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Abstract To address the challenges of performing in-situ tests on riverbed overburden gravel, this study employs three scaling methods—equal mass substitution, similar gradation, and the mixed method—to investigate the original gradation of the gravel. Large-scale triaxial consolidated drained shear tests were conducted to evaluate the effects of the maximum particle size reduction ratio (M) and confining pressure on the stress–strain behavior, fractal dimension, particle breakage, and the parameters of the Duncan-Chang model (an elastic model describing nonlinear stress-strain relationships). The study explores how scaling, based on fractal dimension and particle breakage rate, impacts the strength and deformation characteristics of gravel materials. The results show that increasing confining pressure typically leads to higher material strength. As confining pressure increases, particle breakage becomes more pronounced across the various scaling methods. Gravel processed using the similar gradation method exhibited the highest strength, the smallest change in fractal dimension, and the lowest breakage rate, followed by the mixed method. Furthermore, as the M value increases, peak stress also rises, with the modulus coefficient (k) and bulk modulus coefficient (K b ) in the Duncan-Chang model increasing by 4.5 times and 3.3 times, respectively, for M = 15 compared to M = 0. A clear relationship was observed between the change in fractal dimension before and after testing and the breakage index (B g ). As the M value increases, both the difference in fractal dimension and the breakage rate decrease, suggesting that larger M values lead to reduced particle breakage and improved mechanical stability.

Abstract Background The efficacy and safety of anti-angiogenic combination therapy in patients with driver gene-negative non-small cell lung cancer (NSCLC) with brain metastases (BM) are uncertain. Methods Eighty-eight records of driver gene-negative patients with NSCLC treated with craniocerebral radiotherapy (RT) and programmed death factor-1 (PD-1) inhibitors between May 2021 and May 2023 were collected. Based on whether anti-angiogenic therapy (AT) is combined or not, patients are categorized into the AT group and the non anti-angiogenic therapy (NAT) group. The NAT group patients received craniocerebral RT and PD-1 inhibitor and those in the AT group received craniocerebral RT and PD-1 inhibitor with ≥ 4 cycles of AT. Comparing the clinical efficacy and safety in these two patient cohorts was the main goal of the study. Results By May 1, 2024, the iORR was 94.0% and 63.2% for AT and NAT group, respectively. The 1- and 2-year iLPFS for AT and NAT group were 93.6%, 80.9% and 69.7%, 36.4%, respectively. The 1- and 2-year iDPFS were 86.7%, 56.3% and 59.1%, 48.3%, respectively. The 1- and 2-year OS were 82.0%, 36.6% and 68.4%, 34.6%, respectively. Compared to the standard treatment (RT and PD-1 inhibitors), the addition of AT prolonged the median iLPFS (NR vs. 22.0 months, hazard ratio [HR] = 11.004, P

Abstract Despite the importance of radiation therapy as a non-surgical treatment for non-small cell lung cancer (NSCLC), radiation resistance has always been a concern, due to poor patient response and prognosis. Therefore, it is crucial to uncover novel targets to enhance radiotherapy and investigate the mechanisms underlying radiation resistance. Previously, we demonstrated that NRP1 was connected to radiation resistance in NSCLC cells. In the present study, bioinformatics analysis of constructed radiation-resistant A549 and H1299 cell models revealed that transcription coactivator YAP is a significant factor in cell proliferation and metastasis. However, there has been no evidence linking YAP and NRP1 to date. In this research, we have observed that YAP contributes to radiation resistance in NSCLC cells by stimulating cell proliferation, migration, and invasion. Mechanistically, YAP dephosphorylation after NSCLC cell radiation. YAP acts as a transcription co-activator by binding to the transcription factor TEAD4, facilitating TEAD4 to bind to the NRP1 promoter region and thereby increasing NRP1 expression. NRP1 has been identified as a new target gene for YAP/TEAD4. Notably, when inhibiting YAP binds to TEAD4, it inhibits NRP1 expression, and Rescue experiments show that YAP/TEAD4 influences NRP1 to regulate cell proliferation, metastasis and leading to radiation resistance generation. According to these results, YAP/TEAD4/NRP1 is a significant mechanism for radioresistance and can be utilized as a target for enhancing radiotherapy efficacy.

Single-atom catalysts (SACs) have provoked significant curiosity in heterogeneous catalysis due to the benefits of maximum metal atoms usage, robust metal-support interaction, single-metal-atom active sites, and high catalytic efficiency. In this study, the electronic structures and catalytic mechanism of ethyne hydrogenation of SACs with the group-9 metal atoms M1 (M1= Co, Rh, Ir) anchored on PTA (phosphotungstic acid) cluster have been explored by using first-principles quantum calculations. It is found that the catalytic activity of ethyne (C2H2) hydrogenation is determined by two critical parameters: the adsorption energies of the adsorbate (H2, C2H2) and the activation energy barrier of ethyne hydrogenation. We have shown that the reaction pathway of ethyne hydrogenation reaction on the experimentally characterized Rh1/PTA at room temperature consists of three steps: C2H2 and H2 coadsorption on Rh1/PTA, H2 attacking C2H2 to form C2H4, then C2H4 desorbing or further reacting with H2 to produce C2H6 and completing the catalytic cycle. The Rh1/PTA possesses fair catalytic activity with a C2H4 desorption energy of 1.46 eV and a 2.59 eV barrier for ethylene hydrogenation. Moreover, micro-kinetics analysis is also carried out to understand the mechanism and catalytic performance further. The work reveals that the PTA-supported SACs can be a promising catalyst for alkyne hydrogenation.

Abstract Background Root canal therapy is one of the main treatments for root canal diseases, and effective irrigation is the key to successful treatment. Side-vented needle is one of the commonly used needle types in clinic. In the real root canal, due to the influence of the curvature of the root canal, the irrigation flow field in different needle directions shows obvious differences. At the same time, changes in root canal curvature and working depth will lead to changes in irrigation efficiency and the flow field. Both the mainstream of the irrigation flow and the shear stress near the wall changes significant. Consequently, either the replacement in the root canal or the removal efficiency of the smear layers is apparently modified. Materials and methods In this paper, the permanent root canal of the maxillary first molar prepared until 15/04 were scanned by micro-CT, and then imported into the software for 3D reconstruction. The key parameters of flushing efficiency of 30G side needle at different working depths of 4.75 mm, 5 mm, 5.25 mm and 5.5 mm were compared. Meanwhile, the simulated models with different curvatures of 0°, 5°, 10°, 20° and 30° based on the real root canal were reconstructed to investigate the curvature effect on the irrigation efficiency. Results The results show that moderate working depth (such as 4.75 mm and 5.25 mm in present paper) helps to improve the replacement capacity of irrigation flow. At the same time, the apical pressure decreased as the working depth increased. The curvature of the root canal seriously affects the removal depth of the smear layers of the root canal. A root canal with a large curvature (especially 20° and 30°) can significantly improve the difficulty of irrigation. Conclusions (1) Moderate working depth helps to improve the displacement capacity, the ERD of the irrigation flow is generally improved at the working depths of 4.75 mm and 5.25 mm, and the apical pressure will decrease with the increase of working depth. (2) The large curvature of the root canal can significantly improve the difficulty of irrigation. The curvature of the root canal can severely influence the removal depth of the smear layer on the wall. It can be found both the span and the depth of the ESS for little curvatures (5° and 10°) root canals are higher than those for large curvatures (20° and 30°).

The regional water cycle reflects the dual processes of nature and society. A healthy and benign water cycle is a fundamental guarantee for achieving regional sustainable development.The Yangtze River Economic Belt, as a densely populated urban cluster with abundant water resources in China, plays a crucial role in promoting the sustainable development of Chinese urban clusters. It is of significant importance to optimize the water cycle health of the Yangtze River Economic Belt and explore its primary obstacles.This study integrates the natural-social attributes of the water cycle and selects 25 evaluation indicators from six dimensions: Drivers (D), Pressures (P), States (S), Impacts (I), Responses (R), and Management (M), to construct the water cycle evaluation system for the Yangtze River Economic Belt.Combining Analytic Hierarchy Process (AHP), Decision-Making Trial and Evaluation Laboratory (DEMATEL), and the Criteria Importance Through Intercriteria Correlation (CRITIC) method, the comprehensive weights of subjective and objective factors are obtained based on the principle of minimum relative entropy.Based on this, an Extended Cloud Model is constructed to evaluate the water cycle health status of the region from 2012 to 2022.Furthermore, the Obstacle Degree Model is introduced to identify the primary obstacles affecting the water cycle health in the region. Finally, the ARIMA model is applied to forecast the water cycle health status in the region from 2023 to 2030.The results indicate that the comprehensive water cycle health level in the region improved gradually from initially sub-pathological to sub-healthy status from 2012 to 2022.Per capita GDP, industrial water consumption per ten thousand yuan of industrial value added, per capita water consumption, forest coverage rate, sediment transport module, proportion of environmental protection investment to GDP, and proportion of water resources management investment to GDP are the primary obstacles affecting the improvement of health in this region.The forecast indicates that the overall water cycle health status in the region will remain at a sub-healthy level from 2023 to 2030.The research results can provide a scientific reference for further promoting the high-quality development of the Yangtze River Economic Belt, better supporting and serving China's modernization, and providing scientific reference basis.

Backgrounds: Mature angiogenesis plays a critical role in improving cerebral ischemia-reperfusion injury (CIRI). Glycolysis serves as the primary energy source for brain microvascular endothelial cells (BMECs), whereas other vascular cells rely on aerobic respiration. Therefore, intercellular variations in energy metabolism could influence mature angiogenesis. Taohong Siwu Decoction (THSWD) has demonstrated efficacy in treating ischemic stroke (IS), yet its potential to promote mature angiogenesis through glycolysis activation remains unclear.Methods: In this study, we established a middle cerebral artery occlusion/reperfusion (MCAO/R) model in vivo and an oxygen-glucose deprivation/reoxygenation (OGD/R) model in vitro. We assessed neuroprotective effects using neurobehavioral scoring, 2,3,5-triphenyltetrazolium chloride (TTC) staining, Hematoxylin-eosin (HE) staining, and Nissl staining in MCAO/R rats. Additionally, we evaluated mature angiogenesis and glycolysis levels through immunofluorescence, immunohistochemistry, and glycolysis assays. Finally, we investigated THSWD’s mechanism in linking glycolysis to mature angiogenesis in OGD/R-induced BMECs.Results:In vivo experiments demonstrated that THSWD effectively mitigated cerebral damage and restored neurological function in MCAO/R rats. THSWD significantly enhanced CD31, Ang1, PDGFB, and PDGFR-β expression levels, likely associated with improved glucose, pyruvate, and ATP levels, along with reduced lactate and lactate/pyruvate ratios. In vitro findings suggested that THSWD may boost the expression of mature angiogenesis factors (VEGFA, Ang1, and PDGFB) by activating glycolysis, increasing glucose uptake and augmenting lactate, pyruvate, and ATP content, thus accelerating mature angiogenesis.Conclusion: THSWD could alleviate CIRI by activating the glycolysis pathway to promote mature angiogenesis. Targeting the glycolysis-mediated mature angiogenesis alongside THSWD therapy holds promise for IS treatment.

Radiation therapy has been a critical and effective treatment for cancer. However, not all cells are destroyed by radiation due to the presence of tumor cell radioresistance. In the current study, we investigated the effect of low-dose radiation (LDR) on the tumor suppressive effect of high-dose radiation (HDR) and its mechanism from the perspective of tumor cell death mode and DNA damage repair, aiming to provide a foundation for improving the efficacy of clinical tumor radiotherapy. We found that LDR pre-irradiation strengthened the HDR-inhibited A549 cell proliferation, HDR-induced apoptosis, and G2 phase cell cycle arrest under co-culture conditions. RNA-sequencing showed that differentially expressed genes after irradiation contained pyroptosis-related genes and DNA damage repair related genes. By detecting pyroptosis-related proteins, we found that LDR could enhance HDR-induced pyroptosis. Furthermore, under co-culture conditions, LDR pre-irradiation enhances the HDR-induced DNA damage and further suppresses the DNA damage-repairing process, which eventually leads to cell death. Lastly, we established a tumor-bearing mouse model and further demonstrated that LDR local pre-irradiation could enhance the cancer suppressive effect of HDR. To summarize, our study proved that LDR pre-irradiation enhances the tumor-killing function of HDR when cancer cells and immune cells were coexisting.

Water resource health is one of the necessary conditions for society to achieve sustainable development. Due to the predominant focus of most studies on relatively short time spans, with limited attention to long time series and spatial trends, this study, using various regions of Henan Province as a case study, constructs a water resource security assessment framework based on the DPSIR model encompassing Drivers (D), Pressures (P), State (S), Impact (I), and Response (R) dimensions, with a selection of 19 evaluation indicators. Based on this evaluation index system, the CRITIC-TOPSIS evaluation method is formulated by integrating the CRITIC (Criteria Importance Through Intercriteria Correlation) and TOPSIS (Technique for Order Preference by Similarity to Ideal Solution) models. This method is employed to assess the degree of water resource security in Henan Province from 2013 to 2022. And the Obstruction Degree Model is introduced to diagnose the water resource security levels in various regions of Henan Province. The assessment results indicate that over the past decade, the overall level of water resource security in various regions of Henan Province has shown an increasing trend. Irrigated area, per capita water resources, water consumption per unit of industrial value added, per acre water consumption for agricultural irrigation, the ratio of river length meeting water quality standards, groundwater supply proportion, and sewage treatment rate are identified as the primary obstacles influencing the water resource security levels in different regions of Henan Province. The research outcomes of this study can serve as theoretical foundations to enhance urban water resource security globally, ultimately facilitating sustainable development.

The health status of the water cycle has a significant impact on the sustainable development of a region. As a densely populated urban cluster, the Central Plains Urban Agglomeration plays an important role in promoting the sustainable development of China urban agglomerations. It is of great significance to optimize the water cycle health of the Central Plains Urban Agglomeration and explore its main barriers. In this article, we propose a conceptual model called DSWU NWU SWS NWS A (“Driving force—Social development uses water—Natural development uses water—Situation of social water resources—Situation of natural water resources—Ameliorate”) and establish an assessment system for the water cycle health of the Central Plains Urban Agglomeration. By combining the FAHP and ICV, we use linear programming to obtain comprehensive weight values that combine subjective and objective factors. Based on this, in order to quantify the degree of WCH, we introduce the Water Cycle Health Index (WCHI) and evaluate the water cycle health of the Central Plains Urban Agglomeration from 2002 to 2022, taking into account the randomness and fuzziness of water cycle health. By introducing an obstacle degree model, we identify the main barriers to water cycle health in the Central Plains Urban Agglomeration in 2022. The results show that the proposed method for evaluating the WCH based on DSWU NWU SWS NWS A — WCHI is feasible. According to the evaluation results, the WCH of most cities in the Central Plains Urban Agglomeration is trending towards “Very healthy,” with a gradual increase in WCHI, and the gap between cities is gradually narrowing. The analysis of barrier factors shows the eight main influencing factors affecting the water cycle health of the Central Plains Urban Agglomeration. The research findings of this article can provide theoretical basis for water resource evaluation, indicator construction, and policy guidance in densely populated urban clusters worldwide.

Phosvitin (PV) was treated with high-temperature, mild pressure (HTMP), and enzyme combination, and then phosvitin phosphopeptides-calcium (PPP-Ca) complexes were prepared. The low-calcium specific pathogen free-Kunming (SPF-KM) mice were used to determine the effect of PPP-Ca complexes on intestinal calcium absorption and their utilization for bone formation. The serum calcium content was the highest with the HTMP-Enz-PPP-Ca treatment (2.19 mmol/L), and it significantly down-regulated the abnormal elevation of serum alkaline phosphatase (AKP) caused by calcium deficiency. The low-calcium control group had the lowest calcium deposited to the femur (80.41 mg/g) and the lowest femur bone mineral density (BMD) (0.17 g/cm3), while HTMP-Enz-PPP-Ca significantly improved bone calcium content (94.33 mg/g) and BMD (0.29 g/cm3). The micro-computed tomography (MCT) images showed that the femur with the normal control, PV-Ca, and HTMP-Enz-PPP-Ca treatments had a more compact, complete, and thicker trabecular network than the low-calcium and CaCl2 treatments. These results indicated that the organic calcium (HTMP-Enz-PPP-Ca) promoted calcium absorption and bone deposition, and the effect of HTMP-Enz-PPP-Ca was better than the inorganic CaCl2.

The ecological health level of water resources plays a crucial role in achieving sustainable development in society. This study focuses on the core area of the Central Plains urban agglomeration. A comprehensive evaluation system, based on the Water Resources - Socio-Economic - Ecological Environment model framework, was constructed, incorporating 22 evaluation indicators in the indicator layer. Using an improved entropy weighting method combined with the ITOPSIS model, the water ecological health level in the study area from 2013 to 2022 was evaluated, and corresponding measures were proposed based on the evaluation results. Furthermore, the Barrier Degree model was applied to identify the eight major hindering factors influencing the water resource ecological environment in the research area. The results show that: The overall water resource ecological health level in the core area of the Central Plains urban agglomeration from 2013 to 2022 showed a generally improving trend. The eight major hindering factors indicate that cities should focus on green urban development while promoting the construction of smart water management systems and sponge cities.

The aim of this article is to reduce the environmental harm caused by industrial solid waste, specifically tannery sludge, and enable its reutilization. This study prepared an alkali-activated tannery sludge–slag solidification product (ATSSP) with high mechanical properties using blast furnace slag and tannery sludge as raw materials. The response surface methodology (RSM) was used to optimize the product mix ratio. The hydration mechanism and solidification method of ATSSP for Cr in tannery sludge were studied using X-ray diffraction (XRD), scanning electron microscope-energy dispersive spectrometer (SEM-EDS), and Fourier transform infrared reflection (FT-IR). The results indicate that the compressive strength regression model established through RSM has high accuracy and credibility. When the ratio of activator to binder is 0.2174, the alkali activation modulus is 1.02, and the water-to-cement ratio is 0.37; the 28 d compressive strength of ATSSP can reach 71.3 MPa. The sulfate in tannery sludge can promote the secondary hydration reaction of slag, and the generated hydrated calcium silicate and calcite greatly improve the strength of the ATSSP. The reducing substances contained in slag can reduce Cr (VI) in tannery sludge to Cr (III) in the form of uvarovite. The total Cr and Cr (VI) precipitation concentrations of the product are far less than the specification requirements.

Phosvitin and its phosphopeptides contain a large amount of phosphorylated amino groups and exhibit a series of unique bioactivities including metal-binding, antioxidant, bacteriostatic and biomineralization activities due to strong interactions between phosphate groups and metal ions. In this article, the structures and preparation of phosvitin phosphopeptides, the interactions of phosphopeptides with metal ions, and the biological activities associated with their metal-binding capacity, as well as future potential application prospects are discussed.

The regional water cycle reflects both natural and social processes. The health of the regional water cycle is of great significance to the sustainable development of human beings. Focusing on the nine provinces and regions in the Yellow River Basin, this study utilized the DPSIRM model, including 21 basic indicators. In this paper, according to the principle of minimum information entropy, the three-scale AHP and EFAST algorithms were combined and weighted, and water cycle health status in the nine provinces and regions was evaluated based on the hook trapezoidal fuzzy TOPSIS model. Moreover, the traditional TOPSIS model was compared with the FCE method so as to evaluate the objectivity of the results. The obstacle degree model was introduced to obtain the main obstacle factors affecting the improvement of water circulation health in the nine provinces and regions. The results show that the water circulation health status in the nine provinces and regions is tending towards health, coordination, and balance. Water consumption in the ecological environment, water consumption per CNY 10,000 of GDP and forest coverage rate are the key factors that influence the improvement of water circulation health in the nine provinces and regions. The research results herein provide a scientific reference for the nine provinces and regions to achieve a healthy urban water cycle and regional sustainable development.

The western region of China is rich in hydropower resources and characterized by unique geological conditions. For the construction or planned construction of high dams in this region, different types of cover layers are formed due to special geological structures, most of which are located in high seismic intensity zones. This study focuses on four different site conditions: hard ground, medium–hard ground, medium–soft ground, and weak ground. By simulating the dynamic response of concrete-face rockfill dams under near-fault earthquake excitation, the vertical settlement of the dam and the attenuation of seismic motion under different site conditions are analyzed. The research findings reveal a consistent trend where the vertical settlement of the dams progressively escalates with increasing dam height across all four site conditions. This settlement phenomenon is especially pronounced in weak ground conditions, posing a potential risk of failure. Furthermore, when subjected to near-fault pulse-type earthquake motions, the existence of weak soil layers significantly dampens the seismic forces experienced by the dam. This finding suggests that the weaker the geological conditions of the site, the more pronounced the attenuation effect of the seismic motion. Additionally, the overburden layers have a noticeable amplification effect on near-fault pulse-type earthquake motion. However, this amplification effect is not significant in weak ground, possibly due to the presence of weak soil layers restricting the propagation and amplification of seismic motion. In conclusion, these research findings have practical significance for the dynamic response of high dam construction in different site conditions in the western region of China. They provide a scientific basis for the design and construction of high dams and serve as a reference for the implementation of seismic mitigation measures and earthquake disaster prevention in engineering projects.

Phosvitin (PV) from egg yolk is an excellent substrate for the production of phosphopeptides, which have a strong calcium chelating capacity and promoting calcium absorption and bone mineralization. This study investigated the effect of PV hydrolysates produced using a effective preparation method (high temperature (121°C) and mild pressure (0.1 MPa), HTMP) or HTMP pretreatment and trypsin hydrolysis combination (HTMP-PV18) on the physiology of an osteoblast MC3T3-E1 cells line. The proliferation, apoptosis, and differentiation of MC3T3-E1 cells were analyzed using the CCK-8, flow cytometry, and RT-PCR reactions, respectively. Both the HTMP-PV and HTMP-PV18 increased the proliferation, and inhibited the apoptosis of MC3T3-E1 cells significantly. The HTMP-PV increased the proliferation of MC3T3-E1 cells by 147.12 ± 2.11% and the HTMP-PV18 by 136.43 ± 4.51%. In addition, the HTMP-PV and HTMP-PV18 effectively promoted the expression of genes related to the OPG/RANKL signaling channel during cell differentiation. This indicated that both the HTMP-PV and HTMP-PV18 have the potential to promote bone mineralization by improving the proliferation and differentiation of osteoblastic cells.

Seepage analysis is always a concern in dam safety and stability research. The prediction and analysis of seepage pressure monitoring data is an effective way to ensure the safety and stability of dam seepage. With the timeliness of a change in a monitoring value and lag due to external influences, a RS-LSTM model written in Python is developed in this paper which combines rough set theory (RS) and the long- and short-term memory network model (LSTM). The model proposed calculates the prediction score of the seepage pressure of a dam experiencing multiple effects by preordering factor importance values to eliminate the interference of redundant factors. A case study shows that the water level, rainfall, temperature, and duration are all factors that affect the seepage pressure, and their importance values decrease successively. Thus, the seepage pressure of a dam can be predicted with a determination coefficient R2 of 0.96. Compared with the recurrent neural network (RNN) model and BP neural network model, the training time of the RS-LSTM model proposed is 6.37 s, and the operation efficiency is 41% and 59% higher than that of the RNN and BP models, respectively. The mean relative error is also 3.00%, which is 50% lower than that of the RNN model and 31% lower than that of the BP model. Based on these results, this model has the advantages of fast computation speed and high accuracy in prediction.