Acute Promyelocytic Leukemia, Retinoic Acid, and Arsenic: A Tale of Dualities.

Acute promyelocytic leukemia (APL) is driven by the promyelocytic leukemia (PML)/retinoic acid receptor α (RARA) fusion oncoprotein. Over the years, it has emerged as a model system to understand how this simple (and sometimes sole) genetic alteration can transform hematopoietic progenitors through the acquisition of dominant-negative properties toward both transcriptional control by nuclear receptors and PML-mediated senescence. The fortuitous identification of two drugs, arsenic trioxide (ATO) and all--retinoic acid (ATRA), that respectively bind PML and RARA to initiate PML/RARA degradation, has allowed an unprecedented dissection of the cellular and molecular mechanisms involved in patients' cure by the ATO/ATRA combination.

Assessing the sustainability of smart healthcare applications using a multi-perspective fuzzy comprehensive evaluation approach.

A smart healthcare application can be judged as sustainable if it was already widely used before and will also be prevalent in the future. In contrast, if a smart healthcare application developed during the COVID-19 pandemic is not used after it, then it is not sustainable. Assessing the sustainability of smart healthcare applications is a critical task for their users and suppliers.

Optical Imaging Deformation Inspection and Quality Level Determination of Multifocal Glasses.

Multifocal glasses are a new type of lens that can fit both nearsighted and farsighted vision on the same lens. This property allows the glass to have various curvatures in distinct regions within the glass during the grinding process. However, when the curvature varies irregularly, the glass is prone to optical deformation during imaging.

Cystine uptake inhibition potentiates front-line therapies in acute myeloid leukemia.

By querying metabolic pathways associated with leukemic stemness and survival in multiple AML datasets, we nominated SLC7A11 encoding the xCT cystine importer as a putative AML dependency. Genetic and chemical inhibition of SLC7A11 impaired the viability and clonogenic capacity of AML cell lines in a cysteine-dependent manner. Sulfasalazine, a broadly available drug with xCT inhibitory activity, had anti-leukemic activity against primary AML samples in ex vivo cultures.

A fuzzy analytic hierarchy process-enhanced fuzzy geometric mean-fuzzy technique for order preference by similarity to ideal solution approach for suitable hotel recommendation amid the COVID-19 pandemic.

Cities around the world have reopened from the lockdown caused by the COVID-19 pandemic, and more and more people are planning regional travel. Therefore, it is a practical problem to recommend suitable hotels to travelers amid the COVID-19 pandemic. However, it is also a challenging task since the critical factors that affect hotel selection amid the COVID-19 pandemic may be different from those usually considered.

Effects of compression garment on muscular efficacy, proprioception, and recovery after exercise-induced muscle fatigue onset for people who exercise regularly.

Fatigue is a major cause of exercise-induced muscle damage (EIMD). Compression garments (CGs) can aid post-exercise recovery, therefore, this study explored the effects of CGs on muscular efficacy, proprioception, and recovery after exercise-induced muscle fatigue in people who exercise regularly. Twelve healthy participants who exercised regularly were enrolled in this study.

Biological Effects of BET Inhibition by OTX015 (MK-8628) and JQ1 in NPM1-Mutated (NPM1c) Acute Myeloid Leukemia (AML).

BET inhibitors (BETi) including OTX015 (MK-8628) and JQ1 demonstrated antileukemic activity including AML cells. Nevertheless, the biological consequences of BETi in AML were not fully investigated. Even if of better prognosis AML patients with may relapse and treatment remains difficult.

PML/RARA destabilization by hyperthermia: a new model for oncogenic fusion protein degradation?

In this issue, Maimaitiyiming and colleagues demonstrate thermic stress-induced PML/RARA oncogenic fusion protein destabilization driven by corepressor aggregation. Hyperthermia synergizes with PML/RARA degradation by ATO and may circumvent ATO-resistance in historical APL patients. This novel approach could be extended to other corepressor-associated oncogenic fusion proteins.

A novel leukemic route of mutant NPM1 through nuclear import of the overexpressed long noncoding RNA LONA.

The most frequent genetic alteration in acute myeloid leukemia (AML) is the mutation of nucleophosmin 1 (NPM1). Yet, its downstream oncogenic routes are not fully understood. Here, we report the identification of one long noncoding RNA (lncRNA) overexpressed in NPM1-mutated AML patients (named LONA) whose intracellular localization inversely reflects that of NPM1.

A Pin1/PML/P53 axis activated by retinoic acid in acute myeloid leukemia.

Retinoic acid (RA) was proposed to increase survival of chemotherapy- treated patients with nucleophosmin-1 (NPM-1c)-mutated acute myeloid leukemia. We reported that, ex vivo, RA triggers NPM-1c degradation, P53 activation and growth arrest. PML organizes domains that control senescence or proteolysis.

Usp11 controls cortical neurogenesis and neuronal migration through Sox11 stabilization.

The role of protein stabilization in cortical development remains poorly understood. A recessive mutation in the gene is found in a rare neurodevelopmental disorder with intellectual disability, but its pathogenicity and molecular mechanism are unknown. Here, we show that mouse is expressed highly in embryonic cerebral cortex, and deficiency impairs layer 6 neuron production, delays late-born neuronal migration, and disturbs cognition and anxiety behaviors.

Analyzing the Impact of Vaccine Availability on Alternative Supplier Selection Amid the COVID-19 Pandemic: A cFGM-FTOPSIS-FWI Approach.

The supply chain disruption caused by the coronavirus disease 2019 (COVID-19) pandemic has forced many manufacturers to look for alternative suppliers. How to choose a suitable alternative supplier in the COVID-19 pandemic has become an important task. To fulfill this task, this research proposes a calibrated fuzzy geometric mean (cFGM)-fuzzy technique for order preference by similarity to ideal solution (FTOPSIS)-fuzzy weighted intersection (FWI) approach.

Extract Prevents Cisplatin-Induced Myelotoxicity and .

Cisplatin chemotherapy causes myelosuppression and often limits treatment duration and dose escalation in patients. Novel approaches to circumvent or lessen myelotoxicity may improve clinical outcome and quality of life in these patients. (CS) is a freshwater unicellular green alga and exhibits encouraging efficacy in immunomodulation and anticancer in preclinical studies.

PML nuclear bodies, membrane-less domains acting as ROS sensors?

PML Nuclear bodies (PML NBs) are spherical domains associated with a broad range of activities upon stress responses such as apoptosis, senescence DNA repair, epigenetic control, as well as control of oncogenesis. These bodies are considered as privileged sites for post-translational modifications, where sumoylation plays a key role. Here we summarize recent in vitro and in vivo findings on the link between PML NBs and ROS, in particular PML contributions to oxidative stress response.

Erratum: USP11 regulates PML stability to control Notch-induced malignancy in brain tumours.

This corrects the article DOI: 10.1038/ncomms4214.

Insights into the coordinated interplay of the sHP hairpin and its co-existing and mutually-exclusive dengue virus terminal RNA elements for viral replication.

Terminal RNA elements of the dengue virus (DENV) genome are necessary for balanced stability of linear and circular conformations during replication. We examined the small hairpin (sHP) and co-existing and mutually-exclusive terminal RNA elements by mutagenesis analysis, compensatory mutation screening, and by probing with RNA fragments to explore localized RNA folding and long-range RNA interactions. We found that the first base pair of the sHP and the stability of SLB and the 3'SL bottom stem affected circularization; sHP/C10631G+G10644C prohibited circularization, sHP accelerated and stabilized 5'-to-3' RNA hybridization, while C94A and A97G and C10649 mutations loosened SLB and 3'SL, respectively, for circularization.

Imidazoquinoxaline derivative EAPB0503: A promising drug targeting mutant nucleophosmin 1 in acute myeloid leukemia.

Background: Nucleophosmin 1 (NPM1) is a nucleocytoplasmic shuttling protein mainly localized in the nucleolus. NPM1 is frequently mutated in acute myeloid leukemia (AML). NPM1c oligomerizes with wild-type nucleophosmin 1 (wt-NPM1), and this leads to its continuous cytoplasmic delocalization and contributes to leukemogenesis.

Antrodia cinnamomea Extract Inhibits Th17 Cell Differentiation and Ameliorates Imiquimod-Induced Psoriasiform Skin Inflammation.

Antrodia cinnamomea (A. cinnamomea) is a Chinese medicinal herb that possesses a broad range of bioactivities, including anti-inflammation. Given that the proinflammatory cytokine IL-17 plays a critical role in the pathogenesis of autoimmune diseases, we investigated whether A.

The adjuvant effects of high-molecule-weight polysaccharides purified from Antrodia cinnamomea on dendritic cell function and DNA vaccines.

The biological activity of the edible basidiomycete Antrodia cinnamomea (AC) has been studied extensively. Many effects, such as anti-cancer, anti-inflammatory, and antioxidant activities, have been reported from either crude extracts or compounds isolated from AC. However, research addressing the function of AC in enhancing immunity is rare.

USP11 regulates PML stability to control Notch-induced malignancy in brain tumours.

The promyelocytic leukaemia (PML) protein controls multiple tumour suppressive functions and is downregulated in diverse types of human cancers through incompletely characterized post-translational mechanisms. Here we identify USP11 as a PML regulator by RNAi screening. USP11 deubiquitinates and stabilizes PML, thereby counteracting the functions of PML ubiquitin ligases RNF4 and the KLHL20-Cul3 (Cullin 3)-Roc1 complex.