Stabilizing Fe Single Atoms on Rutile-TiO2(110) Surface Via Atomic Substitution.

Stable anchoring of dispersed metal atoms through either surface adsorption or lattice substitution on support surfaces is a prerequisite for highly efficient catalytic performance. Atomic-level insights into these processes are necessary to understand the metal-support interactions. Here, we identify multiple Fe single-atom configurations on the rutile-TiO2(110) surface using scanning tunneling microscopy (STM) and density functional theory (DFT). Our results show that an Fe atom can either adsorb on a surface O site (configuration I) or stably substitute a surface lattice Ti atom (configuration II). A transformation from configuration I to configuration II can be induced by STM manipulation. Furthermore, the substitutional Fe atom can capture an additional Fe atom to form a dual Fe-Fe complex (configuration III). DFT calculations reveal that these Fe species contribute different states in either the bandgap or the conduction band. These atomistic insights pave the way for interrogating the integrated performance of nonprecious, TiO2-supported Fe single-atom catalysts.

Seasonal drought promotes citrate accumulation in citrus fruit through the CsABF3-activated CsAN1-CsPH8 pathway.

Plenty of rainfall but unevenly seasonal distribution happens regularly in southern China. Seasonal drought from summer to early autumn leads to citrus fruit acidification, but how seasonal drought regulates citrate accumulation remains unknown. Herein, we employed a set of physiological, biochemical, and molecular approaches to reveal that CsABF3 responds to seasonal drought stress and modulates citrate accumulation in citrus fruits by directly regulating CsAN1 and CsPH8. Here, we demonstrated that irreversible acidification of citrus fruits is caused by drought lasting for > 30 d during the fruit enlargement stage. We investigated the transcriptome characteristics of fruits affected by drought and corroborated the pivotal roles of a bHLH transcription factor (CsAN1) and a P3A-ATPase gene (CsPH8) in regulating citrate accumulation in response to drought. Abscisic acid (ABA)-responsive element binding factor 3 (CsABF3) was upregulated by drought in an ABA-dependent manner. CsABF3 activated CsAN1 and CsPH8 expression by directly and specifically binding to the ABA-responsive elements (ABREs) in the promoters and positively regulated citrate accumulation. Taken together, this study sheds new light on the regulatory module ABA-CsABF3-CsAN1-CsPH8 responsible for citrate accumulation under drought stress, which advances our understanding of quality formation of citrus fruit.

Unveiling diverse coordination-defined electronic structures of reconstructed anatase TiO2(001)-(1 × 4) surface.

Transition metal oxides (TMOs) exhibit fascinating physicochemical properties, which originate from the diverse coordination structures between the transition metal and oxygen atoms. Accurate determination of such structure-property relationships of TMOs requires to correlate structural and electronic properties by capturing the global parameters with high resolution in energy, real, and momentum spaces, but it is still challenging. Herein, we report the determination of characteristic electronic structures from diverse coordination environments on the prototypical anatase-TiO2(001) with (1 × 4) reconstruction, using high-resolution angle-resolved photoemission spectroscopy and scanning tunneling microscopy/atomic force microscopy, in combination with density functional theory calculation. We unveil that the shifted positions of O 2s and 2p levels and the gap-state Ti 3p levels can sensitively characterize the O and Ti coordination environments in the (1 × 4) reconstructed surface, which show distinguishable features from those in bulk. Our findings provide a paradigm to interrogate the intricate reconstruction-relevant properties in many other TMO surfaces.

An image-based Abplex method for high-throughput GPCRs antibody discovery.

As the field of antibody therapeutics advances rapidly, membrane proteins, particularly G protein-coupled receptors (GPCRs), have emerged as highly sought-after drug targets. However, the challenges associated with extracting membrane proteins have created a demand for effective antibody screening systems targeting these proteins. In this study, we propose developing an innovative antibody screening strategy (Abplex) based on high-content imaging. This approach leverages intact cells that express target membrane proteins, facilitating the presentation of proteins in their native conformation. Furthermore, it acquires both specific and non-specific binding signals in a single well, thereby bolstering the robustness of the outcomes. The technique involves just one step and can be completed within 50 min, enabling the analysis of a single sample in just one second. The amalgamation of dependable experimental findings, a simplified workflow, reduced hands-on time, and a swift analytical pace positions our method for superior throughput and precision when juxtaposed with traditional techniques such as CbELISA and FACS. Moreover, we introduce the concept of cell barcoding, wherein cells are labeled with different fluorescence spatial patterns. This feature allows for multiplexed detection to meet the needs of various experiments. The characteristics of Abplex promise to expedite GPCR-targeting antibody discovery, advance therapeutics and enable new disease treatments.

Application of exosome engineering modification in targeted delivery of therapeutic drugs.

Cancer is the leading cause of premature death in humans. Scientists have developed several therapeutic drugs for cancer treatment. However, drug delivery faces many problems. First, traditional drugs do not target tumors and are prone to causing significant toxic side effects. Second, suitable drug carriers are essential for improving drug delivery to tumors or circulating cancer cells. Exosomes are natural extracellular vesicles with low immunogenicity and prolonged blood circulation in vivo. These characteristics render exosomes ideal drug carriers. This review highlights the properties of exosomes and mechanisms of exosome biogenesis. It also summarizes the engineering modification methods for enhancing exosome yield, targeting, and drug-loading capacity.

Revealing the Polaron State at the MoS2/TiO2 Interface.

Interfacial polarons determine the distribution of free charges at the interface and thus play important roles in manipulating the physicochemical properties of hybridized polaronic materials. In this work, we investigated the electronic structures at the atomically flat interface of the single-layer MoS2 (SL-MoS2) on the rutile TiO2 surface using high-resolution angle-resolved photoemission spectroscopy. Our experiments directly visualized both the valence band maximum and the conduction band minimum (CBM) of SL-MoS2 at the K point, which clearly defines a direct bandgap of ∼2.0 eV. Detailed analyses corroborated by density functional theory calculations demonstrated that the CBM of MoS2 is formed by the trapped electrons at the MoS2/TiO2 interface that couple with the longitudinal optical phonons in the TiO2 substrate through an interfacial Fröhlich polaron state. Such an interfacial coupling effect may register a new route for tuning the free charges in the hybridized systems of two-dimensional materials and functional metal oxides.

Gold Nanorods Inhibit Tumor Metastasis by Regulating MMP-9 Activity: Implications for Radiotherapy.

Dysregulation of matrix metalloproteinase (MMP) is strongly implicated in tumor invasion and metastasis. Nanomaterials can interact with proteins and have impacts on protein activity, which provides a potential strategy for inhibiting tumor invasion and metastasis. However, the regulation of MMP activity by nanomaterials has not been fully determined. Herein, we have found that gold nanorods (Au NRs) are able to induce the change of the secondary structure of MMP-9 and thereby inhibit their activity. Interestingly, the inhibition of MMP-9 activity is highly dependent on the aspect ratio of Au NRs, and an aspect ratio of 3.3 shows the maximum inhibition efficiency. Molecular dynamics simulations combined with mathematical statistics algorithm reveal the binding behaviors and interaction modes of MMP-9 with Au NRs in atomic details and disclose the mechanism of aspect ratio-dependent inhibition effect of Au NRs on MMP-9 activity. Au NRs with an aspect ratio of 3.3 successfully suppress the X-ray-activated invasion and metastasis of tumor by inhibiting MMP-9 activity. Our findings provide important guidance for the modulation of MMP-9 activity by tuning key parameters of nanomaterials and demonstrate that gold nanorods could be developed as potential MMP inhibitors.

From eye movements to scanpath networks: A method for studying individual differences in expository text reading.

Eye movements have been examined as an index of attention and comprehension during reading in the literature for over 30 years. Although eye-movement measurements are acknowledged as reliable indicators of readers' comprehension skill, few studies have analyzed eye-movement patterns using network science. In this study, we offer a new approach to analyze eye-movement data. Specifically, we recorded visual scanpaths when participants were reading expository science text, and used these to construct scanpath networks that reflect readers' processing of the text. Results showed that low ability and high ability readers' scanpath networks exhibited distinctive properties, which are reflected in different network metrics including density, centrality, small-worldness, transitivity, and global efficiency. Such patterns provide a new way to show how skilled readers, as compared with less skilled readers, process information more efficiently. Implications of our analyses are discussed in light of current theories of reading comprehension.

Effects of Fertilization Approaches on Plant Development and Fertilizer Use of Citrus.

Fertilization is an important part of citrus crop management. However, limited details are available about the fertilization approach on citrus plant development. A pot experiment for the fertilization approaches and fertigation levels were conducted in this study. Four fertilization approaches, namely, drip fertigation (DF), broadcast fertilization (CK+), hole fertilization (HF) and pour fertilization (PF) were tested. The fertigation level treatment included 100% (DF-337.5), 80% (DF-270), 60% (DF-202.5) and 40% (DF-135) fertilizer supply with DF, and the 100% fertilizer supply with broadcast fertilization were served as control (CK). The results showed that DF not only increased the absorptions of nitrogen (N), phosphorus (P) and potassium (K) but also promoted citrus plant height, stem diameter and dry weight. In fruit quality, DF had the highest fruit total soluble solid (TSS) and titratable acidity (TA) contents. For fertilizer loss, DF had the lowest N and K leaching losses of 9.26% and 4.05%, respectively, and the lowest N and K runoff losses among the approaches. Isotopic tracing with 15N indicated that DF had the highest fertilizer use efficiency. Based on the analysis of fertigation levels, DF approach with 60% fertilizer reduction could improve citrus plant development. Therefore, DF promoted citrus plant growth and fruit quality by accelerating fertilizer utilization and impairing fertilizer loss. The fertilizer amount in citrus production could be reduced significantly using DF.

Hydrogen-Bond Network Promotes Water Splitting on the TiO2 Surface.

Breaking the strong covalent O-H bond of an isolated H2O molecule is difficult, but it can be largely facilitated when the H2O molecule is connected with others through hydrogen-bonding. How a hydrogen-bond network forms and performs becomes crucial for water splitting in natural photosynthesis and artificial photocatalysis and is awaiting a microscopic and spectroscopic understanding at the molecular level. At the prototypical photocatalytic H2O/anatase-TiO2(001)-(1×4) interface, we report the hydrogen-bond network can promote the coupled proton and hole transfer for water splitting. The formation of a hydrogen-bond network is controlled by precisely tuning the coverage of water to above one monolayer. Under ultraviolet (UV) light irradiation, the hydrogen-bond network opens a cascaded channel for the transfer of a photoexcited hole, concomitant with the release of the proton to form surface hydroxyl groups. The yielded hydroxyl groups provide excess electrons to the TiO2 surface, causing the reduction of Ti4+ to Ti3+ and leading to the emergence of gap states, as monitored by in situ UV/X-ray photoelectron spectroscopy. The density functional theory calculation reveals that the water splitting becomes an exothermic process through hole oxidation with the assistance of the hydrogen-bond network. In addition to the widely concerned exotic activity from photocatalysts, our study demonstrates the internal hydrogen-bond network, which is ubiquitous at practical aqueous/catalyst interfaces, is also indispensable for water splitting.

APLNR Regulates IFN-γ signaling via ß-arrestin 1 mediated JAK-STAT1 pathway in melanoma cells.

The apelin receptor (APLNR) regulates many biological processes including metabolism, angiogenesis, circulating blood volume and cardiovascular function. Additionally, APLNR is overexpressed in various types of cancer and influences cancer progression. APLNR is reported to regulate tumor recognition during immune surveillance by modulating the IFN-γ response. However, the mechanism of APLNR cross-talk with intratumoral IFN-γ signaling remains unknown. Here, we show that activation of APLNR up-regulates IFN-γ signaling in melanoma cells through APLNR mediated ß-arrestin 1 but not ß-arrestin 2 recruitment. Our data suggests that ß-arrestin 1 directly interacts with STAT1 to inhibit STAT1 phosphorylation to attenuate IFN-γ signaling. The APLNR mutant receptor, I109A, which is deficient in ß-arrestins recruitment, is unable to enhance intratumoral IFN-γ signaling. While APLNR N112G, a constitutively active mutant receptor, increases intratumoral sensitivity to IFN-γ signaling by enhancing STAT1 phosphorylation upon IFN-γ exposure. We also demonstrate in a co-culture system that APLNR regulates tumor survival rate. Taken together, our findings reveal that APLNR modulates IFN-γ signaling in melanoma cells and suggest that APLNR may be a potential target to enhance the efficacy of immunotherapy.

Time- and momentum-resolved image-potential states of 2H-MoS2 surface.

Rydberg-like image potential states (IPSs) form special series surface states on metal and semiconducting surfaces. Here, using time-resolved and momentum-resolved multi-photon photoemission (mPPE), we measured the energy positions, band dispersion, and carrier lifetimes of IPSs at the 2H-MoS2 surface. The energy minima of the IPSs (n = 1 and 2) were located at 0.77 and 0.21 eV below the vacuum level. In addition, the effective masses of these two IPSs are close to the rest mass of the free electron, clearly showing nearly-free-electron character. These properties suggest a good screening effect in the MoS2 parallel to the surface. The multi-photon resonances between the valence band and IPS (n = 1) are observed, showing a k‖-momentum-dependent behavior. Our time-resolved mPPE measurements show that the lifetime of photoexcited electrons in the IPS (n = 1) is about 33 fs.

The spatial-temporal evolution of heavy metal accumulation in the offshore sediments along the Shandong Peninsula over the last 100 years: Anthropogenic and natural impacts.

The anthropogenic and natural impacts on the temporal and spatial variations of heavy metals in sediments under the Shandong Peninsula coastal current are still unclear. Here, the concentrations\burial fluxes of Cr, Cu, Zn, As, and Pb in three sediment cores retrieved from the Bohai Sea and the Yellow Sea along the Shandong Peninsula were analyzed to study the spatial-temporal variability of heavy metal accumulation over the last century. The results showed that the buried heavy metal fluxes were relatively low at the end of the Shandong Peninsula coastal current. The enrichment factor (EF) and geoaccumulation index (Igeo) indicated that those metals did not severely pollute the sediments except As that reached a moderate enrichment. Principal component analysis (PCA) revealed that Cr, Cu, Zn, and Pb were mainly derived from natural weathering and As was determined by anthropogenic contamination. The strength of the Shandong Peninsula coastal current, the Yellow River estuary location, and sediment discharge load significantly influenced the concentrations of natural-origin heavy metals by affecting sediment grain size and the source-sink process. The emission of pollutants from agricultural and industrial activities in the Shandong Peninsula region resulted in As enrichment since the 1950s. Moreover, the EF values of heavy metals in sediment cores from China's coastal seas showed apparent spatial variations of heavy metal pollution but had coherent temporal variability with China's economic development process. Heavy metals pollution has weakened in most coastal seas since the 2000s, likely due to the extensive industrial upgrading and the implementation of pollution control. These results have a reference significance for studying the evolution and source-sink process of the heavy metals in offshore sediments and tracing anthropogenic impacts in different periods.

Relations of Lifestyle Behavior Clusters to Dyslipidemia in China: A Compositional Data Analysis.

Dyslipidemia is associated with lifestyle behaviors, while several lifestyle behaviors exist collectively among some populaitons. This study aims to identify lifestyle behavior clusters and their relations to dyslipidemia. This cross-sectional study was conducted in Wuhai City, China. Cluster analysis combined with compositional data analysis was conducted, with 24-h time-use on daily activities and dietary patterns as input variables. Multiple logistic regression was conducted to compare dyslipidemia among clusters. A total of 4306 participants were included. A higher prevalence of newly diagnosed dyslipidemia was found among participants in cluster 1 (long sedentary behavior (SB) and the shortest sleep, high-salt and oil diet) /cluster 5 (the longest SB and short sleep), relative to the other clusters in both age groups (<50 years and ≥50 years). In conclusion, unhealthy lifestyle behaviors may exist together among some of the population, suggesting that these people are potential subjects of health education and behavior interventions. Future research should be conducted to investigate the relative significance of specific lifestyle behaviors in relation to dyslipidemia.

Orphan GPR116 mediates the insulin sensitizing effects of the hepatokine FNDC4 in adipose tissue.

The proper functional interaction between different tissues represents a key component in systemic metabolic control. Indeed, disruption of endocrine inter-tissue communication is a hallmark of severe metabolic dysfunction in obesity and diabetes. Here, we show that the FNDC4-GPR116, liver-white adipose tissue endocrine axis controls glucose homeostasis. We found that the liver primarily controlled the circulating levels of soluble FNDC4 (sFNDC4) and lowering of the hepatokine FNDC4 led to prediabetes in mice. Further, we identified the orphan adhesion GPCR GPR116 as a receptor of sFNDC4 in the white adipose tissue. Upon direct and high affinity binding of sFNDC4 to GPR116, sFNDC4 promoted insulin signaling and insulin-mediated glucose uptake in white adipocytes. Indeed, supplementation with FcsFNDC4 in prediabetic mice improved glucose tolerance and inflammatory markers in a white-adipocyte selective and GPR116-dependent manner. Of note, the sFNDC4-GPR116, liver-adipose tissue axis was dampened in (pre) diabetic human patients. Thus our findings will now allow for harnessing this endocrine circuit for alternative therapeutic strategies in obesity-related pre-diabetes.

Matrix metalloproteinase inhibitors (MMPIs) as attractive therapeutic targets: Recent progress and current challenges.

Matrix metalloproteinase (MMP) plays an essential role in many physiological and pathological processes. An increase in MMP activity contributes to excessive degradation and remodeling of the extracellular matrix (ECM), which has been correlated with invasion and metastasis of tumors. Matrix metalloproteinase inhibitor (MMPI) has been developed as an attractive therapeutic target for decades, suggesting inspiring therapeutic effects in preclinical studies. However, achieving specificity remains an important challenge in the development of MMPIs, limiting their clinical application and bringing about the risk of biosafety. Nanomaterials can be used as alternative candidates for MMPI design, providing a new strategy for this problem. This report reviewed the research about MMPIs, summarized their MMPs activity regulation mechanisms, and discussed their failures in clinical trials. Furthermore, we outlined several schemes of MMPIs screening and design. Finally, we reviewed the therapeutic application prospects of MMPIs and discussed the remaining challenges and solutions, which may offer new insights for the development of MMPIs studies.

Formation of Plasmonic Polarons in Highly Electron-Doped Anatase TiO2.

The existence of various quasiparticles of polarons because of electron-boson couplings plays important roles in determining electron transport in titanium dioxide (TiO2), which affects a wealth of physical properties from catalysis to interfacial superconductivity. In addition to the well-defined Fröhlich polarons whose electrons are dressed by the phonon clouds, it has been theoretically predicted that electrons can also couple to their own plasmonic oscillations, namely, the plasmonic polarons. Here we experimentally demonstrate the formation of plasmonic polarons in highly doped anatase TiO2 using angle-resolved photoemission spectroscopy. Our results show that the energy separation of plasmon-loss satellites follows a dependence on √n, where n is the electron density, manifesting the characteristic of plasmonic polarons. The spectral functions enable to quantitatively evaluate the strengths of electron-plasmon and electron-phonon couplings, respectively, providing an effective approach for characterizing the interplays among different bosonic modes in the complicate many-body interactions.

Interfacial Polarons in van der Waals Heterojunction of Monolayer SnSe2 on SrTiO3 (001).

Interfacial polarons have been demonstrated to play important roles in heterostructures containing polar substrates. However, most of polarons found so far are diffusive large polarons; the discovery and investigation of small polarons at interfaces are scarce. Herein, we report the emergence of interfacial polarons in monolayer SnSe2 epitaxially grown on Nb-doped SrTiO3 (STO) surface using angle-resolved photoemission spectroscopy (ARPES) and scanning tunneling microscopy (STM). ARPES spectra taken on this heterointerface reveal a nearly flat in-gap band correlated with a significant charge modulation in real space as observed with STM. An interfacial polaronic model is proposed to ascribe this in-gap band to the formation of self-trapped small polarons induced by charge accumulation and electron-phonon coupling at the van der Waals interface of SnSe2 and STO. Such a mechanism to form interfacial polaron is expected to generally exist in similar van der Waals heterojunctions consisting of layered 2D materials and polar substrates.

Loss of APJ mediated ß-arrestin signalling improves high-fat diet induced metabolic dysfunction but does not alter cardiac function in mice.

Apelin receptor (APJ) is a G protein-coupled receptor that contributes to many physiological processes and is emerging as a therapeutic target to treat a variety of diseases. For most disease indications the role of G protein vs ß-arrestin signalling in mitigating disease pathophysiology remains poorly understood. This hinders the development of G protein biased APJ agonists, which have been proposed to have several advantages over balanced APJ signalling agonists. To elucidate the contribution of APJ ß-arrestin signalling, we generated a transgenic mouse harbouring a point mutation (APJ I107A) that maintains full G protein activity but fails to recruit ß-arrestin following receptor activation. APJ I107A mutant mice did not alter cardiac function at rest, following exercise challenge or in response to pressure overload induced cardiac hypertrophy. Additionally, APJ I107A mice have comparable body weights, plasma glucose and lipid levels relative to WT mice when fed a chow diet. However, APJ I107A mice showed significantly lower body weight, blood insulin levels, improved glucose tolerance and greater insulin sensitivity when fed a high-fat diet. Furthermore, loss of APJ ß-arrestin signalling also affected fat composition and the expression of lipid metabolism related genes in adipose tissue from high-fat fed mice. Taken together, our results suggest that G protein biased APJ activation may be more effective for certain disease indications given that loss of APJ mediated ß-arrestin signalling appears to mitigate several aspects of diet induced metabolic dysfunction.

Characterization of PtAOS1 Promoter and Three Novel Interacting Proteins Responding to Drought in Poncirus trifoliata.

Jasmonic acid (JA) plays a crucial role in various biological processes including development, signal transduction and stress response. Allene oxide synthase (AOS) catalyzing (13S)-hydroperoxyoctadecatrienoic acid (13-HPOT) to an unstable allene oxide is involved in the first step of JA biosynthesis. Here, we isolated the PtAOS1 gene and its promoter from trifoliate orange (Poncirus trifoliata). PtAOS1 contains a putative chloroplast targeting sequence in N-terminal and shows relative to pistachio (Pistacia vera) AOS. A number of stress-, light- and hormone-related cis-elements were found in the PtAOS1 promoter which may be responsible for the up-regulation of PtAOS1 under drought and JA treatments. Transient expression in tobacco (Nicotiana benthamiana) demonstrated that the P-532 (-532 to +1) fragment conferring drive activity was a core region in the PtAOS1 promoter. Using yeast one-hybrid, three novel proteins, PtDUF886, PtDUF1685 and PtRAP2.4, binding to P-532 were identified. The dual luciferase assay in tobacco illustrated that all three transcription factors could enhance PtAOS1 promoter activity. Genes PtDUF1685 and PtRAP2.4 shared an expression pattern which was induced significantly by drought stress. These findings should be available evidence for trifoliate orange responding to drought through JA modulation.