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This study explored the potential application of plasma coupling ionic liquid on disintegration of waste activated sludge and enhanced production of short-chain fatty acids (SCFAs) in anaerobic fermentation. Under optimal conditions (dosage of ionic liquid [Emim]OTf = 0.1 g/g VSS (volatile suspended solids) and discharge power of dielectric barrier discharge plasma (DBD) = 75.2 W), the [Emim]OTf/DBD pretreatment increased SCFA production by 302 % and acetic acid ratio by 53 % compared to the control. Mechanistic investigations revealed that the [Emim]OTf/DBD combination motivated the generation of various reactive species (such as H2O2, O3, â¢OH, 1O2, ONOO-, and â¢O2-) and enhanced the utilization of physical energies (such as heat). The coupling effects of [Emim]OTf/DBD synergistically improved the disintegration of sludge and biodegradability of dissolved organic matter, promoting the sludge anaerobic fermentation process. Moreover, the [Emim]OTf/DBD pretreatment enriched hydrolysis and SCFAs-forming bacteria while inhibiting SCFAs-consuming bacteria. The net effect was pronounced expression of genes encoding key enzymes (such as alpha-glucosidase, endoglucanase, beta-glucosidase, l-lactate/D-lactate dehydrogenase, and butyrate kinase) involved in the SCFA-producing pathway, enhancing the production of SCFAs from sludge anaerobic fermentation. In addition, [Emim]OTf/DBD pretreatment facilitated sludge dewatering and heavy metal removal. Therefore, [Emim]OTf/DBD pretreatment is a promising approach to advancing sludge reduction, recyclability, and valuable resource recovery.
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Ácido Acético , Fermentación , Líquidos Iónicos , Aguas del Alcantarillado , Ácido Acético/metabolismo , Anaerobiosis , Ácidos Grasos Volátiles/metabolismo , Eliminación de Residuos Líquidos/métodosRESUMEN
PURPOSE: The observation-based prognosis, rather than resection, for small carcinoid tumors is still unclear. This lack of clarity has important implications for counseling elderly patients or patients for whom surgical resection poses a high risk. This study compared the outcomes of observation and surgical resection in patients with pulmonary carcinoid (PC) tumors ≤3 cm in size without metastasis. METHODS: Data of patients with PC tumors with ≤3 cm in diameter and without lymph node and distant metastases were retrieved from Surveillance, Epidemiology, and End Results (SEER) registry. To reduce the inherent bias of retrospective studies, propensity score matching analysis was performed. Overall survival (OS) and lung carcinoid-specific survival (LCSS) were analyzed using Kaplan-Meier plots. Multivariate analysis was used to determine predictors of LCSS in different size subgroups. RESULTS: In total, 4552 patients with early-stage PCs ≤3 cm in diameter, including 435 (9.56%) who were observed and 4117 (90.44%) treated by surgery, were recruited. Patients with surgery had significantly better OS and LCSS than those who were observed. However, patients with observation had comparable LCSS to those with surgery for PCs with tumor diameters ≤1 cm. Multivariate analysis indicated that surgical resection was an independent prognostic factor for LCSS in 1 cm < tumors ≤2 cm, and 2 cm < tumors ≤3 cm groups, but not for tumors ≤1 cm in diameter. CONCLUSION: Surgical resection of small PCs is associated with a survival advantage over observation. However, for early PCs ≤1 cm in diameter, observation may be considered in patients with high risk for surgical resection.
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Tumor Carcinoide , Neoplasias Pulmonares , Programa de VERF , Humanos , Masculino , Tumor Carcinoide/cirugía , Tumor Carcinoide/patología , Tumor Carcinoide/mortalidad , Femenino , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Persona de Mediana Edad , Pronóstico , Anciano , Estudios Retrospectivos , Estadificación de Neoplasias , Carga Tumoral , Adulto , Estimación de Kaplan-Meier , Puntaje de PropensiónRESUMEN
Porous polymer membranes as separator plays important roles in separating cathode and anode, storing electrolytes, and transporting ions in energy storage devices. Here, an effective strategy is reported to prepare an electrolyte superwetting membrane, which shows good Li+ transport rate and uniformity, as well as electrode-friendly properties to afford the reduction and oxidation of electrodes. It thereby improves the cycle stability and safety of Li metal batteries. With the arrayed capillaries technique, a thin layer of polyvinylidene fluoride (PVDF) and polyacrylonitrile (PAN) composite is uniformly coated on the surface and pores of polypropylene (PP) membrane with a total thickness of 30 µm. After treating it with n-butyllithium and LiNO3 in turn, a chemically inert membrane with efficient and uniform ion transport is prepared, and the cycle stability of Li||Li symmetric cells is up to 1500 h, 4 times higher than that of PP membrane. Moreover, the Li||LiFePO4 with as-prepared membranes achieve a higher capacity retention rate of 92% after 190 cycles at a current density of 3.6 mA cm-2 and a capacity of 3.6 mAh cm-2, and the Li||NCM721 batteries achieve a capacity retention rate of 71% after 600 cycles at a current density of 1.8 mA cm-2.
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HCC is the most common fatal malignancy. Although surgical resection is the primary treatment strategy, most patients are not eligible for resection due to tumor heterogeneity, underlying liver disease, or comorbidities. Therefore, this study explores the possibility of multi-molecular targeted drug delivery in treating HCC. In this study, we constructed the recombinant adenovirus co-expressing apoptin and melittin (MEL) genes. The inhibitory effect of the recombinant adenovirus on hepatocellular carcinoma cells was detected through experiments on cell apoptosis, migration, invasion, and other factors. The tumor inhibitory effect in vivo was assessed using subcutaneous HCC mice. Results showed that recombinant adenovirus co-expressing anti-tumor genes TAT and apoptin, RGD and MEL can significantly inhibit the proliferation, migration, and invasion of HCC cells by inducing an increase in reactive oxygen species (ROS) levels, upregulation of apoptotic proteins such as Bax, cleaved caspase-3, and cleaved caspase-9, and downregulation of the anti-apoptotic protein Bcl-2. In subcutaneous HCC mice, recombinant adenovirus induced significant apoptosis in tumor, and inhibited tumor growth. In conclusion, recombinant adenovirus co-expressing apoptin and MEL can inhibit the growth and proliferation of tumor cells both in vivo and in vitro.
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Adenoviridae , Apoptosis , Proteínas de la Cápside , Carcinoma Hepatocelular , Proliferación Celular , Neoplasias Hepáticas , Meliteno , Meliteno/farmacología , Animales , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/genética , Adenoviridae/genética , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/genética , Humanos , Proteínas de la Cápside/genética , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ratones , Movimiento Celular/efectos de los fármacos , Ratones Desnudos , Ratones Endogámicos BALB C , Línea Celular Tumoral , Especies Reactivas de Oxígeno/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Terapia Genética/métodosRESUMEN
Food consumption contributes to the degradation of air quality in regions where food is produced, creating a contrast between the health burden caused by a specific population through its food consumption and that faced by this same population as a consequence of food production activities. Here we explore this inequality within China's food system by linking air-pollution-related health burden from production to consumption, at high levels of spatial and sectorial granularity. We find that low-income groups bear a 70% higher air-pollution-related health burden from food production than from food consumption, while high-income groups benefit from a 29% lower health burden relative to their food consumption. This discrepancy largely stems from a concentration of low-income residents in food production areas, exposed to higher emissions from agriculture. Comprehensive interventions targeting both production and consumption sides can effectively reduce health damages and concurrently mitigate associated inequalities, while singular interventions exhibit limited efficacy.
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Contaminación del Aire , Renta , Pobreza , Alimentos , AgriculturaRESUMEN
Metal electrode with long cycle life is decisive for the actual use of metal rechargeable batteries, while the dendrite growth and side reaction limit their cyclic stability. Herein, the construction of polymer and inorganic-rich SEI tandem layer structure on Li metal can be used for extraordinarily extending its cycle life is reported, which is generated by an in situ PVDF/LiF/LiNO3 (PLL) gel layer on the surface of Li metal with a chemically compatible ether solvent. The cycle life of Li//Li cells with the tandem layer structure is over 6000 h, six times longer than those with LiNO3 homogeneous electrolyte. It highlights the importance of LiNO3 concentration gradient electrolyte formed by the in situ PLL gel layer, in which highly concentrated LiNO3 is confined on the surface of Li metal to generate the uniform and inorganic-rich LiF/Li2O/Li3N layer on the bottom of PVDF/LiF with good mechanical strength, resulting in the dendrite free anode in cell cycling. The assembled Li//LiFePO4 and Li//NMC811 batteries show the capacity retention rate of 80.9% after 800 cycles and 82.3% after 500 cycles, respectively, much higher than those of references.
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The reaction rate bottleneck during interconversion between insulating S8 (S) and Li2 S fundamentally leads to incomplete conversion and restricted lifespan of Li-S battery, especially under high S loading and lean electrolyte conditions. Herein, we demonstrate a new catalytic chemistry: soluble semiquinone, 2-tertbutyl-semianthraquinone lithium (Li+ TBAQâ - ), as both e- /Li+ donor and acceptor for simultaneous S reduction and Li2 S oxidation. The efficient activation of S and Li2 S by Li+ TBAQâ - in the initial discharging/charging state maximizes the amount of soluble lithium polysulfide, thereby substantially improve the rate of solid-liquid-solid reaction by promoting long-range electron transfer. With in situ Raman spectra and theoretical calculations, we reveal that the activation of S/Li2 S is the rate-limiting step for effective S utilization under high S loading and low E/S ratio. Beyond that, the S activation ratio is firstly proposed as an accurate indicator to quantitatively evaluate the reaction rate. As a result, the Li-S batteries with Li+ TBAQâ - deliver superior cycling performance and over 5 times higher S utilization ratio at high S loading of 7.0â mg cm-2 and a current rate of 1â C compared to those without Li+ TBAQâ - . We hope this study contributes to the fundamental understanding of S redox chemical and inspires the design of efficient catalysis for advanced Li-S batteries.
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The chemical industry is a significant source of nonmethane volatile organic compounds (NMVOCs), pivotal precursors to ambient ozone (O3), and secondary organic aerosol (SOA). Despite their importance, precise estimation of these emissions remains challenging, impeding the implementation of NMVOC controls. Here, we present the first comprehensive plant-level assessment of NMVOC emissions from the chemical industry in China, encompassing 3461 plants, 127 products, and 50 NMVOC compounds from 2010 to 2019. Our findings revealed that the chemical industry in China emitted a total of 3105 (interquartile range: 1179-8113) Gg of NMVOCs in 2019, with a few specific products accounting for the majority of the emissions. Generally, plants engaged in chemical fibers production or situated in eastern China pose a greater risk to public health due to their higher formation potentials of O3 and SOA or their proximity to residential areas or both. We demonstrated that targeting these high-risk plants for emission reduction could enhance health benefits by 7-37% per unit of emission reduction on average compared to the current situation. Consequently, this study provides essential insights for developing effective plant-specific NMVOC control strategies within China's chemical industry.
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Contaminantes Atmosféricos , Ozono , Compuestos Orgánicos Volátiles , Contaminantes Atmosféricos/análisis , Compuestos Orgánicos Volátiles/análisis , Compuestos Orgánicos Volátiles/química , Industria Química , Monitoreo del Ambiente , Ozono/análisis , China , Aerosoles/análisis , PlantasRESUMEN
Metastasis remains major cause of treatment failure in non-small cell lung cancer (NSCLC). A comprehensive characterization of the transcriptomic landscape of NSCLC-cells with organ-specific metastatic potentials would advance our understanding of NSCLC metastasis process. In this study, we established NSCLC bone-metastatic (BoM), brain-metastatic (BrM), and lymph-metastatic (LnM) cells by an in vivo spontaneous metastatic model. Subsequently, by analyzing the entire transcriptomic profiles of BoM, BrM, LnM, LuM, in comparison with their parental cell line L9981, we identified miR-660-5p as a key driver that is associated with NSCLC progression and distant metastasis, potentially through its targeting of LIMCH1, SMARCA5 and TPP2. In addition, a six-gene signature (ADRB2, DPYSL2, IL7R, LIMCH1, PIK3R1, and SOX2) was subsequently established to predict NSCLC metastasis based on differentially expressed genes, three of which (DPYSL2, PIK3R1, LIMCH1) along with the transcriptional factors RB1 and TP63, were ultimately validated by experiments. Taken together, aberrant gene signature and miRNA can serve as biomarkers for predicting NSCLC distant metastasis, and targeting them could potentially contribute to the development of novel therapeutic strategies.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , MicroARNs , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Pulmonares/patología , ARN Mensajero , Línea Celular Tumoral , Regulación Neoplásica de la Expresión GénicaRESUMEN
The iron and steel industry (ISI) is important for socio-economic progress but emits greenhouse gases and air pollutants detrimental to climate and human health. Understanding its historical emission trends and drivers is crucial for future warming and pollution interventions. Here, we offer an exhaustive analysis of global ISI emissions over the past 60 years, forecasting up to 2050. We evaluate emissions of carbon dioxide and conventional and unconventional air pollutants, including heavy metals and polychlorinated dibenzodioxins and dibenzofurans. Based on this newly established inventory, we dissect the determinants of past emission trends and future trajectories. Results show varied trends for different pollutants. Specifically, PM2.5 emissions decreased consistently during the period 1970 to 2000, attributed to adoption of advanced production technologies. Conversely, NOx and SO2 began declining recently due to stringent controls in major contributors such as China, a trend expected to persist. Currently, end-of-pipe abatement technologies are key to PM2.5 reduction, whereas process modifications are central to CO2 mitigation. Projections suggest that by 2050, developing nations (excluding China) will contribute 52-54% of global ISI PM2.5 emissions, a rise from 29% in 2019. Long-term emission curtailment will necessitate the innovation and widespread adoption of new production and abatement technologies in emerging economies worldwide.
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Contaminantes Atmosféricos , Contaminación del Aire , Humanos , Contaminación del Aire/análisis , Hierro , Material Particulado/análisis , Acero , Contaminantes Atmosféricos/análisis , ChinaRESUMEN
BACKGROUND: An increasing body of evidence supports the noninferiority of sublobar resection compared with lobectomy in terms of survival for patients with early-stage lung cancer with ground-glass opacities (GGOs). However, few studies have focused on the incidence of lymph node (LN) metastases in these patients. We aimed to analyze N1 and N2 lymph node involvement in patients with non-small cell lung cancer (NSCLC) with GGO components stratified with different consolidation tumor ratio (CTR). PATIENTS AND METHODS: We performed two-center studies by retrospectively reviewing a total of 864 patients with NSCLC with semisolid or pure GGO manifestation (diameter ≤ 3 cm). Clinicopathologic features and outcomes were analyzed. We also reviewed 35 studies to characterize the patient with NSCLC population with the GGO manifestation. RESULTS: In both cohorts, there was no LN involvement for pure GGO NSCLC, while solid predominant GGO exhibited a relatively high LN involvement rate. On the basis of a pooled literature analysis, the incidence of pathologic mediastinal LN was 0% and 3.8% for pure and semisolid GGOs, respectively. GGO NSCLCs with CTR ≤ 0.5 also had rare LN involvement (0.1%). CONCLUSIONS: From two cohorts and pooled literature analysis, LN involvement was not observed in patients with pure GGO, and very few patients with semisolid GGO NSCLC with CTR ≤ 0.5 had LN involvement, revealing that it may be unnecessary to perform lymphadenectomy for pure GGOs, while mediastinal lymph node sampling (MLNS) is enough for semisolid GGOs with CTR ≤ 0.5. For the patients with GGO CTR > 0.5, mediastinal lymphadenectomy (MLD) or MLNS should be considered.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Estudios Retrospectivos , Metástasis Linfática , Pronóstico , Tomografía Computarizada por Rayos XRESUMEN
A comprehensive search regarding programmed cell death protein 1 (PD1)/programmed deathligand 1 (PDL1) inhibitor monotherapy or combination therapy in neoadjuvant settings of 11 types of solid cancer was performed using the PubMed, Cochrane and Embase databases, and the abstracts of various conferences were screened. Data presented in 99 clinical trials indicated that preoperative treatment with PD1/PDL1 combined therapy, particularly immunotherapy plus chemotherapy, could achieve a higher objective response rate, a higher major pathologic response rate and a higher pathologic complete response rate, as well as a lower number of immunerelated adverse events compared with PD1/PDL1 monotherapy or dual immunotherapy. Although PD1/PDL1 inhibitor combination caused more treatmentrelated adverse events (TRAEs) in patients, most of the TRAEs were acceptable and did not cause marked delays in operation. The data suggest that patients with pathological remission after neoadjuvant immunotherapy exhibit improved postoperative diseasefree survival compared with those without pathological remission. Further studies are still required to evaluate the longterm survival benefit of neoadjuvant immunotherapy.
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Inhibidores de Puntos de Control Inmunológico , Terapia Neoadyuvante , Neoplasias , Humanos , Antígeno B7-H1 , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias/tratamiento farmacológico , Receptor de Muerte Celular Programada 1RESUMEN
The construction of high sulfur (S) loading cathode is one of the critical parameters to obtain lithium-sulfur (Li-S) batteries with high energy density, but the slow redox reaction rate of high S loading cathode limits the development process. In this paper, a metal coordinated polymer-based three-dimensional network binder, which can improve the reaction rate and stability of S electrode. Compared with traditional linear polymer binders, the metal coordinated polymer binder can not only increase the load amount of S through the three-dimensional cross-linking, but also promote the interconversion reactions between S and lithium sulfide (Li2 S), avoiding the passivation of electrode and improving the stability of the positive electrode. At an S load of 4-5 mg cm-2 and an E/S ratio of 5.5 µL mg-1 , the discharged voltage in the second platform is 2.04 V and the initial capacity is 938 mA h g-1 with metal coordinated polymer binder. Moreover, the capacity retention rate approaches 87% after 100 cycles. In comparison, the discharged voltage in the second platform is lost and the initial capacity is 347 mA h g-1 with PVDF binder. It demonstrates the advanced properties of metal-coordinated polymer binders for improving the performance of Li-S batteries.
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OBJECTIVE: This study evaluated whether sublobar resection (sub-L) is non-inferior to lobectomy (L) for stage I (T1-T2aN0M0) small cell lung cancer (SCLC) regarding long-term overall survival (OS). METHODS: Clinicopathological and prognostic data of patients with stage I (pT1-T2aN0M0) SCLC were retrieved. Kaplan-Meier curves and Breslow tests were performed for the assessment of OS. Propensity score matching (PSM) analysis was used to mediate the inherent bias of retrospective researches. RESULTS: A total of 188 patients with stage I SCLC were included in this study after PSM. For resected stage I SCLC, surgery plus adjuvant therapy was related to a better OS compared with surgery only (p = 0.016). For resected stage I SCLC, no matter adjuvant therapy was performed or not, no significant difference was observed in long-term OS between the L and sub-L groups (p = 0.181). Further subgroup analysis demonstrated that the OS disadvantage of sub-L over L was not statistically significant for stage I SCLC patients underwent surgery only (p = 0.653), but also for the patients underwent surgery plus adjuvant therapy (p = 0.069). Moreover, in the subgroup analyses according to TNM stage (IA and IB), sex (male and female), and age (≥70 and <70 years), OS did not differ between the L and sub-L groups except in female patients (p = 0.008). Multivariate Cox regression analysis indicated that adjuvant therapy was positively associated with OS. CONCLUSIONS: Surgery plus adjuvant therapy confers a better survival benefit than surgery only for stage I SCLC patients. However, as far as the range of surgical resection is concerned, sublobar resection may be non-inferior to lobectomy regarding OS. Our study could conduce to the development of optimal therapeutic strategies for stage I SCLC patients. Further validation is warranted in larger retrospective and prospective cohort studies.
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Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Masculino , Femenino , Anciano , Carcinoma Pulmonar de Células Pequeñas/patología , Neoplasias Pulmonares/patología , Estudios Retrospectivos , Estudios Prospectivos , Puntaje de Propensión , Estadificación de Neoplasias , NeumonectomíaRESUMEN
PURPOSE OF REVIEW: Lung cancer is one of the most common malignant tumours worldwide. Metastasis is a serious influencing factor for poor treatment effect and shortened survival in lung cancer. But the complicated underlying molecular mechanisms of tumour metastasis remain unclear. In this review, we aim to further summarize and explore the underlying mechanisms of tumour-derived exosomes (TDEs) in lung cancer metastasis. RECENT FINDINGS: TDEs are actively produced and released by tumour cells and carry messages from tumour cells to normal or abnormal cells residing at close or distant sites. Many studies have shown that TDEs promote lung cancer metastasis and development through multiple mechanisms, including epithelial-mesenchymal transition, immunosuppression and the formation of a premetastatic niche. TDEs regulate these mechanisms to promote metastasis by carrying DNA, proteins, miRNA, mRNA, lncRNA and ceRNA. Further exploring TDEs related to metastasis may be a promising treatment strategy and deserve further investigation. SUMMARY: Overall, TDEs play a critical role in metastatic of lung cancer. Further studies are needed to explore the underlying mechanisms of TDEs in lung cancer metastasis.
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Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/genéticaRESUMEN
Integrins are involved in extracellular and intracellular signaling and are often aberrantly expressed in tumors. Integrin beta 2 (ITGB2) has previously been demonstrated to be correlated with the host defense. However, the expression profile and role of ITGB2 in non-small-cell lung cancer (NSCLC) remain unclear. Here, we found that the genetic alterations in ITGB2 was predominated by gene mutation and copy number deletion using cBioPortal analysis, and its expression was downregulated in the NSCLC tissues, as validated by the UALCAN, TCGA, and GEO databases and our tissue samples. Kaplan-Meier (KM) plotter analysis revealed that patients with a lower ITGB2 expression had a shorter overall survival (OS) time (p = 0.01). Moreover, 1089 differentially expressed genes (DEGs) in the NSCLC tissues were screened using the TCGA database. The GO and KEGG enrichment analysis showed that the DEGs were closely associated with immune processes and cell adhesion. The protein-protein interaction (PPI) network revealed that 10 of 15 EMT-related genes among the DEGs might lead to the metastasis of NSCLC. Concomitantly, the expression of ITGB2 was positively correlated with the infiltration of Treg cells and Myeloid-derived suppressor cells (MDSC). Biologically, the ectopic expression of ITGB2 significantly inhibited the proliferation and metastasis of NSCLC cells. Mechanistically, we demonstrated that ITGB2 suppressed the expression of N-cadherin, Vimentin, Slug, Snail, and Twist, while it promoted E-cadherin expression, according to gain-of-function studies. In conclusion, ITGB2 can inhibit the proliferation and migration of NSCLC cells, leading to a poor prognosis, via epithelial-mesenchymal transition (EMT) signaling.
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Background: Although immune checkpoint inhibitors (ICIs) are one of the most important treatments for advanced-stage non-small-cell lung cancer (NSCLC), NSCLC patients with ALK-rearranged usually don't obtain a clinical benefit. The reason may be related to the unique tumor microenvironment (TME). We evaluated the characteristics of immune biomarkers of the TME and their prognostic value in ALK-rearranged NSCLC. Methods: Tumor samples from patients with ALK-rearranged (N = 39) and EGFR- (N = 40)/KRAS- (N = 30) mutated NSCLC were collected. Immunohistochemistry (IHC) was used to assess the expression of 9 tumor immune markers as well as 6 immune markers of tumor-infiltrating cells. To research the TME of ALK-rearranged NSCLC, EGFR/KRAS-positive patients were used as controls. Furthermore, the correlation between the efficacy and prognosis of patients with advanced-stage (IIIC-IV) ALK rearrangements treated with targeted drugs was analyzed in terms of the TME. Results: The proportion of PD-L1+ tumors was lower in ALK-positive NSCLC than in KRAS-positive NSCLC. Besides, the proportion of T cells expressing TIM-3-CD8+ (15.38%), CTLA4-CD8+ (12.82%), LAG3-CD8+ (33.33%) and PD-1-CD8+ (2.56%) in ALK-positive NSCLC was lower than that in EGFR/KRAS-positive NSCLC. The expression of CD3, CD8 T cells and CD20 B cells was lower in ALK-positive NSCLC than in KRAS-positive NSCLC (p < 0.0001, < 0.005, and < 0.001, respectively). Nevertheless, the level of CD4 helper T cells was higher in ALK-positive NSCLC than in EGFR/KRAS-positive NSCLC (p < 0.0001 and p < 0.05, respectively). The repression of TIM3 was higher in ALK-positive NSCLC than in KRAS-positive NSCLC (p < 0.001). In addition, our data showed that high expression of PD-L1 (HR = 0.177, 95% CI 0.038-0.852, p = 0.027) and CTLA4 (HR = 0.196, 95% CI 0.041-0.947, p = 0.043) was related to lower OS in advanced-stage ALK- rearranged NSCLC patients treated with ALK tyrosine kinase inhibitors (TKIs). Conclusions: Immunosuppressive status was characteristic of the TME in patients with ALK-positive NSCLC compared with EGFR/KRAS-positive NSCLC. High expression of PD-L1 and CTLA4 was an adverse prognostic factor in advanced-stage ALK-rearranged NSCLC patients treated with ALK-TKIs. Immunotherapy for ALK-rearranged patients requires further exploration and validation by clinical trials.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Quinasa de Linfoma Anaplásico/genética , Quinasa de Linfoma Anaplásico/metabolismo , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/genética , Antígeno CTLA-4/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Receptores ErbB/metabolismo , Receptor 2 Celular del Virus de la Hepatitis A/genética , Receptor 2 Celular del Virus de la Hepatitis A/metabolismo , Humanos , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Mutación , Receptor de Muerte Celular Programada 1/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas p21(ras)/genética , Microambiente TumoralRESUMEN
The mechanism of improving the anaerobic fermentation performance of waste active sludge by using dielectric barrier discharge (DBD) plasma pretreatment technology was investigated. The maximum accumulation of short-chain fatty acids (SCFAs) was observed on the 7th day of anaerobic fermentation when the DBD power was 76.50 W, which was 1726.70 mg COD/L, 1.50 times of the control group. The ratio of acetic acid in DBD group was 9.30% higher than that in the control. Further mechanism research indicated that DBD pretreatment can destroy the structure of extracellular polymer substances and release organic substances such as protein and polysaccharide. The dissolved organic matter analysis indicated that the DBD technique could increase the release of biodegradable organics (eg., tyrosine proteins, soluble microbial by-products), thus accelerate the biotransformation of organic substance. Bacterial community structure analysis showed that the increase in the abundance of Firmicutes and Bacteroidetes and the decrease in the abundance of Proteobacteria in DBD group were beneficial to the accumulation of SCFAs. Besides, further archaeal analysis indicated that the decrease of Methanosaeta sp. and Methanosarcina sp. abundance in the DBD group facilitate acetic acid accumulation. This study demonstrated that the DBD technique can be used as an effective and potential pretreatment method to improve sludge anaerobic fermentation performance.
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In this study, the combination of dielectric barrier discharge plasma (DBD) with calcium peroxide (CaO2) achieved significant synergistic effects in promoting hydrolysis of waste activated sludge (WAS) and short-chain fatty acid (SCFA) production during anaerobic fermentation. Compared with the control, DBD/CaO2 pretreatment increased SCFA production by 116 %, acetic acid ratio by 39 %, and sludge reduction by 30 % under the optimal conditions (discharge power = 76.5 W, CaO2 dosage = 0.05 g/g VSS). Mechanism investigations elucidated that DBD/CaO2 enhanced the generation of â¢OH, 1O2, and â¢O2-, synergistically promoted decomposing extracellular polymeric substances (EPS), lysing cells, releasing biodegradable substances, and enhancing acetic acid-enriched SCFA accumulation from fermentation. Meanwhile, Illumina MiSeq sequencing analysis revealed that the enrichment of hydrolytic and SCFAs-forming bacteria and the decrease in SCFAs-consuming bacteria by DBD/CaO2 treatment also contributed. This work provides an effective method to boost the SCFA production from WAS fermentation.
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Ácidos Grasos Volátiles , Aguas del Alcantarillado , Anaerobiosis , Fermentación , Concentración de Iones de Hidrógeno , PeróxidosRESUMEN
The SAUR (small auxin-up RNA) gene family is the biggest family of early auxin response genes in higher plants and has been associated with the control of a variety of biological processes. Although SAUR genes had been identified in several genomes, no systematic analysis of the SAUR gene family has been reported in Chinese white pear. In this study, comparative and systematic genomic analysis has been performed in the SAUR gene family and identified a total of 116 genes from the Chinese white pear. A phylogeny analysis revealed that the SAUR family could be classified into four groups. Further analysis of gene structure (introns/exons) and conserved motifs showed that they are diverse functions and SAUR-specific domains. The most frequent mechanisms are whole-genome duplication (WGD) and dispersed duplication (DSD), both of which may be important in the growth of the SAUR gene family in Chinese white pear. Moreover, cis-acting elements of the PbrSAUR genes were found in promoter regions associated with the auxin-responsive elements that existed in most of the upstream sequences. Remarkably, the qRT-PCR and transcriptomic data indicated that PbrSAUR13 and PbrSAUR52 were significantly expressed in fruit ripening. Subsequently, subcellular localization experiments revealed that PbrSAUR13 and PbrSAUR52 were localized in the nucleus. Moreover, PbrSAUR13 and PbrSAUR52 were screened for functional verification, and Dangshan pear and frandi strawberry were transiently transformed. Finally, the effects of these two genes on stone cells and lignin were analyzed by phloroglucinol staining, Fourier infrared spectroscopy, and qRT-PCR. It was found that PbrSAUR13 promoted the synthesis and accumulation of stone cells and lignin, PbrSAUR52 inhibited the synthesis and accumulation of stone cells and lignin. In conclusion, these results indicate that PbrSAUR13 and PbrSAUR52 are predominantly responsible for lignin inhibit synthesis, which provides a basic mechanism for further study of PbrSAUR gene functions.