Programmed cell death protein-1/programmed cell death ligand-1 (PD-1/PD-L1) pathway blockade is a promising new cancer therapy. Although PD-1/PD-L1 treatment has yielded clinical benefits in several ...types of cancer, further studies are required to clarify predictive biomarkers for drug efficacy and to understand the fundamental mechanism of PD-1/PD-L1 interaction between host and tumor cells. Here, we show that exosomes derived from lung cancer cells express PD-L1 and play a role in immune escape by reducing T-cell activity and promoting tumor growth. The abundance of PD-L1 on exosomes represented the quantity of PD-L1 expression on cell surfaces. Exosomes containing PD-L1 inhibited interferon-gamma (IFN-γ) secretion by Jurkat T cells. IFN-γ secretion was restored by PD-L1 knockout or masking on the exosomes. Both forced expression of PD-L1 on cells without PD-L1 and treatment with exosomes containing PD-L1 enhanced tumor growth in vivo. PD-L1 was present on exosomes isolated from the plasma of patients with non-small cell lung cancer, and its abundance in exosomes was correlated with PD-L1 positivity in tumor tissues. Exosomes can impair immune functions by reducing cytokine production and inducing apoptosis in CD8
T cells. Our findings indicate that tumor-derived exosomes expressing PD-L1 may be an important mediator of tumor immune escape.
Cognitive Radio (CR) is a promising technology that can alleviate the spectrum shortage problem by enabling unlicensed users equipped with CRs to coexist with incumbent users in licensed spectrum ...bands while causing no interference to incumbent communications. Spectrum sensing is one of the essential mechanisms of CRs and its operational aspects are being investigated actively. However, the security aspects of spectrum sensing have garnered little attention. In this paper, we identify a threat to spectrum sensing, which we call the primary user emulation (PUE) attack . In this attack, an adversary's CR transmits signals whose characteristics emulate those of incumbent signals. The highly flexible, software-based air interface of CRs makes such an attack possible. Our investigation shows that a PUE attack can severely interfere with the spectrum sensing process and significantly reduce the channel resources available to legitimate unlicensed users. To counter this threat, we propose a transmitter verification scheme, called LocDef (localization-based defense) , which verifies whether a given signal is that of an incumbent transmitter by estimating its location and observing its signal characteristics. To estimate the location of the signal transmitter, LocDef employs a non-interactive localization scheme. Our security analysis and simulation results suggest that LocDef is effective in identifying PUE attacks under certain conditions.
Enzymes are the most proficient catalysts, offering much more competitive processes compared to chemical catalysts. The number of industrial applications for enzymes has exploded in recent years, ...mainly owing to advances in protein engineering technology and environmental and economic necessities. Herein, we review recent progress in enzyme biocatalysis, and discuss the trends and strategies that are leading to broader industrial enzyme applications. The challenges and opportunities in developing biocatalytic processes are also discussed.
As knowledge of cell metabolism has advanced, glutamine has been considered an important amino acid that supplies carbon and nitrogen to fuel biosynthesis. A recent study provided a new perspective ...on mitochondrial glutamine metabolism, offering mechanistic insights into metabolic adaptation during tumor hypoxia, the emergence of drug resistance, and glutaminolysis-induced metabolic reprogramming and presenting metabolic strategies to target glutamine metabolism in cancer cells. In this review, we introduce the various biosynthetic and bioenergetic roles of glutamine based on the compartmentalization of glutamine metabolism to explain why cells exhibit metabolic reliance on glutamine. Additionally, we examined whether glutamine derivatives contribute to epigenetic regulation associated with tumorigenesis. In addition, in discussing glutamine transporters, we propose a metabolic target for therapeutic intervention in cancer.
Recent studies have identified a specialized subset of CD31
endomucin
(CD31
EMCN
) vascular endothelium that positively regulates bone formation. However, it remains unclear how CD31
EMCN
endothelium ...levels are coupled to anabolic bone formation. Mice with an osteoblast-specific deletion of Shn3, which have markedly elevated bone formation, demonstrated an increase in CD31
EMCN
endothelium. Transcriptomic analysis identified SLIT3 as an osteoblast-derived, SHN3-regulated proangiogenic factor. Genetic deletion of Slit3 reduced skeletal CD31
EMCN
endothelium, resulted in low bone mass because of impaired bone formation and partially reversed the high bone mass phenotype of Shn3
mice. This coupling between osteoblasts and CD31
EMCN
endothelium is essential for bone healing, as shown by defective fracture repair in SLIT3-mutant mice and enhanced fracture repair in SHN3-mutant mice. Finally, administration of recombinant SLIT3 both enhanced bone fracture healing and counteracted bone loss in a mouse model of postmenopausal osteoporosis. Thus, drugs that target the SLIT3 pathway may represent a new approach for vascular-targeted osteoanabolic therapy to treat bone loss.
The manipulation of the transition states of a chemical process is essential to achieve the desired selectivity. In particular, transition states of chemical reactions can be significantly modified ...in a confined environment. We report a catalytic reaction with remarkable amplification of stereochemical information in a confined water cage. Surprisingly, this amplification is significantly dependent on droplet size. This water-induced chirality amplification stems from the hydrophobic hydration effects, which ensures high proximity of the catalyst and substrates presumably at the transition state, leading to higher enantioselectivity. Flow and batch reactors were evaluated to confirm the generality of this water-induced chirality amplification. Our observation on efficient chiral induction in confined water cages might lead to an understanding of the chirality amplification in the prebiotic era, which is a key feature for the chemical evolution of homochirality.
Adventitious root (AR) formation is a complex genetic trait, which is controlled by various endogenous and environmental cues. Auxin is known to play a central role in AR formation; however, the ...mechanisms underlying this role are not well understood.
In this study, we showed that a previously identified auxin signaling module, AUXIN RESPONSE FACTOR(ARF)7/ARF19-LATERAL ORGAN BOUNDARIES DOMAIN(LBD)16/LBD18 via AUXIN1(AUX1)/LIKE-AUXIN3 (LAX3) auxin influx carriers, which plays important roles in lateral root formation, is involved in AR formation in Arabidopsis. In aux1, lax3, arf7, arf19, lbd16 and lbd18 single mutants, we observed reduced numbers of ARs than in the wild type. Double and triple mutants exhibited an additional decrease in AR numbers compared with the corresponding single or double mutants, respectively, and the aux1 lax3 lbd16 lbd18 quadruple mutant was devoid of ARs. Expression of LBD16 or LBD18 under their own promoters in lbd16 or lbd18 mutants rescued the reduced number of ARs to wild-type levels. LBD16 or LBD18 fused to a dominant SRDX repressor suppressed promoter activity of the cell cycle gene, Cyclin-Dependent Kinase(CDK)A1;1, to some extent. Expression of LBD16 or LBD18 was significantly reduced in arf7 and arf19 mutants during AR formation in a light-dependent manner, but not in arf6 and arf8. GUS expression analysis of promoter-GUS reporter transgenic lines revealed overlapping expression patterns for LBD16, LBD18, ARF7, ARF19 and LAX3 in AR primordia.
These results suggest that the ARF7/ARF19-LBD16/LBD18 transcriptional module via the AUX1/LAX3 auxin influx carriers plays an important role in AR formation in Arabidopsis.
Magnetic skyrmions are topologically protected spin textures with attractive properties suitable for high-density and low-power spintronic device applications. Much effort has been dedicated to ...understanding the dynamical behaviours of the magnetic skyrmions. However, experimental observation of the ultrafast dynamics of this chiral magnetic texture in real space, which is the hallmark of its quasiparticle nature, has so far remained elusive. Here, we report nanosecond-dynamics of a 100nm-diameter magnetic skyrmion during a current pulse application, using a time-resolved pump-probe soft X-ray imaging technique. We demonstrate that distinct dynamic excitation states of magnetic skyrmions, triggered by current-induced spin-orbit torques, can be reliably tuned by changing the magnitude of spin-orbit torques. Our findings show that the dynamics of magnetic skyrmions can be controlled by the spin-orbit torque on the nanosecond time scale, which points to exciting opportunities for ultrafast and novel skyrmionic applications in the future.
Abstract
The International Telecommunication Union announced a new color gamut standard of broadcast service television (BT 2020) for ultra-high-definition TV in 2012. To satisfy the wide-color gamut ...standard of BT 2020, monochromatic red (R), green (G), and blue (B) emissions require a small full width at half-maximum, which is an important property for improving color purity. Although organic light-emitting diode (OLED) displays are currently one of the main types of display technologies, their broad emission via strong vibronic coupling between ground and excited states is a major hurdle to overcome in the development of next-generation wide-color gamut displays. Thus, the development of OLED emitters with narrowband R–G–B emissions is of great significance. In this review, the recent progress in the development of OLED materials with narrowband emission is summarized by grouping them into fluorescent, phosphorescent, and thermally activated delayed fluorescent emitters to reveal the correlation between molecular structures, optical properties, and device characteristics. We discuss rational molecular design strategies to achieve narrow photoluminescence and electroluminescence and the underlying mechanisms for controlling the emission bandwidth. Finally, the challenges in the realization of wide-color gamut OLED displays and the future prospects of such devices are discussed.
There are conflicting data regarding the benefit of intravascular ultrasound (IVUS)–guided percutaneous coronary intervention (PCI) over angiography-guided PCI. Since the last meta-analysis was ...published, several new studies have been reported. We performed a comprehensive meta-analysis to evaluate the clinical impact of IVUS-guided PCI with drug-eluting stent compared with conventional angiography-guided PCI. This meta-analysis included 26,503 patients from 3 randomized and 14 observational studies; 12,499 patients underwent IVUS-guided PCI and 14,004 underwent angiography-guided PCI. Main outcome measures were total mortality, myocardial infarction (MI), stent thrombosis, and target lesion revascularization (TLR). IVUS-guided PCI was significantly associated with more stents, longer stents, and larger stents. Regarding clinical outcomes, IVUS-guided PCI was associated with a significantly lower risk of TLR (odds ratio OR 0.81, 95% confidence interval CI 0.66 to 1.00, p = 0.046). In addition, the risk of death (OR 0.61, 95% CI 0.48 to 0.79, p <0.001), MI (OR 0.57, 95% CI 0.44 to 0.75, p <0.001), and stent thrombosis (OR 0.59, 95% CI 0.47 to 0.75, p <0.001) were also decreased. In conclusion, our meta-analysis demonstrated that IVUS-guided PCI was associated with lower risk of death, MI, TLR, and stent thrombosis after drug-eluting stent implantation.
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