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Objective: The immune response initiated by SARS-CoV-2 infection in pregnancy is poorly elucidated. We aimed to access and compare the antiviral cellular responses and lymphocytes activation between healthy pregnancies and pregnant women infected with SARS-CoV-2. Methods: We detected the immunological changes of lymphocytes in peripheral blood of healthy non-pregnant women, non-pregnant women with COVID-19, healthy pregnant women, pregnant women with COVID-19 and convalescent group by flow cytometry. In vitro blockade was used to identify NKT-like cell activation through ICOS-ICOSL pathway. Results: We found that CD3+CD56+ NKT-like cells decreased significantly in COVID-19 positive pregnant women compared to healthy pregnant women. NKT-like cells of pregnant women expressed higher level of activating receptors CD69 and NKp46 after SARS-CoV-2 infection. Particularly, they also increased the expression of the co-stimulatory molecule ICOS. NKT-like cells of pregnant women with COVID-19 up-regulated the expression of IFN-γ, CD107a and Ki67. Meanwhile, we found that ICOSL expression was significantly increased on pDCs in pregnant women with COVID-19. Blocking ICOS in vitro significantly decreased the antiviral activity of NKT-like cells in COVID-19 positive pregnant women, suggesting that ICOS-ICOSL may play an important role in the virus clearance by NKT-like cells. Conclusions: During SARS-CoV-2 infection, NKT-like cells of pregnant women activated through ICOS-ICOSL pathway and played an important role in the antiviral response.
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COVID-19 , Ligante Coestimulador de Linfócitos T Induzíveis , Proteína Coestimuladora de Linfócitos T Induzíveis , Células T Matadoras Naturais , Complicações Infecciosas na Gravidez , SARS-CoV-2 , Humanos , Feminino , Gravidez , Células T Matadoras Naturais/imunologia , Células T Matadoras Naturais/metabolismo , COVID-19/imunologia , COVID-19/virologia , Proteína Coestimuladora de Linfócitos T Induzíveis/metabolismo , Adulto , Ligante Coestimulador de Linfócitos T Induzíveis/metabolismo , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/virologia , SARS-CoV-2/imunologia , Ativação Linfocitária/imunologia , Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/metabolismo , Transdução de Sinais/imunologia , Interferon gama/metabolismo , Receptor 1 Desencadeador da Citotoxicidade Natural/metabolismo , Lectinas Tipo C/metabolismoRESUMO
Noncovalent spatial interaction has become an intriguing and important tool for constructing optoelectronic molecules. In this study, we linearly attached three conjugated units in a multi π-stacked manner by using just one trident bridge based on indeno[2,1-b]fluorene. To achieve this structure, we improved the synthetic approach through double C-H activation, significantly simplifying the preparation process. Due to the proximity of the C10, C11, and C12 sites in indeno[2,1-b]fluorene, we derived two novel donor|acceptor|donor (D|A|D) type molecules, 2DMB and 2DMFB, which exhibited closely packed intramolecular stacking, enabling efficient through-space charge transfer. This molecular construction is particularly suitable for developing high-performance thermally activated delayed fluorescence materials. With donor(s) and acceptor(s) constrained and separated within this spatially rigid structure, elevated radiative transition rates, and high photoluminescence quantum yields were achieved. Organic light-emitting diodes incorporating 2DMB and 2DMFB demonstrated superior efficiency, achieving maximum external quantum efficiencies of 28.6 % and 16.2 %, respectively.
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Thin endometrium (TE) is a significant factor contributing to fertility challenges, and addressing this condition remains a central challenge in reproductive medicine. Menstrual blood-derived mesenchymal stem cells (MenSCs) play a crucial role in tissue repair and regeneration, including that of TE. The Wnt signaling pathway, which is highly conserved and prevalent in eukaryotes, is essential for cell proliferation, tissue development, and reproductive functions. MALAT1 is implicated in various transcriptional and molecular functions, including cell proliferation and metastasis. However, the combined effects of the Wnt signaling pathway and the long non-coding RNA (lncRNA) MALAT1 on the regulation of MenSCs' regenerative capabilities in tissue engineering have not yet been explored. To elucidate the regulatory mechanism of MALAT1 in TE, we analyzed its expression levels in normal endometrium and TE tissues, finding that low expression of MALAT1 was associated with poor clinical prognosis. In addition, we conducted both in vitro and in vivo functional assays to examine the role of the MALAT1/miR-7-5p/TCF4 axis in cell proliferation and migration. Techniques such as dual-luciferase reporter assay, fluorescent in situ hybridization, and immunoblot experiments were utilized to clarify the molecular mechanism. To corroborate these findings, we established a TE model and conducted pregnancy experiments, demonstrating a strong association between MALAT1 expression and endometrial fertility. In conclusion, our comprehensive study provides strong evidence supporting that lncRNA MALAT1 modulates TCF4 expression in the Wnt signaling pathway through interaction with miR-7-5p, thus enhancing MenSCs-mediated improvement of TE and improving fertility.
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Endométrio , Células-Tronco Mesenquimais , MicroRNAs , RNA Longo não Codificante , Via de Sinalização Wnt , Feminino , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Endométrio/metabolismo , Endométrio/citologia , MicroRNAs/metabolismo , MicroRNAs/genética , Animais , Fator de Transcrição 4/metabolismo , Fator de Transcrição 4/genética , Proliferação de Células/genética , Adulto , Camundongos , Fertilidade/genéticaRESUMO
Chronic hepatitis B (CHB) virus infection, which can be divided into immune-tolerant (IT), immune-active (IA), inactive carrier (IC) phases, and HBeAg-negative hepatitis (ENEG), can induce liver cirrhosis and eventually hepatocellular carcinoma (HCC). CD3+CD56+ NKT-like cells play an important role in antiviral immune response. However, the mechanism of NKT-like cells to mediate immune tolerance remains largely elusive. In this study, we observed circulating NKT-like cells from IC and IT CHB patients were phenotypically and functionally impaired, manifested by increased expression of inhibitory receptor TIGIT and decreased capacity of secreting antiviral cytokines. Besides, TIGIT+ NKT-like cells of IC and IT CHB patients expressed lower levels of cytotoxic cytokines than the TIGIT- subset. Furthermore, increased expression of CD155, the ligand of TIGIT, on plasmacytoid dendritic cells (pDCs) was detected in IC and IT CHB patients. Importantly, the co-culture of NKT-like cells and pDCs showed that NKT-like cells restored their antiviral ability after TIGIT blockade upon HBV peptide stimulation in IC and IT CHB patients. In conclusion, our findings suggest that the TIGIT pathway may mediate immune tolerance in IT CHB patients and lead to functional impairment in IC patients, indicating that TIGIT may be a potential therapeutic checkpoint for immunotherapy of CHB patients.
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Complexo CD3 , Antígeno CD56 , Células Dendríticas , Vírus da Hepatite B , Hepatite B Crônica , Tolerância Imunológica , Células T Matadoras Naturais , Receptores Imunológicos , Humanos , Receptores Imunológicos/metabolismo , Hepatite B Crônica/imunologia , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Antígeno CD56/metabolismo , Masculino , Vírus da Hepatite B/imunologia , Feminino , Células T Matadoras Naturais/imunologia , Adulto , Células Dendríticas/imunologia , Tolerância Imunológica/imunologia , Complexo CD3/imunologia , Complexo CD3/metabolismo , Pessoa de Meia-Idade , Receptores Virais/metabolismo , Receptores Virais/imunologia , Citocinas/metabolismo , Citocinas/imunologiaRESUMO
Pregnancy complicated with pulmonary arterial hypertension (PAH) is a severe and dangerous condition for both the mother and the fetus. Pregnancy-specific alterations in the maternal cardiovascular system suggest that PAH in pregnancy may manifest more severe symptoms compared with those in non-pregnant patients. Although most societal guidelines recommend early termination in the case of PAH, some recent data suggests that maternal mortality among patients with PAH is lower than previously observed and suggests if a woman decides to proceed with the pregnancy, she should be counseled about the potential risks of continuing with the pregnancy. This review paper starts with a real clinical case of PAH complicating with pregnancy, then summarizes the clinical features, diagnosis, and risk stratification. Effective treatments were also clarified, including pre-conception counseling and monitoring, general and supportive care, medication and immune therapy, delivery and postpartum care, counseling on contraception and breastfeeding, maternal and fetal outcomes, and cardiac surgery. The article summarizes points of uncertainty in both laboratory and clinical practices, as well as current guidelines and clinical recommendations.
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STUDY QUESTION: The objective was to construct a model for predicting the probability of recurrent implantation failure (RIF) after assisted reproductive technology (ART) treatment based on the clinical characteristics and routine laboratory test data of infertile patients. A model was developed to predict RIF. The model showed high calibration in external validation, helped to identify risk factors for RIF, and improved the efficacy of ART therapy. WHAT IS KNOWN ALREADY: Research on the influencing factors of RIF has focused mainly on embryonic factors, endometrial receptivity, and immune factors. However, there are many kinds of examinations regarding these aspects, and comprehensive screening is difficult because of the limited time and economic conditions. Therefore, we should try our best to analyse the results of routine infertility screenings to make general predictions regarding the occurrence of RIF. STUDY DESIGN, SIZE, DURATION: A retrospective study was conducted with 5212 patients at the Reproductive Center of the First Affiliated Hospital of USTC from January 2018 to June 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study included 462 patients in the RIF group and 4750 patients in the control group. The patients' basic characteristics, clinical treatment data, and laboratory test indices were compared. Logistic regression was used to analyse RIF-related risk factors, and the prediction model was evaluated by receiver operating characteristic (ROC) curves and the corresponding areas under the curve (AUCs). Further analysis of the influencing factors of live births in the first cycle of subsequent assisted reproduction treatment in RIF patients was performed, including the live birth subgroup (n = 116) and the no live birth subgroup (n = 200). MAIN RESULTS AND THE ROLE OF CHANCE: (1) An increased duration of infertility (1.978; 95% CI, 1.264-3.097), uterine cavity abnormalities (2.267; 95% CI, 1.185-4.336), low AMH levels (0.504; 95% CI, 0.275-0.922), insulin resistance (3.548; 95% CI, 1.931-6.519), antinuclear antibody (ANA)-positive status (3.249; 95% CI, 1.20-8.797) and anti-ß2-glycoprotein I antibody (A-ß2-GPI Ab)-positive status (5.515; 95% CI, 1.481-20.536) were associated with an increased risk of RIF. The area under the curve of the logistic regression model was 0.900 (95% CI, 0.870-0.929) for the training cohort and 0.895 (95% CI, 0.865-0.925) for the testing cohort. (2) Advanced age (1.069; 95% CI, 1.015-1.126) was a risk factor associated with no live births after the first cycle of subsequent assisted reproduction treatment in patients with RIF. Blastocyst transfer (0.365; 95% CI = 0.181-0.736) increased the probability of live birth in subsequent cycles in patients with RIF. The area under the curve of the logistic regression model was 0.673 (95% CI, 0.597-0.748). LIMITATIONS, REASONS FOR CAUTION: This was a single-centre regression study, for which the results need to be evaluated and verified by prospective large-scale randomized controlled studies. The small sample size for the analysis of factors influencing pregnancy outcomes in subsequent assisted reproduction cycles for RIF patients resulted in the inclusion of fewer covariates, and future studies with larger samples and the inclusion of more factors are needed for assessment and validation. WIDER IMPLICATIONS OF THE FINDINGS: Prediction of embryo implantation prior to transfer will facilitate the clinical management of patients and disease prediction and further improve ART treatment outcomes. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the General Project of the National Natural Science Foundation of China (Nos. 82,201,792, 82,301,871, 81,971,446, and 82,374,212) and the Natural Science Foundation of Anhui Province (No. 2208085MH206). There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: This study was registered with the Chinese Clinical Trial Register (Clinical Trial Number: ChiCTR1800018298 ).
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Infertilidade , Técnicas de Reprodução Assistida , Gravidez , Feminino , Humanos , Estudos Retrospectivos , Estudos Prospectivos , Implantação do Embrião , Infertilidade/terapia , Nascido Vivo , Taxa de GravidezRESUMO
Shape memory hydrogels provide a worldwide scope for functional soft materials. However, most shape memory hydrogels exhibit poor mechanical properties, leading to low actuation strength, which severely limits their applications in smart biomimetic devices. Herein, a strategy for muscle-inspired shape memory-oriented polyvinyl alcohol (PVA)-natural rubber latex (NRL) hydrogel (OPNH) with multiscale oriented structure is demonstrated. The shape memory function comes from the stretch-induced crystallization of natural rubber (NR), while PVA forms strong hydrogen bonding interactions with proteins and phospholipids on the surface of NRL particles. Meanwhile, the reconfigurable interactions of PVA and NR produce a multiscale-oriented structure during stretch-drying, improving the mechanical and shape memory properties. The resultant OPNH shows excellent interfacial compatibility, exhibiting outstanding mechanical performance (3.2 MPa), high shape fixity (≈80%) and shape recovery ratio (≈92%), high actuation strength (206 kPa), working capacity (105 kJ m- 3), extremely short response time (≈2 s), low response temperature (28 °C) and smart thermal responsiveness. It can even maintain muscle-like working capacity when lifting a load equivalent to 372 times its weight, providing a new class shape memory material for the application in smart biomimetic muscles and multistimulus responsive devices.
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Cellulose II nanocrystals (CNC II) possess a higher thermal stability and improved emulsifying capability than cellulose I nanocrystals (CNC I) owing to the higher density of their hydrogen bonds and more larger surface areas. Therefore, CNC II exhibit substantial advantages for value-added nanocomposite materials. Current CNC II preparation methods are mainly based on a two-pot reaction involving acid hydrolysis and crystal transformation. In this study, considering the oxidative nature of potassium ferrate (K2FeO4) in an alkaline environment containing a small amount of sodium hypochlorite (NaClO), a one-step and efficient approach was developed for the preparation of carboxyl-bearing CNC II from cotton pulp, affording a maximum CNC II yield of 45.14 %. Atomic force microscopy analysis revealed that the prepared CNCs exhibited a "rod-like" shape with a width of ~7 nm and a length of ~269 nm. The resulting CNC II also exhibited excellent thermal stability (Tonset = 311.4 °C). Furthermore, high-internal-phase Pickering emulsions (HIPPEs) stabilized by CNC II were prepared to stabilize liquid paraffin in the absence of surfactant. The results revealed that CNC II could be used as an effective emulsifier to fabricate the stable and gel-like HIPPEs, and are promising for the preparation of high value-added nanocomposite materials.
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Adhesive hydrogels (AHs) are considered ideal materials for flexible sensors. However, the lack of effective energy dissipation networks and sparse surface polar groups in AHs lead to poor mechanical properties and interfacial adhesion, which limit their practical application. Herein, a tough, long-lasting adhesive and highly conductive nanocomposite hydrogel (PACPH) was fabricated via the synergy of interfacial entanglement and adhesion group densification. PACPH was obtained by the in situ polymerization of highly carboxylated cellulose nanocrystals (SCNCPA, surface pre-grafted polyacrylic acid chains, C-COOH = 11.5 mmol g-1) with the acrylic acid precursor. The unique tacticity of SCNCPA provides strong interface entanglement and multiple hydrogen bonds with the PACPH network, which further increases the energy dissipated during SCNCPA displacements, and enhances the mechanical properties of PACPH (tensile strength = 1.45 MPa, modulus = 332 kPa, and fracture toughness = 13.2 MJ m-3). Meanwhile, SCNCPA increases the density of surface polar groups in PAPCH and also acts as an anchor point to improve the adhesion strength (>2-3 times) of PACPH on various substrates. The combination of excellent mechanical, adhesive, and conductive properties of the PAPCH-integrated patches enables long-term monitoring of human daily activities and electrocardiogram (ECG) signals, verifying that PAPCH is a promising material platform for the further development of flexible sensors and other health management devices.
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Influenza A virus (IAV) remains a pressing global health concern, yet our understanding of the specific nature and functional roles of certain circulating cell subsets in relation to this viral infection remains unclear. We performed single-cell RNA sequencing (scRNA-seq) on single-cell whole-blood (scWB) isolated from various populations using the Singleron Matrix platform. Our investigation showed a significant upregulation of the IFN-stimulated gene, IFN-α-inducible protein 27 (IFI27), in patients affected by IAV infection and further found that the heightened expression of IFI27 was primarily concentrated in specific immune cell populations, including monocytes and conventional dendritic cells (cDCs). Notably, we identified a specific subset of neutrophils, neutrophil_ISG15, which implicates interferon (IFN) signaling in IAV infection. Our findings provide a comprehensive understanding of the cellular subtypes and molecular characteristics of scWB across different populations with IAV infection.
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Organic multilayer heterostructures with accurate spatial organization demonstrate strong light-matter interaction from excitonic responses and efficient carrier transfer across heterojunction interfaces, which are considered as promising candidates toward advanced optoelectronics. However, the precise regulation of the heterojunction surface area for finely adjusting exciton conversion and energy transfer is still formidable. Herein, organic bilayer heterostructures (OBHs) with controlled face-to-face heterojunction via a stepwise seeded growth strategy, which is favorable for efficient exciton propagation and conversion of optical interconnects are designed and synthesized. Notably, the relative position and overlap length ratio of component microwires (LDSA /LBPEA = 0.39-1.15) in OBHs are accurately regulated by modulating the crystallization time of seeded crystals, resulting into a tailored heterojunction surface area (R = Loverlap /LBPEA = 37.6%-65.3%). These as-prepared OBHs present the excitation position-dependent waveguide behaviors for optical outcoupling characteristics with tunable emission colors and intensities, which are applied into two-dimensional (2D) photonic barcodes. This strategy opens a versatile avenue to purposely design OBHs with tailored heterojunctions for efficient energy transfer and exciton conversion, facilitating the application possibilities of advanced integrated optoelectronics.
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ABSTRACT: Genetic risk factors have been shown to contribute to the development of sexual dysfunction. However, the role of methylenetetrahydrofolate reductase (MTHFR) gene variants in the risk of erectile dysfunction (ED) remains unclear. In this study, we recruited 1254 participants who underwent ED assessed by the International Index of Erectile Function-5. The MTHFR c.677C>T variant was also measured by fluorescence polymerase chain reaction (PCR). No significant difference in the genotypic frequency of the MTHFR C677T polymorphism (CC, CT, and TT) was observed between men from the ED and non-ED groups. In addition, on binary logistic regression analysis, both crude and adjusted models showed that the risk of ED was not significantly associated with the C677T polymorphism. Interestingly, a significantly higher frequency of the 677TT polymorphism was found in severe and moderate ED (P = 0.02). The positive correlation between the MTHFR 677TT polymorphism and severe ED was confirmed by logistic regression analysis, even after adjusting for potential confounders (odds ratio [OR] = 2.46, 95% confidence interval [CI]: 1.15-5.50, P = 0.02). These findings suggest a positive correlation between the MTHFR 677TT polymorphism and the risk of severe ED. Identification of MTHFR gene polymorphisms may provide complementary information for ED patients during routine clinical diagnosis.
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Lightweight porous hydrogels provide a worldwide scope for functional soft mateirals. However, most porous hydrogels have weak mechanical strength, high density (>1 g cm-3 ), and high heat absorption due to weak interfacial interactions and high solvent fill rates, which severely limit their application in wearable soft-electronic devices. Herein, an effective hybrid hydrogel-aerogel strategy to assemble ultralight, heat-insulated, and tough polyvinyl alcohol (PVA)/SiO2 @cellulose nanoclaws (CNCWs) hydrogels (PSCG) via strong interfacial interactions with hydrogen bonding and hydrophobic interaction is demonstrated. The resultant PSCG has an interesting hierarchical porous structure from bubble template (≈100 µm), PVA hydrogels networks introduced by ice crystals (≈10 µm), and hybrid SiO2 aerogels (<50 nm), respectively. PSCG shows unprecedented low density (0.27 g cm-3 ), high tensile strength (1.6 MPa) & compressive strength (1.5 MPa), excellent heat-insulated ability, and strain-sensitive conductivity. This lightweight porous and tough hydrogel with an ingenious design provides a new way for wearable soft-electronic devices.
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RESEARCH QUESTION: What are the clinical outcomes and safety implications of early cumulus cell removal after short-term insemination combined with early rescue intracytoplasmic sperm injection (ICSI) in preventing fertilization failure? DESIGN: In this retrospective study, a total of 14,360 cycles were divided into four groups based on insemination method and fertilization ability: conventional IVF group (nâ¯=â¯5519); early cumulus cell removal group (nâ¯=â¯4107); conventional ICSI group (nâ¯=â¯4215); and early rescue ICSI group (where failed or low fertilization was predicted, nâ¯=â¯519). Fertilization outcomes, pregnancy outcomes, neonatal outcomes and birth defects were analysed by comparing the early cumulus cell removal group with the conventional IVF group, and the early rescue ICSI group with the conventional ICSI group. RESULTS: There were no significant differences in the outcomes of fertilization, pregnancy, neonates or birth defects between the conventional IVF group and the early cumulus cell removal group (P > 0.05). When compared with the conventional ICSI group, the early rescue ICSI group had similar rates of two pronuclei (2PN) at fertilization, clinical pregnancy, miscarriage, ectopic pregnancy, live birth, sex, mean gestational age, very low birthweight, macrosomia and birth defects (P > 0.05) but a higher polyploidy rate, lower high-quality embryo rate (both P < 0.001), lower twin pregnancy rate (P < 0.01), lower rate of low birthweight, and a higher rate of normal birthweight (both Pâ¯=â¯0.024). CONCLUSIONS: Early cumulus cell removal combined with early rescue ICSI led to good pregnancy and neonatal outcomes without an increase in birth defects. This approach could therefore be an effective and safe method for patients with fertilization failure in conventional IVF.
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Fertilização in vitro , Injeções de Esperma Intracitoplásmicas , Gravidez , Recém-Nascido , Feminino , Humanos , Masculino , Injeções de Esperma Intracitoplásmicas/métodos , Fertilização in vitro/métodos , Estudos Retrospectivos , Células do Cúmulo , Peso ao Nascer , Sêmen , Taxa de Gravidez , FertilizaçãoRESUMO
Rod-shaped cellulose nanocrystals (CNCs), also called cellulose nanorods (CNRs), possess anisotropic properties that allow for their self-organization into chiral nematic liquid crystals. Interestingly, spherical cellulose nanocrystals (cellulose nanospheres, CNSs) have also been shown to form a chiral liquid-crystalline phase in recent years. Herein, to understand how the similar assembly takes places as particle dimension changes, the organization features of CNSs were investigated. Results of this study demonstrate that above a critical concentration in suspension, CNSs organize into a liquid-crystal phase consisting of periodically parallel-aligned layer structures. This structure persists after suspension drying. In comparison with CNRs, the alignment of CNSs exhibits a shorter layer distance, lower order degree, and weaker long-range orientation. To explain the early stages of tactoid formation, a "caterpillar-like" model was proposed, which was captured by freezing the CNS suspension in an intermediate aggregation state. This structure serves as the fundamental unit for further liquid-crystal assembly.
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Cristais Líquidos , Nanosferas , Nanotubos , Celulose/química , Cristais Líquidos/química , Anisotropia , SuspensõesRESUMO
Graphene aerogels (GAs) possess workable deformation and sensing properties at extreme temperatures. However, their poor tensile properties have restricted their applications in stretchable electronic devices, smart soft robots, and aerospace. Herein, an ultra-stretchable and elastic graphene aerogel with record elongation from -95% to 400% was achieved by constructing a highly crimped and crosslinked graphene network using a microbubble-filled GA precursor by a simple compress-annealing process. This conductive aerogel with near zero Poisson's ratio showed rubber-like but temperature-invariant elasticity from 196.5 °C to 300 °C, and special strain insensitivity from 50% to 400% tensile strain and high sensitivity below 50% tensile strain. Therefore, it can be used as a highly stretchable but strain-insensitive conductor under extreme environments, in which these polymer-based stretchable conductive materials are not workable. Moreover, this work provides new thoughts on constructing inorganic ultra-stretchable materials.
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CD39-mediated inhibition of natural killer (NK) cell activity has been demonstrated, but the characteristics of CD39+ NK cells in humans are not known. We investigated the characteristics of human circulating CD39+ NK cells. In healthy donors, the proportion of circulating CD39+ NK cells in total NK cells was relatively low compared with that of CD39- NK cells. Nonetheless, a higher proportion of CD39+ NK cells expressed CD107a. Similarly, a higher proportion of CD39+ NK cells expressed CD107a in patients with hepatitis B virus or patients with hepatocellular carcinoma. Stimulation with NK-sensitive K562 cells or interleukin (IL)-12/IL-18 activated CD39+ NK cells to express higher levels of CD107a, IFN-γ and TNF-α, relative to CD39- NK cells. Importantly, IL-15 induced the generation of CD39+ NK cells. In contrast, A2A adenosine receptor (A2AR) ligation suppressed the generation of CD39+ NK cells by inhibiting IL-15 signaling. These data for the first time demonstrated that A2AR counteracts IL-15-induced generation of human CD39+ NK cells, which have a stronger cytotoxicity than CD39- NK cells. IL-15-induced human CD39+ NK cells might be better choice for immunotherapy based on adoptive transfer of NK cells.
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Interleucina-15 , Células Matadoras Naturais , Humanos , Citotoxicidade Imunológica , Receptor A2A de Adenosina/metabolismoRESUMO
Severe fever with thrombocytopenia syndrome (SFTS), which is caused by a novel Bunyavirus, has gradually become a threatening infectious disease in rural areas of Asia. Studies have identified a severe cytokine storm and impaired humoral immune response in SFTS. However, the cellular immune response to SFTS virus (SFTSV) infection remains largely unknown. Here we report that SFTS patients had a cytokine storm accompanied by high levels of chemokines. CD8+ T cells in peripheral blood mononuclear cells of SFTS patients exhibited a more activated phenotype and enhanced the antiviral responses. They increased the expression of CD69 and CD25, secreted a higher level of IFN-γ and granzyme, and had a stronger proliferative ability than in healthy controls. In convalescent SFTS patients, the expression of CD69 and CD25 on CD8+ T cells was reduced. In addition, we found the ratio and cellularity of CD14+ CD16+ intermediate monocytes were increased in peripheral blood of SFTS patients. Both the expression of C-X-C motif chemokine ligand 10 (CXCL10) on CD14+ CD16+ intermediate monocytes and the expression of C-X-C motif chemokine receptor 3 (CXCR3) on CD8+ T cells increased dramatically in SFTS patients. Our studies reveal a potential pathway that CD8+ T cells rapidly activate and are mostly recruited by intermediate monocytes through CXCL10 in SFTSV infection. Our results may be of clinical relevance for further treatment and discharge instructions in SFTSV infections.
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Infecções por Bunyaviridae , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Trombocitopenia , Humanos , Febre Grave com Síndrome de Trombocitopenia/tratamento farmacológico , Infecções por Bunyaviridae/tratamento farmacológico , Linfócitos T CD8-Positivos , Leucócitos Mononucleares , Síndrome da Liberação de Citocina , Trombocitopenia/tratamento farmacológico , Antivirais/uso terapêuticoRESUMO
Preeclampsia is one of the leading causes of maternal and fetal morbidity and mortality worldwide. Preeclampsia is linked to mitochondrial dysfunction as a contributing factor in its progression. This study aimed to develop a novel diagnostic model based on mitochondria-related genes(MRGs) for preeclampsia using machine learning and further investigate the association of the MRGs and immune infiltration landscape in preeclampsia. In this research, we analyzed GSE75010 database and screened 552 DE-MRGs between preeclampsia samples and normal samples. Enrichment assays indicated that 552 DE-MRGs were mainly related to energy metabolism pathway and several different diseases. Then, we performed LASSO and SVM-RFE and identified three critical diagnostic genes for preeclampsia, including CPOX, DEGS1 and SH3BP5. In addition, we developed a novel diagnostic model using the above three genes and its diagnostic value was confirmed in GSE44711, GSE75010 datasets and our cohorts. Importantly, the results of RT-PCR confirmed the expressions of CPOX, DEGS1 and SH3BP5 were distinctly increased in preeclampsia samples compared with normal samples. The results of the CIBERSORT algorithm revealed a striking dissimilarity between the immune cells found in preeclampsia samples and those found in normal samples. In addition, we found that the levels of SH3BP5 were closely associated with several immune cells, highlighting its potential involved in immune microenvironment of preeclampsia. Overall, this study has provided a novel diagnostic model and diagnostic genes for preeclampsia while also revealing the association between MRGs and immune infiltration. These findings offer valuable insights for further research and treatment of preeclampsia.