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To elucidate the development patterns and influencing factors of natural fractures in deep-buried tight oil reservoirs, a comprehensive evaluation was conducted using a large amount of core samples, thin section, physical property data, imaging and conventional logging, water injection pressure testing and other data. The focus was on the tight oil reservoirs within the Ⅱ-Ⅵ oil layers of the third member of the Paleogene Hetaoyuan Formation in the southeastern An'peng area of the Biyang Depression, Nanxiang Basin. These oil formations, deposited in fan-delta front environment, are characterized by a high content of rock debris, indicating proximal deposition. A strong positive correlation between reservoir porosity and permeability was observed. Among the various sandstone lithologies, fractures predominantly developed in fine sandstone, followed by siltstone, while gravelly sandstone generally lacked fractures. High-angle and vertical fractures were predominant, constituting 87.8% of the total, while low-angle oblique and horizontal fractures accounted for 7.3% and 4.9%, respectively. The main controlling factors for fracture development in these tight reservoirs included lithology, depositional microfacies, and local structures. Thin and fine-grained single or composite sand bodies typically had more deve-loped fractures, particularly in front channel, channel flank, mouth bar, and outer edge of distal bars. Conversely, fractures were less developed in sheet sands or delta front microfacies. Moreover, fractures primarily formed at structural inflection points, predominantly at the tops and wings of forward structures and were primarily oriented along the WE and NE directions, followed by the NW direction. These fractures predominantly formed during the Neogene depression period (late Himalayan). Fractures significantly influence water channeling in tight oil reservoirs, necessitating enhanced dynamic and static monitoring of the degree, extent, and orientation of fracture development.

Abstract Lakes are hotspots for the biogeochemical processing of carbon, including dissolved organic matter (DOM). A less degradable fraction of DOM, preserved for a long time, can be categorized as recalcitrant DOM (RDOM). Lake RDOM is an important but neglected carbon sink, and its characteristics and transformation processes remain largely unknown.

Various biological effects of ionizing radiation, especially continuous exposure to low-dose radiation (LDR), have attracted considerable attention. Impaired bone structure caused by LDR has been reported, but little is known about the mechanism involved in the disruption of bone metabolism. In this study, given that LDR was found to (at a cumulative dose of 0.10 Gy) disturb the serum Mg2+ level and Notch1 signal in the mouse femur tissues, the effects of LDR on osteogenesis and the underlying molecular mechanisms were investigated based on an in vitro culture system for bone marrow stromal cells (BMSCs). Our data showed that cumulative LDR suppressed the osteogenic potential in BMSCs as a result of upregulation of Notch1 signaling. Further analyses indicated that the upregulation of NICD1 (Notch1 intracellular domain), the key intracellular domain for Notch1 signaling, under LDR was a consequence of enhanced protein stabilization caused by SUMOylation (small ubiquitin-like modification). Specifically, the downregulation of SENP1 (sentrin/SUMO-specific protease 1) expression induced by LDR enhanced the SUMOylation of NICD1, causing the accumulation of Notch1 signaling, which eventually inhibited the osteogenic potential of BMSCs. In conclusion, this work expounded on the mechanisms underlying the impacts of LDR on bone metabolism and shed light on the research on bone regeneration under radiation.

Abstract Evidence for the involvement of N6-Methyladenosine (m6A) modification in the etiology and progression of liver fibrosis has emerged and holds promise as a therapeutic target. Insulin-like growth factor 2 (IGF2) mRNA-binding protein 2 (IGF2BP2) is a newly identified m6A-binding protein that functions to enhance mRNA stability and translation. However, its role as an m6A-binding protein in liver fibrosis remains elusive. Here, we observed that IGF2BP2 is highly expressed in liver fibrosis and activated hepatic stellate cells (HSCs), and inhibition of IGF2BP2 protects against HSCs activation and liver fibrogenesis. Mechanistically, as an m6A-binding protein, IGF2BP2 regulates the expression of Aldolase A (ALDOA), a key target in the glycolytic metabolic pathway, which in turn regulates HSCs activation. Furthermore, we observed that active glycolytic metabolism in activated HSCs generates large amounts of lactate as a substrate for histone lactylation. Importantly, histone lactylation transforms the activation phenotype of HSCs. In conclusion, our findings reveal the essential role of IGF2BP2 in liver fibrosis by regulating glycolytic metabolism and highlight the potential of targeting IGF2BP2 as a therapeutic for liver fibrosis.

The presence of organic matter in lakes profoundly impacts drinking water supplies, yet treatment processes involving coagulants and disinfectants can yield carcinogenic disinfection by-products. Traditional assessments of organic matter, such as chemical oxygen demand (CODMn) and biochemical oxygen demand (BOD5), are often time-consuming. Alternatively, optical measurements of dissolved organic matter (DOM) offer a rapid and reliable means of obtaining organic matter composition data. Here we employed DOM optical measurements in conjunction with parallel factor analysis to scrutinize CODMn and BOD5 variability. Validation was performed using an independent dataset encompassing six lakes on the Yungui Plateau from 2014 to 2016 (n = 256). Leveraging multiple linear regressions (MLRs) applied to DOM absorbance at 254 nm (a254) and fluorescence components C1–C5, we successfully traced CODMn and BOD5 variations across the entire plateau (68 lakes, n = 271, R2 > 0.8, P 0.9) in mesotrophic lakes compared to oligotrophic and eutrophic lakes. This study underscores the utility of MLR-based DOM indices for inferring CODMn and BOD5 variability in plateau lakes and highlights the potential of integrating in situ and remote sensing platforms for water pollution early warning.

Abstract The world's 1.4 million lakes (≥10 ha) provide many ecosystem services that are essential for human well‐being; however, only if their health status is good. Here, we reviewed common lake health issues and classified them using a simple human health‐based approach to outline that lakes are living systems that are in need of oxygen, clean water and a balanced energy and nutrient supply. The main reason for adopting some of the human health terminology for the lake health classification is to increase the awareness and understanding of global lake health issues. We show that lakes are exposed to various anthropogenic stressors which can result in many lake health issues, ranging from thermal, circulatory, respiratory, nutritional and metabolic issues to infections and poisoning. Of particular concern for human well‐being is the widespread lake drying, which is a severe circulatory issue with many cascading effects on lake health. We estimated that ∼115,000 lakes evaporate twice as much water as they gain from direct precipitation, making them vulnerable to potential drying if inflowing waters follow the drying trend, putting more than 153 million people at risk who live in close vicinity to those lakes. Where lake health issues remain untreated, essential ecosystem services will decline or even vanish, posing a threat to the well‐being of millions of people. We recommend coordinated multisectoral and multidisciplinary prevention and treatment strategies, which need to include a follow‐up of the progress and an assessment of the resilience of lakes to intensifying threats. Priority should be given to implementing sewage water treatment, mitigating climate change, counteracting introductions of non‐native species to lakes and decreasing uncontrolled anthropogenic releases of chemicals into the hydro‐, bio‐, and atmosphere.

In consideration of the practical demand for the reuse of mined-out areas as construction land, the assessment of foundation stability over mined-out areas has become a critical issue. Using a goaf in China as an example, this study investigates the overburden structure, void distribution law, and goaf treatment process through theoretical analysis, similar material simulation, and field measurements. The results show that the mining-induced voids in the compression zone are small and stable in distribution, whereas the voids in the tensile zone are subject to mutation, especially under external factors. Therefore, the tensile zone is the key processing position when dealing with long-wall goaf. To ensure accurate evaluation for the different positions of the goaf under the building, various methods are proposed. The compression zone in the middle of the goaf is evaluated using the additional stress method, which is modified under the grouting condition through theoretical analysis. The boundary tensile area is evaluated based on the inclination angle of the first key block of the masonry beam, ensuring evaluation accuracy. Furthermore, a void distribution model of longwall goaf is established. Under the guidance of the theoretical model, the goaf is reinforced by grouting and the optimal design of grouting materials is carried out. The final grouting test results show that the average strength of the gob after grouting treatment is high, which can ensure the stability of the gob, and the grouting treatment effect is good. This study provides a theoretical foundation and practical experience for similar goaf grouting treatments.

Abstract Background Tumor cell density is a basic pathological feature of solid tumors. Chemotherapy, radiotherapy, and targeted therapy reduce tumor cell density, whereas unrestricted tumor cell proliferation promotes this feature. The impact of tumor cells on the microenvironment following changes in tumor cell density is still unclear. In this study, we focused on the response of key immune cell subsets to tumor cell density in hepatocellular carcinoma (HCC). Methods We determined the density of tumor and immune cells in the same area by section staining. We then identified potential mediators using polymerase chain reaction (PCR), enzyme-linked immunofluorescence assay (ELISA), 3D and co-culture, flow cytometry, and lentivirus intervention. The mechanism of lactate promotion was verified using lactate tests, bioinformatics, western blotting, and the above methods. The IL-8/DAPK1/lactate/regulatory T cell (Treg) axis was verified using a mouse liver cancer model. Tumor mutation burden was calculated using maftools in R. Results We found that the Treg/CD8 + T cell ratio is not consistent with tumor cell density in HCC, and a decreased Treg/CD8 + T cell ratio in the range of 5000–6000 cells/mm2 may elicit the possibility for immunotherapy in an immunosuppressive microenvironment. We showed that IL-8 mediates this immune fluctuation and promotes the infiltration of Tregs through the DAPK1/pyruvate kinase activity/lactate axis in HCC. Based on tumor ploidy and mutation burden data, we discussed the potential significance of immune fluctuation in the homeostasis of HCC mutation burden and proposed a “density checkpoint” and “entropy model” to describe this phenomenon. Conclusions In summary, we report the mode of infiltration of Tregs/CD8 + T cells in response to tumor cell density and provide a new theoretical basis for IL-8 as a therapeutic target and the selection of an immunotherapy window in HCC.

Abstract Immune escape is a hallmark of cancer. The dynamic and heterogeneous tumour microenvironment (TME) causes insufficient infiltration and poor efficacy of natural killer (NK) cell-based immunotherapy, which becomes a key factor triggering tumour progression. Understanding the crosstalk between NK cells and the TME provides new insights for optimising NK cell-based immunotherapy. Here, we present new advances in direct or indirect crosstalk between NK cells and 9 specialised TMEs, including immune, metabolic, innervated niche, mechanical, and microbial microenvironments, summarise TME-mediated mechanisms of NK cell function inhibition, and highlight potential targeted therapies for NK-TME crosstalk. Importantly, we discuss novel strategies to overcome the inhibitory TME and provide an attractive outlook for the future.

Various methods of longwall full mining with partial filling have been extensively researched to satisfy the specific mining needs of pressurized-coal and residual-coal resources. This study introduces three longwall partial-filling-mining techniques: room–pillar filling mining, parallel-strip filling mining, and vertical-strip filling mining. Numerical simulations are employed to evaluate the efficacy of these methods. The findings indicate that vertical-strip filling mining results in minimal surface deformation and a more uniform distribution of displacements. In practical operations, the effectiveness of filling largely depends on the choice of filling technology and materials. The research further includes an optimization analysis of the filling technology, emphasizing the composition of the coal-gangue-paste filling system and the refinement of its components. Additionally, the study aims to explore the optimization analysis of filling materials, specifically focusing on performance-optimization methods. The experimental results illustrate that optimizing the filling materials can enhance the performance of filling paste, improving both early-stage and long-term compressive strength. Moreover, the paper examines the quantitative characterization of paste-filling-mining subsidence at various stages in conjunction with theoretical knowledge. Subsequently, mining-subsidence-control measures are recommended to address the primary deformation factors across different stages. Through an in-depth examination of filling-method designs, enhancements in filling technology, and predictions regarding filling-mining subsidence, this research offers valuable insights for optimizing longwall partial-filling-mining methods.

Ardisia crenata Sims, an important ethnic medicine, is recorded in the Chinese Pharmacopoeia for treating laryngeal diseases and upper respiratory tract infections. This study aimed to evaluate the antimicrobial effect of extracts and potential antimicrobial compounds of A. crenata Sims. It was found that the roots of A. crenata Sims have a potential inhibitory effect on Candida albicans and Aspergillus flavus, with MICs of 1.56 mg/mL and 0.39 mg/mL, and the leaves of A. crenata Sims have a potential inhibitory effect on Pseudomonas aeruginosa and Staphylococcus aureus, with MICs of 3.12 mg/mL and 6.77 mg/mL, respectively. Meanwhile, five compounds including one catechin and four bergenins were obtained from roots. These components were identified on the fingerprint spectrum, representing chromatographic peaks 16, 21, 22, 23, and 25, respectively. Among these, 11-β-d-glucopyranosyl-bergenin and (−)-gallocatechin showed potential inhibition for Staphylococcus aureus and Pseudomonas aeruginosa with MIC of 0.26 and 0.33 mg/mL, respectively. The roots, stems, and leaves of A. crenata Sims are very similar in chemical composition, with large differences in content. Principal component analysis (PCA) and Hierarchical cluster analysis (HCA) showed that 16 batches of A. crenata Sims could be divided into four main production areas: Guizhou, Jiangsu, Guangxi, and Jiangxi. Furthermore, molecular docking results showed that 11-β-d-glucopyranosyl-bergenin had a better affinity for Casein lytic proteinase P (ClpP), and (−)-gallocatechin possessed a strong affinity for LasA hydrolysis protease and LasB elastase. These findings suggest catechin and bergenins from A. crenata Sims can be used as antimicrobial activity molecules.

Secchi disk depth (SDD) is a simple but particularly important indicator for characterizing the overall water quality status and assessing the long-term dynamics of water quality for diverse global waters. For this reason, countless efforts have been made to collect SDD data from the field and through remote sensing systems. Many empirical and semianalytical algorithms have been proposed to estimate SDD from different satellite images for a specific or regional water. However, the construction of a robust global SDD estimation model is still challenging due to the nonlinear response of SDD to optical properties and the complex physical and biogeochemical processes of different waters. Therefore, machine learning methods to better interpret nonlinear processes were used to improve remote sensing estimations of SDD for global lakes and reservoirs based on a global matchup dataset from Landsat TM (N = 4099), ETM+ (N = 2420), and OLI (N = 1249) covering in situ SDD from 0.01 m to over 18 m. Overall, extreme gradient boosting (XGBoost) and random forest (RF) had better SDD retrievals than back propagation neural network, support vector regression, empirical and quasi-analytical models showing high precision with mean relative error of approximately 30% and good agreements with the long-term in situ SDD in different waters with various optical properties. Our results can support long-term global-level water quality evaluation and thus making informed decisions about development policy.

With complex topographic and hydrological characteristics, the landslide-induced surge disaster chain readily develops in mountainous and gorge areas, posing a huge challenge for infrastructure construction. This landslide-induced surge disaster chain involves a complex fluid-solid coupling between the landslide mass and a water body and exhibits complex energy conversion and dissipation characteristics, which is challenging to deal with using traditional finite element analysis. In this study, the energy evolution characteristics in the whole process of the disaster chain were first investigated, and the momentum-conservation equations for different stages were established. Then, the two-phase double-point material point method (TPDP-MPM) was used to model the landslide-induced surge disaster chain, and an experiment involving block-induced surge was modeled and simulated to validate this method. Finally, three generalized models were established for the landslide-induced surge process in a U-shaped valley, including subaerial, partly submerged, and submarine scenarios. The interaction mechanism between the landslide mass and the water body in the disaster chain was revealed by defining the system energy conversion ratio and the mechanism of evolution of the disaster chain from the perspective of energy. The results help further evaluate the secondary disasters, given the submerged position of the landslide mass.

Surrounding rock pressure is a crucial parameter in tunnel engineering design, and its calculation is a classic challenge. The surrounding rock pressure is influenced by geostress, but existing calculation methods often do not take into account the effect of geostress. In this paper, finite discrete element method (FDEM) is used to study the design values of tunnel surrounding rock pressure under different geostress fields. Firstly, a set of calibration methods for input parameters of FDEM is summarized based on previous studies. Then, taking a high-speed railway tunnel in IV-level surrounding rock as an example, the excavation-induced failure process of the tunnel under the influence of gravity stress field and geostress field is simulated using the FDEM. By comparing the results with those of the finite element method simulation, the rationality of applying FDEM to the simulation of tunnel excavation is demonstrated. Next, a calculation method of surrounding rock pressure design value based on FDEM is proposed by introducing tunnel displacement criterion, and its validity is verified by comparing with the results of the theoretical formula. Finally, the surrounding rock pressure design values under different geostress are analyzed by using this calculation method. The results show that there are significant differences between the gravity stress field and the geostress field in the maximum principal stress distribution, failure zone form and crack distribution. The geostress directly influences the design value of surrounding rock pressure. As the geostress varies from 4MPa to 12MPa, the corresponding design value increases from 49KPa to 1,288KPa, illustrating a quadratic relationship between them. With the corresponding design support force, the displacement of the surrounding rock is controlled within a reasonable range, ensuring the stability of the tunnel is maintained.

In the construction project, rock mass is often destroyed from the joint plane, and the jointed rock mass is easy to be eroded by freeze-thaw environment. Therefore, the damage mechanical properties of filled jointed rock mass under freeze-thaw action are very important for construction disaster prevention, engineering safety evaluation and reinforcement. In order to research the effect of the freeze-thaw cycle on the mechanical deterioration properties and damage characteristics of filled jointed rocks, prefabricated filled jointed rock samples are tested with different numbers of freeze-thaw cycles under the temperature range of -20°C~20°C. Then the wave velocity test, static compression test and SHPB impact test are conducted on the rock samples after freeze-thaw. Based on the test results, the change regularity of wave velocity degradation, static compression mechanical properties and dynamic compression mechanical properties of filled jointed rocks under the effect of freeze-thaw cycles were analyzed. The results show that the wave velocity, static compressive strength and dynamic compressive strength of the filled jointed rocks all show a downtrend with the increase of the number of freeze-thaw cycles, and each parameter is positively correlated with the strength of the filling materials. Among them, the decrease in the wave velocity of the rock sample after 30 freeze-thaw cycles is greater than 30%, and the strength loss of the static peak compressive strength exceeds half of its initial strength. The static peak strain rises exponentially with the increase of the number of freeze-thaw cycles while the dynamic peak strain does not show a clear trend. The dynamic peak strain is about 1/10 to 1/5 of the static peak strain. Under the same freeze-thaw action, the lower the strength of filling material, the more serious the damage.

The cutting hills to back ditches (CHBD) project has been widely implemented since urbanization in hilly areas is steadily rising. The stability of the high-filled slope and the problem of foundation settlement deformation has become one of the vital issues for safe construction. This paper focused on the deformation evolution law and stability assessment of the high-filled deposit slope composed of the soil-rock mixture (S-RM) in the CHBD project, in Shiyan City, Hubei Province as examples. First, large-scale direct shear tests of S-RM with different rock block proportions (RBPs) under different various normal stresses were carried out, and its mechanical properties were analyzed. Next, the finite element method was used to simulate the processes of the step-by-step filling, and the deformation evolution law was analyzed. Then, the limited equilibrium method (LEM) was used to obtain the potential sliding surfaces and the corresponding safety factors of the high-filled slope, and the safety of the construction was assessed. Finally, automated monitoring of the step-by-step settlement and deep soil deformation was computerized for the typical locations, and the long-term stability of the high-filled slope was studied. The results demonstrate that the first layer of backfill in the F area contains the largest incremental settlement displacement in the y-direction, whereas the value in the G area occurs at the site of the fill layer close to the slope surface at each filling timestep. The displacement response value steadily declines with the increasing filling depth and horizontal displacement, presenting a clear spatial influence range, with the site of maximum incremental displacement as the center. After filling, the safety factors of the potential sliding surface in the F and G areas are 2.531 and 1.118, respectively, and the slope is in a stable state. The monitoring data show that the deformation mostly takes place within 10 m of the surface. The study’s findings are thought to offer technical and practical knowledge for the slope risks.

Abstract Earth's lakes at northern latitudes are mostly ice‐covered in winter. When lake water freezes, some organic matter dissolved in the water is excluded from the ice. We performed complementary field sampling and laboratory freeze‐up experiments to explore how freeze‐up may impact the partitioning and composition of dissolved organic matter (DOM) in boreal lakes. We found that 16.2 ± 4.7% of dissolved organic carbon (DOC) was retained in the overlying ice, 81.3 ± 5.7% of DOC was expelled to underlying unfrozen water, and 1.3 ± 0.7% was expelled as flocs. During ice formation, nitrogen (TDN, total dissolved nitrogen), ions (specific conductance), and oxidized and aromatic DOM were preferentially expelled to the underlying water column. The apparent retention factor DOCIce: DOCBefore decreased from clearwater to brownwater lakes, that is, with increasing allochthonous DOC lost from lake ice, indicating that DOM exclusion from the ice cover will become more prevalent as lakes experience browning.

In the field of shield tunnels, the occurrence of uneven longitudinal settlement in segment linings has presented persistent challenges, including heightened risks of localized damage and water leakage. While the adoption of a secondary lining has been proposed as a viable solution to these issues, the question of how to select an appropriate construction time for the secondary lining, one that enables it to fully harness its load-bearing capacity while optimizing the tunnel’s overall stress and deformation characteristics, continues to be a pressing concern. To address this issue, this study established a three-dimensional longitudinal refined numerical model of double-layer-lined shield tunnel. In addition, the deformation degree of the segment lining was used as a time indicator to define the construction time for the secondary lining. Subsequently, an analysis of the impact of the construction time of the secondary lining on the longitudinal mechanical properties of the double-layer-lined shield tunnel is conducted through an assessment of tunnel longitudinal deformation and structural stress. The research findings indicated that the construction of the secondary lining improved the longitudinal deformation resistance of shield tunnels. Simultaneously, it led to a significant increase in the longitudinal shear forces within the segment lining and a notable reduction in longitudinal bending moments. Moreover, the construction time of the secondary lining played a pivotal role in these alterations. Considering the longitudinal force situations and load-bearing characteristics of the double-layer lining structure, it was determined that the optimal construction time for the secondary lining fell within the range of 20% to 40% of the total construction duration. In this scenario, the deformation and internal forces within the segment lining remained within permissible limits. Additionally, both the segment lining and the secondary lining were able to fully utilize their load-bearing capacities, ensuring the economic and safety aspects of the tunnel.

This study investigated the influence of water injection timing on the compression deformation of loose rock blocks in the goaf. The study used a confined gradient loading compression test to examine the deformation of loose rock blocks under initial saturation and later immersion conditions. The results showed that under initial saturation, the deformation of each loading gradient and the whole loading stage was greater than that of the later immersion stage. Additionally, the deformation of different stages in the initial saturated state was relatively regular, while in the later immersion state, the deformation changed abruptly after immersion. To explain the deformation mechanism of loose rock blocks, the mesostructure of loose rock blocks was granulated and the contact mechanism of particles was studied. The study found that water weakens the effective contact stress and strength between the skeleton particles, leading to sliding deformation as the dominant deformation mode. The study provides a theoretical basis for understanding the deformation characteristics of loose rock blocks in the goaf under different water environments.

Long-term geological storage of carbon dioxide in underground engineering is the most economically viable option for reducing emissions of this greenhouse gas to the atmosphere. Underground engineering projects are often subjected to earthquakes during their lives, thus it is essential to investigate the deformation characteristics of surrounding rock of those underground engineering works subjected to seismic load under different confining pressures. To date, however, there have been notably few studies on the characteristics of rock materials under seismic load and the influences of seismic load on dynamic deformation properties of rock material under different confining pressures remain unclear. Therefore, a numerical study of the dynamic mechanical properties of a rock material (T2y6 marble) under Kobe seismic load with four different maximum stresses and four different confining pressures was conducted. The results show cyclic behavior, strain rate effect and damage are found in the stress-strain curves of the rock under simulated Kobe seismic load. Confining pressure can significantly limit the increases in lateral strain and volumetric strain, thus dilation can occur in the rock when the maximum stress of seismic load is large, and the confining pressure is small. Seismic load with small maximum stress cannot cause severe damage to the rock, but the influence is larger than that of static load. The maximum stress can be treated as a main factor affecting the damage to rock under seismic loads, while the effect of confining pressure thereon is smaller than that of the maximum stress. Furthermore, the relationships between deformation characteristics of the rock under these seismic loads, such as maximum strain, residual strain, plastic internal variable, deformation modulus, and maximum stress are different from that between the deformation characteristics and confining pressure.

As an important traditional medicine of Buyi and Miao ethnic groups in Guizhou, Sabia parviflora Wall. provides antiviral properties against hepatitis, eliminates wind and dampness, and exhibits anti-inflammatory and pain relief properties. It has also been shown to treat rheumatoid arthritis (RA) and other diseases. However, the pharmacodynamic mechanism of S. parviflora Wall. for RA has not been reported. In this study, we identified the effective compounds of S. parviflora Wall. leaves against RA and discussed the mechanism against complete Freund’s adjuvant-induced arthritis (AIA) based on inflammatory proteins and transient receptor potential (TRP) proteins. S. parviflora Wall. leaf extracts (0.64 g/kg, 0.32 g/kg, and 0.16 g/kg, once daily) were given orally for 21 days. On the 15th day of complete Freund’s adjuvant-induced RA, the effects of this medicine on RA rats were investigated. S. parviflora Wall. extracts increased body weight, decreased foot swelling, and reduced thymus and spleen indices in model rats. Most of pannus in the synovial tissue of RA rats disappeared upon treatment, and the local inflammatory cells were greatly reduced when given the fraction of n-butanol (0.64 g/kg/d, 0.32 g/kg/d, and 0.16 g/kg/d) of 70% alcohol-soluble fraction of S. parviflora Wall. leaves. In addition, the release of inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-15 (IL-15), and vascular endothelial growth factor (VEGF) in the RA rat serum was inhibited. The active compounds inhibited the expression of TNF-α, IL-1β, IL-6, IL-10, IL-15 and nuclear factor kappa-Bp65 (NF-κBp65) inflammatory protein and TRP protein transient receptor potential melastatin-5 (TRPM-5) and transient receptor potential channel-6 (TRPC-6), to reduce the expression of VEGF in synovial tissue of RA rats and relieve redness and edema. High-performance liquid chromatography identified six flavonoids and three triterpenoid saponins as active compounds. These findings suggest S. parviflora Wall. leaves may play a role in RA treatment by inhibiting the release of inflammatory factors as well as participating in the inflammatory protein expression in the NF-κB pathway and TRP protein family.

To extend the lifetime of energy-constrained wireless networks, this paper proposes a three-node model of the wireless-powered cooperative communication network (WPCCN). The model consists of an energy-constrained source node, an energy-sufficient relay node, and a destination node and considers two different cochannel interference (CCI) sources at the relay and destination nodes. To ensure the reliability of data transmission, we introduce the cooperative automatic retransmission request (CARQ) protocol, propose the energy-constrained source that harvests and cooperates automatic retransmission request (ECS-HTCARQ) protocol in interference scenario, derive a closed-form expression for the outage probability under Rayleigh fading channels, and establish a discrete-time Markov chain (DTMC) model to analyze the system throughput. The relationship between parameters such as the energy harvesting time allocation factor and energy harvesting efficiency on the outage probability and the system throughput is obtained. Numerical results show that the difference in system throughput is small as the increasing number of transmissions at a high signal-to-interference ratio (SIR), but there is a significant reduction in the outage probability. Finally, the optimal value of the energy harvesting time allocation factor is given under this model.

To prolong the lifetime of energy-constrained cooperative networks, radio frequency energy harvesting (RFEH) technology can effectively solve the energy constraints of nodes batteries, and we consider the maximum ratio combining (MRC) method at the destination node to improve the reliability of the link transmission. Thus, we propose the power splitting-based double-relay cooperative transmission (PSDRCT) protocol with RFEH in the decode-and-forward (DF) mode in this study. According to the transmission process of the proposed protocol, the analytical expressions of outage probability, throughput, and energy efficiency are obtained. Numerical simulation results demonstrate that the location of the relay nodes, power allocation ratio, energy conversion efficiency, and transmission power are the key factors affecting the performance of the protocol. In addition, the proposed protocol has lower outage probability than the time switching-based double-relay cooperative transmission (TSDRCT) protocol under the same power allocation ratio and energy conversion efficiency.

Celastrol, an active triterpenoid extracted from one of the most famous traditional Chinese medicines (TCMs), Tripterygium wilfordii Hook.f., is a novel anti-cancer drug with significant anti-angiogenesis activity. However, the exact molecular mechanisms underlying its anti-tumor angiogenesis effect remain unclear. The process of angiogenesis needs lots of energy supply, which mostly derives from mitochondria, the “energy factory” in our body. This study shows that celastrol exerts visible suppression on tumor growth and angiogenesis in a cell-derived xenograft (CDX). Likewise, it reduced the tube formation and migration of human umbilical vein endothelial cells (HUVECs), suppressed the energy metabolism of mitochondria in the Seahorse XF Mito Stress Test, and triggered mitochondrial fragmentation and NF-κB activation. Mechanically, celastrol downregulated the expression of mitochondrial-sharping protein optic atrophy protein 1 (OPA1), which was further estimated by the OPA1 knockdown model of HUVECs. Specifically, celastrol directly suppressed OPA1 at the mRNA level by inhibiting the phosphorylation of STAT3, and stattic (STAT3 inhibitor) showed the same effects on OPA1 suppression and anti-angiogenesis activity. Overall, this study indicates that celastrol inhibits tumor angiogenesis by suppressing mitochondrial function and morphology via the STAT3/OPA1/P65 pathway and provides new insight for mitochondrion-targeted cancer therapy.

Deposit landslides are one of the most representative geological hazards around the world, and the poor understanding of the mechanical characteristics of the soilrock mixture (S-RM) increases the difficulties in evaluating the stability of the deposit slope subjected to rainfall. This study attempted to propose an innovative strength parameter estimation method of the S-RM based on the concept and format of the generalized HoekBrown criterion. The system of “rock blocks–soil–contact surface” was considered the main source providing resistance to the external force, and the effect of the soil matrix, rock blocks, and the contact surface between them was taken into account. The verification of the estimation method was proved based on the abundant test data. A typical deposit slope located in the Taoyuan region of Yunnan Province, China, was selected as a case study, and the estimation method was applied to provide the shear parameters of the S-RM. The slope stability subjected to different types of rainfall was analyzed considering the parameter deteriorations, and the results show that the deposit landslide is more prone to the wave-type rainfall, which shows a deeper response depth of pore water pressure and a smaller safety factor. The present study suggests a simple estimation method for the shear parameters of the S-RM using a few parameters for the engineers and provides an understanding of the deposit slope stability during the rainfall process.

Resistance spot-welding of dissimilar metals, medium manganese TRIP steel 7Mn and DP590, is carried out. The effects of single-pulse welding parameters and a double-pulse-tempering current on the quality characteristic parameters and mechanical properties of 7Mn/DP590 spot-welded joints are studied. The welding process parameters are optimized using the control variable method. The results show that the optimal process parameters under a single pulse are as follows: electrode pressure: 4.5 kN, welding current: 9 kA and welding time: 300 ms. The failure mode of the welding joint is partial pull-out failure (PF-TT). The welding parameters have great influence on the nugget diameter and thickness reduction. Expulsion, crack and shrinkage are displayed in the joint under high electrode pressure. Softening occurs in the heat-affected zone due to a strong halo effect in the single-pulse weld. The tempering zone on the DP590 side is 202.49 HV, which is the lowest hardness point, while the hardness of the nugget zone is 450 HV. The addition of the tempering current homogenizes the microstructure with different failure paths and eliminates the stress. The tensile shear force of the joint increases by 17.13%. The 7Mn Steel/DP590 resistance spot-welding joint is from the fusion line to the center of the nugget, and the microstructure is composed of plane crystal, cellular crystal, dendritic crystal and columnar crystal, in turn. The nugget zone is composed of lath martensite and a small amount of residual austenite. Fine quasi-spherical and lamellar interbedded cementites are formed in the tempering zone of the DP590-side heat-affected zone.

Bimetallic components welded by Ta and stainless steel have great promise for engineering applications, but there is relatively little relevant research. In this study, 0.6 mm-thick Ta and 304L stainless steel plates were laser welded, and the forming characteristics, microstructure, and mechanical properties of the welded joints were analyzed. First-principles calculations were also performed to explore the structural stabilization mechanisms of the two intermetallic compounds, TaFe2 and TaCr2, in terms of mechanical properties as well as electronic structure. The results showed that the weld surface was smooth and free from any defects. Fe-based solid solutions formed grains, while TaFe2, TaCr2, and some Fe-based solid solutions formed intergranular and eutectic structures. In addition, due to the presence of the brittle phases of TaFe2 and TaFe, the microhardness of the weld area can reach 650HV, with an average hardness of 530HV, which is much higher than that of the base material. The tensile shear of the joint at room temperature was 154.77 N/mm, and the fracture occurred in the weld zone on the steel side, showing brittle fracture. TaFe2 is a brittle intermetallic compound, while TaCr2 is ductile. Both TaFe2 and TaCr2 systems have dual properties of metallic and covalent bonding within them, and metallic bonding dominates.

Two new lactones, named Ardisicreolides A–B (1–2), together with four known flavonoids, Quercetin (3), Myricetrin (4), Quercitrin (5), Tamarixetin 3-O-rhamnoside (6), were isolated from the ethyl acetate portion of 70% ethanol extracts of dried leaves from Ardisia crenata Sims. These compounds were identified from Ardisia crenata Sims for the first time. The structures of 1–6 were elucidated according to 1D and 2D-NMR methods and together with the published literature. All of the isolated compounds were evaluated for in vitro anti-microbial effect against Escherichia coli, Pseudomonas aeuroginosa, Enterococcus faecalis, Proteus vulgaris, Staphylococcus aureus, and Bacillus subtilis. In addition, compounds 1–2 were assessed for anti-inflammatory activity by acting on LPS-induced RAW 264.7 macrophage cells in vitro. The results showed that only compound 2 exhibited moderate antibacterial activity on Bacillus subtilis. Moreover, compounds 1 and 2 were found to significantly inhibit the production of nitric oxide (NO) and reduce the release of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-4 (IL-4), and interleukin-10 (IL-10) in LPS-induced RAW 264.7 macrophage cells. The present data suggest that lactones from the leaves of A. crenata Sims might be used as a potential source of natural anti-inflammatory agents.

The damage of a long tunnel is found in parts with an adverse geological structure zone under an earthquake. The phenomenon is normally the consequence of a non-uniform seismic load. Thus, to reveal the mechanism of the phenomenon, the dynamic response of the lining structure in a long tunnel passing through an adverse geological structure zone subjected to a non-uniform seismic load is mainly studied in this paper. Firstly, based on the random ground motion synthesis theory, the non-uniform ground motion acceleration–time history curves that reflect local site effects, such as traveling wave effects and attenuation effects, are generated. Secondly, the behavior of the tunnel with a different adverse geological structure zone (including different inclinations, thicknesses, and lithologies) under non-uniform seismic input is studied. Then, the impact of the different adverse geological structure zone on the internal force and safety factor of the tunnel lining is analyzed. Finally, the failure characteristics of the lining structure in the tunnel crossing through the adverse geological structure zone subjected to a non-uniform seismic load are revealed. The results show that the seismic dynamic responses significantly increase under non-uniform seismic input compared with the results under uniform seismic input, and the dynamic responses distribution along the tunnel axial is distinctly different under non-uniform seismic input. The inclination and thickness of the adverse geological structure zone have a significant influence on the internal force and safety factor of the tunnel lining, while the lithology mainly acts around the adverse geological structure zone. When the inclination angle of the adverse geological structure zone is 45°, a large number of compression-bending cracks appear in the entrance and exit sections of the tunnel, and the tunnel is in the most dangerous state.

Ardisiacrispin D–F (1–3), three new 13,28 epoxy bridged oleanane-type triterpenoid saponins, together with four known analogues (4–7) were isolated from the roots of Ardisia crispa. The structures of 1–7 were elucidated based on 1D and 2D-NMR experiments and by comparing their spectroscopic data with values from the published literatures. Ardisiacrispin D–F (1–3) are first examples that the monosaccharide directly linked to aglycone C-3 of triterpenoid saponins in genus Ardisia are non-arabinopyranose. In the present paper, all compounds are evaluated for the cytotoxicity against three cancer cell lines (HeLa, HepG2 and U87 MG) in vitro. The results show that compounds 1, 4 and 6 exhibited significant cytotoxicity against Hela and U87 MG cells with IC50 values in the range of 2.2 ± 0.6 to 9.5 ± 1.8 µM. The present investigation suggests that roots of A. crispa could be a potential source of natural anti-tumor agents and their triterpenoid saponins might be responsible for cytotoxicity.