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Due to global warming, it is necessary to study the influence of extreme climate and concurrent events on crop growth. The study area was the Songliao Plain, where drought events frequently occur. First, the daily meteorological data of 14 meteorological stations from 1981 to 2016 were collected to analyze the temporal and spatial changes in the crop water surplus and deficit index, extreme growing degree-days, and heat stress intensity during different growth stages of maize. Second, the cloud model was used to describe the fuzziness of concurrent events (simultaneous drought and heat), and mutual mapping between qualitative and quantitative data was undertaken. The fuzzy certainty degree of the influence of different degrees of concurrent events on maize was calculated. Third, the copula function was used to describe the randomness of concurrent extreme events and calculate the joint probability distribution and return period. An assessment method was proposed for concurrent events from the perspective of system uncertainty. Finally, we analyzed the relationship between concurrent events and maize yield, which showed different degrees of water deficit and warming trends during each growth period. Crops were most affected by extreme weather during the reproductive growth period (RGP). During the vegetative growth period (VGP), the temperature increase was higher than in other periods, especially in the high-latitude region. The frequency of mild concurrent events was higher during the VGP and RGP. During the vegetative and reproductive period, the average occurrence probability of mild, moderate, and severe concurrent events was 21.9%, 1.7%, and 0.35%, respectively, whereas during the RGP, it was 23.1%, 8.2%, and 0.12%, respectively. The present study provides a meaningful reference for a better understanding of the occurrence laws of drought, heat, and concurrent events during crop growth periods and how to optimize the agricultural management of maize. • Cloud model qualitative and quantitative mapping of drought and heat events. • Copula function was used to describe the randomness of concurrent extreme events. • Vegetative growth periods (VGP) and reproductive growth periods (RGP) were modelled. [ABSTRACT FROM AUTHOR]

mTOR, mLST8 and RAPTOR are the core components of mTORC1, which has been found to be closely related to tumorigenesis. Currently, multiple single nucleotide polymorphisms (SNPs) in mTOR gene (rs2295080, rs17036508 and rs1034528) , mLST8 gene (rs3160 and rs26865) and RPTOR gene (rs1062935, rs3751932, rs3751834, rs12602885) have been extensively studied for their associations with cancer risk. However, the results remained inconclusive and conflicting. Therefore, we here performed a meta-analysis of all available studies to investigate the association between these SNPs and cancer risk. Up to April 2021, 25 related publications were retrieved and included in this meta-analysis. The odds ratios (ORs) and 95% confidence intervals (CIs) calculated by fixed or random effects models were applied to assess the strength of association. Trial Sequential Analysis (TSA) was conducted to weaken the random error and enhance the reliability of evidence. After Bonferroni correction, it was revealed that rs3160, rs26865, rs1062935, rs3751932, rs3751834 and rs10602885 were not associated with cancer risk. However, rs17036508 and rs1034528 showed significant association with total cancer risk. A significant association was also found between rs2295080 and total cancer risk, and stratified analysis by cancer type suggested that rs2295080 was specifically associated with acute lymphoblastic leukemia risk, prostate cancer risk, and breast cancer risk. The present meta-analysis suggested that the rs2295080, rs17036508 and rs1034528 polymorphisms in mTOR gene may be the susceptive factors for cancer development, while the target genetic polymorphisms in mLST8 gene or RPTOR gene may not be associated with cancer risk. However, these findings remain to be confirmed or further reinforced in large and well-designed studies in different ethnic populations. [ABSTRACT FROM AUTHOR]

Abstract: Cytotoxic CD8+ T cells are key effectors in the immunotherapy of malignant and viral diseases. However, the lack of efficient methods for their in vitro priming and expansion has become a bottleneck to the development of vaccines and adoptive transfer strategies. Synthetic artificial antigen-presenting cells (aAPCs) are now emerging as an attractive tool for eliciting and expanding CTL responses. This study reported a novel approach for targeting malignant melanoma with pTRP2-specific cytotoxic T lymphocytes (CTLs) expanded from the C57BL/6 splenocytes by multiple stimulations with aAPCs made by coating H-2Kb-Ig/pTRP2 dimeric complexes, anti-CD28 antibody, 4-1BBL molecules and CD83 molecules to cell-sized latex beads. The induced CTLs exhibited specific lysis against RMA-S cells pulsed with the peptide pTRP2 and H-2Kb+ melanoma cells expressing TRP2, while a murine Lewis lung carcinoma cell line 3LL could not be recognized by the CTLs. The peptide-specific activity was inhibited by anti-H-2Kb monoclonal antibody Y3. Adoptive Transfer of CTLs specific for malignant melanoma expanding by the aAPCs can mediate effective anti-melanoma response. These results suggested the bead-based aAPCs coated with an MHC-Ig/peptide complex, anti-CD28 antibody, 4-1BBL and CD83 could provide a useful tool for the reproducible expansion of specific CTLs for adoptive immunotherapy. [Copyright &y& Elsevier]

Aggregated eutectic intermetallic phases in a casting Mg-Ag-Al alloy were characterized using transmission electron microscopy. Three kinds of intermetallic phases, namely ε-Mg 3 Ag (or ε-Mg 26 − x Ag 7+x), β′-Mg 2 (Al,Ag) 3 , and γ-Mg 17 Al 12 , were observed to aggregate together following certain crystallographic orientation relationships (ORs) as: (001) ε //(1 1 ¯ 2) γ and [100] ε //[110] γ (OR1), (001) ε //(110) γ and [001] ε //[110] γ (OR2), (01 1 ¯) β ′ //(1 ¯ 10) γ and [100] β ′ //[110] γ , and (001) β ′ //(010) ε and [100] β ′ //[100] ε. TEM observations combined with the corresponding phase diagrams reveal that the ε phase firstly formed during solidification, then the γ phase nucleated on the ε phase, and finally, the β′ phase nucleated on the γ phase. This special intermetallic phase composition which owns numerous fine particles and many semi-coherent interphase boundaries results in high-strength and high-ductility for the casting QA61 alloy. Unlabelled Image • Both binary and ternary intermetallic phases were observed in Mg-Ag-Al alloy. • Three aggregated intermetallic phases are semi-coherent with each other. • Two orientation relationships between ε-Mg 3 Ag and γ-Mg 17 Al 12 were revealed. • Mg-6Ag-1Al alloy has high-strength/ductility due to aggregated intermetallic phases. [ABSTRACT FROM AUTHOR]

Aspect-based sentiment analysis (ABSA) aims to conduct fine-grained sentiment analysis, necessitating the extraction of three key components: target entity, aspect category and sentiment polarity. These three components collectively form an integrated ABSA task known as TASD (Target-Aspect-Sentiment jointly Detection). Most of existing approaches on ABSA usually employ Recurrent neural networks(RNNs), Convolutional neural networks(CNNs) or pre-training models such as Bidirectional Encoder Representations from Transformers(BERT). However, they have some common weaknesses. First, most of the existing methods focus on one or two sub-tasks instead of triplet detection, thus they do not establish an end-to-end (training a complex learning system represented by a single model) ABSA model and cannot utilize the relevance of multiple ABSA sub-tasks during training. Second, they cannot achieve accuracy and efficiency simultaneously due to the coupling of context and given aspects. Third, they are poor in recognizing implicit targets. To tackle these limitations, this paper proposes a novel method named the Twin Towers End to End model (TTEE) to solve TASD task. It transforms complex TASD task into a simple end-to-end multi-task framework, simultaneously conducting target and aspect-sentiment detection. It builds twin towers system based on BERT or its updated versions to decouple context and given aspects, which can reduce redundant calculation to improve computational efficiency significantly. It offers great advantage to identify implicit target entity and its associated aspect-sentiment in the context without introducing extra model architecture. Experiments on three public datasets in different domains demonstrate that our approach not only achieves better performance on various evaluation metrics, but also has high efficiency in both training and inference phases, over a wide range of sample size and number of aspect categories. • The T-A-S triplets can be decoded from the end-to-end output of TTEE. • BERT-based model is employed to encode context and aspect-sentiment pairs separately. • TTEE efficiently reduces redundant calculations of embedding process. • TTEE excels in detecting implicit targets within the context. [ABSTRACT FROM AUTHOR]

Background & Aims In this study, we investigated the role of salt-inducible kinase 1 (SIK1) and its possible mechanisms in human hepatocellular carcinoma (HCC). Methods Immunoprecipitation, immunohistochemistry, luciferase reporter, Chromatin immunoprecipitation, in vitro kinase assays and a mouse model were used to examine the role of SIK1 on the β-catenin signaling pathway. Results SIK1 was significantly downregulated in HCC compared with normal controls. Its introduction in HCC cells markedly suppresses epithelial-to-mesenchymal transition (EMT), tumor growth and lung metastasis in xenograft tumor models. The effect of SIK1 on tumor development occurs at least partially through regulation of β-catenin, as evidenced by the fact that SIK1 overexpression leads to repression of β-catenin transcriptional activity, while SIK1 depletion has the opposite effect. Mechanistically, SIK1 phosphorylates the silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) at threonine (T)1391, which promotes the association of nuclear receptor corepressor (NCoR)/SMRT with transducin-beta-like protein 1 (TBL1)/transducing-beta-like 1 X-linked receptor 1 (TBLR1) and disrupts the binding of β-catenin to the TBL1/TBLR1 complex, thereby inactivating the Wnt/β-catenin pathway. However, SMRT-T1391A reverses the phenotype of SIK1 and promotes β-catenin transactivation. Twist1 is identified as a critical factor downstream of SIK1/β-catenin axis, and Twist1 knockdown (Twist1 KD ) reverses SIK1 KD -mediated changes, whereas SIK1 KD /Twist1 KD double knockdown cells were less efficient in establishing tumor growth and metastasis than SIK1 KD cells. The promoter activity of SIK1 were negatively regulated by Twist1, indicating that a double-negative feedback loop exists. Importantly, levels of SIK1 inversely correlate with Twist1 expression in human HCC specimens. Conclusions Our findings highlight the critical roles of SIK1 and its targets in the regulation of HCC development and provides potential new candidates for HCC therapy. [ABSTRACT FROM AUTHOR]

This work is devoted to exploring the streamer dynamic of a nanosecond pulsed sliding dielectric barrier discharge (SLDBD) based on a three-electrode geometry, and evaluating its effectiveness for the degradation of a representative chlorinated volatile organic compound (VOC)-trichloroethylene (TCE) at ambient temperature. The surface streamer of nanosecond pulsed SLDBD presents two distinct phases: primary streamer with higher velocity and secondary streamer with lower velocity. The luminous intensity, propagation distance, and propagation velocity of the primary streamer are greatly promoted by increasing the negative DC voltage (U -DC) applied at the third electrode, whereas only a little difference can be observed in the luminous intensity and propagation velocity for the secondary streamer with different U -DC. The surface potential difference between the pulsed excited high-voltage and the negatively biased third electrodes (U pulse-DC) is the major cause for streamers propagation because of the increased electric field at the streamer head. The production of excited species such as N 2 (C 3 Π u) , N 2 + (B 2 Σ u +) , and OH (A 2 Σ) are promoted with increasing U -DC. The formation of N 2 (C 3 ∏ u → B 3 ∏ g , 337 nm) accompanies the streamer propagation process by electrons impact process. The TCE degradation experiment exhibits that the degradation efficiency and energy yield are significantly improved when U pulse-DC exceeds 20 kV where an SLDBD plasma is ignited, which can be attributed to the promoted surface streamers propagation as well as greater number of chemical active species. [Display omitted] • The surface streamer behavior of the three-electrode nanosecond pulsed SLDBD was explored. • The feasibility and superiority of the SLDBD plasma in TCE removal was evaluated. • Both the propagation and velocity of the primary streamer are promoted by the increased U -DC. • The contribution of key parameters on TCE degradation was modeled by a three-layer ANN model. [ABSTRACT FROM AUTHOR]

Highlights • Using one antigens (α-Gal) for the first time to prepare tumor/DC fusion cells. • Tumor (Gal+)/DC fusion cells were demonstrated as a novel strategy against cancer. Abstract Tumor cells/dendritic cells (DCs) fusion cells (tumor/DC) represent a promising immunotherapeutic strategy but are still under performed in clinical trials for cancer treatment. To further boost their anticancer efficacy, here we developed a novel design for fusing dendritic cells with MDA-MB-231 cells expressing the heterologous α-galactose (α-gal) epitope and assessed its anticancer activities both in vitro and in vivo. The high expression of α-gal in MDA-MB-231 (Gal+)/DC correlated with enhanced DC activation. When applied to T cells, MDA-MB-231 (Gal+)/DC significantly stimulated T-cell proliferation and activation, promoted productions of cytokines IL-2 and IFN-γ, and enhanced T-cell-mediated cytotoxicity against MDA-MB-231 cells. MDA-MB-231 (Gal+)/DC inhibited proliferation and promoted apoptosis of tumor cells in vivo , prolonged mouse survival, and significantly boosted anticancer immunity by increasing CD4+ and CD8+ T cells systemically and elevating serum levels of cytokines and IgG. These results suggested that fusing dendritic cells with tumor cells expressing the heterologous α-gal epitope provides a novel therapeutic strategy for cancer treatment. [ABSTRACT FROM AUTHOR]

Abstract Objective Apoptosis plays a crucial role in many biological processes, especially in cancer. However, real-time monitoring of apoptosis is challenging. [99mTc]duramycin can selectively target an apoptosis biomarker: phosphatidylethanolamine (PE), which is normally located on the intracellular cell-membrane surface but redistributes onto the outer cell-membrane upon apoptosis. Therefore, 99mTc-duramycin is a potential probe for non-invasive detection of apoptosis in real-time. The aim of this study was to evaluate the value of [99mTc]duramycin for detecting early apoptotic response in tumors after chemotherapy, thus providing a tool for early prediction of curative effects in tumors. Methods Human breast cancer MDA-MB-468 model mice, randomly divided into two groups, were injected with cisplatin or vehicle once per day. [99mTc]duramycin imaging was performed for group 1 before treatment and 24 h after the third day of treatment to evaluate treatment response through animal single-photon emission computed tomography (SPECT/CT). Mice in group 2 were treated for 10 days consecutively, to observe treatment response by tumor volume changes. Treatment response was further demonstrated through TdT-mediated dUTP nick-end labeling (TUNEL) and cleaved caspase-3 (CC3). Results [99mTc]duramycin uptake in MDA-MB-468 tumors was significantly higher in the treatment group than the control group after as few as 3 days of cisplatin treatment (p = 0.0001), and it also increased after treatment as comparison with that before treatment (p = 0.0001). Moreover, [99mTc]duramycin uptake in tumors clearly correlated with immunohistochemistry results (TUNEL: r = 0.892, p = 0.0001, and CC3: r = 0.89, p = 0.0001). Additionally, tumor size reduction, indicating effective treatment, was not observed until the eighth day after treatment, far later than the time when diagnosis could be made through [99mTc]duramycin imaging. Conclusions [99mTc]duramycin SPECT/CT provides a non-invasive molecular imaging strategy for early detection of tumor apoptosis after chemotherapy and thus may have great potential value in the clinic. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) T-cell immunotherapy has become one of the research hotspots in the treatment of malignant tumors nowadays. However, the available tumor surface antigens are limited in number. Most tumor-associated antigens are intracellular molecules that can't be targeted by conventional CAR T cells. As the major histocompatibility complex (MHC)/peptide complex is a presentation form of intracellular proteins on the surface of tumor cells, here, we chose the Glypican-3 (GPC3) oncoprotein and Wilms tumor 1 (WT1) oncoprotein as examples to explore whether nanobody (Nb)-based T cell receptor (TCR)-like CAR T cells could kill tumor cells by targeting the MHC/peptide complexes. Using the immune nanobody phage display library, we developed human leukocyte antigen (HLA)-A2/GPC3- and HLA-A2/WT1-specific nanobodies for the first time and then incorporated these nanobodies in two TCR-like CARs, targeting HLA-A2/GPC3 and HLA-A2/WT1 respectively. These TCR-like Nb CAR-redirected T cells could selectively recognize and lyse MHC/peptide complex-expressing tumor cells in vitro assays and subcutaneous mouse tumor models. This study offers a possible strategy for targeting intracellular antigens and widening the application of CAR T-cell therapy. [Display omitted] • Two TCR-like nanobodies were selected from immune phage display library. • Our strategy provides a new approach to target intracellular tumor antigens. • The nanobody-based TCR-like CAR T cells showed potent antitumor efficacy. • The novel design of CARs will contribute to a wider application of T-cell therapies. [ABSTRACT FROM AUTHOR]

High phytoplankton biomass usually appears off the coastal waters southeast of Vietnam (SV) during summer and southwest of the Luzon Strait (SLS) in winter. Although this seasonal upwelling has been recognized in SV and SLS for more than half a century, there has been limited documentation comparing the characteristics and formation mechanisms of these two upwelling systems. To understand the dynamic features of phytoplankton growth in SV and SLS, seasonal and interannual variabilities of Chlorophyll- a (Chl- a) concentration were studied based on decadal-scale satellite-derived datasets (2003–2018). Bivariate wavelet coherence (BWC) and multiple wavelet coherence (MWC) were performed to evaluate the temporal variability of multiple controlling factors. The results demonstrated that there were different patterns of seasonal cycles and interannual variability of Chl- a concentrations in the two upwelling regions. In SV, high Chl- a concentrations during summer were primarily formed by the interactions of multiple factors, causing the mixed layer depth to increase during summer and sufficient nutrient concentrations on the surface (supplied by the mixed water column). In contrast, the high Chl- a concentrations in SLS are caused by a combination of deep mixing (induced by wind and buoyancy forcing) and enhanced upward advection (induced by strong eddy activities). These factors support intense levels of phytoplankton biomass during winter. The sea surface temperature (SST) was the best single factor to explain the Chl- a variance in both regions. The addition of more factors to the MWC analysis changed the main factors influencing the Chl- a variations. The two-factor combination of SST-Niño 3.4 in SV and the SST-mixed layer depth (MLD) in SLS controlled the Chl- a variations on an interannual scale. Moreover, the three-factor combination of SST-Niño 3.4-MLD was still meaningful for explaining the Chl- a variations. This indicated that the influencing the Chl- a variations differed in these two upwelling systems. • Patterns of variations of Chl- a were different in upwelling systems. • High Chl- a formed by different physical mechanisms in upwelling systems. • Chl- a both exhibited slightly decreasing trends during the study period. • Main factors explaining in Chl- a variance differed in upwelling systems. [ABSTRACT FROM AUTHOR]