Research progress of MDSCs-targeted immunotherapy for pancreatic cancer

Pancreatic cancer (PC) is a highly malignant digestive system tumor with a poor survival rate and prognosis. Most patients with pancreatic cancer have no obvious clinical manifestations in the early stage of the disease, and are found to be in the middle and late stage of the disease when they seek treatment.A unique and complex tumor microenvironment (TME) is formed during its development and evolution. Due to the occult nature of pancreatic cancer, for patients with advanced pancreatic cancer, some traditional treatment methods such as surgical resection and chemotherapy are very limited, and there is a lack of effective treatment programs. Of course, this is also related to the immunosuppression of the TME of pancreatic cancer. Some immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), play an important immunosuppressive role in helping tumor immune escape. Therefore, it is considered to be a major difficulty in the treatment of pancreatic cancer. In recent years, with the in-depth study of TME, immunotherapy has gradually become a new therapeutic strategy, and has made great progress in the treatment of various malignant tumors. The study found that targeted MDSCs therapy is a new and effective treatment for pancreatic cancer.In this paper, we introduce the role of MDSCs in TME and their progress as potential targets for immunotherapy of pancreatic cancer, hoping to provide new directions for the treatment of pancreatic cancer and other tumors

An analysis of teacher's role as motivator to student's learning motivation in English lesson at SMPN 1 Sedati Sidoarjo

Teacher is one of the important components in the process of learning and teaching to form the potential human resource in developed era. One of the teacher's roles is as motivator. Teacher's role as motivator is important to improve student's motivation in learning. Teacher has to stimulate, motivate and reinforce the students to stick out their potency, activity and creativity. When the writer observed the school, he found the school that has a good motivation. The school is SMPN 1 Sedati Sidoarjo. All of the students were enthusiastic to learn English. The grade of the students was good. Their average grade was eight. It was caused by the motivation that had been given by teacher. From that reason, the writer has two problems of the study. These are: (1) How is teacher's role as motivator done by English teacher and (2) how far students are motivated by teacher. And to answer problem of the study, the researcher used qualitative-descriptive method and used four instruments. These are check list observation, interview, questionnaire, and documentation. The teacher of that school was very innovative in teaching the students. He used the application program that he took when he had training in America. It was suitable to be applied in that school because it was supported by complete facilities because laptop and LCD were available in that school and it was suitable with the school's curriculum. Teacher often invite the students to be participated in the English event. It can be proved by the appreciation of students was very more. The relationship between teacher and students was very close. So the students were very enthusiastic to learn English. The students made the teacher as their inspiration and motivation to learn especially in English because the teacher always shared the important to learn English and anything about life

Identification of a venetoclax-resistance prognostic signature base on 6-senescence genes and its clinical significance for acute myeloid leukemia

BackgroundSatisfactory responses can be obtained for acute myeloid leukemia (AML) treated by Venetoclax (VEN)-based therapy. However, there are still quite a few AML patients (AMLs) resistant to VEN, and it is critical to understand whether VEN-resistance is regulated by senescence.MethodsHere, we established and validated a signature for predicting AML prognosis based on VEN resistance-related senescence genes (VRSGs). In this study, 51 senescence genes were identified with VEN-resistance in AML. Using LASSO algorithms and multiple AML cohorts, a VEN-resistance senescence prognostic model (VRSP-M) was developed and validated based on 6-senescence genes.ResultsAccording to the median score of the signature, AMLs were classified into two subtypes. A worse prognosis and more adverse features occurred in the high-risk subtype, including older patients, non-de novo AML, poor cytogenetics, adverse risk of European LeukemiaNet (ELN) 2017 recommendation, and TP53 mutation. Patients in the high-risk subtype were mainly involved in monocyte differentiation, senescence, NADPH oxidases, and PD1 signaling pathway. The model’s risk score was significantly associated with VEN-resistance, immune features, and immunotherapy response in AML. In vitro, the IC50 values of ABT-199 (VEN) rose progressively with increasing expression of G6PD and BAG3 in AML cell lines.ConclusionsThe 6-senescence genes prognostic model has significant meaning for the prediction of VEN-resistance, guiding personalized molecularly targeted therapies, and improving AML prognosis

Cellular requirements for PIN polar cargo clustering in Arabidopsis thaliana

Cell and tissue polarization is fundamental for plant growth and morphogenesis. The polar, cellular localization of Arabidopsis PIN‐FORMED (PIN) proteins is crucial for their function in directional auxin transport. The clustering of PIN polar cargoes within the plasma membrane has been proposed to be important for the maintenance of their polar distribution. However, the more detailed features of PIN clusters and the cellular requirements of cargo clustering remain unclear. Here, we characterized PIN clusters in detail by means of multiple advanced microscopy and quantification methods, such as 3D quantitative imaging or freeze‐fracture replica labeling. The size and aggregation types of PIN clusters were determined by electron microscopy at the nanometer level at different polar domains and at different developmental stages, revealing a strong preference for clustering at the polar domains. Pharmacological and genetic studies revealed that PIN clusters depend on phosphoinositol pathways, cytoskeletal structures and specific cell‐wall components as well as connections between the cell wall and the plasma membrane. This study identifies the role of different cellular processes and structures in polar cargo clustering and provides initial mechanistic insight into the maintenance of polarity in plants and other systems

Developing a BLE Beacon-Based Location System Using Location Fingerprint Positioning for Smart Home Power Management

In recent years, smart homes have begun to use various sensors to detect the location of users indoors. However, such sensors may not be stable, resulting in high detection error rates. Thus, how to improve indoor positioning accuracy has become an important topic. This study explored Bluetooth Low Energy (BLE) Beacon indoor positioning for smart home power management. A novel system framework using BLE Beacon was proposed to detect the user location, and to perform power management in the home through a mobile device application. Since the BLE Beacon may produce a multipath effect, this study used the positioning algorithm and hardware configuration to reduce the error rate. Location fingerprint positioning algorithm and filter modification were used to establish a positioning method for facilitating deployment, and to reduce the required computing resources. The experiments included an observation of the Received Signal Strength Indicators (RSSI) and selecting filters and a discussion of the relationship between the characteristics of the BLE Beacon signal accuracy and the number of the BLE Beacons deployed in the observation space. The BLE Beacon multilateration positioning was combined with the In-Snergy intelligent energy management system for smart home power management. The contribution of this study is to allow users to enjoy smart home services based on their location within the home using a mobile device application

Auxin controls circadian flower opening and closure in the waterlily

Abstract Background Flowers open at sunrise and close at sunset, establishing a circadian floral movement rhythm to facilitate pollination as part of reproduction. By the coordination of endogenous factors and environmental stimuli, such as circadian clock, photoperiod, light and temperature, an appropriate floral movement rhythm has been established; however, the underlying mechanisms remain unclear. Results In our study, we use waterlily as a model which represents an early-diverging grade of flowering plants, and we aim to reveal the general mechanism of flower actions. We found that the intermediate segment of petal cells of waterlily are highly flexible, followed by a circadian cell expansion upon photoperiod stimuli. Auxin causes constitutively flower opening while auxin inhibitor suppresses opening event. Subsequent transcriptome profiles generated from waterlily’s intermediate segment of petals at different day-time points showed that auxin is a crucial phytohormone required for floral movement rhythm via the coordination of YUCCA-controlled auxin synthesis, GH3-mediated auxin homeostasis, PIN and ABCB-dependent auxin efflux as well as TIR/AFB-AUX/IAA- and SAUR-triggered auxin signaling. Genes involved in cell wall organization were downstream of auxin events, resulting in the output phenotypes of rapid cell expansion during flower opening and cell shrinkage at flower closure stage. Conclusions Collectively, our data demonstrate a central regulatory role of auxin in floral movement rhythm and provide a global understanding of flower action in waterlily, which could be a conserved feature of angiosperms

Ascorbic Acid Alleviates Damage from Heat Stress in the Photosystem II of Tall Fescue in Both the Photochemical and Thermal Phases

L-Ascorbate (Asc) plays important roles in plant development, hormone signaling, the cell cycle and cellular redox system, etc. The higher content of Asc in plant chloroplasts indicates its important role in the photosystem. The objective of this study was to study the roles of Asc in tall fescue leaves against heat stress. After a heat stress treatment, we observed a lower value of the maximum quantum yield for primary photochemistry (φPo), which reflects the inhibited activity of the photochemical phase of photosystem II (PSII). Moreover, we observed a higher value of efficiency of electron transfer from QB to photosystem I acceptors (δR0), which reflects elevated activity of the thermal phase of the photosystem of the tall fescue. The addition of Asc facilitate the behavior of the photochemical phase of the PSII by lowering the ROS content as well as that of the alternative electron donor to provide electron to the tyrosine residue of the D1 protein. Additionally, exogenous Asc reduces the activity of the thermal phase of the photosystem, which could contribute to the limitation of energy input into the photosystem in tall fescue against heat stress. Synthesis of the Asc increased under heat stress treatment. However, under heat stress this regulation does not occur at the transcription level and requires further study

Additional file 1 of Development and validation of a prediction model for in-hospital death in patients with heart failure and atrial fibrillation

Additional file 1: Supplementary Table 1. The characteristics of patients from eICU in the survival group and death group

Additional file 2: of Auxin controls circadian flower opening and closure in the waterlily

Global transcriptome description of the flower opening and closure. Corresponding to Fig. 4. Global analysis of GO items and KEGG pathways during the flower opening and closure processes are shown. The transcriptome at 6:00 (T1) was used as the control, and the transcriptomes at 7:00 (T2), 10:00(T3), 14:00 (T4) and 18:00 (T5) were individually compared with each other (T/T comparisons). The total changed numbers are listed below. Red represents the upregulated groups, and blue marks the downregulated groups (TIF 1165 kb