Although single-atomically dispersed metal-N
on carbon support (M-NC) has great potential in heterogeneous catalysis, the scalable synthesis of such single-atom catalysts (SACs) with high-loading ...metal-N
is greatly challenging since the loading and single-atomic dispersion have to be balanced at high temperature for forming metal-N
. Herein, we develop a general cascade anchoring strategy for the mass production of a series of M-NC SACs with a metal loading up to 12.1 wt%. Systematic investigation reveals that the chelation of metal ions, physical isolation of chelate complex upon high loading, and the binding with N-species at elevated temperature are essential to achieving high-loading M-NC SACs. As a demonstration, high-loading Fe-NC SAC shows superior electrocatalytic performance for O
reduction and Ni-NC SAC exhibits high electrocatalytic activity for CO
reduction. The strategy paves a universal way to produce stable M-NC SAC with high-density metal-N
sites for diverse high-performance applications.
Idiopathic pulmonary fibrosis (IPF) is characterized by fibrotic change in alveolar epithelial cells and leads to the irreversible deterioration of pulmonary function. Transforming growth factor-beta ...1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) in type 2 lung epithelial cells contributes to excessive collagen deposition and plays an important role in IPF. Atractylodin (ATL) is a kind of herbal medicine that has been proven to protect intestinal inflammation and attenuate acute lung injury. Our study aimed to determine whether EMT played a crucial role in the pathogenesis of pulmonary fibrosis and whether EMT can be utilized as a therapeutic target by ATL treatment to mitigate IPF. To address this topic, we took two steps to investigate: 1. Utilization of anin vitro EMT model by treating alveolar epithelial cells (A549 cells) with TGF-β1 followed by ATL treatment for elucidating the underlying pathways, including Smad2/3 hyperphosphorylation, mitogen-activated protein kinase (MAPK) pathway overexpression, Snail and Slug upregulation, and loss of E-cadherin. Utilization of an in vivo lung injury model by treating bleomycin on mice followed by ATL treatment to demonstrate the therapeutic effectiveness, such as, less collagen deposition and lower E-cadherin expression. In conclusion, ATL attenuates TGF-β1-induced EMT in A549 cells and bleomycin-induced pulmonary fibrosis in mice.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Summary
Topological cytonuclear discordance is commonly observed in plant phylogenetic and phylogeographic studies, yet few studies have attempted to detect two other forms of cytonuclear discordance ...(branch length and geographical) and to uncover the causes of the discordance.
We used the whole nuclear and chloroplast genome data from 80 individual Asian butternuts to reveal the pattern and processes of cytonuclear discordance.
Our findings indicate that the chloroplast genome had substantially deeper divergence (branch‐length discordance) and a steeper cline in the contact zone (geographic discordance) compared with the nuclear genome. After various hypothesis have been tested, the results suggest that incomplete lineage sorting, positive selection and cytonuclear incompatibility are probably insufficient to explain this pattern. However, isolation‐by‐distance analysis and gene flow estimation point to a much higher level of gene flow by pollen compared with by seeds, which may have slowed down lineage divergence and mediated wider contact for nuclear genome compared with the chloroplast genome.
Altogether, this study highlights a critical role of sex‐biased dispersal in causing discordance between the nuclear and plastid genome of Asian butternuts. Given its ubiquity among plants, asymmetric gene flow should be given a high priority in future studies of cytonuclear discordance.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Group‐10 layered transitional metal dichalcogenides including PtS2, PtSe2, and PtTe2 are excellent potential candidates for optoelectronic devices due to their unique properties such as high carrier ...mobility, tunable bandgap, stability, and flexibility. Large‐area platinum diselenide (PtSe2) with semiconducting characteristics is far scarcely investigated. Here, the development of a high‐performance photodetector based on vertically aligned PtSe2‐GaAs heterojunction which exhibits a broadband sensitivity from deep ultraviolet to near‐infrared light, with peak sensitivity from 650 to 810 nm, is reported. The Ilight/Idark ratio and responsivity of photodetector are 3 × 104 and 262 mA W−1 measured at 808 nm under zero bias voltage. The response speed of τr/τf is 5.5/6.5 µs, which represents the best result achieved for Group‐10 TMDs based optoelectronic device thus far. According to first‐principle density functional theory, the broad photoresponse ranging from visible to near‐infrared region is associated with the semiconducting characteristics of PtSe2 which has interstitial Se atoms within the PtSe2 layers. It is also revealed that the PtSe2/GaAs photodetector does not exhibit performance degradation after six weeks in air. The generality of the above good results suggests that the vertically aligned PtSe2 is an ideal material for high‐performance optoelectronic systems in the future.
This work shows the large‐area growth of high‐quality vertically aligned PtSe2, and its application to photodetectors based on PtSe2‐GaAs heterojunctions which exhibit a broadband sensitivity to illumination ranging from deep ultraviolet to near‐infrared light, with a peak sensitivity in the region from 650 to 810 nm. The high‐performance broadband photodetector will develop the next‐generation 2D Group‐10 materials based optoelectronic devices.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
MoS2 quantum dots (QDs)‐based white‐light‐emitting diodes (QD‐WLEDs) are designed, fabricated, and demonstrated. The highly luminescent, histidine‐doped MoS2 QDs synthesized by microwave induced ...fragmentation of 2D MoS2 nanoflakes possess a wide distribution of available electronic states as inferred from the pronounced excitation‐wavelength‐dependent emission properties. Notably, the histidine‐doped MoS2 QDs show a very strong emission intensity, which exceeds seven times of magnitude larger than that of pristine MoS2 QDs. The strongly enhanced emission is mainly attributed to nitrogen acceptor bound excitons and passivation of defects by histidine‐doping, which can enhance the radiative recombination drastically. The enabled electroluminescence (EL) spectra of the QD‐WLEDs with the main peak around 500 nm are found to be consistent with the photoluminescence spectra of the histidine‐doped MoS2 QDs. The enhanced intensity of EL spectra with the current increase shows the stability of histidine‐doped MoS2 based QD‐WLEDs. The typical EL spectrum of the novel QD‐WLEDs has a Commission Internationale de l'Eclairage chromaticity coordinate of (0.30, 0.36) exhibiting an intrinsic broadband white‐light emission. The unprecedented and low‐toxicity QD‐WLEDs based on a single light‐emitting material can serve as an excellent alternative for using transition metal dichalcogenides QDs as next generation optoelectronic devices.
A “single light‐emitting material,” “low‐toxicity,” and “economical fabrication process” white‐light‐emitting diode based on histidine‐doped MoS2 quantum dots is successfully designed, fabricated, and demonstrated. This work overcomes the low‐luminescence problem for traditional 2D transition metal dichalcogenides and achieves high performance white‐light‐emitting diodes with an intrinsic broadband white‐light electroluminescence and a Commission Internationale de l'Eclairage chromaticity coordinate of (0.30, 0.36).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Post-radiation nasopharyngeal necrosis (PRNN) is a severe adverse event following re-radiotherapy for patients with locally recurrent nasopharyngeal carcinoma (LRNPC) and associated with decreased ...survival. Biological heterogeneity in recurrent tumors contributes to the different risks of PRNN. Radiomics can be used to mine high-throughput non-invasive image features to predict clinical outcomes and capture underlying biological functions. We aimed to develop a radiogenomic signature for the pre-treatment prediction of PRNN to guide re-radiotherapy in patients with LRNPC.
This multicenter study included 761 re-irradiated patients with LRNPC at four centers in NPC endemic area and divided them into training, internal validation, and external validation cohorts. We built a machine learning (random forest) radiomic signature based on the pre-treatment multiparametric magnetic resonance images for predicting PRNN following re-radiotherapy. We comprehensively assessed the performance of the radiomic signature. Transcriptomic sequencing and gene set enrichment analyses were conducted to identify the associated biological processes.
The radiomic signature showed discrimination of 1-year PRNN in the training, internal validation, and external validation cohorts (area under the curve (AUC) 0.713-0.756). Stratified by a cutoff score of 0.735, patients with high-risk signature had higher incidences of PRNN than patients with low-risk signature (1-year PRNN rates 42.2-62.5% vs. 16.3-18.8%, P < 0.001). The signature significantly outperformed the clinical model (P < 0.05) and was generalizable across different centers, imaging parameters, and patient subgroups. The radiomic signature had prognostic value concerning its correlation with PRNN-related deaths (hazard ratio (HR) 3.07-6.75, P < 0.001) and all causes of deaths (HR 1.53-2.30, P < 0.01). Radiogenomics analyses revealed associations between the radiomic signature and signaling pathways involved in tissue fibrosis and vascularity.
We present a radiomic signature for the individualized risk assessment of PRNN following re-radiotherapy, which may serve as a noninvasive radio-biomarker of radiation injury-associated processes and a useful clinical tool to personalize treatment recommendations for patients with LANPC.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats
. ...Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans
. Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor-angiotensin converting enzyme II (ACE2)-as SARS-CoV.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
unc‐51‐like autophagy activating kinase 1 and 2 (Ulk1/2) regulate autophagy initiation under various stress conditions. However, the physiological functions of these Ser/Thr kinases are not well ...characterized. Here, we show that mice with liver‐specific double knockout (LDKO) of Ulk1 and Ulk2 (Ulk1/2 LDKO) are viable, but exhibit overt hepatomegaly phenotype. Surprisingly, Ulk1/2 LDKO mice display normal autophagic activity in hepatocytes upon overnight fasting, but are strongly resistant to acetaminophen (APAP)‐induced liver injury. Further studies revealed that Ulk1/2 are also dispensable for APAP‐induced autophagy process, but are essential for the maximum activation of c‐Jun N‐terminal kinase (JNK) signaling both in vivo and in isolated primary hepatocytes during APAP treatment. Mechanistically, APAP‐induced inhibition of mechanistic target of rapamycin complex 1 releases Ulk1 from an inactive state. Activated Ulk1 then directly phosphorylates and increases the kinase activity of mitogen‐activated protein kinase kinase 4 and 7 (MKK4/7), the upstream kinases and activator of JNK, and mediates APAP‐induced liver injury. Ulk1‐dependent phosphorylation of MKK7 was further confirmed by a context‐dependent phosphorylation antibody. Moreover, activation of JNK and APAP‐induced cell death was markedly attenuated in Mkk4/7 double knockdown hepatocytes reconstituted with an Ulk1‐unphosphorylatable mutant of MKK7 compared to those in cells rescued with wild‐type MKK7. Conclusion: Together, these findings reveal an important role of Ulk1/2 for APAP‐induced JNK activation and liver injury, and understanding of this regulatory mechanism may offer us new strategies for prevention and treatment of human APAP hepatotoxicity. (Hepatology 2018;67:2397‐2413).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Objectives: Epithelial‐mesenchymal transition (EMT) is an important process in tumor development, and several studies suggest that the Wnt/β‐catenin signal pathway may play an important role in EMT. ...However, there is no direct evidence showing that the Wnt/β‐catenin pathway actually determines the EMT induced by an exogenous signal. Our previous research has successfully proved that overexpression of hypoxia‐inducible factor‐1α (HIF‐1α) could induce EMT in LNCaP cells, but not in PC‐3. The present study aims to determine whether the signal of HIF‐1α for inducing prostate cancer cells to undergo EMT might possibly pass through the Wnt/β‐catenin pathway.
Methods: Epithelial‐mesenchymal transition associated proteins were detected in several human prostate carcinoma cell lines by Western blot, and then we distinguished the EMT positive cell lines from the EMT negative cell lines. Furthermore, we evaluated the possible correlation between potency of invasiveness and proliferation among these cell lines with different characteristics of EMT using Matrigel transwell and thiazolyl blue tetrazolium bromide (MTT) assays. Finally, the different expression of some critical proteins and genes in Wnt/β‐catenin signaling pathway were analyzed by Western blot and reverse transcription‐polymerase chain reaction (RT‐PCR) in these cells with different characteristics of EMT.
Results: Among several prostate cancer cell lines, PC‐3, LNCaP and PC‐3/HIF‐1α are EMT negative cell lines, whereas LNCaP/HIF‐1α and IA8 have undergone the EMT process. EMT positive cells (LNCaP/HIF‐1α and IA8) exhibit much stronger potency of invasiveness and proliferation than those of PC‐3 and LNCaP, which belong to EMT negative cells. Interestingly, although PC‐3/HIF‐1α had not completed the EMT process, it still displayed stronger potency of invasion and proliferation, resembling EMT positive cells. The protein expression level of total glycogensynthase kinase 3β (GSK‐3β) and phospho‐GSK‐3β in LNCaP/HIF‐1α, IA8 and PC‐3/HIF‐1α cells significantly decreased; however, the relative ratios of p‐GSK3β/t‐GSK3β in LNCaP/HIF‐1α, IA8 and PC‐3/HIF‐1α cells were significantly higher than PC‐3 and LNCaP. Consistently, β‐catenin protein expression increased in LNCaP/HIF‐1α and IA8 cells, but not in PC‐3/HIF‐1α; RT‐PCR confirmed these results, except for the enhanced transcription activity of β‐catenin mRNA in PC‐3/HIF‐1α.
Conclusion: Our data suggests that activation of the Wnt/β‐catenin signaling pathway correlates with the characteristic of EMT and potency of invasiveness and proliferation. This may be the critical factor that directly controls the process of EMT induced by HIF‐1α in prostate cancer cells.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The clinical prospect of sonodynamic therapy (SDT) has not been fully realized due to the scarcity of efficient sonosensitizers. Herein, we designed phthalocyanine–artesunate conjugates (e.g. ...ZnPcT4A), which could generate up to ca. 10‐fold more reactive oxygen species (ROS) than the known sonosensitizer protoporphyrin IX. Meanwhile, an interesting and significant finding of aggregation‐enhanced sonodynamic activity (AESA) was observed for the first time. ZnPcT4A showed about 60‐fold higher sonodynamic ROS generation in the aggregated form than in the disaggregated form in aqueous solutions. That could be attributed to the boosted ultrasonic cavitation of nanostructures. The level of the AESA effect depended on the aggregation ability of sonosensitizer molecules and the particle size of their aggregates. Moreover, biological studies demonstrated that ZnPcT4A had high anticancer activities and biosafety. This study thus opens up a new avenue the development of efficient organic sonosensitizers.
An interesting aggregation‐enhanced sonodynamic activity (AESA) effect was first observed based on the studies of phthalocyanine–artesunate conjugates and common organic sonosensitizers, which arose from boosted ultrasonic cavitation caused by nanostructured aggregates. We believed that the AESA effect in this work could open up a new avenue for the development of efficient sonosensitizers.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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