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Cancer stem cells (CSCs) are a small subpopulation of cells within a tumor that can both self-renew and differentiate into other cell types forming the heterogeneous tumor bulk. Since CSCs are involved in all aspects of cancer development, including tumor initiation, cell proliferation, metastatic dissemination, therapy resistance, and recurrence, they have emerged as attractive targets for cancer treatment and management. Salinomycin, a widely used antibiotic in poultry farming, was identified by the Weinberg group as a potent anti-CSC agent in 2009. As a polyether ionophore, salinomycin exerts broad-spectrum activities, including the important anti-CSC function. Studies on the mechanism of action of salinomycin against cancer have been continuously and rapidly published since then. Thus, it is imperative for us to update its literature of recent research findings in this area. We here summarize the notable work reported on salinomycin's anticancer activities, intracellular binding target(s), effects on tumor microenvironment, safety, derivatives, and tumor-specific drug delivery; after that we also discuss the translational potential of salinomycin toward clinical application based on current multifaceted understandings.High-dimensional potential energy surface (PES) for van der Waals systems with spectroscopic accuracy, is of great importance for quantum dynamics and an extremely challenge job. CO-N2 is a typical van der Waals system and its high-precision PES may help elucidate weak interaction mechanisms. Taking CO-N2 potential energies calculated by CCSD(T)-F12b/aug-cc-pVQZ as the benchmark, we establish an accurate, robust, and efficient machine learning model by using only four molecular structure descriptors based on 7966 benchmark potential energies. The highest accuracy is obtained by a stacking ensemble DNN (SeDNN). Its evaluation parameters MAE, RMSE, and R2 reach 0.096, 0.163, 0.9999 cm-1 , respectively, and the spectroscopic accuracy for vibration spectrum is achieved with predicted PES, which shows SeDNN superior goodness-of-fit and prediction performance. An elaborated PES with the reported global minimum has been predicted with the model, which perfectly reproduces CCSD(T) potential energies and the analytical MLR PES [PCCP, 2018, 20, 2036]. The critical points (global minimum, TSI, TSII, and their barriers), potential curve, and entire PES profile are remarkably consistent with CCSD(T) calculations. To further improve the usability of constructing PESs in practice, the size of the training set (energy points) for the model is reduced to 50%, 30%, and 20% of the database, respectively. The results show that even training with the smallest training set (1593 points), the PES only differs 2.555 cm-1 with the analytic MLR PES. Therefore, the proposed SeDNN is promisingly an alternative efficient tool to construct subtle PES for van der Waals systems.Emerging reports of SARS-CoV-2 breakthrough infections entail methodical genomic surveillance for determining the efficacy of vaccines. This study elaborates genomic analysis of isolates from breakthrough infections following vaccination with AZD1222/Covishield and BBV152/Covaxin. Variants of concern B.1.617.2 and B.1.1.7 responsible for cases surge in April-May 2021 in Delhi, were the predominant lineages among breakthrough infections.Mitochondrial ribosomes are complex molecular machines indispensable for respiration. Their assembly involves the import of several dozens of mitochondrial ribosomal proteins (MRPs), encoded in the nuclear genome, into the mitochondrial matrix. Proteomic and structural data as well as computational predictions indicate that up to 25% of yeast MRPs do not have a conventional N-terminal mitochondrial targeting signal (MTS). We experimentally characterized a set of 15 yeast MRPs in vivo and found that five use internal MTSs. Further analysis of a conserved model MRP, Mrp17/bS6m, revealed the identity of the internal targeting signal. Similar to conventional MTS-containing proteins, the internal sequence mediates binding to TOM complexes. The entire sequence of Mrp17 contains positive charges mediating translocation. The fact that these sequence properties could not be reliably predicted by standard methods shows that mitochondrial protein targeting is more versatile than expected. We hypothesize that structural constraints imposed by ribosome assembly interfaces may have disfavored N-terminal presequences and driven the evolution of internal targeting signals in MRPs.Statistical methods generating individualized treatment rules (ITRs) often focus on maximizing expected benefit, but these rules may expose patients to excess risk. For instance, aggressive treatment of type 2 diabetes (T2D) with insulin therapies may result in an ITR which controls blood glucose levels but increases rates of hypoglycemia, diminishing the appeal of the ITR. This work proposes two methods to identify risk-controlled ITRs (rcITR), a class of ITR which maximizes a benefit while controlling risk at a prespecified threshold. A novel penalized recursive partitioning algorithm is developed which optimizes an unconstrained, penalized value function. The final rule is a risk-controlled decision tree (rcDT) that is easily interpretable. A natural extension of the rcDT model, risk controlled random forests (rcRF), is also proposed. Simulation studies demonstrate the robustness of rcRF modeling. Three variable importance measures are proposed to further guide clinical decision-making. Both rcDT and rcRF procedures can be applied to data from randomized controlled trials or observational studies. An extensive simulation study interrogates the performance of the proposed methods. A data analysis of the DURABLE diabetes trial in which two therapeutics were compared is additionally presented. An R package implements the proposed methods ( https//github.com/kdoub5ha/rcITR).Histone chaperones modulate the stability of histones beginning from histone synthesis, through incorporation into DNA, and during recycling during transcription and replication. Following histone removal from DNA, chaperones regulate histone storage and degradation. Here, we demonstrate that UBR7 is a histone H3.1 chaperone that modulates the supply of pre-existing post-nucleosomal histone complexes. We demonstrate that UBR7 binds to post-nucleosomal H3K4me3 and H3K9me3 histones via its UBR box and PHD. UBR7 binds to the non-nucleosomal histone chaperone NASP. In the absence of UBR7, the pool of NASP-bound post-nucleosomal histones accumulate and chromatin is depleted of H3K4me3-modified histones. We propose that the interaction of UBR7 with NASP and histones opposes the histone storage functions of NASP and that UBR7 promotes reincorporation of post-nucleosomal H3 complexes.<br />Besides being a potential component of (some species of) colophonium, D-limonene is also used as a tackifier in the production of adhesives. Hydroperoxides of limonene are well-known skin sensitizers.<br />To show that D-limonene may be present in colophonium-containing but also colophonium-free ("hypoallergenic") adhesives, and that patients suffering from allergic contact dermatitis (ACD) from both types of adhesives might display positive patch test reactions to limonene hydroperoxides in this regard.<br />Five patients with suspected ACD from adhesives were patch tested to the baseline series (containing limonene hydroperoxides 0.3 and 0.2% pet.), additional series and, if available, to the culprit adhesives. The adhesives labelled as containing colophonium (n=3) or free from it (n=2) were analysed with gas chromatography - mass spectrometry (GC-MS) for the presence of D-limonene.<br />All five patients sensitised to adhesives had (strong) positive patch test reactions to limonene hydroperoxides. [https://www.selleckchem.com/products/Verteporfin(Visudyne).html selleck inhibitor] The presence of D-limonene, and/or related components, could be demonstrated in all three colophonium-containing and, surprisingly, also in two colophonium-free ("hypoallergenic") tapes.<br />D-limonene may be present in both regular and "hypoallergenic" adhesives, with limonene hydroperoxides potentially contributing to ACD from such medical devices. The use of fragrance chemicals in adhesives deserves further research.<br />D-limonene may be present in both regular and "hypoallergenic" adhesives, with limonene hydroperoxides potentially contributing to ACD from such medical devices. The use of fragrance chemicals in adhesives deserves further research.<br />Several studies have identified disparities in pancreatic cancer treatment associated with gender, race, and ethnicity. There are limited data examining disparities in short-term adverse outcomes after pancreatic resection for cancer. The aim of this study is to evaluate associations of gender, race, and ethnicity with morbidity and mortality after pancreatic resection for malignancy.<br />The American College of Surgeons National Surgical Quality Improvement database was retrospectively reviewed. The χ<br />test and Student's t-test were used for univariable analysis and hierarchical logistic regression for multivariable analysis.<br />Morbidity and major morbidity after pancreaticoduodenectomy are associated with male gender, Asian race, and Hispanic ethnicity, whereas 30-day mortality is associated with the male gender. Morbidity and major morbidity after distal pancreatectomy are associated with the male gender. Morbidity after pancreaticoduodenectomy is independently associated with male gender, Asian race, and Hispanic ethnicity; major morbidity is independently associated with male gender and Asian race, and mortality is independently associated with Hispanic ethnicity.<br />Gender, race, and ethnicity are independently associated with morbidity after pancreaticoduodenectomy for cancer; gender and race are independently associated with major morbidity; and ethnicity is independently associated with mortality. Further studies are warranted to determine the basis of these associations.<br />Gender, race, and ethnicity are independently associated with morbidity after pancreaticoduodenectomy for cancer; gender and race are independently associated with major morbidity; and ethnicity is independently associated with mortality. Further studies are warranted to determine the basis of these associations.<br />Youth with obesity are likely to experience weight-based bullying victimization, and adolescents have the highest obesity rates among children. Factors that protect youth from traditional bullying victimization may protect youth from weight-based bullying victimization internal assets such as positive identity and social competence, and external assets such as perceived support from parents and friends.<br />To examine this proposition, data from 8th, 9th, and 11th graders were obtained from the 2016 Minnesota Student Survey (N=126,495). Logistic regressions were conducted to identify the relationship between assets and weight-based bullying and to determine possible moderation by weight status.<br />Results demonstrate that positive identity, parent support, and friend support were associated with lower odds of experiencing weight-based bullying victimization. Moderation analyses revealed that perceived parent support was most protective against experiencing weight-based bullying victimization among youth with obesity compared to youth with overweight, normal weight, or underweight.