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Soft tissue integration around titanium (Ti) implants is weaker than that around natural teeth, compromising long-term success of Ti implants. Carbon monoxide (CO) possesses distinctive therapeutic properties, rendering it as a highly promising candidate for enhancing STI. However, achieving controlled CO generation at the STI interface remains challenging. Herein, a controlled CO-releasing dual-function coating was constructed on Ti surfaces. Under near-infrared (NIR) irradiation, the designed surface could actively accelerate CO generation for antibiosis against both aerobic and anaerobic bacteria. More importantly, in the absence of NIR, the slow release of CO induces macrophage polarization from pro-inflammatory phenotype towards pro-regenerative phenotype. In a rat implantation model with induced infection, the designed surface effectively controlled the bacterial infection, alleviates accompanying inflammation and modulated immune microenvironment, leading to enhanced STI. Single-cell sequencing revealed that the coating alters the cytokine profile within the soft tissue, thereby influencing cellular functions. Differentially expressed genes in macrophages are highly enriched in the PIK3-Akt pathway. Furthermore, the cellular communication between fibroblasts and macrophages was significantly enhanced through the CXCL12/CXCL14/CXCR4 and CSF1-CSF1R ligand-receptor pair. These findings indicate that our coating showed an appealing prospect for enhancing STI around Ti implants, which would ultimately contribute to the improved long-term success of Ti implants.
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Tuning the oxygen activity in perovskite oxides (ABO3) is promising to surmount the trade-off between activity and selectivity in redox reactions. However, this remains challenging due to the limited understanding in its activation mechanism. Herein, we propose the discovery that generating subsurface A-site cation (Lasub.) vacancy beneath surface Fe-O layer greatly improved the oxygen activity in LaFeO3, rendering enhanced methane conversion that is 2.9-fold higher than stoichiometric LaFeO3 while maintaining high syngas selectivity of 98% in anaerobic oxidation. Experimental and theoretical studies reveal that absence of Lasub.-O interaction lowered the electron density over oxygen and improved the oxygen mobility, which reduced the barrier for C-H bond cleavage and promoted the oxidation of C-atom, substantially boosting methane-to-syngas conversion. This discovery highlights the importance of A-site cations in modulating electronic state of oxygen, which is fundamentally different from the traditional scheme that mainly credits the redox activity to B-site cations and can pave a new avenue for designing prospective redox catalysts.
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Aseptic loosening and bacterial infection pose significant challenges in the clinical application of titanium (Ti) orthopedic implants, which are primarily caused by insufficient osseointegration and bacterial contamination. To address these issues, a responsive coating on Ti surface is constructed, which achieves enhanced osseointegration and infection elimination by on-demand release of therapeutic gas hydrogen sulfide (H2S) and antibiotic. TiO2 nanotubes (TNT) are anodized on the Ti surface to enhance its bioactivity and serve as reservoirs for the antibiotic. An infection microenvironment-responsive macromolecular H2S donor layer is coated on top of TNT to inhibit premature leakage of antibiotic. This layer exhibits a sustained release of low-dosage H2S, which is capable of promoting the osteogenic differentiation and migration of cells. Moreover, the compactness of the macromolecular H2S donor layer could be broken by bacterial invasion, leading to rapid antibiotic release thus preventing infection. In vitro antibacterial experiments validates significant antibacterial activity of the coating against both Gram-negative (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus). Crucially, this coating effectively suppresses implant-associated infection with 98.7% antibacterial efficiency in a rat femoral bone defect model, mitigates inflammation at the defect site and promotes osseointegration of the Ti orthopedic implant.
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Antibacterianos , Materiales Biocompatibles Revestidos , Escherichia coli , Sulfuro de Hidrógeno , Staphylococcus aureus , Titanio , Titanio/química , Titanio/farmacología , Animales , Antibacterianos/farmacología , Antibacterianos/química , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Staphylococcus aureus/efectos de los fármacos , Ratas , Escherichia coli/efectos de los fármacos , Sulfuro de Hidrógeno/química , Sulfuro de Hidrógeno/farmacología , Oseointegración/efectos de los fármacos , Nanotubos/química , Ratas Sprague-Dawley , Propiedades de Superficie , Prótesis e Implantes , Osteogénesis/efectos de los fármacos , HumanosRESUMEN
Chitin and chitosan-based bioink for 3D-printed flexible electronics have tremendous potential for innovation in healthcare, agriculture, the environment, and industry. This biomaterial is suitable for 3D printing because it is highly stretchable, super-flexible, affordable, ultrathin, and lightweight. Owing to its ease of use, on-demand manufacturing, accurate and regulated deposition, and versatility with flexible and soft functional materials, 3D printing has revolutionized free-form construction and end-user customization. This study examined the potential of employing chitin and chitosan-based bioinks to build 3D-printed flexible electronic devices and optimize bioink formulation, printing parameters, and postprocessing processes to improve mechanical and electrical properties. The exploration of 3D-printed chitin and chitosan-based flexible bioelectronics will open new avenues for new flexible materials for numerous industrial applications.
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Performing efficient wound management is essential for infected diabetic wounds due to the complex pathology. Flexible electronics have been recognized as one of the promising solutions for wound management. Herein, a kind of skin-adhesive and self-healing flexible bioelectronic was developed, which could be employed as a diagnostic wound dressing to record diabetic wound healing and monitor electrophysiological signals of the patients. The flexible substrate of diagnostic wound dressings showed excellent tissue adhesive (to various substrates including biological samples), self-healing (fracture strength restores by 96%), and intrinsic antibacterial properties (antibacterial ratio >96% against multidrug-resistant bacteria). The diagnostic wound dressings could record the glucose level (1-30 mM), pH values (4-7), and body temperature (18.8-40.0 °C) around the infected diabetic wounds. Besides, the dressings could help optimize treatment strategies based on electrophysiological signals of patients monitored in real-time. This study contributes to developing flexible bioelectronics for the diagnosis and management of diabetic wounds.
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Vendajes , Cicatrización de Heridas , Humanos , Adhesivos Tisulares , Antibacterianos/uso terapéutico , Fenómenos Electrofisiológicos/fisiología , Diabetes Mellitus/terapia , AnimalesRESUMEN
Hepatocellular carcinoma (HCC) is a challenging disease to evaluate in terms of prognosis, requiring close attention to the prognosis of HCC patients. Exosomes have been shown to play an important role in HCC development and have significant potential in managing HCC patient prognosis, as they are detectable in patients' blood. By using small extracellular vesicular RNA, liquid biopsies can reflect the underlying physiological and pathological status of the originating cells, providing a valuable assessment of human health. No study has explored the diagnostic value of mRNA expression changes in exosomes for liver cancer. The present study investigated establishing a risk prognosis model based on mRNA expression levels in exosomes from blood samples of liver cancer patients and evaluated its diagnostic and prognostic value, providing new targets for liver cancer detection. We obtained mRNA data from HCC patients and normal controls from the TCGA and exoRBase 2.0 databases and established a risk prognostic assessment model using exosomes-related risk genes selected through prognostic analysis and Lasso Cox analysis. The patients were divided into high-risk and low-risk groups based on median risk score values to validate the independence and evaluability of the risk score. The clinical value of the model was further analyzed using a nomograph model, and the efficacy of immunotherapy and cell-origin types of prognostic risk genes were further assessed in the high- and low-risk groups by immune checkpoint and single-cell sequencing. A total of 44 genes were found to be significantly associated with the prognosis of HCC patients. From this group, we selected six genes (CLEC3B, CYP2C9, GNA14, NQO1, NT5DC2, and S100A9) as exosomal risk genes and used them as a basis for the risk prognosis model. The clinical information of HCC patients from the TCGA and ICGC databases demonstrated that the risk prognostic score of the model established in this study was an independent prognostic factor with good robustness. When pathological stage and risk prognostic score were incorporated into the model to predict clinical outcomes, the nomograph model had the best clinical benefit. Furthermore, immune checkpoint assays and single-cell sequencing analysis suggested that exosomal risk genes were derived from different cell types and that immunotherapy in the high-risk groups could be beneficial. Our study demonstrated that the prognostic scoring model based on exosomal mRNA was highly effective. The six genes selected using the scoring model have been previously reported to be associated with the occurrence and development of liver cancer. However, this study is the first to confirm that these related genes existed in the blood exosomes, which could be used for liquid biopsy of patients with liver cancer, thereby avoiding the need for puncture diagnosis. This approach has a high value in clinical application. Through single-cell sequencing, we found that the six genes in the risk model originate from multiple cell types. This finding suggests that the exosomal characteristic molecules secreted by different types of cells in the microenvironment of liver cancer may serve as diagnostic markers.
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Immunotherapy, including ICIs, has emerged as an invaluable treatment option for advanced PLC. Nevertheless, the expression patterns of PD-L1 and PD-1 in PLC remain incompletely understood. In this study, the expression pattern and clinical correlation of PD-L1 and PD-1 were analysed in 5245 PLC patients. The positivity rates of PD-L1 and PD-1 were very low in the patient PLCs, but the positivity rates of PD-L1 and PD-1 were higher in the ICC and cHCC-ICC than in HCC. The expression of PD-L1 and PD-1 correlated with the malignant phenotypes and clinicopathological characteristics of PLC. Interestingly, PD-1 positivity might serve as an independent prognostic factor. Based on a systematic analysis of a large amount of PLC tissues, we proposed a novel classification of PD-1/PD-L1 expression in HCC and ICC. In light of this stratification, we observed a close correlation between PD-L1 levels and PD-1 expression in HCC and ICC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Receptor de Muerte Celular Programada 1 , Antígeno B7-H1 , InmunoterapiaRESUMEN
Brain-computer interface (BCI) has been the subject of extensive research recently. Governments and companies have substantially invested in relevant research and applications. The restoration of communication and motor function, the treatment of psychological disorders, gaming, and other daily and therapeutic applications all benefit from BCI. The electrodes hold the key to the essential, fundamental BCI precondition of electrical brain activity detection and delivery. However, the traditional rigid electrodes are limited due to their mismatch in Young's modulus, potential damages to the human body, and a decline in signal quality with time. These factors make the development of flexible electrodes vital and urgent. Flexible electrodes made of soft materials have grown in popularity in recent years as an alternative to conventional rigid electrodes because they offer greater conformance, the potential for higher signal-to-noise ratio (SNR) signals, and a wider range of applications. Therefore, the latest classifications and future developmental directions of fabricating these flexible electrodes are explored in this paper to further encourage the speedy advent of flexible electrodes for BCI. In summary, the perspectives and future outlook for this developing discipline are provided.
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Interfaces Cerebro-Computador , Humanos , Electroencefalografía , Electrodos , EncéfaloRESUMEN
Soft-tissue integration (STI) plays an essential role in the long-term success of percutaneous Ti implants since it acts as a biological barrier that protects the soft and hard tissue around implants. Surface modification of Ti implants with drug-release properties to achieve soft-tissue regeneration has been proven to be effective in STI. However, the short-acting effect caused by the uncontrolled drug release of the topical delivery system limits long-term STI enhancement. Herein, a long-acting protein delivery system for Ti implants that involved micro-arc oxidation of Ti surfaces (MAO-Ti) and localized immobilization of cellular communication network factor 2 (CCN2) bearing mesoporous silica nanoparticles (MSNs) on MAO-Ti was prepared, namely, CCN2@MSNs-Ti. The CCN2 release study of CCN2@MSNs-Ti demonstrated a sustained-release profile for 21 days, which was able to maintain long-term stable STI. In addition, in vitro cell behavior evaluation results indicated that CCN2@MSNs-Ti could promote the STI-related biological response of human dermal fibroblasts via the FAK-MAPK pathway. More importantly, the system could effectively enhance STI after 4 weeks and proinflammatory factors in the soft tissue decreased significantly in a rat model of implantation. These results denote that CCN2@MSNs-Ti showed an appealing application prospect for enhanced STI around transcutaneous Ti implants, which would ultimately result in an increased success rate of percutaneous Ti implants.
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Prótesis e Implantes , Titanio , Ratas , Humanos , Animales , Titanio/farmacología , Oxidación-Reducción , Propiedades de SuperficieRESUMEN
Due to protection of extracellular polymeric substances, the therapeutic efficiency of conventional antimicrobial agents is often impeded by their poor infiltration and accumulation in biofilm. Herein, one type of surface charge adaptable nitric oxide (NO) nanogenerator was developed for biofilm permeation, retention and eradication. This nanogenerator (PDG@Au-NO/PBAM) is composed of a core-shell structure: thermo-sensitive NO donor conjugated AuNPs on cationic poly(dopamine-co-glucosamine) nanoparticle (PDG@Au-NO) served as core, and anionic phenylboronic acid-acryloylmorpholine (PBAM) copolymer was employed as a shell. The NO nanogenerator featured long circulation and good biocompatibility. Once the nanogenerator reached acidic biofilm, its surface charge would be switched to positive after shell dissociation and cationic core exposure, which was conducive for the nanogenerator to infiltrate and accumulate in the depth of biofilm. In addition, the nanogenerator could sustainably generate NO to disturb the integrity of biofilm at physiological temperature, then generate hyperthermia and explosive NO release upon NIR irradiation to efficiently eradicate drug-resistant bacteria biofilm. Such rational design offers a promising approach for developing nanosystems against biofilm-associated infections.
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Biofilm-associated infections (BAI) have posed serious threats to public health. Novel therapy based on carbon monoxide (CO) is being increasingly appreciated. However, CO therapy like inhaled gas treatment was impeded owing to its low bioavailability. Besides, the direct use of CO releasing molecules (CORM) showed low therapeutic efficacy in BAI. Therefore, it is vital to improve the efficiency of CO therapy. Herein, we proposed polymeric CO releasing micelles (pCORM) from self-assembly of amphiphilic copolymers containing CORM bearing block as hydrophobic part and acryloylmorpholine block as hydrophilic part. The catechol modified CORM were conjugated through pH cleavable boronate ester bonds and releasing CO passively under biofilm microenvironment. When combined with subminimal inhibitory concentration antibiotic amikacin, pCORM could significantly enhance its bactericidal efficiency against biofilm-encapsulated multidrug-resistant bacteria, representing a promising approach to combat BAI.
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Amicacina , Micelas , Polímeros/química , Antibacterianos/farmacología , Biopelículas , Portadores de Fármacos/químicaRESUMEN
Gastric cancer (GC) has been identified as the third deadly cancer in the world. Accumulating researches suggest a potential role of microorganisms in tumorigenesis. However, the composition of microbiota in GC tissues is not clear and it changes throughout the different stages of GC remain mostly elusive. Our study integrated RNA-Seq data of 727 samples derived from gastric tissues across four datasets and revealed its microbial composition. In order to remove the false positive results, core taxa were defined and characterized. Based on it, we analyzed the influence of biological factors on its composition. The pan-microbiome of gastric tissues was estimated to be over than 1400 genera. Seventeen core genera were identified. Among them, Helicobacter, Lysobacter were significantly enriched in normal tissues, while Pseudomonas was enriched in tumor tissues. Interestingly, Acinetobacter, Pasteurella, Streptomyces, Chlamydia, and Lysobacter, showed a significant increase trend during tumor development and formed strong intra/inter-correlations among them or with other genera. Furthermore, we found that tumor stage played an important role in altering the microbial composition of GC tissues. This study provides support for the in-depth study of tumor microbiome, and the specific microbiome excavated provides a possibility for the subsequent identification of potential biomarkers for GC.
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Microbioma Gastrointestinal , Microbiota , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Carcinogénesis , ARN Ribosómico 16SRESUMEN
Introduction: RNA editing, a wide-acknowledged post-transcriptional mechanism, has been reported to be involved in the occurrence and development of cancer, especially the abnormal alteration of adenosine to inosine. However, fewer studies focus on pancreaticcancer. Therefore, we aimed to explore the possible linkages between altered RNA editing events and the development of PDAC. Method: We characterized the global A-to-I RNA editing spectrum from RNA and matched whole-genome sequencing data of 41 primary PDAC and adjacent normal tissues. The following analyses were performed: different editing level and RNA expression analysis,pathway analysis, motif analysis, RNA secondary structure analysis, alternative splicing events analysis, and survival analysis.The RNA editing of single-cell RNA public sequencing data was also characterized. Result: A large number of adaptive RNA editing events with significant differences in editing levels were identified, which are mainly regulated by ADAR1. Moreover, RNA editing in tumors has a higher editing level and more abundant editing sites in general. 140genes were screened out since they were identified with significantly different RNA editing events and were significantly different in expression level between tumor and matched normal samples. Further analysis showed a preference that in the tumor-specific group, they are mainly enriched in cancer-related signal pathways, while in the normal tissue-specific group, they are mainly enriched in pancreatic secretion. At the same time, we also found positively selected differentially edited sites in a series of cancer immune genes, including EGF, IGF1R, and PIK3CD. RNA editing might participate in pathogenisis of PDAC through regulating the alternative splicing and RNA secondary structure of important genesto further regulate gene expression and protein synthesis, including RAB27B and CERS4. Furthermore, single cell sequencing results showed that type2 ductal cells contributed the most to RNA editing events in tumors. Conclusion: RNA editing is an epigenetic mechanism involved in the occurrence and development of pancreatic cancer, which has the potential to diagnose of PDAC and is closely related to the prognosis.
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Current treatments for infections caused by multidrug-resistant bacteria still remain challenging and therapeutic materials with high efficacy are of demand. Herein, a bactericidal nanocomposite was constructed by loading Roxarsone (ROX) onto nitrosylated mesoporous polydopamine (named mPDA@NO-ROX). The designed nanocomposite exhibited considerable photothermal effect and controlled NO and ROX co-delivery under the irradiation of near-infrared laser (NIR) to achieve enhanced chemo-photothermal antibacterial therapy. The inâ vitro antibacterial evaluation of the mPDA@NO-ROX demonstrated the effective elimination of the Gram-negative tetracycline-resistant Escherichia coil and Gram-positive methicillin-resistant Staphylococcus aureus under mild NIR irradiation compared to merely ROX loaded unmodified mPDA, indicating the NO enhanced chemo-photothermal therapy. In addition, the cytotoxicity experiments indicated that mPDA@NO-ROX exhibited only 5 % of hemolysis rate and high cell viability at 1â mg mL-1 against mammalian fibroblasts, suggesting the excellent biocompatibility. In conclusion, the mPDA@NO-ROX could be a promising candidate for anti-infection therapy of multidrug-resistant bacteria.
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Infecciones Bacterianas , Staphylococcus aureus Resistente a Meticilina , Nanocompuestos , Nanopartículas , Roxarsona , Animales , Terapia Fototérmica , Nitritos , Antibacterianos/farmacología , MamíferosRESUMEN
The inheritance of knowledge and experience was crucial to the development of Traditional Chinese Medicine (TCM). However, the existing methods of inheriting the unique clinical experience of famous veteran TCM doctors still followed the outdated and inefficient Master-Prentice schema. In addition, the inherited medical books and records were usually lack of standardization and systematization. In this article, a new method for inheriting the academic thoughts and clinical experience of famous veteran doctors with the help of artificial intelligence technology was explored. Due to the individualized treatment characteristics namely "same disease with different treatments, different diseases with the same treatment," the intelligent inheritance of TCM faced many technical barriers. To tackle these problems, we proposed a prototype system framework for the intelligent inheritance of famous veteran doctors based on rules and deep learning models and performed a case study on the treatment of pediatric asthma. The architecture could not only make full use of the advantages of deep learning, but also integrate the valuable knowledge and experience analysis of famous veteran doctors from injected rules. Specifically, the study took pediatric asthma medical records as training and test samples and calculated the similarity between the generated prescriptions and the real-world clinical prescriptions from the famous veteran doctors. Experimental results showed that the generated prescription could achieve a similarity of more than 90%. It proved that the proposed framework provided a feasible way for the intelligent inheritance and research of the academic thoughts and clinical experience of famous veteran TCM doctors.
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Asma , Medicamentos Herbarios Chinos , Médicos , Niño , Humanos , Medicina Tradicional China , Inteligencia Artificial , Asma/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéuticoRESUMEN
Hydrogen sulfide (H2S) plays an important role in regulating various pathological processes such as protecting mammalian cell from harmful injuries, promoting tissue regeneration, and regulating the process of various diseases caused by physiological disorders. Studies have revealed that the physiological effects of H2S are highly associated with its concentrations. At relatively low concentration, H2S shows beneficial functions. However, long-time and high-dose donation of H2S would inhibit regular biological process, resulting in cell dysfunction and apoptosis. To regulate the dosage of H2S delivery for precision medicine, H2S delivery systems with intelligent characteristics were developed and a variety of biocompatibility polymers have been utilized to establish intelligent polymeric H2S delivery systems, with the abilities to specifically target the lesions, smartly respond to pathological microenvironments, as well as real-timely monitor H2S delivery and lesion conditions by incorporating imaging-capable moieties. In this review, we focus on the design, preparation, and therapeutic applications of intelligent polymeric H2S delivery systems in cardiovascular therapy, inflammatory therapy, tissue regenerative therapy, cancer therapy and bacteria-associated therapy. Strategies for precise H2S therapies especially imaging-guided H2S theranostics are highlighted. Since H2S donors with stimuli-responsive characters are vital components for establishing intelligent H2S delivery systems, the development of H2S donors is also briefly introduced.
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Wounds are usually irregular in shapes, and accompanied with a series of disorders such as hemorrhage and bacteria contamination. Here, we report a multifunctional hydrogel prepared by phase-transited lysozyme (PTL), which presents antimicrobial, injectable, self-healing, tissue adhesive, hemostatic and biodegradable properties that fit the requirements of wound treatment. The lysozyme was unfolded under the action of tris(2-carboxyethyl)phosphine (TCEP), and then self-assembled into a hydrogel (PTLG). The phase transition expanded the antibacterial spectrum of lysozyme, PTLG effectively killed both Gram-positive bacteria (Staphylococcus aureus, Staphylococcus epidermidis) and Gram-negative bacteria (Escherichia coli, Acinetobacter baumannii) on contact. This dynamically cross-linked hydrogel exhibited injectable and self-healing abilities, and was capable of adapting to various wound morphologies. The tissue-adhesive nature derived from phase-transition, endowed PTLG with hemostatic effect. Meanwhile, PTLG exhibited biocompatibility towards mammalian cells. Furthermore, its anti-infective ability in vivo was verified in a mouse subcutaneous infection model, more than 98 % of S. epidermidis was reduced under PTLG injection. And PTLG could be biodegraded within four weeks in mice body. Overall, the proposed PTLG is a promising multifunctional dressing material that could accommodate the various demands of complex and deep wounds.
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Based on engineering practice and practical needs, this paper takes ordinary concrete specimens as the research object, and adopts a high-temperature true triaxial loading test system to carry out high-temperature uniaxial and true triaxial static compression tests of concrete under high-temperature conditions. By comparing with normal temperature conditions, this paper analyzes the influence of the coupling effect of high-temperature and biaxial unequal lateral pressure on the static mechanical properties of concrete. By analyzing the experimental data, we reached a series of conclusions and carried out theoretical research on this basis. High temperatures can significantly affect the uniaxial static pressure strength characteristics, deformation characteristics, and failure mode of concrete. When the temperature exceeds 400 °C, the compressive strength decreases significantly, the peak strain increases sharply, and the plasticity of concrete is further enhanced. The coupling effect of high-temperature deterioration and lateral pressure strengthening makes the true triaxial mechanical properties of concrete change significantly; 0.6:0.2 and 400 °C are the turning points of side pressure ratio and temperature that affect the change law of the true triaxial mechanical properties of concrete, respectively. Based on the study of the high-temperature deterioration factor and lateral pressure strengthening factor, this paper further puts forward a concrete strength formula under the coupling action of high temperature and biaxial unequal lateral pressure. It was verified that the formula has a high accuracy.
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This paper investigated the preparation method and the dispersion behaviour of Modified Carbon Nanotube-fiber Reinforcements (MCNF), the change laws and the effect mechanisms of dynamic compressive strength of MCNF concretes. Electrophoresis method was used to prepare MCNF and its interfacial shear performance was tested by interfacial shear strength (IFSS) test. In addition, the dispersion behavior of MCNF in simulated concrete solution was verified by turbidity method. Split Hopkinson Pressure Bar (SHPB), Scanning Electron Microscope (SEM) and Mercury Intrusion Porosimetry (MIP) tests were carried on concrete samples with different volume fractions (0%, 0.1%, 0.2%, 0.3%, 0.4%) of MCNF. The results show that carbon nanotubes are easier to deposit to the negative electrode, and the higher the content of polycarboxylate superplasticizer, the more obvious the dispersity of MCNF in alkaline environment. The dynamic compressive strength of MCNF concrete was 14.0-35.5% higher than that of untreated concrete, and reached the maximum when the MCNF content was about 0.3%. The MCNF was wrapped in concrete matrix and promoted hydration reaction of interface between cement and MCNF from microscopic observation. The addition of MCNF could increase the porosity. The volume percentage of ≥ 100 nm pore decreased first and then increased. Reasons for the improvement strength of MCNF concrete is that the bridging effect is stronger with the increase of MCNF content (≤ 0.3%) and limited when the MCNF content is equal to 0.4%. MCNF concrete could be used in actual engineering with high requirements for dynamic load.
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BACKGROUND: Enolase is an essential enzyme in the process of glycolysis and has been implicated in cancer progression. Though dysregulation of ENOs has been reported in multiple cancers, their prognostic value and specific role in bladder cancer (BLCA) remain unclear. METHODS: Multiple databases were employed to examine the expression of ENOs in BLCA. The expression of ENO1 was also validated in BLCA cell lines and tissue samples by western blotting and immunohistochemistry. Kaplan-Meier analysis, ROC curve, univariate and multivariate Cox regression were performed to evaluate the predictive capability of the ENO1. Gene ontology (GO) and Gene Set Enrichment Analyses (GSEA) analysis were employed to perform the biological processes enrichment. Function experiments were performed to explore the biological role of ENO1 in BLCA. The correlation of ENO1 with immune cell infiltration was explored by CIBERSORT. RESULTS: By analyzing three ENO isoforms in multiple databases, we identified that ENO1 was the only significantly upregulated gene in BLCA. High expression level of ENO1 was further confirmed in BLCA tissue samples. Aberrant ENO1 overexpression was associated with clinicopathological characteristics and unfavorable prognosis. Functional studies demonstrated that ENO1 depletion inhibited cancer cell aggressiveness. Furthermore, the expression level of ENO1 was correlated with the infiltration levels of immune cells and immune-related functions. CONCLUSIONS: Taken together, our results indicated that ENO1 might serve as a promising prognostic biomarker for prognosticating prognosis associated with the tumor immune microenvironment, suggesting that ENO1 could be a potential immune-related target against BLCA.