By shaping T cell immunity, tolerogenic dendritic cells (tDCs) play critical roles in the induction of immune tolerance after transplantation. However, the role of long noncoding RNAs (lncRNAs) in ...the function and immune tolerance of dendritic cells (DCs) is largely unknown. Here, we found that the lncRNA MALAT1 is upregulated in the infiltrating cells of tolerized mice with cardiac allografts and activated DCs. Functionally, MALAT1 overexpression favored a switch in DCs toward a tolerant phenotype. Mechanistically, ectopic MALAT1 promoted dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN) expression by functioning as an miR155 sponge, which is essential for the tolerogenic maintenance of DCs and the DC-SIGN-positive subset with more potent tolerogenic ability. The adoptive transfer of MALAT1-overexpressing DCs promoted cardiac allograft survival and protected from the development of experimental autoimmune myocarditis, accompanied with increasing antigen-specific regulatory T cells. Therefore, overexpressed MALAT1 induces tDCs and immune tolerance in heart transplantation and autoimmune disease by the miRNA-155/DC-SIGH/IL10 axis. This study highlights that the lncRNA MALAT1 is a novel tolerance regulator in immunity that has important implications in settings in which tDCs are preferred.
A diffuse optical tomography system with chaotic laser is proposed for the three-dimensional optical phantom. The high signal-to-noise ratio is beneficial to improve the spatial resolution of diffuse ...optical tomography. It is essential to drive the chaotic laser as the incident light into the optical phantom. The transmitted light emitted from phantom as the detection light and a part of the incident light as the reference light to carry out cross-correlation analysis. The high-density source-detector configuration in parallel plate structure is designed for detecting targets in the phantom. The propagation of chaotic laser in the phantom is studied theoretically and experimentally based on the diffusion equation. Image reconstruction is achieved by the cross-correlation analysis of chaotic laser and the Newton-Raphson nonlinear algorithm. The performance of the proposed system has been assessed by reconstruction localization accuracy and contrast-noise-ratio. The results show that the spatial resolution of the proposed system can reach 1.5 mm and the localization error is less than 1 mm.
Herein, a small library of Pt(IV) prodrugs based on cisplatin and chemosensitizer adjudin (ADD) were explored for efficient cisplatin resistant triple-negative breast cancer (TNBC) treatment. We ...further elucidated the detail relationship of chemical structure, alkyl chain length (ethyl to dodecyl) and ADD substituted degree, with respect to the self-assembly ability and cytotoxic effect of prodrugs. It demonstrated that all prodrugs could self-assemble into nanomedicine, which was in consist with the molecule structure building and self-assembly simulation. All nanomedicines possessed small particle size, uniform morphology and ultra-high drug loading content (84.0%–86.5%). Moreover, the length of alkyl chain was of great importance for the structure-transformable character and cytotoxicity of nanomedicines. Interestingly, ADD monosubstituted with butyl or hexyl contralateral substituted prodrug (C4-Pt-ADD or C6-Pt-ADD) assembled nanomedicine could convert to wire or sheet structure. These transformable nanoparticles showed great potential in improving the sensitivity of cisplatin to TNBC with up to 266-fold lower IC50 value and significantly enhanced in vivo tumor growth inhibition. Therefore, the self-assembled nanomedicine based on Pt(IV)-ADD could be a promising strategy for TNBC therapy.
A series of self-assembled nanomedicine based on Pt(IV)-ADD prodrug were fabricated here for cisplatin resistant triple-negative breast cancer (TNBC) therapy. Interestingly, the length of alkyl chain was of great importance for the structure-transformable character and cytotoxicity of nanomedicines. ADD monosubstituted with butyl or hexyl contralateral substituted prodrug (C4-Pt-ADD or C6-Pt-ADD) assembled nanomedicine could convert to wire or sheet structure. These transformable nanoparticles showed great potential in improving cisplatin sensitive to TNBC with up to 266-fold lower IC50 value and significantly enhanced in vivo tumor growth inhibition. Display omitted
•A series of self-assembled nanomedicine based on Pt(IV)-ADD prodrug were developed.•The introduction of ADD endowed the prodrugs with self-assembly ability.•The length of alkyl chain was of great importance for structure-transformable character and cytotoxicity of nanomedicines.•C4-Pt-ADD or C6-Pt-ADD prodrug assembled nanomedicine could convert to wire or sheet structure.•These structure-transformable nanoparticles showed great potential in improving cisplatin sensitive to TNBC.
Esophageal cancer (EC) is a common malignant gastrointestinal (GI) cancer in adults. Although surgical technology combined with neoadjuvant chemoradiotherapy has advanced rapidly, patients with EC ...are often diagnosed at an advanced stage and the five-year survival rate remains unsatisfactory. The poor prognosis and high mortality in patients with EC indicate that effective and validated therapy is of great necessity. Recently, immunotherapy has been successfully used in the clinic as a novel therapy for treating solid tumors, bringing new hope to cancer patients. Several immunotherapies, such as immune checkpoint inhibitors (ICIs), chimeric antigen receptor T-cell therapy, and tumor vaccines, have achieved significant breakthroughs in EC treatment. However, the overall response rate (ORR) of immunotherapy in patients with EC is lower than 30%, and most patients initially treated with immunotherapy are likely to develop acquired resistance (AR) over time. Immunosuppression greatly weakens the durability and efficiency of immunotherapy. Because of the heterogeneity within the immune microenvironment and the highly disparate oncological characteristics in different EC individuals, the exact mechanism of immunotherapy resistance in EC remains elusive. In this review, we provide an overview of immunotherapy resistance in EC, mainly focusing on current immunotherapies and potential molecular mechanisms underlying immunosuppression and drug resistance in immunotherapy. Additionally, we discuss prospective biomarkers and novel methods for enhancing the effect of immunotherapy to provide a clear insight into EC immunotherapy.
In order to solve the problems of poor mechanical properties and stability of chitosan and easy agglomeration and oxidation of nano zero-valent iron, Zr4+ crosslinked chitosan-coated nano zero-valent ...iron composites (CS-Zr@nZVI) were prepared for Cr(VI) removal from wastewater. The Zr-O, Zr-N and chitosan characteristic peaks in FTIR spectrum and the nZVI characteristic peaks in XRD pattern confirmed its successful synthesis. SEM and TEM showed that nZVI was dispersed on the surface of CS-Zr@nZVI, which solved the problem of easy agglomeration of nZVI. CS-Zr@nZVI has a wide operating pH range (pH= 2.0–10.0), high pHpzc, good stability and regeneration ability. The removal of Cr(VI) by CS-Zr@nZVI accords with pseudo-second-order kinetic model and Langmuir isotherm model, and it is a spontaneous, disordered and endothermic process. The maximum adsorption capacity was 344.82 mg g−1 at 318 K and pH = 2.0. At the dosage of 1.0 g L−1, CS-Zr@nZVI can treat 134.56 mg L−1 chromium-containing wastewater (pH = 3.5) to meet the discharge standard, which proves that CS-Zr@nZVI has the application prospect of removing Cr(VI). The main mechanisms of Cr(VI) removal by CS-Zr@nZVI are electrostatic interaction, ion exchange, reduction, complexation and co-precipitation. XPS analysis showed that 84.87 % of Cr(VI) was reduced to Cr(III). The above results provide a reference for the design of efficient Cr(VI) removal materials.
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•A Zr4+ cross-linked chitosan-coated nZVI composite was successfully prepared.•CS-Zr@nZVI is available in a wide pH range.•CS-Zr@nZVI has good stability and reduction properties.•CS-Zr@nZVI removed Cr(VI) by electrostatic adsorption, ion exchange, reduction and co-precipitation.
Adverse childhood experiences (ACEs) might be associated with maternal spontaneous fetal loss, while evidence among Chinese population is limited. This study aims to explore the associations of ...adverse childhood experiences (ACEs) among women and their spouses with the risk of spontaneous abortion and stillbirth.
Data were from the China Health and Retirement Longitudinal Study (CHARLS) 2014 survey. ACEs were categorized into intra-familial ACEs and extra-familial ACEs. The associations of maternal and paternal ACEs with women's history of spontaneous abortion and stillbirth were investigated by logistic regression.
7,742 women were included with 9.05% and 2.47% experiencing at least one spontaneous abortion or stillbirth, respectively. Women exposed to 2, 3, and ≥ 4 ACEs were at significantly higher odds of spontaneous abortion, with adjusted odds ratios (ORs) of 1.52 (95% CI, Confidence Interval 1.10-2.10), 1.50 (95% CI 1.07-2.09) and 1.68 (95% CI 1.21-2.32), respectively. A significant association between ≥ 4 maternal intra-familial ACEs and stillbirth (OR 2.23, 95% CI 1.12-4.42) was also revealed. Furthermore, paternal exposures to 3 and ≥ 4 overall ACEs were significantly associated with their wives' history of spontaneous abortion, with adjusted ORs of 1.81 (95% CI 1.01-3.26) and 1.83 (95% CI 1.03-3.25), respectively.
Both maternal and paternal ACEs were associated with spontaneous abortion, and potential mediators might need to be considered to further explore impacts of maternal and paternal ACEs on maternal reproductive health.
A better understanding of how the prevalence of hearing loss and its associated factors change over time could help in developing an appropriate program to prevent the development of hearing loss.
...Population-representative cross-sectional data from the United States National Health and Nutrition Examination Survey (NHANES) were used to estimate the trends in the prevalence of hearing loss among adults in the USA over the period 1999-2018. A total of 15,498 adult participants aged 20 years or older had complete audiometric examination data. Logistic regression was employed to evaluate the trend in hearing loss; weighted Rao-Scott χ2 tests and univariate logistic regression analyses were used to examine the association between hearing loss and relevant factors.
The overall hearing loss prevalence in 1999-2018 was 19.1% 19.1 (95% CI, 18.0-20.2%). The prevalence of hearing loss decreased in cycles (P for trend < 0.001). For participants aged 20-69 years, the prevalence decreased from 15.6% (95% CI, 12.9-18.4%) in 1999-2000 to 14.9% (95% CI, 13.2- 16.6%) in 2015-2016; for participants aged > 70 years the prevalence decreased from 79.9% (95% CI, 76.1-83.8%) in 2005-2006 to 64.5% (95% CI, 58.8-70.2%) in 2017-2018. Participants with hearing loss were likely to be older, male, non-Hispanic white, and to have not completed high school. Mild hearing loss was more prevalent among those aged 20-79 years; in those aged over 80 years the prevalence of moderate hearing loss exceeded that of mild loss. Among all otologically normal participants, hearing thresholds increased with age across the entire frequency range.
The prevalence of hearing loss in USA adults changed over the period 1999-2018. The trends observed provide valuable insight for making public health plans and allocating resources to hearing care. Further investigation is necessary to monitor hearing loss and its potential risk factors.
•A double Z-scheme heterojunction Ce-UiO-66/g-C3N4/Bi2WO6/Ti photoanode was prepared and applied to PFC.•Excellent performance of the PFC is attributed to strong redox ability of Bi2WO6 and g-C3N4, ...and special e- transfer mode of Ce-UiO-66.•The RhB degradation rate, Voc, Jsc and Pmax of the PFC were respectively 90.9 %, 0.37 V, 0.152 mA cm-2 and 7.53 µW cm-2.•The turnover frequency of RhB degradation by the PFC reached 0.98 h-1.•RhB was degraded by •O2-, h+ and •OH through deethylation and ring-opening reactions.
In order to enhance the carrier separation efficiency and redox ability of photoanode, a dual Z-scheme heterojunction Ce-UiO-66/g-C3N4/Bi2WO6/Ti photoanode was prepared and assembled with Cu cathode to form PFC. The characterization results show that Ce-UiO-66/g-C3N4/Bi2WO6 uniformly distributed on the Ti substrate, with average crystallite size of 9.04 nm and average particle size of 33.05 nm, which provides sufficient reactive active sites for RhB degradation. The RhB degradation rate, Pmax, Jsc, Voc and FF of the PFC were 90.9 % (90 min), 7.53 µW cm-2, 0.152 mA cm-2, 0.37 V and 0.134, respectively. The turnover frequency (TOF) for RhB degradation by the PFC reached 0.98 h-1. Fermi energy level analysis shows that a double-Z heterojunction is formed between Bi2WO6 and g-C3N4, and between Bi2WO6 and Ce-UiO-66, which not only effectively separates photogenerated e--h+, but also retains the high redox ability of the composite. Moreover, with the introduction of Ce-UiO-66, the composite photoanode has larger specific surface area and wider visible light absorption range. In addition, because of the built-in electric field, the photogenerated electrons can migrate to the surface of composite particles more easily and react with dissolved oxygen to generate more •O2- to participate in the degradation of RhB. This work provides a valuable reference for developing PFC photoanode with high efficiency and visible light response.
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Aptamers are widely used in numerous biochemical, bioanalytical, and biological studies. Most aptamers are developed through an in vitro selection process called SELEX against either purified targets ...or living cells expressing targets of interest. We report here an in vivo SELEX in mice using a PEGylated RNA library for the identification of a 2′-F RNA aptamer (RA16) that specifically binds to NCI-H460 non-small-cell lung cancer cells with an affinity (KD) of 9 ± 2 nM. Interestingly, RA16 potently inhibited cancer cell proliferation in a dose-dependent manner with an IC50 of 116.7 nM. When tested in vivo in xenografted mice, RA16 showed gradual migration toward tumor and accumulation at tumor site over time. An in vivo anti-cancer study showed that the average inhibition rate for mouse tumors in the RA16-treated group was 54.26% ± 5.87% on day 16 versus the control group. The aptamer RA16 adducted with epirubicin (RA16-epirubicin) showed significantly higher toxicity against targeted NCI-H460 cells and low toxicity against non-targeted tumor cells. Furthermore, RA16-epirubicin adduct exhibited in vivo anti-cancer efficacy, with an inhibition rate of 64.38% ± 7.92% when administrated in H460 xenograft mouse model. In summary, a specific bi-functional RNA aptamer RA16 was selected targeting and inhibiting toward NCI-H460 in vitro and in vivo.
Apart from single hemostasis, antibacterial and other functionalities are also desirable for hemostatic materials to meet clinical needs. Cationic materials have attracted great interest for ...antibacterial/hemostatic applications, and it is still desirable to explore rational structure design to address the challenges in balanced hemostatic/antibacterial/biocompatible properties. In this work, a series of cationic microspheres (QMS) were prepared by the facile surface modification of microporous starch microspheres with a cationic tannic acid derivate, the coating contents of which were adopted for the first optimization of surface structure and property. Thermoresponsive gels with embedded QMS (F-QMS) were further prepared by mixing a neutral thermosensitive polymer and QMS for second structure/function optimization through different QMS and loading contents.
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results confirmed that the coating content plays a crucial role in the hemostatic/antibacterial/biocompatible properties of QMS, but varied coating contents of QMS only lead to a classical imperfect performance of cationic materials. Inspiringly, the F-QMS-4 gel with an optimal loading content of QMS4 (with the highest coating content) achieved a superior balanced
hemostatic/antibacterial/biocompatible properties, the mechanism of which was revealed as the second regulation of cell-material/protein-material interactions. Moreover, the optimal F-QMS-4 gel exhibited a high hemostatic performance in a femoral artery injury model accompanied by the easy on-demand removal for wound healing endowed by the thermoresponsive transformation. The present work offers a promising approach for the rational design and facile preparation of cationic materials with balanced hemostatic/antibacterial/biocompatible properties.
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