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BACKGROUND: Atherosclerotic (AS) plaques require a dense necrotic core and a robust fibrous cap to maintain stability. While previous studies have indicated that the traditional Chinese medicine Huang Lian Jie Du Decoction (HLJDD) possesses the capability to stabilize AS plaques, the underlying mechanisms remain obscure. This study aims to delve deeper into the potential mechanisms by which HLJDD improves AS through an integrated research strategy. METHODS: Leveraging an AS model in ApoE-/- mice exposed to a high-fat diet (HFD), we scrutinized the therapeutic effects of HLJDD using microscopic observations, oil red O staining, HE staining and Masson staining. Employing comprehensive techniques of network pharmacology, bioinformatics, and molecular docking, we elucidated the mechanism by which HLJDD stabilizes AS plaques. In vitro experiments, utilizing ox-LDL-induced macrophages and apoptotic vascular smooth muscle cells (VSMCs), assessed the impact of HLJDD on efferocytosis and the role of SLC2A1. RESULTS: In vivo experiments showcased the efficacy of HLJDD in reducing the quantity of aortic plaques, diminishing lipid deposition, and enhancing plaque stability in AS mice. Employing network pharmacology and machine learning, we pinpointed SLC2A1 as a crucial regulatory target. Molecular docking further validated the binding of HLJDD components with SLC2A1. The experiments demonstrated a dose-dependent upregulation in SLC2A1 expression by HLJDD, amplifying efferocytosis. Importantly, this effect was reversed by the SLC2A1 inhibitor STF-31, highlighting the pivotal role of SLC2A1 as a target. CONCLUSION: The HLJDD can modulate macrophage efferocytosis by enhancing the expression levels of SLC2A1, thereby improving the stability of atherosclerotic plaques.
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BACKGROUND: Atherosclerosis (AS) is the main cause of coronary heart disease, cerebral infarction, and peripheral vascular disease. QingRe HuoXue Formula (QRHXF), a common prescription of traditional Chinese medicine, has a definite effect on the clinical treatment of AS, but its mechanism remains to be further explored. PURPOSE: The current study aimed to demonstrate the effectiveness of the QRHXF in the treatment of AS and further reveal its potential pharmacological mechanisms. METHODS: Explore the potential mechanisms of QRHXF in treating AS through network pharmacology, machine learning, transcriptome analysis, and molecular docking, then validate them through animal experiments and PCR experiments. RESULTS: The results indicate that through network pharmacology and machine learning methods, 10 genes including COL1A1 and CCR7 have been identified as potential candidate genes for QRHXF treatment of atherosclerosis. Molecular docking indicates that the key active compounds of QRHXF have good binding affinity with the predicted genes. Two key genes, COL1A1 and CCR7, were identified through transcriptome sequencing analysis of the aortic tissue of APOE-/- mice in the AS model. Finally, the animal and PCR experiment found that QRHXF can effectively reduce the formation of aortic plaques in APOE-/- mice of the AS model, lower blood lipid levels in mice, and upregulate the mRNA expression level of COL1A1, promoting the formation of fibrosis within plaques. CONCLUSIONS: We revealed the inflammatory and immune pathways underlying QRHXF treatment for AS, and verified through transcriptome sequencing and experiments that QRHXF can promote the expression of COL1A1, thereby increasing the stability of AS plaques.
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Stable solid-electrolyte interphase (SEI) is crucial for cycling reversibility of Na-ion batteries by mitigating continuous side reactions. So far, the severe SEI dissolution leads to low Coulombic efficiency (CE) and short cycle life. Meanwhile, the quantified relationship between SEI components and their solubility remains unclear. In this work, we establish the direct correlation between SEI components and SEI solubility, and quantify that the solubility of organic-rich SEI is 3.26 times of inorganic-rich SEI. We further propose a feasible strategy to preform inorganic-rich insoluble SEI and demonstrate a practical hard carbon (HC)||NaMn0.33Fe0.33Ni0.33O2 full cell in commercial electrolyte of 1 M NaPF6 in propylene carbonate (PC) with 80.0% capacity retention for 900 cycles, and achieve a record-high average CE of 99.95% for a practical Na-ion full cell. This study provides an effective strategy of preforming insoluble SEI to suppress its dissolution towards highly reversible Na-ion batteries.
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Background: We aim to investigate genes associated with myasthenia gravis (MG), specifically those potentially implicated in the pathogenesis of dilated cardiomyopathy (DCM). Additionally, we seek to identify potential biomarkers for diagnosing myasthenia gravis co-occurring with DCM. Methods: We obtained two expression profiling datasets related to DCM and MG from the Gene Expression Omnibus (GEO). Subsequently, we conducted differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) on these datasets. The genes exhibiting differential expression common to both DCM and MG were employed for protein-protein interaction (PPI), Gene Ontology (GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Additionally, machine learning techniques were employed to identify potential biomarkers and develop a diagnostic nomogram for predicting MG-associated DCM. Subsequently, the machine learning results underwent validation using an external dataset. Finally, gene set enrichment analysis (GSEA) and machine algorithm analysis were conducted on pivotal model genes to further elucidate their potential mechanisms in MG-associated DCM. Results: In our analysis of both DCM and MG datasets, we identified 2641 critical module genes and 11 differentially expressed genes shared between the two conditions. Enrichment analysis disclosed that these 11 genes primarily pertain to inflammation and immune regulation. Connectivity map (CMAP) analysis pinpointed SB-216763 as a potential drug for DCM treatment. The results from machine learning indicated the substantial diagnostic value of midline 1 interacting protein1 (MID1IP1) and PI3K-interacting protein 1 (PIK3IP1) in MG-associated DCM. These two hub genes were chosen as candidate biomarkers and employed to formulate a diagnostic nomogram with optimal diagnostic performance through machine learning. Simultaneously, single-gene GSEA results and immune cell infiltration analysis unveiled immune dysregulation in both DCM and MG, with MID1IP1 and PIK3IP1 showing significant associations with invasive immune cells. Conclusion: We have elucidated the inflammatory and immune pathways associated with MG-related DCM and formulated a diagnostic nomogram for DCM utilizing MID1IP1/PIK3IP1. This contribution offers novel insights for prospective diagnostic approaches and therapeutic interventions in the context of MG coexisting with DCM.
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Background: The glucan extract of Oudemansiella raphanipes (Orp) has multiple biological properties, similar to extracts of other natural edible fungi. Drugs traditionally used in cancer treatment are associated with several drawbacks, such as side effects, induction of resistance, and poor prognosis, and many recent studies have focused on polysaccharides extracted from natural sources as alternatives. Our study focuses on the therapeutic role and molecular mechanism of action of Orp in breast cancer progression. Methods: MMTV-PyMT transgenic mice were used as the spontaneous breast cancer mice model. Immunoblotting, hematoxylin-eosin staining, immunohistochemistry, and immunofluorescence were used to evaluate the tumor behaviors in breast cancer. The inflammatory cell model was constructed using TNF-α. Macrophage activation and WNT/ß-catenin signaling were assayed using western blotting and immunofluorescence. Results: Orp management significantly inhibited tumor growth and promoted tumor cell apoptosis in MMTV-PyMT transgenic mice. Besides, the Orp challenge also attenuated the ability of breast tumors to metastasize into lung tissues. Mechanistically, Orp treatment restrained the polarization of M1 macrophages to M2 macrophages and suppressed WNT/ß-catenin signaling in mouse tumor tissues, which implied that Orp-mediated tumor inhibition partly occurred via regulating the inflammatory response. Findings from in vitro experiments confirmed that Orp inhibited the TNF-α-induced nuclear transportation of ß-catenin, thus preventing inflammation signaling and the expression of c-Myc in MCF-7 cells. Conclusion: Orp inhibits breast cancer growth and metastasis by regulating macrophage polarization and the WNT/ß-catenin signaling axis. The findings of this study suggest that Orp may be a promising therapeutic strategy for breast cancer.
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Microwave imaging is a promising method for early diagnosing and monitoring brain strokes. It is portable, non-invasive, and safe to the human body. Conventional techniques solve for unknown electrical properties represented as pixels or voxels, but often result in inadequate structural information and high computational costs. We propose to reconstruct the three dimensional (3D) electrical properties of the human brain in a feature space, where the unknowns are latent codes of a variational autoencoder (VAE). The decoder of the VAE, with prior knowledge of the brain, acts as a module of data inversion. The codes in the feature space are optimized by minimizing the misfit between measured and simulated data. A dataset of 3D heads characterized by permittivity and conductivity is constructed to train the VAE. Numerical examples show that our method increases structural similarity by 14% and speeds up the solution process by over 3 orders of magnitude using only 4.8% number of the unknowns compared to the voxel-based method. This high-resolution imaging of electrical properties leads to more accurate stroke diagnosis and offers new insights into the study of the human brain.
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Microondas , Accidente Cerebrovascular , Humanos , Imagenología Tridimensional/métodos , Accidente Cerebrovascular/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Conductividad EléctricaRESUMEN
Introduction: Radical cystectomy with dissection of pelvic lymph nodes and urethral diversion is the standard surgical treatment for muscle-invasive non-metastatic bladder cancer. In rare cases where patients with bladder cancer without distant metastasis have pelvic multi-organ invasion, the cancer compresses or invades the ureter and, in severe cases, leads to bilateral upper urinary tract obstruction and renal damage. The treatment recommended by guidelines often cannot improve the patients' clinical symptoms immediately, and patients cannot complete the treatment owing to severe side effects, resulting in poor survival benefits. Case presentation: A 69-year-old woman with facial edema was treated at the First Affiliated Hospital of Jinan University. The serum creatinine and potassium values were 1244 umol/L and 5.86 mmol/L, respectively. Pelvic magnetic resonance and abdominal computed tomography revealed that the bladder tumor had infiltrated the uterus, anterior vaginal wall, rectum, right ureter, right fallopian tube, and right ovary and metastasized to multiple pelvic lymph nodes. Tumor invasion of the right ureter resulted in severe hydronephrosis of the right kidney and loss of function and obstructive symptoms in the left kidney. Four days later, the patient's creatinine level decreased to 98 u mol/L, the general condition significantly improved, and the patient and family members strongly desired surgical treatment of the tumor. Through a comprehensive preoperative discussion, possible intraoperative and postoperative complications were evaluated. Right nephrectomy, right ureterectomy, total pelvic organ resection, extended pelvic lymph node dissection, and bowel and urinary diversion were conducted under 3D laparoscopy-assisted treatment. The patient was followed-up for 1.5 years and showed good tumor control, self-care, and mental status. Conclusion: Minimally invasive surgery is a curative option for patients with bladder cancer with pelvic multi-organ invasion without distant metastasis. Surgeons should strictly control the indications for surgery and warn patients about the occurrence of related post-surgical complications.
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The utilization of the sol-gel method for fabricating planar SnO2 as the electron transport layer (ETL) induces numerous defects on the SnO2 layer surface and perovskite film bottom, causing considerable deterioration of the device performance. Conventional inorganic salt-doped SnO2 precursor solutions used for passivation may cause incomplete substrate coverage due to the presence of inorganic salt crystals, further degrading the device performance. Here, a substrate modification approach involving the pretreatment of a fluorine-doped SnO2 (FTO) substrate with NH4PF6 is proposed. The interaction between PF6- ions and the FTO substrate enhances SnO2 film quality; excess PF6- ions decrease the number of defects on the film surface. NH4+ ions react with an -OH stabilizing agent in the SnO2 solution and are eliminated during annealing. The combined effects suppress nonradiative recombination and ion migration at the ETL-perovskite interface. The corresponding high-quality perovskite solar cells (PSCs) exhibit a fill factor of â¼0.825; PSC efficiency increases from 19.59% to 22.32%.
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The Pulmonary Function Test (PFT) is a widely utilized and rigorous classification test for evaluating lung function, serving as a comprehensive diagnostic tool for lung conditions. Meanwhile, Electrical Impedance Tomography (EIT) is a rapidly advancing clinical technique that visualizes conductivity distribution induced by ventilation. EIT provides additional spatial and temporal information on lung ventilation beyond traditional PFT. However, relying solely on conventional isolated interpretations of PFT results and EIT images overlooks the continuous dynamic aspects of lung ventilation. This study aims to classify lung ventilation patterns by extracting spatial and temporal features from the 3D EIT image series. The study uses a Variational Autoencoder (VAE) with a MultiRes block to compress the spatial distribution in a 3D image into a one-dimensional vector. These vectors are then stacked to create a feature map for the exhibition of temporal features. A simple convolutional neural network is used for classification. Data from 137 subjects were utilized for the training phase. Initially, the model underwent validation through a leave-one-out cross-validation process. During this validation, the model achieved an accuracy and sensitivity of 0.96 and 1.00, respectively, with an f1-score of 0.98 when identifying the normal subjects. To assess pipeline reliability and feasibility, we tested it on 9 newly recruited subjects, with accurate ventilation mode predictions for 8 out of 9. In addition, we included 2D EIT results for comparison and conducted ablation experiments to validate the effectiveness of the VAE. The study demonstrates the potential of using image series for lung ventilation mode classification, providing a feasible method for patient prescreening and presenting an alternative form of PFT.
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Defects present on the top surface of perovskite films have a pronounced detrimental impact on the photovoltaic performance and stability of perovskite solar cells (PSCs). Consequently, the development of effective defect passivation strategies has become key in enhancing both the power conversion efficiency (PCE) and stability of PSCs. In this study, a small molecule material, 4-Aminophthalonitrile (4-APN), was introduced as a means to mitigate surface defects within perovskite films. Obviously, 4-APN effectively passivates the defects at grain boundaries by combining cyano groups (-C≡N) with Pb2+ , significantly reducing the density of defect states, inhibiting non-radiative recombination at the interface, and promoting the charge transfer efficiency from the perovskite layer to the hole transport layer. The 4-APN modification led to a significant upswing in the PCE, while concurrently bolstering the overall device stability. Importantly, the devices on 4-APN as passivation additive exhibited negligible performance degradation aging for 1200â h.
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To investigate the value of drug exposure and host germline genetic factors in predicting apatinib (APA)-related toxicities. METHOD: In this prospective study, plasma APA concentrations were quantified using liquid chromatography with tandem mass spectrometry, and 57 germline mutations were genotyped in 126 advanced solid tumor patients receiving 250 mg daily APA, a vascular endothelial growth factor receptor II inhibitor. The correlation between drug exposure, genetic factors, and the toxicity profile was analyzed. RESULTS: Non-small cell lung cancer (NSCLC) was more prone to APA-related toxicities and plasma concentrations of APA, and its main metabolite M1-1 could be associated with high-grade adverse events (AEs) (P < 0.01; M1-1, P < 0.01) and high-grade antiangiogenetic toxicities (APA, P = 0.034; P < 0.05), including hypertension, proteinuria, and hand-foot syndrome, in the subgroup of NSCLC. Besides, CYP2C9 rs34532201 TT carriers tended to have higher levels of APA (P < 0.001) and M1-1 (P < 0.01), whereas CYP2C9 rs1936968 GG carriers were predisposed to higher levels of M1-1 (P < 0.01). CONCLUSION: Plasma APA and M1-1 exposures were able to predict severe AEs in NSCLC patients. Dose optimization and drug exposure monitoring might need consideration in NSCLC patients with CYP2C9 rs34532201 TT and rs1936968 GG. SIGNIFICANCE STATEMENT: Apatinib is an anti-VEGFR2 inhibitor for the treatment of multiple cancers. Though substantial in response, apatinib-induced toxicity has been a critical issue that is worth clinical surveillance. Few data on the role of drug exposure and genetic factors in apatinib-induced toxicity are available. Our study demonstrated a distinct drug-exposure relationship in NSCLC but not other tumors and provided invaluable evidence of drug exposure levels and single nucleotide polymorphisms as predictive biomarkers in apatinib-induced severe toxicities.
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Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Polimorfismo de Nucleótido Simple , Antineoplásicos/efectos adversos , Estudios Prospectivos , Factor A de Crecimiento Endotelial Vascular/uso terapéutico , Citocromo P-450 CYP2C9RESUMEN
Lentinan (LNT) isolated from Lentinus edodes is a vital host defense potentiator previously utilized as an adjuvant in cancer therapy. The present study investigated the effect of LNT on the mouse hepatocellular carcinoma (HCC) cell line Hepa16 and its possible mechanism. Mouse HCC apoptosis and its potential associated mechanism were then explored using in vitro and in vivo approaches. For in vitro approaches, the effect of LNT on the proliferation of Hepa16 cells was investigated by Cell Counting Kit8 assay. Annexin VFITC staining and flow cytometry were applied to explore HCC apoptosis. Western blotting was used to analyze related proteins, such as EGR1, phosphatase and tensin homolog (PTEN), phosphorylated protein kinase B (pAkt), protein kinase B (Akt), B lymphocyte2 (Bcl2), Bcl2 familyassociated X protein (Bax), etc. Cellular immunofluorescence staining was employed to assess the localization and expression of EGR1 and PTEN in nuclear and cytoplasmic fractions of Hepa16 cells. The association between EGR1 and PTEN was explored by EGR1 overexpression in cell lines. For in vivo methods, a mouse model of diethylnitrosamine (DEN)induced primary liver cancer was established using C57BL/6 mice to investigate the inhibitory effect of LNT on liver cancer. Histopathology of liver tissue from mice was detected by hematoxylineosin staining and immunohistochemical assay. In vitro and in vivo results showed that LNT can inhibit the proliferation and promote the apoptosis of mouse HCC cells. Besides, LNT increased the expression of EGR1 in Hepa16 cells, which is translocated to the nucleus to function as a transcriptional factor. EGR1 then activates the expression of the tumor suppressor PTEN, thereby inhibiting the activation of the AKT signaling pathway. These data revealed a novel antitumor mechanism by which LNT can induce apoptosis to inhibit mouse HCC progression through the EGR1/PTEN/AKT axis. These results provide a scientific basis for the potential use of LNT in drug development and clinical applications associated with primary liver cancer.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Ratones , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Lentinano/farmacología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Línea Celular Tumoral , Ratones Endogámicos C57BL , Ratones Endogámicos , Transducción de Señal , Apoptosis , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Proliferación Celular , Proteína 1 de la Respuesta de Crecimiento Precoz/genética , Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismoRESUMEN
Malignant melanoma is an invasive and highly aggressive skin cancer that-if diagnosed-poses a serious threat to the patient's health and life. In this work, a novel purified cell-wall polysaccharide (termed Abwp) was obtained from the discarded stipe of Agaricus bisporus (A. bisporus) and characterized to be a novel homogeneous polysaccharide consisted of a ß-(1 â 4)- glucosyl backbone with ß-(1 â 2) and (1 â 6)-d-glucosyl side-chains. The anti-melanoma effects of Abwp and its associated mechanisms in mice were then explored using in vitro and in vivo approaches. In vitro results showed that Abwp inhibited B16 melanoma cell proliferation and promoted their apoptosis in both time- and dose-dependent manners. In B16 cells induced with tumor necrosis factor (TNF-α), Abwp significantly decreased the protein expression of inflammatory-related signaling pathway (e.g., p38 MAPK and NF-κB) in time-, concentration-, and dose-dependent manners. Moreover, Abwp blocked nuclear entry of NF-κB-p65. In an in vivo mouse model featuring neoplasm transplantation with B16 melanoma cells, Abwp significantly inhibited the growth and proliferation of mouse melanoma. Hematoxylin staining showed that the invasion of melanoma cells into the lung tissue of the Abwp-treated group was significantly reduced. Immunohistochemical analysis showed that the expression of proliferation cell nuclear antigen (PCNA), N-cadherin, MMP-9, and Snail in the lung of mouse was significantly inhibited. Immunofluorescence showed that Abwp significantly interfered with the nuclear transcription of NF-κB-p65 in a dose-dependent manner. Collectively, these results showed that Abwp mediated p38 MAPK and NF-κB signaling pathways to inhibit the inflammatory response and malignant proliferation and metastasis of melanoma in mice.
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Melanoma Experimental , FN-kappa B , Animales , Ratones , FN-kappa B/metabolismo , Melanoma Experimental/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Proliferación Celular , Polisacáridos/farmacología , Polisacáridos/uso terapéutico , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Línea Celular TumoralRESUMEN
PURPOSE: To investigate the performance of an artificial intelligence (AI) algorithm for assessing the malignancy and invasiveness of pulmonary nodules in a multicenter cohort. METHODS: A previously developed deep learning system based on a 3D convolutional neural network was used to predict tumor malignancy and invasiveness. Dataset of pulmonary nodules no more than 3 cm was integrated with CT images and pathologic information. Receiver operating characteristic curve analysis was used to evaluate the performance of the system. RESULTS: A total of 466 resected pulmonary nodules were included in this study. The areas under the curves (AUCs) of the deep learning system in the prediction of malignancy as compared with pathological reports were 0.80, 0.80, and 0.75 for all, subcentimeter, and solid nodules, respectively. Additionally, the AUC in the AI-assisted prediction of invasive adenocarcinoma (IA) among subsolid lesions (n = 184) was 0.88. Most malignancies that were misdiagnosed by the AI system as benign diseases with a diameter measuring greater than 1 cm (26/250, 10.4%) presented as solid nodules (19/26, 73.1%) on CT. In an exploratory analysis involving nodules underwent intraoperative pathologic examination, the concordance rate in identifying IA between the AI model and frozen section examination was 0.69, with a sensitivity of 0.50 and specificity of 0.97. CONCLUSION: The deep learning system can discriminate malignant diseases for pulmonary nodules measuring no more than 3 cm. The AI model has a high positive predictive value for invasive adenocarcinoma with respect to intraoperative frozen section examination, which might help determine the individualized surgical strategy.
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Adenocarcinoma , Neoplasias Pulmonares , Nódulos Pulmonares Múltiples , Humanos , Inteligencia Artificial , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Secciones por Congelación , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Nódulos Pulmonares Múltiples/diagnóstico por imagen , Nódulos Pulmonares Múltiples/cirugíaRESUMEN
In perovskite solar cells (PSCs), the numerous defects present on the surface of the SnO2 electron transport layer (ETL) and the bottom of the perovskite film limit their power conversion efficiency (PCE) and stability. In view of this, a bidirectional modification strategy is designed using formamidine acetate (FAAc) to passivate the defects on the SnO2 ETL surface and bottom of the perovskite simultaneously. FA+ cations act on the harmful hydroxyl groups on the SnO2 ETL surface, whereas Ac- anions act on the iodine vacancy defect at the bottom of the perovskite. Because the interface defect is well passivated by FAAc, the interfacial charge recombination is restrained. This results in a significant increase in the filling factor of the PSC to â¼0.83 and the consequent increase in PCE to 23.05%, which considerably improves the stability. Bidirectional modification technology is an effective strategy for improving the PCE and stability of PSCs.
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BACKGROUND: Preoperative immunotherapy has shed light on the management of resectable non-small cell lung cancer (NSCLC). However, whether neoadjuvant immunotherapy benefits patients with oncogene-positive NSCLC remains unknown. METHODS: Data were retrieved from 4 institutions in the period from August 2018 to May 2021. Eligible patients were aged ≥18 years with histologically confirmed stage IIA to stage IIIB (T1-2 N1-2 or T3-4 N0-2) NSCLC that was deemed to be surgically resectable. The neoadjuvant regimen included immune checkpoint inhibitors alone or in combination with platinum-based doublets. Surgical resection was performed 4 to 6 weeks after the first day of the last cycle of treatment. The primary end point was major pathologic response (MPR; ≤10% viable tumor cells). Analyses were categorized according to the patients' oncogene (EGFR, ALK, KRAS, MET, BRAF, ROS1, RET) status. RESULTS: Overall, 137 patients were identified; 46 (33%) patients had nonsquamous cell cancer, and 114 (83%) had stage IIIA/B disease. Oncogene alterations were identified in 22 (16%) patients, of whom only 2 patients (2/22 [9%]) had an MPR compared with 65 (65/115 [56.5%]) in the oncogene-negative population (P < .001). Similar results were retained after propensity score matching for age, sex, smoking status, histologic type, stage, and cycles of neoadjuvant treatment. Squamous cell carcinoma (odds ratio, 2.54; 95% CI, 1.08-5.99) and positive oncogene status (odds ratio, 0.13; 95% CI, 0.03-0.64) were found to be indicators for MPR by logistic regression. The 1-year event-free survival rate was 75.4% in the oncogene-positive group, which was not significantly different from 85.5% in the oncogene-negative population (P = .23). CONCLUSIONS: Patients with stage II-III oncogene-positive NSCLCs respond less than patients with oncogene-negative NSCLCs after neoadjuvant immunotherapy.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Adolescente , Adulto , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/tratamiento farmacológico , Terapia Neoadyuvante/efectos adversos , Proteínas Tirosina Quinasas/genética , Proteínas Proto-Oncogénicas/genética , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Oncogenes , InmunoterapiaRESUMEN
The electrocatalytic 2e- oxygen reduction reaction (2e- ORR) provides an appealing pathway to produce hydrogen peroxide (H2O2) in a decentralized and clean manner, which drives the demand for developing high selectivity electrocatalysts. However, current understanding on selectivity descriptors of 2e- ORR electrocatalysts is still insufficient, limiting the optimization of catalyst design. Here we study the catalytic performances of a series of metal phthalocyanines (MPcs, M = Co, Ni, Zn, Cu, Mn) for 2e- ORR by combining density functional theory calculations with electrochemical measurements. Two descriptors (ΔG *O - ΔG *OOH and ΔG *H2O2 ) are uncovered for manipulating the selectivity of H2O2 production. ΔG *O - ΔG *OOH reflects the preference of O-O bond breaking of *OOH, affecting the intrinsic selectivities. Due to the high value of ΔG *O - ΔG *OOH, the molecularly dispersed electrocatalyst (MDE) of ZnPc on carbon nanotubes exhibits high selectivity, even superior to the previously reported NiPc MDE. ΔG *H2O2 determines the possibility of further H2O2 reduction to affect the measured selectivities. Enhancing the hydrophobicity of the catalytic layer can increase ΔG *H2O2 , leading to selectivity improvement, especially under high H2O2 production rates. In the gas diffusion electrode measurements, both ZnPc and CoPc MDEs with polytetrafluoroethylene (PTFE) exhibit low overpotentials, high selectivities, and good stability. This study provides guidelines for rational design of 2e- ORR electrocatalysts.
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SnO2 is a candidate material for electron transport layers (ETLs) in perovskite solar cells (PSCs). However, a large number of defects at the SnO2/perovskite interface lead to notable non-radiative interfacial recombination. Moreover, the energy level arrangement between SnO2/perovskite does not match well. In this study, a SnO2/CsF-SnO2 double-layer ETL was prepared by doping CsF into SnO2, effectively passivating the defects of the SnO2 ETL and SnO2/perovskite interface. The formation of a good energy level arrangement with the perovskite layer reduces the interface non-radiative recombination and improves the performance of the interface charge extraction. The photoelectric conversion efficiency of the optimal CsF-modified PSC reached 22.18%, owing to the significant increase in the open-circuit voltage to 1.180 V.
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Background: Based on bioinformatics analysis and experimental validation, we investigated the expression, clinical significance, immune infiltration, and potential signaling pathways of miR-3940-5p in lung adenocarcinoma (LUAD). Methods: 521 LUAD tissue samples and 46 normal lung tissue samples from The Cancer Genome Atlas (TCGA) database. We evaluated the relationship between clinical features and miR-3940-5p expression using Kruskal-Wallis, Wilcoxon sign-rank, and logistic regression, explored the relationship between miR-3940-5p expression and the prognosis of LUAD patients using Kaplan-Meier survival curve analysis. Several databases were used to identify miRNA targets. MiR-3940-5p target genes were analyzed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The significant role of miR-3940-5p in function was evaluated using immune infiltration analysis. LUAD cell lines were tested for miR-3940-5p expression using QRT-PCR. Results: There was a significant association between high miR-3940-5p expression in LUAD and T stage (P=0.005), pathologic stage (P=0.047), race (White vs Asian & Black or African American) (P=0.041), residual tumor (P=0.043), and anatomic neoplasm subdivision2 (P=0.030). MiR-3940-5p expression predicted poor overall survival (HR: 1.35; 95% CI: 1.01-1.81; P=0.045), disease-specific survival (HR: 1.53; 95% CI: 1.05-2.23; P=0.026), and progression-free survival (HR: 1.35; 95% CI: 1.03-1.77; P=0.032). BAP1, BBS1, CCR2, KCNE3, PEBP1, and RABL2A were all associated with poor OS in LUAD patients with low miR-3940-5p expression levels. According to GO and KEGG analyses, miR-3940-5p may play a role in LUAD development by regulating pathways such as measles, PI3K-Akt signaling pathway, and p53 signaling pathway. There was a correlation between the expression level of miR-3940-5p and immune infiltration. LUAD cell lines showed significantly higher levels of miR-3940-5p than Beas-2B cells. Conclusion: A high expression of miR-3940-5p is significantly associated with a poor prognosis in patients with LUAD, suggesting that it could be used as a prognostic biomarker.
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BACKGROUND: The treatment of lung cancer patients, especially those with epidermal growth factor receptor (EGFR)-mutant T790M-negative adenocarcinoma, after first- or second-line tyrosine kinase inhibitor (TKI) treatment failure is challenging due to the poor prognosis and limited effectiveness of platinum two-drug chemotherapy or chemotherapy plus anti-angiogenesis therapy. It is well-known that pembrolizumab monotherapy exhibits low toxicity and long-term survival, but it is unknown in these patients. METHODS: From September 2018 to March 2021, 460 patients in Jiangmen Central Hospital were included and 82 patients with disease progression in lung adenocarcinoma who remained T790M-negative on the second biopsy were screened. Two groups were divided according to treatment status, and simple random sampling was performed to obtain 32 cases respectively. The safety of the patients was subsequently evaluated by telephone follow-up. RESULTS: The objective response rate (ORR) and disease control rate (DCR) in the pembrolizumab group were 15.63% and 53.13%. In the chemotherapy group, the ORR was 8.33% and the DCR was 25% (P<0.05). In the pembrolizumab group, the progression-free survival (PFS) [14.65 months, 95% confidence interval (CI): 13.03 to 16.28] was significantly higher than that of the control group (9.54 months, 95% CI: 8.43 to 10.65) (P<0.05). In the univariate analysis, programmed cell death protein 1 ligand (PD-L1) expression, smoking status, gender, and whether first-line chemotherapy was associated with survival. In the multivariate analysis, gender [P=0.001; hazard ratio (HR) 10.98, 95% CI: 2.49-46.67], first-line chemotherapy (P=0.037; HR 4.5, 95% CI: 1.1-4.81), and PD-L1 expression (P=0.039; HR 0.16, 95% CI: 0.04-0.68) were correlated with patient survival. Grade 3 or grade 4 treatment-related adverse events were not found in the pembrolizumab group, while 2 cases of grade 3 or 4 treatment-related adverse events occurred in the control group. CONCLUSIONS: In advanced lung adenocarcinoma patients with EGFR-mutant T790M-negative after TKI treatment, pembrolizumab had a higher ORR and PFS. Pembrolizumab in women with first-line chemotherapy and PD-L1 ≥25% of those patients may have a good response and a low rate of adverse reactions. A multicenter, prospective, evidence-based study of pembrolizumab salvage therapy in those patients is warranted for posterior line treatment.