As a type of elementary organic compounds containing N−N single bond, hydrazone involved chemical conversions are extremely extensive, but they are mainly limited to N2‐retention and N2‐removal ...modes. We report herein an unprecedented protocol for the realization of division utilization of the N2‐moiety of hydrazone by a radical facilitated N−N bond deconstruction strategy. This new conversion mode enables the successful combination of alkene carboamination and Hofmann‐Löffler‐Freytag reaction by the reaction of N‐homoallyl mesitylenesulfonyl hydrazones with ethyl difluoroiodoacetate under photocatalytic redox neutral conditions. Mechanism studies reveal that the reaction undergoes a radical relay involving addition, crucial remote imino‐N migration and H‐atom transfer. Consequently, a series of structurally significant ϵ‐N‐sulphonamide‐α,α‐difluoro‐γ‐amino acid esters are efficiently produced via continuous C−C bond and dual C−N bonds forging.
A novel conversion mode for hydrazone by the division use of N2‐moiety is developed by the photocatalytic redox neutral reaction of N‐homoallyl‐N‐mesitylenesulfonyl (Mts)‐hydrazones with ICF2CO2Et. The reaction merges olefin carboamination and Hofmann‐Löffler‐Freytag (HLF) reaction by radical addition/crucial distal N and H transfer sequences to yield ϵ‐N‐sulphonamide‐α,α‐difluoro‐γ‐amino acid esters under tandem C−C and dual C−N bonds forging.
Metastasis is the main cause of death in individuals with cancer. Immune checkpoint blockade (ICB) can potentially reverse CD8+ cytotoxic T lymphocytes (CTLs) dysfunction, leading to significant ...remission in multiple cancers. However, the mechanism underlying the development of CTL exhaustion during metastatic progression remains unclear. Here, we established an experimental pulmonary metastasis model with melanoma cells and discovered a critical role for melanoma‐released exosomes in metastasis. Using genetic knockdown of nSMase2 and Rab27a, 2 key enzymes for exosome secretion, we showed that high levels of effector‐like tumor‐specific CD8+ T cells with transitory exhaustion, instead of terminal exhaustion, were observed in mice without exosomes; these cells showed limited inhibitory receptors and strong proliferation and cytotoxicity. Mechanistically, the immunosuppression of exosomes depends on exogenous PD‐L1, which can be largely rescued by pretreatment with antibody blockade. Notably, we also found that exosomal PD‐L1 acts as a promising predictive biomarker for ICB therapies during metastasis. Together, our findings suggest that exosomal PD‐L1 may be a potential immunotherapy target, suggesting a new curative therapy for tumor metastasis.
We demonstrate a crucial role for tumor‐released exosomes in promoting metastatic progression. We provide extensive evidence that exosomes from tumor cells act alone as contributors to driving tumor‐specific CD8+ T cell exhaustion in vivo. We also find that exosomal PD‐L1 acts as a promising predictive biomarker for ICB therapies during metastasis.
Abstract
As the third paper in the multiple-part series, we report the statistical properties of radio bursts detected from the repeating fast radio burst (FRB) source FRB 20201124A with the ...Five-hundred-meter Aperture Spherical radio Telescope during an extremely active episode between the 25th and 28th of September 2021 (UT). We focus on the polarization properties of 536 bright bursts with S/N > 50. We found that the Faraday rotation measures (RMs) monotonically dropped from −579 to −605 rad m
−2
in the 4 day window. The RM values were compatible with the values (−300 to −900 rad m
−2
) reported 4 months ago. However, the RM evolution rate in the current observation window was at least an order of magnitude smaller than the one (∼500 rad m
−2
day
−1
) previously reported during the rapid RM-variation phase, but is still higher than the one (≤1 rad m
−2
day
−1
) during the later RM no-evolution phase. The bursts of FRB 20201124A were highly polarized with the total degree of polarization (circular plus linear) greater than 90% for more than 90% of all bursts. The distribution of linear polarization position angles (PAs), degree of linear polarization (
L
/
I
) and degree of circular polarization (
V
/
I
) can be characterized with unimodal distribution functions. During the observation window, the distributions became wider with time, i.e., with larger scatter, but the centroids of the distribution functions remained nearly constant. For individual bursts, significant PA variations (confidence level 5
σ
) were observed in 33% of all bursts. The polarization of single pulses seems to follow certain complex trajectories on the Poincaré sphere, which may shed light on the radiation mechanism at the source or the plasma properties along the path of FRB propagation.
The renovation of cities' urban industrial heritage fabric is becoming increasingly recognized as an opportunity for post-industrial urban development, suggesting a complex interplay between the ...renovation of industrial heritage sites and urban regeneration effects in surrounding areas. However, prior research on industrial heritage renovation rarely transcends the arts-led gentrification narrative, and whether/to what extent industrial heritage renovation can catalyze sustainable urban regeneration in surrounding areas-and the driving forces underpinning that process-remains unclear, especially within the Chinese context. In this research, we focus on Shanghai's top-down policy of renovating industrial heritage sites into locations for creative industry clusters. By comparing Yishan Road and Changyuan Districts from 2008 to 2018, we arrived at a nuanced understanding of the urban regeneration effects of industrial heritage renovation as a policy-induced gentrification model. We further concluded that the renovation of a city's industrial heritage fabric could catalyze sustainable urban regeneration if implemented through an integrated development model that considered the physical, economic, social, and cultural aspects that resonated with the current policy and institutional system. These findings have important theoretical and practical implications in urban policy and planning discussions on the strategic value of industrial heritage renovation in post-industrial cities.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Lithium metal batteries (LMBs) with Ni-rich cathode materials providing ultra-high energy density (∼500 W h kg−1) are expected to be the next generation of batteries. However, high-voltage LMBs ...exhibit inferior electrochemical performance at elevated temperatures, due to severe dendrite growth in lithium metal anodes and the structural degradation of Ni-rich cathodes, which should be paid attention to in terms of their practical application. Herein, by introducing 1,3-propane sultone (PS) into the carbonate electrolytes, satisfying cycling stability of Li‖LiNi0.8Co0.1Mn0.1O2 (NCM811) batteries at a high cut-off voltage of 4.45 V and an elevated temperature of 45 °C was achieved, which also shows higher ionic conductivity, wettability and thermodynamic stability. This approach enables uniform lithium plating/stripping at elevated temperatures, because of the construction of a LiF/Li2SO3-rich interphase layer. Besides, PS inhibits drastic structural change and interfacial side reactions on NCM811. It is also noteworthy that Li‖NCM811 full cells delivered decent performance at high-load cathodes, ultra-thin lithium anodes and lean electrolytes cycling at 4.45 V and 45 °C. This strategy provides a feasible solution for boosting high energy density LMBs under extreme conditions.
Background Dengue virus serotype 2 (DENV-2) was the major serotype in the 2015 dengue outbreak in Taiwan, while DENV-1 and DENV-3 were dominant between 2005 and 2014. We aimed to investigate whether ...DENV-2 contributed to disease severity and mortality in the outbreak in Kaohsiung city, Taiwan. Methods We collected serum samples from dengue patients to detect the presence of DENV and determine the serotypes by using quantitative reverse transcription-polymerase chain reaction. Our cohorts comprised 105 DENV-1-infected cases and 1,550 DENV-2-infected cases. Demographic data, DENV serotype, and comorbidities were covariates for univariate and multivariate analyses to explore the association with severity and mortality. Results The results suggested that DENV-1 persisted and circulated, while DENV-2 was dominant during the dengue outbreak that occurred between September and December 2015. However, DENV-2 did not directly contribute to either severity or mortality. Aged patients and patients with diabetes mellitus (DM) or moderate to severe chronic kidney disease (CKD) had a higher risk of developing severe dengue. The mortality of dengue patients was related to a higher Charlson comorbidity index score and severe dengue. Among DENV-2-infected patients and older patients, preexisting anti-dengue IgG, DM, and moderate to severe CKD were associated with severe dengue. Moreover, female sex and severe dengue were associated with a significantly higher risk of death. Conclusions Our findings highlight the importance of timely serological testing in elderly patients to identify potential secondary infections and focus on the meticulous management of elderly patients with DM or moderate to severe CKD to reduce dengue-related death. Keywords: DENV-1, DENV-2, Dengue fever, Severe dengue, Mortality, Anti-dengue IgG
The unique properties of engineered nanoparticles (ENs) that make their industrial applications so attractive simultaneously raise questions regarding their environmental safety. ENs exhibit ...behaviors different from bulk materials with identical chemical compositions. Though the nanotoxicity of ENs has been studied intensively, their unintended environmental impacts remain largely unknown. Herein we report experimental results of EN interactions with exopolymeric substances (EPS) from three marine phytoplankton species: Amphora sp., Ankistrodesmus angustus and Phaeodactylum tricornutum. EPS are polysaccharide-rich anionic colloid polymers released by various microorganisms that can assemble into microgels, possibly by means of hydrophobic and ionic mechanisms. Polystyrene nanoparticles (23 nm) were used in our study as model ENs. The effects of ENs on EPS assembly were monitored with dynamic laser scattering (DLS). We found that ENs can induce significant acceleration in Amphora sp. EPS assembly; after 72 hours EN-EPS aggregation reached equilibrium, forming microscopic gels of ∼4-6 µm in size. In contrast, ENs only cause moderate assembly kinetic acceleration for A. angustus and P. tricornutum EPS samples. Our results indicate that the effects of ENs on EPS assembly kinetics mainly depend on the hydrophobic interactions of ENs with EPS polymers. The cycling mechanism of EPS is complex. Nonetheless, the change of EPS assembly kinetics induced by ENs can be considered as one potential disturbance to the marine carbon cycle.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Epstein-Barr virus (EBV)-associated epithelial cancers, including nasopharyngeal carcinoma (NPC) and approximately 10% of gastric cancers, termed EBVaGC, represent 80% of all EBV-related ...malignancies. However, the exact role of EBV in epithelial cancers remains elusive. Here, we report that EBV functions in vasculogenic mimicry (VM). Epithelial cancer cells infected with EBV develop tumor vascular networks that correlate with tumor growth, which is different from endothelial-derived angiogenic vessels and is VEGF-independent. Mechanistically, activation of the PI3K/AKT/mTOR/HIF-1α signaling cascade, which is partly mediated by LMP2A, is responsible for EBV-induced VM formation. Both xenografts and clinical samples of NPC and EBVaGC exhibit VM histologically, which are correlated with AKT and HIF-1α activation. Furthermore, although anti-VEGF monotherapy shows limited effects, potent synergistic antitumor activities are achieved by combination therapy with VEGF and HIF-1α-targeted agents. Our findings suggest that EBV creates plasticity in epithelial cells to express endothelial phenotype and provides a novel EBV-targeted antitumor strategy.
The genetic basis of colorectal cancer (CRC) and its clinical associations remain poorly understood due to limited samples or targeted genes in current studies. Here, we perform ultradeep whole-exome ...sequencing on 1015 patients with CRC as part of the ChangKang Project. We identify 46 high-confident significantly mutated genes, 8 of which mutate in 14.9% of patients: LYST, DAPK1, CR2, KIF16B, NPIPB15, SYTL2, ZNF91, and KIAA0586. With an unsupervised clustering algorithm, we propose a subtyping strategy that classisfies CRC patients into four genomic subtypes with distinct clinical characteristics, including hypermutated, chromosome instability with high risk, chromosome instability with low risk, and genome stability. Analysis of immunogenicity uncover the association of immunogenicity reduction with genomic subtypes and poor prognosis in CRC. Moreover, we find that mitochondrial DNA copy number is an independent factor for predicting the survival outcome of CRCs. Overall, our results provide CRC-related molecular features for clinical practice and a valuable resource for translational research.
Janus transition-metal dichalcogenides (TMDCs) are emerging as special 2D materials with different chalcogen atoms covalently bonded on each side of the unit cell, resulting in interesting ...properties. To date, several synthetic strategies have been developed to realize Janus TMDCs, which first involves stripping the top-layer S of MoS2 with H atoms. However, there has been little discussion on the intermediate Janus MoSH. It is critical to find the appropriate plasma treatment time to avoid sample damage. A thorough understanding of the formation and properties of MoSH is highly desirable. In this work, a controlled H2-plasma treatment has been developed to gradually synthesize a Janus MoSH monolayer, which was confirmed by the TOF-SIMS analysis as well as the subsequent fabrication of MoSSe. The electronic properties of MoSH, including the high intrinsic carrier concentration (∼2 × 1013 cm–2) and the Fermi level (∼ – 4.11 eV), have been systematically investigated by the combination of FET device study, KPFM, and DFT calculations. The results demonstrate a method for the creation of Janus MoSH and present the essential electronic parameters which have great significance for device applications. Furthermore, owing to the metallicity, 2D Janus MoSH might be a potential platform to observe the SPR behavior in the mid-infrared region.
PDF
