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Group 2 innate lymphoid cells (ILC2s) play a crucial role in the progression of asthma, yet the regulatory mechanisms modulating ILC2 responses in asthma remain underexplored. Human milk oligosaccharides (HMOs), vital non-nutritive components of breast milk, are known to significantly shape immune system development and influence the incidence of allergic diseases. However, their impact on ILC2-driven asthma is not fully understood. Our research reveals that dietary HMOs act as potent inhibitors of ILC2 responses and allergic airway inflammation. Treatment with 2'-fucosyllactose (2'-FL) and 6'-sialyllactose (6'-SL) significantly reduced ILC2-related airway inflammation induced by papain or Alternaria alternata in mice, evidenced by decreased eosinophil (EOS) infiltration and lower IL-5 and IL-13 levels in BALF. Notably, while ILC2 expresses HMO receptors, HMO did not act directly on ILC2 but potentially modulated their activity through alterations in gut microbiota derived SCFAs. HMO treatments alleviated airway inflammation in SCFA-dependent manners, with SCFA depletion or receptor blocking reversing these beneficial effects. This study reveals the potential of dietary HMOs in managing asthma through modulation of ILC2 activity and the gut-lung axis, proposing a new therapeutic avenue that utilises the immunomodulatory capacities of nutritional components to combat respiratory diseases.
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Background Ascending thoracic aortic aneurysms (aTAA) can lead to life-threatening dissection and rupture. Recent studies highlighted aTAA mechanical properties as relevant factors associated with progression. The aim of this study was to quantify in vivo aortic wall stretch in healthy participants and aTAA patients using displacement encoding with stimulated echoes (DENSE) MRI. Moreover, aTAA wall stretch between surgical and non-surgical patients were investigated. Finally, DENSE measurements were compared to reference-standard mechanical testing on aTAA specimens from surgical repairs. Methods In total, 18 subjects were recruited, six healthy participants and 12 aTAA patients, for this prospective study. ECG-gated DENSE imaging was performed to measure systole-diastole wall stretch, as well as the ratio of aTAA stretch to unaffected descending thoracic aorta stretch. Free-breathing and breath-held DENSE protocols were used. Uniaxial tensile testing-measured indices were correlated to DENSE measurements in five specimens. Results In vivo aortic wall stretch was significantly lower in aTAA compared to healthy subjects (P=.0004). There was no correlation between stretch and maximum aTAA diameter. The ratio of aTAA to unaffected thoracic aorta wall stretch was significantly lower in surgical candidates compared to non-surgical candidates (P=.0442). Finally, in vivo aTAA wall stretch correlated to wall failure stress and peak modulus of the intima (P=.017 and P=.034, respectively), while the stretch ratio correlated to whole-wall thickness failure stretch and stress (P=.013 and P=.040, respectively). Conclusion Aortic DENSE has the potential to assess differences in aTAA mechanical properties and progressions.
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Organic near-infrared room temperature phosphorescence (RTP) materials offer remarkable advantages in bioimaging due to their characteristic time scales and background noise elimination. However, developing near-infrared RTP materials for deep tissue imaging still faces challenges since the small band gap may increase the non-radiative decay, resulting in weak emission and short phosphorescence lifetime. In this study, fused-ring pyrrole-based structures were employed as the guest molecules for the construction of long wavelength emissive RTP materials. Compared to the decrease of the singlet energy level, the triplet energy level showed a more effectively decrease with the increase of the conjugation of the substituent groups. Moreover, the sufficient conjugation of fused ring structures in the guest molecule suppresses the non-radiative decay of triplet excitons. Therefore, a near-infrared RTP material (764â nm) was achieved for deep penetration bioimaging. Tumor cell membrane is used to coat RTP nanoparticles (NPs) to avoid decreasing the RTP performance compared to traditional coating by amphiphilic surfactants. RTP NPs with tumor-targeting properties show favorable phosphorescent properties, superior stability, and excellent biocompatibility. These NPs are applied for time-resolved luminescence imaging to eliminate background interference with excellent tissue penetration. This study provides a practical solution to prepare long-wavelength and long-lifetime organic RTP materials and their applications in bioimaging.
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Luminescência , Nanopartículas , Membrana Celular , PirróisRESUMO
Protein N- and C-termini have specific biochemical properties and functions. They play vital roles in various biological processes, such as protein stability and localization. In addition, post-translational modifications and proteolytic processing generate different proteoforms at protein termini. In recent years, terminomics has attracted significant attention, and numerous strategies have been developed to achieve high-throughput and global terminomics analysis. This review summarizes the recent protein N-termini and C-termini enrichment methods and their application in different samples. We also look ahead further application of terminomics in profiling protease substrates and discovery of disease biomarkers and therapeutic targets.
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Processamento de Proteína Pós-Traducional , Proteoma , Proteoma/análise , Proteólise , Peptídeo Hidrolases/metabolismoRESUMO
"Candidatus Accumulibacter" is the major polyphosphate-accumulating organism (PAO) in global wastewater treatment systems, and its phylogenetic and functional diversity have expanded in recent years. In addition to the widely recognized type I and II sublineages, we discovered a novel type enriched in laboratory bioreactors. Core gene and machine learning-based gene feature profiling supported the assertion that type III "Ca. Accumulibacter" is a potential PAO with the unique function of using dimethyl sulfoxide as an electron acceptor. Based on the correlation between ppk1 and genome similarity, the species-level richness of Accumulibacter was estimated to be over 100, suggesting that the currently recognized species are only the tip of the iceberg. Meanwhile, the interstrain transcriptional and morphological features of multiple "Ca. Accumulibacter" strains co-occurring in a bioreactor were investigated. Metatranscriptomics of seven co-occurring strains indicated that the expression level and interphasic dynamics of PAO phenotype-related genes had minimal correlation with their phylogeny. In particular, the expression of denitrifying and polyphosphate (poly-P) metabolism genes exhibited higher interstrain and interphasic divergence than expression of glycogen and polyhydroxyalkanoate metabolic genes. A strategy of cloning rRNA genes from different strains based on similar genomic synteny was successfully applied to differentiate their morphology via fluorescence in situ hybridization. Our study further expands the phylogenetic and functional diversity of "Ca. Accumulibacter" and proposes that deciphering the function and capability of certain "Ca. Accumulibacter" should be tailored to the environment and population in question. IMPORTANCE In the last 2 decades, "Ca. Accumulibacter" has garnered significant attention as the core functional but uncultured taxon for enhanced biological phosphorus removal due to its phylogenetic and functional diversity and intragenus niche differentiation. Since 2002, it has been widely known that this genus has two sublineages (type I and II). However, in this study, a metagenomic approach led to the discovery of a novel type (type III) with proposed novel functional features. By comparing the average nucleotide identity of "Ca. Accumulibacter" genomes and the similarity of ppk1, a phylogenetic biomarker largely deposited in databases, the global species-level richness of "Ca. Accumulibacter" was estimated for the first time to be over 100. Furthermore, we observed the co-occurrence of multiple "Ca. Accumulibacter" strains in a single bioreactor and found the simultaneous transcriptional divergence of these strains intriguing with regard to their niche differentiation within a single community. Our results indicated a decoupling feature between transcriptional pattern and phylogeny for co-occurring strains.
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Betaproteobacteria , Filogenia , Hibridização in Situ Fluorescente , Betaproteobacteria/genética , RNA Ribossômico 16S/genética , Fósforo/metabolismo , Reatores Biológicos , Polifosfatos/metabolismo , EsgotosRESUMO
OBJECTIVE: This study aimed to investigate the relationship between serum superoxide dismutase (SOD) and interstitial lung disease (ILD) among patients with anti-melanoma differentiation-associated gene 5 antibody (MDA5)-positive DM. METHOD: In this retrospective study, serum SOD of 90 health check-ups were tested in our hospital. A total of 94 hospitalized patients with anti-MDA5-positive DM had ILD. Their serum SOD, serum ferritin and autoantibody levels were determined and lung high-resolution CT was performed. RESULTS: The serum SOD level was significantly lower in the anti-MDA5-positive DM group compared with the control group. The SOD level was significantly lower in patients positive for both anti-MDA5 antibodies and anti-Ro-52 antibodies than in those positive for only anti-MDA5 antibodies before treatment. The SOD level was significantly lower in the higher serum ferritin group compared with the lower serum ferritin group before treatment. After treatment, the serum SOD level decreased in patients with exacerbation of ILD, while it increased in those with alleviated ILD. The SOD level was significantly lower in the death group than in the survival group before treatment. CONCLUSIONS: In patients with anti-MDA5-positive DM, the low SOD level before treatment indicated the presence of oxidative stress in the disease; the serum SOD level was affected by anti-Ro-52 antibodies and ferritin; there is a close relationship between serum SOD level and ILD among patients with anti-MDA5-positive DM, suggesting that SOD might serve as an effective indicator to evaluate the changes in ILD in these patients; and the low SOD level is an important indicator of poor prognosis in these patients, which deserves attention from rheumatologists.
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Dermatomiosite , Doenças Pulmonares Intersticiais , Humanos , Prognóstico , Estudos Retrospectivos , Progressão da Doença , Helicase IFIH1 Induzida por Interferon , Autoanticorpos , FerritinasRESUMO
A KOH-promoted cascade C-Cl bond activation and amidation of trichloromethyl aromatic compounds with formamides using water as a solvent has been developed. This methodology suggested an alternative synthetic approach for the synthesis of aryl amide compounds in the absence of catalysts, additives and organic solvents. In addition, the yields of gram-scale reactions are good and provide a basis for synthetic application.
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Fluorescent probes with a microsecond lifetime have attracted much attention in biological detection. The luminescence properties and responsive mechanisms of a probe [DCF-MPYM-lev-H]- for detecting sulfite and its corresponding product [DCF-MPYM-2H]2- are studied based on density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations as well as the thermal vibration correlation function method. It is found that the luminescence efficiency of the probe increases obviously after reacting with sulfite, which is induced by increased radiative decay rates and decreased nonradiative rates. In addition, the thermally activated delayed fluorescence (TADF) properties of products are confirmed by analyzing the spin-orbital constants and energy gaps between the singlet excited states and the triplet excited states. The calculation results favor the understanding of the luminescence properties and responsive mechanism of a turn-on TADF probe for sulfite, which may provide a theoretical reference for the development of new TADF probes.
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Multi-resonance thermally activated delayed fluorescence (MR-TADF) molecules with narrow full width at half maximum (FWHM) have attracted much attention recently. In this work, 36 borane/amine (B/N) type MR-TADF molecules were theoretically designed by using an intramolecular-lock strategy and systematically studied based on first-principles calculations. It was found that intramolecular-lock at different positions and in different manners could induce different luminescent properties. The calculated oscillator strengths for PXZ-L2 and PTZ-L2 locking systems are weaker than that for 2DPABN (without intramolecular-lock), while the Cz-L1 and TMCZ-L1 locking could result in stronger oscillator strength. Though the calculated FWHM of all the systems with intramolecular-lock is higher than that of 2DPABN, the Cz, TMCz and DMAC locking at L1 or L2 would induce relatively small FWHM which is comparable to that of 2DPABN. Our calculation results indicate that intramolecular-lock could enhance the SOC values and decrease the energy gap between the first singlet excited state and the first triplet excited state, which is quite favorable to reverse intersystem crossing. The Cz, TMCz and DMAC locking systems could realize comparable and higher efficiency than 2DPABN, thus higher quantum efficiency could be obtained. Our calculation results indicate that the intramolecular-lock strategy is an effective method to realize the design of highly efficient MR-TADF emitters.
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OBJECTIVE: To investigate the genetic causes of 22 patients with clinically high suspicion of X-linked hypohidrotic ectodermal dysplasia from 20 unrelated Chinese families, expand the spectrum of ectodysplasin-A mutations, and provide more evidence for variants of uncertain significance. SUBJECTS AND METHODS: Whole-exome sequencing was performed and potentially pathogenic variants were verified by Sanger sequencing. Western blotting, real-time PCR and immunofluorescence analyses were performed to investigate the preliminary functions of the candidate variants. RESULTS: Nineteen ectodysplasin-A variants were identified, six of which were not previously reported. Among these variants, we identified a patient who carried two mutations in ectodysplasin-A and exhibited more severe phenotypes. Additionally, mutant protein expression levels decreased, whereas mRNA transcription levels increased. Cellular sublocalisation of the variants located in the tumour necrosis factor homologous domain showed that the proteins accumulated in the nucleus, whereas wild-type proteins remained in the cell membrane. A rare indel variant and two classical splicing variants that lead to exon 7 skipping were detected. CONCLUSIONS: This study provides definitive diagnoses for 20 families with suspected X-linked hypohidrotic ectodermal dysplasia and additional information on clinical heterogeneity and genotype-phenotype relationships.
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Secondary dysmenorrhea is a pain associated with disease such as endometriosis, pelvic inflammatory disease, leiomyomas, and interstitial cystitis. Treatment of secondary dysmenorrhea always focuses on the causative pelvic pathology or medical condition. Here, we found a rare case with secondary dysmenorrhea that resulted from traumatic separation of the uterine corpus from the cervix. In this case, the patient experienced a childhood blunt trauma of the pelvic crush and was successfully diagnosed by magnetic resonance imaging and 3-dimensional ultrasonography. Moreover, laparoscopic anastomosis could be a minimally invasive way to resolve this problem.
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Endometriose , Laparoscopia , Feminino , Humanos , Criança , Colo do Útero/diagnóstico por imagem , Colo do Útero/patologia , Dismenorreia/etiologia , Dismenorreia/cirurgia , Dismenorreia/diagnóstico , Útero/cirurgia , Endometriose/cirurgia , Laparoscopia/efeitos adversosRESUMO
As a severe public health concern directly endangering life safety, adolescent suicide has been extensively investigated in variable-centered studies. However, gaps remain in the knowledge of heterogeneous suicide risk patterns and their developmental nature. Additionally, little is known about protective factors associated with suicide risk patterns and changes. This study applied person-centered approaches to explore suicide risk profiles and transitions over time in early Chinese adolescents, along with their protective factors. A total of 1518 junior high school students (49.6% girls, Mage = 13.57, SD = 0.75) participated in two surveys within a 12-month interval. Latent Profile Analysis and Latent Transition Analysis were used to model the profiles and transitions of suicide risk. Three risk profiles were identified at both time points: low risk profile (73.9, 78.3%), medium risk-high threat profile (16.2, 10.2%), and high risk profile (9.9, 10.2%). Low risk profile was stable, while medium risk-high threat and high risk profiles showed great transitions over 12 months. Sense of control, meaning in life, and regulatory emotional self-efficacy served as protective factors against suicide risk profiles and transitions. Findings underscore the importance of comprehensively illustrating suicide risk states from multiple aspects, as well as understanding the fluid nature of transitions between different risk states. Prevention and intervention strategies aimed at enhancing resilience, such as increasing sense of control, perceived meaningfulness, and belief in emotional regulation, may contribute to reducing the risk of suicide among adolescents.
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População do Leste Asiático , Fatores de Proteção , Suicídio , Adolescente , Feminino , Humanos , Masculino , Fatores de Risco , Suicídio/psicologia , Resiliência PsicológicaRESUMO
Photonic crystals (PCs) have emerged as a promising electrochemiluminescence (ECL) matrix in the domain of immunoassay. Making maximum use of light manipulation properties of PCs is highly desired for improving the sensitivity. In this work, we proposed a band-edge effect-induced ECL enhancement strategy based on silica inverse opal PCs (SIOPCs). By fine-tuning the lattice constant and carefully calibrating the stopband position, we found that the band edge of the stopband exerted significant influences on the ECL intensity and spectral distribution. The high density of states at the blue edge of the photonic band gap increased the radiative transition probability of ECL emitters and enhanced the photon extraction during propagation, giving rise to â¼20-fold ECL signal amplification accompanied by a redistributed ECL spectrum for the Ru(bpy)32+-TPrA system. In combination with the intrinsic structural superiority, like large specific surface area and interconnected macropores, the developed SIOPC electrode was successfully applied in constructing a sandwich-type immunosensor. The fabricated immunosensor displayed a very low detection limit of 0.032 pg/mL and a wide linear range of 0.1 pg/mL-150 ng/mL for a carcinoembryonic antigen assay, showing its potential application in disease diagnosis.
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Técnicas Biossensoriais , Antígeno Carcinoembrionário , Técnicas Eletroquímicas , Imunoensaio , Limite de Detecção , Medições Luminescentes , Dióxido de Silício/químicaRESUMO
With the progress of modern integrated optical technology, organic-inorganic composite materials have been widely used in integrated optoelectronic devices. Because of satisfying optical response properties among azobenzene, it will be an ideal choice to introduce the material into organic-inorganic composite materials. TiO2/GeO2/ormosils composite films containing azobenzene were prepared by combining the solgel technique with the spin-coating process. The optical transmission modes and loss of as-prepared samples at different transmission wavelengths were researched by a prism coupler. The result shows that the composite film is multi-mode transmission at the transmission wavelength of 633 nm and single-mode transmission at 1538 nm. The transmission loss is sufficient for applications in optical elements. The response properties and Fourier transform infrared spectroscopy of as-prepared samples at different heating temperatures were also studied. The composite films obtained at 50°C have the best optical response properties. Furthermore, the banding energy and chemical composition among the films were measured through x-ray photoelectron spectroscopy. Finally, the surface topography of as-prepared samples was observed by atomic force microscopy. The surface of the composite film appears with patterns of relief under the appropriate temperature. The above results show that the as-prepared TiO2/GeO2/ormosils composite films containing azobenzene will be a kind of ideal material in the field of integrated optics applications.
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Protein termini play pivotal roles in various biological processes. Although several terminomic strategies have been proposed for the analysis of protein N-termini or protein C-termini separately, few can analyze both ends of proteins at the same time. Herein, we developed a workflow, termed Simultaneous Analysis of Protein N- and C-Terminome (SAPT) based on strong cation exchange chromatography (SCX) fractionation. Taking advantage of terminal peptides' reduced charge states in low pH SCX for their selective separation, we identified 3724 canonical human protein N-termini and 3129 canonical human protein C-termini, as well as 1463 neo-N-termini from the HeLa cell line, representing the largest human protein C-termini data set and the second largest human protein N-termini data set so far. The whole fractionation procedure was simple and rapid with considerable selectivity by utilizing a commercially available SCX-SPE column. In addition, we report for the first time the comprehensive screening of protein N-terminal and C-terminal modifications, leading to an identification of 8 kinds of protein N-terminal PTMs other than acetylation and 1 kind of protein C-terminal PTM other than amidation. Our results demonstrate the excellent performance and great potential of SAPT in terminomic studies. Data are available via ProteomeXchange with identifier PXD024573.
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Peptídeos , Proteína C , Células HeLa , Humanos , Peptídeos/metabolismo , Processamento de Proteína Pós-Traducional , ProteínasRESUMO
In this study, a cyclodextrin derivative (R6RGD-CMßCD) nanoparticle with tumor targeting and cell penetration ability was successfully synthesized and loaded with tyroserleutide (YSL) to obtain YSL-loaded nanoparticles (YSL/R6RGD-CMßCD NPs). The characterization of these NPs revealed a smooth surfaces and an average diameter of approximately 170 nm. YSL/R6RGD-CMßCD NPs increased the NP uptake in Caco-2 cells. As regard the mechanism of action, the cell uptake was related to endocytosis mediated by reticulin and megacytosis. In addition, YSL/R6RGD-CMßCD NPs induced significantly higher cytotoxicity on tumor cells and better tumor targeting compared with the effect of CMßCD NPs. Most importantly, the good anti-cancer effect of YSL/R6RGD-CMßCD NPs might be due to the interference with the function of mitochondria. On the other hand, YSL/R6RGD-CMßCD NPs were not toxic for normal cells. Taken together, our results indicated that R6RGD-CMßCD could be considered as a nanopharmaceutical material with good tumor targeting abilities, and their combination with YSL could represent an effective anti-cancer system.
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Ciclodextrinas/química , Nanopartículas/química , Oligopeptídeos/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Células CACO-2 , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Endocitose , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Oligopeptídeos/farmacologiaRESUMO
Copper elbows are an important product in industry. They are used to connect pipes for transferring gas, oil, and liquids. Defective copper elbows can lead to serious industrial accidents. In this paper, a novel model named YOT-Net (YOLOv3 combined triplet loss network) is proposed to automatically detect defective copper elbows. To increase the defect detection accuracy, triplet loss function is employed in YOT-Net. The triplet loss function is introduced into the loss module of YOT-Net, which utilizes image similarity to enhance feature extraction ability. The proposed method of YOT-Net shows outstanding performance in copper elbow surface defect detection.
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Algoritmos , Cobre , CotoveloRESUMO
The underlying mechanisms of microalgal host-pathogen interactions remain largely unknown. In this study, we applied physiological and simultaneous dual transcriptomic analysis to characterize the microalga Graesiella emersonii-Amoeboaphelidium protococcarum interaction. Three infection stages were determined according to infection rate and physiological features. Dual RNA-seq results showed that the genes expression of G. emersonii and A. protococcarum were strongly dynamically regulated during the infection. For microalgal hosts, similar to plant defense response, the expression of defense genes involved in the pattern recognition receptors, large heat shock proteins, and reactive oxygen scavenging enzymes (glutathione, ferritin, and catalase) were significantly upregulated during infection. However, some genes encoding resistance proteins (R proteins) with a leucine-rich repeat domain exhibited no significant changes during infection. For endoparasite A. protococcarum, genes for carbohydrate-active enzymes, pathogen-host interactions, and putative effectors were significantly upregulated during infection. Furthermore, the genes in cluster II were significantly enriched in pathways associated with the modulation of vacuole transport, including endocytosis, phagosome, ubiquitin-mediated proteolysis, and SNARE interactions in vesicular transport pathways. These results suggest that G. emersonii has a conserved defense system against pathogen and that endoparasite A. protococcarum possesses a robust pathogenicity to infect the host. Our study characterizes the first transcriptomic profile of microalgae-endoparasite interaction, providing a new promising basis for complete understanding of the algal host defense strategies and parasite pathogenicity.
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Microalgas/genética , Parasitos/genética , Doenças das Plantas/parasitologia , Animais , Eucariotos , Perfilação da Expressão Gênica/métodos , Interações Hospedeiro-Patógeno , Microalgas/metabolismo , Doenças das Plantas/genética , Doenças das Plantas/imunologia , VirulênciaRESUMO
SR splicing-factors (SRSFs) play a vital role in carcinogenesis. SRSF5 was demonstrated to be upregulated in lung cancer and identified as a novel prognostic indicator for small-cell lung cancer. However, the role of SRSF5 in the pathogenesis of non-small cell lung cancer (NSCLC) and the molecular mechanism involved are still undefined. The expression of SRSF5 in NSCLC cells was detected by quantitative real-time polymerase chain reaction and Western blot analysis. The proliferation of cells was evaluated by cell counting kit-8 and BrdU assays. Apoptosis was assessed by flow cytometry and Western blot analysis of apoptosis-associated proteins including B-cell lymphoma 2 (Bcl-2), Bax, and cytochrome C (Cyt C). Glycolysis was detected by determining glucose consumption, lactate production, and pyruvate kinase M2 (PKM2) expression. We found that SRSF5 messenger RNA and protein levels were elevated in NSCLC cells. SRSF5 knockdown inhibited the proliferation and Ki67 expression in NSCLC cells. SRSF5 silencing increased the apoptotic rate, upregulated Bax and Cyt C, and decreased Bcl-2 level in NSCLC cells. Moreover, Knockdown of SRSF5 repressed glycolysis in NSCLC cells via reducing PKM2 expression. Enhanced glycolysis by PKM2 overexpression attenuated the effects of SRSF5 silencing on NSCLC cell proliferation and apoptosis. Overall, knockdown of SRSF5 inhibited proliferative ability and induced apoptosis by suppressing PKM2 expression in NSCLC cells.
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Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas de Transporte/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/patologia , Proteínas de Membrana/metabolismo , Fatores de Processamento de Serina-Arginina/metabolismo , Hormônios Tireóideos/metabolismo , Apoptose , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proteínas de Transporte/genética , Proliferação de Células , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Proteínas de Membrana/genética , Fatores de Processamento de Serina-Arginina/genética , Hormônios Tireóideos/genética , Células Tumorais Cultivadas , Proteínas de Ligação a Hormônio da TireoideRESUMO
BACKGROUND: Pulmonary autograft dilatation after Ross operation often necessitates reoperation. To understand autograft remodeling, a biomechanical understanding of human autografts after exposure to systemic pressure is required. We previously developed an ex vivo human pulmonary autograft finite element (FE) model to predict wall stress after exposure to systemic pressure. However, autograft material properties vary significantly among individuals. Our study aim was to quantify range of wall stress changes in a human autograft after Ross operation prior to remodeling based upon normal variation in human autograft mechanical properties. METHODS: A normal human autograft FE model was loaded to pulmonary and systemic arterial pressures. Stress-strain data of normal human autografts (n=24) were incorporated into an Ogden hyper-elastic model to describe autograft mechanical behavior. Autograft wall stresses at pulmonary vs. systemic pressures were examined. Autograft volume-based stress analysis was performed, based on percentage of autograft element volume exceeding 1 standard deviation (SD) above group mean stress at systemic systole. RESULTS: Mean first principal wall stresses (FPS) at systole of systemic versus pulmonary pressures were 129.29±17.47kPa versus 24.42±3.85kPa (p<0.001) at the annulus, 187.53±20.06kPa versus 35.98±2.15kPa at sinuses (p<0.001), and 268.68±23.40kPa versus 50.15±5.90kPa (p<0.001) at sinotubuluar junction (STJ). The percentage of autograft element volume that exceeded one SD above the group mean was 14.3±5.6% for FPS and 12.6±10.1% for second principal stresses. CONCLUSION: We quantified normal human autograft biomechanical responses to systemic pressure based on patient-specific material properties. Regions of peak stresses were observed in autograft sinuses and STJ regions, which corresponded clinically to locations of autograft dilation. Our results provide valuable information on predicting variations in patient-specific ex vivo FE models when population-based material properties are used in settings where patient-specific properties are unknown.