Kirkegaardbjerring7682

Core-shell structure is routinely used for enhancing luminescence of optical nanoparticles, where the luminescent core is passivated by an inert shell. It has been intuitively accepted that the luminescence would gradually enhance with the coverage of inert shell. Here we report an "off-on" effect at the interface of core-shell upconversion nanoparticles, i.e., regardless of the shell coverage, the luminescence is not much enhanced unless the core is completely encapsulated. This effect indicates that full shell coating on the luminescent core is critical to significantly enhance luminescence, which is usually neglected. Inspired by this observation, a cation exchange approach is used to block the energy transfer between core nanoparticle and surface quenchers. We find that the luminescent core exhibits enhanced luminescence after cation exchange creates an effective shell region. These findings are believed to provide a better understanding of the interfacial energy dynamics and subsequent luminescence changes.Although the hollow icosahedral M12 kernel has been extensively observed in metal nanoclusters, its origin remains a mystery. Here we report a reasonable avenue for the generation of the hollow icosahedron the kernel collapse from several small nano-building blocks to an integrated hollow icosahedron. On the basis of the Au alloying processes from Ag28Cu12(SR)24 to the template-maintained AuxAg28-xCu12(SR)24 and then to the template-transformed Au12CuyAg32-y(SR)30, the kernel evolution/collapse from "tetrahedral Ag4 + 4∗Ag3" to "tetrahedral Au4 + 4∗M3 (M = Au/Ag)" and then to "hollow icosahedral Au12" is mapped out. Significantly, the "kernel collapse" from small-sized nano-building blocks to large-sized nanostructures not only unveils the formation of hollow icosahedral M12 in this work, but also might be a very common approach in constructing metallic kernels of nanoclusters and nanoparticles (not limited to the M12 structure).NF-κB signaling pathway is a critical link between inflammation and cancer. Emerging evidence suggested that long non-coding RNAs (lncRNAs) were involved in dysregulation of NF-κB. Herein, we reported a novel lncRNA IKBKBAS that activated NF-κB in lung adenocarcinoma (LUAD) by upregulating IKKβ, a key member of NF-κB signaling pathway, thereby promoting the metastasis of LUAD both in vitro and in vivo. The upregulated IKBKBAS functioned as a competing endogenous RNA (ceRNA) via competing with IKKβ mRNA for binding miR-4741, consequently leading to upregulation and activation of IKKβ, and ultimately activation of NF-κB. The abnormally elevated IKBKBAS in LUAD was mainly resulted from the extremely decrease of miR-512-5p that targeting IKBKBAS. Furthermore, we identified a positive feedback loop between NF-κB and IKBKBAS, in which NF-κB activation induced by overexpression of IKBKBAS could promote the transcription of IKBKBAS by binding the κB sites within IKBKBAS promoter. Our studies revealed that IKBKBAS was involved in the activation of NF-κB signaling by upregulating the expression of IKKβ, which made it serve as a potential novel target for therapies to LUAD.Pulmonary hypertension (PH) is a progressive cardiopulmonary disease characterized by pulmonary arterial remodeling. Clonal somatic mutations including JAK2V617F, the most frequent driver mutation among myeloproliferative neoplasms, have recently been identified in healthy individuals without hematological disorders. Pentetic Acid Here, we reveal that clonal hematopoiesis with JAK2V617F exacerbates PH and pulmonary arterial remodeling in mice. JAK2V617F-expressing neutrophils specifically accumulate in pulmonary arterial regions, accompanied by increases in neutrophil-derived elastase activity and chemokines in chronic hypoxia-exposed JAK2V617F transgenic (JAK2V617F) mice, as well as recipient mice transplanted with JAK2V617F bone marrow cells. JAK2V617F progressively upregulates Acvrl1 (encoding ALK1) during the differentiation from bone marrow stem/progenitor cells peripherally into mature neutrophils of pulmonary arterial regions. JAK2V617F-mediated STAT3 phosphorylation upregulates ALK1-Smad1/5/8 signaling. ALK1/2 inhibition completely prevents the development of PH in JAK2V617F mice. Finally, our prospective clinical study identified JAK2V617F-positive clonal hematopoiesis is more common in PH patients than in healthy subjects. These findings indicate that clonal hematopoiesis with JAK2V617F causally leads to PH development associated with ALK1 upregulation.The nature of the quantum-to-classical crossover remains one of the most challenging open question of Science to date. In this respect, moving objects play a specific role. Pioneering experiments over the last few years have begun exploring quantum behaviour of micron-sized mechanical systems, either by passively cooling single GHz modes, or by adapting laser cooling techniques developed in atomic physics to cool specific low-frequency modes far below the temperature of their surroundings. Here instead we describe a very different approach, passive cooling of a whole micromechanical system down to 500 μK, reducing the average number of quanta in the fundamental vibrational mode at 15 MHz to just 0.3 (with even lower values expected for higher harmonics); the challenge being to be still able to detect the motion without disturbing the system noticeably. With such an approach higher harmonics and the surrounding environment are also cooled, leading to potentially much longer mechanical coherence times, and enabling experiments questioning mechanical wave-function collapse, potentially from the gravitational background, and quantum thermodynamics. Beyond the average behaviour, here we also report on the fluctuations of the fundamental vibrational mode of the device in-equilibrium with the cryostat. These reveal a surprisingly complex interplay with the local environment and allow characteristics of two distinct thermodynamic baths to be probed.Staphylococcus aureus bi-component pore-forming leukocidins are secreted toxins that directly target and lyse immune cells. Intriguingly, one of the leukocidins, Leukocidin AB (LukAB), is found associated with the bacterial cell envelope in addition to secreted into the extracellular milieu. Here, we report that retention of LukAB on the bacterial cells provides S. link2 aureus with a pre-synthesized active toxin that kills immune cells. On the bacteria, LukAB is distributed as discrete foci in two distinct compartments membrane-proximal and surface-exposed. Through genetic screens, we show that a membrane lipid, lysyl-phosphatidylglycerol (LPG), and lipoteichoic acid (LTA) contribute to LukAB deposition and release. Furthermore, by studying non-covalently surface-bound proteins we discovered that the sorting of additional exoproteins, such as IsaB, Hel, ScaH, and Geh, are also controlled by LPG and LTA. Collectively, our study reveals a multistep secretion system that controls exoprotein storage and protein translocation across the S. aureus cell wall.This study (ORIENT-4) aimed to assess the efficacy and safety of sintilimab, a humanized anti-PD-1 antibody, in patients with relapsed/refractory extranodal NK/T cell lymphoma (r/r ENKTL). ORIENT-4 is a multicenter, single-arm, phase 2 clinical trial (NCT03228836). Patients with r/r ENKTL who failed to at least one asparaginase-based regimen were enrolled to receive sintilimab 200 mg intravenously every 3 weeks for up to 24 months. The primary endpoint was the objective response rate (ORR) based on Lugano 2014 criteria. Twenty-eight patients with r/r ENKTL were enrolled from August 31, 2017 to February 7, 2018. Twenty-one patients (75.0%, 95% CI 55.1-89.3%) achieved an objective response. With a median follow-up of 30.4 months, the median overall survival (OS) was not reached. The 24-month OS rate was 78.6% (95% CI, 58.4-89.8%). Most treatment-related adverse events (TRAEs) were grade 1-2 (71.4%), and the most common TRAE was decreased lymphocyte count (42.9%). Serious adverse events (SAEs) occurred in 7 (25.0%) patients, and no patient died of adverse events. Sintilimab is effective and well tolerated in patients with r/r ENKTL and could be a novel therapeutic approach for the control of ENKTL in patients.The topology of polymers affects their characteristic features, i.e., their microscopic structure and macroscopic properties. link3 However, the topology of a polymer is usually fixed during the construction of the polymer chain and cannot be transformed after its determination during the synthesis. In this study, topology-transformable block copolymers that are connected via rotaxane linkages are introduced. We will present systems in which the topology transformation of block copolymers changes their 1) microphase-separated structures and 2) macroscopic mechanical properties. The combination of a rotaxane structure at the junction point and block copolymers that spontaneously form microphase-separated structures in the bulk provides access to systems that cannot be attained using conventional covalent bonds.Empirical analysis of social mobility is typically framed by outcomes recorded for only a single, recent generation, ignoring intergenerational preconditions and historical conferment of opportunity. We use the detailed geography of relative deprivation (hardship) to demonstrate that different family groups today experience different intergenerational outcomes and that there is a distinct Great Britain-wide geography to these inequalities. We trace the evolution of these inequalities back in time by coupling family group level data for the entire Victorian population with a present day population-wide consumer register. Further geographical linkage to neighbourhood deprivation data allows us to chart the different social mobility outcomes experienced by every one of the 13,378 long-established family groups. We identify clear and enduring regional divides in England and Scotland. In substantive terms, use of family names and new historical digital census resources are central to recognising that geography is pivotal to understanding intergenerational inequalities.In this study, we detected a novel pathogenic variant and a previously reported variant in RAB3GAP1 by whole-exome sequencing (NM_001172435.2 c.1552C>T, p.Gln518*; c.1471C>T, p.Arg491*). The first patient is a 3-year-old girl who presented with bilateral congenital cataracts, developmental delay, abnormal craniofacial features, drug-resistant constipation, and corpus callosum hypoplasia. The proband of the second family is a 13-year-old boy who suffers from developmental delay, quadriplegia, intellectual disability, abnormal craniofacial features, and corpus callosum hypoplasia.Aging is a natural and progressive process characterized by an increased frequency of age-related diseases such as cancer. But its mechanism is unclear. TNFAIP8L2 (Tipe2) is an important negative regulator for homeostasis through inhibiting TLR and TCR signaling. Our work reveals that Tipe2 might have dual function by regulating senescence. One side, the overexpression of Tipe2 in CRC cells could induce typical senescent phenotype, especially exposure to oxidative stress. Tipe2 inhibits telomerase activity by regulating c-Myc and c-Est-2 binding to the hTERT promotor. Interestingly, Tipe2 KO mice treated with D-Gal showed a less serious inverse of CD4CD8 ratio, a lower percentage of Treg compared to WT. Besides, Tipe2 KO mice were more tolerant to the initiation of AOM/DSS-induced CRC, accompanied by a lower level of Treg within IEL. Therefore, specific antibodies against CD25 effectively ameliorate tumorigenesis. These data suggest strongly that the overexpressed Tipe2 suppresses tumor cells proliferation and survival, but endogenous Tipe2 promotes the initiation of tumorigenesis when exposure to dangerous environment such as AOM/DSS-related inflammation.