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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.

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.

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.

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.

Abstract Background Patients with mantle cell lymphoma (MCL) exhibit a wide variation in clinical presentation and outcome. However, the commonly used prognostic models are outdated and inadequate to address the needs of the current multidisciplinary management of this disease. This study aims to investigate the clinical and pathological features of MCL in the immunochemotherapy era and improve the prognostic models for a more accurate prediction of patient outcomes. Methods The North American Mantle Cell Lymphoma Project is a multi-institutional collaboration of 23 institutions across North America to evaluate and refine prognosticators for front-line therapy. A total of 586 MCL cases diagnosed between 2000 and 2012 are included in this study. A comprehensive retrospective analysis was performed on the clinicopathological features, treatment approaches, and outcomes of these cases. The establishment of novel prognostic models was based on in-depth examination of baseline parameters, and subsequent validation in an independent cohort of MCL cases. Results In front-line strategies, the use of hematopoietic stem cell transplantation was the most significant parameter affecting outcomes, for both overall survival (OS, p

Expanded polystyrene concrete (EPSC) is increasingly utilized in buildings as a green building material. To investigate the effect of high-tenacity polypropylene (HTPP) fibers on the carbonation resistance (CR) of EPSC, five groups of EPSC specimens with HTPP fiber volume fractions of 0%, 0.6%, 0.9%, 1.2%, and 1.5% were prepared. Rapid carbonation tests were conducted to measure the carbonation depth (CD) and uniaxial compression strength (UCS) of the specimens at different carbonation ages (3, 7, 14, and 28 days). The CD and UCS of the specimens were calculated and analyzed. The results indicated that the HTPP fibers dramatically improved the CR of EPSC, with a decrease in the CD of up to 29.5% at 28 days. A model for predicting the CD of EPSC was developed. The model for the strength after carbonation also showed good agreement with the experimental results. Scanning electron microscopy (SEM) was used to examine the microstructure of the HTPP-reinforced EPSC, while the mechanism of HTPP fibers to enhance the CR of EPSC was elucidated. The findings of this study provide valuable insights for the application of EPSC as a structural material.

Abstract Pluripotent stem cell‐derived small extracellular vesicles (PSC‐sEVs) have demonstrated great clinical translational potential in multiple aging‐related degenerative diseases. Characterizing the PSC‐sEVs is crucial for their clinical applications. However, the specific marker pattern of PSC‐sEVs remains unknown. Here, the sEVs derived from two typical types of PSCs including induced pluripotent stem cells (iPSC‐sEVs) and embryonic stem cells (ESC‐sEVs) were analysed using proteomic analysis by liquid chromatography with tandem mass spectrometry (LC‐MS/MS), and surface marker phenotyping analysis by nanoparticle flow cytometry (NanoFCM). A group of pluripotency‐related proteins were found to be enriched in PSC‐sEVs by LC‐MS/MS and then validated by Western Blot analysis. To investigate whether these proteins were specifically expressed in PSC‐sEVs, sEVs derived from seven types of non‐PSCs (non‐PSC‐sEVs) were adopted for analysis. The results showed that PODXL, OCT4, Dnmt3a, and LIN28A were specifically enriched in PSC‐sEVs but not in non‐PSC‐sEVs. Then, commonly used surface antigens for PSC identification (SSEA4, Tra‐1‐60 and Tra‐1‐81) and PODXL were gauged at single‐particle resolution by NanoFCM for surface marker identification. The results showed that the positive rates of PODXL (>50%) and SSEA4 (>70%) in PSC‐sEVs were much higher than those in non‐PSC‐sEVs (

Intercity rail planning and construction generates improved regional accessibility and contributes to changes in the spatial organization of the region, incorporating more areas into the 'integrated corridor economy' through the increased attractiveness of new connection locations in a dynamic process involving multi-level impacts in social and economic domains. In addition, the development of areas outside the intercity rail corridor could also be altered by new intercity rail plans; these improvements, often referred to as efficiency impacts, are mainly related to accessibility benefits. Traditional assessment methods do not address the conflicts between efficiency and equity concerns. Achieving a single efficiency objective would bias intercity rail planning towards providing efficient connections between major centers of economic activity, negatively impacting spatial equity as it would lead to polarized spatial development patterns. Equity considerations are receiving increasing attention in current regional transport planning studies, in which intercity rail planning needs to maximize economic growth while maintaining an acceptable level of equity. We divided the scenarios based on different stages of intercity railway planning and construction, built the model of spatial equity and efficiency, adopted weighted average travel time, potential accessibility, and coefficient of variation as evaluation indexes, and conducted an empirical analysis of the changes in spatial equity and efficiency in the Shenzhen-Dongguan-Huizhou region under the scenarios of no intercity railway, current intercity railway, and planned intercity railway, to discuss the development of an equitable and efficient regional spatial model through intercity railway planning and construction. The findings indicate that: Firstly, the planning of intercity railways in Shenzhen-Dongguan-Huizhou region effectively promotes the overall improvement of accessibility, and the economic development potential of the areas along the routes is much higher than that of areas not located along the routes. Secondly, the core growth poles of Shenzhen-Dongguan-Huizhou region continue to be reinforced, and the planning of intercity railways significantly increases the economic radiation capacity of Shenzhen; however, the imbalance of regional development increases concurrently. Thirdly, the spatial equity layout of the Shenzhen-Dongguan-Huizhou region is characterized by a high level in the central and western areas and a low level in the two wings under the influence of the intercity railway plan, with the western coastal area of Dongguan and the northeastern part of Huizhou gaining inferior benefits. Lastly, the intercity railway plan has led to a more balanced pattern of economic linkages in the Shenzhen-Dongguan-Huizhou region, with a greater enhancement of spatial equity in areas close to Shenzhen. In general, the difference in the accessibility of the intercity railways in the Shenzhen-Dongguan-Huizhou region is significantly associated with factors related to the direct connection with the intercity railways and the location in contact with the core areas. The time-space compression effect produced by the construction of intercity railways has led to the expansion of the radiation range of the regional hinterland of the Shenzhen-Dongguan-Huizhou region, thus achieving optimal regional spatial distribution. In addition to enhancing the economic benefits of the transport network, the Shenzhen-Dongguan-Huizhou region should also take into account the equity of resource allocation and promote sustainable optimization as well as a balanced development of the spatial structure.

Venetoclax with azacitidine (ven/aza) is a lower-intensity therapeutic regimen that has been shown to improve outcomes in elderly patients with acute myeloid leukemia (AML). Measurable residual disease (MRD) using flow cytometry is a valuable tool for the prediction of relapse in AML using conventional therapies and ven/aza; however, the prognostic value for broadscale molecular MRD after ven/aza treatment is less clear. We aimed to determine the utility of retrospective assessment using multi-gene molecular MRD by droplet digital polymerase chain reaction (ddPCR). We found this approach correlates with outcomes in a cohort of patients receiving frontline ven/aza for AML. The predictive value of ddPCR MRD persisted when NPM1 mutations were removed from analysis, as well as after adjustment for the impact of stem cell transplant on outcomes. Late achievement of MRD negativity, including after SCT, was still associated with superior outcomes compared to persistently detectable MRD. We further explored the impact of ven/aza on the burden of different classes of mutations, and identified the persistence of splicing factor mutations, commonly associated with MDS, as a consistent finding after ven/aza treatment. These data add to our understanding of the effects of ven/aza on AML disease biology and provide details on molecular depth of remission that can guide prospective trials in the future.

Objective: Abdominal aortic aneurysms (AAA) involving branches of the visceral arteries mainly refer to AAA with flat renal artery (neck length ≤5 mm) or beyond the renal artery, and the branch of the visceral arteries needs to be reconstructed during treatment. Endoluminal repair (EVR) surgery refers to the isolation of AAA with less surgical trauma through vascular puncture, guidewire, catheter, stent and double suturer technology. However, postoperative endoleak is a complication specific to open surgery. This study aimed to analyze the efficacy of EVR for AAA involving visceral vessels (AAA-Vs) and the factors influencing the occurrence of postoperative endoleak. Methods: A total of 106 patients with AAA-Vs in our hospital during the period of January 2018 to January 2022 were distinguished as the observation group (received EVR, n = 48) and the control group (received laparotomy, n = 58). The operation time, intraoperative bleeding, intraoperative blood transfusion, postoperative intensive care unit (ICU) observation time, postoperative food-taking time, first time out of bed, hospital stay, complications and the one-year mortality of two groups were compared. According to the occurrence of postoperative endoleak, the patients underwent endoluminal repair surgery were graded as non-endoleak group (n = 39) and endoleak group (n = 9). The clinical data, including aneurysm anatomical conditions (proximal neck length, neck diameter, proximal neck angle), tumor shape (normal, calcification, mural thrombus), and internal iliac artery embolism of two groups were compared. Logistic regression analysis was employed to analyze the risk factors of endoleak after EVR of AAA. Results: The operation time, intraoperative blood loss, intraoperative blood transfusion, postoperative ICU observation time, postoperative food-taking time, first time out of bed and hospitalization days were sharply lower in the observation group than the control group (P 0.05). The observation group had much lower incidence of incision infection complications than the control group (P

In this paper, the effect of High-Toughness Polypropylene (HTPP) fibers admixture (0, 0.3 %, 0.6 %, 0.9 %) on the mechanical properties of ceramsite concrete was investigated, and four kinds of ceramsite concrete specimens were prepared and tested for various kinds of ceramsite concrete compressive strength, flexural strength, and stress-strain curves, and the performance characteristics obtained include the strength-to-weight ratio, flexural-to-compressive ratio, tensile-to-compressive ratio, compressive toughness index, and failure morphology. Furthermore, combined with Scanning Electron Microscope (SEM) images, we analyzed the enhancement mechanism of basic mechanical properties of ceramic concrete by HTPP fibers. The results show that HTPP fibers can effectively improve the strength and toughness performance of ceramsite concrete, and the effect on improving toughness performance is more significant; After adding HTPP fibers, the compressive strength of ceramsite concrete increased by 26.3 %, the flexural strength increased by 29.7 %, the toughness index increased by 28.9 %, and the strength to weight ratio increased by 24.1 %; After adding HTPP fibers, the brittle failure characteristics of concrete are significantly weakened, and when it fails under load, it can still maintain good integrity, without scattering or continuous cracking. Based on the SEM test results, the mechanism of HTPP fibers reinforced ceramsite concrete was explained, mainly attributed to three aspects: fibers preventing ceramsite from floating, fiber surface maintaining good bonding with cement matrix, and effective synergistic bearing between fibers and ceramsite concrete. The research findings of this study can provide a theoretical foundation for the structural analysis and design of this type of concrete. It will be beneficial for the use of ceramsite concrete as a structural material and holds significant implications for the advancement of prefabricated lightweight wall panels.

The distribution network structure is complex, the equipment is numerous, and the frequency of pattern and mode changes is high. These characteristics lead to certain difficulties in power distribution automation operation and maintenance graph management. This paper adopts the mathematical statistics method of machine learning to analyze the multi-version hierarchical subscription mechanism of the distribution network graph. We conduct a breadth search on the distribution network graph to realize the automatic topology of the network. This paper implements a dynamic display system of distribution network monitoring information. The research results show that the graph-digital-analog integrated system has practical significance for data integration, application integration, and interoperability between systems.

Based on the theory of fractional differential equations, this paper proposes a simple recursive, iterative scheme for power flow calculation in pure radial networks. The paper determines the network hierarchy formed by the ADT stack through breadth theory. This helps us define the branch sequence of the forward and backward generation in the power flow calculation of the smart distribution network. We ensure that the Jacobian matrix remains unchanged in the smart distribution grid power flow calculation. The interval model is more practical and computationally simpler than the point model. The research results show that the power flow calculation method is efficient based on the fractional differential equation.

AbstractGlobal climate change has led to more frequent and severe droughts, which can negatively affect instream invertebrate communities, but we lack a perspective on the global patterns and drivers of such drought effects. Here, using meta-analysis, we synthesized 997 paired observations extracted from 94 peer-reviewed publications to assess how drought affects the biomass, density, taxonomic richness, and diversity (Shannon–Wiener, Simpson, and Pielou indices) of instream invertebrates at a global scale. We found that (i) drought significantly decreased instream invertebrate density and taxonomic richness by an average of 4.9 and 5.0%, respectively, had marginal negative effects on Shannon–Wiener index, but did not affect biomass, Simpson index or Pielou index; (ii) the effects of drought on instream invertebrate biomass, density, and diversity were not affected by taxonomic level, indicating the robustness of our results; and (iii) stream water physiochemical characteristics such as water flow velocity, pH, conductivity, discharge, total nitrogen concentration, and chlorophyll-a concentration were important moderator variables of drought effects on instream invertebrate communities. Overall, our results clearly showed the global patterns and driving factors of drought effects on instream invertebrate biomass, density, richness, and diversity, which helps scientists better understand the responses of instream invertebrate communities under ongoing global climate change.

This paper reports the interdisciplinary approach of simultaneous use of a stereological method, namely the five parameter analysis (FPA) method and the grain boundary character distribution (GBCD) in cemented carbides. There are six major aspects: i) the background and motivations of the interdisciplinary approach, ii) the principle of the FPA method, iii) orientation texture of boundary planes with specific misorientations via λ(Δg, n) mode in cemented carbide, iv) orientation texture of habit planes regardless of misorientations via λ(n) mode in cemented carbide, v) application of the FPA method to serial cemented carbide samples and vi) boundary sort methods before using the FPA method. The work aims at presenting beneficial reference for studying structural and distribution features of special coincidence site lattice (CSL) boundaries in a statistical manner, and in turn increasing the knowledge about the structure-property relationship in cemented carbides.

Tumor derived small extracellular vesicles (TsEVs) display a great potential as efficient nanocarriers for chemotherapy because of their intrinsic targeting ability. However, the inherited risks of their original cargos (like loaded proteins or RNAs) from parent cancer cells in tumor progression severely hinder the practical application. In this study, a saponin-mediated cargo elimination strategy was established and practiced in glioblastoma (GBM) cell-derived small extracellular vesicles (GBM-sEVs). A high eliminating efficacy of the cargo molecules was confirmed by systematic analysis of the original proteins and RNAs in GBM-sEVs. In addition, the inherited functions of GBM-sEVs to promote GBM progression vanished after saponin treatment. Moreover, the results of cellular uptake analysis and in vivo imaging analysis demonstrated that saponin treatment preserved the homotypic targeting ability of GBM-sEVs. Thus, we developed an efficient nanocarrier with improved biosafety for GBM suppression. Furthermore, doxorubicin (DOX) transported by the saponin-treated GBM-sEVs (sa-GBM-sEVs) displayed an effective tumor suppression in both subcutaneous and orthotopic GBM models of mouse. Collectively, this study provides a feasible way to avoid the potential protumoral risks of TsEVs and can advance the clinical application of TsEVs in chemotherapy.

Plant litter is not only the major component of terrestrial ecosystem net productivity, the decomposition of which is also an important process for the returns of elements, including sodium (Na) and aluminum (Al), which can be beneficial or toxic for plant growth. However, to date, the global characteristics and driving factors of Na and Al concentrations in freshly fallen litter still remain elusive. Here, we evaluated the concentrations and drivers of litter Na and Al with 491 observations extracted from 116 publications across the globe. Results showed that (1) the average concentrations of Na in leaf, branch, root, stem, bark, and reproductive tissue (flowers and fruits) litter were 0.989, 0.891, 1.820, 0.500, 1.390, and 0.500 g/kg, respectively, and the concentrations of Al in leaf, branch, and root were 0.424, 0.200 and 1.540 g/kg, respectively. (2) mycorrhizal association significantly affected litter Na and Al concentration. The highest concentration of Na was found in litter from trees associated with both arbuscular mycorrhizal fungi (AM) and ectomycorrhizal fungi (ECM), followed by litter from trees with AM and ECM. Lifeform, taxonomic, and leaf form had significant impacts on the concentration of Na and Al in plant litter of different tissues. (3) leaf litter Na concentration was mainly driven by mycorrhizal association, leaf form and soil phosphorus concentration, while leaf litter Al concentration was mainly controlled by mycorrhizal association, leaf form, and precipitation in the wettest month. Overall, our study clearly assessed the global patterns and influencing factors of litter Na and Al concentrations, which may help us to better understand their roles in the associated biogeochemical cycles in forest ecosystem.

The polarization of microglia plays an important role in the outcome of ischemic stroke (IS). In the aged population, senescent microglia show a predominant pro-inflammatory phenotype, which leads to worse outcomes in aged ischemic stroke compared to young ischemic stroke. Recent research demonstrated that inducible pluripotent stem cell-derived small extracellular vesicles (iPSC-sEVs) possess the significant anti-ageing ability. We hypothesized that iPSC-sEVs could alleviate microglia senescence to regulate microglia polarization in aged ischemic stroke. In this study, we showed that treatment with iPSC-sEVs significantly alleviated microglia senescence as indicated by the decreased senescence-associated proteins including P16, P21, P53, and γ-H2AX as well as the activity of SA-β-gal, and inhibited pro-inflammatory activation of microglia both in vivo and in vitro. Furthermore, iPSC-sEVs shifted microglia from pro-inflammatory phenotype to anti-inflammatory phenotype, which reduced the apoptosis of neurons, and improved the outcome of aged stroke mice. Mechanism studies showed that iPSC-sEVs reversed the loss of Rictor and downstream p-AKT (s473) in senescent microglia, which was involved in the senescence and pro-inflammatory phenotype regulation of microglia. Inhibition of Rictor abolished the iPSC-sEVs-afforded phosphorylation of AKT and alleviation of inflammation of senescent microglia. Proteomics results indicated that iPSC-sEVs carried transforming growth factor-β1 (TGF-β1) to upregulate Rictor and p-AKT in senescent microglia, which could be hindered by blocking TGF-β1. Taken together, our work demonstrates iPSC-sEVs reverse the senescent characteristic of microglia in aged brains and therefore improve the outcome after stroke, at least, via delivering TGF-β1 to upregulate Rictor and p-AKT. Our data suggest that iPSC-sEVs might be a novelty therapeutic method for aged ischemic stroke and other diseases involving senescent microglia.

In this article, a new technology of surface wrapping and strengthening of expandable polystyrene (EPS) beads is proposed. Three wrapping materials including magnesium phosphate cement (MPC), ultra-high performance concrete (UHPC), and water-borne polyurethane (WPU) were evaluated. Four groups of uniaxial compression tests of EPS concrete specimens were conducted: the failure process and the characteristics of the specimens were analyzed; and the complete stress–strain equation is proposed based on these analyses. The research shows that the EPS beads were strengthened by wrapping, and the axial compressive strength of concrete is increased by 50–75%; the concrete with EPS beads wrapped by MPC and WPU has obvious brittleness; the concrete with EPS beads wrapped by UHPC has axial compressive strength close to that of EPS concrete wrapped with MPC and WPU but has a larger ductility coefficient (150%), a larger toughness coefficient (50–90% larger), a higher energy dissipation coefficient (40% larger), and larger residual stress. The proposed stress–strain model is in good agreement with the experimental results, which can accurately describe the stress and deformation characteristics of EPS concrete under uniaxial compression and has good applicability. The discovery of this study provides background knowledge for the structural analysis and design of this kind of concrete; it provides a basis for selecting EPS concrete as structural materials.

Expanded polystyrene (EPS) concrete is a low-carbon green building material, which has the properties of thermal insulation, but its strength is not high at present. To improve the strength of EPS concrete, EPS particles were wrapped on the surface by magnesium phosphate cement, ultra-high performance concrete, and waterborne polyurethane, they were used to make concrete after aging, and then the strength and microproperties of concrete were tested. The test results show that the wrapping material form a shell structure on the surface of EPS particles; the hydrophilic property of the wrapped EPS particles and the uniformity of the concrete have been significantly improved; the contact between the wrapped EPS particles and the cement base has become more closer; the cube compressive strength of concrete is increased by 80–110%, the flexural strength of concrete is increased by 40–90%. The research results of this study are of great significance for EPS concrete used as structural material and fabricated lightweight wallboard.

Abstract Patients with large granular lymphocytic leukemia (LGLL) frequently present with neutropenia. When present, anemia is usually accompanied by neutropenia and/or thrombocytopenia and isolated anemia is uncommon. We evaluated a cohort of 244 LGLL patients spanning 15 years and herein report the clinicopathologic features of 34 (14%) with isolated anemia. The patients with isolated anemia showed a significantly male predominance (p = 0.001), a lower level of hemoglobulin (p

Abstract Background Aberrant alternative splicing plays critical role in aging and age-related diseases. Heterogeneous nuclear ribonucleoproteins (hnRNPs) reportedly regulate RNA splicing process. Whether and how hnRNPs contribute to age-related neurodegenerative diseases, especially Alzheimer’s disease (AD), remain elusive. Methods Immunoblotting and immunostaining were performed to determine expression patterns and cellular/subcellular localization of the long isoform of hnRNP D-like (L-DL), which is a hnRNP family member, in mouse hippocampus. Downregulation of L-DL in WT mice was achieved by AAV-mediated shRNA delivery, followed by memory-related behavioural tests. L-DL interactome was analysed by affinity-precipitation and mass spectrometry. Alternative RNA splicing was measured by RNA-seq and analyzed by bioinformatics-based approaches. Downregulation and upregulation of L-DL in APP/PS1 mice were performed using AAV-mediated transduction. Results We show that L-DL is specifically localized to nuclear speckles. L-DL levels are decreased in the hippocampus of aged mouse brains and downregulation of L-DL impairs cognition in mice. L-DL serves as a structural component to recruit other speckle proteins, and regulates cytoskeleton- and synapse-related gene expression by altering RNA splicing. Mechanistically, these splicing changes are modulated via L-DL-mediated interaction of SF3B3, a core component of U2 snRNP, and U2AF65, a U2 spliceosome protein that guides U2 snRNP’s binding to RNA. In addition, L-DL levels are decreased in APP/PS1 mouse brains. While downregulation of L-DL deteriorates memory deficits and overexpression of L-DL improves cognitive function in AD mice, by regulating the alternative splicing and expression of synaptic gene CAMKV. Conclusions Our findings define a molecular mechanism by which hnRNP L-DL regulates alternative RNA splicing, and establish a direct role for L-DL in AD-related synaptic dysfunction and memory decline.

Abstract Background Female sex workers (FSW) are highly susceptible to chlamydia and gonorrhea infection. However, there is limited literature examining their testing uptake to date. This study aimed to assess the uptake and determinants of chlamydia and gonorrhea testing among FSW in Southern China. Methods A cross-sectional study with convenience sampling was performed in five cities in Southern China. Data on socio-demographic characteristics, sexual behaviors, chlamydia and gonorrhea testing, and the utilization of health care services from participants were collected through face-to-face interviews. Univariate and multivariable logistic regressions were used to determine factors associated with chlamydia and gonorrhea testing, respectively. Results Overall, 1207 FSWs were recruited, with the mean age of 30.7 ± 6.8 years and an average number of clients of 7.0 (4.0–10.0) per week. 65.4% participants constantly used condoms with clients during the past month. Only 7.5 and 10.4% had been tested for chlamydia and gonorrhea in the last year, respectively. Multivariable analysis indicated that FSW who worked at low tiers (adjusted Odds Ratio (aOR) = 2.36, 95%CI:1.23–10.14), had more clients in the last month (aOR = 1.03, 95%CI:1.01–1.05), used condoms consistently (aOR = 1.79, 95%CI:1.12–2.86), had STD symptoms (aOR = 4.09,95%CI:2.62–6.40), had been tested for HIV (aOR = 5.16, 95%CI:3.21–8.30) or syphilis (aOR = 6.90, 95%CI:4.21–11.22) in the last year were more likely to have chlamydia testing. In addition, FSW who had more clients in the past month (aOR = 1.02,95%CI:1.00–1.04), had STD symptoms (aOR = 3.33, 95%CI:2.03–5.46), had been tested for HIV (aOR = 3.94, 95%CI:2.34–6.65) and syphilis (aOR = 3.27, 95%CI:1.96–5.46) in the last year were more likely to have gonorrhea testing. Conclusions The testing rates of chlamydia and gonorrhea are low among Chinese FSW. Integrating chlamydia and gonorrhea testing into HIV testing promotion programs may help bridge the gap among FSW.

Lignocellulose is a major component of plant litter and plays a dominant role in regulating the process of litter decomposition, but we lack a global perspective on plant litter initial lignocellulose concentration. Here, we quantitatively assessed the global patterns and drivers of litter initial concentrations of lignin, cellulose, and hemicellulose using a dataset consisting of 6,021 observations collected from 795 independent publications. We found that (1) globally, the median concentrations of leaf litter lignin, cellulose, and hemicellulose were 20.3, 22.4, and 15.0% of litter mass, respectively; and (2) litter initial concentrations of lignin, cellulose, and hemicellulose were regulated by phylogeny, plant functional type, climate, and soil properties, with mycorrhizal association and lifeform the dominant predictors. These results clearly highlighted the importance of mycorrhizal association and lifeform in controlling litter initial lignocellulose concentration at the global scale, which will help us to better understand and predict the role of lignocellulose in global litter decomposition models.

With the increasing prevalence of deep foundation pit projects in modern urban construction, the deformation control of the associated support structures is crucial to ensuring construction safety. Despite the growing importance of this issue, research on deep foundation pit excavation in soft soil areas near the sea is limited. This study investigates the deformation characteristics and impact of a geometrically complex deep foundation pit project in Taizhou, utilizing both long-term in-situ monitoring and numerical simulation. The results of this study indicated that the maximum horizontal displacement of the foundation pit was approximately within the depth range of 5 m, with a value of 34.5 mm. The maximum settlement of both the top of the pit and the surrounding structures were determined to be less than 25 mm, confirming the safety of the excavation process. The excavation process of the foundation pit was simulated and analyzed by the Midas GTS finite element software. The results showed a similar variation pattern to the measured results, but the numerical results were generally lower than the measured values. This study provides valuable insights into the deformation characteristics of deep foundation pit excavation in soft soil areas and serves as a reference for future projects in similar conditions.

Abstract Background Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is an intractable nonbacterial inflammatory disease. Mesenchymal stem cells (MSCs) derived from human induced pluripotent stem cells (hiPSCs, iMSCs) have been well documented for the management of inflammatory and autoimmune disorders because of their powerful immunoregulatory and anti-inflammatory capacities. Recently, studies have indicated that extracellular vesicles (EVs) released from iMSCs hold biological functions similar to their parental cells. This study aimed to evaluate the therapeutic efficacy of EVs released from iMSCs (iMSCs-EVs) on CP/CPPS and to explore the underlying mechanisms. Methods An experimental autoimmune prostatitis (EAP) model was established in rats by subcutaneous injection of prostate antigen with adjuvant. Then, iMSCs-EVs were injected into EAP rats via the tail vein. Pain behavioral measurements, urodynamic tests, and histopathological analyses were performed at 2, 4, and 6 weeks. The expression of cyclooxygenase-2 (COX-2) was evaluated by immunofluorescence staining and Western blot. The alterations of B cells, Th1 cells, Th2 cells, Th17 cells, and Treg cells in peripheral blood and spleen were analyzed using flow cytometry. The levels of Th1-, Th2-, Th17-, and Treg-related inflammatory mediators were determined by ELISA. Results After iMSCs-EVs administration, rats had reduced pain as indicated by the recovery of nociceptive responses to baseline. The voiding pressure was significantly reduced, and the intercontraction interval was increased. The findings of histopathological analysis revealed that iMSCs-EVs could significantly decrease inflammatory cell infiltration and promote basal lamina and glandular epithelial tissue repair. Further studies demonstrated that the overexpression of COX-2 was downregulated by iMSCs-EVs. Meanwhile, the increases in the percentages of Th1 and Th17 cells were dramatically reversed. Also, rats that received iMSCs-EVs showed markedly increased percentages of Treg cells. The levels of those inflammatory mediators showed the same changing tendency. Conclusions iMSCs-EVs administration has the potential to ameliorate chronic pelvic pain, improve voiding dysfunction, suppress inflammatory reactions, and facilitate prostatic tissue repair. The functions are mediated by downregulating the overexpression of COX-2 and restoring the imbalance of Th1/Th2 and Treg/Th17 cells.

Monitoring the early treatment effect of sorafenib in advanced hepatocellular carcinoma (HCC) patients is a diagnostic challenge. In a previous study, we reported the potential role of liver computed tomography perfusion (CTP) in the assessment of the response to sorafenib therapy in HCC. The present study aims to investigate whether sorafenib-targeted genes is correlated with CTP parameter, and investigate the potential of sorafenib-targeted genes in early prediction of therapeutic response to sorafenib in advanced HCC.

Abstract Background Premature ovarian failure (POF) has a great impact on reproductive endocrine function in females, and it is an important cause of infertility. Previous studies have demonstrated that small extracellular vesicles (sEVs) derived from stem cells play an important role in tissue regeneration. This study aimed to investigate the therapeutic effect of sEVs derived from embryonic stem cells (ESCs-sEVs) on damaged ovaries and explore the underlying molecular mechanisms. Methods Mice POF models were established by injecting mice with cyclophosphamide and busulfan. Then, ESCs-sEVs were intravenously transplanted into POF mice. The plasma of mice was harvested at 1 and 2 weeks after treatment to analyze the levels of anti-Mullerian hormone (AMH), estradiol (E2), and follicle stimulating hormone (FSH) by ELISA. The morphology of ovaries and follicles was observed by H&E staining, and apoptosis of granulosa cells was detected by TUNEL. In vitro, EdU and CCK-8 tests were used to evaluate the proliferation of cultured granulosa cells stimulated by ESCs-sEVs. Western blotting was used to determine the expression of PI3K/AKT and apoptotic-related proteins. Results After transplantation of ESCs-sEVs, the levels of serum sex hormones recovered to normal levels. In addition, the number of follicles was significantly increased, and the number of apoptotic cells was decreased. The results in vitro revealed that ESCs-sEVs could significantly improve the proliferation rate of granulosa cells and increase the expression of phosphorylated PI3K and AKT. Meanwhile, the positive effect on proliferation and the negative effect on apoptosis observed in granulosa cells were obviously decreased when the PI3K/AKT signaling pathway was inhibited. Conclusion Our findings suggested that ESCs-sEVs could improve ovarian function by regulating the PI3K/AKT signaling pathway, which could provide a promising clinical therapy for POF.

Abstract Mesenchymal stem cell‐derived small extracellular vesicles (MSC‐sEVs) possess a great therapeutical potential for osteoarthritis (OA) treatment. However, the steric and electrostatic hindrance of cartilage matrix leads to very limited distribution of MSC‐sEVs in cartilage and low bioavailability of MSC‐sEVs after intra‐articular injection. To overcome this, a strategy to reverse the surface charge of MSC‐sEVs by modifying the MSC‐sEVs with a novel cationic amphiphilic macromolecule namely ε‐polylysine‐polyethylene‐distearyl phosphatidylethanolamine (PPD) was developed in this study. Through incubation with 100 μg/ml PPD, positively charged MSC‐sEVs (PPD‐sEVs) were obtained, and the modification process showed nearly no disturbance to the integrity and contents of sEVs and exhibited good stability under the interference of anionic macromolecules. A more effective cellular uptake and homeostasis modulation ability of PPD‐sEVs than unmodified MSC‐sEVs to chondrocytes was demonstrated. More importantly, PPD‐sEVs demonstrated significantly enhanced cartilage uptake, cartilage penetration, and joint retention capacity as compared to MSC‐sEVs. Intra‐articular injection of PPD‐sEVs into a mouse OA model showed significantly improved bioavailability than MSC‐sEVs, which resulted in enhanced therapeutic efficacy with reduced injection frequency. In general, this study provides a facile and effective strategy to improve the intra‐articular bioavailability of MSC‐sEVs and has a great potential to accelerate the clinical practice of MSC‐sEVs based OA therapy.

Camellia confuse Craib 1914 is an industrially valuable oil crop from southern China for which little genetic information is available. Here, we found that its complete chloroplast genome is a circular sequence (156,905 bp) with a large single-copy region (LSC) of 67,724 bp, a small single copy region (SSC) of 18,400 bp, and two inverted repeats (IRs). In total, 130 genes were identified, including 86 protein-coding genes, 36 transfer RNAs, and 8 rRNA genes. Phylogenetic analysis showed that C. confusa is close to C. meiocarpa. These results provide valuable information for accelerating research on the evolution of camellias.

BackgroundLymphoma-associated macrophages (LAMs) are key components in the lymphoma microenvironment, which may impact disease progression and response to therapy. There are two major subtypes of LAMs, CD68+ M1 and CD163+ M2. M2 LAMs can be transformed from M1 LAMs, particularly in certain diffuse large B-cell lymphomas (DLBCL). While mantle cell lymphoma (MCL) is well-known to contain frequent epithelioid macrophages, LAM characterization within MCL has not been fully described. Herein we evaluate the immunophenotypic subclassification, the expression of immune checkpoint molecule PD-L1, and the prognostic impact of LAMs in MCL.Materials and MethodsA total of 82 MCL cases were collected and a tissue microarray block was constructed. Immunohistochemical staining was performed using CD68 and CD163, and the positive cells were recorded manually in four representative 400× fields for each case. Multiplexed quantitative immunofluorescence assays were carried out to determine PD-L1 expression on CD68+ M1 LAMs and CD163+ M2 LAMs. In addition, we assessed Ki67 proliferation rate of MCL by an automated method using the QuPath digital imaging analysis. The cut-off points of optimal separation of overall survival (OS) were analyzed using the X-Tile software, the SPSS version 26 was used to construct survival curves, and the log-rank test was performed to calculate the p-values.ResultsMCL had a much higher count of M1 LAMs than M2 LAMs with a CD68:CD163 ratio of 3:1. Both M1 and M2 LAMs were increased in MCL cases with high Ki67 proliferation rates (>30%), in contrast to those with low Ki67 (

Abstract Vascular dementia (VD) is one of the most common types of dementia, however, the intrinsic mechanism is unclear and there is still lack of effective medications. In this study, the VD rats exhibit a progressive cognitive impairment, as well as a time‐related increasing in hippocampal neural stem cells (H‐NSCs) senescence, lost and neurogenesis decline. Then, embryonic stem cell‐derived small extracellular vesicles (ESC‐sEVs) are intravenously injected into VD rats. ESC‐sEVs treatment significantly alleviates H‐NSCs senescence, recovers compromised proliferation and neuron differentiation capacity, and reverses cognitive impairment. By microarray analysis and RT‐qPCR it is identified that several miRNAs including miR‐17‐5p, miR‐18a‐5p, miR‐21‐5p, miR‐29a‐3p, and let‐7a‐5p, that can inhibit mTORC1 activation, exist in ESC‐sEVs. ESC‐sEVs rejuvenate H‐NSCs senescence partly by transferring these miRNAs to inhibit mTORC1 activation, promote transcription factor EB (TFEB) nuclear translocation and lysosome resumption. Taken together, these data indicate that H‐NSCs senescence cause cell depletion, neurogenesis reduction, and cognitive impairment in VD. ESC‐sEVs treatment ameliorates H‐NSCs senescence by inhibiting mTORC1 activation, and promoting TFEB nuclear translocation and lysosome resumption, thereby reversing senescence‐related neurogenesis dysfunction and cognitive impairment in VD. The application of ESC‐sEVs may be a novel cell‐free therapeutic tool for patients with VD, as well as other aging‐related diseases.

Tissue-resident stem cell senescence leads to stem cell exhaustion, which is a major cause of physiological and pathological ageing. Stem cell-derived extracellular vesicles (SC-EVs) have been reported in preclinical studies to possess therapeutic potential for diverse diseases. However, whether SC-EVs can rejuvenate senescent tissue stem cells to prevent age-related disorders still remains unknown. Here, we show that chronic application of human embryonic stem cell-derived small extracellular vesicles (hESC-sEVs) rescues the function of senescent bone marrow mesenchymal stem cells (BM-MSCs) and prevents age-related bone loss in ageing mice. Transcriptome analysis revealed that hESC-sEVs treatment upregulated the expression of genes involved in antiaging, stem cell proliferation and osteogenic differentiation in BM-MSCs. Furthermore, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis identified 4122 proteins encapsulated in hESC-sEVs. Bioinformatics analysis predicted that the protein components in the hESCs-sEVs function in a synergistic way to induce the activation of several canonical signalling pathways, including Wnt, Sirtuin, AMPK, PTEN signalling, which results in the upregulation of antiaging genes in BM-MSCs and then the recovery of senescent BM-MSCs function. Collectively, our findings reveal the effect of hESC-sEVs in reversing BM-MSCs senescence and age-related osteogenic dysfunction, thereby preventing age-related bone loss. Because hESC-sEVs could alleviate senescence of tissue-resident stem cells, they might be promising therapeutic candidates for age-related diseases.

Mouse models of gastroesophageal junction (GEJ) cancer strive to recapitulate the intratumoral heterogeneity and cellular crosstalk within patient tumors to improve clinical translation. GEJ cancers remain a therapeutic challenge due to the lack of a reliable mouse model for preclinical drug testing. In this study, a novel patient-derived orthotopic xenograft (PDOX) was established from GEJ cancer via transabdominal surgical implantation. Patient tumor was compared to subcutaneously implanted patient-derived tumor xenograft (PDX) and PDOX by Hematoxylin and Eosin staining, immunohistochemistry and next-generation sequencing. Treatment efficacy studies of radiotherapy were performed. We observed that mechanical abrasion of mouse GEJ prior to surgical implantation of a patient-derived tumor in situ promotes tumor engraftment (100%, n=6). Complete PDOX engraftment was observed with rapid intra- and extraluminal tumor growth, as evidenced by magnetic resonance imaging. PDOXs contain fibroblasts, tumor-associated macrophages, immune and inflammatory cells, vascular and lymphatic vessels. Stromal hallmarks of aggressive GEJ cancers are recapitulated in a GEJ PDOX mouse model. PDOXs demonstrate tumor invasion into vasculature and perineural space. Next-generation sequencing revealed loss of heterozygosity with very high allelic frequency in NOTCH3, TGFB1, EZH2 and KMT2C in the patient tumor, the subcutaneous PDX and the PDOX. Immunohistochemical analysis of Her2/neu (also known as ERBB2), p53 (also known as TP53) and p16 (also known as CDKN2A) in PDX and PDOX revealed maintenance of expression of proteins found in patient tumors, but membranous EGFR overexpression in patient tumor cells was absent in both xenografts. Targeted radiotherapy in this model suggested a decrease in size by 61% according to Response Evaluation Criteria in Solid Tumors (RECIST), indicating a partial response to radiation therapy. Our GEJ PDOX model exhibits remarkable fidelity to human disease and captures the precise tissue microenvironment present within the local GEJ architecture, providing a novel tool for translating findings from studies on human GEJ cancer. This model can be applied to study metastatic progression and to develop novel therapeutic approaches for the treatment of GEJ cancer. This article has an associated First Person interview with the first author of the paper.

Primary effusion lymphoma (PEL) is a rare type of large B-cell lymphoma associated with human herpesvirus 8 (HHV8) infection. Patients with PEL usually present with an effusion, but occasionally with an extracavitary mass. In this study, we reported a cohort of 70 patients with PEL: 67 men and 3 women with a median age of 46 years (range 26–91). Of these, 56 (80%) patients had human immunodeficiency virus (HIV) infection, eight were HIV-negative, and six had unknown HIV status. Nineteen (27%) patients had Kaposi sarcoma. Thirty-five (50%) patients presented with effusion only, 27 (39%) had an extracavitary mass or masses only, and eight (11%) had both effusion and extracavitary disease. The lymphoma cells showed plasmablastic, immunoblastic, or anaplastic morphology. All 70 (100%) cases were positive for HHV8. Compared with effusion-only PEL, patients with extracavitary-only PEL were younger (median age, 42 vs. 52 years, p = 0.001), more likely to be HIV-positive (88.9% vs. 68.6%, p = 0.06) and EBV-positive (76.9% vs. 51.9%, p = 0.06), and less often positive for CD45 (69.2% vs. 96.2%, p = 0.01), EMA (26.7% vs. 100%, p = 0.0005), and CD30 (60% vs. 81.5%, p = 0.09). Of 52 (50%) patients with clinical follow-up, 26 died after a median follow-up time of 40.0 months (range 0–96), and the median overall survival was 42.5 months. The median OS for patients with effusion-only and with extracavitary-only PEL were 30.0 and 37.9 months, respectively (p = 0.34), and patients with extracavitary-only PEL had a lower mortality rate at the time of last follow-up (35% vs. 61.5%, p = 0.07). The median OS for HIV-positive and HIV-negative patients were 42.5 and 6.8 months, respectively (p = 0.57), and they had a similar mortality rate of 50% at last follow-up. In conclusion, patients presenting with effusion-only versus extracavitary-only disease are associated with different clinicopathologic features. PEL is an aggressive lymphoma with a poor prognosis, regardless of extracavitary presentation or HIV status.

A serious groundwater inrush occurred at the Wangjialing coal mine on March 28, 2010. Great effort from all over the country was taken during the postaccident rescue. However, triggered by accumulated water in the upper abandoned tunnels and goafs of a nearby closed individually owned coal mine, it caused great damage, including 38 deaths and direct economic losses of over 49 million yuan. The inrush water was from the abandoned tunnels and goafs, which were filled subsequently by groundwater from the sandstone aquifer in the roof of the coal seam. The passage formed in the west roof of the heading face of the air return tunnel in the 20101 first mining face. Unidentified distribution and water-filled degree of the abandoned tunnels and goafs are critical bases for the accident. That important regulations for abundant groundwater exploration and release were not carried out thoroughly was another fatal cause leading to the accident. The poor awareness of water hazard controlling also contributed to the accident to a large extent.