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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.

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.

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).

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.

Cancer immunotherapy has reached a critical point, now that immune checkpoint inhibitors and two CAR-T products have received market approval in treating 16 types of cancers and 1 tissue-agnostic cancer indication. Accompanying these advances, the 2018 Nobel Prize was awarded for the discovery of immune checkpoint pathways, which has led to the revolution of anti-cancer treatments. However, expanding the indications of immuno-oncology agents and overcoming treatment resistance face mounting challenges. Although combination immunotherapy is an obvious strategy to pursue, the fact that there have been more failures than successes in this effort has served as a wake-up call, placing emphasis on the importance of building a solid scientific foundation for the development of next-generation immuno-oncology (IO) agents. The 2019 China Cancer Immunotherapy Workshop was held to discuss the current challenges and opportunities in IO. At this conference, emerging concepts and strategies for IO development were proposed, focusing squarely on correcting the immunological defects in the tumor microenvironment. New targets such as Siglec-15 and new directions including neoantigens, cancer vaccines, oncolytic viruses, and cytokines were reviewed. Emerging immunotherapies were discussed in the areas of overcoming primary and secondary resistance to existing immune checkpoint inhibitors, activating effector cells, and targeting immunosuppressive mechanisms in the tumor microenvironment. In this article, we highlight old and new waves of IO therapy development, and provide perspectives on the latest momentum shifts in cancer immunotherapy.

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.

Graphene photodetectors have exhibited high bandwidth and capability of being integrated with silicon photonics (SiPh), holding promise for future optical communication devices. However, they usually suffer from a low photoresponsivity due to weak optical absorption. In this work, we have implemented SiPh-integrated twisted bilayer graphene (tBLG) detectors and reported a responsivity of 0.65 A W –1 for telecom wavelength 1,550 nm. The high responsivity enables a 3-dB bandwidth of >65 GHz and a high data stream rate of 50 Gbit s –1 . Such high responsivity is attributed to the enhanced optical absorption, which is facilitated by van Hove singularities in the band structure of high-mobility tBLG with 4.1 o twist angle. The uniform performance of the fabricated photodetector arrays demonstrates a fascinating prospect of large-area tBLG as a material candidate for heterogeneous integration with SiPh. Silicon-integrated graphene photodetectors exhibit promising bandwidths at telecom wavelengths, but their responsivity is usually limited. Here, the authors report the wafer-scale fabrication of waveguide-integrated detectors based on twisted bilayer graphene, showing responsivities up to 0.65 A/W and 3-dB bandwidths >65 GHz.

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.

Gut microbiota plays a critical role in the maintenance of host health. As a low-cost and genetically tractable vertebrate model, zebrafish have been widely used for biological research. Zebrafish and humans share some similarities in intestinal physiology and function, and this allows zebrafish to be a surrogate model for investigating the crosstalk between the gut microbiota and host. Especially, zebrafish have features such as high fecundity, external fertilization, and early optical transparency. These enable the researchers to employ the fish to address questions not easily addressed in other animal models. In this review, we described the intestine structure of zebrafish. Also, we summarized the methods of generating a gnotobiotic zebrafish model, the factors affecting its intestinal flora, and the study progress of gut microbiota functions in zebrafish. Finally, we discussed the limitations and challenges of the zebrafish model for gut microbiota studies. In summary, this review established that zebrafish is an attractive research tool to understand mechanistic insights into host-microbe interaction.

The development of high-performance memory devices has played a key role in the innovation of modern electronics. Non-volatile memory devices have manifested high capacity and mechanical reliability as a mainstream technology; however, their performance has been hampered by low extinction ratio and slow operational speed. Despite substantial efforts to improve these characteristics, typical write times of hundreds of micro- or milliseconds remain a few orders of magnitude longer than that of their volatile counterparts. Here we demonstrate non-volatile, floating-gate memory devices based on van der Waals heterostructures with atomically sharp interfaces between different functional elements, achieving ultrahigh-speed programming/erasing operations in the range of nanoseconds with extinction ratio up to 10 10 . This enhanced performance enables new device capabilities such as multi-bit storage, thus opening up applications in the realm of modern nanoelectronics and offering future fabrication guidelines for device scale up. Atomically sharp interfaces in van der Waals heterostructures enable the realization of ultrafast non-volatile memory devices.