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Abstract Small molecule inhibitors of apoptosis proteins (IAPs) antagonists, known as Smac mimetics (SMs), activate non-canonical NF-κB and sensitize cancer cells to TNF-induced cell death. SMs are currently in phase III clinical trials for head and neck squamous cell carcinoma (HNSCC) after promising phase II trials. To explore the utility of SMs in oral squamous cell carcinoma (OSCC), we tested nine human OSCC cell lines and correlated SM sensitivity with both IAP mutation and expression levels. cIAP1 protein expression was shown to be higher in OSCC and a predictor of poor prognosis. However, our in vitro and in vivo testing demonstrated differential sensitivity to SMs, which did not correlate with cIAP1 and cIAP2 expression in these OSCC cell lines. Exogenous TNF failed to effectively increase the sensitivity of SM-resistant OSCC cells to SM-induced cell death. SM resistance was associated with a deficiency in Complex IIa formation, but activation of non-canonical NF-κB was not a determinant of SM efficacy. Finally, metabolic analysis revealed that the ABC transporter pathway was activated in SM-resistant OSSC cells, and SMs combined with ABC transporter inhibitors improved cell death sensitivity to overcome SM resistance. These studies highlight the therapeutic potential of SMs in OSCC and support patient stratification to improve efficacy with the addition of adjuvant therapy.

Abstract Liquid biopsy is a minimally invasive method that uses biofluid samples instead of tissue samples for cancer diagnosis. Exosomes are small extracellular vesicles secreted by donor cells and act as mediators of intercellular communication in human health and disease. Due to their important roles, exosomes have been considered as promising biomarkers for liquid biopsy. However, traditional methods for exosome isolation and cargo detection methods are time-consuming and inefficient, limiting their practical application. In the past decades, many new strategies, such as microfluidic chips, nanowire arrays and electrochemical biosensors, have been proposed to achieve rapid, accurate and high-throughput detection and analysis of exosomes. In this review, we discussed about the new advance in exosome-based liquid biopsy technology, including isolation, enrichment, cargo detection and analysis approaches. The comparison of currently available methods is also included. Finally, we summarized the advantages and limitations of the present strategies and further gave a perspective to their future translational use. Graphical Abstract

Abstract Tumor cells remodel the phenotype and function of tumor microenvironment (TME) cells to favor tumor progression. Previous studies have shown that neutrophils in TME are polarized to N2 tumor-associated neutrophils (TANs) by tumor derived factors, thus promoting tumor growth and metastasis, angiogenesis, therapy resistance, and immunosuppression. Exosomes act as critical intercellular messengers in human health and diseases including cancer. So far, the biological roles of exosomes from N2 TANs in gastric cancer have not been well characterized. Herein, we represented the first report that exosomes from N2 TANs promoted gastric cancer metastasis in vitro and in vivo. We found that exosomes from N2 TANs transferred miR-4745-5p/3911 to gastric cancer cells to downregulate SLIT2 (slit guidance ligand 2) gene expression. Adenovirus-mediated overexpression of SLIT2 reversed the promotion of gastric cancer metastasis by N2 TANs derived exosomes. We further revealed that gastric cancer cells induced glucose metabolic reprogramming in neutrophils through exosomal HMGB1 (high mobility group protein B1)/NF-κB pathway, which mediated neutrophil N2 polarization and miR-4745-5p/3911 upregulation. We further employed ddPCR (droplet digital PCR) to detect the expression of miR-4745-5p/3911 in N2 TANs exosomes from human serum samples and found their increased levels in gastric cancer patients compared to healthy controls and benign gastric disease patients. Conclusively, our results indicate that N2 TANs facilitate cancer metastasis via regulation of SLIT2 in gastric cancer cells by exosomal miR-4745-5p/3911, which provides a new insight into the roles of TME cells derived exosomes in gastric cancer metastasis and offers a potential biomarker for gastric cancer diagnosis.

Niobium (Nb) is considered as candidate material for heat pipe in space nuclear reactors due to high melting point, low density, excellent compatibility with alkali liquid metals, irradiation resistance, workability and welding performance, but low strength restricts it's engineering application. In this work, yttrium (Y) was introduced into Nb matrix to achieve solution strengthening from Y atoms and dispersion strengthening from yttrium oxides. The latter one was realized by oxygen carrier route and vacuum electromagnetic levitation melting technique. Finally, one Nb521 (Nb-5.0 wt%W-1.7 wt%Mo-1.0 wt%Zr-0.07 wt%C) and four kinds of Nb521-xY (x = 0.1, 0.2 0.3 and 0.4 wt%) alloys were prepared. TEM characterization indicated that 80 nm Y2O3 particles were formed in Nb521-0.1Y, which exhibited the highest yield strength of 673 MPa, ultimate tensile strength of 740 MPa as well as larger elongation of 12.8%. Moreover, the solution strengthening of Y atoms and Orowan strengthening of yttrium oxides were evaluated quantitatively.

Abstract Perovskite oxides show promise for the oxygen evolution reaction. However, numerical chemical compositions remain unexplored due to inefficient trial-and-error methods for material discovery. Here, we develop a transfer learning paradigm incorporating a pre-trained model, ensemble learning, and active learning, enabling the prediction of undiscovered perovskite oxides with enhanced generalizability for this reaction. Screening 16,050 compositions leads to the identification and synthesis of 36 new perovskite oxides, including 13 pure perovskite structures. Pr0.1Sr0.9Co0.5Fe0.5O3 and Pr0.1Sr0.9Co0.5Fe0.3Mn0.2O3 exhibit low overpotentials of 327 mV and 315 mV at 10 mA cm−2, respectively. Electrochemical measurements reveal coexistence of absorbate evolution and lattice oxygen mechanisms for O-O coupling in both materials. Pr0.1Sr0.9Co0.5Fe0.3Mn0.2O3 demonstrates enhanced OH- affinity compared to Pr0.1Sr0.9Co0.5Fe0.5O3, with the emergence of oxo-bridged Mn-Co conjugate facilitating charge redistribution and dynamic reversibility of Olattice/VO, thereby slowing down Co dissolution. This work paves the way for accelerated discovery and development of high-performance perovskite oxide electrocatalysts for this reaction.

Abstract Background Circular RNAs (circRNAs) play important roles in cancer progression and metastasis. However, the expression profiles and biological roles of circRNAs in non-small cell lung cancer (NSCLC) remain unclear. Methods In this study, we identified a novel circRNA, hsa_circ_0006834 (termed circ6834), in NSCLC by RNA-seq and investigated the biological role of circ6834 in NSCLC progression in vitro and in vivo. Finally, the molecular mechanism of circ6834 was revealed by tagged RNA affinity purification (TRAP), western blot, RNA immunoprecipitation, dual luciferase reporter gene assays and rescue experiments. Results Our results showed that circ6834 was downregulated in NSCLC tumor tissues and cell lines. Circ6834 overexpression inhibited NSCLC cell growth and metastasis both in vitro and in vivo, while circ6834 knockdown had the opposite effect. We found that TGF-β treatment decreased circ6834 expression, which was associated with the QKI reduction in NSCLC cells and circ6834 antagonized TGF-β-induced EMT and metastasis in NSCLC cells. Mechanistically, circ6834 bound to AHNAK protein, a key regulator of TGF-β/Smad signaling, and inhibited its stability by enhancing TRIM25-mediated ubiquitination and degradation. In addition, circ6834 acted as a miRNA sponge for miR-873-5p and upregulated TXNIP gene expression, which together inactivated the TGF-β/Smad signaling pathway in NSCLC cells. Conclusion In conclusion, circ6834 is a tumor-suppressive circRNA that inhibits NSCLC progression by forming a negative regulatory feedback loop with the TGF-β/Smad signaling pathway and represents a novel therapeutic target for NSCLC.

In order to achieve favorable heat corrosion resistance, it is effective to add high Si contents to F/M heat resistant steel. Unfortunately, the high Si content results in a significant deterioration of impact toughness. Determining how to balance heat corrosion resistance and impact toughness has been a challenge. In this paper, we optimize austenite isothermal hot-rolling (AIHR) technique to the 10Cr1SiY F/M dual-phase heat resistant steel with 1% Si(wt.), to obtain layered microstructure with thread-like δ-ferrite. This decreases ductile-brittle transition temperature (DBTT) from 149 °C to 15 °C, and increases impact energy from 8 J to 107 J, compared to the quenched and tempered steel with the same chemical composition. According to the instrumented Charpy impact tests, higher impact energy derives from the absorbing energy during crack propagation, accounting for 94.9% of the total absorbing energy. The weak interfaces in the layered microstructure effectively deflect cracks, while the {110} slip plane induced by strong textures from multi-pass rolling promoted dislocation slip, thus rendering plastic deformation and weakening the crack tip stress; synergistic interaction is responsible for the improved toughness, resulting in the delamination fracture of the steel. The reduced grain size and M23C6 phases also contributes to the improved toughness.

AbstractHorizontal platelet-rich fibrin (H-PRF) contains a variety of bioactive growth factors and cytokines that play a key role in the process of tissue healing and regeneration. The blood collection tubes used to produce Solid-PRF (plasmatrix (PM) tubes) have previously been shown to have a great impact on the morphology, strength and composition of the final H-PRF clot. Therefore, modification to PM tubes is an important step toward the future optimization of PRF. To this end, we innovatively modified the inner wall surface of the PM tubes with plasma and adjusted the gas environment inside the PM tubes to prepare super-hydrophilic anaerobic plasmatrix tubes (SHAP tubes). It was made anaerobic for the preparation of H-PRF with the aim of improving mechanical strength and bioactivity. The findings demonstrated that an anaerobic environment stimulated platelet activation within the PRF tubes. After compression, the prepared H-PRF membrane formed a fibrous cross-linked network with high fracture strength, ideal degradation characteristics, in addition to a significant increase in size. Thereafter, the H-PRF membranes prepared by the SHAP tubes significantly promoted collagen synthesis of gingival fibroblast and the mineralization of osteoblasts while maintaining excellent biocompatibility, and advantageous antibacterial properties. In conclusion, the newly modified PRF tubes had better platelet activation properties leading to better mechanical strength, a longer degradation period, and better regenerative properties in oral cell types including gingival fibroblast and alveolar osteoblasts. It also improves the success rate of H-PRF preparation in patients with coagulation dysfunction and expands the clinical application scenario.

ABSTRACT: China is the biggest muskmelon producing country across the world. Extreme application of fertilizer during planting of muskmelon poses a serious threat to the environment and food safety, so how to promote farmers to use organic fertilizer has become an important topic. This study creatively introduced green awareness into the extended framework of theory of planned behavior to explore the decisive factors of muskmelon farmers’ behavior intention to apply green organic fertilizer. The structural equation model is used for investigating behavior intention of 543 muskmelon farmers in Leting County, China. The results suggested that both subjective norm and green awareness can affect muskmelon farmers’ behavior intention positively and significantly. When the subjective norm increases by 1 standard deviation, the farmers’ intention increases by 1.028 standard deviation; for every 1 standard deviation increase in green awareness, the farmers’ intention increased by 0.703 standard deviation.

Abstract M2‐polarized tumor‐associated macrophages (M2 TAMs) promote cancer progression. Exosomes mediate cellular communication in the tumor microenvironment (TME). However, the roles of exosomes from M2 TAMs in gastric cancer progression are unclear. Herein, it is reported that M2 TAMs‐derived exosomes induced aerobic glycolysis in gastric cancer cells and enhanced their proliferation, metastasis, and chemoresistance in a glycolysis‐dependent manner. It is identified that MALAT1 (metastasis‐associated lung adenocarcinoma transcript 1) is enriched in M2 TAM exosomes and confirmed that MALAT1 transfer from M2 TAMs to gastric cancer cells via exosomes mediates this effect. Mechanistically, MALAT1 interacted with the δ‐catenin protein and suppressed its ubiquitination and degradation by β‐TRCP. In addition, MALAT1 upregulated HIF‐1α expression by acting as a sponge for miR‐217‐5p. The activation of β‐catenin and HIF‐1α signaling pathways by M2 TAM exosomes collectively led to enhanced aerobic glycolysis in gastric cancer cells. Finally, a dual‐targeted inhibition of MALAT1 in both gastric cancer cells and macrophages by exosome‐mediated delivery of siRNA remarkably suppressed gastric cancer growth and improved chemosensitivity in mouse tumor models. Taken together, these results suggest that M2 TAMs‐derived exosomes promote gastric cancer progression via MALAT1‐mediated regulation of glycolysis. The findings offer a potential target for gastric cancer therapy.

Abstract As the interplanetary magnetic field (IMF) carried by the solar wind encounters the martian atmosphere, it tends to pile up and drape around the planet, forming looping magnetic fields and inducing marsward ion flows on the nightside. Previous statistical observations revealed asymmetrical distribution features within this morphology; however, the underlying physical mechanism remains unclear. In this study, utilizing a three‐dimensional multi‐fluid magnetohydrodynamic simulation model, we successfully reproduce the asymmetrical distributions of the looping magnetic fields and corresponding marsward flows on the martian nightside. Analyzing the magnetic forces resulting from the bending of the IMF over the polar area, we find that the asymmetry is guided by the orientation of the solar wind motional electric field (ESW). A higher solar wind velocity leads to enhanced magnetic forces, resulting in more tightly wrapped magnetic fields with an increased efficiency in accelerating flows as they approach closer to Mars.

The 15-15Ti austenitic stainless steel is commonly used as a fast reactor cladding material due to its favorable comprehensive properties. To further enhance its high temperature strength, yttrium (Y) modified 15-15Ti (15-15Ti-Y) steel was developed. In this study, the tensile properties of 15-15Ti-Y were evaluated across the temperature range of 200–700 °C, and the constant load creep properties of 20 % cold worked (CW) 15-15Ti-Y were measured at temperatures of 550–700 °C under various applied stresses. The results indicated that Y addition led to enhanced intragranular precipitates and delayed intergranular precipitates, which resulted in a YS (YS) that was ∼ 100 MPa higher than that of Y-free steel at temperatures ranging from 200 to 600 °C, without compromising the plasticity and ductility. The creep fracture life of 15-15Ti-Y steel ranged from 21 to 5761 h, and the deformation and damage processes were found to adhere to the Norton power-law and Modified Monkman Grant relationship. The stress exponent revealed that the deformation was dislocation creep mechanism, while the creep damage tolerance parameter suggested that the creep fracture was caused by necking. These findings provide data and theoretical support for the application of Y-modified 15-15Ti steel as a fast reactor cladding material in high temperature environments.

Abstract Background Exosomes released from decidual stromal cells (DSC-exos) play a crucial role in facilitating the epithelial–mesenchymal transition (EMT) of trophoblasts and insufficient trophoblasts EMT are associated with URSA (unexplained recurrent spontaneous abortion). However, the mechanisms underlying DSC-exos inducing EMT is not completely understood. Methods DSC-exos of normal pregnant women (N-DSC-exos) and URSA patients (URSA-DSC-exos) were extracted and characterized. Characterization of the isolated DSC-exos was performed using with TEM (transmission electron microscopy), NTA (nanoparticle tracking analysis), and WB (western blot) techniques. Subsequently, these DSC-exos were co-cultured with trophoblasts cell lines (HTR-8/SVneo). The influence of both N-DSC-exos and URSA-DSC-exos on trophoblasts proliferation, invasion and migration, as well as on the expression of EMT-related proteins, was evaluated through a series of assays including CCK8 assays, wound healing assays, transwell assays, and western blot, respectively. Then rescue experiments were performed by β-TrCP knockdown or β-TrCP overexpressing trophoblasts with snail-siRNA transfection or β-TrCP overexpressing Lentivirus infection, respectively. Finally, animal experiments were employed to explore the effect of N-DSC-exos on embryo absorption in mice. Results We found increased β-TrCP expression in the villus of URSA patients when compared to the normal pregnant women, alongside reduction in the levels of both snail and N-cadherin within URSA patients. N-DSC-exos can promote the EMT of the trophoblast by inhibiting β-TrCP-mediated ubiquitination and degradation of transcription factor snail. Moreover the capacity to promote EMT was found to be more potent in N-DSC-exos than URSA-DSC-exos. Down-regulation of snail or overexpression of β-TrCP can reverse the effects of N-DSC-exos on trophoblast. Finally, in vivo experiment suggested that N-DSC-exos significantly reduced the embryo resorption rate of spontaneous abortion mouse model. Conclusions Our findings indicate that URSA-DSC-exos caused insufficient migration and invasion of trophoblast because of disturbing of β-TrCP-mediated ubiquitination and degradation of EMT transcription factor snail. Elucidating the underlying mechanism of this dysregulation may shed light on the novel pathways through which DSC-exos influence trophoblast function, thereby contributing to our understanding of their role in URSA.

Abstract Backgroud Regardless of application scenarios, proper mechanical characteristics and degradation properties are prerequisites for horizontal platelet rich fibrin (H-PRF) to manifest its ability. Among the methods used to modify PRF, thermal manipulation is promising as it is easy to handle without adding extra additives. Yet there is no consensus on optimal temperature treatment. This study aimed to investigate the effects of heating on the biological and mechanical characteristics of H-PRF and explore the optimum heating temperature for H-PRF thermal treatment. Methods We employed a series of temperature gradients, room temperature, 50℃, 75℃, 90℃, 105℃. The microstructure and the mechanical properties were recorded by Scanning Electron Microscope (SEM) and tensile strength tests respectively. The degradation rate of H-PRF membranes was examined by digestion assay with plasmin and trypsin. The viability of cells within H-PRF membranes and the proliferation of osteoblasts cultured with extracts from different H-PRF groups was evaluated using CCK-8 assays. Results Compared with the nonheated group, overheated manipulation beyond 90℃ can significantly prolong the degradation properties for up to 3 to 4 weeks and enhance the mass stress of H-PRF membranes. A high-temperature treatment of 105℃ accompanied by the cell activity beneath H-PRF reduced more than half, and thus, the biological effect on human osteoblasts (hFOBs) also reduced dramatically. Conclusions High thermal manipulation can prolong the degradation properties and enhance the mechanical properties of PRF membranes accompanied by the loss of biological effect.

Atmospheric gravity waves are one of the important dynamic processes in near space and are widely present in the atmosphere. They play a crucial role in the transfer of energy and momentum between different regions of the atmosphere. The Sun, as the ultimate source of gravity wave energy, significantly influences the intensity of gravity wave disturbances through its activity variations. This paper utilizes data from the Global Navigation Satellite System Occultation Sounder (GNOS) onboard the Fengyun-3C (FY-3C) satellite to invert global stratospheric gravity wave disturbances. It provides the global stratospheric gravity wave distribution from 2015 to 2023, nearly covering one solar activity cycle, and focuses on analyzing the response of gravity waves at different latitudes, altitudes, and wavelengths to the solar activity cycle. We found that short-wavelength gravity waves respond more noticeably to solar activity compared to long-wavelength gravity waves. Through analyzing the intensity of stratospheric gravity wave disturbances across different latitude bands, we found that in high-latitude regions, stratospheric gravity wave disturbances are most sensitive and respond most quickly to variations in solar activity. Furthermore, the Southern Hemisphere exhibits a stronger response to the current year’s solar activity changes compared to the Northern Hemisphere. In the mid-latitude and equatorial regions, the response to changes in solar activity intensity is delayed. The correlation gradually strengthens with this lag, reaching a very strong level after a 2-year lag. Additionally, the correlation between the Southern Hemisphere and solar activity is generally higher than that of the Northern Hemisphere.

Soil bacterial α and β diversity patterns under nitrogen (N) addition have been intensively examined, but γ diversity patterns remain largely unknown, especially, the mechanisms that concurrently control changes in α, β and γ diversity remain elusive. Therefore, we formulated a conceptual framework that simultaneously considers candidate drivers including ubiquitous species, rare species, and community assembly processes to elucidate the driving mechanisms of α, β and γ diversity under N addition. The conceptual framework was tested by compiling the sequence data of seven studies published from January 1997 to May 2022 and following the same analysis as our own two long-term multilevel N addition experiments. We demonstrate that subtractive heterogenization based on environment selection simultaneously predicts the changes in α, β and γ diversity under long-term N addition. That is, long-term N addition led to the decline of ubiquitous species (subtractive processes) through low soil pH, and promoted the strength of heterogeneous selection (heterogeneous processes) via enhancing environmental heterogeneity, subsequently causing lower α diversity and γ diversity but higher β diversity. These results mean that N addition may lead to a significant loss of soil bacterial diversity around the world. Together, these findings offer a way to simultaneously predict soil bacterial α, β and γ diversity responses to the ongoing atmospheric nitrogen deposition.

It has been proven that martensite matrix accompanied by fine reversed austenite is beneficial to improve the strength and toughness in martensitic steels to a certain extent. In order to achieve this unique microstructure, the existing methods, like quenching at high temperatures, multiple heat treatment processes, increasing Ni content, raise the economic cost and operation difficulty. In this work, fine reversed austenite was formed in Fe13Cr4NiMo steel with relatively low nickel content (4 wt%) by one-time relatively low temperature quenching (860 °C) and tempering process. Then the formation mechanism and effect on mechanical properties of reversed austenite were discussed. The 0.55 vol% reversed austenite with the size of 260 nm can be formed in Fe13Cr4NiMo steel under quenching at 860 °C for 40 min and tempering at 650 °C for 2 h. The reversed austenite maintained a deviation of ∼2° from K-S relationship with the martensite matrix. In addition, the formation of reversed austenite was caused by short circuit diffusion of element-free redistribution, which caused the reversed austenite to be more inclined to nucleate at subgrain boundaries and grow up restrictedly. Furthermore, the Fe13Cr4NiMo steel that contained reversed austenite hindering dislocation movement and coordinating deformation possessed excellent plasticity of 18.4 % and Charpy impact energy of 289 J while maintaining high strength of 872 MPa at room temperature.

FeCrAl alloy is one of the potential candidates of structural materials due to its high strength, low radiation swelling and good oxidation resistance for the application of lead-cooled fast reactors (LFRs). Particularly, FeCrAl alloy can form protective Al-containing oxide scales after exposure to liquid oxygen-rich Pb and lead–bismuth eutectic (LBE) at 400–800 ℃, showing better performance than traditional commercial stainless steels such as T91, 316L and 15-15Ti. Given the possibility that oxygen in liquid metal could be consumed and not be supplied timely in some quasi-static regions of the actual coolant circuit, to figure out the corrosion behavior of FeCrAl alloy in oxygen-depleted LBE is necessary. In this work, the commercial FeCrAl alloy was exposed to static liquid LBE containing Ni impurities with 10−9 wt% oxygen concentration at 600 ℃ for up to 5000 h, and the surface and cross-sectional morphology of the samples was characterized and analysed. It is found that FeCrAl alloy underwent severe dissolution corrosion, and the maximum penetration depth of LBE reached 161.4 μm after the test for 5000 h; PbBi infiltrated into alloy matrix along the GBs and selectively leached Al from the affected grains. Besides, an interesting discovery is the Cr-rich thin layer at LBE/matrix interface and Ni3Al precipitates in LBE penetration front which should be attributed to the deposition of impurity elements dissolved in liquid LBE during the cooling process.

Abstract Dietary methylmercury (MeHg) exposure increases the risk of many human diseases. The Guangdong-Hong Kong-Macao Greater Bay Area (GBA) is the world’s most populous bay area and people there might suffer a high risk of dietary MeHg exposure. However, there lacks a time-series high spatial resolution dataset for dietary MeHg exposure in the GBA. This study constructs a high spatial resolution (1 km × 1 km) dataset for dietary MeHg exposure in the GBA during 2009–2019. It first constructs the dietary MeHg exposure inventory for each county/district of the GBA, based on MeHg concentrations of foods (i.e., rice and fish in this study) and per capita rice and fish intake. Subsequently, this study spatializes the dietary MeHg exposure inventory at 1 km × 1 km scale, using gridded data for food consumption expenditure as the proxy. This dataset can describe the spatially explicit hotspots, distribution patterns, and variation trend of dietary MeHg exposure in the GBA. This dataset can support spatially explicit evaluation of MeHg-related health risks in the GBA.

Abstract The interaction between tumor cells and stromal cells within the tumor microenvironment plays a critical role in cancer progression. Mesenchymal stem cells (MSCs) are important tumor stromal cells that exhibit pro-oncogenic activities when reprogrammed by the tumor. However, the precise mechanisms underlying MSC reprogramming in gastric cancer remain not well understood. QRT-PCR, western blot, and immunohistochemistry were used to examine gene and protein expression levels. In vitro and in vivo experiments were conducted to assess the biological functions of gastric cancer cells. RNA-sequencing, RNA immunoprecipitation (RIP), and meRIP assays were performed to investigate underlying molecular mechanisms. We found a significant increase in the expression and N6-methyladenosine (m6A) modification levels of colony-stimulating factor 2 (CSF2) in gastric cancer MSCs. CSF2 gene overexpression induced the reprogramming of normal MSCs into cancer-promoting MSCs, thereby enhancing the proliferation, migration, and drug resistance of gastric cancer cells through the secretion of various pro-inflammatory factors. Additionally, we demonstrated that the m6A reader IGF2BP2 bound to and stabilized CSF2 mRNA in gastric cancer MSCs. Notably, overexpression of IGF2BP2 mimicked the effect of CSF2 on MSCs, promoting gastric cancer progression. Finally, we unveiled that CSF2 induced the ubiquitination of Notch1 to reprogram MSCs. Our study highlights a critical role of IGF2BP2-mediated m6A modification of CSF2 in reprogramming MSCs, which presents a promising therapeutic target for gastric cancer.

We use the High-energy Electron Experiments (HEP) instrument onboard Arase (ERG) to conduct an energy-dependent cross-satellite calibration of electron fluxes measured by the High Energy Particle Detector (HEPD) onboard FengYun-4A (FY-4A) spanning from April 1, 2017, to September 30, 2019. By tracing the two-dimensional magnetic positions (L, magnetic local time [MLT]) of FY-4A at each time, we compare the datasets of the conjugate electron fluxes over the range of 245–894 keV in 6 energy channels for the satellite pair within different sets of L × MLT. The variations in the electron fluxes observed by FY-4A generally agree with the Arase measurements, and the percentages of the ratios of electron flux conjunctions within a factor of 2 are larger than 50%. Compared with Arase, FY-4A systematically overestimates electron fluxes at all 6 energy channels, with the corresponding calibration factors ranging from 0.67 to 0.81. After the cross-satellite calibration, the electron flux conjunctions between FY-4A and Arase show better agreement, with much smaller normalized root mean square errors. Our results provide a valuable reference for the application of FY-4A high-energy electron datasets to in-depth investigations of the Earth’s radiation belt electron dynamics.

Attributed to the lack of an Earth-like global intrinsic dipole magnetic field on Mars, the induced electromagnetic field environment plays a crucial role in the evolution of its atmosphere. The dominant motional electric field (EM) induced by the bulk motion of the magnetic field within the Martian magnetosheath serves to accelerate ions toward escape velocity, thereby forming a plume escape channel. However, the distribution morphology of EM itself has received limited attention in previous research. In this study, by taking advantage of the multi-fluid Hall-MHD model cooperating with the Martian crustal field model, we focus on elucidating the physical mechanisms underlying the asymmetrical distribution of EM and examining the influence of the crustal field on this asymmetry. The results obtained from the simulation conducted in the absence of the crustal field indicate that the EM is more intense within the −ZMSE magnetosheath, where EM is directed toward Mars, primarily due to its corresponding higher velocity and a stronger magnetic field at lower solar zenith angles. The Martian crustal field has the ability to enhance the local EM around the inner boundary of the magnetosheath by amplifying both the magnetic field and its associated velocity. Accordingly, these findings provide valuable insights into the asymmetric nature of EM within the Martian magnetosheath under typical quiet-time solar wind conditions.

Abstract Lung cancer is the leading cause of cancer-related deaths worldwide. Long non-coding RNAs (lncRNAs) have emerged as key regulators of cancer development and progression, and as promising biomarkers for the diagnosis and prognosis of cancer. In this study, we identified a new lncRNA (LINC02159) that was upregulated in the tumor tissues and serum of non-small cell lung cancer (NSCLC) patients. We demonstrated that knockdown of LINC02159 inhibited NSCLC cell proliferation, migration, and invasion, but induced cell apoptosis and cell cycle arrest in vitro and retarded tumor growth in vivo, while overexpression of LINC02159 led to the opposite effect. We discovered that LINC02159 was highly correlated with cancer growth and metastasis-related pathways by using transcriptomic analysis and that YAP1 was a potential target gene of LINC02159. Mechanistically, LINC02159 bound to the Aly/REF export factor (ALYREF) to enhance the stability of YAP1 messenger RNA (mRNA) via m5C modification, which led to the overexpression of YAP1 and the activation of the Hippo and β-catenin signaling pathways in NSCLC cells. Rescue experiments showed that LINC01259 promoted NSCLC progression in a YAP1- and ALYREF-dependent manner. In conclusion, LINC02159 plays an oncogenic role in NSCLC progression by regulating ALYREF/YAP1 signaling, and it has the potential to be utilized as a diagnostic marker and therapeutic target for NSCLC.

Abstract Background Spalt-like protein 4 (SALL4) is a stemness-related transcription factor whose abnormal re-expression contributes to cancer initiation and progression. However, the role of SALL4 in cancer angiogenesis remains unknown. Methods Analyses of clinical specimens via TCGA datasets were performed to determine the expression level and clinical significance of SALL4 in STAD (Stomach Adenocarcinoma). SALL4 knockdown, knockout, and overexpression were achieved by siRNA, CRISPR/Cas9, and plasmid transfection. The effects of conditioned medium (CM) from SALL4 knockdown or overexpression of gastric cancer cells on endothelial cell proliferation, migration, and tube formation were investigated by CCK-8 assay, transwell migration assay, and tube formation assay. The regulation of VEGF gene expression by SALL4 was studied by qRT-PCR, western blot, chromatin immunoprecipitation (ChIP) assay, and electrophoretic mobility shift assay (EMSA). Engineered exosomes from 293T cells loaded with si-SALL4-B and thalidomide were produced to test their therapeutic effect on gastric cancer progression. Results SALL4 expression was increased in STAD and positively correlated with tumor progression and poor prognosis. SALL4-B knockdown or knockout decreased while over-expression increased the promotion of human umbilical vein endothelial cells (HUVEC) cell proliferation, migration, and tube formation by gastric cancer cell-derived CM. Further investigation revealed a widespread association of SALL4 with angiogenic gene transcription through the TCGA datasets. Additionally, SALL4-B knockdown reduced, while over-expression enhanced the expression levels of VEGF-A, B, and C genes. The results of ChIP and EMSA assays indicated that SALL4 could directly bind to the promoters of VEGF-A, B, and C genes and activate their transcription, which may be associated with increased histone H3-K79 and H3-K4 modifications in their promoter regions. Furthermore, si-SALL4-B and thalidomide-loaded exosomes could be efficiently uptaken by gastric cancer cells and significantly reduced SALL4-B and Vascular Endothelial Growth Factor (VEGF) expression levels in gastric cancer cells, thus inhibiting the pro-angiogenic role of their derived CM. Conclusion These findings suggest that SALL4 plays an important role in angiogenesis by transcriptionally regulating VEGF expression. Co-delivery of the functional siRNA and anticancer drug via exosomes represents a useful approach to inhibiting cancer angiogenesis by targeting SALL4/VEGF pathway.

Abstract Atrial fibrillation (AF) is a frequent arrhythmia associated with cardiovascular morbidity and mortality. Neutrophil extracellular traps (NETs) are DNA fragments with cytoplasm proteins released from neutrophils, which are involved in various cardiovascular diseases. To elucidate the role of NETs in AF, we investigated the effect of NETs on AF progression and the secretion of NETs in AF. Results showed that: NETs induced the autophagic apoptosis of cardiomyocytes, and NETs also led to mitochondrial injury by promoting mitochondrial depolarization and ROS production. Ongoing tachy-pacing led to the structural loss of cardiomyocytes and provided potent stimuli to induce NETs secretion from neutrophils. In the meanwhile, increased Ang II in AF facilitated NETs formation through the upregulation of AKT phosphorylation, while it could not directly initiate NETosis as the autophagy was not induced. In vivo, DNase I was administrated to abrogate NETs formation, and AF-related fibrosis was ameliorated as expected. Correspondingly, the duration of the induced AF was reduced. Our study addresses the formation mechanism of NETs in AF and demonstrates the lethal effects of NETs on cardiomyocytes through the induction of mitochondrial injury and autophagic cell death, which comprehensively describes the positive feedback comprised of NETs and stimuli secreted by cardiomyocytes that sustains the progression of AF and AF related fibrosis.

Abstract Forest expansion has been observed in China over the past decades, but the typically applied coarse resolution satellite data does not reveal spatial details about China’s forest transition. By using three decades of satellite observations at a 30-m spatial resolution, we reveal here the complex spatiotemporal patterns of individual forest stands forming the forest return history of southern China. We calculate forest age, forest densification rates, and annual forest fragmentation and show that the observed forest area surge around 2010 is a result of trees planted after 2000 that formed dense forests about a decade later. We document that old forests in the 1980s were mostly fragmented into scattered patches located on mountain tops, but forests rapidly expanded downhill by 729,540 km2 and alleviated the clear-cut and logging pressure from old forests. Our study provides a detailed documentation of forest densification and expansion for a country that had been largely deforested three decades ago.

As an important part of the inner magnetosphere, the Earth's plasmasphere plays a vital role in linking the occurrence and development of space weather processes. The Earth's plasmasphere is a torus-shaped cold (< 10 eV) and dense (10~104 cm−3) plasma region of ionospheric origin co-rotating with the planet. The plasmasphere contains several populations of particles such as electrons, H+, He+, and O+ ions. The outer boundary of the plasmasphere is defined by a sharp gradient of density called the plasmapause, in which the density decreases by 1~ 2 orders of magnitude within 0.5 RE (the Earth radius). Additionally, large scale plasmaspheric features have been observed, including shoulders, plumes, notches, bulges, and refiling. The Earth's plasmasphere is dynamic, and the abundance of particles in it changes substantially with interplanetary and geomagnetic activity. The large-scale structure evolution of the plasmasphere during geomagnetic storms controls the generation and propagation of waves in the plasmasphere, thus affecting the wave-particles interaction, resulting in a change in the spatial distribution of electrons and ions in the plasmasphere, and then affecting other magnetospheric and ionospheric processes. During periods of geomagnetic storms, the plasmaspheric material eroded is transported sunward and observed near the dayside magnetopause regularly. This local plasmaspheric density enhancement greatly impacts global large-scale convection. Therefore, the plasmaspheric density is undoubtedly an important parameter in space weather. The structural dynamic change of the Earth's plasmasphere is an indicator of the disturbance state of the space weather environment. Its structural form and dynamic process are controlled by the geomagnetic activity, and the short-term changes in the geomagnetic field originate from the sun-terrestrial disturbance caused by solar activity. The high-speed plasma ejected from the solar corona impacts the Earth and induces large-scale convective motion in the magnetosphere. Part of the energy enters the magnetosphere, causing disturbances in its inner regions, including the plasmasphere. Further research on the Earth’s plasmasphere is of great significance to reveal the mass transport and energy transfer in the solar wind-magnetosphere-ionosphere coupling process, and space weather forecast. Here, we introduce the research progress in the response of the plasmasphere to geomagnetic activities, the waves in the plasmasphere, variation of the electron content in the topside ionosphere and plasmasphere, and plasmasphere models. Finally, we also list some important issues for future studies.

China has experienced a rapid urbanization during recent decades, strongly affecting vegetation dynamics in areas undergoing a transformation from rural to urban areas. At the same time, national greening policies have been implemented to promote urban sustainability and urban greening in China in recent years. However, it is unclear how urban greening compensates vegetation losses from urban expansion at national scale. Here, we use Moderate Resolution Imaging Spectroradiometer and Landsat satellite normalized difference vegetation index time series to study 974 major cities (urban area > 20 km2) in China during 2000 to 2020 and develop an urban vegetation change typology including 5 types of vegetation dynamics (greening, browning, stable, reversal, and recovery). We document a rapid urban expansion associated with a browning in urban areas before 2011, followed by widespread regreening of the urban areas after 2011. This recovery in greenness was found in 63.45% of the cities, while 14.68% showed a continuous browning, and 8.13% a continuous greening. Our findings reveal to what extent, where, and when vegetation browning from urban expansion is balanced by urban greening in urban core areas, which may indicate that initial vegetation losses are offset by urban greening initiatives.

Abstract The Multiband Ultraviolet Spectrum Imager (MUSI) is an optical remote sensing instrument scheduled to launch on the Fengyun‐4C meteorological satellite in 2024. MUSI is designed to measure the airglow emissions between ∼120 and 160 nm above the East Asia and Pacific region from a geostationary orbit to infer ionospheric parameters. Here we develop a lookup‐table algorithm for retrieving the peak electron density (nmF2) and the Total Electron Content (TEC) from nighttime observations of the OI 135.6 nm emission. The algorithm takes into account the north‐south asymmetry of the equatorial ionization anomaly and the atmospheric variations with solar activity and local time. Analysis of synthetic observations shows that the assumptions made in the algorithm only lead to ∼2%–4% uncertainties in the retrievals under the modeled ionospheric conditions. The algorithm is verified by retrieving nmF2 and TEC from the Global‐Scale Observations of the Limb and Disk (GOLD) mission and comparing with coincided radio measurements. The comparison indicates almost negligible systematic differences (typically less than ∼3%) between the GOLD and the ionosonde nmF2, which are within the error limit of the GOLD retrievals. The accuracy of the GOLD TEC retrievals is shown to be comparable to (or in some sense even better than) that of the measurements from the Global Navigation Satellite System. Several simplified yet robust retrieval methods are also developed, which can be readily implemented for both existing and upcoming missions. Our results promote far ultraviolet (FUV) remote sensing to be a key technology for accurate determination of the ionospheric state.

Objective: Recently, liquid platelet-rich fibrin (PRF), a rich source of concentrated platelets and growth factors, has emerged as a promising agent for stimulating tissue regeneration. However, its specific efficacy in chondrocyte proliferation and cartilage regeneration remains underexplored. To address this question, we investigated liquid PRF obtained through horizontal centrifugation and compared its effects with hyaluronic acid (HA), a high molecular weight glucosamine supplement widely used in clinical practice to safeguard against chondral damage.Materials and Methods: Liquid PRF, produced using horizontal centrifugation (liquid H-PRF) at 500 g for 8 min, served as our experimental agent. We conducted cell viability and proliferation assays using PRF-conditioned medium. We assessed the chondrocyte phenotype of ATDC5 cells through toluidine blue and alcian blue staining, real-time polymerase chain reaction (RT-PCR), Western blotting, and immunofluorescence staining. Furthermore, we examined the expression of genes involved in inflammation through RT-PCR and Western blot analysis.Results: Liquid H-PRF exerted notable effects on chondrocytes, influencing proliferation, inflammatory responses, and chondrogenic differentiation. The H-PRF group displayed significantly higher expression of chondrogenic markers, including Col2a1, compared to HA-treated cells, whereas aggrecan expression was significantly higher in the HA group. PRF also demonstrated the ability to reduce inflammatory levels in chondrogenic ATDC5 cells, and this effect was further enhanced when PRF from the buffy coat zone was added. In comparison, chondrocytes cultured in the HA group produced significantly fewer inflammatory factors than those in the PRF group, as confirmed qualitatively by Western blot analysis.Conclusion: Liquid H-PRF emerged as a potent stimulator for chondrogenesis and a regulator of the inflammatory response, achieving levels similar to HA. Moreover, liquid H-PRF exhibited strong potential for enhancing the production of cartilage extracellular matrix and promoting chondrogenic regeneration with notably increased Col2a1 levels. Future research should encompass animal studies and human trials to further evaluate the comparative effectiveness of liquid PRF versus HA, potentially as an alternative or complementary strategy for future clinical applications.

The dune aurora, at a scale of ~30 kilometers, was reported recently using ground camera. The small-scale dune aurora occurs on the duskside and exhibits a monochromatic oscillation in the auroral emission, implying fundamental energy conversions. However, whether the dune auroras correspond to atmospheric waves or are associated with magnetospheric dynamics should be determined. This paper reports a dune aurora that occurred during a storm; further, we demonstrate that it was the substructure of the sawtooth aurora that was generated by plasmapause surface waves. Conjugate observations in the magnetospheric source region suggest that the exohiss waves, which are periodically modulated by the plasmapause surface wave-excited ultralow frequency wave, might be responsible for the generation of the dune aurora. Most reported dune aurora events have occurred simultaneously with sawtooth auroras, suggesting that both are plasmapause-driven cross-scale auroral structures.

Structural bolted connections of steel plates must fulfill the requirements specified by the standard EN 1090-2:2018 in the European Union. For the slip-resistant joints, the standard establishes the experimental procedure to obtain the delayed slip under a constant loading, which should not exceed 2 μm from the first five minutes to three hours. However, the usual extensometers available in laboratories, like LVDTs, lack the necessary precision to obtain a reliable measurement of such a small displacement because, even if their resolution is 1 μm, the scatter of repeated measurements of the same distance is normally higher. In contrast, the resolution and precision in optical methods like Digital Image Correlation (DIC) can be easily set under 1 μm depending on the number of pixels covering the studied area and the performed subpixel interpolation. This work introduces the use of DIC for delayed slip tests. In comparison with an LVDT, it is verified that this technique is a valid alternative to measure displacements at that scale with a simpler experimental setup.

Abstract Oxide scales play a pivotal role in obstructing surface chemical and electrochemical reactions, hence hindering chemo‐mechanical effects such as liquid metal embrittlement of steels. Therefore, the critical conditions and failure mechanism of the oxide film are of major interest in the safe service of steels. Though in situ microscopic methods may directly visualize the failure mechanism, they are often challenged by the lack of statistically reliable evaluation of the critical conditions. Here, by combining in situ scanning electron microscopy with a tapered specimen tensile test in a single experiment, we uniquely achieve a mechanistic study with statistically reliable quantification of the critical strains for each step of the dynamic process of film rupture. This is demonstrated with the oxide films formed on a ferrite–martensite steel in liquid lead–bismuth eutectic alloy at elevated temperatures, with in situ results falling right into the predictions of the statistical analysis. Explicitly, the integrated experimental methodology may facilitate the materials genome engineering of steels with superior service performance.

Abstract Small extracellular vesicles (sEVs) play a key role in exchanging cargoes between cells in tumour microenvironment. This study aimed to elucidate the functions and mechanisms of hepatocellular carcinoma (HCC) derived sEV‐clathrin light chain A (CLTA) in remodelling microvascular niche. CLTA level in the circulating sEVs of HCC patients was analysed by enzyme‐linked immunosorbent assay (ELISA). The functions of sEV‐CLTA in affecting HCC cancerous properties were examined by multiple functional assays. Mass spectrometry was used to identify downstream effectors of sEV‐CLTA in human umbilical vein endothelial cells (HUVECs). Tube formation, sprouting, trans‐endothelial invasion and vascular leakiness assays were performed to determine the functions of sEV‐CLTA and its effector, basigin (BSG) in HUVECs. BSG inhibitor, SP‐8356, was tested in a mouse model of patient‐derived xenografts (PDXs). Circulating sEVs of HCC patients had markedly enhanced CLTA levels than control individuals and were reduced in patients after surgery. HCC derived sEV‐CLTA enhanced HCC cancerous properties, disrupted endothelial integrity and induced angiogenesis. Mechanistically, CLTA remodels microvascular niche by stabilizing and upregulating BSG. Last, SP‐8356 alone or in combination with sorafenib attenuated PDXs growth. The study reveals the role of HCC derived sEV‐CLTA in microvascular niche formation. Inhibition of CLTA and its mediated pathway may illuminate a new therapeutic strategy for HCC patients.

Single-port laparoscopic appendectomy (SPLA) has become a good alternative to the traditional surgical treatment of acute appendicitis, due to its advantages of small incision, mild postoperative pain, short hospital stay, and good cosmetic effect. However, the further application of SPLA has been restricted by its relatively long operating time, high level of operating difficulty, and increased equipment and technical requirements. Clinical teams worldwide have attempted to improve and optimize SPLA technical protocols and equipment to maintain stable intraoperative pneumoperitoneal pressure, improve the ‘triangle relationship’ of operating angles, and develop new surgical procedures with less trauma and higher cost-effectiveness. Here, new SPLA techniques reported over the past decade are reviewed and compared, with the aim of providing new insights into technical improvements, equipment upgrades and clinical studies in the coming years.

During geomagnetic storms, which are the primary periods for heavy ions from the solar wind to enter Earth’s magnetospheric space, the charge state of solar wind heavy ions during these storms has significant implications for studying the distribution and effects of heavy ions in the magnetosphere. We analyzed the states and variations of heavy ions during 158 interplanetary coronal mass ejection (ICME)–driven geomagnetic storm events using data from the Advanced Composition Explorer satellite and examined four of these events in detail. We found that the increase in the average charge state of heavy ions such as O, Mg, Si, and Fe is positively correlated with the intensity of the geomagnetic storm. Regarding the abundance ratio of heavy ions such as Ne, Mg, Si, and Fe relative to oxygen ions, the rate and magnitude of increase in abundance ratios during extreme geomagnetic storms ( Kp = 9) triggered by ICME events are significantly higher than those during other levels of geomagnetic storms. Additionally, we observed that although the average charge states of heavy ions such as O and Fe are correlated with the geomagnetic storm intensity induced by ICMEs, there are significant individual differences in the charge state variations of heavy ions.

In the solar wind, the fluctuation of heavy ion abundance serves as a crucial physical metric. This not only mirrors the attributes of the solar wind’s originating solar region but also signifies its influence on Earth’s magnetosphere. Utilizing data from the Advanced Composition Explorer satellite, this investigation scrutinizes heavy ion variations in stream interaction region (SIR)- and interplanetary coronal mass ejection (ICME)-driven shocks. We further delineate the disparities in heavy ion fluctuations between these two types of interplanetary shocks across diverse solar activity cycles. Our findings reveal that ICME-driven shocks typically manifest elevated shock velocities and magnetic field strengths relative to their SIR-driven counterparts. Additionally, heavy ion abundance ratios, such as C ^6+ /O ^4+ , O ^7+ /O ^6+ , He/O, Si/O, and Fe/O, are consistently higher in ICME-driven shocks than in SIR-driven shocks. During varying solar activity cycles, these ratios surge postarrival of ICME-driven shocks. At solar maximum, these elevated ratios persist, whereas they revert to baseline levels swiftly during solar minimum. For SIR-driven shocks, the alteration in heavy ion abundance ratios is comparatively subdued, yet a noteworthy correlation with the solar activity cycle is evident.

The FY-4B satellite is one of the second generation of China’s geosynchronous meteorological satellites aiming at numerical weather forecasts. The space environment monitoring package (SEMP) onboard the FY-4B is a comprehensive instrument package for plasma, high-energy particle, and energetic neutral particle measurements. The low-energy particle analyzer (LEPA) is one of the instruments of the SEMP and consists of two top hat electrostatic analyzers designed for plasma detection. The electron and ion sensors are back-to-back assembled and are integrated to a shared electronic box. It measures the three-dimensional velocity distribution of low-energy electrons and ions on the geosynchronous orbit. In this paper, we present the ground calibration and in-flight performance of the instrument. With the electrostatic deflectors and the cylindrically symmetric structure, the instrument provides high-cadence measurements of electron and ion velocity distributions with a wide field of view (FOV) of 180° by 100°, an angular resolution of 16.7° × 20°, and a broad energy range for both the electrons and ions from tens of eV to above 30 keV, with a 1 s time resolution. The geometric factors of the electron and ion analyzers are 1.1 × 10−3 cm2·sr·eV/eV and 1.4 × 10−3 cm2·sr·eV/eV, respectively, which fulfills the requirements of the low-energy plasma measurement. The LEPA monitored typical space environment disturbance such as geomagnetic storms and successfully recorded the responses of plasma energy fluxes. Satellite surface charging events were measured, with the highest potentials of −2000 V in the shadow period and −500 V in the nonshadow period.

Worst pattern of invasion (WPOI) is a parameter used to quantify tumor invasiveness of oral squamous cell carcinoma (OSCC). Here the authors show that a fibroblast subset characterized by the expression of the oxytocin receptor is enriched in highly invasive WPOI 4-5 OSCC tumors and can be targeted to reduce the desmoplastic stroma and tumor metastasis.

A developed tungsten (W) grade was prepared by powder metallurgy technology plus multi-step low-temperature rolling. The relative density, thermal conductivity, microstructure, tensile properties of original and high-temperature annealed states, micro-hardness and transient thermal shock resistance were characterized. The results of tensile test with a strain rate of 2 × 10-4 s−1 show that the ductile–brittle transition temperature (DBTT) of rolled-W in the original and recrystallized state are 150–200 °C and 250–300 °C, respectively. The rolled-W presents high strength and great plasticity simultaneously. For example, the maximum ultimate tensile strength (UTS) below DBTT is as high as ∼ 1189 MPa, and the maximum total elongation (TE) above DBTT reaches 28.9 %. In particular, the TE of recrystallized W achieves an incredible 81.4 % at 500 °C, which is the highest value among all the published literatures so far. The results of transient thermal shock tests indicate that the rolled-W has an outstanding transient thermal shock resistance. It can withstand the thermal bombardment at an absorbed power densities (APD) of 0.33 GW·m−2 without causing any surface damages, and still no cracks are observed as the APD rises to 0.88 GW·m−2. Moreover, the failure mechanism of rolled-W was also studied in details. This work plays an important role in establishing a dependable China Fusion Engineering Test Reactor (CFETR) data-library on a unitary W grade, which can provide an effective reference for the identification of material performance under the high heat flux and subsequent numerical simulation.

Alveolar bone defects caused by tooth loss often lead to challenges in implant dentistry, with a need for development of optimal bone biomaterials to predictably rebuild these tissues. To address this problem, we fabricated a novel bone block using platelet-rich fibrin (PRF) and Deproteinized Bovine Bone Mineral (DBBM), and characterized their mechanical and biological properties. The bone block was prepared by mixing DBBM, Liquid-PRF, and Solid-PRF fragments in various combinations as follows: (1) BLOCK-1 made with Solid-PRF fragments + DBBM, (2) BLOCK-2 made with Liquid-PRF + DBBM, (3) BLOCK-3 made with Solid-PRF fragments + Liquid-PRF + DBBM. The time for solidification and the degradation properties were subsequently recorded. Scanning electron microscopy (SEM) and tensile tests were carried out to investigate the microstructure and mechanical properties of each block. The bioactivity of the three groups towards osteoblast differentiation was also evaluated by culturing cells with the conditioned medium from each of the three groups including cell proliferation assay, cell migration assay, alkaline phosphatase (ALP) staining, and alizarin red staining (ARS), as well as by real-time PCR for genes encoding runt-related transcription factor 2 (RUNX2), ALP, collagen type I alpha1(COL1A1) and osteocalcin (OCN). BLOCK-3 made with Solid-PRF fragments + Liquid-PRF + DBBM had by far the fastest solidification period (over a 10-fold increase) as well as the most resistance to degradation. SEM and tensile tests also revealed that the mechanical properties of BLOCK-3 were superior in strength when compared to all other groups and further induced the highest osteoblast migration and osteogenic differentiation confirmed by ALP, ARS and real-time PCR. PRF bone blocks made through the combination of Solid-PRF fragments + Liquid-PRF + DBBM had the greatest mechanical and biological properties when compared to either used alone. Future clinical studies are warranted to further support the clinical application of PRF bone blocks in bone regeneration procedures.

BackgroundPreterm birth-related complications are the leading cause of death in newborns and children under the age of 5 years. Maternal heat exposure has been associated with both sleep status during pregnancy and the increased risk of preterm birth. However, whether sleep status could mediate the association between heat exposure and preterm birth remains unclear.ObjectiveTo evaluate the association between maternal heat exposure in early pregnancy and preterm birth, and to further explore potential mediation effect of sleep status on the association between heat exposure and preterm birth.MethodsA birth cohort was established in Guangzhou Panyu Maternal Child Health Hospital (Guangzhou Panyu District He Xian Memorial Hospital) from 2017 until now. Pregnant women (with gestational age between 8 and 13 weeks) were included in this study when they presented to the hospital for their first prenatal care visit and signed an informed consent. Then they were followed up until delivery. A total of 3 268 pregnant women were included for the final analysis. Questionnaires were distributed to collect the demographic characteristics, lifestyles, and sleep status of pregnant women. Daily meteorological data during the study period were collected from meteorological monitoring stations in Guangzhou and the average ambient mean temperature of four weeks before the survey was calculated and assigned for each pregnancy. The 75th, 80th, 85th, 90th, and 95th percentiles (P75, P80, P85, P90, and P95) of the average ambient temperature of all pregnant women were used as the thresholds to define heat exposure. Logistic regression was used to evaluate the effects of heat exposure in different definitions on preterm birth and sleep status (sleep duration, night sleep timing, and wake up timing). The mediation effects of sleep status on the relationship between heat exposure and preterm birth were also analyzed.ResultsAmong all the included participants, 165 newborns were preterm births with an incidence rate of 5.0%. Heat exposures with thresholds of P90 and P95 increased the risk of preterm birth, with ORs (95%CIs) of 1.66 (1.04-2.57) and 1.90 (1.03-3.33), respectively (P

The plasma analyzer (PMA) on the Fengyun-3E (FY-3E) meteorological satellite series is a critical sensor of the space environment monitoring package that is capable of the comprehensive in situ detection of the thermal plasma environment and surface discharge effects. In this paper, we conducted a thorough evaluation of the PMA’s performance and reliability through a combination of ground-based laboratory calibration and in-orbit testing. During the ground-based calibration, the PMA underwent assessments for the energy range, field of view (FOV), and measurement accuracy, and obtained the detection accuracy and the geometric factors. During the in-orbit testing, the PMA successfully obtained the typical distribution characteristics of low-energy ions and electrons in orbital space regions, as well as the precipitating particles in the middle and high latitudes of both hemispheres. Notably, the PMA observed an expansion of the particle distribution in the high-latitude regions during a moderate geomagnetic storm. The results from both the ground-based calibration and in-orbit testing demonstrated that the PMA met the requirements for thermal plasma detection, with reliable and scientifically valid in-orbit detection data. These results provide a crucial foundation for studying spatial weather variations, improving the accuracy of space environment forecasts and enhancing disaster detection and monitoring capabilities.

This study assessed an innovative temporary edge protection system (TEPS) designed and developed to improve the ergonomics, health and safety at trench works in the construction industry, which ranks as one of the most hazardous worldwide. A wooden prototype of this innovative TEPS was built, and its mechanical resistance was compared to a conventional one. Thereafter, field tests were carried out to evaluate the efficacy of this pioneering TEPS. Both in analytical studies and field tests, the mechanical resistance to static loads of the TEPS complied with EU standards, and outperformed the conventional TEPS. The novel TEPS is effective as fall protection for different trench shoring systems and in buildings without edge protection systems. Moreover, this novel lightweight TEPS is easy to transport, with simple and safe on-site installation.

Accurate measurements of the oxygen concentration in liquid lead-bismuth eutectic (LBE) alloys are essential for ensuring optimum cooling conditions in heavy liquid metal coolant fast reactors. However, while unavoidable variations in the Bi contents of these alloys can affect the accuracy of these measurements, this issue has not yet been rigorously evaluated. The present work addresses this issue by evaluating variations in oxygen concentration measurements obtained experimentally for oxygen-saturated liquid LBE alloys with different Bi contents at different temperatures using a solid electrolyte oxygen sensor. Theoretical relationships are established between sensor voltage, oxygen concentration, temperature, and Bi content under the applied experimental conditions, and excellent agreement is obtained between the experimental and theoretical results. The theoretical relationships establish that the voltage decreases by about 1 mV for every 1 wt% increase in Bi content at a temperature of 400 °C. At a fixed voltage, with the increase of T, the influence of the Bi content on the CO calculation results gradually increased. Finally, the impact of varying Bi contents on the accuracy of oxygen concentration measurements is evaluated under practical reactor operation conditions, and higher requirements for the control of dissolved oxygen in LBE-cooled fast reactors are proposed.

Abstract Hypoxic microenvironment is common in solid tumors, particularly in pancreatic ductal adenocarcinoma (PDAC). The Warburg effect is known to facilitate cancer aggressiveness and has long been linked to hypoxia, yet the underlying mechanism remains largely unknown. In this study, we identify that lysyl oxidase-like 2 (LOXL2) is a hypoxia-responsive gene and is essential for the Warburg effect in PDAC. LOXL2 stabilizes hypoxia-inducible factor 1α (HIF1α) from prolyl hydroxylase (PHD)-dependent hydroxylation via hydrogen peroxide generation, thereby facilitating the transcription of multiple glycolytic genes. Therefore, a positive feedback loop exists between LOXL2 and HIF1α that facilitates glycolytic metabolism under hypoxia. Moreover, LOXL2 couples the Warburg effect to tumor growth and metastasis in PDAC. Hijacking glycolysis largely compromises LOXL2-induced oncogenic activities. Collectively, our results identify a hitherto unknown hypoxia-LOXL2-HIF1α axis in regulating the Warburg effect and provide an intriguing drug target for PDAC therapy.

Abstract Objective To compare three commonly used low-molecular-weight heparins (LWMHs) in the treatment of recurrent spontaneous abortion (RSA) by evaluating the anti-Xa peak levels and adverse reactions. Methods In this single-center, observational study, we enrolled 310 patients with RSA in whom anti-Xa levels were measured during pregnancy. Patients were divided into three groups according to the LMWH they used: the nadroparin group, enoxaparin group and dalteparin group. We compared the peak anti-Xa levels and the coagulation status of each group, and analyzed the incidence of adverse reactions, including local allergy, liver and renal dysfunction, and the impact on platelet. Results Patients in the enoxaparin group had a higher anti-Xa peak level than those in the nadroparin group (0.80 ± 0.22 IU/ml vs. 0.61 ± 0.24 IU/ml; P

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor in the oral and maxillofacial regions, with a high rate of metastasis. Cancer-associated fibroblasts (CAFs) play critical roles in tumor growth, metastasis and invasion, making them attractive therapeutic targets for cancer treatment. As an old anti-coccidiosis drug for poultry, Halofuginone (HF) has also been reported to possess anti-fibrosis and anti-cancer activities in the recent decades. However, whether it works by targeting CAFs in OSCC, and the mechanisms involved remain unclear. In the present study, we observed HF dose-dependently inhibits OSCC-derived CAF viability and proliferation. Meanwhile, HF decreased the expressions of α-SMA, FSP-1 and PDGFRβ, markers of the malignant phenotype of CAFs, both at mRNA and protein levels. Furthermore, functional studies demonstrated that HF dramatically attenuates the promotion effect of CAFs on OSCC cell migration and invasion. Mechanistically, the inhibition of MMP2 secretion and the upstream TGF-β/Smad2/3 signaling pathway played an important role in these processes. In the orthotopic transplanted tongue carcinoma in mice model, we confirmed that HF administration inhibited tumor growth and lymph node metastasis (LNM) with reduced CAF population, MMP2 expression and collagen deposition in tumor. Altogether, these results indicate that HF can inhibit the migration and invasion of OSCC by targeting CAFs, which will provide new ideas for the treatment of OSCC.

Endothelial cells are highly sensitive to hemodynamic shear stresses, which act in the blood flow’s direction on the blood vessel’s luminal surface. Thus, endothelial cells on that surface are exposed to various physiological and pathological stimuli, such as disturbed flow-induced shear stress, which may exert effects on adaptive vascular diameter or structural wall remodeling. Here we showed that plasma thioredoxin-interactive protein (TXNIP) and malondialdehyde levels were significantly increased in patients with slow coronary flow. In addition, human endothelial cells exposed to disturbed flow exhibited increased levels of TXNIP in vitro. On the other hand, deletion of human endothelial TXNIP increased capillary formation, nitric oxide production and mitochondrial function, as well as lessened oxidative stress response and endothelial cell inflammation. Additional beneficial impacts from TXNIP deletion were also seen in a glucose utilization study, as reflected by augmented glucose uptake, lactate secretion and extracellular acidification rate. Taken together, our results suggested that TXNIP is a key component involved in mediating shear stress-induced inflammation, energy homeostasis, and glucose utilization, and that TXNIP may serve as a potentially novel endothelial dysfunction regulator.