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As one of the hot materials in biomedical research, alginate gel shows great potential in tumor therapy with its unique physical and chemical properties. In order to better meet the complex needs of cancer treatment, alginate brine gel composite system has come into being. This system not only inherits many advantages of single alginate brine gel, but also significantly improves the mechanical properties of the material through compounding, and effectively overcomes the limitations of application. These composites have been applied to drug delivery carriers, tumor targeting systems and three-dimensional tumor cell models in various forms, showing a wide range of application prospects. This paper aims to review the basic structure and properties of alginate gel and analyze the research progress of alginate gel composite systems in the field of cancer in recent years, to provide a valuable reference for the further expansion of the application of this material in tumor therapy.

The interfacial properties between carbon fiber (CF) and thermoplastic resin are relatively weak, which can be problematic for composites in structural applications. Improving the surface roughness of CF is regarded as an effective way to enhance the interface of composites. However, most CF modifying methods are complex and time-consuming, which cannot meet the demand for industrial production. Therefore, it is of great significance to research a fast technique of CF surface modification to strengthen the interface of composites. Herein, a one-pot reaction based on the aryl diazonium salt modification was applied to enhance the interface between CF and poly ether ether ketone (PEEK) resin. Carbon nanotubes (CNTs) were linked to CF by p-phenylenediamine (PPD) via cyclic voltammetry (CV). The surface morphology, chemical characteristics and surface energy of modified CF illustrated the effectiveness of this method, and the interfacial properties of as-prepared modified CF/PEEK demonstrated the increased tendency. All the CF was treated within 5 min and the interfacial shear strength (IFSS) of CF/PEEK was increased to the maximum of 99.62 MPa by aryl diazonium salt modification. This work may shed some light on the industrialized application of CF reinforced high-performance engineering thermoplastic composites.

Abstract Background Lung adenocarcinoma (LUAD) is a common type of lung cancer with a high risk of metastasis, but the exact molecular mechanisms of metastasis are not yet understood. Methods This study acquired single-cell transcriptomics profiling of 11 distal normal lung tissues, 11 primary LUAD tissues, and 4 metastatic LUAD tissues from the GSE131907 dataset. The lung multicellular ecosystems were characterized at a single-cell resolution, and the potential mechanisms underlying angiogenesis and metastasis of LUAD were explored. Results We constructed a global single-cell landscape of 93,610 cells from primary and metastatic LUAD and found that IGF2BP2 was specifically expressed both in a LUAD cell subpopulation (termed as LUAD_IGF2BP2), and an endothelial cell subpopulation (termed as En_IGF2BP2). The LUAD_IGF2BP2 subpopulation progressively formed and dominated the ecology of metastatic LUAD during metastatic evolution. IGF2BP2 was preferentially secreted by exosomes in the LUAD_IGF2BP2 subpopulation, which was absorbed by the En_IGF2BP2 subpopulation in the tumor microenvironment. Subsequently, IGF2BP2 improved the RNA stability of FLT4 through m6A modification, thereby activating the PI3K-Akt signaling pathway, and eventually promoting angiogenesis and metastasis. Analysis of clinical data showed that IGF2BP2 was linked with poor overall survival and relapse-free survival for LUAD patients. Conclusions Overall, these findings provide a novel insight into the multicellular ecosystems of primary and metastatic LUAD, and demonstrate that a specific LUAD_IGF2BP2 subpopulation is a key orchestrator promoting angiogenesis and metastasis, with implications for the gene regulatory mechanisms of LUAD metastatic evolution, representing themselves as potential antiangiogenic targets.

Abstract The prevalence and mortality of hepatocellular carcinoma (HCC) are still increasing. This study aimed to identify potential therapeutic targets related to patient prognosis. Data were downloaded from TCGA, GSE25097, GSE36376, and GSE76427 datasets. Differential analysis and enrichment analysis were performed in HCC. Cell deaths were evaluated, and least absolute shrinkage and selection operator regression (LASSO) regression was analyzed to screen candidate genes. Additionally, immune cell infiltration in HCC was assessed. We identified 4088 common DEGs with the same direction of differential expression in all four datasets, they were mainly enriched in immunoinflammation and cell cycle pathways. Apoptosis was significantly suppressed in HCC in GSEA and GSVA. After LASSO regression analysis, we screened CD69, CDC25B, MGMT, TOP2A, and TXNIP as candidate genes. Among them, CD69 significantly influenced the overall survival of HCC patients in both TCGA and GSE76427. CD69 may be a protective factor for outcome of HCC patients. In addition, CD69 was positive correlation with T cells and CD3E. CD69, CDC25B, MGMT, TOP2A, and TXNIP were potential diagnostic and prognostic target for HCC, especially CD69.

Carbon-fiber-reinforced polyimide (PI) resin composites have gained significant attention in the field of continuous-fiber-reinforced polymers, in which the interfacial bonding between carbon fiber and matrix resin has been an important research direction. This study designed and prepared a water-soluble thermoplastic polyamide acid sizing agent to improve the wettability of carbon fiber, enhance the van der Waals forces between carbon fiber and resin and strengthen the chemical bonding between the sizing agent and the alkyne-capped polyimide resin by introducing alkyne-containing functional groups into the sizing agent. This study found that the addition of a sizing layer effectively bridged the large modulus difference between the fiber and resin regions, resulting in the formation of an interfacial layer approximately 85 nm thick. This layer facilitated the transfer of stress from the matrix to the reinforced carbon fiber, leading to a significant improvement in the interfacial properties of the composites. Adjusting the concentration of the sizing agent showed that composites treated with 3% had the best interfacial properties. The interfacial shear strength increased from 82.08 MPa to 108.62 MPa (32.33%) compared to unsized carbon fiber. This research is significant for developing sizing agents suitable for carbon-fiber-reinforced polyimide composites.

The toughening modification of epoxy resin has received widespread attention. The addition of the second-phase resin has a good toughening effect on epoxy resin. In order to investigate the effect of the second-phase resin on the interphase of composites, in this work the interfacial properties of carbon fiber (CF)/epoxy resin with the second-phase resin structure were investigated. Methodologies including surface structure observation, chemical characteristics, surface energy of the CF, and micro-phase structure characterization of resin were tested, followed by the micro-interfacial performance of CF/epoxy composites before and after hygrothermal treatment. The results revealed that the sizing process has the positive effect of increasing the interfacial bonding properties of CF/epoxy. From the interfacial shear strength (IFSS) test, the introduction of the second phase in the resin reduced the interfacial bonding performance between the CF and epoxy. After the hygrothermal treatment, water molecules diffused along the interfacial paths between the two resins, which in turn created defects and consequently brought about a reduction in the IFSS.

Both environmental and genetic factors contribute to the etiology of autoimmune thyroid disease (AITD) including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT). However, the exact pathogenesis and interactions that occur between environmental factors and genes remain unclear, and therapeutic targets require further investigation due to limited therapeutic options. To solve such problems, this study utilized single-cell transcriptome, whole transcriptome, full-length transcriptome (Oxford nanopore technology), and metabolome sequencing to examine thyroid lesion tissues from 2 HT patients and 2 GD patients as well as healthy thyroid tissue from 1 control subject. HT patients had increased ATF4-positive thyroid follicular epithelial (ThyFoEp) cells, which significantly increased endoplasmic reticulum stress. The enhanced sustained stress resulted in cell death mainly including apoptosis and necroptosis. The ATF4-based global gene regulatory network and experimental validation revealed that N6-methyladenosine (m6A) reader hnRNPC promoted the transcriptional activity, synthesis, and translation of ATF4 through mediating m6A modification of ATF4. Increased ATF4 expression initiated endoplasmic reticulum stress signaling, which when sustained, caused apoptosis and necroptosis in ThyFoEp cells, and mediated HT development. Targeting hnRNPC and ATF4 notably decreased ThyFoEp cell death, thus ameliorating disease progression. Collectively, this study reveals the mechanisms by which microenvironmental cells in HT and GD patients trigger and amplify the thyroid autoimmune cascade response. Furthermore, we identify new therapeutic targets for the treatment of autoimmune thyroid disease, hoping to provide a potential way for targeted therapy.

Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically devastating diseases affecting the swine industry worldwide. To investigate the role of miRNAs in the infection and susceptibility of PRRS virus (PRRSV), twenty-four miRNA libraries were constructed and sequenced from PRRSV-infected and mock-infected Porcine alveolar macrophages (PAMs) of Meishan, Landrace, Pietrain and Qingping pigs at 9 hours post infection (hpi), 36 hpi, and 60 hpi. The let-7 family miRNAs were significantly differentially expressed between PRRSV-infected and mock-infected PAMs from 4 pig breeds. The let-7 family miRNAs could significantly inhibit PRRSV-2 replication by directly targeting the 3'UTR of the PRRSV-2 genome and porcine IL6, which plays an important role in PRRSV replication and lung injury. NEAT1 acts as a competing endogenous lncRNA (ceRNA) to upregulate IL6 by attaching let-7 in PAMs. EMSA and ChIP results confirmed that ARID3A could bind to the promoter region of pri-let-7a/let-7f/let-7d gene cluster and inhibit the expression of the let-7 family. Moreover, the NF-κB signaling pathway inhibits the expression of the let-7 family by affecting the nuclear import of ARID3A. The pEGFP-N1-let-7 significantly reduced viral infections and pathological changes in PRRSV-infected piglets. Taken together, NEAT1/ARID3A/let-7/IL6 play significant roles in PRRSV-2 infection and may be promising therapeutic targets for PRRS.

Ionizing radiation (IR) has been widely used in the diagnosis and treatment of clinical diseases, with radiation therapy (RT) being particularly rapid, but it can induce “bystander effects” that lead to biological responses in non-target cells after their neighboring cells have been irradiated. To help clarify how radiotherapy induces these effects, To help clarify how radiotherapy induces these effects, we analyzed single-cell RNA sequencing data from irradiated intestinal tissues on day 1 (T1 state), day 3 (T3 state), day 7 (T7 state), and day 14 (T14 state) after irradiation, as well as from healthy intestinal tissues (T0 state), to reveal the cellular level, molecular level, and involvement of different time irradiated mouse intestinal tissues in biological signaling pathways. In addition, changes in immune cell subpopulations and myeloid cell subpopulations after different radiation times were further explored, and gene regulatory networks (GRNs) of these cell subpopulations were constructed. Cellular communication between radiation-specific immune cells was explored by cell-to-cell communication events. The results suggest that radiotherapy trigger changes in immune cell subsets, which then reprogram the immune ecosystem and mediate systemic bystander effects. These radiation-specific immune cells participate in a wide range of cell-to-cell communication events. In particular, radiation-specific CD8+T cells appear to be at the core of communication and appear to persist in the body after recovery from radiotherapy, with enrichment analysis showing that radiation-specific CD8+ T cells are associated with ferroptosis. Thus, radiation-specific CD8+ T cells may be involved in cellular ferroptosis-mediated adverse effects caused by RT.

Summary: Abundant immune cells reside in barrier tissues. Understanding the regulation of these cells can yield insights on their roles in tissue homeostasis and inflammation. Here, we report that the chemokine CCL27 is critical for establishment of resident lymphocytes and immune homeostasis in barrier tissues. CCL27 expression is associated with normal skin and hair follicle development independent of commensal bacterial stimulation, indicative of a homeostatic role for the chemokine. Accordingly, in the skin of CCL27-knockout mice, there is a reduced presence and dysregulated localization of T cells that express CCR10, the cognate receptor to CCL27. Besides, CCL27-knockout mice have overreactive skin inflammatory responses in an imiquimod-induced model of psoriasis. Beyond the skin, CCL27-knockout mice have increased infiltration of CCR10+ T cells into lungs and reproductive tracts, the latter of which also exhibit spontaneous inflammation. Our findings demonstrate that CCL27 is critical for immune homeostasis across barrier tissues.

Melanoma has gradually entered the public view because of its high morbidity and rising prevalence rate, which is a serious threat to human life and health. Recently, N6-methyladenine (m6A) modification has been increasingly confirmed as a potential role in the development of tumogenesis. The purpose of this study is to explore the role and function of m6a-related regulators in the development of melanoma disease at the molecular, cellular and clinical levels through bioinformatics and traditional experiments. We screened and validated differential expression genes (DEGs) in m6A regulators via the GEO, GTEx, TCGA database. The biological processes and signaling pathway involved by DEGs were improved by constructing bioinformational methods such as PPI, GO enrichment, KEGG enrichment, GSEA enrichment, and immune infiltration analysis. And then, we explored the biological function of the key gene, SPRR1B, through cell invasion, migration, infiltration, and tissue chips. The gene IGF2BP3 which was differentially expressed in m6A regulatory factor gene was screened. The results of the enrichment analysis are significantly enriched in the biological processes and pathways of the skin barrier, epidermal differentiation, cytoskeleton, lymphocyte migration and other pathways, pointing to the direction of tumor immunity and tumor metastasis. Tumor immune-related genes YTHDC1, YTHDC2 and ALKBH5 were found. Knock SPRR1B reduction group had a significantly lower invasive ability, the ability to migrate. Nomogram prediction model shows that SPRR1B increased, expressing a worse prognosis. For this purpose, the relationship between m6A regulatory factor and melanoma progression was explored. At the same time, it was found that the abnormal up-regulated expression of SPRR1B before metastasis would lead to poor prognosis of melanoma. SPRR1B promotes the proliferation, invasion and migration of human melanoma cells.

Porcine reproductive and respiratory syndrome (PRRS) caused by a single-stranded RNA virus (PRRSV) is a highly infectious respiratory disease and leads to huge economic losses to the swine industry worldwide. To investigate the role of miRNAs in the infection and lung injury induced by PRRSV, the differentially expressed miRNAs (DE-miRs) were isolated from PRRSV-2 infected/mock-infected PAMs of Meishan, Landrace, Pietrain, and Qingping pigs at 9, 36, and 60 hpi. Mir-331-3p was the only common DE-miR in each set of miRNA expression profile at 36 hpi. Mir-210 was one of 7 common DE-miRs between PRRSV infected and mock-infected PAMs of Meishan, Pietrain, and Qingping pigs at 60 hpi. Mir-331-3p/mir-210 could target PRRSV-2 ORF1b, bind and downregulate porcine TNF-α/STAT1 expression, and inhibit PRRSV-2 replication, respectively. Furthermore, STAT1 and TNF-α could mediate the transcriptional activation of MCP-1, VCAM-1, and ICAM-1. STAT1 could also upregulate the expression of TNF-α by binding to its promoter region. In vivo, pEGFP-N1-mir-331-3p could significantly reduce viral replication and pathological changes in PRRSV-2 infected piglets. Taken together, Mir-331-3p/mir-210 have significant roles in the infection and lung injury caused by PRRSV-2, and they may be promising therapeutic targets for PRRS and lung injury/inflammation.

Abstract This study evaluated the prevalence and factors associated with sleep disturbance in a large cohort of HIV-infected patients across China. A cross-sectional study was conducted among HIV-infected patients on antiretroviral therapy at 20 AIDS clinics. The Pittsburgh Sleep Quality Index was self-administered by subjects. Socio-demographic characteristics, medical history and HIV-related clinical data were collected. 4103 patients had complete data for analysis. Sleep disturbances were observed in 43.1% of patients. Associated factors in multivariable analysis included psychological factors: anxiety (odds ratio [OR], 3.13; 95% confidence interval [CI], 2.44–4.00; P

Series of displacement tests of water by cold n-hexanol (below 0 °C) in a straight tube were conducted to investigate the freezing-accompanied displacement process, which occurs during the cryogenic fracturing process. The interrelationship between water freezing and displacement flow was studied. It was found that the displacement flow could significantly affect the water distribution in the flow channel. Along with the displacement proceeding, the n-hexanol overtook the water in the flow direction gradually, and the water in the center of the channel was driven to the edge area. Moreover, the initially integrated water phase split into several parts during the displacement process. Once the water freezing occurred, two typical ice blockage patterns, i.e., complete ice blockage and incomplete ice blockage, were observed. In incomplete ice blockage pattern, the channel cross-section was partly occupied by the ice phase, which mainly affected the rate of subsequent fluid flow. In complete ice blockage pattern, the channel cross-section was fully occupied by the ice phase, which cut off the fluid flow in the original direction. Based on the test results, the influences of the initial water temperature, initial water column length and flow rate of n-hexanol on the formation of different ice blockage patterns are discussed. The decrease of the initial water temperature and the increase of the initial water column length are preferred to induce the occurrence of complete ice blockage. However, changing n-hexanol flow rate could lead to the occurrence of both incomplete ice blockage and complete ice blockage, which depends on the actual situations.

A 2D computational fluid dynamics (CFD) model in consideration of nucleation characteristics (homogeneous/heterogeneous nucleation) using the volume of fluid (VOF) method and Lee model was proposed. The model was used to predict the process of a multiphase flow accompanied by freezing phase change during cryogenic fracturing. In this model, nucleation characteristic (homogeneous and heterogeneous nucleation) during the freezing process and the influence of the formed ice phase on the flowing behavior was considered. Validation of the model was done by comparing its simulation results to Neumann solutions for classical Stefan problem. The comparison results show that the numerical results are well consistent with the theoretical solution. The maximum relative differences are less than 7%. The process of multiphase flow accompanied by the freezing of water was then simulated with the proposed model. Furthermore, the transient formation and growth of ice as well as the evolution of temperature distribution in the computational domain was studied. Results show that the proposed method can better consider the difference between homogeneous nucleation in the fluid domain and heterogeneous nucleation on the wall boundary. Finally, the main influence factors such as the flow velocity and initial distribution of ice phase on the fracturing process were discussed. It indicates that the method enable to simulate the growth of ice on the wall and its effect on the flow of multiphase fluid.

Background: Anxiety and depression continue to be significant comorbidities for people with HIV infection. We investigated the prevalence of and factors associated with anxiety and depression among adult HIV-infected patients across China.Methods: In this cross-sectional study, we described clinical and psychosocial variables related to depression and anxiety in 4103 HIV-infected persons. Doctors assessed anxiety and depression by asking patients whether they had experienced anxiety or depression in the prior month. Patients also self-administered the Hospital Anxiety and Depression (HAD) scale; those with score ≥8 on HAD-A/D were considered to be at high risk of anxiety or depression.Results: Associations between socio-demographic, psychosocial, and ART-related clinical factors and risk of depression or anxiety were investigated using multivariable logistic regression. Among patients assessed between 9/2014 and 11/2015, 27.4% had symptoms of anxiety, 32.9% had symptoms of depression, and 19.0% had both. Recentness of HIV diagnoses (P = 0.046) was associated with elevated odds of anxiety. Older age (P = 0.004), higher educational attainment (P < 0.001), employment (P = 0.001), support from family / friends (P < 0.001), and sleep disturbance (P < 0.001), and number of ART regimen switches (P = 0.046) were associated with risk of depression, while neither sex nor transmission route showed any associations. There were no significant associations with HIV-specific clinical factors including current CD4+ T cell count and current viral load.Conclusions: Prevalence of symptoms of anxiety and depression is high in this cohort of treatment-experienced HIV patients. Psychological and social-demographic factors, rather than HIV disease status, were associated with risk of depression and anxiety. This finding highlights the need to deliver interventions to address the mental health issues affecting HIV-infected persons with fully successful immune restoration across China.