RESUMEN
Systemic immunosuppression greatly affects the chemotherapeutic antitumor effect. Here, we showed that CD19+ extracellular vesicles (EVs) from B cells through CD39 and CD73 vesicle-incorporated proteins hydrolyzed ATP from chemotherapy-treated tumor cells into adenosine, thus impairing CD8+ T cell responses. Serum CD19+ EVs were increased in tumor-bearing mice and patients. Patients with fewer serum CD19+ EVs had a better prognosis after chemotherapy. Upregulated hypoxia-inducible factor-1α (HIF-1α) promoted B cells to release CD19+ EVs by inducing Rab27a mRNA transcription. Rab27a or HIF-1α deficiency in B cells inhibited CD19+ EV production and improved the chemotherapeutic antitumor effect. Silencing of Rab27a in B cells by inactivated Epstein-Barr viruses carrying Rab27a siRNA greatly improved chemotherapeutic efficacy in humanized immunocompromised NOD PrkdcscidIl2rg-/- mice. Thus, decreasing CD19+ EVs holds high potential to improve the chemotherapeutic antitumor effect.
Asunto(s)
Linfocitos B/inmunología , Linfocitos T CD8-positivos/inmunología , Vesículas Extracelulares/inmunología , Animales , Antígenos CD19/inmunología , Línea Celular , Línea Celular Tumoral , Femenino , Células HEK293 , Herpesvirus Humano 4/inmunología , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , Células 3T3 NIH , ARN Mensajero/inmunología , Transcripción Genética/inmunología , Proteínas rab27 de Unión a GTP/inmunologíaRESUMEN
A large amount of sludge is inevitably produced during sewage treatment. Ultrasonication (US) as anaerobic digestion (AD) pretreatment was implemented on different sludges and its effects on batch and semi-continuous AD performance were investigated. US was effective in sludge SCOD increase, size decrease, and CH4 production in the subsequent AD, and these effects were enhanced with an elevated specific energy input. As indicated by semi-continuous AD experiments, the mean daily CH4 production of US-pretreated A2O-, A2O-MBR-, and AO-AO-sludge were 176.9, 119.8, and 141.7 NmL/g-VSadded, which were 35.1%, 32.1% and 78.2% higher than methane production of their respective raw sludge. The US of A2O-sludge achieved preferable US effects and CH4 production due to its high organic content and weak sludge structure stability. In response to US-pretreated sludge, a more diverse microbial community was observed in AD. The US-AD system showed negative net energy; however, it exhibited other positive effects, e.g., lower required sludge retention time and less residual total solids for disposal. US is a feasible option prior to AD to improve anaerobic bioconversion and CH4 yield although further studies are necessary to advance it in practice.
Asunto(s)
Reactores Biológicos , Metano , Aguas del Alcantarillado , Eliminación de Residuos Líquidos , Metano/metabolismo , Metano/análisis , Anaerobiosis , Eliminación de Residuos Líquidos/métodos , SonicaciónRESUMEN
Electrocoagulation (EC) is a promising alternative for decentralized drinking water treatment in rural areas as a chemical-free technology. However, seasonal fluctuations of water quality in influent remain a significant challenge for rural decentralized water supply, which was a potential threat to water safety. The frequent operation was required to ensure the effluent water quality by the experienced technicians, who were in shortage in rural areas. If the operational parameters prediction model based on water quality could be established, it might reduce the dependence on technicians. Therefore, an artificial neural network (ANN) model combined with genetic algorithm (GA) was used to establish a prediction model for unattended intelligent operation. Data on water quality and operational parameters were collected from a practical EC system in a decentralized water treatment plant. Seven water quality parameters (e.g., turbidity, temperature, pH and conductivity) were selected as input variables and the operational current was employed as the output. A non-linear relationship between water quality parameters and the operational current was verified by correlation analysis and principal component analysis (PCA). The mean squared error (MSE) and coefficient of determination (R2) were used as evaluation indexes to optimize the structure of the GA-ANN model. Influent turbidity was identified to be crucial in the GA-ANN model by model interpretation using sensitivity analysis and scenario analysis. The Garson weight of turbidity in the seven input variables achieved 45.4%. The predictive accuracy of the GA-ANN model sharply declined from 90% to 67.1% when influent turbidity data were absent. In addition, it was estimated that energy consumption savings of the GA-ANN method declined by 14.2% in comparison with the gradient control method. This study verifies the feasibility and stability of machine learning strategy for unattended operation in the rural decentralized water treatment plant.
Asunto(s)
Redes Neurales de la Computación , Purificación del Agua , Calidad del Agua , Purificación del Agua/métodos , Electrocoagulación , Aprendizaje AutomáticoRESUMEN
Although applications of the integrated ultrafiltration (UF) membrane have been investigated for years, most studies have been conducted at the lab scale. Here, a case study on the integrated Fe-based floc-UF process was presented. To enhance membrane performance, both pre-filtration (bag filter) and pre-oxidation were used as pretreatments to remove particles and inhibit the development of microorganisms. Results showed that the integrated process operated stably with pre-treatments, and the UF membrane fouling behavior could be divided into three different phases: slow increase rate (phase I), medium increase rate (phase II), and fast increase rate (phase III). In comparison to those in phases II and III, both natural organic matters and colloids were the main membrane fouling mechanisms during phase I, as the pollutants were not successfully removed by flocs initially. With the continuous injection of flocs, a loose cake layer became the main fouling mechanism during phase II, resulting in the deterioration of membrane fouling. During phase III, however, microorganisms (e.g., Proteobacteria) were inevitably nourished within the cake layer and played an important role in aggravating the degree of membrane fouling. During this integrated membrane-based process, several operating factors, including floc concentration, sludge discharge frequency, and the aeration rate during backwashing, played important roles in determining membrane performance. In addition, except for oxygen consumption, all the effluent quality parameters met the drinking water criteria followed in China (GB5749-2006).
Asunto(s)
Agua Potable , Purificación del Agua , Membranas Artificiales , Proyectos Piloto , Aguas del Alcantarillado , Ultrafiltración/métodos , Purificación del Agua/métodosRESUMEN
Epidemiological and clinical studies have shown that exposure to particulate matter (PM) is associated with an increased incidence of lung cancer and metastasis. However, the underlying mechanism remains unclear. Here, we demonstrated the central role of PM-induced neutrophil recruitment in promoting lung cancer metastasis. We found that reactive oxygen species (ROS)-mediated alveolar epithelial macroautophagy/autophagy was essential for initiating neutrophil chemotaxis and pre-metastatic niche formation in the lungs in response to PM exposure. During PM-induced autophagy, the E3 ubiquitin ligase TRIM37 was degraded and protected TRAF6 from proteasomal degradation in lung epithelial cells, which promoted the NFKB-dependent production of chemokines to recruit neutrophils. Importantly, ROS blockade, autophagy inhibition or TRAF6 knockdown abolished PM-induced neutrophil recruitment and lung metastasis enhancement. Our study indicates that host lung epithelial cells and neutrophils coordinate to promote cancer metastasis to the lungs in response to PM exposure and provides ideal therapeutic targets for metastatic progression.Abbreviations: ACTA2/α-SMA: actin alpha 2, smooth muscle, aorta; ATII: alveolar type II; Cho-Traf6 siRNA: 5'-cholesterol-Traf6 siRNA; EMT: epithelial-mesenchymal transition; HBE: human bronchial epithelial; HCQ: hydroxychloroquine; MAPK: mitogen-activated protein kinase; NAC: N-acetyl-L-cysteine; NFKB: nuclear factor of kappa light polypeptide gene enhancer in B cells; NS: normal saline; PM: particulate matter; ROS: reactive oxygen species; TRAF6: TNF receptor-associated factor 6; TRIM37: tripartite motif-containing 37.
Asunto(s)
Neoplasias Pulmonares , Factor 6 Asociado a Receptor de TNF , Proteínas de Motivos Tripartitos , Animales , Autofagia/fisiología , Células Epiteliales/metabolismo , Neoplasias Pulmonares/patología , Ratones , Metástasis de la Neoplasia , Material Particulado/efectos adversos , ARN Interferente Pequeño/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Factor 6 Asociado a Receptor de TNF/metabolismo , Proteínas de Motivos Tripartitos/metabolismo , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
TGF-ß is essential for inducing systemic tumor immunosuppression; thus, blocking TGF-ß can greatly enhance antitumor immunity. However, there are still no effective TGF-ß inhibitors in clinical use. Here, we show that the clinically approved compound ursodeoxycholic acid (UDCA), by degrading TGF-ß, enhances antitumor immunity through restraining Treg cell differentiation and activation in tumor-bearing mice. Furthermore, UDCA synergizes with anti-PD-1 to enhance antitumor immunity and tumor-specific immune memory in tumor-bearing mice. UDCA phosphorylates TGF-ß at T282 site via TGR5-cAMP-PKA axis, causing increased binding of TGF-ß to carboxyl terminus of Hsc70-interacting protein (CHIP). Then, CHIP ubiquitinates TGF-ß at the K315 site, initiating p62-dependent autophagic sorting and subsequent degradation of TGF-ß. Notably, results of retrospective analysis shows that combination therapy with anti-PD-1 or anti-PD-L1 and UDCA has better efficacy in tumor patients than anti-PD-1 or anti-PD-L1 alone. Thus, our results show a mechanism for TGF-ß regulation and implicate UDCA as a potential TGF-ß inhibitor to enhance antitumor immunity.
Asunto(s)
Neoplasias , Factor de Crecimiento Transformador beta , Animales , Línea Celular Tumoral , Humanos , Terapia de Inmunosupresión , Ratones , Neoplasias/tratamiento farmacológico , Estudios Retrospectivos , Factor de Crecimiento Transformador beta/metabolismo , Ácido Ursodesoxicólico/farmacología , Ácido Ursodesoxicólico/uso terapéuticoRESUMEN
Organic-inorganic halide perovskites solar cells have garnered increasing attention in recent years due to the dramatic rise in power conversion efficiencies (PCEs). In perovskite solar cells (PSCs), selecting appropriate hole transport materials to insert between perovskite layer and electrodes can improve Schottky contact, facilitate the hole transport, therefore reduce charge recombination, and therefore improve cell performance. Doping of metal cation is an effective means to regulate energy level structure and change its conductivity. In this study, we novelly introduce the Pb2+ doped NiOx as the hole transport materials to decrease the energy loss between NiOx and the perovskite layer, which improves open-circuit voltage (Voc) of the PSCs. In order to improve the conductivity of the NiOx film, the Li+ co-doping is introduced. We introduce Pb and Li co-doping strategy to match the work function of doped NiOx with perovskite valence band energy level, and increase the conductivity of NiOx for high-efficiency inverted planar PSCs. The Pb and Li co-doped NiOx devices exhibit efficient hole extraction and enhanced conductivity, which improve the performance of inverted planar PSCs to 17.02% compared with 15.40% of the undoped device.
RESUMEN
BACKGROUND: Knee osteoarthritis (KOA) is the most common form of arthritis, leading to pain disability in seniors and increased health care utilization. Acupotomy has been widely used to treat KOA. But its efficiency has not been scientifically and methodically evaluated. The aim of this study is to evaluate the efficacy and safety of acupotomy for the treatment of patients with KOA. METHODS: Relevant studies will be searched from the databases of PubMed, EMBASE, Cochrane Library, China Knowledge Resource Integrated Database, Weipu Database for Chinese Technical Periodicals, SinoMed, and Wanfang Database from their inception to June 10, 2019. Two researchers will independently select studies, collect data, and assess the methodology quality by the Cochrane risk of bias tool. RESULTS: The systematic review will provide high-quality evidence to assess the efficacy and safety of acupotomy for KOA by pain, stiffness, and dysfunction of knee joint, and quality of life, as well as adverse events. CONCLUSION: The systematic review will provide evidence to assess the effectiveness and safety of acupotomy therapy for KOA patients. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019132082.
Asunto(s)
Terapia por Acupuntura/métodos , Osteoartritis de la Rodilla/terapia , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Articulación de la Rodilla/fisiopatología , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/fisiopatología , Dimensión del Dolor , Calidad de Vida , Proyectos de Investigación , Revisiones Sistemáticas como Asunto , Resultado del TratamientoRESUMEN
Fas induces apoptosis in activated T cell to maintain immune homeostasis, but the effects of non-apoptotic Fas signaling on T cells remain unclear. Here we show that Fas promotes TH9 cell differentiation by activating NF-κB via Ca2+-dependent PKC-ß activation. In addition, PKC-ß also phosphorylates p38 to inactivate NFAT1 and reduce NFAT1-NF-κB synergy to promote the Fas-induced TH9 transcription program. Fas ligation exacerbates inflammatory bowel disease by increasing TH9 cell differentiation, and promotes antitumor activity in p38 inhibitor-treated TH9 cells. Furthermore, low-dose p38 inhibitor suppresses tumor growth without inducing systemic adverse effects. In patients with tumor, relatively high TH9 cell numbers are associated with good prognosis. Our study thus implicates Fas in CD4+ T cells as a target for inflammatory bowel disease therapy. Furthermore, simultaneous Fas ligation and low-dose p38 inhibition may be an effective approach for TH9 cell induction and cancer therapy.