (0.577 [95% CI, 0.482–0.672]). Further, the final screening model, which incorporated cfDNA methylation and protein features, achieved an AUC of 0.963 (95% CI, 0.942–0.984). In the independent validation cohort, the multi-omics screening model showed a sensitivity of 99.2% (95% CI, 0.957–1.000) at a specificity of 56.3% (95% CI, 0.472–0.652). For the AI-aided pulmonary nodules diagnostic model, which incorporated cfDNA methylation and CT images features, it yielded a sensitivity of 81.1% (95% CI, 0.732–0.875), a specificity of 76.0% (95% CI, 0.549–0.906) in the independent validation cohort. Furthermore, four differentially methylated regions (DMRs) were shared in the lung cancer screening model and the AI-aided pulmonary nodules diagnostic model. Interpretation: We developed and validated a liquid biopsy-based comprehensive lung cancer screening and management system called PKU-LCSMS which combined a blood multi-omics based lung cancer screening model incorporating cfDNA methylation and protein features and an AI-aided pulmonary nodules diagnostic model integrating CT images and cfDNA methylation features in sequence to streamline the entire process of lung cancer screening and post-screening pulmonary nodules management. It might provide a promising applicable solution for lung cancer screening and management. Funding: This work was supported by Science, Science, Technology & Innovation Project of Xiongan New Area, Beijing Natural Science Foundation, CAMS Innovation Fund for Medical Sciences (CIFMS), Clinical Medicine Plus X-Young Scholars Project of Peking University, the Fundamental Research Funds for the Central Universities, Research Unit of Intelligence Diagnosis and Treatment in Early Non-small Cell Lung Cancer, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, Peking University People's Hospital Research and Development Funds, National Key Research and Development Program of China, and the fundamental research funds for the central universities.

The exposure of organic UV filters has been increasingly confirmed to induce adverse effects on humans. However, the critical exposure pathway and the vulnerable population of organic UV filters are not clearly identified. This paper attempts to evaluate the health risk of commonly used organic UV filters from various exposure routes based on comprehensive analysis strategy. The estimated daily intakes (EDI) and hazard quotient (HQ) values of organic UV filters through four pathways (dermal exposure, indoor dust, indoor air, and drinking water) for various age groups were determined. Although the total HQ values (0.01–0.4) from comprehensive exposure of organic UV filters were below risk threshold (1.0), infants were identified as the most vulnerable population, with EDI (75.71 ng/kg-bw/day) of 2–3 times higher than that of adults. Additionally, the total EDI values of individual exposure pathways were estimated and ranked as follows: indoor air (138.44 ng/kg-bw/day) > sunscreen application (37.2 ng/kg-bw/day) > drinking water (21.87 ng/kg-bw/day) > indoor dust (9.24 ng/kg-bw/day). Moreover, we successfully tailored the Sankey diagram to depict the EDI proportion of individual organic UV filters from four exposure pathways. It was noted that EHMC (ethylhexyl methoxycinnamate) and EHS (ethylhexyl salicylate) dominated the contribution of EDI (72 %) via indoor air exposure routes. This study serves as a crucial reference for enhancing public health risk awareness concerning organic UV filters, with a special focus on the vulnerable populations such as infants and children.

The efficacy of PD-1 therapy in non-small cell lung cancer (NSCLC) patients remains unsatisfactory. Activating the STING pathway is a promising strategy to improve PD-1 inhibitor efficacy. Here, we found tetrandrine (TET), an anti-tumor compound extracted from a medicinal plant commonly used in traditional Chinese medicine, has the ability to inhibit NSCLC tumor growth. Mechanistically, TET induces nuclear DNA damage and increases cytosolic dsDNA, thereby activating the STING/TBK1/IRF3 pathway, which in turn promotes the tumor infiltration of dendritic cells (DCs), macrophages, as well as CD8+ T cells in mice. In vivo imaging dynamically monitored the increased activity of the STING pathway after TET treatment and predicted the activation of the tumor immune microenvironment. We further revealed that the combination of TET with αPD-1 monoclonal antibody (αPD-1 mAb) yields significant anti-cancer effects by promoting CD8+ T cell infiltration and enhancing its cell-killing effect, which in turn reduced the growth of tumors and prolonged survival of NSCLC mice. Therefore, TET effectively eliminates NSCLC cells and enhances immunotherapy efficacy through the activation of the STING pathway, and combining TET with anti-PD-1 immunotherapy deserves further exploration for applications.

ABSTRACT: Exposure to copper (Cu) has been associated with metabolic disorders in animals and humans, but the underlying mechanism remains unclear. One-day-old broiler chickens, numbering a total of 192, were nourished with dietary intakes that contained varying concentrations of Cu, specifically 11, 110, 220, and 330 mg/kg of Cu, for a period extending over a duration of 7 wk. As a result of the study, Cu exposure resulted in vacuolization, fragmentation of mitochondria cristae, and the increase of autophagosomes in hepatocytes. Metabolomics analysis illustrated that Cu caused a total of 59 different metabolites in liver, predominantly associated with the glycerophospholipid metabolic pathway, leading to metabolic disruption. Moreover, high-Cu diet markedly reduced the levels of AMPKα1, p-AMPKα1, mTOR, and p-mTOR and enhanced the expression levels of the autophagy-related factors (Atg5, Dynein, Beclin1, and LC3-II). Overall, Cu exposure caused chicken liver injury and resulted in disturbed metabolic processes and mediated autophagy primarily through the AMPK-mTOR axis.

ABSTRACT: Inactivated vaccines play an important role in preventing and controlling the epidemic caused by the H5 subtype avian influenza virus. The vaccine strains are updated in response to alterations in surface protein antigens, while an avian-derived vaccine internal backbone with a high replicative capacity in chicken embryonated eggs and MDCK cells is essential for vaccine development. In this study, we constructed recombinant viruses using the clade 2.3.4.4d A/chicken/Jiangsu/GY5/2017(H5N6, CkG) strain as the surface protein donor and the clade 2.3.4.4b A/duck/Jiangsu/84512/2017(H5N6, Dk8) strain with high replicative ability as an internal donor. After optimization, the integration of the M gene from the CkG into the internal genes from Dk8 (8GM) was selected as the high-yield vaccine internal backbone, as the combination improved the hemagglutinin1/nucleoprotein (HA1/NP) ratio in recombinant viruses. The r8GMΔG with attenuated hemagglutinin and neuraminidase from the CkG exhibited high-growth capacity in both chicken embryos and MDCK cell cultures. The inactivated r8GMΔG vaccine candidate also induced a higher hemagglutination inhibition antibody titer and microneutralization titer than the vaccine strain using PR8 as the internal backbone. Further, the inactivated r8GMΔG vaccine candidate provided complete protection against wild-type strain challenge. Therefore, our study provides a high-yield, easy-to-cultivate candidate donor as an internal gene backbone for vaccine development.

Water-land transition zones (WLTZs) are quintessential, complex human-land systems where aquatic and terrestrial environments intermingle, playing a pivotal role in bolstering global ecological resilience (ER). Human terrestrial production activities have encroached upon ecologically sensitive aquatic areas, weakening the inherent ER patterns in WLTZs. To address these issues, we developed an ER assessment process chain across the disturbance-carrying-recovery (D-C-R) dimensions. Applied it to the Dongting Lake region, this model diagnosed the spatiotemporal variations in ER from 2000 to 2020 and revealed the stress mechanisms of various driving factors. The results indicate: (1) The ER spatial pattern in the Dongting Lake region featured a radiating enhancement structure originating from a low-value core in the central plain’s lake network area, displaying distinct water-land gradient variations. Areas with declining ER levels were mainly distributed around the main body of the lake, water system runoff areas, and near governmental centers. (2) The spatiotemporal differentiation effects of ER manifested as an east–west axial development trend, tending toward polarization. The spatiotemporal aggregation effect appeared as L-L clustering and cold spots in the north, gradually expanding toward the peripheral forest areas. (3) Factors related to land use were the dominant drivers of spatiotemporal changes in ER. Simultaneously, the nonlinear interaction intensity among these driving factors showed a significant annual increase. This research framework can be extended to assess ER in similar regions, potentially offering policy recommendations for the ecological protection and sustainable management of WLTZs.

The disorderly expansion of human production-living construction activities into aquatic ecological sensitive areas has triggered severe production-living-ecological space (PLES) conflicts. However, research on the risk-triggering mechanisms of PLES conflicts in lake network regions and multidimensional scenario simulation techniques is relatively lacking. To address these issues, this study constructs an integrated model chain by coupling the Markov-GMOP-PLUS model to achieve a quantified diagnosis and simulated regulation of spatial conflict strength index (SCSI) under sustainable development goals. Applying it to the Dongting Lake region reveals that: (1) The overall PLES exhibited a distribution pattern where “ecological space encompasses production space, with living space interspersed within”. The category conversion mainly reflected the encroachment of agricultural production space on the plain water ecological space, with a conversion area of up to 899.48 km2. (2) The distinctive “high in the north, low in the south” PLES conflict pattern was closely aligned with the land use structure and water system distribution, with conflict hotspots persistently clustering in the core lake network regions amid rapid urbanization. Among these, the growth rate of severe conflicts in the last ten years was 3.86 times that of the previous ten years. (3) The sustainable development scenario showcased the most effective conflict mitigation by curtailing production-living space expansion and ecological space encroachment. This scenario reversed the growth trend in conflict high-value zones and the reduction trend in low-value zones, with change rates of −3.30 % and 7.05 %, respectively, compared to 2020. This study provides a scientific basis for formulating sustainable land-use policies in lake network regions.

In previous research, the prevailing assumption was that Graph Neural Networks (GNNs) precisely depicted the interconnections among nodes within the graph's architecture. Nonetheless, real-world graph datasets are often rife with noise, elements that can disseminate through the network and ultimately affect the outcome of the downstream tasks. Facing the complex fabric of real-world graphs and the myriad potential disturbances, we introduce the Sparse Graph Dynamic Attention Networks (SDGAT) in this research. SDGAT employs the L0 regularization technique to achieve a sparse representation of the graph structure, which eliminates noise and generates a more concise sparse graph. Building upon this foundation, the model integrates a dynamic attention mechanism, allowing it to selectively focus on key nodes and edges, filter out irrelevant data, and simultaneously facilitate effective feature aggregation with important neighbors. To evaluate the performance of SDGAT, we conducted experiments on three citation datasets and compared its performance against commonly employed models. The outcomes indicate that SDGAT excels in node classification tasks, notably on the Cora dataset, with an accuracy rate of 85.29%, marking a roughly 3% enhancement over the majority of baseline models. The experimental findings provide evidence that SDGAT delivers effective performance on all three citation datasets, underscoring the efficacy of the dynamic attention network built upon a sparse graph.

Summary: Background: Severe burn wounds face two primary challenges: dysregulated cellular impairment functions following infection and an unbalanced wound hydration microenvironment leading to excessive inflammation and collagen deposition. These results in hypertrophic scar contraction, causing significant deformity and disability in survivors. Methods: A three-dimensional (3D) printed double-layer hydrogel (DLH) was designed and fabricated to address the problem of scar formation after burn injury. DLH was developed using methacrylated silk fibroin (SFMA) and gelatin methacryloyl (GelMA) for the upper layer, and GelMA and hyaluronic acid methacryloyl (HAMA) for the lower layer. To combat infection, copper-epigallocatechin gallate (Cu-EGCG) was incorporated into the lower layer bioink, collectively referred to as DLS. To balance wound hydration levels, HaCaT cells were additionally encapsulated in the upper layer, designed as DLS/c. Findings: DLH demonstrated suitable porosity, appropriate mechanical properties, and excellent biocompatibility. DLS exhibited potent antimicrobial properties, exerted anti-inflammatory effects by regulating macrophage polarisation, and may enhance angiogenesis through the HIF-1α/VEGF pathway. In the DLS/c group, animal studies showed significant improvements in epidermal formation, barrier function, and epidermal hydration, accompanied by reduced inflammation. In addition, Masson’s trichrome and Sirius red staining revealed that the structure and ratio of dermal collagen in DLS/c resembled that of normal skin, indicating considerable potential for scarless wound healing. Interpretation: This biomimetic matrix shows promise in addressing the challenges of burn wounds and aiming for scarless repair, with benefits such as anti-infection, epidermal hydration, biological induction, and optimised topological properties. Funding: Shown in Acknowledgements.

Condition-based maintenance is very desirable for minimizing the maintenance and failure costs of power systems without sacrificing reliability. A systematic approach including an adaptive maintenance advisor and a system maintenance optimizer is proposed here for effectively handling the operational variations and uncertainties for condition-based maintenance. First, the maintenance advisor receives and implements the maintenance plans for its key components from the system maintenance optimizer, which optimizes the maintenance schedules with multi-objective evolutionary algorithm, considering only major system variables and the overall system performance. During operation, the offshore substation will experience continuing ageing and shifts in control, weather and load factors, measurement and human judgment detected from the connected grid and all other equipments with uncertainties. Then, the advisor estimates the changes of reliability indices due to operational variations and uncertainties of its key components by hierarchical fuzzy logic and sends the changes back to the maintenance optimizer. The maintenance optimizer will upgrade the load-point reliability and report any drastic deterioration of reliability within each substation, which may lead to re-optimization of the substation's maintenance activities for meeting its desired reliability. The offshore substation connected to a medium-sized onshore grid will be studied here to demonstrate the ability of this proposed approach in dealing with uncertainties in the implementation of maintenance with significant reduction of computational complexity and rule base.

Objective: The main objective of this study was to create and assess a detailed diagnostic model with an optimizing feature selection algorithm that combines computed tomography (CT) imaging characteristics, demographic information, and genetic markers to enhance the accuracy of benign and malignant classification of osteosarcoma. This research seeks to enhance the early identification and categorization of benign and malignant of osteosarcoma, ultimately enabling more personalized and efficient treatment approaches. Methods: Data from 225 patients diagnosed with osteosarcoma at two different medical institutions between June 2018 and June 2021 were gathered for this research study. A novel feature selection approach that combined Principal Component Analysis (PCA) with Improved Particle Swarm Optimization (IPSO) was utilized to analyze 1743 image-derived features. The performance of the resulting model was evaluated using metrics such as area under the receiver operating characteristic curve (AUC), accuracy (ACC), sensitivity (SEN), and specificity (SPE), and compared to models developed using conventional feature selection methods. Results: The proposed model showed promising predictive performance with an AUC of 0.87, accuracy of 0.80, sensitivity of 0.75, and specificity of 0.85. These results suggest improved predictive ability compared to models built using traditional feature selection techniques, particularly in terms of accuracy and specificity. However, there is room for improvement in enhancing sensitivity. Conclusion: Our study introduces a novel predictive model for distinguishing between benign and malignant osteosarcoma., emphasizing its potential significance in clinical practice. Through the utilization of CT imaging features, our model shows improved accuracy and specificity, marking progress in the early detection and classification of osteosarcoma as either benign or malignant. Future investigations will concentrate on enhancing the model’s sensitivity and validating its effectiveness on a larger dataset, aiming to boost its clinical relevance and support personalized treatment approaches for osteosarcoma.

To achieve all-organic polymer with high dielectric performances, we have designed a novel side-chain liquid crystalline polymer (P7) with strong polar mesogen of (Z)-4-(2-cyano-2-phenylvinyl)benzonitrile (CSCN) attached to polycyclooctene backbone. The bis-cyano-substituted CSCN is board-shaped and exhibits a large dipole moment (8.54 D) which tilts ∼34.2° away from its molecular long axis. Consequently, CSCN shows unique dual molecular anisotropy: one from biaxial shape anisotropy and the other from polarization anisotropy. The complex phase behaviors of P7 were investigated employing mainly the techniques of differential scanning calorimetry and X-ray diffraction. Four liquid crystal (LC) phases are identified as K0, K1, K2 and K3, which are SmA, highly-ordered biaxial SmA, B5-like and B7-like, respectively, with the thermal stability increased in sequence. The experimental results indicate that the different LC phases are arisen from the competition and balance between π-π stacking and dipole-dipole interaction. While the face-to-face π-π stacking is dominant in K0 and K1, optimizing the dipole-dipole interaction causes the CSCN mesogens within the smectic layer to tilt and rotate, resulting in K2 and K3. We further investigated the dielectric properties of P7 films using polarization-electric field loops test. The dielectric constant (εr) of P7 is found to be LC structure dependent, which is increased when the LC phase is varied from K0 to K3. With an average εr of 9.7 achieved in K3 and the low dielectric loss (tan δ = 0.001), P7 film offers a promising material in advanced applications like energy storage and electronic devices.

This paper describes the two-dimensional (2D) crystallization of side-chain giant molecules (SCGMs) having the fixed number ratio of two types of functionalized building blocks with 1:1. SCGMs are regarded to a certain degree as size-amplified versions of universal synthetic polymers that are prepared by precisely connecting molecular nanoparticles (MNPs) to polymer chains. Our previous experimental results have shown that individually changing the number ratio of one of the building blocks would significantly affect the structural parameters of molecular crystals, mainly the longitudinal thickness. Herein, we systematically discussed the 2D crystallization of two categories of POSS-based SCGMs with constant building blocks ratio. Solution self-assembly of such SCGMs resulted in well-defined 2D nanosheets with similar structural configurations, showing great tolerance in the number of building blocks. Subsequently, we proposed a “sandwiched-type” mode to illustrate the bilayer 2D supramolecular framework, in which crystalline blocks pack in head-to-head manner. In addition, sequence isomers provide an ideal platform to further verify that the thickness of 2D nanocrystal is linked with the tethering density determined by the number ratio of building blocks. We believe that this study could be a better complement to our previous work and then make us to be more in-depth understand the crystallization mechanism of SCGMs.

Objective: To develop a model combining clinical and radiomics features from CT scans for a preoperative noninvasive evaluation of Huvos grading of neoadjuvant chemotherapy in patients with HOS. Methods: 183 patients from center A and 42 from center B were categorized into training and validation sets. Features derived from radiomics were obtained from unenhanced CT scans.Following dimensionality reduction, the most optimal features were selected and utilized in creating a radiomics model through logistic regression analysis. Integrating clinical features, a composite clinical radiomics model was developed, and a nomogram was constructed. Predictive performance of the model was evaluated using ROC curves and calibration curves. Additionally, decision curve analysis was conducted to assess practical utility of nomogram in clinical settings. Results: LASSO LR analysis was performed, and finally, three selected image omics features were obtained.Radiomics model yielded AUC values with a good diagnostic effect for both patient sets (AUCs: 0.69 and 0.68, respectively). Clinical models (including sex, age, pre-chemotherapy ALP and LDH levels, new lung metastases within 1 year after surgery, and incidence) performed well in terms of Huvos grade prediction, with an AUC of 0.74 for training set. The AUC for independent validation set stood at 0.70. Notably, the amalgamation of radiomics and clinical features exhibited commendable predictive prowess in training set, registering an AUC of 0.78. This robust performance was subsequently validated in the independent validation set, where the AUC remained high at 0.75. Calibration curves of nomogram showed that the predictions were in good agreement with actual observations. Conclusion: Combined model can be used for Huvos grading in patients with HOS after preoperative chemotherapy, which is helpful for adjuvant treatment decisions.

H1N1 influenza virus is a significant global public health concern. Monoclonal antibodies (mAbs) targeting specific viral proteins such as hemagglutinin (HA) have become an important therapeutic strategy, offering highly specific targeting to block viral transmission and infection. This study focused on the development of mAbs targeting HA of the A/Victoria/2570/2019 (H1N1pdm09, VIC-19) strain by utilizing hybridoma technology to produce two mAbs with high binding capacity. Notably, mAb 2B2 has demonstrated a strong affinity for HA proteins in recent H1N1 influenza vaccine strains. In vitro assessments showed that both mAbs exhibited broad-spectrum hemagglutination inhibition and potent neutralizing effects against various vaccine strains of H1N1pdm09 viruses. 2B2 was also effective in animal models, offering both preventive and therapeutic protection against infections caused by recent H1N1 strains, highlighting its potential for clinical application. By individually co-cultivating each of the aforementioned mAbs with the virus in chicken embryos, four amino acid substitution sites in HA (H138Q, G140R, A141E/V, and D187E) were identified in escape mutants, three in the antigenic site Ca2, and one in Sb. The identification of such mutations is pivotal, as it compels further investigation into how these alterations could undermine the binding efficacy and neutralization capacity of antibodies, thereby impacting the design and optimization of mAb therapies and influenza vaccines. This research highlights the necessity for continuous exploration into the dynamic interaction between viral evolution and antibody response, which is vital for the formulation of robust therapeutic and preventive strategies against influenza.

Supervised machine learning (SML) has become a crucial tool for estimating water quality parameters (WQPs) from satellite images. Its effectiveness relies heavily on synchronised in-situ datasets covering diverse water bodies. However, collecting such datasets is time-consuming, resulting in temporal gaps between sampling and imaging. In addition, the in situ dataset may exhibit an imbalance. These imperfections could introduce uncertainties to SML-derived models, compromising the accuracy of the WQP estimates. Using in situ data collected automatically every four hours, the estimation of both optically active parameters (OAPs) and non-optically active parameters (nOAPs) in the Middle Reaches of the Yangtze River (MRYR) serves as an example to illustrate the importance of this challenge in freshwater remote sensing. Additionally, the investigation was extended to estimate OAPs and nOAPs in lakes of Wuhan through manual sampling measurements, thereby bridging theoretical insights with real-world applications. Employing four ML algorithms, the SML-based models for each WQP were calibrated using in situ datasets with different spatio-temporal distributions. The results demonstrated that precision decreased with increasing time gaps, whereas most nOAPs (COD, TP, TN, pH, and DO) showed greater robustness to the time gap than the OAPs (turbidity, Secchi depth, Chl-a, and algae density). The mean absolute percentage errors (MAPEs) of these nOAPs were as follows: for all models, pH MAPEs

Myclobutanil (MYC) is a common triazole fungicide widely applied in agriculture. MYC extensively exists in the natural environment and can be detected in organisms. However, little is known about MYC-induced embryonic developmental damage. This study aimed to unravel the cardiotoxicity of MYC and the underlying mechanisms, as well as the cardioprotective effect of curcumin (CUR, an antioxidant polyphenol) using the zebrafish model. Here, zebrafish embryos were exposed to MYC at concentrations of 0, 0.5, 1 and 2 mg/L from 4 to 96 h post fertilization (hpf) and cardiac development was assessed. As results, MYC reduced the survival and hatching rate, body length and heart rate, but increased the malformation rate and spontaneous movement. MYC caused abnormal cardiac morphology and function in myl7:egfp transgenic zebrafish, and downregulated cardiac developmental genes. MYC promoted oxidative stress through excessive reactive oxygen species (ROS) accumulation and suppressed the activities of antioxidant enzymes, triggering cardiomyocytic apoptosis via upregulated expression of apoptosis-related genes. These adverse toxicities could be significantly ameliorated by the antioxidant properties of CUR, indicating that CUR rescued MYC-induced cardiotoxicity by inhibiting oxidative stress and apoptosis. Overall, our study revealed the potential mechanisms of oxidative stress and apoptosis in MYC-induced cardiotoxicity in zebrafish and identified the cardioprotection of CUR in this pathological process.

ABSTRACT: The current study aimed to investigate the pharmacokinetics of bromhexine hydrochloride in broilers after single intravenous (IV) and oral (PO) administration at 2.5 mg/kg body weight (BW). The trial adopted a randomized, parallel-controlled design, where 20 twelve-wk-old broilers were randomly assigned to either the PO or IV group. Blood samples were collected at predetermined time points, and plasma was further separated for analysis. The bromhexine hydrochloride concentrations in plasma samples were determined using an ultra-performance liquid chromatography-tandem quadrupole mass spectrometry (UPLC-MS/MS) method. Noncompartmental analysis (NCA) using Phoenix software was conducted to analyze the concentration versus time data of bromhexine hydrochloride in every chicken. Subsequently, the main pharmacokinetic parameters between the 2 groups were statistically analyzed using SPSS software. Results from NCA revealed that after oral administration at 2.5 mg/kg BW, bromhexine hydrochloride exhibited slow absorption, reaching an average peak concentration of 32.72 ng/mL at 1.78 h. However, incomplete absorption was observed, with an absolute bioavailability of only 20.06% ± 10.84%. Additionally, bromhexine hydrochloride displayed wide distribution, with a steady-state distribution volume (VSS) of 22.55 ± 13.45 L/kg, and slow elimination, with a clearance (Cl) of 1.52 ± 0.38 L/h/kg. Furthermore, gender effects were assessed on the pharmacokinetics of bromhexine hydrochloride in broilers, revealing better absorption in male broilers compared to females. This disparity may be attributed to the faster blood flow and richer blood volume typically found in male broilers.

Hippocampal neural stem/progenitor cells (NSPCs) are highly vulnerable to different stress stimuli, resulting in adult neurogenesis decline and eventual cognitive defects. Our previous study demonstrated that NOD-like receptor family pyrin domain-containing 6 (Nlrp6) highly expressed in NSPCs played a critical role in sustaining hippocampal neurogenesis to resist stress-induced depression, but the underlying mechnistms are still unclear. Here, we found that Nlrp6 depletion led to cognitive defects and hippocampal NSPC loss in mice. RNA-sequencing analysis of the primary NSPCs revealed that Nlrp6 deficiency altered gene expression profiles of mitochondrial energy generation and ferroptotic process. Upon siNlrp6 transfection, as well as corticosterone (CORT) exposure, downregulation of Nlrp6 suppressed retinoic acid-inducible gene I (RIG-1)/mitochondrial antiviral signaling proteins (MAVS)-mediated autophagy, but drove NSPC ferroptotic death. More interesting, short chain fatty acids (SCFAs) upregulated Nlrp6 expression and promoted RIG-1/MAVS-mediated mitophagy, preventing CORT-induced NSPC ferroptosis. Our study further demonstrates that Nlrp6 should be a sensor for RIG-1/MAVS-mediated mitophagy and play a critical role in maintain mitochondrial homeostasis of hippocampal NSPCs. These results suggests that Nlrp6 should be a potential drug target to combat neurodegenerative diseases relative with chronic stress.

Crotonylation is an importantly conserved post-translational modification, which is completely different from acetylation. In recent years, it has been confirmed that crotonylation occurs on histone and non-histone. Crotonylated Histone primarily affects gene expression through transcriptional regulation, while non-histone Crotonylation mainly regulates protein functions including protein activity, localization, and stability, as well as protein-protein interactions. The change in protein expression and function will affect the physiological process of cells and even cause disease. Reviewing previous studies, this article summarizes the mechanisms of histone and non-histone crotonylation in regulating diseases and cellular physiological processes to explore the possibility of precise regulation of crotonylation sites as potential targets for disease treatment.

20CrMnTi gear steel has high low-temperature impact toughness and is widely used in the manufacturing of engineering machinery such as automotive transmission gears. The sizes and distributions of TiN inclusions have a significant impact on the service performances of 20CrMnTi gear steel. Controlling the growth behaviors and size distributions of TiN inclusions are the foundation for stable, high-quality, and efficient production of 20CrMnTi gear steel. This paper uses experimental and computational methods to study the effects of different ratios of Al–Ce composite deoxidizers on the modification behaviors of TiN inclusions in 20CrMnTi steel. The results show that the TiN inclusions in 20CrMnTi steel without Al–Ce composite deoxidizer are square in shape, with a size of approximately 4 μm. After Al–Ce composite deoxidation, a composite phase inclusion is formed in the steel, which has contracted edges and corners. The center is the nucleation core composed of elements such as Ce, Al, O, etc. The elements of Ti and N are wrapped around the periphery of the composite inclusion, reducing its size to 2 μm. When the ratio of Al and Ce in the Al–Ce composite deoxidizer is 7:3, the number of TiN inclusions in steel is the highest, accounting for 51.7% of the total amount of titanium inclusions. The average diameter of inclusions in the modified steel decreases to 2.4 μm. When the ratio of Al and Ce elements is 8:2 and 7:3, the final deoxygenation product is CeAlO3, which is more conducive to the modification of TiN inclusions in 20CrMnTi steel.

Background: Human epidermal growth factor receptor 2 (HER2)-targeted agents have significantly improved the outcomes of patients with HER2-positive breast cancer; however, a large proportion of patients still develop resistance to trastuzumab. In this study, we investigated the efficacy and safety of inetetamab, another anti-HER2 antibody, combined with pyrotinib and oral vinorelbine in patients with HER2-positive advanced breast cancer so as to provide new ideas for the treatment. Methods: In this prospective, single-arm, phase 2 trial, patients with HER2-positive advanced breast cancer with disease progression after trastuzumab were recruited. Patients received a combination of inetetamab (loading dose of 8 mg/kg and subsequent doses of 6 mg/kg intravenously once every 3 weeks), pyrotinib (400 mg orally once daily), and vinorelbine (60 mg/m2 orally once weekly) until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), overall survival (OS), disease control rate (DCR), and safety. Results: Between February 13, 2022 and December 25, 2022, 30 patients were screened and enrolled in this study. The median age of the patients at enrollment was 54 years, 12 patients (40.0 %) had hormone-receptor-positive disease and 23 patients (76.7 %) had visceral metastasis. The median PFS was 8.63 months (95 % confidence interval [CI] 4.15–13.12 months). The median OS was not reached. The ORR was 53.3 % (16/30) and the DCR was 96.7 % (29/30). The most common Grade III/IV adverse events were leukopenia (n = 5, 16.7 %), neutropenia (n = 4, 13.3 %), and diarrhea (n = 3, 10 %). No treatment-related serious adverse events or deaths occurred. Conclusions: The combination regimen of inetetamab, pyrotinib, and oral vinorelbine showed encouraging efficacy and favorable safety in patients with HER2-positive advanced breast cancer and could be considered as an alternative treatment option for the patients. Trial registration: No.NCT05823623; https://www.clinicaltrials.gov/.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS–USP25 protein–protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS–USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APCmin/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS–USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Waterborne epoxy resin (WER) has excellent chemical stability, heat resistance, and mechanical properties, and its application in emulsified asphalt modification is receiving widespread attention in road maintenance. In this paper, the mechanical properties of waterborne epoxy resin modified emulsified asphalt (WEA) binder through different preparation processes were investigated, and the influence of WER on the microstructure, rheological properties, and low-temperature stability of emulsified asphalt was analyzed. The results show that WEA binders prepared using a two-step method can make the curing reaction of the modifier more complete and the mechanical properties more excellent. With the increase of modifier content, WER gradually formed a continuous skeleton structure in emulsified asphalt, and the critical content for the continuous phase of the system to transform from emulsified asphalt to WER was about 15 %. WER could undergo polymerization reactions in emulsified asphalt, and its modification process of emulsified asphalt was mainly physical modification. With the increase of modifier content, the linear viscoelasticity range of the WEA binder gradually decreased, and the high-temperature deformation resistance was significantly improved. The influence of loading frequency on rheological properties also gradually weakened. In addition, WER could significantly improve the high-temperature elastic recovery performance of emulsified asphalt. The elastic recovery rate of the WEA binder exceeded 98 % when the content of the modifier exceeded 15 %. However, WER had certain adverse effects on emulsified asphalt's low-temperature performance, so the modifiers' content should be strictly controlled.

ABSTRACT: This experiment aimed to investigate the in vitro antimicrobial activity of danofloxacin against Escherichia coli (E. coli) isolated from pigeons, as well as the pharmacokinetics of danofloxacin in pigeons following oral (PO), intramuscular (IM), and intravenous (IV) administration. The minimum inhibitory concentration (MIC) of danofloxacin was first determined for 38 clinical E. coli strains using the micro broth dilution method. Subsequently, 30 healthy pigeons were weighed and randomly divided into 3 groups: IM, IV, and PO, with 10 pigeons in each group. Danofloxacin was given at 5 mg/kg body weight (BW) through 3 different routes. Blood was collected, and plasma was separated at various time points from 0 to 48 h. Plasma samples were analyzed for danofloxacin concentrations using a validated HPLC method. Pharmacokinetic analysis was performed using Phoenix software and a noncompartmental analytical (NCA) method. The results indicated that danofloxacin had a strong antibacterial effect on E. coli, with a MIC50 of 0.5 μg/mL. The noncompartmental analysis showed that after PO and IM administration at 5 mg/kg in pigeons, peak plasma concentrations (Cmax) of 0.61 and 1.62 μg/mL were reached at 4.5 and 0.53 h, respectively. The oral and intramuscular bioavailability (F) were 68.08% ± 24.82% and 87.82% ± 25.36%, respectively. Following IV administration, danofloxacin was widely distributed in pigeons, with volume of distribution (VZ) and volume of distribution at steady state (VSS) values of 6.11 ± 2.01 and 4.65 ± 1.62 L/kg, respectively, and was eliminated slowly, with an elimination half-life (t1/2λz) of 6.41 ± 2.15 h. Based on the calculated ratio values of AUC/MIC, the current IV, IM, and PO doses of 5 mg/kg of danofloxacin would be expected to effectively treat pigeons infected with E. coli strains with MIC values equal to or less than 0.5 μg/mL.

To investigate the changes of phenolic metabolite during different grains fermentation stages of Chinse Baijiu, the ultra-performance liquid chromatography-quadrupole time of-flight mass spectrometry (UHPLC-QTOF-MS) was applied to identify and analyze the different phenolic metabolites, combined with principal component analysis and partial least squares discriminant analysis. Results indicated that significant differences in phenolic metabolites during different fermentation stages were found. Among the 231 phenolic metabolites detected, 36, 31, 19, 23, 14, and 50 differential phenolic metabolites were screened between different groups using partial least squares discriminant analysis. Twelve metabolic pathways with high correlation of differential phenolic metabolites and 23 main participating differential metabolites were identified through KEGG metabolic pathway enrichment analysis. The present study preliminarily revealed the differences of phenolic metabolites at different fermentation stages, and providing a theoretical basis for the further improving of the taste and quality of Chinese Baijiu.

Aim: This study aims to investigate the influence of ASAP1 (ADP ribosylation factor guanylate kinase 1) on the malignant behavior of gastric cancer (GC) cells and to elucidate the potential molecular mechanisms involved in cancer development and progression. Methods: We assessed the impact of ASAP1 overexpression and knockdown on GC cell malignancy using CCK8, colony formation, flow cytometry (Annexin V/propidium iodide), Transwell migration, invasion, and scratch assays. Western blot analysis was used to assess the effects of ASAP1 on angiogenesis, matrix metalloproteinases (MMPs), apoptotic proteins, epithelial-mesenchymal transition (EMT)-related proteins, as well as AKT and p-AKT. The influence of ASAP1 knockdown was also evaluated in nude mice bearing BGC823 cell-derived tumors. Results: Our findings revealed that ASAP1 was significantly overexpressed in GC cells, enhancing their proliferation, invasion, and migration, while reducing apoptosis. Conversely, ASAP1 knockdown reversed these effects, markedly increasing the expression of cleaved-caspase 3 (Casp3), PARP, and the epithelial marker E-cadherin, and significantly decreasing MMP2, MMP9, VEGFA, and mesenchymal markers such as N-cadherin and vimentin. Additionally, it reduced AKT, and p-AKT levels (P

Objective: The objective of this study was to assess the pharmacological activity and therapeutic mechanism of Dahuang Mudan Decotion (DHMDD) for colorectal cancer using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS), network pharmacology and in vitro experiments. Methods: The chemical components of DHMDD were identified by UPLC-MS. Network pharmacological analysis was utilized to screen the active ingredients and targets associated with DHMDD for colorectal cancer. Based on the results of network pharmacology, the potential mechanism of DHMDD on colorectal cancer predicted was experimentally studied and verified in vitro. Results: DHMDD primarily exerts its effects on colorectal cancer through 52 active ingredients. AKT1, ESR1, HSP90AA1, JUN, PIK3CA, PIK3CB, PIK3R1, SRC, STAT3, TP53 were the top 10 targets. The top 10 ingredient nodes were Quercetin, Physcione, Pontigenin, Crysophanol, Linolenic acid, Piceatannol, Adenosine, Emodin, Sambunigrin, and Prunasin. The main compounds and the target proteins exhibited strong binding ability in molecular docking studies. The results of cell experiments demonstrated that DHMDD can inhibit the proliferation, invasion and migration of CRC cells through the PI3K/Akt pathway. Conclusion: Through network pharmacology analysis and cell experiments, this study suggests that DHMDD can exert its therapeutic effects on colorectal cancer through a combination of multiple components and targets.

Purpose: To identify the biometric factors associated with postoperative visual performance after uneventful phacoemulsification with multifocal intraocular lens (MIOL) implantation. Methods: In this retrospective cohort study, 72 eyes of 72 patients implanted with the HumanOptics Diff-aAY MIOL were included. Preoperative examination data including the white-to-white distance (WTW), anterior chamber depth (ACD), axial length and corneal astigmatism were gathered through the electronic medical records. One month postoperatively, the pupil parameters, corneal aberrations, corneal astigmatism, IOL tilts and IOL decentrations were measured using an OPD-Scan III aberrometer. Postoperative visual performance parameters were recorded as the visual acuity, depth of focus, modulation transfer function (MTF) and point spread function (PSF) values, area under log contrast sensitivity function (AULCSF), retinal straylight and visual function questionnaire scores. Univariate and multivariate linear regression analyses were then performed to evaluate the associations between the potential biometric factors and postoperative visual outcomes. Results: Younger age predicted greater MTF and PSF values, better AULCSF and better retinal straylight (P

As a typical representative of nanomaterials, carbon nanomaterials have attracted widespread attention in the construction of electronic devices owing to their unique physical and chemical properties, multi-dimensionality, multi-hybridization methods, and excellent electronic properties. Especially in the recent years, memristors based on carbon nanomaterials have flourished in the field of building non-volatile memory devices and neuromorphic applications. In the current work, the preparation methods and structural characteristics of carbon nanomaterials of different dimensions were systematically reviewed. Afterwards, in depth discussion on the structural characteristics and working mechanism of memristors based on carbon nanomaterials of different dimensions was conducted. Finally, the potential applications of carbon-based memristors in logic operations, neural network construction, artificial vision systems, artificial tactile systems, and multimodal perception systems were also introduced. It is believed that this paper will provide guidance for the future development of high-quality information storage, high-performance neuromorphic applications, and high-sensitivity bionic sensing based on carbon-based memristors.

Osteosarcoma (OS), a malignant tumor, originates from the bone marrow. Currently, treatment for OS remains limited, making it urgent to understand the immune response in the tumor microenvironment of patients with OS. A comprehensive bioinformatics analysis was performed, including cell clustering subgroups, differential expression genes screening, proposed temporal order, and genomic variant analysis on single-cell RNA-sequencing data, from ten pre-chemotherapy patients and eleven post-chemotherapy patients. Subsequently, we analyzed the differentiation trajectories of osteoblasts, osteoclasts, fibroblasts, myeloid cells, and tumor-infiltrating lymphocytes (TILs) in detail to compare the changes in cell proportions and differential genes pre- and post-chemotherapy. The nine cell types were identified, including fibroblasts, myeloid cells, osteoblasts, TILs, osteoclasts, proliferative osteoblasts, pericytes, endothelial cells, and B cells. Post-chemotherapy treatment, the proportions of myeloid cells and TILs in OS were declined, while the number of osteoblasts was elevated. Besides, a decrease was observed in CD74, FTL, FTH1, MT1X and MT2A, and an increase in PTN, COL3A1, COL1A1, IGFBP7 and FN1. Meanwhile, EMT, DNA repair, G2M checkpoint, and E2F targets were highly enriched post-chemotherapy. Furthermore, there was a down-regulation in the proportions of CD14 monocytes, Tregs, NK cells and CD1C-/CD141-DCs, while an up-regulation was observed in the proportions of SELENOP macrophages, IL7R macrophages, COL1A1 macrophages, CD1C DCs, CD4+ T cells and CD8+ T cells. Overall, these findings revealed changes in the tumor microenvironment of OS post-chemotherapy treatment, providing a new direction for investigating OS treatment.

Nowadays, a wide variety of labels of items are widely available, and human consumption is increasingly tailored to meet their individual needs. So, many businesses are starting to focus on improving the functionality of modern packaging. Sensorial paradigms and emotional reactions could change during the user-product interaction lifecycle. The designer's emotional imagination and past experiences are the backbone of conventional product package design, which has limitations due to unmanageable content and an absence of professional advice—the majority of previous research on emotional image analysis aimed to forecast the most common viewer emotions. Since the feelings a picture evokes are quite individual and vary from viewer to viewer, this overarching feeling isn't always enough for practical uses. The research presented an approach to packaging design evaluation based on image emotion perception computing (PDE-IEPC), which combines emotion perception technology with a deep LSTM (Long short-term model), resulting in an immersive and dynamic experience for the human senses. Emotion Perception Computing's Dynamic Multi-task Hypergraph Learning (DMHL) approach considers graphical data, social context, spatial evolution, and location, among other criteria, to evaluate packaging designs efficiently based on their emotional impact. Image-Emotion-Social-Net is a large dataset used to evaluate multidimensional and categorical attitude representation. The dataset is sourced from Flickr and contains over 1 million images presented by over 9000 users. Personalized emotion categorization is an area where research on this dataset shows that the suggested strategy outperforms many modern techniques. The experimental results show that the proposed method achieves a high packaging design quality rate of 94.1 %, a performance success rate of 97.5 %, and a mean square error rate of 2 % compared to other existing methods.

Health insurance fraud is becoming more common and impacting the fairness and sustainability of the health insurance system. Traditional health insurance fraud detection primarily relies on recognizing established data patterns. However, with the ever-expanding and complex nature of health insurance data, it is difficult for these traditional methods to effectively capture evolving fraudulent activity and tactics and keep pace with the constant improvements and innovations of fraudsters. As a result, there is an urgent need for more accurate and flexible analytics to detect potential fraud. To address this, the Multi-channel Heterogeneous Graph Structured Learning-based health insurance fraud detection method (MHGSL) was proposed. MHGSL constructs a graph of health insurance data from various entities, such as patients, departments, and medicines, and employs graph structure learning to extract topological structure, features, and semantic information to construct multiple graphs that reflect the diversity and complexity of the data. We utilize deep learning methods such as heterogeneous graph neural networks and graph convolutional neural networks to combine multi-channel information transfer and feature fusion to detect anomalies in health insurance data. The results of extensive experiments on real health insurance data demonstrate that MHGSL achieves a high level of accuracy in detecting potential fraud, which is better than existing methods, and is able to quickly and accurately identify patients with fraudulent behaviors to avoid loss of health insurance funds. Experiments have shown that multi-channel heterogeneous graph structure learning in MHGSL can be very helpful for health insurance fraud detection. It provides a promising solution for detecting health insurance fraud and improving the fairness and sustainability of the health insurance system. Subsequent research on fraud detection methods can consider semantic information between patients and different types of entities.

The risk warning for steady-state power quality in the power grid is essential for its prevention and management. However, current risk warning methods fall short in predicting the power quality trend while accounting for potential risks. Consequently, this study introduces a novel steady-state power quality risk warning method utilizing VMD-LSTM and a fuzzy model. Firstly, a power quality index prediction method based on variational mode decomposition (VMD) and long short-term memory (LSTM) is proposed. This approach significantly enhances prediction accuracy. Secondly, a power quality risk warning method incorporating kernel density estimation (KDE) and a fuzzy model is proposed, which systematically addresses the uncertainty associated with power quality risks. To validate the effectiveness and practicality of the proposed method, experiments are conducted using field monitoring data from a residential load in southern China. The results affirm the reliability and applicability of the proposed method. The simulation results show that the median error of prediction of power quality indexes by the proposed method is 5.03 % during the evaluated time period, and the prediction accuracy is mostly maintained above 90 %.

In this study, bibliometric analysis was carried out to comprehend the global research trends, hotspots, scientific frontiers, and output characteristics of the links between dendritic cells (DCs) and allergic diseases from 2004 to 2023. Publications and their recorded information were retrieved from the Web of Science Core Collection (WoSCC). VOSviewer and Citespace were used to visualize the hotspots and trends of research area. ChemBio 3D, Autodock tools, and Discovery Studio were used to visualize the molecular docking results of hotspots. A total of 4861 articles were retrieved. The number of publications (Np) was in a high and stable state. Years 2011 and 2017 were two peaks in Np. The largest contributor in terms of publications, scholars, and affiliations was the USA. The paper published in NATURE MEDICINE (IF: 82.9) and written by Trompette, A in 2006 had the highest global citation score (GCS). Keywords, such as “asthma,” “t-cells,” “inflammation,” “expression,” “atopic dermatitis,” “food allergy,” “gut microbiota,” “murine model,” and “cytokines related to immunity” appeared the most frequently. Most of the binding free energy of the key active components of Saposhnikovia divaricata docked with toll-like receptor proteins well. This bibliometric study aimed to help better comprehend the present state and make decisions from a macro viewpoint.

Lattice structures are featured by their extraordinary mechanical performances in specific stiffness, specific strength, energy absorption, and sound absorption, etc. The recent trend of multifunctionality in engineering applications has raised new requirements for the integration of their mechanical and acoustic properties. In this paper, a multifunctional hybrid plate lattice structure denoted as SBHP is proposed by hybridizing the traditional body-centered cubic plate (BCCP) and simple cubic plate (SCP) lattice structures, and its acoustic and energy absorption properties are investigated by theoretical modeling, simulation analysis and experimental verification. The effects of hole diameters and plate thicknesses on the sound absorption performance are investigated by impedance matching and system damping state analysis. The results show that the average sound absorption coefficient of SBHP-1 is increased by 24% and 62%, and the normalized half-absorption bandwidth is enlarged by 45% and 89% than those of BCCP and SCP, respectively. Heterogeneous lattice structures constructed by using the synergistic mechanism of strong and weak coupling have a more outstanding broadband sound absorption effect. This work provides an effective approach for the design of multifunctional lightweight structures with excellent broadband sound absorption and high energy absorption.

China's coastal zones, characterized by their ecological vulnerability and significant economic growth, demand effective water conservation management. Such management is pivotal not only for safeguarding water resources but also for ensuring ecological stability and promoting sustainable socio-economic development. In this study, based on the water balance model, the spatiotemporal dynamics of water conservation in the ecosystems of China's coastal areas from 2001 to 2021 were characterized by three dimensions: overall, zonal, and raster. The results show that: ① the distribution pattern of ecosystem water conservation in China's coastal areas from 2001 to 2021 is “high in the south and low in the north”, with a total amount of 117.726 billion m3/a, with the Pearl River Delta and Southwest Coastal Areas as the main high-value areas, and the overall water conservation and its capacity show a “ decreasing-rising-decreasing” pattern. The overall water conservation and its capacity show a fluctuating trend of “falling-rising-falling”. Additionally, water conservation capacity varied significantly among different vegetation types and across marine-terrestrial gradients, with the highest capacity recorded in evergreen coniferous forests and areas situated 140 km from the coastline. ②From 2001 to 2021, the water conservation capacity of China's coastal ecosystems exhibited significant temporal patterns and spatial differentiation along the marine-terrestrial gradient. The research suggests that these patterns of change are intricately linked with the stages of regional development strategies and ecological construction within these coastal zones. ③In China's coastal areas, a mere 11.63 % of the rasters showed significant changes in water conservation, dominated by highly significant and significant increases, mainly in the Southeast Coastal Area, the Pearl River Delta and Southwest Coastal Areas, and the Bohai Bay Coastal Area. This included areas such as the Yangtze River Delta silty coastal plain area, the Bohai Bay silty coastal plain area, the sandy silt coastal hilly terrace area of western Guangdong and Guinan, and other China coastal protection forest system construction projects. ④ Water conservation function within China's coastal ecosystems demonstrates a profound interconnection with both natural and socio-economic determinants. Natural elements such as elevation, slope, and precipitation positively correlate with water conservation metrics. Conversely, evapotranspiration and temperature are inversely related to conservation outcomes. In terms of social factors, water conservation has a significant negative correlation with GDP density and population density, with the highest negative correlation with the GDP2 density.

ABSTRACT: This study aimed to compare the residue depletion of gamithromycin in yellow-feather and white-feather broilers, using Sanhuang and Arbor Acres chickens as typical examples, respectively. Each breed (54 chickens) received a single subcutaneous dose of gamithromycin at 7.5 mg/kg bodyweight (BW). Tissues, including muscle, skin + fat, liver, kidney, and injection site, were collected at 6 h, 3, 5, 7, 10, 14, 21, 28, and 35 d postdrug administration. Gamithromycin concentrations in these tissues were determined using ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC‐MS/MS). The kinetics of gamithromycin were analyzed in different tissues using a noncompartmental method in the Phoenix software. Differences were observed in gamithromycin concentrations and kinetic characteristics in both breeds of chickens, with higher residue concentrations and longer residue times found in yellow-feathered broilers. In Sanhuang broilers, the elimination rates of gamithromycin followed this order: injection site > muscle > liver > kidney > skin + fat. The corresponding elimination half-lives (t1/2λzs) in these samples were 1.22, 1.30, 1.71, 2.04, and 2.52 d, respectively. In contrast, in Arbor Acres broilers, a different order was noted: muscle > injection site > kidney > liver > skin + fat, with corresponding t1/2λzs of 1, 1.23, 1.88, 1.93, and 2.21 d, respectively. These differences may be related to variations in pigments in various tissues of chickens of the 2 breeds. However, further investigations are warranted to discern the underlying reasons.

Immune checkpoint inhibitors (ICB) therapy have emerged as effective treatments for melanomas. However, the response of melanoma patients to ICB has been highly heterogenous. Here, by analyzing integrated scRNA-seq datasets from melanoma patients, we revealed significant differences in the TiME composition between ICB-resistant and responsive tissues, with resistant or responsive tissues characterized by an abundance of myeloid cells and CD8+ T cells or CD4+ T cell predominance, respectively. Among CD4+ T cells, CD4+ CXCL13+ Tfh-like cells were associated with an immunosuppressive phenotype linked to immune escape-related genes and negative regulation of T cell activation. We also develop an immunotherapy response prediction model based on the composition of the immune compartment. Our predictive model was validated using CIBERSORTx on bulk RNA-seq datasets from melanoma patients pre- and post-ICB treatment and showed a better performance than other existing models. Our study presents an effective immunotherapy response prediction model with potential for further translation, as well as underscores the critical role of the TiME in influencing the response of melanomas to immunotherapy.

Transportation is a major sector of anthropogenic emissions in urban areas and deteriorates air quality. The surface and vertical observational data were combined with the model results to reveal its impact on the horizontal and vertical variations of pollutants during the COVID-19 lockdown period. The evident reductions in ambient PM2.5 (∼30%) and NO2 (∼50%) concentrations but a ∼25% increase in O3 concentration were observed at the transportation sites. On the vertical scale, a uniform decrease of ∼28% in PM2.5 concentrations was observed within 600 m. However, the vertical profiles of NO2 and O3 exhibited increasing vertical variation rates with concentrations varying significantly within 400 m. Meanwhile, Ox shared a similar pattern of vertical profile with O3, with a uniform increase (∼5%) within 600 m in the urban area. The WRF-CMAQ model reproduced the variations, and revealed that the reduction of transportation emissions was the key factor contributing to the increase of urban O3 and Ox due to the weakened NO titration effect. The simulated vertical profile of NO2 was featured by a decreasing curve, while that of O3 exhibited the opposite trend. We find that the transportation emissions impact vertical concentrations of NO2 and O3 within at most 400 m. The process analysis revealed that the vertical transport and horizontal transport from bay areas contributed to O3 in the urban area, while chemical processes mainly consumed it. The reduction in transportation emissions weakened the consumption and resulted in O3 accumulation during rush hours and at night. The variation of planetary boundary layer height also favored the rise of urban O3 by promoting vertical transport at daytime and trapping it at night. The reduction in NOx emissions from the transportation enhanced O3 pollution, suggesting that collaborative reductions in VOCs from multiple sectors should be conducted. This study also indicated that regional collaborations in emission reductions were necessary for comprehensive air pollution prevention.

Chitin is a polysaccharide similar to cellulose that contains abundant hydrogen bonds. Expansin-like proteins disrupt hydrogen bond networks, causing cellulose to swell and accelerating its degradation. We examined the effects of pretreatment with two expansin-like proteins, CxEXL22 (Arthrobotrys sp. CX1) and HcEXL (Hahella chejuensis), on chitin depolymerisation and enzymatic degradation. The efficiency of chitin degradation increased more than two-fold after pretreatment with expansin-like proteins. Following pretreatment with expansin-like proteins, chitin had a lower crystallinity index, greater d-spacing and crystallite size, and weaker hydrogen bonds, and the loosened porous microfibrils were more exposed than in untreated chitin. The rupture characterisation of crystalline chitin indicated that expansin-like proteins loosened the hydrogen bonds of the chitin polysaccharide chains, causing significant depolymerisation to expose more porous structures and enhance chitin accessibility.

Background: Inflammation and stress response may be related to the occurrence of sepsis-associated acute kidney injury (SA-AKI) in patients with sepsis.Insulin resistance (IR) is closely related to the stress response, inflammatory response, immune response and severity of critical diseases. We assume that the triglyceride-glucose (TyG) index, an alternative indicator for IR, is associated with the occurrence of SA-AKI in patients with sepsis. Methods: Data were obtained from The Medical Information Mart for Intensive Care-IV(MIMIC-IV) database in this retrospective cohort study. Univariate and multivariate logistic regression analysis and multivariate restricted cubic spline(RCS) regression were conducted to evaluate the association between TyG index and SA-AKI, length of stay (LOS). Subgroup and sensitivity analyses were performed to verify the robustness of the results. Results: The study ultimately included data from 1426 patients with sepsis, predominantly of white ethnicity (59.2%) and male sex (56.4%), with an SA-AKI incidence rate of 78.5%. A significant linear association was observed between the TyG index and SA-AKI (OR, 1.40; 95% confidence interval(CI) [1.14–1.73]). Additionally, the TyG index demonstrated a significant correlation with the length of stay (LOS) in both the hospital (β, 1.79; 95% CI [0.80–2.77]) and the intensive care unit (ICU) (β, 1.30; 95% CI [0.80–1.79]). Subgroup and sensitivity analyses confirmed the robustness of these associations. Conclusion: This study revealed a strong association between the TyG index and both SA-AKI and length of stay in patients with sepsis. These findings suggest that the TyG index is a potential predictor of SA-AKI and the length of hospitalization in sepsis cases, broadening its application in this context. However, further research is required to confirm whether interventions targeting the TyG index can genuinely enhance the clinical outcomes of patients with sepsis.

Background: The role of Ferroptosis in the course of sepsis-induced myopathy is yet unclear. The objective of our work is to identify key genes connected with Ferroptosis in sepsis-induced myopathy and investigate possible pharmaceutical targets related to this process. This research aims to provide new insights into the management of sepsis-induced myopathy. Methods: We got the GSE13205 dataset from the Gene Expression Omnibus (GEO) and extracted Ferroptosis-associated genes from the FerrDb database. After conducting a functional annotation analysis of these genes, we created a protein-protein interaction network using Cytoscape software to identify important genes. Subsequently, we employed CMap to investigate prospective pharmaceuticals that could target these crucial genes. Results: A total of 61 genes that are expressed differently (DEGs) have been found concerning Ferroptosis. These genes are involved in a wide range of biological functions, including reacting to signals from outside the cell and the availability of nutrients, programmed cell death, controlling apoptosis, and responding to peptides, chemical stressors, and hormones. The KEGG pathway study revealed that these pathways are involved in Ferroptosis, autophagy, P53 signaling, PI3K-Akt signaling, mTOR signaling, HIF-1 signaling, endocrine resistance, and different tumorigenic processes. In addition, we created a network that shows the simultaneous expression of important genes and determined the top 10 medications that have the potential to treat sepsis-induced myopathy. Conclusion: The bioinformatics research undertaken sheds insight into the probable role of Ferroptosis-associated genes in sepsis-induced myopathy. The identified critical genes show potential as therapeutic targets for treating sepsis-induced myopathy, offering opportunities for the development of tailored medicines.