Despite rapid progress and wide applications of room temperature phosphorescence (RTP) materials, it is still a great challenge to optimize the RTP activity through rational structural design at a ...molecular level. Herein, a successful cationic engineering strategy is demonstrated to modulate the crystal flexibility achieving controllable RTP in a new pair of metal halides APMLZnCl4 (APML = N‐(3‐Aminopropyl)morpholine) and AEMLZnCl4 (AEML = N‐(2‐Aminoethyl)morpholine). Both halides display blue fluorescence under 365 nm UV. Comparing with longer APML+, shorter AEML+ significantly enhances crystal rigidity and restrains non‐radiative scattering, boosting photoluminescence quantum yield (PLQY) from 18.89% to 22.41%. Synchronously, enhanced crystal rigidity significantly promotes the inter‐system crossing from singlet to triplet excited states. As a consequence, AEMLZnCl4 displays long‐lived green RTP property with millisecond scale lifetime in contrast to the blank RTP activity of APMLZnCl4. Comprehensive investigations demonstrate that the energy transfer between inorganic and organic components greatly changes the redistribution of singlet and triplet excited states, resulting in distinct phosphorescence activity. The different short‐lived blue fluorescence and long‐lived green phosphorescence provide a color‐time‐dual‐resolved luminescent tag with advanced applications in anti‐counterfeiting, etc. This work highlights a new structural engineering strategy to achieve controllable RTP affording a guide to rationally design RTP materials.
A successful cationic engineering strategy is demonstrated to achieve controllable room‐temperature phosphorescence in a new pair of metal halides APMLZnCl4 and AEMLZnCl4. Comparing with the single blue fluorescence of APMLZnCl4, the enhanced crystal rigidity of AEMLZnCl4 significantly promotes the inter‐system crossing from singlet to triplet excitons, which results in dual blue fluorescence and green afterglow with higher quantum yield. The different blue fluorescence and green afterglow provide a color‐time‐dual‐resolved luminescent tag with advanced applications in anti‐counterfeiting, etc.
R-spondin proteins are identified as secreted agonists of the canonical Wnt/β-catenin signaling pathway, and leucine-rich repeat-containing G-protein-coupled receptors (LGR) are recognized as ...R-spondin receptors. The potential role of R-spondin 2 (Rspo2) and LGR4 in mediating osteogenesis remains poorly understood. In our in vitro experiments, we found that Rspo2 could promote osteogenesis through activating the Wnt signaling pathway in MC3T3-E1 cells. However, this effect of Rsop2 disappeared in the cells with functional disruption of LGR4. Meanwhile, Rspo2 significantly inhibited osteoclastogenesis and this effect of Rspo2 was dependent on the presence of osteoblasts with normal function of LGR4. In our in vivo experiments, we found that application of exogenous Rspo2 rescued the bone loss and improved the microarchitecture of bone in OVX mice. Rspo2 could be a positive regulator of bone metabolism through activating the canonical Wnt/β-catenin signaling, and LGR4 acted as a key receptor for Rspo2 to promote osteogenesis.
•R-spondin 2 promoted osteogenesis through activating the Wnt/β-catenin signaling pathway.•LGR4 acted as a pivotal receptor for R-spondin 2 to promote osteogenesis.•Rspo2 inhibited osteoclastogenesis and this effect of Rspo2 was dependent on osteoblasts.•Exogenous recombinant R-spondin 2 could rescue the bone loss in OVX mice.
It remains unclear whether the outcomes of ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PPCI) during off-hours are as favorable as ...those treated during on-hours, especially those with a first medical contact-to-device (FMC-to-device) time within 90 min. We aimed to determine whether off-hours admission impacted late outcomes in patients undergoing PPCI and with an FMC-to-device time ≤90 min.
This multicenter retrospective study included 670 STEMI patients who underwent successful PPCI and had an FMC-to-device time ≤90 min from 19 chest pain centers in Beijing from January 2018 to December 2018. Patients were divided into on-hours group and off-hours group based on their arrival time. Baseline characteristics, clinical data, and key time intervals during treatment were collected from the Quality Control & Improvement Center of Cardiovascular Intervention of Beijing by the "Heart and Brain Green Channel" app.
Overall, the median age of the patients was 58.8 years and 19.9% (133/670) were female. Of these, 296 (44.2%) patients underwent PPCI during on-hours and 374 (55.8%) patients underwent PPCI during off-hours. Compared with the on-hours group, the off-hours group had a longer FMC-to-device time and fewer patients with FMC-to-device time ≤60 min (P < 0.05). During the mean follow-up period of 24 months, a total of 64 (9.6%) participants experienced a major adverse cardiovascular event (MACE), with 28 (9.1%) in the on-hours group and 36 (9.6%) in the off-hours group (P > 0.05). According to the Cox regression analyses, off-hours admission was not a predictor of 2-year MACEs (P = 0.788). Similarly, the Kaplan-Meier curves showed that the risks of a MACE, all-cause death, reinfarction, and target vessel revascularization were not significantly different between the two groups (P > 0.05).
This real-world, multicenter retrospective study demonstrated that for STEMI patients who underwent PPCI within 90 min, off-hours admission was safe, with no difference in the risk of 2-year MACEs compared with those with on-hours admission.
Drought is frequently recorded as a result of climate warming and elevated concentration of greenhouse gases, which affect the carbon and water cycles in terrestrial ecosystems, particularly in arid ...and semi-arid regions. To identify the drought in grassland ecosystems and to determine how such drought affects grassland ecosystems in terms of carbon and water cycles across the globe, this study evaluated the drought conditions of global grassland ecosystems from 2000 to 2011 on the basis of the remotely sensed Drought Severity Index (DSI) data. The temporal dynamics of grassland carbon use efficiency (CUE) and water use efficiency (WUE), as well as their correlations with DSI, were also investigated at the global scale. Results showed that 57.04% of grassland ecosystems experienced a dry trend over this period. In general, most grassland ecosystems in the northern hemisphere (N.H.) were in near normal condition, whereas those in the southern hemisphere (S.H.) experienced a clear drying and wetting trend, with the year 2005 regarded as the turning point. Grassland CUE increased continually despite the varied drought conditions over this period. By contrast, WUE increased in the closed shrublands and woody savannas but decreased in all the other grassland types. The drought conditions affected the carbon and water use mainly by influencing the primary production and evapotranspiration of grass through photosynthesis and transpiration process. The CUE and WUE of savannas was most sensitive to droughts among all the grassland types. The areas of grassland DSI that showed significant correlations with CUE and WUE were 52.92% and 22.11% of the total grassland areas, respectively. Overall, droughts sufficiently explained the dynamics of grassland CUE, especially in the S.H. In comparison with grassland CUE, the grassland WUE was less sensitive to drought conditions at the global scale.
Silicone rubber is widely used as an insulating material. In this article, silicone rubber samples were prepared by varying the content of crosslinker (2,5-bis(tert-butyl-peroxy)-2,5-dimethylhexane, ...DBPMH), and the free volume holes in the samples were investigated by means of positron annihilation lifetime spectroscopy (PALS) measurement. The surface chemical structure, surface micromorphology and water diffusion of the samples after corona discharge treatment were studied by FTIR, SEM and EIS measurements, respectively. As the crosslinker weight ratio increased from 0.2 wt.% to 1.5 wt.%, the mean free volume hole size first decreased and then remained unchanged. However, the concentration of free volume holes did not vary as the crosslinker weight ratio increased. SEM morphologies show that surface cracks were produced on samples having high crosslinking levels after corona treatment. The water diffusion coefficient of samples after corona treatment increased from 3.13 × 10−10 cm2 s−1 to 17.68 × 10−10 cm2 s−1 in the initial immersion period, as the crosslinker weight ratio increased from 0.2 wt.% to 3.0 wt.%. The results indicated that deterioration of samples with high crosslinking levels were more serious and water repellency more easily lost. The corona resistance ability of low crosslinking level silicone rubber stems from internal low molecular weight molecules.
Developing efficient catalysts for organic pollutants degradation is crucial for remediating the current severe water environment, yet remains a great challenge. Herein, we report silver ...nanoparticles immobilized on an amine-functionalized metal-organic framework (MOFs) (Ag/UiO-66-NH
2
) as a robust catalyst for the reduction of 4-nitrophenol (4-NP). The fabricated Ag/UiO-66-NH
2
catalyst exhibits the merits of superior activities (high turnover frequency (TOF) 3.2 × 10
4
h
−1
and
k
value 6.9 × 10
−2
s
−1
), cost-effectiveness under the lowest NaBH
4
concentration (
n
NaBH4
/
n
4-NP
, 200), outstanding cyclability (10 recycling runs), and observable long-term durability, significantly outperforming previously reported catalytic system. The excellent degradation efficiency is ascribed to the favorable microenvironment modulation of unique MOF structure, which regulates the intrinsic properties of active sites and improves the electron-transfer process. Notably, the Ag/UiO-66-NH
2
also promotes the catalytic degradation of several organic pollutants at room temperature and hence could find a broad application for water remediation. This work offers a new avenue for the development of high-performance MOF-based catalysts with excellent activity and durability.
Revealing the mechanisms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry and cell-to-cell spread might provide insights for understanding the underlying mechanisms of viral ...pathogenesis, tropism, and virulence. The signaling pathways involved in SARS-CoV-2 entry and viral spike–mediated cell-to-cell fusion remain elusive. In the current study, we found that macropinocytosis inhibitors significantly suppressed SARS-CoV-2 infection at both the entry and viral spike–mediated cell-to-cell fusion steps. We demonstrated that SARS-CoV-2 entry required the small GTPase Rac1 and its effector kinase p21-activated kinase 1 by dominant-negative and RNAi assays in human embryonic kidney 293T–angiotensin-converting enzyme 2 cells and that the serine protease transmembrane serine protease 2 reversed the decrease in SARS-CoV-2 entry caused by the macropinocytosis inhibitors. Moreover, in the cell-to-cell fusion assay, we confirmed that macropinocytosis inhibitors significantly decreased viral spike–mediated cell-to-cell fusion. Overall, we provided evidence that SARS-CoV-2 utilizes a macropinocytosis pathway to enter target cells and to efficiently promote viral spike–mediated cell-to-cell fusion.
Abstract
The accurate prediction of the effect of amino acid mutations for protein–protein interactions (PPI $\Delta \Delta G$) is a crucial task in protein engineering, as it provides insight into ...the relevant biological processes underpinning protein binding and provides a basis for further drug discovery. In this study, we propose MpbPPI, a novel multi-task pre-training-based geometric equivariance-preserving framework to predict PPI $\Delta \Delta G$. Pre-training on a strictly screened pre-training dataset is employed to address the scarcity of protein–protein complex structures annotated with PPI $\Delta \Delta G$ values. MpbPPI employs a multi-task pre-training technique, forcing the framework to learn comprehensive backbone and side chain geometric regulations of protein–protein complexes at different scales. After pre-training, MpbPPI can generate high-quality representations capturing the effective geometric characteristics of labeled protein–protein complexes for downstream $\Delta \Delta G$ predictions. MpbPPI serves as a scalable framework supporting different sources of mutant-type (MT) protein–protein complexes for flexible application. Experimental results on four benchmark datasets demonstrate that MpbPPI is a state-of-the-art framework for PPI $\Delta \Delta G$ predictions. The data and source code are available at https://github.com/arantir123/MpbPPI.
Doubled haploid technology has been widely applied to multiple plant species and is recognized as one of the most important technologies for improving crop breeding efficiency. Although mutations in ...MATRILINEAL/Zea mays PHOSPHOLIPASE A1/NOT LIKE DAD (MTL/ZmPLA1/NLD) and Zea mays DOMAIN OF UNKNOWN FUNCTION 679 MEMBRANE PROTEIN (ZmDMP) have been shown to generate haploids in maize, knowledge of the genetic basis of haploid induction (HI) remains incomplete. Therefore, cloning of new genes underlying HI is important for further elucidating its genetic architecture. Here, we found that loss-of-function mutations of Zea mays PHOSPHOLIPASE D3 (ZmPLD3), one of the members from the phospholipase D subfamily, could trigger maternal HI in maize. ZmPLD3 was identified through a reverse genetic strategy based on analysis of pollen-specifically expressed phospholipases, followed by validation through the clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR-Cas9) system. Mutations of ZmPLD3 resulted in a haploid induction rate (HIR) similar to that of mtl/zmpla1/nld and showed synergistic effects rather than functional redundancy on tripling the HIR (from 1.19% to 4.13%) in the presence of mtl/zmpla1/nld. RNA-seq profiling of mature pollen indicated that a large number of pollen-specific differentially expressed genes were enriched in processes related to gametogenesis development, such as pollen tube development and cell communication, during the double-fertilization process. In addition, ZmPLD3 is highly conserved among cereals, highlighting the potential application of these in vivo haploid-inducer lines for other important crop plant species. Collectively, our discovery identifies a novel gene underlying in vivo maternal HI and provides possibility of breeding haploid inducers with further improved HIR.