Until recently, acute myeloid leukemia (AML) patients used to have limited treatment options, depending solely on cytarabine + anthracycline (7 + 3) intensive chemotherapy and hypomethylating agents. ...Allogeneic stem cell transplantation (Allo-SCT) played an important role to improve the survival of eligible AML patients in the past several decades. The exploration of the genomic and molecular landscape of AML, identification of mutations associated with the pathogenesis of AML, and the understanding of the mechanisms of resistance to treatment from excellent translational research helped to expand the treatment options of AML quickly in the past few years, resulting in noteworthy breakthroughs and FDA approvals of new therapeutic treatments in AML patients. Targeted therapies and combinations of different classes of therapeutic agents to overcome treatment resistance further expanded the treatment options and improved survival. Immunotherapy, including antibody-based treatment, inhibition of immune negative regulators, and possible CAR T cells might further expand the therapeutic armamentarium for AML. This review is intended to summarize the recent developments in the treatment of AML.
Ultraviolet-B (UV-B) light is an intrinsic part of sunlight that has significant effects on plant development and acclimation responses. UVR8 (UV Resistance Locus 8) is the long sought-after UV-B ...photoreceptor that mediates UV-B light perception and signal transduction. UV-B irradiation induces the monomerization and nuclear accumulation of UVR8 in plant cells to activate the UV-B signaling pathway. The photoactivated UVR8 could transduce UV-B signal via multiple mechanisms to regulate transcription and plant growth. Here, we summarize current understanding of UVR8-mediated UV-B signal transduction pathways, including UVR8–COP1 (CONSTITUTIVELY PHOTOMORPHOGENIC 1) and UVR8–WRKY36 (WRKY DNA-BINDING PROTEIN 36), UVR8–BES1 (BRI1-EMS-SUPPRESSOR1) and BIM1 (BES1-INTERACTING MYC-LIKE 1).
Immunotherapies such as immune checkpoint blockade (ICB) and adoptive cell therapy (ACT) have revolutionized cancer treatment, especially in patients whose disease was otherwise considered incurable. ...However, primary and secondary resistance to single agent immunotherapy often results in treatment failure, and only a minority of patients experience long-term benefits. This review article will discuss the relationship between cancer immune response and mechanisms of resistance to immunotherapy. It will also provide a comprehensive review on the latest clinical status of combination therapies (e.g., immunotherapy with chemotherapy, radiation therapy and targeted therapy), and discuss combination therapies approved by the US Food and Drug Administration. It will provide an overview of therapies targeting cytokines and other soluble immunoregulatory factors, ACT, virotherapy, innate immune modifiers and cancer vaccines, as well as combination therapies that exploit alternative immune targets and other therapeutic modalities. Finally, this review will include the stimulating insights from the 2020 China Immuno-Oncology Workshop co-organized by the Chinese American Hematologist and Oncologist Network (CAHON), the China National Medical Product Administration (NMPA) and Tsinghua University School of Medicine. Keywords: Immunotherapy, Immune checkpoint inhibitor, Cancer vaccine, Oncolytic virus, CAR-T, Cytokine
Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of dysregulated lipid and glucose metabolism, which is often associated with obesity, dyslipidemia and insulin resistance. In ...view of the high morbidity and health risks of NAFLD, the lack of effective cure has drawn great attention. In recent years, a line of evidence has suggested a close linkage between the intestine and liver diseases such as NAFLD. We summarized the composition and characteristics of intestinal microbes and reviewed molecular insights into the intestinal microbiome in development and progression of NAFLD. Intestinal microbes mainly include bacteria, archaea, viruses and fungi, and the crosstalk between non-bacterial intestinal microbes and human liver diseases should be paid more attention. Intestinal microbiota imbalance may not only increase the intestinal permeability to gut microbes but also lead to liver exposure to harmful substances that promote hepatic lipogenesis and fibrosis. Furthermore, we focused on reviewing the latest “gut–liver axis”-targeting treatment, including the application of antibiotics, probiotics, prebiotics, synbiotics, farnesoid X receptor agonists, bile acid sequestrants, gut-derived hormones, adsorbents and fecal microbiota transplantation for NAFLD. In this review, we also discussed the potential mechanisms of “gut–liver axis” manipulation and efficacy of these therapeutic strategies for NAFLD treatment.
Peak shaving of power systems and the improvement of balance adjustment capabilities are important issues that need to be resolved in the energy sector to carbon neutrality. Moderately constructing ...some gas-steam combined cycle power stations is one feasible way to alleviate this issue. Heat recovery steam generator plays a vital role in the safe and reliable operation of gas-steam combined cycle power plant. Startup process of heat recovery steam generator in a typical F-class peak shaving combined cycle plant under cold, warm and hot modes was researched in this paper. Parameters of heat recovery steam generator increase with the increase of gas turbine load. The shortest cold, warm and hot start-up time are 60 minutes, 50 minutes and 35 minutes, respectively. Temperature and pressure rise rate of heat recovery steam generator should be strictly controlled during start-up process. It is recommended to start-up the heat recovery steam generator in hot or warm mode.
The power conversion efficiency of organic solar cells (OSCs) has made exceptionally rapid progress in the past five years owing to the emergence of fused‐ring electron acceptors (FREAs). To achieve ...the commercialization, it is urgent to resolve the stability issues of OCSs from materials to devices. In particular, the state‐of‐the‐art FREAs, often synthesized by Knoevenagel condensation, generally contain two exocyclic vinyl groups (CC bond) as the conjugated bridges, which inevitably exhibit an obvious electron‐deficient characteristic due to the strong push‐pull electronic effect. As a result, these vinyl bridges are vulnerable to nucleophile attacking and/or photooxidation, leading to poor chemical and photochemical stabilities of FREAs that easily cause the degradation of device performance. In this perspective, an in‐depth understanding of the degradation mechanism of FREAs is provided, and then effective strategies reported recently are reviewed for improving the chemical and photochemical stabilities of FREAs from interfacial engineering to molecular engineering to additive engineering. Finally, a conclusion and outlook for the future design of highly efficient and stable FREAs are also presented.
Research on the stability of organic solar cells based on fused‐ring electron acceptors (FREAs) is now becoming more urgent. This perspective focuses on discussing the possible degradation mechanisms of FREAs and effective strategies of enhancing their stability reported recently. Also, a conclusion and outlook for the future design of highly efficient and stable FREAs are presented.
Vertical heterojunctions of two two-dimensional (2D) transition metal dichalcogenides (TMDs) have attracted considerable attention recently. A variety of heterojunctions can be constructed by ...stacking different TMDs to form fundamental building blocks in different optoelectronic devices such as photodetectors, solar cells, and light-emitting diodes. However, these applications are significantly hampered by the challenges of large-scale production of van der Waals stacks of atomically thin materials. Here, we demonstrate scalable production of periodic patterns of few-layer WS2, MoS2, and their vertical heterojunction arrays by a thermal reduction sulfurization process. In this method, a two-step chemical vapor deposition approach was developed to effectively prevent the phase mixing of TMDs in an unpredicted manner, thus affording a well-defined interface between WS2 and MoS2 in the vertical dimension. As a result, large-scale, periodic arrays of few-layer WS2, MoS2, and their vertical heterojunctions can be produced with desired size and density. Photodetectors based on the as-produced MoS2/WS2 vertical heterojunction arrays were fabricated, and a high photoresponsivity of 2.3 A·W–1 at an excitation wavelength of 450 nm was demonstrated. Flexible photodetector devices using MoS2/WS2 heterojunction arrays were also demonstrated with reasonable signal/noise ratio. The approach in this work is also applicable to other TMD materials and can open up the possibilities of producing a variety of vertical van der Waals heterojunctions in a large scale toward optoelectronic applications.
Cryptochromes (CRY) are blue-light receptors that mediate various light responses in plants. The photoexcited CRY molecules undergo several biophysical and biochemical changes, including electron ...transfer, phosphorylation and ubiquitination, resulting in conformational changes to propagate light signals. Two modes of CRY signal transduction have recently been discovered: the cryptochrome-interacting basic-helix-loop-helix 1 (CIB)-dependent CRY2 regulation of transcription; and the SUPPRESSOR OF PHYA1/CONSTITUTIVELY PHOTOMORPHOGENIC1 (SPA1/COP1)-dependent cryptochrome regulation of proteolysis. Both CRY signaling pathways rely on blue light-dependent interactions between the CRY photoreceptor and its signaling proteins to modulate gene expression changes in response to blue light, leading to altered developmental programs in plants.
Cryptochrome 1 (CRY1) is a blue light receptor that mediates primarily blue-light inhibition of hypocotyl elongation. Very little is known of the mechanisms by which CRY1 affects growth. Blue light ...and temperature are two key environmental signals that profoundly affect plant growth and development, but how these two abiotic factors integrate remains largely unknown. Here, we show that blue light represses high temperature-mediated hypocotyl elongation via CRY1. Furthermore, CRY1 interacts directly with PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) in a blue light-dependent manner to repress the transcription activity of PIF4. CRY1 represses auxin biosynthesis in response to elevated temperature through PIF4. Our results indicate that CRY1 signal by modulating PIF4 activity, and that multiple plant photoreceptors CRY1 and PHYTOCHROME B (PHYB) and ambient temperature can mediate morphological responses through the same signaling component—PIF4.
Arabidopsis thaliana cryptochrome 2 (CRY2) mediates light control of flowering time. CIB1 (CRY2-interacting bHLH 1) specifically interacts with CRY2 in response to blue light to activate the ...transcription of FT (Flowering Locus T). In vitro, CIB1 binds to the canonical E-box (CACGTG, also referred to as G-box) with much higher affinity than its interaction with non-canonical E-box (CANNTG) DNA sequences. However, in vivo, CIB1 binds to the chromatin region of the FT promoter, which only contains the non-canonical E-box sequences. Here, we show that CRY2 also interacts with at least CIB5, in response to blue light, but not in darkness or in response to other wavelengths of light. Our genetic analysis demonstrates that CIB1, CIB2, CIB4, and CIB5 act redundantly to activate the transcription of FT and that they are positive regulators of CRY2 mediated flowering. More importantly, CIB1 and other CIBs proteins form heterodimers, and some of the heterodimers have a higher binding affinity than the CIB homodimers to the non-canonical E-box in the in vitro DNA-binding assays. This result explains why in vitro CIB1 and other CIBs bind to the canonical E-box (G-box) with a higher affinity, whereas they are all associated with the non-canonical E-boxes at the FT promoter in vivo. Consistent with the hypothesis that different CIB proteins play similar roles in the CRY2-midiated blue light signaling, the expression of CIB proteins is regulated specifically by blue light. Our study demonstrates that CIBs function redundantly in regulating CRY2-dependent flowering, and that different CIBs form heterodimers to interact with the non-canonical E-box DNA in vivo.
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