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Climate change is a global concern for all life on our planet, including humans and plants. Plants' growth and development are significantly affected by abiotic stresses, including adverse temperature, inadequate or excess water availability, nutrient deficiency, and salinity. The circadian clock is a master regulator of numerous developmental and metabolic processes in plants. In an effort to identify new clock-related genes and outputs through bioinformatic analysis, we have revealed that CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY) play a crucial role in regulating a wide range of abiotic stress responses and target ABSCISIC ACID RESPONSIVE ELEMENTS-BINDING FACTOR3 (ABF3), a key transcription factor in the plant hormone Abscisic acid (ABA)-signaling pathway. Specifically, we found that CCA1 and LHY regulate the expression of ABF3 under diel conditions, as well as seed germination under salinity. Conversely, ABF3 controls the expression of core clock genes and orchestrates the circadian period in a stress-responsive manner. ABF3 delivers the stress signal to the central oscillator by binding to the promoter of CCA1 and LHY. Overall, our study uncovers the reciprocal regulation between ABF3 and CCA1/LHY and molecular mechanisms underlying the interaction between the circadian clock and abiotic stress. This finding may aid in developing molecular and genetic solutions for plants to survive and thrive in the face of climate change.
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Proteínas de Arabidopsis , Arabidopsis , Relógios Circadianos , Humanos , Relógios Circadianos/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Ácido Abscísico/metabolismo , Ritmo Circadiano/genética , Regulação da Expressão Gênica de Plantas , Estresse Fisiológico , Fatores de Transcrição/metabolismoRESUMO
Water oxidation on magnetic catalysts has generated significant interest due to the spin-polarization effect. Recent studies have revealed that the disappearance of magnetic domain wall upon magnetization is responsible for the observed oxygen evolution reaction (OER) enhancement. However, an atomic picture of the reaction pathway remains unclear, i.e., which reaction pathway benefits most from spin-polarization, the adsorbent evolution mechanism, the intermolecular mechanism (I2M), the lattice oxygen-mediated one, or more? Here, using three model catalysts with distinguished atomic chemistries of active sites, we are able to reveal the atomic-level mechanism. We found that spin-polarized OER mainly occurs at interconnected active sites, which favors direct coupling of neighboring ligand oxygens (I2M). Furthermore, our study reveals the crucial role of lattice oxygen participation in spin-polarized OER, significantly facilitating the coupling kinetics of neighboring oxygen radicals at active sites.
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Several key technologies for advancing biopharmaceutical manufacturing depend on the successful implementation of process analytical technologies that can monitor multiple product quality attributes in a continuous in-line setting. Raman spectroscopy is an emerging technology in the biopharma industry that promises to fit this strategic need, yet its application is not widespread due to limited success for predicting a meaningful number of quality attributes. In this study, we addressed this very problem by demonstrating new capabilities for preprocessing Raman spectra using a series of Butterworth filters. The resulting increase in the number of spectral features is paired with a machine learning algorithm and laboratory automation hardware to drive the automated collection and training of a calibration model that allows for the prediction of 16 different product quality attributes in an in-line mode. The demonstrated ability to generate these Raman-based models for in-process product quality monitoring is the breakthrough to increase process understanding by delivering product quality data in a continuous manner. The implementation of this multiattribute in-line technology will create new workflows within process development, characterization, validation, and control.
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Análise Espectral Raman , Proteína Estafilocócica A , Análise Espectral Raman/métodos , Automação , Cromatografia , Aprendizado de MáquinaRESUMO
BACKGROUND: Chronic lung and heart diseases are more likely to lead an intensive end point after stroke onset. We aimed to investigate characteristics and outcomes of endovascular thrombectomy (EVT) in patients with acute large vessel occlusion stroke (ALVOS) and identify the role of comorbid chronic cardiopulmonary diseases in ALVOS pathogenesis. METHODS: In this single-center retrospective study, 191 consecutive patients who underwent EVT due to large vessel occlusion stroke in neurological intensive care unit were included. The chronic cardiopulmonary comorbidities and several conventional stroke risk factors were assessed. The primary efficacy outcome was functional independence (defined as a mRS of 0 to 2) at day 90. The primary safety outcomes were death within 90 days and the occurrence of symptomatic intracranial hemorrhage(sICH). Univariate analysis was applied to evaluate the relationship between factors and clinical outcomes, and logistic regression model were developed to predict the prognosis of ALVOS. RESULTS: Endovascular therapy in ALVOS patients with chronic cardiopulmonary diseases, as compared with those without comorbidity, was associated with an unfavorable shift in the NHISS 24 h after EVT [8(4,15.25) versus 12(7.5,18.5), P = 0.005] and the lower percentage of patients who were functionally independent at 90 days, defined as a score on the modified Rankin scale of 0 to 2 (51.6% versus 25.4%, P = 0.000). There was no significant between-group difference in the frequency of mortality (12.1% versus 14.9%, P = 0.580) and symptomatic intracranial hemorrhage (13.7% versus 19.4%, P = 0.302) or of serious adverse events. Moreover, a prediction model showed that existence of cardiopulmonary comorbidities (OR = 0.456, 95%CI 0.209 to 0.992, P = 0.048) was independently associated with functional independence at day 90. CONCLUSIONS: EVT was safe in ALVOS patients with chronic cardiopulmonary diseases, whereas the unfavorable outcomes were achieved in such patients. Moreover, cardiopulmonary comorbidity had certain clinical predictive value for worse stroke prognosis.
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Comorbidade , Procedimentos Endovasculares , Trombectomia , Humanos , Masculino , Feminino , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Procedimentos Endovasculares/métodos , Trombectomia/métodos , Trombectomia/estatística & dados numéricos , Trombectomia/efeitos adversos , Cardiopatias/epidemiologia , Cardiopatias/complicações , Cardiopatias/cirurgia , Idoso de 80 Anos ou mais , Estudos de Coortes , Pneumopatias/epidemiologia , Pneumopatias/cirurgia , Resultado do Tratamento , AVC Isquêmico/cirurgia , AVC Isquêmico/epidemiologia , Acidente Vascular Cerebral/cirurgia , Acidente Vascular Cerebral/epidemiologiaRESUMO
OBJECTIVES: To investigate the wound healing of rabbit cornea following infrared laser irradiations at the wavelengths of 1.319 and 10.6 µm. MATERIALS AND METHODS: Twelve New Zealand rabbits were selected to establish a corneal injury model. The right and left eyes were irradiated with a neodymium-doped yttrium aluminum garnet laser at the wavelength of 1.319 µm (140 J/cm2 ) for 0.7 s and a CO2 laser at the wavelength of 10.6 µm (5.94 J/cm2 ) for 0.14 s, respectively. The incident spot diameter was 3 mm. Optical coherence tomography (OCT) was used to monitor injuries at 0 h, 0.5 h, 1 h, 3 h, 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h, 66 h, 3 d, 7 d, 14 d, 28 d, 3 m, and 6 m postexposure. Meanwhile, slit-lamp microscopy and histopathology were performed at 6 h, 24 h, 3 d, 7 d, 14 d, 28 d, 3 m, and 6 m postexposure. RESULTS: After the two types of infrared laser injuries, distinct white circular lesions on the corneal surface were directly observed. Deeper corneal injury, more severe edema, and faster migration of new epithelium were found for the wavelength of 1.319 µm, compared to the wavelength of 10.6 µm. CONCLUSIONS: OCT combined with histopathology and slit-lamp microscopy can clearly observe the dynamic process of corneal wound healing after infrared laser irradiation. The damage characteristics for the two different wavelengths were visibly different, but the whole wound healing process was similar. The obtained results may provide references for the diagnosis, treatment, and evaluation of laser-induced damages.
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Lesões da Córnea , Lasers de Estado Sólido , Animais , Coelhos , Córnea/diagnóstico por imagem , Córnea/cirurgia , Cicatrização , Luz , Lasers de Estado Sólido/uso terapêuticoRESUMO
The present study was to determine the characteristics of the ankle skeletal structure in patients with talus Hepple V type. We conducted a retrospective study on the skeletal structure of the talus in 110 patients with Hepple V osteochondral lesions of the talus and in control participants. The radiographic measurements taken include the following: in the coronal plane - depth of talus frontal curvature, length of the lateral and medial malleolus; in the sagittal plane - radius and height of talus, angle of tibial lateral surface, tibiotalar sector, and vertical neck angle. The osteochondral lesion of the talus showed a significantly larger mean radius (mean ± SD, 21.4 ± 2.5 mm; p < .001) and height (mean ± SD, 26.0 ± 2.7 mm; p < .005). It also demonstrated a longer mean medial malleolus length (mean ± SD, 15.7 ± 2.4 mm; p < .005), a larger mean vertical neck angle (mean ± SD, 86.2 ± 5.4°; p < .050), and a greater mean tibial lateral surface angle (mean ± SD, 80.0 ± 4.5°; p < .001). And there was a greater mean frontal curvature depth (mean ± SD, 3.9 ± 0.6 mm; p < .005). Overall, this study found that patients with Hepple V osteochondral lesions of the talus had a larger vertical neck angle and tibial lateral surface angle, a longer talus radius and medial malleolus length, a higher talus height, and a deeper frontal curvature depth. STUDY DESIGNS: Retrospective Case-Control Study.
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Water electrolysis is one promising and eco-friendly technique for energy storage, yet its overall efficiency is hindered by the sluggish kinetics of oxygen evolution reaction (OER). Therefore, developing strategies to boost OER catalyst performance is crucial. With the advances in characterization techniques, an extensive phenomenon of surface structure evolution into an active amorphous layer was uncovered. Surface reconstruction in a controlled fashion was then proposed as an emerging strategy to elevate water oxidation efficiency. In this work, Cr substitution induces the reconstruction of NiFexCr2-xO4 during cyclic voltammetry (CV) conditioning by Cr leaching, which leads to a superior OER performance. The best-performed NiFe0.25Cr1.75O4 shows a ~1500 % current density promotion at overpotential η=300â mV, which outperforms many advanced NiFe-based OER catalysts. It is also found that their OER activities are mainly determined by Ni : Fe ratio rather than considering the contribution of Cr. Meanwhile, the turnover frequency (TOF) values based on redox peak and total mass were obtained and analysed, and their possible limitations in the case of NiFexCr2-xO4 are discussed. Additionally, the high activity and durability were further verified in a membrane electrode assembly (MEA) cell, highlighting its potential for practical large-scale and sustainable hydrogen gas generation.
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This study focuses on enhancing the pozzolanic activity of bentonite through heat treatment to improve its compressive strength, while also considering its expansion properties for applications. Sodium bentonite was subjected to various temperatures and analyzed using thermogravimetric-differential scanning calorimetry (TG-DSC), X-ray diffraction (XRD), and scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS). The results indicated that at 100 °C, adsorbed and interlayer water in montmorillonite was lost, and constitution water was eliminated at 700 °C. With further temperature increases, montmorillonite decomposes into an amorphous phase at 900 °C. At 1100 °C, the amorphous phase recrystallized into magnesium-aluminum silicate, which further decomposed into cristobalite. The study concludes that bentonite heat-treated at 800-900 °C can be effectively used as an additive in mining backfill materials to enhance compressive strength while maintaining its expansion properties.
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Refinery filtration processes often face challenges related to rapidly increasing permeate pressure differentials and the consequent need for frequent back-flushing. This study investigates the impact of high-intensity immersed sonotrode ultrasound device on flow patterns to address these issues, both numerically and experimentally. Numerical simulations reveal that ultrasound promotes axial circular mixing of the bulk fluid, increasing average flow velocities around the filter tube from 5.11 × 10-5 m/s to 8.76 × 10-3-6.09 × 10-2 m/s, thereby facilitating cleansing of filter tube surfaces. Additionally, high-frequency pressure fluctuations contribute to enhancing the filtration process during positive pressure phases, while robust online back-flushing effects are generated during negative pressure phases. Although the wire-wrapped filter tube attenuates ultrasound energy as it penetrates the tube gaps, ultrasound still induces turbulent mixing inside and outside the filter tubes, aiding in the removal of impurities from the gaps. The utilization of ultrasound is demonstrated to not inflict harm on upstream and downstream facilities. Experimental results demonstrate that ultrasound-assisted filtration with 600 W and 1000 W power inputs reduces filtration pressure differences by 18 % and 73 %, respectively, affirming ultrasound's effectiveness in mitigating and preventing blockages, highlighting its significance for industrial applicability.
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Raman spectroscopy is considered a Process Analytical Technology (PAT) tool in biopharmaceutical downstream processes. In the past decade, researchers have shown Raman spectroscopy's feasibility in determining Critical Quality Attributes (CQAs) in bioprocessing. This study verifies the feasibility of implementing a Raman-based PAT tool in Protein A chromatography as a CQA monitoring technique, for the purpose of accelerating process development and achieving real-time release in manufacturing. A system connecting Raman to a Tecan liquid handling station enables high-throughput model calibration. One calibration experiment collects Raman spectra of 183 samples with 8 CQAs within 25 h. After applying Butterworth high-pass filters and k-nearest neighbor (KNN) regression for model training, the model showed high predictive accuracy for fragments (Q2 = 0.965) and strong predictability for target protein concentration, aggregates, as well as charge variants (Q2≥ 0.922). The model's robustness was confirmed by varying the elution pH, load density, and residence time using 19 external validation preparative Protein A chromatography runs. The model can deliver elution profiles of multiple CQAs within a set point ± 0.3 pH range. The CQA readouts were presented as continuous chromatograms with a resolution of every 28 s for enhanced process understanding. In external validation datasets, the model maintained strong predictability especially for target protein concentration (Q2 = 0.956) and basic charge variants (Q2 = 0.943), except for overpredicted HCP (Q2 = 0.539). This study demonstrates a rapid, effective method for implementing Raman spectroscopy for in-line CQA monitoring in process development and biomanufacturing, eliminating the need for labor-intensive sample pooling and handling.
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Cromatografia , Análise Espectral Raman , Calibragem , Preparações Farmacêuticas , Tecnologia Farmacêutica/métodosRESUMO
This article provides a unified analysis of the multistability of fraction-order multidimensional-valued memristive neural networks (FOMVMNNs) with unbounded time-varying delays. Firstly, based on the knowledge of fractional differentiation and memristors, a unified model is established. This model is a unified form of real-valued, complex-valued, and quaternion-valued systems. Then, based on a unified method, the number of equilibrium points for FOMVMNNs is discussed. The sufficient conditions for determining the number of equilibrium points have been obtained. By using 1-norm to construct Lyapunov functions, the unified criteria for multistability of FOMVMNNs are obtained, these criteria are less conservative and easier to verify. Moreover, the attraction basins of the stable equilibrium points are estimated. Finally, two numerical simulation examples are provided to verify the correctness of the results.
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Salmonella is a foodborne pathogen that causes disruption of intestinal mucosal immunity, leading to acute gastroenteritis in the host. In this study, we found that Salmonella Typhimurium (STM) infection of the intestinal tract of mice led to a significant increase in the proportion of Lacticaseibacillus, while the secretion of IL-22 from type 3 innate lymphoid cells (ILC3) increased significantly. Feeding Lacticaseibacillus rhamnosus GG (LGG) effectively alleviated the infection of STM in the mouse intestines. TLR2-/- mice experiments found that TLR2-expressing dendritic cells (DCs) are crucial for LGG's activation of ILC3. Subsequent in vitro experiments showed that heat-killed LGG (HK-LGG) could promote DCs to secrete IL-23, which in turn further promotes the activation of ILC3 and the secretion of IL-22. Finally, organoid experiments further verified that IL-22 secreted by ILC3 can enhance the intestinal mucosal immune barrier and inhibit STM infection. This study demonstrates that oral administration of LGG is a potential method for inhibiting STM infection.
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Interleucina 22 , Interleucinas , Lacticaseibacillus rhamnosus , Linfócitos , Infecções por Salmonella , Salmonella typhimurium , Receptor 2 Toll-Like , Animais , Camundongos , Salmonella typhimurium/imunologia , Receptor 2 Toll-Like/imunologia , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Linfócitos/imunologia , Lacticaseibacillus rhamnosus/imunologia , Infecções por Salmonella/imunologia , Infecções por Salmonella/microbiologia , Interleucinas/imunologia , Interleucinas/metabolismo , Camundongos Knockout , Camundongos Endogâmicos C57BL , Células Dendríticas/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Imunidade Inata , Probióticos/administração & dosagem , Imunidade nas MucosasRESUMO
The chromosomal position effect can significantly affect the transgene expression, which may provide an efficient strategy for the inauguration of alien genes in new hosts, but has been less explored rationally. The bacterium Myxococcus xanthus harbors a large circular high-GC genome, and the position effect in this chassis may result in a thousand-fold expression variation of alien natural products. In this study, we conducted transposon insertion at TA sites on the M. xanthus genome, and used enrichment and dilution indexes to respectively appraise high and low expression potentials of alien genes at insertion sites. The enrichment sites are characteristically distributed along the genome, and the dilution sites are overlapped well with the horizontal transfer genes. We experimentally demonstrated the enrichment sites as high expression integration sites (HEISs), and the dilution sites unsuitable for gene integration expression. This work highlights that HEISs are the plug-and-play sites for efficient expression of integrated genes.
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This study aimed to investigate the fundamental properties, solubility, mechanical properties, barrier performance, and microstructural features of films composed of corn starch and glycerol. Changes in the microstructure were analyzed to understand how they relate to the physical and chemical properties of these films. Specifically, we found that increasing the gelatinization time decreased the film thickness, solubility, water vapor permeability, and maximum degradation temperature and increased the water content. A gradual increase in the water contact angle of the corn starch-glycerol films was observed with increasing gelatinization time. This trend is likely due to the disruptive effect of gelatinization on the crystalline and amorphous structures inherent in corn starch, resulting in reduced film crystallinity, degree of order (DO) and degree of double helix (DD).
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The generally undesirable bandgap and electron-hole complexation of inorganic sonosensitizers limit the efficiency of reactive oxygen species (ROS) generation, affecting the effectiveness of sonodynamic therapy (SDT). Comparatively, the novel polyvinylpyrrolidone-modified copper bismuthate (PCBO) sonosensitizers are manufactured for a "three-step" SDT promotion. In brief, first, the strong hybridization between Bi 6s and O 2p orbitals in PCBO narrows the bandgap (1.83 eV), facilitating the rapid transfer of charge carriers. Additionally, nonequivalent [CuO4]6- layers reduce crystal symmetry, confer PCBO unique piezoelectricity, and improve electron-hole separation under ultrasonic (US) excitation. This allows PCBO to convert US energy into chemical energy to produce ROS, achieving the accumulation of abundant ROS, resulting in apoptosis and tumor suppression. Concurrently, PCBO also acts as a glutathione scavenger to reduce tumor antioxidant capacity and improve efficacy. To the best of authors understanding, this study reveals PCBO as an innovative piezoelectric sonosensitizer and provides a meaningful paradigm for designing energy conversion strategies for tumor suppression.
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Phosphorus is a critical factor in the control of eutrophication. We developed a three-dimensional porous, bimetallic-modified adsorbent La-Ca-CS/ATP to remove excess phosphate from water. Langmuir model showed that the theoretical adsorption capacity of La-Ca-CS/ATP was up to 123 mg P/g. The amount of La and Ca leached by La-Ca-CS/ATP was small, and the adsorption of 36.08 mg P/g was maintained during the five cycles of La-Ca-CS/ATP. The La-Ca-CS/ATP adsorption mechanism mainly involved surface precipitation, ligand exchange, electrostatic attraction, and inner-sphere complexation. Molecular dynamics demonstrated that La and Ca had complementary effects on binding sites and energy barriers within the range of 0.5-0.7 nm and 1.2-2 nm, enhancing the adsorption effect of La-Ca-CS/ATP. The life cycle assessment results showed that adding calcium could help reduce the environmental impact of lanthanum and chitosan. The production of La-Ca-CS/ATP adsorbed 73.88 P mg/g and emitted 24.73 kg CO2 eq, which was less than other adsorbents.
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Providing many millions of rural households with decentralized sanitation facilities remains challenging. In undeveloped areas, cesspools have still been widely used due to technologically simple and low-cost. However, the influence of cesspools on the surrounding soil remains unclear. In this study, we investigated the influence of a 25-year-old household cesspool on soil physicochemical factors, microbial community composition and function, pathogens and antibiotic resistance genes (ARGs). Soil at the depth around the sewage liquid level (D70) was mostly disturbed where TOC, NO3-N and TP was increased to 16.8 g/kg, 18.2 mg/kg and 1.02 mg/kg respectively. Correspondingly, the element cycling genes of carbon fixation, methanotrophy, nitrogen fixation, ammonia oxidation, and nitrate reduction etc., were increased at D70. Notably, human derived pathogens such as Enterobacter, Salmonella, Pseudomonas aeruginosa, Klebsiella pneumoniae, Prevotella, and Vibrio were highly enriched by 5-10 folders in D70, indicating the potential health risk to human. Mantel tests suggested that EC, TP, pH, NH3-N and particularly NO3-N are important factors that influence the microbial community and element cycling genes in cesspool-affected soil. Overall, this study revealed the impact of household cesspool leakage on the surrounding soil and provided information for the selection and construction of basic sanitation facilities in poor regions.
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Microbiota , Esgotos , Microbiologia do Solo , Solo , Esgotos/microbiologia , Solo/química , Resistência Microbiana a Medicamentos/genética , Bactérias/genética , Bactérias/classificação , HumanosRESUMO
In the aquaculture system of ornamental fish, the interaction between bacterial microbiota and ciliate protozoa can prevent or promote disease outbreaks, and different physicochemical conditions will affect the relationships between them. We investigated the interaction between bacterial microbiota and the parasite Tetrahymena pyriformis when infecting Poecilia reticulata (guppy) under different physicochemical conditions. The abundance of T. pyriformis in water, the relative abundance of bacterial species, and histopathological observation were studied or monitored using environmental DNA (eDNA) extraction technology, the qPCR method, and 16s rRNA sequencing, respectively. The morphological identification and phylogenetic analysis of T. pyriformis were carried out. The infected guppy tissue was also stained by the hematoxylin and eosin methods. The results showed: (1) the bacterial communities of water samples were mainly composed of species assigned to Proteobacteria and Bacteroidetes, and Tabrizicola and Puniceicoccaceae were positively correlated with fish mortality, T. pyriformis abundance, and temperature. (2) Arcicella and Methyloversatilis universalis with different correlations between ciliates appeared in different treatment groups, the result of which proved that environmental factors affected the interaction between bacteria and T. pyriformis. (3) Lower temperatures and a higher pH were more beneficial for preventing disease outbreaks.
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BACKGROUND: Patients with non-small cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD) experience worse clinical outcomes but respond better to immunotherapy than patients with NSCLC without COPD. Mucosal-associated invariant T (MAIT) cells, a versatile population of innate immune T lymphocytes, have a crucial function in the response to infection and tumors. This study investigated the distribution of MAIT cells in COPD-associated NSCLC and their involvement in the immune response. METHODS: Flow cytometry, immunohistochemistry, and immunofluorescence were performed on tissue samples of patients with NSCLC, with or without COPD, treated with or without anti-programmed death 1 (PD1) immunotherapy. MAIT cells were stimulated with 5-OP-RU using a mouse subcutaneous tumor model. RESULTS: Tumors contained significantly more MAIT cells than paraneoplastic tissues, and CD8+ MAIT cells accounted for more than 90% of these cells. Patients with NSCLC and COPD had higher CD8+ MAIT cell counts than those with NSCLC without COPD. Additionally, patients with NSCLC and COPD displayed reduced expression of the activation marker, CD69, and functional markers, granzyme B (GZMB) and interferon γ (IFNγ), and higher expression of the immune exhaustion marker, PD1. Among patients who received immunotherapy, the proportion with a complete or partial response was higher in those with COPD than in those without COPD. In patients with NSCLC and COPD, the major pathologic response (MPR) group had higher MAIT levels than those in the no major pathologic response (NPR) group. In the mouse subcutaneous tumor model stimulation of MAIT cells using 5-OP-RU enhanced the antitumor effects of anti-PD1. CONCLUSIONS: In patients with NSCLC and COPD, response to immunotherapy is associated with accumulation of CD8+ MAIT cells showing immune exhaustion. These findings may contribute to innovative approaches for immunotherapy targeting CD8+ MAIT cells.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Células T Invariantes Associadas à Mucosa , Doença Pulmonar Obstrutiva Crônica , Ribitol/análogos & derivados , Uracila/análogos & derivados , Humanos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Células T Invariantes Associadas à Mucosa/metabolismo , Células T Invariantes Associadas à Mucosa/patologia , Neoplasias Pulmonares/metabolismo , Terapia Neoadjuvante , Biomarcadores/metabolismo , Doença Pulmonar Obstrutiva Crônica/terapia , ImunoterapiaRESUMO
Therapeutic resistance and metastasis largely contribute to mortality from breast cancer and therefore understanding the underlying mechanisms of such remains an urgent challenge. By cross-analysis of TCGA and GEO databases, LINC00460 was identified as an oncogenic long non-coding RNA, highly expressed in Doxorubicin resistant breast cancer. LINC00460 was further demonstrated to promote stem cell-like and epithelial-mesenchymal transition (EMT) characteristics in breast cancer cells. LINC00460 interacts with FUS protein with consequent enhanced stabilization, which further promotes MYC mRNA maturation. LINC00460 expression was transcriptionally enhanced by c-MYC protein, forming a positive feedback loop to promote metastasis and Doxorubicin resistance. LINC00460 depletion in Doxorubicin-resistant breast cancer cells restored sensitivity to Doxorubicin and increased the efficacy of c-MYC inhibitor therapy. Collectively, these findings implicate LINC00460 as a promising prognostic biomarker and potential therapeutic target to overcome Doxorubicin resistance in breast cancer.