Notes

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CXCR4 is expressed on leukaemia cells and haematopoietic stem cells (HSCs), and its ligand stromal-derived factor 1 (SDF-1) is produced abundantly by stromal cells in the bone marrow (BM). The SDF-1/CXCR4 axis plays important roles in homing to and retention in the protective BM microenvironment of malignant leukaemia cells and normal HSCs. CXCR4 expression is regulated by multiple mechanisms and the level of CXCR4 expression on leukaemia cells has prognostic indications in patients with acute leukaemia. CXCR4 antagonists can mobilize leukaemia cells from BM to circulation, which render them effectively eradicated by chemotherapeutic agents, small molecular inhibitors or hypomethylating agents. Therefore, such combinational therapies have been tested in clinical trials. However, new evidence emerged that drug-resistant leukaemia cells were not affected by CXCR4 antagonists, and the migration of certain leukaemia cells to the leukaemia niche was independent of SDF-1/CXCR4 axis. In this review, we summarize the role of CXCR4 in progression and treatment of acute leukaemia, with a focus on the potential of CXCR4 as a therapeutic target for acute leukaemia. We also discuss the potential value of using CXCR4 antagonists as chemosensitizer for conditioning regimens and immunosensitizer for graft-vs-leukaemia effects of allogeneic haematopoietic stem cell transplantation.Reconstruction induced by external environment (such as applied voltage bias and test electrolytes) changes catalyst component and catalytic behaviors. Investigations of complete reconstruction in energy conversion recently receive intensive attention, which promote the targeted design of top-performance materials with maximum component utilization and good stability. However, the advantages of complete reconstruction, its design strategies, and extensive applications have not achieved the profound understandings and summaries it deserves. Here, this review systematically summarizes several important advances in complete reconstruction for the first time, which includes 1) fundamental understandings of complete reconstruction, the characteristics and advantages of completely reconstructed catalysts, and their design principles, 2) types of reconstruction-involved precatalysts for oxygen evolution reaction catalysis in wide pH solution, and origins of limited reconstruction degree as well as design strategies/principles toward complete reconstruction, 3) complete reconstruction for novel material synthesis and other electrocatalysis fields, and 4) advanced in situ/operando or multiangle/level characterization techniques to capture the dynamic reconstruction processes and real catalytic contributors. Finally, the existing major challenges and unexplored/unsolved issues on studying the reconstruction chemistry are summarized, and an outlook for the further development of complete reconstruction is briefly proposed. This review will arouse the attention on complete reconstruction materials and their applications in diverse fields.Immunotherapy that can activate immunity or enhance the immunogenicity of tumors has emerged as one of the most effective methods for cancer therapy. Nevertheless, single-mode immunotherapy is still confronted with several critical challenges, such as the low immune response, the low tumor infiltration, and the complex immunosuppression tumor microenvironment. Recently, the combination of immunotherapy with other therapeutic modalities has emerged as a powerful strategy to augment the therapeutic outcome in fighting against cancer. In this review, recent research advances of the combination of immunotherapy with chemotherapy, phototherapy, radiotherapy, sonodynamic therapy, metabolic therapy, and microwave thermotherapy are summarized. Critical challenges and future research direction of immunotherapy-based cancer therapeutic strategy are also discussed.
Risk stratification beyond the endoscopic classification of esophageal varices (EVs) to predict first episode of variceal bleeding (VB) is currently limited in patients with compensated advanced chronic liver disease (cACLD). We aimed to assess if machine learning (ML) could be used for predicting future VB more accurately.

In this retrospective analysis, data from patients of cACLD with EVs, laboratory parameters and liver stiffness measurement (LSM) were used to generate an extreme-gradient boosting (XGBoost) algorithm to predict the risk of VB. The performance characteristics of ML and endoscopic classification were compared in internal and external validation cohorts. Bleeding rates were estimated in subgroups identified upon risk stratification with combination of model and endoscopic classification.

Eight hundred twenty-eight patients of cACLD with EVs, predominantly related to non-alcoholic fatty liver disease (28.6%), alcohol (23.7%) and hepatitis B (23.1%) were included, with 455 (55%) having the high-risk varices. https://www.selleckchem.com/products/sovilnesib.html Over a median follow-up of 24 (12-43) months, 163 patients developed VB. The accuracy of machine learning (ML) based model to predict future VB was 98.7 (97.4-99.5)%, 93.7 (88.8-97.2)%, and 85.7 (82.1-90.5)% in derivation (n=497), internal validation (n=149), and external validation (n=182) cohorts, respectively, which was better than endoscopic classification [58.9 (55.5-62.3)%] alone. Patients stratified high risk on both endoscopy and model had 1-year and 3-year bleeding rates of 31-43% and 64-85%, respectively, whereas those stratified as low risk on both had 1-year and 3-year bleeding rates of 0-1.6% and 0-3.4%, respectively. Endoscopic classification and LSM were the major determinants of model's performance.

Application of ML model improved the performance of endoscopic stratification to predict VB in patients with cACLD with EVs.
Application of ML model improved the performance of endoscopic stratification to predict VB in patients with cACLD with EVs.
Westernized high-fat diet increases the risk for inflammatory bowel diseases (IBDs), yet with insufficient understanding of the role of high-protein diet. We aimed to identify the effect of high-protein diets from different dietary proteins (casein, whey protein, soy protein) on experimental colitis and its impact on microbiota, structure and function of colonic mucus layer.

Female BALB/c mice were fed by standard diet, high-casein diet (HCD), high whey protein diet or high soy protein diet for 4weeks. The susceptibility of dextran sulfate sodium (DSS)-induced colitis in mice and thickness of colonic mucus layer were compared after different dietary interventions, associated with the identification of the reversal effect of broad-spectrum antibiotic intervention (0.5g/L of vancomycin and 1g/L of neomycin sulfate, metronidazole and ampicillin in drinking water). Further analysis was performed on the synthesis of mucin, microbiota and sialidase involved in degradation of mucus layer.

High-protein diets aggravated acute DSS-induced colitis independent of protein composition, while broad-spectrum antibiotics reversed this effect.
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