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Quantum-size metal clusters with multiple delocalized electrons could support collective plasmon excitation, and thus, theoretically, coupling of plasmons in the few-atom limit might exist between assembled metal clusters, while currently few experimental observations about this phenomenon have been reported. Here we examined the optical absorption of DNA-templated Ag nanoclusters (DNA-AgNCs) assembled through DNA hybridization and found their absorption peaks were sensitive to the assembled distances, which share common characteristics with classical plasmon coupling. Dipolar charge distribution, multiple transition contributed optical absorption, and strongly enhanced electric field simulated by time-dependent density functional theory (TDDFT) indicated the origin of the absorption of individual DNA-AgNCs is a plasmon. The consistency of the peak-shifting trend between experimental and simulation results for assembled DNA-AgNCs suggested the possible presence of plasmon coupling. Our data imply the possibility for quantum-size structures to support plasmon coupling and also show that DNA-AgNCs possess the potential to be promising materials for construction of plasmon-coupling devices with ultrasmall size, site-specific and stoichiometric binding abilities, and biocompatibility.

Van der Waals heterostructures offer a new platform to engineer the properties of two-dimensional (2D) materials. Large scale heterostructures of MoS 2 and ReSe 2 monolayers were fabricated and fully investigated using time-resolved terahertz (THz) spectroscopy (TRTS), THz emission spectroscopy, and optical pump-probe spectroscopy (OPPS). The charge transfer (CT) time was estimated to be 170 fs by fitting the photocurrent model to the emitted THz pulse. In TRTS, free carrier dominated dynamic has been unambiguous investigated. In addition, it is found that interlayer and intralayer excitons are dominant in carrier dynamics before and after CT saturation in the OPPS. The intriguing results pave the way for further understanding the ultrafast carrier relaxation dynamics in 2D heterostructures and potential applications in opto-electronic devices.

Photoreceptor connecting cilium (CC) is structurally analogous to the transition zone (TZ) of primary cilia and gates the molecular trafficking between the inner and the outer segment (OS). Retinal dystrophies with underlying CC defects are manifested in a broad array of syndromic conditions known as ciliopathies as well as non-syndromic retinal degenerations. Despite extensive studies, protein trafficking across the photoreceptor CC is largely unknown. Here we genetically inactivated mouse Tmem138, a gene encoding a ciliary membrane protein localized to the ciliary TZ and linked to Joubert syndrome (JBTS). Germline deletion of Tmem138 abolished OS morphogenesis followed by rapid photoreceptor degeneration. Tmem138 was found localized to the photoreceptor CC and, accordingly, the molecular compartments of the CC and axoneme of the mutant photoreceptors were altered despite ciliogenesis proceeding normally at the early stage of photoreceptor development. To gain further insights into Tmem138 function in OS biogenesis, we focused on trafficking of rhodopsin, the most abundant protein of the OS. Mislocalization of rhodopsin was readily observed as early as P5 in the mutant photoreceptors prior to growth of the OS. Ablation of Tmem138 in mature rods recapitulated the molecular changes in the germline mutants, causing well-formed outer segment discs to disintegrate accompanied by mislocalization of rhodopsin in the cell body. Furthermore, Tmem138 interacted with rhodopsin, and two additional CC compartment proteins Ahi1 and Tmem231, which were both altered in the mutant photoreceptors. Taken together, these results suggest that Tmem138 has a distinct role in gating the transport of rhodopsin and likely other OS bound proteins through formation of CC transport complex(es).

Pressure effects on photocarrier dynamics such as interband relaxations and intraband cooling in GaAs have been investigated using in situ time-resolved terahertz spectroscopy with a diamond anvil cell. The interband photocarrier lifetime significantly decreases by nearly two orders of magnitude as the external hydrostatic pressure is increased up to 10 GPa. Considerable pressure tuning for the intervalley scattering processes has also been observed, and the time constants under different pressures are extracted based on the three-state rate model. This work provides new perspectives on tailoring nonequilibrium carrier dynamics in semiconductors using hydrostatic pressure and may serve as the impetus for the development of high-pressure terahertz spectroscopy.

Many evidences for gas hydrate bearing sediments had been found in the continental slope of the East China Sea, such as bottom simulating reflections (BSRs), undersea gas springs, pyrite associated with methane leakage, mud diapirs/mud volcanos, bottom-water methane anomalies and so on. In this study, six key stratigraphic interfaces including T0 (seafloor), T1 (LGM, 23 kyr B.P.), T2 (2.58 Myr), T3 (5.33 Myr), T4 (11.02 Myr) and T5 (16.12 Myr) were identified, and then five third-order sequences of SQIII1 to SQIII5 were divided. However, T5 in southern continental slope is not found, which shows that the middle-northern Okinawa Trough had begun to rift in the early Miocene, earlier than the southern segment. Four system tracts including lowstand systems tract (LST), transgressive systems tract (TST), highstand systems tract (HST) and falling stage systems tract (FSST) are further divided. The marine erosion interface of 11.02 Myr and regressive unconformity interface of 23 kyr B.P. indicate two large-scale sea level drop events in the research area. Seven typical seismic facies identified in the continental slope are continental shelf-edge deltas, littoral fluvial-delta plains, incised channels or submarine canyons, slope fans, submarine fans or coastal sandbars, littoral-neritic finegrained sediments, mud volcanos and some other geological bodies respectively. The minimum water depth for hydrate occurrence in the Okinawa Trough is 630 m, and the thickness of gas hydrate stability zone in continental slope is between 0 and 590 m. The calculated bottom boundary of hydrate stability zone is slightly deeper than BSRs on the seismic sections. The re-depositional turbidite sand bodies, such as canyon channels, slope fans and submarine fans developed in Quaternary strata, are the predominant hydrate reservoirs. According to developing process, the dynamic accumulation of hydrate systems can be divided into three evolutionary stages including canyon erosion and hydrate stability zone migration stage, sediments destabilizing and methane leakage stage, and channel filling and hydrate re-occurrence stage.

A covalent organic framework, Schiff base network-1 (SNW-1), was synthesized and incorporated into cellulase based poly(glycidyl methacrylate-co-ethylene dimethacrylate) (cellulase@poly(GMA-EDMA-SNW-1)) monolith to afford a novel chiral stationary phase for capillary electrochromatography (CEC). SNW-1 is attractive as a stationary phase for CEC because it not only features high surface areas but also provides conjugate structures and abundant amine groups to give π-π electrostatic stacking and hydrogen bonding property. Incorporation of SNW-1 into monolithic column could improve the column efficiency and increase the interactions between the tested racemates and the stationary phase thus significantly improved their CEC separation. The obtained monoliths were characterized by scanning electron microscopy, elemental analysis and nitrogen adsorption. Moreover, effects of SNW-1 concentration, immobilization pH of cellulase and CEC conditions were also investigated. Under the optimized conditions, the cellulase@poly(GMA-EDMA-SNW-1) monolith exhibited excellent enantioseparation performance for eight pairs of different classes of chiral drugs including β-blockers, antihistamines and anticoagulants. Satisfactory repeatability was achieved with relative standard deviations for intra-day, inter-day and column-to-column runs less than 4.5%, and batch-to-batch runs less than 6.8%. The experiment results reveal that the combination of the versatile features of monoliths and unique properties of SNW-1 could be a promising strategy for chiral separation.

Excessive mechanical tension can lead to the degeneration of endplate chondrocytes. The presence of tension-sensitive circRNA_0058097 molecules has been detected in human endplate chondrocytes, where it was found to be a potential competing endogenous RNA. Indeed, inhibiting the expression of circRNA_0058097 effectively enhanced the stress resistance of endplate chondrocytes, suggesting that it may be an important trigger point for the degeneration of endplate cartilage. Through a series of experiments, we reveal that circRNA_0058097 can upregulate the expression of downstream target gene histone deacetylase 4 by sponge adsorption of miR-365a-5p, which promoted morphological changes of endplate chondrocytes, and increased extracellular matrix degradation and degeneration of endplate cartilage. Therefore, circRNA_0058097 may provide a new way to prevent and treat endplate cartilage degeneration.

O-GlcNAcylation and phosphorylation are two posttranslational modifications that antagonistically regulate protein function. However, the regulation of and the cross talk between these two protein modifications are poorly understood in plants. Here we investigated the role of O-GlcNAcylation during vernalization, a process whereby prolonged cold exposure promotes flowering in winter wheat (Triticum aestivum), and analyzed the dynamic profile of O-GlcNAcylated and phosphorylated proteins in response to vernalization. Altering O-GlcNAc signaling by chemical inhibitors affected the vernalization response, modifying the expression of VRN genes and subsequently affecting flowering transition. Over a vernalization time-course, O-GlcNAcylated and phosphorylated peptides were enriched from winter wheat plumules by Lectin weak affinity chromatography and iTRAQ-TiO2, respectively. Subsequent mass spectrometry and gene ontology term enrichment analysis identified 168 O-GlcNAcylated proteins that are mainly involved in responses to abiotic stimulus and hormones, metabolic processing, and gene expression; and 124 differentially expressed phosphorylated proteins that participate in translation, transcription, and metabolic processing. Of note, 31 vernalization-associated proteins were identified that carried both phosphorylation and O-GlcNAcylation modifications, of which the majority (97%) exhibited the coexisting module and the remainder exhibited the potential competitive module. Among these, TaGRP2 was decorated with dynamic O-GlcNAcylation (S87) and phosphorylation (S152) modifications, and the mutation of S87 and S152 affected the binding of TaGRP2 to the RIP3 motif of TaVRN1 in vitro. Our data suggest that a dynamic network of O-GlcNAcylation and phosphorylation at key pathway nodes regulate the vernalization response and mediate flowering in wheat.

Aims The interplay between bone marrow stromal cells (BMSCs) and acute myeloid leukemia (AML) cells plays a critical role in AML drug resistance by secreting growth factors, cytokines, and extracellular vesicles. As kind of extracellular vesicles, exosomes consist of proteins and RNAs and regulate communication among cells. Main methods The BMSCs, HS5 cells, and AML cells were co-cultivated with transwell membranes, and treated with different doses of AML chemotherapy drug, etoposide. Key findings Findings of our research proved that co-cultivation of BMSCs with AML cells defended AML against cell death triggered via etoposide, without having an impact on cell growth. An increase in the expression of the 70 kDa heat shock proteins (HSP70) as well as lysosomal associated membrane protein 3 (CD63) was observed in the exosomes from BMSC and AML, co-cultivated in conditioned media. Exosome repression in BMSC and AML co-cultivating system rebuilt the sensitivity of the KG1A cells to apoptosis triggered via etoposide, indicating that exosome modulated drug resistance in AML. Our study proved that exosomes arising from KG1A cells could propel BMSCs to generate IL-8, which could regulate the effect of etoposide treatment. Furthermore, IL-8 inhibition by its antibody increased the sensitivity of AML cells to cell death triggered via etoposide. Significance Our results suggested that exosomes secreted by AML cells is an essential communicator for the interaction of BMSCs and AML, which can protect AML cells from chemotherapy drug induced apoptosis.

Vernalisation is the programmed physiological process in which prolonged cold-exposure provides competency to flower in plants; widely found in winter and biennial species, such as Arabidopsis, fruit trees, vegetables and wheat. This phenomenon is regulated by diverse genetic networks, and memory of vernalisation in a life cycle mainly depends on epigenetic mechanisms. However, less is known about how to count winter-dosage for flowering in plants. Here, we compare the vernalisation genetic framework between the dicots Arabidopsis, temperate grasses, wheat, barley and Brachypodium. We discuss vernalisation mechanisms involving crosstalk between phosphorylation and O-GlcNAcylation modification of key proteins, and epigenetic modifications of the key gene VRN1 in wheat. We also highlight the potential evolutionary origins of vernalisation in various species. Current progress toward understanding the regulation of vernalisation requirements provides insight that will inform the design of molecular breeding strategies for winter crops. A Review summarizes our current understandings of vernalization mechanisms by comparing the vernalization genetic framework between Arabidopsis and grasses, and highlights the potential evolutionary origins of vernalization in various species.

Capillary tubes are widely used in micro-devices because of their tubular structure, high efficiency, small dead volume and good flexibility. In micro-devices, such as miniaturized chromatography and solid phase microextraction, capillary tubes play a crucial role as stationary phases, carriers or adsorbents for complex sample analysis. Many strategies have been proposed to improve their performance and extend their application by surface engineering. One of the most promising strategies is mussel-inspired chemistry, polydopamine surface modification, which has become a powerful tool in capillary fabrication and modification, as it provides a versatile platform for the construction of diverse hybrid materials with specific functionalities. This review focuses on recent advances in the fabrication of polydopamine-coated capillary tubes for microextraction and miniaturized chromatography systems. In the first part, the preparation strategies of polydopamine coatings are discussed in detail. Next, the application of polydopamine as a novel capillary coating are described. Finally, a conclusion and the key issues that exist in this emerging field are given.

Background Disruption of microbiota balance may result in severe diseases in animals and phytotoxicity in plants. While substantial concerns have been raised on engineered nanomaterial (ENM) induced hazard effects (e.g., lung inflammation), exploration of the impacts of ENMs on microbiota balance holds great implications. Results This study found that rare earth oxide nanoparticles (REOs) among 19 ENMs showed severe toxicity in Gram-negative (G−) bacteria, but negligible effects in Gram-positive (G+) bacteria. This distinct cytotoxicity was disclosed to associate with the different molecular initiating events of REOs in G− and G+ strains. La2O3 as a representative REOs was demonstrated to transform into LaPO4 on G− cell membranes and induce 8.3% dephosphorylation of phospholipids. Molecular dynamics simulations revealed the dephosphorylation induced more than 2-fold increments of phospholipid diffusion constant and an unordered configuration in membranes, eliciting the increments of membrane fluidity and permeability. Notably, the ratios of G−/G+ reduced from 1.56 to 1.10 in bronchoalveolar lavage fluid from the mice with La2O3 exposure. Finally, we demonstrated that both IL-6 and neutrophil cells showed strong correlations with G−/G+ ratios, evidenced by their correlation coefficients with 0.83 and 0.92, respectively. Conclusions This study deciphered the distinct toxic mechanisms of La2O3 as a representative REO in G− and G+ bacteria and disclosed that La2O3-induced membrane damages of G− cells cumulated into pulmonary microbiota imbalance exhibiting synergistic pulmonary toxicity. Overall, these findings offered new insights to understand the hazard effects induced by REOs.

Background Encephalomyocarditis virus, member of Cardiovirus genus within Picornaviridae family, is an important pathogen that infects different domestic and wild animals. However, the molecular mechanism of its entry remains unclear. In this study, we investigated the mechanism of EMCV infectivity in relation to endocytic pathway using BHK-21 cells. Methods The function of numerous cellular key factors implicated in the various endocytic mechanisms were systematically explored using chemical inhibitors. Furthermore, RNA interference (RNAi) as well as the overexpression of dominant protein combined to virus infectivity assays, and confocal microscopy was used to examine EMCV infection in details. Results The results indicated that the EMCV entry into BHK-21 cells depends on caveolin, dynamin, and actin but not clathrin nor macropinocytosis pathways. The effects of overexpression and knockdown of caveolin-1, one components of the caveolae, was examined on EMCV infection. The results showed that EMCV infection was positive correlation with caveolin-1 expression. Confocal microscopy analysis and internalization assay showed that caveolin-1 is required at the early stage of EMCV infection. Conclusions Caveolin-1, dynamin, and actin-dependent endocytosis pathways are necessary for EMCV infection in vitro.

Type I interferon (IFN)-mediated antiviral responses are critical for modulating host-virus responses, and indeed, viruses have evolved strategies to antagonize this pathway. Encephalomyocarditis virus (EMCV) is an important zoonotic pathogen, which causes myocarditis, encephalitis, neurological disease, reproductive disorders, and diabetes in pigs. This study aims to understand how EMCV interacts with the IFN pathway. EMCV circumvents the type I IFN response by expressing proteins that antagonize cellular innate immunity. Here, we show that EMCV VP2 is a negative regulator of the IFN-β pathway. This occurs via the degradation of the MDA5-mediated cytoplasmic double-stranded RNA (dsRNA) antiviral sensing RIG-I-like receptor (RLR) pathway. We show that structural protein VP2 of EMCV interacts with MDA5, MAVS, and TBK1 through its C terminus. In addition, we found that EMCV VP2 could significantly degrade RLRs by the proteasomal and lysosomal pathways. For the first time, EMCV VP2 was shown to play an important role in EMCV evasion of the type I IFN signaling pathway. This study expands our understanding that EMCV utilizes its capsid protein VP2 to evade the host antiviral response. IMPORTANCE Encephalomyocarditis virus is an important pathogen that can cause encephalitis, myocarditis, neurological diseases, and reproductive disorders. It also causes huge economic losses for the swine industry worldwide. Innate immunity plays an important role in defending the host from pathogen infection. Understanding pathogen microorganisms evading the host immune system is of great importance. Currently, whether EMCV evades cytosolic RNA sensing and signaling is still poorly understood. In the present study, we found that viral protein VP2 antagonized the RLR signaling pathway by degrading MDA5, MAVS, and TBK1 protein expression to facilitate viral replication in HEK293 cells. The findings in this study identify a new mechanism for EMCV evading the host’s innate immune response, which provide new insights into the virus-host interaction and help develop new antiviral approaches against EMCV.

Chronic lymphocytic leukemia (CLL) is a clonal proliferative disease of mature B lymphocytes. To further improve the prognosis of patients, it is necessary to further elucidate the pathogenesis of CLL and find more effective therapeutic targets. Nuclear Factor of Activated T cells 5 (NFAT5) is the major activated transcription factor (TF) upon osmotic pressure increase in mammalian cells, and it also regulates many target genes to affect various cellular functions. The effects of NFAT5 on tumor growth and metastasis have also been widely revealed. However, the effects of NFAT5 on the progression of CLL are still unclear. In this study, we found abnormally high expression of NFAT5 in human CLL patients. Additionally, NFAT5 depletion suppressed proliferation and stimulated apoptosis of CLL cells. Our data further confirmed NFAT5 regulated AQP5 expression and the phosphorylation of p38 MAPK. We also found that AQP5 overexpression reversed the inhibitory effect of NFAT5 depletion on cell proliferation in CLL cells. Furthermore, we revealed STUB1 directly bound to NFAT5 and promoted its degradation. Taken together, our results indicate the involvement of NFAT5 in CLL progression and suggest that NFAT5 could serve as a promising therapeutic target for CLL treatment.

Although ferroptosis is an iron-dependent cell death mechanism involved in the development of some severe diseases (e.g., Parkinsonian syndrome, stroke and tumours), the combination of nanotechnology with ferroptosis for the treatment of these diseases has attracted substantial research interest. However, it is challenging to differentiate nanoparticle-induced ferroptosis from other types of cell deaths (e.g., apoptosis, pyroptosis, and necrosis), elucidate the detailed mechanisms and identify the key property of nanoparticles responsible for ferroptotic cell deaths. Therefore, a summary of these aspects from current research on nano-ferroptosis is important and timely. In this review, we endeavour to summarize some convincing techniques that can be employed to specifically examine ferroptotic cell deaths. Then, we discuss the molecular initiating events of nanosized ferroptosis inducers and the cascade signals in cells, and therefore elaborate the ferroptosis mechanisms. Besides, the key physicochemical properties of nano-inducers are also discussed to acquire a fundamental understanding of nano-structure-activity relationships (nano-SARs) involved in ferroptosis, which may facilitate the design of nanomaterials to deliberately tune ferroptosis. Finally, future perspectives on the fundamental understanding of nanoparticle-induced ferroptosis and its applications are provided.

We perform femtosecond pump-probe spectroscopy to in situ investigate the ultrafast photocarrier dynamics in bilayer graphene and observe an acceleration of energy relaxation under pressure. In combination with in situ Raman spectroscopy and ab initio molecular dynamics simulations, we reveal that interlayer shear and breathing modes have significant contributions to the faster hot-carrier relaxations by coupling with the in-plane vibration modes under pressure. Our work suggests that further understanding the effect of interlayer interaction on the behaviors of electrons and phonons would be critical to tailor the photocarrier dynamic properties of bilayer graphene.

Additional file 1.

Background: Encephalomyocarditis virus, member of Cardiovirus genus within Picornaviridae family, is an important pathogen that infects different domestic and wild animals. However, the molecular mechanism of its entry remains unclear. In this study, we investigated the mechanism of EMCV infectivity in relation to endocytic pathway using BHK-21 cells. Methods: The function of numerous cellular key factors implicated in the various endocytic mechanisms were systematically explored using chemical inhibitors. Furthermore, RNA interference (RNAi) as well as the overexpression of dominant protein combined to virus infectivity assays, and confocal microscopy was used to examine EMCV infection in details. Results: The results indicated that the EMCV entry into BHK-21 cells depends on caveolin, dynamin, and actin but not clathrin nor macropinocytosis pathways. The effects of overexpression and knockdown of caveolin-1, one components of the caveolae, was examined on EMCV infection. The results showed that EMCV infection was positive correlation with caveolin-1 expression. Confocal microscopy analysis and internalization assay showed that caveolin-1 is required at the early stage of EMCV infection. Conclusions: Caveolin-1, dynamin, and actin-dependent endocytosis pathways are necessary for EMCV infection in vitro.

Objective To investigate if the modification of human adipose-derived mesenchymal stem cells (hADSCs) by the antioxidants superoxide dismutase 2 (Sod2) and catalase (Cat) can attenuate the pathological conditions of intervertebral disc degeneration (IVD). Methods In vitro, MTT assay and qRT-PCR was used to detect cell proliferation and gene expressions in hADSCs transduced with Ad-null (an adenovirus vector containing no transgene expression cassette), Ad-Sod2 (recombinant adenovirus Sod2) and Ad-Cat. IVD mouse models were generated by needle puncture and treated with hADSCs with/without Ad-null/Ad-Sod2/Ad-Cat. X-ray evaluation, magnetic resonance imaging (MRI) analysis, histological analysis, immunohistochemistry, Western blots, ELISAs and qRT-PCR were performed. Results hADSCs transduced with Ad-Sod2 and Ad-Cat showed enhanced cell proliferation with the upregulation of SOX9, ACAN, and COL2. In vivo, IVD mice injected with hADSCs showed increased disc height index, MRI index and mean T2 intensities, as well as the attenuated histologic grading of the annulus fibrosus (AF) and NP accompanied by the upregulation of GAG and COL2, which were further improved in the Ad-Sod2 hADSC + IVD and Ad-Cat hADSC + IVD groups. Furthermore, the increased expression of IL-1β, IL-6 and TNF-α was reduced in IVD mice injected with hADSCs. Compared with the hADSC + IVD group, the Ad-Sod2 hADSC/Ad-Cat hADSC + IVD groups had lower expression of pro-inflammatory factors. Conclusion Modification of hADSCs by the antioxidants Sod2 and Cat improved the pathological condition of intervertebral disc tissues with increased GAG and COL2 expression, as well as reduced inflammation, thereby demonstrating a therapeutic effect in IVD.

Background: Encephalomycarditis virus is a member of Cardiovirus, belongs to the family Picornaviridae, and can infect different domestic and wild animals. However, the endocytic pathway by which EMCV infected BHK-21 cells remains unclear. In this study, endocytic pathway used by EMCV replication in BHK-21 cells was elucidated.Methods: The function of numerous cellular key factors implicated in the various endocytic mechanisms known to date were systematic detected using chemical inhibitors. Furthermore, RNA interference (RNAi) silencing, the overexpression of dominant protein combined to virus infectivity assays, and confocal imaging to examine which cellular molecules involved in the infection process were also analyzed.Results: The results indicated that the EMCV replication was related to endocytosis. However, neither clathrin nor macropinocytosis pathway was involved in virus infection. QRT-PCR and WB analyses showed that caveolin-1 were significantly up-regulated in EMCV infected BHK-21 cells. Immune-fluorescent confocal microscopy analysis showed that caveolin-1 was temporally co-localized with EMCV VP1 at the early stage of EMCV infection. Overexpressed caveolin-1 or downregulated caveolin-1 expression influenced the EMCV infection. Furthermore, EMCV infection was found to depend on dynamin and actin by chemical inhibitors resulted in diminished of virus infection.Conclusions: EMCV replication in BHK-21 cells via caveolin-1, dynamin, and actin-dependent endocytosis pathways.

Background: Although substantial concerns about the inflammatory effects of engineered nanomaterial (ENM) have been raised, experimentally assessing toxicity of various ENMs is challenging and time-consuming. Alternatively, quantitative structure–activity relationship (QSAR) models have been employed to assess nanosafety. However, no previous attempt has been made to predict the inflammatory potential of ENMs. Objectives: By employing metal oxide nanoparticles (MeONPs) as a model ENM, we aimed to develop QSAR models for prediction of the inflammatory potential by their physicochemical properties. Methods: We built a comprehensive data set of 30 MeONPs to screen a proinflammatory cytokine interleukin (IL)-1 beta (IL-1β) release in THP-1 cell line. The in vitro hazard ranking was validated in mouse lungs by oropharyngeal instillation of six randomly selected MeONPs. We established QSAR models for prediction of MeONP-induced inflammatory potential via machine learning. The models were further validated against seven new MeONPs. Density functional theory (DFT) computations were exploited to decipher the key mechanisms driving inflammatory responses of MeONPs. Results: Seventeen out of 30 MeONPs induced excess IL-1β production in THP-1 cells. In vivo disease outcomes were highly relevant to the in vitro data. QSAR models were developed for inflammatory potential, with predictive accuracy (ACC) exceeding 90%. The models were further validated experimentally against seven independent MeONPs (ACC=86%). DFT computations and experimental results further revealed the underlying mechanisms: MeONPs with metal electronegativity lower than 1.55 and positive ζ-potential were more likely to cause lysosomal damage and inflammation. Conclusions: IL-1β released in THP-1 cells can be an index to rank the inflammatory potential of MeONPs. QSAR models based on IL-1β were able to predict the inflammatory potential of MeONPs. Our approach overcame the challenge of time- and labor-consuming biological experiments and allowed for computational assessment of MeONP inflammatory potential by characterization of their physicochemical properties. https://doi.org/10.1289/EHP6508

Highlights • Type I IFN and IFITMs showed marked upregulation following PRV infection in PK15 cells. • IFITM proteins restricted PRV infection by interfering virus binding and entry. • IFITM2-mediated inhibition of PRV entry requires the cholesterol pathway., Pseudorabies virus (PRV) is one of the most destructive swine pathogens and leads to huge economic losses to the global pig industry. Type I interferons (IFNs) plays a pivotal role in the innate immune response to virus infection via induction of a series of interferon-stimulated genes (ISGs) expression. IFN-induced transmembrane (IFITM) proteins, a group of ISGs, are important host self-restriction factors, possessing a broad spectrum of antiviral effects. They are known confer resistance to a variety of RNA and DNA viruses. However, little is known about the role of IFITMs in PRV infection. In this study, we show that IFITM is crucial for controlling PRV infection and that IFITM proteins can interfere with PRV cell binding and entry. Furthermore, we showed that IFITM2-mediated inhibition of PRV entry requires the cholesterol pathway. Collectively, these results provide insight into the anti-PRV role of IFITM proteins and this inhibition possible associated with the change of cholesterol in the endosome, further underlying the importance of cholesterol in virus infection.

The use of aptamers in bioanalytical and biomedical applications exploits their ability to recognize cell surface protein receptors. Targeted therapeutics and theranostics come to mind in this regard. However, protein receptors occur on both cancer and normal cells; as such, aptamers are now taxed with identifying high vs. low levels of protein expression. Inspired by the flexible template mechanism and elegant control of natural nucleic acid-based structures, we report an allosteric regulation strategy for constructing a structure-switching aptamer for enhanced target cell recognition by engineering aptamers with DNA intercalated motifs (i-motifs) responsive to the microenvironment, such as pH. Structure-switching sensitivity can be readily tuned by manipulating i-motif sequences. However, structure-switching sensitivity is difficult to estimate, making it equally difficult to effectively screen modified aptamers with the desired sensitivity. To address this problem, we selected a fluorescent probe capable of detecting G-quadruplex in complicated biological media., The authors have successfully developed allosterically regulated, and binding switchable aptamers from conventional G-quadruplex aptamer that can be readily, economically built, and can achieve more precise recognition of target cells according to the cellular microenvironment.

The application of NIR‐II emitters for gastrointestinal (GI) tract imaging remains challenging due to fluorescence quenching in the digestive microenvironment. Herein, we report that red‐shifting of the fluorescence emission of Au nanoclusters (AuNCs) into NIR‐II region with improved quantum yields (QY) could be achieved by engineering a protein corona structure consisting of a ribonuclease‐A (RNase‐A) on the particle surfaces. RNase‐A‐encapsulated AuNCs (RNase‐A@AuNCs) displayed emissions at 1050 nm with a 1.9 % QY. Compared to rare earth and silver‐based NIR‐II emitters, RNase‐A@AuNCs had excellent biocompatibility, showing >50‐fold higher sensitivity in GI tract, and migrated homogenously during gastrointestinal peristalsis to allow visualization of the detailed structures of the GI tract. RNase‐A@AuNCs could successfully examine intestinal tumor mice from healthy mice, indicating a potential utility for early diagnosis of intestinal tumors.

It is a big challenge to reveal the intrinsic cause of a nanotoxic effect due to diverse branches of signaling pathways induced by engineered nanomaterials (ENMs). Biotransformation of toxic ENMs involving biochemical reactions between nanoparticles (NPs) and biological systems has recently attracted substantial attention as it is regarded as the upstream signal in nanotoxicology pathways, the molecular initiating event (MIE). Considering that different exposure routes of ENMs may lead to different interfaces for the arising of biotransformation, this work summarizes the nano-bio interfaces and dose calculation in inhalation, dermal, ingestion, and injection exposures to humans. Then, five types of biotransformation are shown, including aggregation and agglomeration, corona formation, decomposition, recrystallization, and redox reactions. Besides, the characterization methods for investigation of biotransformation as well as the safe design of ENMs to improve the sustainable development of nanotechnology are also discussed. Finally, future perspectives on the implications of biotransformation in clinical translation of nanomedicine and commercialization of nanoproducts are provided.

The inner region of solid tumors is found to be high-pressure, hypoxic, and immunosuppressive, providing a breeding ground for tumor aggressiveness and metastasis. While intratumoral accumulation of nanomedicines combined with immunomodulation would significantly enhance therapeutic efficacy, such potential is challenged by the compressed environment and distinct heterogeneity of the tumor bulk. By using an apoptotic body (AB) as the carrier, we develop an effective and universal intratumoral nanomedicine delivery system for the long-lasting remission of tumors. Our results show that the AB-encapsulated nanomedicine (using CpG immunoadjuvant-modified gold-silver nanorods as a model), after intravenous injection, can be specifically phagocytosed by inflammatory Ly-6C+ monocytes, which then actively infiltrate the tumor center via their natural tumor-homing tendency. With the integration of AB-facilitated intratumoral accumulation, the nanorod-based photothermal effect, and CpG-promoted immunostimulation, this cell-mediated delivery system can not only efficiently ablate primary tumors but also elicit a potent immunity to prevent tumors from metastasizing and recurring.

The negative impacts of aggressive environment on the durability of concrete materials have raised great concerns in recent years. Although the nano modification has been considered as a promising approach to enhance the durability of concrete materials with exposure to synergistic attacks from complicated aggressive environment, the investigation of the impacts of various chemicals on low dosage nano modified concrete, especially along with freeze/thaw and wet/dry cycles, is still very limited. In this study, the impacts of sodium chloride (NaCl) and potassium acetate (KAc) on laboratory fabricated concrete samples, which were modified with low dosage of nano SiO2 and nano TiO2 particles, were investigated. The mass loss, flexural strength, compressive strength, and relative dynamic modulus of elasticity were tested to evaluate the deterioration of low dosage nano modified concrete samples after exposure to F/T along with W/D cycles in KAc and NaCl solutions. The microstructure analyses demonstrate that both NaCl and KAc have negative impacts on the durability of concrete samples after F/T and W/D cycles. However, the addition of low dosage nano particles shows a distinctive enhancement of environment resistance of concrete samples. Through the microstructure analysis, three potential reasons were presented to help elucidate the deterioration mechanisms of concrete with exposure to aggressive environment. Moreover, based on the microstructure analysis, the different modification mechanisms corresponding to various nano materials were presented. This study not only shows the possibility of low dosage nano modification on the durability enhancement of concrete, but also provides potential modification mechanisms which help to design and fabricate durable concrete materials with exposure to complicated aggressive environment.

G-quadruplex has attracted considerable attention due to their prevalent distribution in functional genomic regions and transcripts, which can importantly influence biological processes such as regulation of telomere maintenance, gene transcription and gene translation. Artificial receptor study has been developed for accurate identification of G-quadruplex from DNA species, since it is important for the G-quadruplex related basic research, clinical diagnosis, and therapy. Herein, fluorescent dye ThT-E, a derivative of the known fluorescence probe Thioflavin T (ThT), was designed and synthesized to effectively differentiate various G-quadruplex structures from other nucleic acid forms. Compared with methyl groups in ThT, three ethyl groups were introduced to ThT-E, which leads to strengthened affinity, selectivity and little inducing effect on the G-quadruplex formation. More importantly, ThT-E could be served as a visual tool to directly differentiate G-quadruplex solution even with naked eyes under illumination of ultraviolet light. Thus, this probe reported herein may hold great promise for high-throughput assay to screen G-quadruplex, which may widely apply to G-quadruplex-based potential diagnosis and therapy.

Summary Plants modify their development to adapt to their environment, protecting themselves from detrimental conditions such as chilling stress by triggering a variety of signaling pathways; however, little is known about how plants coordinate developmental patterns and stress responses at the molecular level.Here, we demonstrate that interacting transcription factors OsMADS57 and OsTB1 directly target the defense gene OsWRKY94 and the organogenesis gene D14 to trade off the functions controlling/moderating rice tolerance to cold.Overexpression of OsMADS57 maintains rice tiller growth under chilling stress. OsMADS57 binds directly to the promoter of OsWRKY94, activating its transcription for the cold stress response, while suppressing its activity under normal temperatures. In addition, OsWRKY94 was directly targeted and suppressed by OsTB1 under both normal and chilling temperatures. However, D14 transcription was directly promoted by OsMADS57 for suppressing tillering under the chilling treatment, whereas D14 was repressed for enhancing tillering under normal condition.We demonstrated that OsMADS57 and OsTB1 conversely affect rice chilling tolerance via targeting OsWRKY94.Our findings highlight a molecular genetic mechanism coordinating organogenesis and chilling tolerance in rice, which supports and extends recent work suggesting that chilling stress environments influence organ differentiation.

A new mixed selector chiral stationary phase (CSP) was prepared with co-immobilized human serum albumin and cellulase on a poly(glycidylmethacrylate-co-ethylene glycol dimethacrylate) (poly(GMA-co-EDMA)) monolith and the evaluation of its usefulness in chiral separation research was presented. For comparison, two single selector chiral stationary phases (CSPs) were also fabricated with the corresponding proteins. The enantioseparation ability of these CSPs was investigated by capillary electrochromatography (CEC) with various racemates. The mixed selector CSP exhibited a broader range of enantioselectivities than the single selectors and it could separate 10 chiral analytes while the two single selector CSPs resolved 3 and 8 respectively. Moreover, for (±)-warfarin, the enantioresolution was improved on the mixed selector CSP. Meanwhile, compared with the single selector CSPs, no additional preparation stage or reagent consumption was required in the simultaneous immobilization of different proteins, which is more favorable from economical and practical points of view. Consequently, by mixing HSA and cellulase together, the composite column combines the enantioselectivities of both individual proteins, thus expanding their application range practically.

The dynamics of carrier relaxation and charge transport of photoinduced carriers in Lead Sulfide nanocrystals with quantum confinement, synthesized by chemical bath deposition method, have been simultaneously determined using time-resolved terahertz spectroscopy with sub-picosecond time resolution. We use both Drude-Smith and Drude Lorenz model to successfully reproduce the photoconductivity spectra, which manifest that localized free-carriers not bounded excitons are responsible to the THz transport in PbS nanocrystals. The pump fluence dependence of carrier dynamics reveals the process of Auger recombination through the interaction between free carriers and excitons.

Background: Osteoarthritis is a disorder of joints featuring inflammation and degeneration of articular cartilage. Recently, miRs have been found to be associated in the regulation of chondrocytes and their apoptosis. miR-18a-3p has been found to be associated in the pathogenesis of rheumatoid arthritis, however, its role in articular cartilage tissues remains unclear. Methods: C57BL/6 strain of mice and human cartilage tissue were used for the study. Histological analysis was done on isolated cartilage samples followed by TUNEL assay and immunohistochemical analysis. The chondrocytes were isolated from mouse and human cartilage tissues, RNA was isolated and subjected for qRT-PCR analysis. The chondrocytes were transfected with miR-18a-3p agomir, antagomir and siHOXA-1. Luciferase assay was done in 293T cells. Flow cytometry analysis was done and western blot analysis for studying the expression of proteins. Results: The expression of miR-18a-3p was upregulated in chondrocytes after exposing them to interlukin- 1β (IL-1β) in vitro. The transfection of miR-18a-3p antagomir halted the IL-1β mediated apoptosis. The luciferase assay suggested that miR-18a-3p targets the 3’UTR region of HOXA1 gene thus blocking its expression. The treatment of HOXA1 siRNA demonstrated the rescuing effect of miR- 18a-3p antagomir on the apoptosis of chondrocytes. Treatment of miR-18a-3p antagomir attenuated the surface of cartilage in osteoarthritis mice and the agomir worsened it. TUNEL assay suggested decreased apoptosis and over-expression of HOAX1 in osteoarthritis mice post miR-18a-3p knockdown. Conclusion: The findings confirmed the involvement of miR-18a-3p/HOXA1 pathway as a potential mechanism in the regulation of Osteoarthritis.

The frequency and time resolved conductivity in a photoexcited large-area monolayer tungsten disulfide (WS

O-GlcNAcylation and phosphorylation are two posttranslational modifications that antagonistically regulate protein function. However, the regulation of and the cross talk between these two protein modifications are poorly understood in plants. Here we investigated the role of O-GlcNAcylation during vernalization, a process whereby prolonged cold exposure promotes flowering in winter wheat (Triticum aestivum), and analyzed the dynamic profile of O-GlcNAcylated and phosphorylated proteins in response to vernalization. Altering O-GlcNAc signaling by chemical inhibitors affected the vernalization response, modifying the expression of VRN genes and subsequently affecting flowering transition. Over a vernalization time-course, O-GlcNAcylated and phosphorylated peptides were enriched from winter wheat plumules by Lectin weak affinity chromatography and iTRAQ-TiO2, respectively. Subsequent mass spectrometry and gene ontology term enrichment analysis identified 168 O-GlcNAcylated proteins that are mainly involved in responses to abiotic stimulus and hormones, metabolic processing, and gene expression; and 124 differentially expressed phosphorylated proteins that participate in translation, transcription, and metabolic processing. Of note, 31 vernalization-associated proteins were identified that carried both phosphorylation and O-GlcNAcylation modifications, of which the majority (97%) exhibited the coexisting module and the remainder exhibited the potential competitive module. Among these, TaGRP2 was decorated with dynamic O-GlcNAcylation (S87) and phosphorylation (S152) modifications, and the mutation of S87 and S152 affected the binding of TaGRP2 to the RIP3 motif of TaVRN1 in vitro. Our data suggest that a dynamic network of O-GlcNAcylation and phosphorylation at key pathway nodes regulate the vernalization response and mediate flowering in wheat.

Anti-icing is a critical topic in durability assessment for pavement infrastructures, and it varies according to local policies. To provide sufficient information to winter maintenance agencies, and help compare the merits and shortcomings of each strategy, this review summarizes the widely used anti-icing strategies, including elastic surfaces or high-friction overlays, asphalt binders mixed with anti-icing additives, pavement heating technologies, deicers, and fixed automated spray technology, from academic and practical perspectives, as well as explore the impact of deicers on the durability of concrete materials. Furthermore, the costs of each method were compared to evaluate the feasibility of them. This review not only provides a summary of previous anti-icing strategies, but also sheds light on future research trends that may help address the challenges of current anti-icing strategies, and further enhance anti-icing efficiency and reduce life cycle costs.

There has been a big challenge in developing the Na(+) sensor that can be practically used in the physiological system with the interference of large amounts of K(+). In this research, a novel Na(+) sensor has been designed based on the G-quadruplex-conformation related DNAzyme activity. The sensor exhibits high selectivity and sensitivity with the detection limit of 0.6 μM, which enables the sensor to be practically used in determination of the Na(+) level in serum. The research not only provides a simple Na(+) sensor but also opens a new way for developing the detection technology of Na(+).

The geologic structure of deep formations, basic geologic pattern of fault depressions, geologic conditions of Lower Cretaceous Shahezi Formation tight gas reservoir, and the exploration direction in the next step in the Songliao Basin are examined based on a comprehensive and comparative analysis of the outcrop, drilling, seismic and geochemical data. Systematic comparison analysis shows that the geologic structure of deep formations in the basin is characterized by a double-layer structure with fault depression in the lower layer and depression in the upper layer. In the deep fault depression (DFD) stage, fault depressions bounded by faults or onlaps and uplifts, developed independently. The faults related to the formation and evolution of the fault depressions can be divided into regional discordogenic fault, basement depression controlling fault, and secondary fault inside depression, and their actions in the evolution of the fault depression groups are presented in the paper. Based on analysis of regional tectonics and basin evolution features, three exploration fields, tight conglomerate gas, volcanic rocks and basement buried hills are pointed out, and it is concluded the tight conglomerate gas in the Shahezi Formation is currently a new strategic field with the most promising exploration prospect. Based on comprehensive analysis of basic oil geologic features of Shahezi Formation, it is proposed that conglomerate is the main category of clastic reservoir in Shahezi Fromation, and parent rock composition, sedimentary structure and facies, and diagenesis are the main factors affecting the distribution of conglomerate reservoirs. Furthermore, the gas reservoirs in Shahezi Formation, all source and reservoir in one, include two types, lithologic and structural types. Favorable sedimentary facies belts in the gentle slope and steep slope control the distribution of the reservoirs, formation of lithologic traps and gas reservoir scale; while secondary faults inside fault depressions control the formation of structural traps and enrichment of natural gas. Finally, seven fault depressions in Shahezi Formation with the most promising prospect of tight gas have been sorted out through comprehensive evaluation. Key words: Songliao Basin, deep geologic structure, Cretaceous, Shahezi Formation, tight conglomerate gas, exploration prospect

Nd0.5Sr0.5MnO3 nanoparticles with average sizes of 32-1000 nm in diameter were prepared by sol-gel method. The synthesized nanoparticles were characterized using X-ray diffraction, high- resolution transmission microscopy, scanning electron microscopy, and vibrating sample magnetometer. All samples have the single-phase orthorhombic structure, and the grain size increases with the increase in annealing temperature. A charge ordering (CO) transition at T(CO) and a ferromagnetic-paramagnetic transition at Tc were observed in 1000 nm nanoparticles. With the decrease in particle size, CO transition gradually shifts to lower temperature, becomes increasingly weak, and disappears for 85 nm nanoparticles. An inverse magnetocaloric effect with positive magnetic entropy change was observed around T(CO), and it decreases with the decrease in size due to the suppression of CO phase. The observed negative magnetic entropy change at Tc shows a surprising nonmonotonic behavior with the variation of particles size. All these results may give rise to a new insight into the magnetothermal behaviors in nanosized CO perovskite manganites.

Multiple cycle regulation of the supramolecular chirality of a cyanine dye has been successfully achieved by using DNA G-quadruplexes as templates, which is easily controllable by repeated addition of Ag(+) and cysteine (Cys). This work provides an easy and controllable strategy for the chiral regulation of supramolecules.

A colorimetric and fluorometric dual-modal DNA logic gate has been constructed, which is based on the response of a cyanine dye supramolecule to K+–Pb2+-switched G-quadruplexes. Only when the input is K+, the output is 1, which made the system an INHIBIT logic gate. The gate operation constructed here is label-free, and is of simple design and low-cost, showing great promise for practical onsite applications.

Pollination services provided by managed honey bee and wild pollinators are essential for a range of crops. Pollination services can be measured as species-related services, which can be quantified by the combination of each species’ pollination efficiency and their abundance, as well as harvest-related services, which can be quantified by the pollinator exclusion method. Species-related pollination services are poorly documented and have never been directly compared to harvest-related services. Here, we aimed to quantify the pollination efficiency for common flower-visiting species of common buckwheat (Fagopyrum esculentum) and to scale it up to estimate pollination services. We assessed pollination efficiency by single-visit pollen deposition and visitation rate for common flower-visiting insect species. We monitored the abundance of these species during the entire flowering period across seven sites, where pollinator exclusion treatments were undertaken by caging. In total, we observed 27 flower-visiting species and calculated the pollination efficiency of 17 species. We found that flower-visiting species had different capabilities in transferring compatible pollen grains for two flower morphs and different visitation rates. The estimated pollination efficiency was highest for two honey bee species (Apis mellifera and A. cerana), followed by the hoverfly species (Eristalis tenax), and wasp species (Tiphia vernalis). Species-related pollination services estimated by pollination efficiency and abundance showed a strong positive relationship with harvest-related services, which were estimated by the pollinator exclusion method. Our results suggest that to achieve substantial pollination services for common buckwheat, it is important to maintain sufficient managed honey bees, particularly in areas lacking highly efficient wild pollinators species. Our study also suggests that it is possible to estimate pollination services by scaling up the pollination efficiency of common flower-visiting insects. We provide recommendations for the application of this technique.

Two-dimensional layered bi-transition metal chalcogenides with exotic physical and optoelectronic properties are becoming attractive and promising candidates for next-generation electronics and optoelectronics. Herein, we report a representative of bi-transition metal sulfide, the strip-shaped CuTaS3 crystal, analyzing its intrinsic electrical transport properties and potential optoelectronic applications by fabricating CuTaS3-based devices. The time-resolved Terahertz (THz) spectroscopy (TRTS) results indicate a rapid quenching of photoconductivity in CuTaS3 bulk within 4.1 ps photoexcitation. PL measurement and CuTaS3-based field effect transistors (FETs) show a typical n-type semiconducting behavior with a small, direct bandgap of 1.24 eV. Density functional theory (DFT) calculations reveal charge transfers between different atoms and phonon dispersion relations to help understand the structural and vibrational properties of CuTaS3. A CuTaS3-based-phototransistor was demonstrated with a responsivity of 7.6 mA W−1 and fast photoresponse time of 0.3–0.4 s, as well as excellent photoswitching stability. Our results may pave the way for developing other layered bi-transition metal chalcogenides and implementations in electronic and optoelectronic applications.

Post‐translational modification of proteins by O‐linked β‐N‐acetylglucosamine (O‐GlcNAc) is catalyzed by O‐GlcNAc transferases (OGTs). O‐GlcNAc modification of proteins regulates multiple important biological processes in metazoans. However, whether protein O‐GlcNAcylation is involved in epigenetic processes during plant development is largely unknown. Here, we show that loss of function of SECRET AGENT (SEC), an OGT in Arabidopsis, leads to an early flowering phenotype. This results from reduced histone H3 lysine 4 trimethylation (H3K4me3) of FLOWERING LOCUS C (FLC) locus, which encodes a key negative regulator of flowering. SEC activates ARABIDOPSIS HOMOLOG OF TRITHORAX1 (ATX1), a histone lysine methyltransferase (HKMT), through O‐GlcNAc modification to augment ATX1‐mediated H3K4me3 histone modification at FLC locus. SEC transfers an O‐GlcNAc group on Ser947 of ATX1, which resides in the SET domain, thereby activating ATX1. Taken together, these results uncover a novel post‐translational O‐GlcNAc modification‐mediated mechanism for regulation of HKMT activity and establish the function of O‐GlcNAc signaling in epigenetic processes in plants.