As crucial antigen presenting cells, dendritic cells (DCs) play a vital role in tumor immunotherapy. Taking into account the many recent advances in DC biology, we discuss how DCs (1) recognize ...pathogenic antigens with pattern recognition receptors through specific phagocytosis and through non-specific micropinocytosis, (2) process antigens into small peptides with proper sizes and sequences, and (3) present MHC-peptides to CD4
and CD8
T cells to initiate immune responses against invading microbes and aberrant host cells. During anti-tumor immune responses, DC-derived exosomes were discovered to participate in antigen presentation. T cell microvillar dynamics and TCR conformational changes were demonstrated upon DC antigen presentation. Caspase-11-driven hyperactive DCs were recently reported to convert effectors into memory T cells. DCs were also reported to crosstalk with NK cells. Additionally, DCs are the most important sentinel cells for immune surveillance in the tumor microenvironment. Alongside DC biology, we review the latest developments for DC-based tumor immunotherapy in preclinical studies and clinical trials. Personalized DC vaccine-induced T cell immunity, which targets tumor-specific antigens, has been demonstrated to be a promising form of tumor immunotherapy in patients with melanoma. Importantly, allogeneic-IgG-loaded and HLA-restricted neoantigen DC vaccines were discovered to have robust anti-tumor effects in mice. Our comprehensive review of DC biology and its role in tumor immunotherapy aids in the understanding of DCs as the mentors of T cells and as novel tumor immunotherapy cells with immense potential.
Long non‐coding RNAs (lncRNAs) have been identified to play vital roles in cancers, including human retinoblastoma (RB). However, the deepgoing mechanism is still ambiguous. In present study, we ...investigate the biological role of lncRNA DANCR (differentiation antagonizing non‐protein coding RNA) in carcinogenesis of RB. Results revealed that DANCR was up‐regulated in RB tissue and cell lines. Moreover, the ectopic overexpression of DANCR indicated poor overall survivals and disease free survival (DFS) for RB patients. In vitro and in vivo experiments, DANCR knockdown suppress the proliferation, migration, invasion, and epithelial‐mesenchymal transition (EMT) correlated protein (N‐cadherin, Vimentin) of RB cells. Bioinformatics analysis predicted that miR‐34c and miR‐613 targeted with 3′‐UTR of DANCR, besides, miR‐34c and miR‐613 also targeted with 3′‐UTR of MMP‐9, which was validated by luciferase reporter assay. Functional experiments demonstrated that miR‐34c and miR‐613 could reverse the oncogenic function of DANCR in RB tumorigenesis. In conclusion, our results reveal that DANCR function as competing endogenous RNA (ceRNA) for miR‐34c and miR‐613 to modulate progression and metastasis in RB oncogenesis via targeting MMP‐9, presenting the in‐depth regulation of DANCR in RB and providing a novel insight for ceRNA mechanism for RB.
DANCR was up‐regulated in RB tissue and cell lines.
The growing understanding of RNA functions and their crucial roles in diseases promotes the application of various RNAs to selectively function on hitherto "undruggable" proteins, transcripts and ...genes, thus potentially broadening the therapeutic targets. Several RNA-based medications have been approved for clinical use, while others are still under investigation or preclinical trials. Various techniques have been explored to promote RNA intracellular trafficking and metabolic stability, despite significant challenges in developing RNA-based therapeutics. In this review, the mechanisms of action, challenges, solutions, and clinical application of RNA-based therapeutics have been comprehensively summarized.
Exploiting anion–π interactions in catalyst design is a fascinating direction to develop new and fundamental catalysis. For the appealing yet flexible π‐face activation, can two or more π‐acidic ...surfaces be manipulated for cooperative activation to achieve efficient transformation and particularly selectivity control is highly desirable. Here, we demonstrate a supramolecular π‐catalysis strategy by establishing cooperative π‐face activation in a confined electron‐deficient cage cavity. The catalysts have a triazine based prism‐like cage core and pendant chiral base sites. Only 2 mol % of cage catalyst efficiently catalyzed the decarboxylate Mannich reactions of sulfamate‐headed cyclic aldimines and a series of malonic acid half thioesters in nearly quantitative yields and up to 97 % ee, enabling an unprecedent organocatalytic approach. The supramolecular π‐cavity is essential in harnessing cooperative anion–π interactions for the efficient activation and excellent selectivity control.
A strategy by building cooperative anion–π interactions in a confined cage cavity to drive efficient and selective catalysis was established. Only 2 mol % of easily made chiral cages enabled excellent conversions and up to 97 % ee in catalyzing a class of decarboxylate Mannich reactions, which was unrealized with conventional organocatalysts.
Chronic inflammation-promoted metastasis has been considered as a major challenge in cancer therapy. Pro-inflammatory cytokine TNFα can induce cancer invasion and metastasis associated with ...epithelial-mesenchymal transition (EMT). However, the underlying mechanisms are not entirely clear. In this study, we showed that TNFα induces EMT in human HCT116 cells and thereby promotes colorectal cancer (CRC) invasion and metastasis. TNFα-induced EMT was characterized by acquiring mesenchymal spindle-like morphology and increasing the expression of N-cadherin and fibronectin with a concomitant decrease of E-cadherin and Zona occludin-1(ZO-1). TNFα treatment also increased the expression of transcription factor Snail, but not Slug, ZEB1 and Twist. Overexpression of Snail induced a switch from E-cadherin to N-cadherin expression in HCT116 cells, which is a characteristic of EMT. Conversely, knockdown of Snail significantly attenuated TNFα-induced EMT in HCT116 cells, suggesting that Snail plays a crucial role in TNFα-induced EMT. Interestingly, exposure to TNFα rapidly increased Snail protein expression and Snail nuclear localization but not mRNA level upregulation. Finally, we demonstrated that TNFα elevated Snail stability by activating AKT pathway and subsequently repressing GSK-3β activity and decreasing the association of Snail with GSK-3β. Knockdown of GSK-3β further verified our finding. Taken together, these results revealed that AKT/GSK-3β-mediated stabilization of Snail is required for TNFα-induced EMT in CRC cells. Our study provides a better understanding of inflammation-induced CRC metastasis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
As one of the three major fields of building energy consumption, public buildings (PBs)are under pressure regarding energy saving and emission reductions, with PB energy consumption accounting for ...38% of the total consumption. Thus, CO2 emissions released in PBs have become crucial for China in achieving its emission mitigation goal in the “Post Paris” period. This paper is the first to develop a support vector machine (SVM) method to predict and diagnose PB energy consumption based on 11 input parameters, including historical energy consumption data, climatic factors and time-cycle factors. Months with air-conditioning energy consumption in Wuhan were considered the study period, and we used June and July data for model prediction training, August data as the test set, and September data to diagnose the air conditioner energy consumption anomaly. The results show that air conditioning energy consumption was abnormal for four days in September. Relevant policies and suggestions are proposed based on the causal analysis. This research is expected to provide theoretical guidance and a practical data reference for building operations management.
► Seven groups of lectins have been identified in shrimp. ► Shrimp lectins show great diversity in structure, expression and immune functions. ► C-type lectins play diverse roles in shrimp immunity.
...Lectins play important roles in many biological processes, including protein trafficking, cell signaling, pathogen recognition, as effector molecules, and so on, because of their capacity to bind carbohydrates. Presently, seven groups of lectins have been identified in shrimp: C-type, L-type, P-type, M-type, fibrinogen-like domain lectins, galectins, and calnexin/calreticulin. These lectins have different structures, diverse expression patterns, and multiple functions in the shrimp immune response. This review summarizes the research progress and analyzes the diversity of shrimp lectins, focusing mainly on the C-type lectin family. Shrimp C-type lectins show considerable diversity in their domain architectures, sugar substrates, tissue distributions, expression patterns responding to pathogen challenge and functions in shrimp immunity.
Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats
. ...Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans
. Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor-angiotensin converting enzyme II (ACE2)-as SARS-CoV.
The oxygen evolution reaction (OER), as the anodic reaction of water electrolysis (WE), suffers greatly from low reaction kinetics and thereby hampers the large-scale application of WE. Seeking ...active, stable, and cost-effective OER catalysts in acidic media is therefore of great significance. In this perspective, studying the reaction mechanism and exploiting advanced anode catalysts are of equal importance, where the former provides guidance for material structural engineering towards a better catalytic activity. In this review, we first summarize the currently proposed OER catalytic mechanisms,
i.e.
, the adsorbate evolution mechanism (AEM) and lattice oxygen evolution reaction (LOER). Subsequently, we critically review several acidic OER electrocatalysts reported recently, with focus on structure-performance correlation. Finally, a few suggestions on exploring future OER catalysts are proposed.
A systematic summary of the acidic OER catalytic mechanism and catalysts is given, and some experimental phenomena are explained.
Catalytic methods allowing for the reliable prediction and control of diverse regioselectivity along with the control of enantioselectivity to access different regio‐ and enantiomers by switching the ...least reaction parameters are one of the most attractive ways in organic synthesis, which provide access to diverse enantioenriched architectures from identical starting materials. Herein, a Co‐catalyzed regiodivergent and enantioselective reductive hydroalkylation of 1,3‐dienes with aldehydes has been achieved, furnishing different enantioenriched homoallylic alcohol architectures in good levels of enantioselectivity. The reaction features the switch of regioselectivity tuned by the selection of proton source. The use of an acid as proton source provided asymmetric 1,2‐hydroalkylation products under reductive conditions, yet asymmetric 4,3‐hydroalkylation products were obtained with silane as hydride source. This catalytic protocol allows for the access of homoallylic alcohols with two continuous saturated carbon centers in good levels of regio‐, diastereo‐, and enantioselectivity.
Catalytic methods to access different regio‐ and enantiomers by switching the least reaction parameters are attractive yet challenging. Herein, a Co‐catalyzed regiodivergent and enantioselective reductive hydroalkylation of 1,3‐dienes with aldehydes have been achieved, allowing for regio‐switchable 1,2‐hydroalkylation and 4,3‐hydroalkylation of 1,3‐dienes to furnish different homoallylic alcohol architectures from identical starting materials.
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