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Although clinical outcomes in chronic lymphocytic leukemia (CLL) have greatly improved with several approved small molecular inhibitors, acquired resistance does occur, leading to disease progression and eventual death. Thus, the effort to explore novel inhibitors and combination therapeutic regimens is needed. The inhibition of MDM2-p53 interaction to restore p53 function has been regarded as a potential strategy for treating different cancers. We investigated the effects of novel MDM2 inhibitor APG-115 in CLL. We found that APG-115 treatment upregulated the expression of p53, MDM2, and p21 at the mRNA and protein level. APG-115 inhibited cell proliferation, induced apoptosis, and arrested the cell cycle at G0/G1 stage. Moreover, APG-115 inhibited the expression of BCL-2, BCL-xL, and MCL-1, and suppressed the activation of AKT and ERK signaling pathways. APG-115 combined with the BCL2 inhibitor, ABT-199 (venetoclax), led to further inhibition of the expression of BCL-2 family anti-apoptotic proteins and consequently enhanced cell death. Collectively, this study demonstrates that APG-115 activates p53 and thus inhibits multiple pro-survival mechanisms, which provides a rational explanation for APG-115 efficiency in inducing cell apoptosis in CLL. The synergistic effect of APG-115 with ABT-199 suggested a potential combination application in CLL therapy.
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OBJECTIVE: The family physician team has become the core carrier for delivery primary health care in China. This study aimed to measure the effect of the network structural characteristics of family physician team processes on health performance. Strategic recommendations for optimizing the family physician team processes with a view to improving performance were presented. METHODS: A cross-sectional survey was conducted from October to December 2021 in Qianjiang in Hubei Province and Changsha in Hunan Province. Task performance, contextual performance, social networks, and sociodemographic characteristics were collected. Social network analysis was conducted to calculate density and centralization, then hierarchical linear regression analysis was employed to explore the relationship between the network structural characteristics of family physician team processes and performance. RESULTS: In total, 88 family physician teams attended in this investigation. The transition processes of family physician team showed a distinctive low density (0.272 ± 0.112), high centralization (0.866 ± 0.197) network structure. For family physician team, the density of action processes significantly and positively affected task performance (B = 0.600, P < 0.05); the centralization of action processes positively affected task performance (B = 0.604, P < 0.01); the density of action processes positively affected contextual performance (B = 0.545, P < 0.01); the density of interpersonal processes significantly and positively affected contextual performance (B = 0.326, P < 0.05). CONCLUSION: The network density and centralization of family physician team processes have positive effects on chronic disease management performance. The results from this study help to enhance our conceptual understanding of social network and its implications for team-dynamics. Optimizing family physician team processes is an effective way to strengthen the construction of family physician team and promote the quality and efficiency of family physician-contracted service. It is recommended to strengthen the management of team processes, enhance the internal collaboration mechanism, and optimize the centralized network structure of family physician team.
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Equipe de Assistência ao Paciente , Médicos de Família , Humanos , Estudos Transversais , Doença Crônica/terapia , Equipe de Assistência ao Paciente/organização & administração , China , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Atenção Primária à Saúde/organização & administração , Gerenciamento ClínicoRESUMO
The C-C motif chemokine receptor 8 (CCR8) is a class A G-protein-coupled receptor that has emerged as a promising therapeutic target in cancer and autoimmune diseases. In the present study, we solved the cryo-electron microscopy (cryo-EM) structure of the human CCR8-Gi complex in the absence of a ligand at 2.58 Å. Structural analysis and comparison revealed that our apo CCR8 structure undergoes some conformational changes and is similar to that in the CCL1-CCR8 complex structure, indicating an active state. In addition, the key residues of CCR8 involved in the recognition of LMD-009, a potent nonpeptide agonist, were investigated by mutating CCR8 and testing the calcium flux induced by LMD-009-CCR8 interaction. Three mutants of CCR8, Y1133.32A, Y1724.64A, and E2867.39A, showed a dramatically decreased ability in mediating calcium mobilization, indicating their key interaction with LMD-009 and key roles in activation. These structural and biochemical analyses enrich molecular insights into the agonism and activation of CCR8 and will facilitate CCR8-targeted therapy.
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Microscopia Crioeletrônica , Receptores CCR8 , Humanos , Receptores CCR8/metabolismo , Receptores CCR8/química , Receptores CCR8/genética , Modelos Moleculares , Conformação Proteica , Cálcio/metabolismo , Células HEK293RESUMO
Porphyromonas gingivalis (Pg), a Gram-negative anaerobic bacterium found in dental plaque biofilm within periodontal pockets, is the primary pathogenic microorganism responsible for chronic periodontitis. Infection by Pg significantly impacts the development and progression of various diseases, underscoring the importance of eliminating this bacterium for effective clinical treatment. While antibiotics are commonly used to combat Pg, the rise of antibiotic resistance poses a challenge to complete eradication. Thus, the prevention of Pg infection is paramount. Research suggests that surface antigens of Pg, such as fimbriae, outer membrane proteins, and gingipains, can potentially be utilized as vaccine antigens to trigger protective immune responses. This article overviews these antigens, discusses advancements in mucosal adjuvants (including immunostimulant adjuvants and vaccine-delivery adjuvants), and their application in Pg vaccine development. Furthermore, the review examines the advantages and disadvantages of different immune pathways and common routes of Pg vaccine immunization. By summarizing the current landscape of Pg vaccines, addressing existing challenges, and highlighting the potential of mucosal vaccines, this review offers new insights for the advancement and clinical implementation of Pg vaccines.
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Hematologic malignancies (HMs), also referred to as hematological or blood cancers, pose significant threats to patients as they impact the blood, bone marrow, and lymphatic system. Despite significant clinical strategies using chemotherapy, radiotherapy, stem cell transplantation, targeted molecular therapy, or immunotherapy, the five-year overall survival of patients with HMs is still low. Fortunately, recent studies demonstrate that the nanodrug delivery system holds the potential to address these challenges and foster effective anti-HMs with precise treatment. In particular, cell membrane camouflaged nanodrug offers enhanced drug targeting, reduced toxicity and side effects, and/or improved immune response to HMs. This review firstly introduces the merits and demerits of clinical strategies in HMs treatment, and then summarizes the types, advantages, and disadvantages of current nanocarriers helping drug delivery in HMs treatment. Furthermore, the types, functions, and mechanisms of cell membrane fragments that help nanodrugs specifically targeted to and accumulate in HM lesions are introduced in detail. Finally, suggestions are given about their clinical translation and future designs on the surface of nanodrugs with multiple functions to improve therapeutic efficiency for cancers.
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HCN channels are important for regulating heart rhythm and nerve activity and have been studied as potential drug targets for treating depression, arrhythmia, nerve pain, and epilepsy. Despite possessing unique pharmacological properties, HCN channels share common characteristics in that they are activated by hyperpolarization and modulated by cAMP and other membrane lipids. However, the mechanisms of how these ligands bind and modulate HCN channels are unclear. In this study, we solved structures of full-length human HCN3 using cryo-EM and captured two different states, including a state without any ligand bound and a state with cAMP bound. Our structures reveal the novel binding sites for cholesteryl hemisuccinate in apo state and show how cholesteryl hemisuccinate and cAMP binding cause conformational changes in different states. These findings explain how these small modulators are sensed in mammals at the molecular level. The results of our study could help to design more potent and specific compounds to influence HCN channel activity and offer new therapeutic possibilities for diseases that lack effective treatment.
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Microscopia Crioeletrônica , AMP Cíclico , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização , Humanos , Sítios de Ligação , AMP Cíclico/metabolismo , Células HEK293 , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/metabolismo , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/química , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Conformação ProteicaRESUMO
Electrophilic ring-expansion of polycyclic arylthiiranes and ketenes generated from alkoxy/aryloxyacetyl chlorides in the presence of triethylamine (TEA) is developed and provides a new strategy for the synthesis of areno[d]-ε-thiolactones, areno[d]thiepinones, directly without catalysts or additives. This strategy features atom- and step-economic one-pot characteristic via a tandem sequence of in situ ketene generation, π-stacking-controlled dearomatic sulfur-shifted ene, and aromatization. The current reaction is a novel strategy of electrophilic ring expansions of three-membered saturated heterocycles.
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Interferon (IFN)-λ1, a member of type III IFN, possesses unique antiviral, anti-tumor, and immune modulation properties. IFN-λ alone or combined with other drugs is considered an essential therapeutic regimen in the clinic. Obtaining high-quality, biologically-active recombinant human IFN-λ1 (rhIFN-λ1) is of great practical significance. In this study, pCold-II-IFN-λ1 expression plasmid was correctly constructed, the rhIFN-λ1 was expressed in BL21(DE3) E.coli and reached the highest level under the optimal condition of 15 °C culture temperature and at 1 µg/L IPTG induction for 12 h. The soluble rhIFN-λ1 was purified by Ni-NTA affinity chromatography. The purified rhIFN-λ1 can effectively activate the JAK1-STAT1 signaling pathway and induce the expression of a large number of interferon-stimulated genes (ISG) including ISG15, ISG54, ISG56, TRAIL, OAS1, MX1, IRF7 and IRF9. In addition, rhIFN-λ1 can effectively inhibit the growth/proliferation of cervical cancer HeLa cells in a dose-dependent pattern. Collectively, the soluble rhIFN-λ1 was successfully expressed in BL21(DE3) E.coli with the cold-shock system, and the purified rhIFN-λ1 demonstrated excellent biological activity. This study lays a solid basis for acquiring high-quality rhIFN-λ1 and its clinical application.
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Escherichia coli , Interferons , Humanos , Células HeLa , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacologia , Interferons/genética , Plasmídeos/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Interleucinas/genéticaRESUMO
The special structure of perovskite-like compounds allows the existence of some open spaces in the crystals that play an important role in their crystal function enhancement and can accommodate active oxygen, which helps to solve some problems in the field of corrosion prevention. The magnetic lanthanum cuprate was obtained through the doping of Co2+ and Sr2+, and compared with La2CuO4 and epoxy resin, its corrosion resistance was improved by 215.2 and 566.7%, respectively. The micromagnetic field in the crystal interfered with the state of motion of the electrons and prolonged their transport path. High concentration doping and substitution of unequal states led to the formation of oxygen vacancy defects, which could trap active oxygen molecules and inhibit cathodic corrosion reactions. The unique alternating interlayer structure of perovskite-like compounds was conducive to the release of Cu2+, thus forming a more stable passivator on the surface of the coating. La1.96Sr0.04Cu0.98Co0.02O4 had both magnetic properties and structural advantages, which enhanced the shielding property of epoxy resin and expanded the application of perovskite-like compounds in the field of corrosion prevention.
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When detecting epikarst water using the self-potential method, the actual location of the anomaly center often deviates from the prospecting result due to the interference of the regional background field, which is comprised of geological noise and artificial electromagnetic fields. Ultimately, this makes it difficult to locate the detection target accurately. To address the potential offset of the anomaly center location, in this study we introduce the differential filtering method into the data processing procedure. This method has smoothing and low-pass filtering effects, facilitating the extraction of meaningful anomalies. Meanwhile, based on the anomalous features of different physical parameters, we propose an integrated method system based on differentially filtered horizontal self-potential gradient data, the composite profile method, and the high-density electrical method, which can effectively improve the accuracy of anomaly localization. This newly established method system was applied at the Xiaguantun test site in Longzhou County, Chongzuo, Guangxi Province, China, and its effectiveness and feasibility was confirmed.
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Long-time-series, high-resolution datasets of the column-averaged dry-air mole fraction of carbon dioxide (XCO2) have great practical importance for mitigating the greenhouse effect, assessing carbon emissions and implementing a low-carbon cycle. However, the mainstream XCO2 datasets obtained from satellite observations have coarse spatial resolutions and are inadequate for supporting research applications with different precision requirements. Here, we developed a new spatial machine learning model by fusing spatial information with CatBoost, called SCatBoost, to fill the above gap based on existing global land-mapped 1° XCO2 data (GLM-XCO2). The 1-km-spatial-resolution dataset containing XCO2 values in China from 2012 to 2019 reconstructed by SCatBoost has stronger and more stable predictive power (confirmed with a cross-validation (R2 = 0.88 and RSME = 0.20 ppm)) than other traditional models. According to the estimated dataset, the overall national XCO2 showed an increasing trend, with the annual mean concentration rising from 392.65 ppm to 410.36 ppm. In addition, the spatial distribution of XCO2 concentrations in China reflects significantly higher concentrations in the eastern coastal areas than in the western inland areas. The contributions of this study can be summarized as follows: (1) It proposes SCatBoost, integrating the advantages of machine learning methods and spatial characteristics with a high prediction accuracy; (2) It presents a dataset of fine-scale and high resolution XCO2 over China from 2012 to 2019 by the model of SCatBoost; (3) Based on the generated data, we identify the spatiotemporal trends of XCO2 in the scale of nation and city agglomeration. These long-term and high resolution XCO2 data help understand the spatiotemporal variations in XCO2, thereby improving policy decisions and planning about carbon reduction.
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Monitoramento Ambiental , Monitoramento Ambiental/métodos , ChinaRESUMO
The electrophilic addition of hydrogen halides to alkynes, also called polar hydrohalogenation of alkynes, is one of the most classical and important organic reactions. Mechanistic and stereoselective insights into the hydrohalogenation of various structurally different distinct alkynes, including both alkyl and aryl substituted acetylenes, in acetic acid were investigated theoretically via density functional theory (DFT) calculations. The results indicate that π-complexes between hydrogen halides and alkynes are first formed, and then all alkynes can undergo a competitive bimolecular intimate ion-pair syn-addition process and a pentamolecular concerted anti-addition process through the cyclic proton transfer mechanism for proton transfer in the absence of tetraalkylammonium halides or a termolecular electrophilic addition (AdE3) process in the presence of tetraalkylammonium halides. All aliphatic alkynes undergo slightly to obviously predominant anti-addition in hydrohalogenations both in the absence and presence of tetraalkylammonium halides. Aromatic 1-arylalk-1-ynes favour syn-additions through bimolecular intimate ion-pair processes with asynchronous concerted characteristics in the absence of tetraalkylammonium halides, while most of them generally prefer anti-addition in the presence of tetraalkylammonium halides. The stereoselectivity is significantly affected by both the electronic and steric effects of 1-arylalk-1-ynes and halides in the reaction mixture. Strongly electron-rich and bulky 1-arylalk-1-ynes generally favour syn-addition in the presence of tetraalkylammonium halides, especially arylethynes in hydrochlorination. Anti-Markovnikov hydrohalogenations of 1-arylalk-1-ynes also prefer anti-addition both in the absence and presence of tetraalkylammonium halides even in small amounts due to high activation energies. The current investigation provides deep insights into the mechanism and stereoselectivity in polar hydrohalogenations of alkynes.
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The settlement in permafrost regions has a significant effect on the safety of the aircraft. Therefore, a numerical model of asphalt concrete pavement and subgrade in permafrost regions is proposed and verified by comparing with previous studies. Numerical models under the dynamic load of aircraft are used to analyze the settlement nephogram, time-dependent curve, and settlement curve. Results show that the influences of different parameters on settlements decrease slowly at the depth of 0-1.45m, then decrease quickly at the depth of 1.45-2m, finally tend to be stable. The peaks of settlements increase with the growth of international roughness index, taxiing speed, and aircraft's weight. The settlement increases little when the international roughness index is more than 3. The settlement varies significantly when the taxiing speed is from 30m/s to 70m/s. The study provides a theoretical basis for the construction and maintenance of asphalt concrete pavement and subgrade in permafrost.
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Pergelissolo , Aeronaves , Automóveis , HidrocarbonetosRESUMO
Continental deep subduction after the closure of large oceanic basins is commonly ascribed to the gravitational pull of the subducting oceanic slab. However, it is not clear how continental lithosphere adjacent to small oceanic basins was subducted to mantle depths. The Sesia Zone in the Western Alps provides an excellent target for exploration of subduction dynamics in such a tectonic setting. Here we report the first finding of coesite in a jadeite-bearing orthogneiss from the Sesia Zone, providing the first evidence for deep subduction of the continental crust to mantle depths for ultrahigh-pressure (UHP) metamorphism in this zone. Three coesite inclusions were identified by laser Raman spectroscopy in two garnet grains. Based on zircon U-Pb dating and trace element analysis, the UHP metamorphic age was constrained to be 76.0 ± 1.0 Ma. The phase equilibrium modeling yields peak metamorphic pressures of 2.8-3.3 GPa, demonstrating the continental deep subduction to mantle depths of >80 km. The subducted continental crust was a rifted hyperextended continental margin, which was converted to the passive continental margin during seafloor spreading and then deeply subducted during the oblique convergence between the Adria microplate and Eurasian plate in the Late Cretaceous. Because the slab pull could only play a limited role in closing small oceanic basins for continental collision, the distal push of either continental breakup or seafloor spreading is suggested as the major driving force for the deep subduction of continental crust in the Western Alps. Therefore, deep subduction of the continental crust bordering small oceanic basins would have been induced by the far-field stress of compression, whereas that bordering large oceanic basins was spontaneous due to the oceanic slab pull. This provides a new insight into the geodynamic mechanism of continental deep subduction.
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BACKGROUND: It is known that the microenvironmental cytokine interferon gamma (IFN-γ) provides a survival advantage for chronic lymphocytic leukemia (CLL) cells. However, the mechanisms involved in this effect have not been properly investigated. METHODS: Herein, we conducted a comprehensive screening of the effects of IFN-γ on signaling pathways and gene expression profiles in CLL cells by using western blotting, real-time quantitative reverse transcription (RT-qPCR) and high-throughput RNA sequencing (RNA-seq). RESULTS: We found that IFN-γ not only activated the pro-survival signal transducer and activator of transcription 3 (STAT3), but also activated the protein kinase B and extracellular signal-regulated kinase signaling pathways. RNA-seq analysis showed that IFN-γ stimulation changed the expression profiles of more than 500 genes, with 391 being up-regulated and 123 down-regulated. These genes are involved in numerous biological processes, including anti-apoptosis, cell migration, and proliferation. IFN-γ significantly up-regulated the expression of CD38, BCL6, CXCL9, BCL2A1, SCOS3, IL-10, HGF, EGFR, THBS-1, FN1, and MUC1, which encode proteins potentially associated with disease progression, worse prognosis or poor response to treatment. Blocking janus kinases1/2 (JAK1/2) or STAT3 signal by specific inhibitors affected the expression of most genes, suggesting a pivotal role of the JAK1/2-STAT3 pathway in IFN-γ pro-survival effects in CLL. CONCLUSIONS: Our data demonstrate that IFN-γ regulates a complex pro-survival signal network in CLL through JAK1/2-STAT3, which provides a rational explanation for IFN-γ promoting CLL cells survival and drug resistance.
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Interferon gama , Leucemia Linfocítica Crônica de Células B , Humanos , Citocinas/metabolismo , Interferon gama/imunologia , Leucemia Linfocítica Crônica de Células B/metabolismo , Transdução de Sinais , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/farmacologiaRESUMO
Although clinical outcomes of CLL have improved with the use of BCL-2 inhibitor, ABT-199, acquired resistance eventually occurs in many cases, which leads to CLL disease progression. Thus, understanding the mechanisms that mediate this relapse is important to design improved therapies. Herein, we report that cytokine IFN-γ, secreted by dysfunctional T cells, enhanced CLL cells resistance to ABT-199. IFN-γ stimulation significantly increased the expression of BCL-2, MCL-1 and BCL-xL. Blocking JAK1/2-STAT3 signaling pathway impaired the expression of these anti-apoptotic proteins after IFN-γ stimulation. The combination of ABT-199 with JAK1/2 inhibitor Ruxolitinib or STAT3 inhibitors Stattic and C188-9 increased malignant B cell death. In summary, we show that IFN-γ enhanced CLL cells resistance to ABT-199 at least in part by up-regulating BCL-2, MCL-1 and BCL-xL expression via JAK1/2-STAT3 pathway, and thus blocking this pathway with inhibitors increased ABT-199 efficiency to induce CLL cell apoptosis, suggesting a potential therapeutically relevant combination to overcome ABT-199 resistance.
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Leucemia Linfocítica Crônica de Células B , Humanos , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/genética , Resistencia a Medicamentos Antineoplásicos , Linhagem Celular Tumoral , Recidiva Local de Neoplasia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais , Interferon gama/farmacologia , Interferon gama/metabolismo , Apoptose , Nitrofenóis/farmacologia , Compostos de Bifenilo/farmacologia , Fator de Transcrição STAT3/metabolismoRESUMO
Poly(rC)-binding proteins (PCBPs), a defined subfamily of RNA binding proteins, are characterized by their high affinity and sequence-specific interaction with poly-cytosine (poly-C). The PCBP family comprises five members, including hnRNP K and PCBP1-4. These proteins share a relatively similar structure motif, with triple hnRNP K homology (KH) domains responsible for recognizing and combining C-rich regions of mRNA and single- and double-stranded DNA. Numerous studies have indicated that PCBPs play a prominent role in hematopoietic cell growth, differentiation, and tumorigenesis at multiple levels of regulation. Herein, we summarized the currently available literature regarding the structural and functional divergence of various PCBP family members. Furthermore, we focused on their roles in normal hematopoiesis, particularly in erythropoiesis. More importantly, we also discussed and highlighted their involvement in carcinogenesis, including leukemia and lymphoma, aiming to clarify the pleiotropic roles and molecular mechanisms in the hematopoietic compartment.
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Micropatterning various ion-based modality materials offers compelling advantages for functionality enhancement in iontronic pressure sensing, piezoionic mechanoreception, and skin-interfaced electrode adhesion. However, most existing patterning techniques for iontronic materials suffer from low flexibility and limited modulation capability. Herein, we propose a facile and robust method to fabricate hierarchical and asymmetrical iontronic micropatterns (denoted as HAIMs) through programmed regulation of the internal stress distribution and the local ionic migration among an iontronic host. The resultant HAIMs with arbitrarily regulated morphologies and region-dependent ionic electrical performance can be readily made via localized photodimerization of an anthracene-functionalized ionic liquid copolymer (denoted as An-PIL) and subsequent vapor oxidative polymerization of 3,4-ethylenedioxythiophene (EDOT). Based on the piezoionic effect within the resultant distinct doped PEDOT, HAIMs can serve as a scalable iontronic potential generator. Successful syntheses of these fascinating micropatterns may accelerate the development of patterned iontronic materials in a flexible, programmable, and functionally adaptive form.
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Líquidos Iônicos , Polímeros , PolimerizaçãoRESUMO
Background: Imbalance of oral salivary microbiota has been linked to the pathogenesis of a variety of systemic diseases, and oral bacterial species have been shown to be useful biomarkers for systemic diseases.This study aimed to characterize the alterations of oral microbiota in patients with esophageal squamous cell carcinoma (ESCC) and to evaluate the diagnostic performance of oral microbial biomarkers for ESCC. Methods: The relative abundance of flora in saliva samples was analyzed by 16S rDNA sequencing, and differences in the species present in samples from ESCC patients and healthy controls (HCs) were identified by analyzing species diversity and performing LEfSe analysis. Receiver operating characteristic (ROC) curve analysis was applied to evaluate the diagnostic performance of the characteristic bacteria individually and in combination. Results: Differences in bacterial diversity indexes were observed for the saliva of ESCC patients versus HCs (P<0.05), but principal coordinate analysis did not detect a significant difference in the composition of oral microbiota between ESCC patients and HCs (P>0.05). LEfSe analysis showed that Leptotrichia, Porphyromonas (Pg), Streptococcus, Rothia, Lactobacillus and Peptostreptococcus were more abundant in ESCC patient saliva than in HC saliva, whereas Haemophilus, Alloprevotella (All), Prevotella_7, Prevotella (Pre), Prevotella_6, Pasteurellaceae and Pasteurellales were significantly less abundant in ESCC patient saliva (P<0.05). From ROC curve analysis, Pg could detect ESCC with an area under the ROC curve (AUC) of 0.599, sensitivity of 62.2%, and specificity of 70%, whereas the ratio of Pg/Pre had an AUC of 0.791, sensitivity of 93.3%, and specificity of 62.3%. Moreover, the combination of the Pg/Pre and Pg/All ratios showed further improved diagnostic performance for ESCC (AUC=0.826) and even good sensitivity and specificity for the diagnosis of early ESCC (68.2% and 86%, respectively; AUC=0.786). Conclusion: This study shows that Pg in saliva can be used as a characteristic marker of ESCC, and the ratios of Pg/Pre and Pg/All offered significantly improved diagnostic performance, especially for early ESCC.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patologia , Porphyromonas gingivalis/genética , Saliva/microbiologia , Prevotella , Carcinoma de Células Escamosas/diagnóstico , BiomarcadoresRESUMO
Conductive hydrogels have been extensively studied because of flexibility and skin-like capability to be used as biopotential electrodes for wearable health monitoring. However, they may suffer from poor mechanical properties and stability problems when used in practical applications caused by water evaporation. Herein, we prepared self-adhesive, transparent, flexible and robust ionic gels that can conformal contact with the skin used as biopotential electrodes for precise health monitoring. Cellulose based iogels were prepared by dissolving cellulose using [Bmim]Cl at 100 °C followed by in situ Ultraviolet light photopolymerization of acrylic acid by adding a mixture of acrylic acid and 2-hydroxy-2-methylpropiophenone. Cellulose/polyacrylic acid-based ionic gels-2 (BCELIG-2) has a Young's modulus of 0.2 MPa, a strain at break of 226 %, a modulus of elasticity of 0.1 MPa, and a toughness of 22.5 MJ m-3. Fixing the strain at 40 %, the ionic gels can recover to their original length after ten tensile-unloading cycles. They can accurately detect subtle physical motions such as arterial pulsations, which can provide important cardiovascular information.