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Abstract Osteosarcoma (OS) derived small extracellular vesicles (OS-sEVs) have been shown to induce the formation of cancer-associated fibroblasts (CAFs), characterized by elevated pro-inflammatory factor expression and enhanced migratory and contractile abilities. These CAFs play a crucial role in priming lung metastasis by orchestrating the pre-metastatic niche (PMN) in the lung. Disrupting the communication between OS-sEVs and lung fibroblasts (LFs) emerges as a potent strategy to hinder OS pulmonary metastasis. Our previously established saponin-mediated cargo-elimination strategy effectively reduces the cancer-promoting ability of tumor-derived small extracellular vesicles (TsEVs) while preserving their inherent targeting capability. In this study, we observed that cargo-eliminated OS-sEVs (CE-sEVs) display minimal pro-tumoral and LFs activation potential, yet retain their ability to target LFs. The uptake of OS-sEVs by LFs can be concentration-dependently suppressed by CE-sEVs, preventing the conversion of LFs into CAFs and thus inhibiting PMN formation and pulmonary metastasis of OS. In summary, this study proposes a potential strategy to prevent LFs activation, PMN formation in the lung, and OS pulmonary metastasis through competitive inhibition of OS-sEVs’ function by CE-sEVs.

Red Culture is one of the symbols of Chinese national spirit in China. With the enhancement of China's international status, the world gets to know the Red Culture stage by stage. And yet, in the process of Red Culture's foreign publicity, the depth and breadth of cultural diffusion have been affected by different factors. This paper objectively analyzes the current situation of foreign publicity translation about Red Culture and then focuses on the Red tourism industry to explore the characteristics and advantages of foreign-oriented publicity translation under the intercultural communicative perspective. In the end, we are trying to come up with some methods to increase the accuracy of Red Culture publicity translation.

Manganese (Mn) is an essential cofactor for lignin-degrading enzymes and crucial for nutrient cycling and ecosystem functions. During litter decomposition, Mn may accumulate to fulfill the microbial demand for degrading recalcitrant substances such as lignin, which is reflected in the relative increase in Mn in decomposing litter compared with its initial amount. However, a global-scale quantification of the patterns and factors influencing Mn behavior at different decomposition stages has not been conducted. Thus, we systematically synthesized 1,466 observations from 53 publications to assess the global patterns and influencing factors of Mn accumulation in litter across various stages of decomposition. Our findings are as follows: (1) Mn primarily accumulated during litter decomposition on a global scale, despite some variability among stages. Notably, Mn accumulation was lower in the early decomposition stage (

Most patients diagnosed with pancreatic cancer are initially at an advanced stage, and radiotherapy resistance impact the effectiveness of treatment. This study aims to investigate the effects of endocrine disruptor Di-(2-ethylhexyl) phthalate (DEHP) on various biological behaviors and the radiotherapy sensitivity of pancreatic cancer cells, as well as its potential mechanisms. Our findings indicate that exposure to DEHP promotes the proliferation of various cancer cells, including those from the lung, breast, pancreas, and liver, in a time- and concentration-dependent manner. Furthermore, DEHP exposure could influence several biological behaviors of pancreatic cancer cells in vivo and vitro. These effects include reducing cell apoptosis, causing G0/G1 phase arrest, increasing migration capacity, enhancing tumorigenicity, elevating the proportion of cancer stem cells (CSCs), and upregulating expression levels of CSCs markers such as CD133 and BMI1. DEHP exposure can also increase radiation resistance, which can be reversed by downregulating BMI1 expression. In summary our research suggests that DEHP exposure can lead to pancreatic cancer progression and radiotherapy resistance, and the mechanism may be related to the upregulation of BMI1 expression, which leads to the increase of CSCs properties.

Abstract Background Aberrant expressions of desmoglein 2 (Dsg2) and desmocollin 2(Dsc2), the two most widely distributed desmosomal cadherins, have been found to play various roles in cancer in a context-dependent manner. Their specific roles on breast cancer (BC) and the potential mechanisms remain unclear. Methods The expressions of Dsg2 and Dsc2 in human BC tissues and cell lines were assessed by using bioinformatics analysis, immunohistochemistry and western blotting assays. Wound-healing and Transwell assays were performed to evaluate the cells’ migration and invasion abilities. Plate colony-forming and MTT assays were used to examine the cells’ capacity of proliferation. Mechanically, Dsg2 and Dsc2 knockdown-induced malignant behaviors were elucidated using western blotting assay as well as three inhibitors including MK2206 for AKT, PD98059 for ERK, and XAV-939 for β-catenin. Results We found reduced expressions of Dsg2 and Dsc2 in human BC tissues and cell lines compared to normal counterparts. Furthermore, shRNA-mediated downregulation of Dsg2 and Dsc2 could significantly enhance cell proliferation, migration and invasion in triple-negative MDA-MB-231 and luminal MCF-7 BC cells. Mechanistically, EGFR activity was decreased but downstream AKT and ERK pathways were both activated maybe through other activated protein tyrosine kinases in shDsg2 and shDsc2 MDA-MB-231 cells since protein tyrosine kinases are key drivers of triple-negative BC survival. Additionally, AKT inhibitor treatment displayed much stronger capacity to abolish shDsg2 and shDsc2 induced progression compared to ERK inhibition, which was due to feedback activation of AKT pathway induced by ERK inhibition. In contrast, all of EGFR, AKT and ERK activities were attenuated, whereas β-catenin was accumulated in shDsg2 and shDsc2 MCF-7 cells. These results indicate that EGFR-targeted therapy is not a good choice for BC patients with low Dsg2 or Dsc2 expression. Comparatively, AKT inhibitors may be more helpful to triple-negative BC patients with low Dsg2 or Dsc2 expression, while therapies targeting β-catenin can be considered for luminal BC patients with low Dsg2 or Dsc2 expression. Conclusion Our finding demonstrate that single knockdown of Dsg2 or Dsc2 could promote proliferation, motility and invasion in triple-negative MDA-MB-231 and luminal MCF-7 cells. Nevertheless, the underlying mechanisms were cellular context-specific and distinct.

Abstract Chemotherapy is an important therapeutic approach for malignant tumors for it triggers apoptosis of cancer cells. However, chemotherapy also induces senescence of stromal cells in the tumor microenvironment to promote tumor progression. Strategies aimed at killing tumor cells while simultaneously eliminating senescent stromal cells represent an effective approach to cancer treatment. Here, we developed an engineered Src-siRNA delivery system based on small extracellular vesicles (sEVs) to simultaneously eliminate senescent stromal cells and tumor cells for cancer therapy. The DSPE-PEG-modified urokinase plasminogen activator (uPA) peptide was anchored to the membranes of induced mesenchymal stem cell-derived sEVs (uPA-sEVs), and Src siRNA was loaded into the uPA-sEVs by electroporation (uPA-sEVs-siSrc). The engineered uPA-sEVs-siSrc retained the basic sEVs properties and protected against siSrc degradation. uPA peptide modification enhanced the sEVs with the ability to simultaneously target doxorubicin-induced senescent stromal cells and tumor cells. Src silencing by uPA-sEVs-siSrc induced apoptosis of both senescent stromal cells and tumor cells. The uPA-sEVs-siSrc displayed preferential tumor accumulation and effectively inhibited tumor growth in a tumor xenograft model. Furthermore, uPA-sEVs-siSrc in combination with doxorubicin significantly reduced the senescence burden and enhanced the therapeutic efficacy of chemotherapy. Taken together, uPA-sEVs-siSrc may serve as a promising therapy to kill two birds with one stone, not only killing tumor cells to achieve remarkable antitumor effect, but also eliminating senescent cells to enhance the efficacy of chemotherapeutic agent in tumor regression. Graphical Abstract

This study investigates the influence of High-Toughness Polypropylene (HTPP) fiber content (0 %, 0.3 %, 0.6 %, 0.9 %) on the axial compressive performance of ceramsite concrete. Four sets of ceramsite concrete cube and prism specimens were prepared, and the cube compressive strength and full stress-strain curves for each set were tested. Based on the experimental results, it analyzed the variation characteristics of HTPP fibers on the stress-strain curve of ceramic concrete at different stages, studied the peak stress, peak strain, elastic modulus, toughness, and energy absorption capacity of ceramic concrete. Finally, the stress-strain curve has been fitted. The results indicate that: HTPP fibers can significantly enhance the strength and toughness of ceramic concrete, the compressive strength of the cube increased by 23.8 %, the axial compressive strength increased by 19.0 %, the residual stress increased by 143.0 %, the absolute modulus increased by 164.1 %, the toughness increased by 51.5 %, and the energy dissipation coefficient increased by 9.4 %. By fitting the experimental curve, the mathematical expression for the uniaxial compressive stress-strain curve of ceramic concrete reinforced with high tenacity polypropylene (HTPP) fibers has been proposed. The model matches well with the experimental results, which provides a theoretical basis for the structural analysis and design of this type of concrete.

BackgroundCavernous angiomas (CAs) affect 0.5% of the population, predisposing to serious neurologic sequelae from brain bleeding. A leaky gut epithelium associated with a permissive gut microbiome, was identified in patients who develop CAs, favoring lipid polysaccharide producing bacterial species. Micro-ribonucleic acids along with plasma levels of proteins reflecting angiogenesis and inflammation were also previously correlated with CA and CA with symptomatic hemorrhage.MethodsThe plasma metabolome of CA patients and CA patients with symptomatic hemorrhage was assessed using liquid-chromatography mass spectrometry. Differential metabolites were identified using partial least squares-discriminant analysis (p

Municipal solid waste incineration fly ash (IFA) can be treated by slurry carbonation and adopted as a supplementary cementitious material (SCM) to reduce the carbon emission of the cement industry. However, effects of control parameters of carbonation on the mineralogy and morphology of the treated IFA require further investigation. In this work, the control parameters were sequentially optimized, aiming at producing more chemically active vaterite during carbonation. The vaterite dominated IFA was subsequently used as an SCM and its performance was studied and compared with limestone (pure calcite). Results indicated that precipitation of vaterite was favored under lower temperature and higher water-ash ratio conditions. CO2 flow rate has relatively smaller impact on the mineralogy of the treated IFA, but a higher rate led to agglomeration of vaterite particles. Under the optimized condition, vaterite dominated IFA containing 60% vaterite and 10% calcite was obtained. For the blended cement, its early hydration was suppressed by calcium sulfite (CaSO3) in the IFA, but the additional sulfate (CaSO4) accelerated the ettringite formation. The vaterite calcium carbonate in the treated IFA stabilized ettringite and reacted with aluminate phases to form hemicarbonate, refining the pore structure. However, hemicarbonate formation was limited by availability of aluminum that was consumed to form ettringite. Compared to limestone, the vaterite dominated IFA behaved better performance as an SCM, and the Porland cement can be substituted by 20% without compromising the 3-day and 28-day compressive strength. Toxicity leaching tests indicated only Pb exceeded regulatory limits in raw IFA, while Pb leaching in mortar samples was greatly declined below 1% of the limit.

Efficient allocation of agricultural scientific and technological talents (ASTTs) is crucial for agricultural innovation and economic development. This study aims to systematically evaluate ASTTs’ allocation efficiency in provincial agricultural research institutions in China, aiding decision-making for local governments and research bodies. Utilizing data from 2009 to 2019 across 31 provinces, an output-oriented data envelopment analysis model measures ASTTs’ allocation efficiency and analyzes its trends, regional differences, and spatial characteristics. Results show: (1) Provincial ASTTs’ mean comprehensive technical efficiency (CTE) in China was 0.786, with room for improvement. (2) Enhanced CTE was driven by scale efficiency improvements, while pure technical efficiency declined, indicating a need for better management systems and technology applications. (3) Disparities in ASTTs’ allocation efficiency among provinces decreased, with higher efficiencies in the East and Central-Southern China regions. At the provincial level, areas like Jiangsu, Shandong, Henan, and Sichuan demonstrated relatively high ASTTs allocation efficiencies. (4) Spatial agglomeration of ASTTs’ allocation efficiency was localized in a few major agricultural provinces without a significant overall effect. These findings advocate for further optimization of ASTTs’ regional layout and management mechanisms in China.