Transforming growth factor-β (TGFβ) is enriched in the bone matrix and serves as a key factor in promoting bone metastasis in cancer. In addition, TGFβ signaling activates mammalian target of ...rapamycin (mTOR) functions, which is important for the malignant progression. Here, we demonstrate that TGFβ regulates the level of microRNA-96 (miR-96) through Smad-dependent transcription and that miR-96 promotes the bone metastasis in prostate cancer. The enhanced effects in cellular growth and invasiveness suggest that miR-96 functions as an oncomir/and metastamir. Supporting this idea, we identified a downstream target of the TGFβ-miR-96 signaling pathway to be AKT1S1 mRNA, whose translated protein is a negative regulator of mTOR kinase. Our findings provide a novel mechanism accounting for the TGFβ signaling and bone metastasis.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Our understanding of when and how humans adapted to living on the Tibetan Plateau at altitudes above 2000 to 3000 meters has been constrained by a paucity of archaeological data. Here we report data ...sets from the northeastern Tibetan Plateau indicating that the first villages were established only by 5200 calendar years before the present (cal yr B.P.). Using these data, we tested the hypothesis that a novel agropastoral economy facilitated year-round living at higher altitudes since 3600 cal yr B.P. This successful subsistence strategy facilitated the adaptation of farmers-herders to the challenges of global temperature decline during the late Holocene.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
In patients with metastatic HER2-positive breast cancer that had progressed after primary therapy, treatment with the antibody–drug conjugate trastuzumab deruxtecan resulted in a higher response rate ...and longer progression-free survival than trastuzumab emtansine. Since trastuzumab deruxtecan was associated with interstitial pulmonary fibrosis, close monitoring of pulmonary function is warranted.
We demonstrate full quantum state control of two species of single atoms using optical tweezers and assemble the atoms into a molecule. Our demonstration includes 3D ground-state cooling of a single ...atom (Cs) in an optical tweezer, transport by several microns with minimal heating, and merging with a single Na atom. Subsequently, both atoms occupy the simultaneous motional ground state with 61(4)% probability. This realizes a sample of exactly two cotrapped atoms near the phase-space-density limit of one, and allows for efficient stimulated-Raman transfer of a pair of atoms into a molecular bound state of the triplet electronic ground potentiala3Σ+. The results are key steps toward coherent creation of single ultracold molecules for future exploration of quantum simulation and quantum information processing.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM, UPUK
Forkhead box M1 (FOXM1) is a proliferation-associated transcription factor essential for cell cycle progression. Numerous studies have documented that FOXM1 has multiple functions in tumorigenesis ...and its elevated levels are frequently associated with cancer progression. Here, we characterized the role of ERK/FOXM1 signaling in mediating the metastatic potential of ovarian cancer cells. Immunohistochemical (IHC), immunoblotting and semi-quantitative RT-PCR analyses found that both phospho-ERK and FOXM1 were frequently upregulated in ovarian cancers. Intriguingly, the overexpressed phospho-ERK (p<0.001) and FOXM1 (p<0.001) were significantly correlated to high-grade ovarian tumors with aggressive behavior such as metastasized lymph node (5 out of 6). Moreover, the expressions of phospho-ERK and FOXM1 had significantly positive correlation (p<0.001). Functionally, ectopic expression of FOXM1B remarkably enhanced cell migration/invasion, while FOXM1C not only increased cell proliferation but also promoted cell migration/invasion. Conversely, inhibition of FOXM1 expression by either thiostrepton or U0126 could significantly impair FOXM1 mediated oncogenic capacities. However, the down-regulation of FOXM1 by either thiostrepton or U0126 required the presence of p53 in ovarian cancer cells. Collectively, our data suggest that over-expression of FOXM1 might stem from the constitutively active ERK which confers the metastatic capabilities to ovarian cancer cells. The impairment of metastatic potential of cancer cells by FOXM1 inhibitors underscores its therapeutic value in advanced ovarian tumors.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Sequentially deposited organic solar cells (SD‐OSCs) have attracted great attention owing to their ability in achieving a more favorable, vertically phase‐separated morphology to avoid the ...accumulation of counter charges at absorber/transporting layer interfaces. However, the processing of SD‐OSCs is still quite challenging in preventing the penetration of small‐molecule acceptors into the polymer donor layer via erosion or swelling. Herein, solid additives (SAs) with varied electrostatic potential distributions and steric hinderance are introduced into SD‐OSCs to investigate the effect of evaporation dynamics and selective interaction on vertical component distribution. Multiple modelings indicate that the π–π interaction dominates the interactions between aromatic SAs and active layer components. Among them, p‐dibromobenzene shows a stronger interaction with the donor while 2‐chloronaphthalene (2‐CN) interacts more preferably with acceptor. Combining the depth‐dependent morphological study aided by multiple X‐ray scattering methods, it is concluded that the evaporation of SAs can drive the stronger‐interaction component upward to the surface, while having minor impact on the overall molecular packing. Ultimately, the 2‐CN‐treated devices with reduced acceptor concentration at the bottom surface deliver a high power conversion efficiency of 19.2%, demonstrating the effectiveness of applying selective interactions to improve the vertical morphology of OSCs by using SAs with proper structure.
Solid additives with varied electrostatic potential and steric hinderance are introduced to investigate the impact of both evaporation dynamics and selective interaction on vertical component distribution. The removal of solid additives can drive the more strongly interacting component upward to the surface, delivering a high performance of 19.2%, among the highest efficiencies achieved in organic solar cells.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
We uncovered two critical issues in earlier studies: (a) some studies have shown that mobile learning technology is not beneficial for all students due to complexity of learning environments and ...student prior knowledge, skills, and experience and (b) familiarity of students with the authentic environments in which they learn using mobile technology did not receive much attention in earlier studies. To address these issues, we designed three learning tasks for a class of 26 junior high school students. The students applied language skills by completing the tasks in authentic environments individually in a first task, loosely collaborating with peers in a second task, and tightly collaborating with peers in a third task. A mobile learning system was also designed in this study to support students to accomplish the tasks. The aim of this study was to explore students' learning experiences using the learning system, their perceptions towards the system, and to assess how differently the students perform on the three tasks. According to our design, in the first task, the students took pictures of objects and described them orally or in writing using the mobile learning system. In the second task, after the students completed assignments, each student received comments from a partner through the system. In comments, the partner indicated flaws in student assignments and suggested how to fix them. In the third task, the students completed assignments, shared them using the system, and then exchanged comments with their partners face to face regarding issues related to their completed assignments and suggested how to improve them. Such learning behaviours in the three tasks enabled the students to practise writing and speaking skills. Our results demonstrate that most of the students highly valued our learning system and intend to use it in the future. Furthermore, the results show that the students performed best when they collaborated; namely, student performance was enhanced the most after the third task that required tight collaboration. Based on our results, we learned that students' familiarity with authentic environments is very important and beneficial for their learning. In addition, we learned that even in complex environment, less skilled and experienced students with low prior knowledge can perform well when they tightly collaborate with more skilled and experienced students with high prior knowledge, and our learning system can facilitate such collaboration.
Lay Description
What is currently known about the subject matter:
Mobile technology supports application of new knowledge outside of school
The results of most related studies on mobile learning have been positive
We identified some gaps in earlier studies on mobile learning
What our paper adds to this:
We filled the void in the literature
We tested the feasibility of our proposed approach
We explored learning experiences, perceptions and performance of students
The implications of study findings for practitioners:
Learning experiences include Learning, Collaboration and Authenticity
Our approach was useful for language learning in familiar authentic contexts
Students had positive perceptions towards our approach
Students performed best when they tightly collaborated
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Photosensitizers (PSs) with multiple characteristics, including efficient singlet oxygen (
1
O
2
) generation, cancer cell-selective accumulation and subsequent mitochondrial localization as well as ...near-infrared (NIR) excitation and bright NIR emission, are promising candidates for imaging-guided photodynamic therapy (PDT) but rarely concerned. Herein, a simple rational strategy, namely modulation of donor-acceptor (D-A) strength, for molecular engineering of mitochondria-targeting aggregation-induced emission (AIE) PSs with desirable characteristics including highly improved
1
O
2
generation efficiency, NIR emission (736 nm), high specificity to mitochondria, good biocompatibility, high brightness and superior photostability is demonstrated. Impressively, upon light irradiation, the optimal NIR AIE PS (DCQu) can generate
1
O
2
with efficiency much higher than those of commercially available PSs. The excellent two-photon absorption properties of DCQu allow two-photon fluorescence imaging of mitochondria and subsequent two-photon excited PDT. DCQu can selectively differentiate cancer cells from normal cells without the aid of extra targeting ligands. Upon ultralow-power light irradiation at 4.2 mW cm
−2
,
in situ
mitochondrial photodynamic activation to specifically damage cancer cells and efficient
in vivo
melanoma ablation are demonstrated, suggesting superior potency of the AIE PS in imaging-guided PDT with minimal side effects, which is promising for future precision medicine.
Mitochondria-targeted photosensitizers with highly efficient singlet oxygen generation, bright near-infrared AIE and good two-photon absorption are obtained through ingenious molecular engineering for cancer cell-selective photodynamic therapy.
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IJS, KILJ, NUK, UL, UM, UPUK
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