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Oxaliplatin is an antineoplastic agent frequently used in the treatment of gastrointestinal tumors. However, it causes dose-limiting sensorimotor neuropathy, referred to as oxaliplatin-induced peripheral neuropathy (OIPN), for which there is no effective treatment. Here, we report that the elevation of neutrophil extracellular traps (NET) is a pathologic change common to both cancer patients treated with oxaliplatin and a murine model of OIPN. Mechanistically, we found that NETs trigger NLR family pyrin domain containing 3 (NLRP3) inflammasome activation and the subsequent release of IL18 by macrophages, resulting in mechanical hyperalgesia. In NLRP3-deficient mice, the mechanical hyperalgesia characteristic of OIPN in our model was reduced. In addition, in the murine model, treatment with the IL18 decoy receptor IL18BP prevented the development of OIPN. We further showed that eicosapentaenoic acid (EPA) reduced NET formation by suppressing the LPS-TLR4-JNK pathway and thereby abolished NLRP3 inflammasome activation and the subsequent secretion of IL18, which markedly prevented oxaliplatin-induced mechanical hyperalgesia in mice. These results identify a role for NET-triggered NLRP3 activation and IL18 release in the development of OIPN and suggest that utilizing IL18BP and EPA could be effective treatments for OIPN.Ultrathin silica films are considered suitable two-dimensional model systems for the study of fundamental chemical and physical properties of all-silica zeolites and their derivatives, as well as novel supports for the stabilization of single atoms. In the present work, we report the creation of a new model catalytic support based on the surface functionalization of different silica bilayer (BL) polymorphs with well-defined atomic structures. The functionalization is carried out by means of in situ H-plasma treatments at room temperature. Low energy electron diffraction and microscopy data indicate that the atomic structure of the films remains unchanged upon treatment. Comparing the experimental results (photoemission and infrared absorption spectra) with density functional theory simulations shows that H2 is added via the heterolytic dissociation of an interlayer Si-O-Si siloxane bond and the subsequent formation of a hydroxyl and a hydride group in the top and bottom layers of the silica film, respectively. Functionalization of the silica films constitutes the first step into the development of a new type of model system of single-atom catalysts where metal atoms with different affinities for the functional groups can be anchored in the SiO2 matrix in well-established positions. In this way, synergistic and confinement effects between the active centers can be studied in a controlled manner.Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 has been a clinical breakthrough for pediatric B-cell acute lymphoblastic leukemia (B-ALL), and loss of the CD19 target antigen on leukemic cells represents a major mechanism of relapse. Previous studies have observed CD19 mutations specific to CD19- relapses, and we sought to clarify and strengthen this relationship using deep whole-exome sequencing in leukemic cells expanded in a patient-derived xenograft. By assessing pre-treatment and relapse cells from 13 patients treated with CAR T-cell therapy, 8 of whom developed CD19- relapse and 5 of whom developed CD19+ relapse, we demonstrate that relapse-specific single-nucleotide variants and small indels with high allele frequency combined with deletions in the CD19 gene in a manner specific to those patients with CD19- relapse. Before CAR T-cell infusion, one patient was found to harbor a pre-existing CD19 deletion in the context of genomic instability, which likely represented the first hit leading to the patient's subsequent CD19- relapse. Across patients, preexisting mutations and genomic instability were not significant predictors of subsequent CD19- relapse across patients, with sample size as a potential limiting factor. Together, our results clarify and strengthen the relationship between genomic events and CD19- relapse, demonstrating this intriguing mechanism of resistance to a targeted cancer immunotherapy.<br />Tuberculosis is a widespread communicable disease, which is one of the top 10 causes of demise globally. Several regression models have been built, and then utilized for the Tuberculosis incidence projections. However, when fitting a multiple linear regression model, an analysis must account for multicollinearity aspects. The present study aimed to develop a parsimonious model that produces unbiased results based on socioeconomic variables as predictors of Tuberculosis incidence.<br />Ecological study.<br />Data were collected from the Karaganda Regional Center of Phthisio-pulmonology and Bureau of National Statistics. By multiple linear regression model, we investigated associations between Tuberculosis incidence rate and socioeconomic determinants in Karaganda region, Kazakhstan, during 2001-2019. A Principal components analysis was performed on the socioeconomic variables with oblique rotation. Furthermore, associations of Tuberculosis incidence with the principal components derived from the Principal componen Tuberculosis.<br />M. Sorokina supervised the study, Ukubayev T. collected the data, performed statistical analysis, and drafted the manuscript; M. Sorokina and B. Koichubekov, reviewed and edited the manuscript. All authors discussed and contributed to the final manuscript.<br />M. Sorokina supervised the study, Ukubayev T. collected the data, performed statistical analysis, and drafted the manuscript; M. Sorokina and B. Koichubekov, reviewed and edited the manuscript. All authors discussed and contributed to the final manuscript.<br />During 2020, COVID-19 had a diversified distribution in Italy, the first nation in Europe to experience the outbreak of the epidemic. This was linked to geographical differences in population density and distribution of healthcare facilities, including Emergency Departments (EDs). This study aims to assess the impact of the pandemic on ED utilization in 2020 across different subpopulations and geographical locations in Italy.<br />We used anonymized data from a survey conducted by the Italian National Institute of Statistics on 25,000 families to analyze the yearly rate of people who used EDs from 2015 to 2020. The rate of persons who accessed ED services in 2020 per 1,000 population was compared with those of the previous non-pandemic years.<br />The number of people accessing EDs in 2020 was 32.3% lower, although this reduction was not uniform across the 21 regions / autonomous provinces. People aged 0-14 years experienced the highest reduction in ED visits. In 2020, low educational level people exhibited a stecies.Reverse electrodialysis (RED) is a technology to generate electricity from two streams with different salinities. While RED systems have been conventionally used for electricity generation, recent works explored combining RED for production of valuable gases. This work investigates the feasibility of producing hydrogen and chlorine in addition to electricity in an RED stack and identifies potential levers for improvement. A simplified one-dimensional model is adopted to assess the technical and economic feasibility of the process. We notice a strong disparity in typical current densities of RED fed with seawater and river water and that in typical water (or chlor-alkali) electrolysis. This can be partly mitigated by using brine and seawater as RED feeds. Considering such an RED system, we estimate a hydrogen production of 1.37 mol/(m2 h) and an electrical power density of 1.19 W/m2. Although this exceeds previously reported hydrogen production rates in combination with RED, the levelized costs of products are 1-2 orders of magnitude higher than the current market prices at the current state. The levelized costs of products are very sensitive to the membrane price and performance. Hence, going forward, manufacturing thinner and highly selective membranes is required to make the system competitive against the consolidated technologies.The Hippo signaling pathway controls cell proliferation and tissue regeneration via its transcriptional effectors yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ). The canonical pathway topology is characterized by sequential phosphorylation of kinases in the cytoplasm that defines the subcellular localization of YAP and TAZ. However, the molecular mechanisms controlling the nuclear/cytoplasmic shuttling dynamics of both factors under physiological and tissue-damaging conditions are poorly understood. By implementing experimental in vitro data, partial differential equation modeling, as well as automated image analysis, we demonstrate that nuclear phosphorylation contributes to differences between YAP and TAZ localization in the nucleus and cytoplasm. Treatment of hepatocyte-derived cells with hepatotoxic acetaminophen (APAP) induces a biphasic protein phosphorylation eventually leading to nuclear protein enrichment of YAP but not TAZ. APAP-dependent regulation of nuclear/cytoplasmic YAP shuttling is not an unspecific cellular response but relies on the sequential induction of reactive oxygen species (ROS), RAC-alpha serine/threonine-protein kinase (AKT, synonym protein kinase B), as well as elevated nuclear interaction between YAP and AKT. Mouse experiments confirm this sequence of events illustrated by the expression of ROS-, AKT-, and YAP-specific gene signatures upon APAP administration. In summary, our data illustrate the importance of nuclear processes in the regulation of Hippo pathway activity. YAP and TAZ exhibit different shuttling dynamics, which explains distinct cellular responses of both factors under physiological and tissue-damaging conditions.High-throughput automated manipulation of microparticles in complex-shaped environments has been demonstrated with great potential in the field of pharmaceutical microfluidics. [https://www.selleckchem.com/ selleck compound] Generally, the development of a highly efficient actuation method for functional microparticle manipulation in complex-shaped chamber structures is the key challenge of this technology. Here, we present a novel traveling surface acoustic wave (TSAW)-based manipulation device that allows for automated and high-throughput maze-solving manipulation of microparticles inside complex round-shaped and square-shaped maze chambers. This technology relies on the localized acoustic streaming effects generated by TSAWs, which are capable of automatically trapping microparticles and driving them to move along the determined trajectories based on the topographic features of the maze chamber. Numerical modelling and simulation were conducted to demonstrate the feasibility of our proposed device for targeted microparticle transportation in complex-shaped maze chamber environments. In addition, by configuring the excitation of electric signals of interdigital transducers (IDTs), such as excitation frequency and input voltage, the motion velocity of microparticles can be rapidly adjusted within 0.1 s. Thus, our device enables low-cost, compact, and contactless trajectory manipulation of high-throughput microparticles inside chambers with complex topographical features and would have application in cell-directed transportation, low-volume chemical mixing, and precise drug delivery.