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The color potato has the function of both a food and vegetable. The color potato not only contains various amino acids and trace elements needed by the human body but also contains anthocyanins. Anthocyanins have many functions, such as antioxidation, inflammation inhibition, vision improvement, and cancer prevention, so colored potatoes are deeply loved by consumers and have good market prospects. However, at present, the detection of anthocyanin content in color potatoes mainly depends on chemical methods, which are time-consuming and laborious, so it is necessary to study a fast and accurate detection method. In this study, microscopic hyperspectral equipment was used to collect the spectral information of the outer skin and inner skin of potatoes. The original spectrum, pretreatment spectrum, and characteristic spectrum variables of the outer skin and inner skin were predicted by the convolution neural network (CNN) algorithm and partial least squares regression (PLS) algorithm, respectively, and the performance of the model was evaluated by the prediction set correlation coefficient (Rp), prediction set root mean square error (RMSEP), correction set correlation coefficient (Rc), correction set root mean square error (RMSEC), and residual prediction deviation (RPD). The results revealed that the inner skin Raw + CNN model constructed under raw spectral data is optimal with Rc = 0.9508, RMSEC = 0.0374%, Rp = 0.9461, RMSEP = 0.2361% and RPD = 4.4933. The inner skin Savitzky-Golay (SG) + Detrend (DET) + CNN model constructed from pre-processed spectral data is optimal with Rc = 0.9499, RMSEC = 0.0359%, Rp = 0.9439, RMSEP = 0.2384%, RPD = 4.6516. The inner skin DET + competitive adaptive reweighted sampling (CARS) +CNN model constructed from the feature-based spectral data was optimal with Rc = 0.9527, RMSEC = 0.0708%, Rp = 0.9457, RMSEP = 0.2711%, and RPD = 4.1623. It can be seen that the Rp, RMSEP, Rc, RMSEC, and RPD values for modeling the spectral information of the inner skin were higher than those of the outer skin under the three different spectral data. The prediction accuracy of the model built by the CNN algorithm was better than the conventional algorithm PLS, the application of the CNN algorithm in inner skin can achieve accurate prediction of anthocyanin content in potato.
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The reactivity and stability of zero-valent iron (ZVI) and sulfidated zero-valent iron (S-ZVI) are inherently contradictory. Iron sulfides (FeSX) on the S-ZVI surface play multiple roles, including electrostatic adsorption and catalyzing reduction. We proposed to balance the reactivity and air stability of S-ZVI by regulating FeSX. Benefiting from the superior coordination and accelerate electron transport capabilities of phosphate, herein, eco-friendly ammonium dihydrogen phosphate (ADP) was employed to synthesize N, P, and S-incorporated ZVI (NPS-ZVI) and regulate the FeSX. Raman, FTIR, XPS, and density functional theory (DFT) calculations were combined to reveal that HPO42- acts as the main P species on the Fe surface. The superior reactivity of NPS-ZVI was quantified by kobs, kSA, and kM of Cr(VI), which were 210.77, 27.44, and 211.17-fold than ZVI, respectively. NPS-ZVI demonstrated excellent reusability, with no risk of secondary pollution. Critically, NPS-ZVI could effectively maintain FeSX stability under the combination of diffusion limitation and surface protection mechanisms of ADP. The superior reactivity of NPS-ZVI was attributed to the fact that ADP maintains FeSX stability and accelerates electron transport. This study provides a novel strategy in balancing the reactivity and air stability of S-ZVI and offers theoretical support for material modification.
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Lung cancer is a highly heterogeneous malignancy, and despite the rapid development of chemotherapy and radiotherapy, acquired drug resistance and tumor progression still occur. Thus, it is urgent to identify novel therapeutic targets. Our research aims to screen novel biomarkers associated with the prognosis of lung carcinoma patients and explore the potential regulatory mechanisms. We obtained RNA sequencing (RNA-seq) data of lung cancer patients from public databases. Clinical signature analysis, weighted gene coexpression network analysis (WGCNA) and the random forest algorithm showed that C1q/tumor necrosis factor-related protein-6 (CTRP6) is a core gene related to lung cancer prognosis, and it was determined to promote tumor proliferation and metastasis both in vivo and in vitro. Mechanistically, silencing CTRP6 was determined to promote xCT/GPX4-involved ferroptosis through functional assays related to lipid peroxidation, Fe2+ concentration and mitochondrial ultrastructure. By performing interactive proteomics analyses in lung tumor cells, we identified the interaction between CTRP6 and suppressor of cytokine signaling 2 (SOCS2) leading to SOCS2 ubiquitination degradation, subsequently enhancing the downstream xCT/GPX4 signaling pathway. Moreover, significant correlations between CTRP6-mediated SOCS2 and ferroptosis were revealed in mouse models and clinical specimens of lung cancer. As inducing ferroptosis has been gradually regarded as an alternative strategy to treat tumors, targeting CTRP6-mediated ferroptosis could be a potential strategy for lung cancer therapy.
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Ferroptose , Neoplasias Pulmonares , Animais , Humanos , Camundongos , Adipocinas/metabolismo , Ferroptose/genética , Pulmão/metabolismo , Neoplasias Pulmonares/genética , Prognóstico , Transdução de Sinais , Proteínas Supressoras da Sinalização de Citocina/metabolismoRESUMO
With the development of shale gas exploration and exploitation, the mechanical and failure characteristics of shale have become one of the focuses. However, few studies have considered the differences in the mechanical properties of shales in different shale gas blocks. In this study, the effects of bedding orientation on the stress-strain curves, elastic modulus, Poisson's ratio, and fracture morphology of shale samples from the Zhaotong block are analyzed by laboratory experiments, first. Then, a standard deviation method is used to characterize the anisotropy degree of the mechanical and fracturing characteristics of shale. The anisotropy ratio of shale samples between the Zhaotong and Chongqing areas has been comparatively studied. Comparison results show that the shale anisotropy induced by the bedding orientations demonstrates apparent regional characteristics. There are significant differences in the mechanical properties of shale obtained from different shale gas blocks. It indicates that the optimization of engineering practices such as the design of hydraulic fracturing should consider the influences of the bedding orientations and shale gas blocks on the shale anisotropy.
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Background: Although many CTC isolation and detection methods can provide information on cancer cell counts, downstream gene and protein analysis remain incomplete. Therefore, it is crucial to develop a technology that can provide comprehensive information on both the number and profile of CTC. Methods: In this study, we developed a novel microfluidics-based CTC separation and enrichment platform that provided detailed information about CTC. Results: This platform exhibits exceptional functionality, achieving high rates of CTC recovery (87.1%) and purification (â¼4 log depletion of WBCs), as well as accurate detection (95.10%), providing intact and viable CTCs for downstream analysis. This platform enables successful separation and enrichment of CTCs from a 4 mL whole-blood sample within 15 minutes. Additionally, CTC subtypes, selected protein expression levels on the CTC surface, and target mutations in selected genes can be directly analyzed for clinical utility using immunofluorescence and real-time polymerase chain reaction, and the detected PD-L1 expression in CTCs is consistent with immunohistochemical assay results. Conclusion: The microfluidic-based CTC enrichment platform and downstream molecular analysis together provide a possible alternative to tissue biopsy for precision cancer management, especially for patients whose tissue biopsies are unavailable.
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MicroRNAs (miRNAs) are a group of small non-coding RNAs that affect gene expression. The role of miRNAs in different types of cancers has been published and it was shown that several miRNAs are inappropriately expressed in different cancers. Among the mechanisms that can cause this lack of proper expression are epigenetics, chromosomal changes, polymorphisms or defects in processing proteins. Recent research shows that phytochemicals, including epigallocatechin-3-gallate (EGCG), exert important epigenetic-based anticancer effects such as pro-apoptotic or anti proliferative through miRNA gene silencing. Given that EGCG is able to modulate a variety of cancer-related process i.e., angiogenesis, proliferation, metastasis and apoptosis via targeting various miRNAs such as let-7, miR-16, and miR-210. The discovery of new miRNAs and the differences observed in their expression when exposed to EGCG provides evidence that targeting these miRNAs may be beneficial as a form of treatment. In this review, we aim to provide an overview, based on current knowledge, on how phytochemicals, including epigallocatechin-3-gallate, can be considered as potential miRNAs modulator to improve efficacy of current cancer treatments.
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BACKGROUND: Histopathological transformation between different types of lung cancer cells has been reported following a variety of anti-tumor treatments. Examples include transformation from lung adenocarcinoma to squamous-cell carcinoma (SCC) and transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC). CASE REPORT: A patient with intermittent hemoptysis for 2 days underwent a computed tomography (CT) scan that revealed interstitial pneumonia in addition to two enlarged paratracheal lymph nodes: one on the right (4R) and one on the left (4L) measuring 10 and 7 mm in diameter, respectively (Fig. 1). There was no evidence of a lung or bronchial mass. Bronchoscopy identified an endoluminal primary mass in a superior segmental bronchus of the left lower lobe and pathological examination following surgery confirmed it to be SCC. At 15 months post operation, a CT scan detected that the 4R lymph node had increased in size from 10 to 16 mm in diameter. At the next follow-up 7 months later, a CT scan showed that the R4 lymph node had further increased in size from 16 to 40 mm in the short axis, making it difficult for a surgeon to resect it "en bloc" immediately. The maximum standardized uptake value was 7.5 on PET-CT images. One month following completion of one cycle of neoadjuvant chemotherapy with gemcitabine and nedaplatin, a further CT scan indicated that the lymph node had decreased in size from 40 to 30 mm in the short axis. A complete mediastinal lymphadenectomy via open thoracotomy was performed and the lymph node was resected. Histological examination identified a main large cell neuroendocrine carcinoma (LCNEC) component with a small fraction of small cell carcinoma, confirmed by immunohistochemical analysis and genetic evidence. CONCLUSION: Histopathological transformation from SCC to LCNEC with a small fraction of SCLC may have occurred spontaneously without any treatment.
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Carcinoma de Células Grandes , Carcinoma Neuroendócrino , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Carcinoma de Células Escamosas/patologia , Carcinoma de Pequenas Células do Pulmão/patologia , Pulmão/patologia , Carcinoma de Células Grandes/cirurgia , Carcinoma de Células Grandes/patologia , Linfonodos/patologia , Carcinoma Neuroendócrino/patologiaRESUMO
BACKGROUND: Iliopsoas plane block (IPB) is a novel analgesic technique for hip surgery that retains quadriceps strength. However, evidence from randomized controlled trial is remains unavailable. We hypothesized that IPB, as a motor-sparing analgesic technique, could match the femoral nerve block (FNB) in pain management and morphine consumption, providing an advantage for earlier functional training in patients underwent hip arthroplasty. METHODS: We recruited ninety patients with femoral neck fracture, femoral head necrosis or hip osteoarthritis who were scheduled for unilateral primary hip arthroplasty were recruited and received either IPB or FNB. Primary outcome was the pain score during hip flexion at 4 h after surgery. Secondary outcomes included quadriceps strength and pain scores upon arrival at post anesthesia care unit (PACU) and at 2, 4, 6, 24, 48 h after surgery, the first time out of bed, total opioids consumption, patient satisfaction, and complications. RESULTS: There was no significant difference in terms of pain score during hip flexion at 4 h after surgery between the IPB group and FNB group. The quadriceps strength of patients receiving IPB was superior to those receiving FNB upon arrival at PACU and at 2, 4, 6 and 24 h after surgery. The IPB group showed a shorter first time out of bed compared to the FNB group. However, there were no significant differences in terms of pain scores within 48 h after surgery, total opioids consumption, patient satisfaction and complications between the two groups. CONCLUSION: IPB was not superior to FNB in terms of postoperative analgesia for hip arthroplasty. However, IPB could serve as an effective motor-sparing analgesic technique for hip arthroplasty, which would facilitate early recovery and rehabilitation. This makes IPB worth considering as an alternative to FNB. TRIAL REGISTRATION: The trial was registered prior to patient enrollment at the Chinese Clinical Trial Registry (ChiCTR2200055493; registration date: January 10, 2022; enrollment date: January 18, 2022; https://www.chictr.org.cn/searchprojEN.html ).
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Artroplastia de Quadril , Bloqueio Nervoso , Humanos , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/etiologia , Analgésicos Opioides , Nervo Femoral , Bloqueio Nervoso/métodos , Artroplastia de Quadril/efeitos adversos , AnalgésicosRESUMO
Background: Genetic variability in DNA double-strand break repair genes such as RAD51 gene and its paralogs XRCC2ãXRCC3 may contribute to the occurrence and progression of breast cancer. To obtain a complete evaluation of the above association, we performed a meta-analysis of published studies. Methods: Electronic databases, including PubMed, EMBASE, Web of Science, and Cochrane Library, were comprehensively searched from inception to September 2022. The Newcastle-Ottawa Scale (NOS) checklist was used to assess all included non-randomized studies. Odds ratios (OR) with 95% confidence intervals (CI) were calculated by STATA 16.0 to assess the strength of the association between single nucleotide polymorphisms (SNPs) in these genes and breast cancer risk. Subsequently, the heterogeneity between studies, sensitivity, and publication bias were performed. We downloaded data from The Cancer Genome Atlas (TCGA) and used univariate and multivariate Cox proportional hazard regression (CPH) models to validate the prognostic value of these related genes in the R software. Results: The combined results showed that there was a significant correlation between the G172T polymorphism and the susceptibility to breast cancer in the homozygote model (OR= 1.841, 95% CI=1.06-3.21, P=0.03). Furthermore, ethnic analysis showed that SNP was associated with the risk of breast cancer in Arab populations in homozygous models (OR=3.52, 95% CI=1.13-11.0, P= 0.003). For the XRCC2 R188H polymorphism, no significant association was observed. Regarding polymorphism in XRCC3 T241M, a significantly increased cancer risk was only observed in the allelic genetic model (OR=1.05, 95% CI= 1.00-1.11, P=0.04). Conclusions: In conclusion, this meta-analysis suggests that Rad51 G172T polymorphism is likely associated with an increased risk of breast cancer, significantly in the Arab population. The relationship between the XRCC2 R188H polymorphism and breast cancer was not obvious. And T241M in XRCC3 may be associated with breast cancer risk, especially in the Asian population.
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With the use of thoracoscopic surgery technology, onelung ventilation (OLV) is becoming more crucial as a basic requirement for enhanced recovery after surgery; however, it can lead to severe pulmonary injury, which is an issue for anesthesiologists. Therefore, it is important to protect pulmonary function during thoracic surgery anesthesia, particularly to protect the function of the collapsed lung. Our previous study on rabbits reported that nicorandil, a US Food and Drug Administrationapproved mitochondrial ATPsensitive potassium channelspecific opener, can protect against lung injury in the collapsed lung. Therefore, the beneficial effect of nicorandil on OLVinduced pulmonary injury in clinical thoracic surgery was further evaluated in the present study. Nicorandil was infused at 2 mg/h for 2 h from induction to 1 h after OLV in the nicorandil group. Trends in arterial oxygen desaturation (SaO2), arterial partial pressure for oxygen (PaO2) and the lung microstructure were assessed. ELISA was used to assess the levels of TNFα and malondialdehyde (MDA), and the activity of superoxide dismutase (SOD). A TUNEL assay was performed to evaluate apoptosis. Western blotting was used to analyze the relative expression levels of signaling proteins associated with apoptosis. Western blotting was performed to evaluate the protein expression levels of hypoxiainducible factor 1α (HIF1α), PI3K, Akt and NFκB, and reverse transcriptionquantitative PCR was used to detect HIF1α mRNA expression levels in the lungs of patients infused with nicorandil and nitroglycerin. Nicorandil treatment was associated with higher SaO2 and PaO2 compared with nitroglycerin treatment in OLV. The levels of MDA and TNFα in the operated lung of the nicorandil group were significantly lower compared with those in the control group. In addition, nicorandil was associated with higher SOD activity compared with nitroglycerin. The nicorandiltreated lung, similar to the sham group, exhibited improved microstructure and less apoptosis in the experimental group. The protein expression levels of PI3K, phosphorylated Akt and HIF1α were significantly increased, whereas NFκB was significantly decreased in the nicorandiltreated lung compared with the control group. Overall, nicorandil demonstrated beneficial effects by decreasing apoptosis in the operated lung, which was collapsed and then reexpanded during OLV in thoracic surgery anesthesia. Nicorandil may serve a vital role by decreasing the overloading of calcium in mitochondria, shutting off the mitochondrial membrane permeability transition pore, reducing the release of cytochrome c, simultaneously triggering activation of the PI3K/Akt signaling pathway around the cell membrane, downregulating NFκB, upregulating HIF1α, and then reducing Bax/Bcl2, caspase3 and apoptosis. The trial registration was ChiCTRIOR17014061 (registered on December 20, 2017).
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Lesão Pulmonar , Nicorandil , Procedimentos Cirúrgicos Torácicos , Apoptose , Canais KATP/metabolismo , Pulmão/metabolismo , Lesão Pulmonar/metabolismo , Mitocôndrias/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Nicorandil/uso terapêutico , Nitroglicerina/farmacologia , Oxigênio/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , HumanosRESUMO
Background: With its growing popularity and potential outcome, preoperative three-dimensional reconstruction of chest computed tomography (CT) has been widely used in video-assisted thoracic surgery (VATS) segmentectomy for treating non-small cell lung cancer (NSCLC). This study aimed to summarize the experience of anatomical variation analysis of left upper pulmonary blood vessels and bronchi based on the three-dimensional reconstruction of chest CT. Materials and methods: A total of 103 patients with early-stage NSCLC were chosen to undergo VATS segmentectomy based on preoperative three-dimensional reconstruction of chest CT in our institute from September 2019 to July 2022. Data such as clinical characteristics and variations in blood vessels and bronchi were reviewed in this study. Results: The branches of the left lingular pulmonary artery may mutate into the LS1 + 2 + 3. A1 + 2 has four subtypes. The distribution of variation is relatively balanced, and the most common variation is type I (35/103, 33.9%). Most lingular arteries originate from the oblique cleft side of the lingular bronchus (79/103,76.7%). Most V(1 + 2)c* are small developments (70/103, 68.0%). The venous return of the proper segment mainly depends on V(1 + 2)b + c. The variation in the left upper lobe bronchus is complex. The most common variant is the bifurcation type (type A to G, 92/103, 89.3%) and bifurcation type A (62/103, 60.2%). The posterior apical segment artery of the left upper lobe is not accompanied by its bronchus. Conclusions: The variation types of blood vessels and bronchus in the upper lobe of the left lung are complex. Preoperative CT-based three-dimensional reconstruction of pulmonary arteries, veins, and bronchi is of great significance. It can help understand the variations, accurately locate lesions before the surgery, and effectively plan surgeries.
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Cervical cancer is a female-specific cancer with relatively high morbidity and mortality. As known to all, immune cell infiltrations in the cancer microenvironment are closely related to the cancer diagnosis and prognosis. Here we revealed that the CD8+ T cell infiltration was significantly upregulated in cervical cancer versus normal cervix uteri samples. Through univariate and multivariate cox analyses, we discovered that the CD8+ T cell infiltration was the only independent beneficial factor for the prognosis of cervical cancer. To explore the genes associated with the CD8+ T cell infiltration in cervical cancer, we performed the WGCNA analysis on the differentially expressed genes (DEGs) of cervical cancer versus normal cervix uteri tissues. As a result, 231 DEGs were found to be associated with CD8+ T cell infiltration in cervical cancer. Subsequently, with the Cytoscape analysis, we identified 105 hub genes out of the 231 DEGs. To further explore the genes that might be responsible for the prognosis of cervical cancer, we performed a univariate cox analysis followed by a LASSO assay on the 105 hub genes and located four genes (IGSF6, TLR10, FCRL3, and IFI30) finally. The four genes could be applied to the prediction of the prognosis of cervical cancer, and relatively higher expression of these four genes predicted a better prognosis. These findings contributed to our understanding of the prognostic values of CD8+ T cell infiltration and its associated genes in cervical cancer and thus might benefit future immune-related therapies.
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BACKGROUND: Hypoxia naturally happens in embryogenesis and thus serves as an important environmental factor affecting embryo development. Hif-1α, an essential hypoxia response factor, was mostly considered to mediate or synergistically regulate the effect of hypoxia on stem cells. However, the function and relationship of hypoxia and Hif-1α in regulating mesendoderm differentiation remains controversial. RESULTS: We here discovered that hypoxia dramatically suppressed the mesendoderm differentiation and promoted the ectoderm differentiation of mouse embryonic stem cells (mESCs). However, hypoxia treatment after mesendoderm was established promoted the downstream differentiation of mesendoderm-derived lineages. These effects of hypoxia were mediated by the repression of the Wnt/ß-Catenin pathway and the Wnt/ß-Catenin pathway was at least partially regulated by the Akt/Gsk3ß axis. Blocking the Wnt/ß-Catenin pathway under normoxia using IWP2 mimicked the effects of hypoxia while activating the Wnt/ß-Catenin pathway with CHIR99021 fully rescued the mesendoderm differentiation suppression caused by hypoxia. Unexpectedly, Hif-1α overexpression, in contrast to hypoxia, promoted mesendoderm differentiation and suppressed ectoderm differentiation. Knockdown of Hif-1α under normoxia and hypoxia both inhibited the mesendoderm differentiation. Moreover, hypoxia even suppressed the mesendoderm differentiation of Hif-1α knockdown mESCs, further implying that the effects of hypoxia on the mesendoderm differentiation were Hif-1α independent. Consistently, the Wnt/ß-Catenin pathway was enhanced by Hif-1α overexpression and inhibited by Hif-1α knockdown. As shown by RNA-seq, unlike hypoxia, the effect of Hif-1α was relatively mild and selectively regulated part of hypoxia response genes, which fine-tuned the effect of hypoxia on mESC differentiation. CONCLUSIONS: This study revealed that hypoxia is fine-tuned by Hif-1α and regulates the mesendoderm and ectoderm differentiation by manipulating the Wnt/ß-Catenin pathway, which contributed to the understanding of hypoxia-mediated regulation of development.
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Proteínas Proto-Oncogênicas c-akt , beta Catenina , Animais , Glicogênio Sintase Quinase 3 beta/metabolismo , Hipóxia , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/farmacologia , Via de Sinalização Wnt , beta Catenina/metabolismoRESUMO
Simultaneous isolation of various circulating tumor cell (CTC) subtypes from whole blood is useful in cancer diagnosis and prognosis. Microfluidic affinity separation devices are promising for CTC separation because of their high throughput capacity and automatability. However, current affinity agents, such as antibodies (mAbs) and aptamers (Apts) alone, are still suboptimal for efficient, consistent, and versatile cell analysis. By introducing a hybrid affinity agent, i.e., an aptamer-antibody (Apt-mAb) conjugate, we developed a universal and regenerative microchip with high efficiency and non-invasiveness in the separation and profiling of various CTCs from blood. The Apt-mAb conjugate consists of a monoclonal antibody that specifically binds the target cell receptor and a surface-bound aptamer that recognizes the conserved Fc region of the mAb. The aptamer then indirectly links the surface functionalization of the microfluidic channels to the mAbs. This hybrid affinity agent and the microchip platform may be widely useful for various bio-particle separations in different biological matrices. Further, the regeneration capability of the microchip improves data consistency between multiple uses and minimizes plastic waste while promoting environmental sustainability. STATEMENT OF SIGNIFICANCE: A hybrid affinity agent, Apt-mAb, consisting of a universal aptamer (Apt) that binds the conserved Fc region of monoclonal antibodies (mAbs) was developed. The invented nano-biomaterial combines the strengths and overcomes the weakness of both Apts and mAbs, thus changing the paradigm of affinity separation of cell subtypes. When Apt-mAb was used to fabricate microfluidic chips using a "universal screwdriver" approach, the microchip could be easily tuned to bind any cell type, exhibiting great universality. Besides high sensitivity and selectivity, the superior regenerative capacity of the microchips makes them reusable, which provides improved consistency and repeatability in cell profiling and opens a new approach towards in vitro diagnostic point-of-care testing devices with environmental sustainability and cost-effectiveness.
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Aptâmeros de Nucleotídeos , Técnicas Analíticas Microfluídicas , Células Neoplásicas Circulantes , Anticorpos Monoclonais , Linhagem Celular Tumoral , Separação Celular , Dimaprit/análogos & derivados , Humanos , Microfluídica , Células Neoplásicas Circulantes/patologia , PlásticosRESUMO
In resected non-small cell lung cancer (NSCLC), ALK rearrangements are associated with worse recurrence-free survival (RFS) than other driver genes. In addition, the micropapillary pattern of NSCLC is associated with a poor prognosis. In recent years, crizotinib tyrosine kinase inhibitors (TKIs) have been widely used to treat patients with advanced NSCLC with ALK fusion. Patient survival outcomes have become highly promising, reflecting the necessity of exploring the application of ALK-TKIs in resected, early stage NSCLC with ALK rearrangements. A 60-year-old Chinese man was diagnosed with stage IIB lung adenocarcinoma harboring a novel SLC8A1/LINC01913 intergenic region-ALK fusion identified by NGS and validated by immunohistochemical staining (IHC) and fluorescence in situ hybridization (FISH). Crizotinib (250 mg orally once daily) was administered to the patient following surgery. The patient remained relapse-free after four months and seven months. This report provided a valuable treatment plan for early lung adenocarcinoma patients with high risks to prevent a postoperative recurrence.
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Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Crizotinibe/uso terapêutico , Crizotinibe/farmacologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Hibridização in Situ Fluorescente , Quinase do Linfoma Anaplásico/genética , DNA Intergênico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Imuno-Histoquímica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas de Fusão Oncogênica/genéticaRESUMO
Two non-ionic reagents, polyethylene glycol 4000 and Tween-80, two anionic reagents, sodium dodecyl benzenesulfonate and sodium lauryl sulfate, and a mixture of these non-ionic and anionic reagents were used as penetrants. The processes of replacement desorption and relief-pressure desorption of gas-containing coal were studied, the influence of the penetrant on the amount of gas replacement desorption and relief-pressure desorption was explored, and the change rule of the amounts of gas replacement desorption and relief-pressure desorption was analysed. The results show that the increase rate of the replacement desorption amount of the mixed penetrant is 11.81%-34.75%, and the decrease rate of the relief-pressure desorption amount is 51.68%-72.69%, which are higher values than those with a single penetrant. As the mass fraction of penetrant increases within the range of 0.5%~2%, the capacity of gas replacement desorption and hindering gas relief-pressure desorption will increase. At the same mass fraction, the effect of the mixed penetrant is better than that of the anionic penetrant, which in turn is better than that of the non-ionic penetrant.
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Carvão Mineral , Dodecilsulfato de SódioRESUMO
Sepsis remains the most lethal infectious disease and substantially impairs patient prognosis after liver transplantation (LT). Our previous study reported a role of the pannexin 1 (PANX1)-interleukin-33 (IL-33) axis in activating innate immunity to protect against methicillin-resistant Staphylococcus aureus infection; however, the role of PANX1 in regulating adaptive immunity in sepsis and the underlying mechanism are unclear. In this study, we examined the role of the PANX1-IL-33 axis in protecting against sepsis caused by a gram-negative bacterial infection in an independent LT cohort. Next, in animal studies, we assessed the immunological state of Panx1-/- mice with lipopolysaccharide (LPS)-induced endotoxemia and then focused on the cytokine storm and regulatory T cells (Tregs), which are crucial for the resolution of inflammation. To generate liver-specific Panx1-deficient mice and mimic clinical LT procedures, a mouse LT model was established. We demonstrated that hepatic PANX1 deficiency exacerbated LPS-induced endotoxemia and dysregulated the immune response in the mouse LT model. In hepatocytes, we confirmed that PANX1 positively regulated IL-33 synthesis after LPS administration. We showed that the adenosine triphosphate-P2X7 pathway regulated the hepatic PANX1-IL-33 axis during endotoxemia in vitro and in vivo. Recombinant IL-33 treatment rescued LPS-induced endotoxemia by increasing the numbers of liver-infiltrating ST2+ Tregs and attenuating the cytokine storm in hepatic PANX1-deficient mice. In conclusion, our findings revealed that the hepatic PANX1-IL-33 axis protects against endotoxemia and liver injury by targeting ST2+ Tregs and promoting the early resolution of hyperinflammation.