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Cristobalite‐type boron phosphate BPO4, an important nonlinear‐optical (NLO) crystal, exhibits nearly the largest bandgap (Eg ≈ 9.3 eV) and a significant second‐harmonic‐generation (SHG) effect (d36 ≈ 0.7 pm V−1) in the deep‐ultraviolet (DUV, < 200 nm) spectral region. However, its conventional tetrahedral framework structure tends to have low structural anisotropy, resulting in a severe deficiency of birefringence (Δn < 0.01), which fails to achieve DUV birefringent phase matching. In this work, the local anisotropy of tetrahedral structures are proposed to enlarge by constructing van der Waals (vdW) anisotropic motifs under synthetic chemical conditions, which can effectively convert unattainable extreme external forces into internal stresses in chemical bond structures. Depending on unique hierarchical vdW assemblies, enormous tetrahedral distortions can be achieved by stable in‐plane or in‐line bond matching between rigid tetrahedral primitives. First‐principles calculations demonstrate that the birefringence of 2D layered and 1D chained BPO4 achieved by vdW engineering are scaled from Δn < 0.01 to 0.07–0.13, with the shortest birefringent phase‐matched wavelengths down to DUV 189–154 nm. The finding is of seminal importance for the design of vdW NLO crystals in structural chemistry and would provide opportunities to explore unique vdW DUV NLO materials under extreme synthetic conditions. [ABSTRACT FROM AUTHOR]

In this paper, the Cr films with preferred orientation evolution from (110) to (200) were deposited on the surface of austenitic stainless steel. These films were driven by a pulsed bias with different duty cycles from 20% to 80%, followed by a postnitriding process for 1 h using a hot wire plasma-enhanced magnetron sputtering system. XRD result showed Cr film had a body-centered cubic lattice structure, and the orientation transformed from (110) to (200) with the increase in the duty cycle. SEM and EDS measurements revealed that Cr film structured with columnar crystals could contribute to the continuous diffusion of nitrogen into austenite lattice. N atoms tended to diffuse along the (200) orientation of Cr films than the close-packed (110) orientation. As a result, the best wear resistance and adhesion strength were obtained when Cr film deposited at 80% duty cycle was nitrided, and the wear volume decreased by 95.7% compared with that before nitriding. [ABSTRACT FROM AUTHOR]

As an important form of posttranslational modification, protein ubiquitination regulates a wide variety of biological processes, including different aspects of T cell development and differentiation. During T cell development, thymic seeding progenitor cells (TSPs) in the thymus undergo multistep maturation programs and checkpoints, which are critical to build a functional and tolerant immune system. Currently, a tremendous amount of research has focused on the transcriptional regulation of thymocyte development. However, in the past few years, compelling evidence has revealed that the ubiquitination system also plays a crucial role in the regulation of thymocyte developmental programs. In this review, we summarize recent findings on the molecular mechanisms and cellular pathways that regulate thymocyte ubiquitination and discuss the roles of E3 ligases and deubiquitinating enzymes (DUBs) involved in these processes. Understanding how T cell development is regulated by ubiquitination and deubiquitination will not only enhance our understanding of cell fate determination via gene regulatory networks but also provide potential novel therapeutic strategies for treating autoimmune diseases and cancer.

Ultrathin and two-dimensional (2D) metals can support strong plasmons, with concomitant tight field confinement and large field enhancement. Accordingly, 2D-metal nanostructures exhibiting plasmonic resonances are highly sensitive to the environment and intrinsically suitable for optical sensing. Here, based on a proof-of-concept numerical study, nano-engineered ultrathin 2D-metal films that support infrared plasmons are demonstrated to enable highly responsive refractive index (RI) sensing. For 3 nm-Au nanoribbons exhibiting plasmonic resonances at wavelengths around 1600 nm, a RI sensitivity of SRI > 650 nm per refractive index unit (RIU) is observed for a 100 nm-thick analyte layer. A parametric study of the 2D-Au system indicates the strong dependence of the RI sensitivity on the 2D-metal thickness. Furthermore, for an analyte layer as thin as 1 nm, a RI sensitivity up to 110 (90 nm/RIU) is observed in atomically thin 2D-In (2D-Ga) nanoribbons exhibiting highly localized plasmonic resonances at mid-infrared wavelengths. Our results not only reveal the extraordinary sensing characteristics of 2D-metal systems but also provide insight into the development of 2D-metal-based plasmonic devices for enhanced IR detection. [ABSTRACT FROM AUTHOR]

Glycosylation is a common modification reaction in plants. The products obtained upon glycosylation have different biological functions, making glycosylation an important mechanism affecting and regulating the balance of plant growth and metabolism. In this study, we first speculated that Group I in the apple glycosyltransferase family may have a predicted function like UGT83A1, according to gene chip data published online. Subsequently, by real-time PCR (polymerase chain reaction), we analyzed whether the expression of nine glycosyltransferase genes in Group I was induced by our previously reported ACCase (Acetyl-CoA carboxylase) inhibition-based herbicide QPP ((R)-ethyl·2-(4-((6-fluoro-3-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)oxy) phenoxy) propanoate). It was found that expression of the MdUGT83K2 gene in Group I was significantly increased by QPP. In order to determine whether MdUGT83K2 can glycosylate QPP, we confirmed the enzymatic reaction of MdUGT83K2 in vitro and the presence of QPP glycosides in MdUGT83K2 transgenic apple seedlings by HPLC (High Performance Liquid Chromatography), and found that MdUGT83K2 can transfer glucose to QPP in vivo, which is glycosylated. In this work, we identified a novel apple glycosyltransferase, MdUGT83K2, which functions to glycosylate the ACCase-inhibiting herbicide QPP and may be involved in plant detoxification. Key Contribution: A novel apple glycosyltransferase, MdUGT83K2, was identified, which may be involved in plant detoxification by glycosylation modification of the ACCase-inhibiting herbicide.

Natural products are one of the resources for discovering novel pesticide leads. Here, by molecular hybridization between the natural enamino diketone skeleton and the reported herbicide lead compound I, a series of 3-(1-aminoethylidene)-6-methyl-2H-pyran-2,4(3H)-dione derivatives (APD) were rationally designed, synthesized and tested for herbicidal activity in a greenhouse. The bioassay results showed that most of the target compounds possessed good herbicidal activity under pre-emergence conditions, of which the analog APD-II-15 displayed good pre-emergent herbicidal activity against Abutilon theophrasti Medicus, Amaranthus retroflexus L., Echinochloa crus-galli, Eragrostis curvula (Schrad.) Nees, Avena fatua L., Cyperus difformis L., Chenopodium album L., Ixeris denticulata, Plantago asiatica L., Capsella bursa-pastoris (Linn.) Medic and Flaveria bidentis (L.) Kuntze with > 60% inhibition even at a dosage of 187.5 g ha−1, and displayed good crop safety for wheat, soybean, millet and sorghum at a dosage of 375 g ha−1. The preliminary study of the molecular mode of action by RNA sequencing suggested that a growth inhibition of weeds by APD-II-15 might result from the disruptions of carbon metabolism and formation of a cytoskeleton. The present work indicated that APD-II-15 might be used as a novel herbicidal lead compound for further optimization.

Aim: To evaluate the effect of age and disease duration on the efficacy and safety of iGlarLixi versus insulin glargine 100 units/ml (iGlar) or lixisenatide (Lixi) alone in Asian people with type 2 diabetes (T2D) uncontrolled on oral antidiabetic drugs (LixiLan‐O‐AP) or basal insulin ± oral antidiabetic drugs (LixiLan‐L‐CN). Materials and Methods: In this post hoc analysis, the glycated haemoglobin (HbA1c) changes were assessed from baseline to week 24 (LixiLan‐O‐AP) or 30 (LixiLan‐L‐CN) in subgroups defined by baseline age (<65, ≥65 years) and duration of T2D. The proportion who achieved the composite of HbA1c <7% (<53.0 mmol/mol) without weight gain and without symptomatic hypoglycaemia (plasma glucose ≤3.9 mmol/L) and the incidences of hypoglycaemia and gastrointestinal disorders were also analysed. Results: HbA1c reductions were consistently greater with iGlarLixi versus iGlar or Lixi across all subgroups, including participants aged ≥65 years and those with T2D for ≥15 or ≥20 years. Greater proportions of participants achieved HbA1c <7% (<53.0 mmol/mol) without weight gain or hypoglycaemia with iGlarLixi versus iGlar or Lixi, regardless of age or T2D duration. Hypoglycaemia incidence was similar with iGlarLixi versus iGlar across most subgroups; the incidence of gastrointestinal disorders was lower with iGlarLixi versus Lixi in all subgroups. Conclusions: iGlarLixi showed consistent efficacy and safety across all age and disease duration subgroups in Asian people with uncontrolled T2D, including older individuals and those with longstanding disease. [ABSTRACT FROM AUTHOR]

Purpose: Triple-negative breast cancer (TNBC) has a poor prognosis due to the absence of effective therapeutic targets. Vascular endothelial growth factor (VEGF) family are expressed in 30–60% of TNBC, therefore providing potential therapeutic targets for TNBC. Aflibercept (Abe), a humanized recombinant fusion protein specifically bound to VEGF-A, B and placental growth factor (PIGF), has proven to be effective in the treatment in some cancers. Therefore, 89Zr/177Lu-labeled Abe was investigated for its theranostic role in TNBC. Methods: Abe was radiolabeled with 89Zr and 177Lu via the conjugation of chelators. Flow cytometry and cell immunofluorescent staining were performed to evaluate the binding affinity of Abe. Sequential PET imaging and fluorescent imaging were conducted in TNBC tumor bearing mice following the injection of 89Zr-labeled Abe and Cy5.5-labeled Abe. Treatment study was performed after the administration of 177Lu-labeled Abe. Tumor volume and survival were monitored and SPECT imaging and biodistribution studies were conducted. Safety evaluation was performed including body weight, blood cell measurement, and hematoxylin–eosin (H&E) staining of major organs. Expression of VEGF and CD31 was tested by immunohistochemical staining. Dosimetry was estimated using the OLINDA software. Results: FITC-labeled Abe showed a strong binding affinity to VEGF in TNBC 4T1 cells and HUVECs by flow cytometry and cell immunofluorescence. Tumor uptake of 89Zr-labeled Abe peaked at 120 h (SUVmax = 3.2 ± 0.64) and persisted before 168 h (SUVmax = 2.54 ± 0.42). The fluorescence intensity of the Cy5.5-labeled Abe group surpassed that of the Cy5.5-labeled IgG group, implying that Cy5.5-labeled Abe is a viable candidate monitoring in vivo tumor targeting and localization. 177Lu-labeled Abe (11.1 MBq) served well as the therapeutic component to suppress tumor growth with standardized tumor volume at 16 days, significantly smaller than PBS group (about 815.66 ± 3.58% vs 3646.52 ± 11.10%, n = 5, P < 0.01). Moreover, SPECT images confirmed high contrast between tumors and normal organs, indicating selective tumor uptake of 177Lu-labeled Abe. No discernible abnormalities in blood cells, and no evident histopathological abnormality observed in liver, spleen, and kidney. Immunohistochemical staining showed that 177Lu-labeled Abe effectively inhibited the expression of VEGF and CD31 of tumor, suggesting that angiogenesis may be suppressed by 177Lu-labeled Abe. The whole-body effective dose for an adult human was estimated to be 0.16 mSv/MBq. Conclusion: 89Zr/177Lu-labeled Abe could be a TNBC-specific marker with diagnostic value and provide insights into targeted therapy in the treatment of TNBC. Further clinical evaluation and translation may be of high significance for TNBC. [ABSTRACT FROM AUTHOR]

Japanese encephalitis virus is mainly prevalent in the tropical and subtropical regions of Asia and Oceania. Through immunoprecipitation-mass spectrometry analysis using monoclonal antibodies targeting JEV E protein, we found that mosquito Histone 2A protein could bind to JEV particles. The binding of H2A and JEV was detected in the salivary gland and supernatant of mosquito cells. Furthermore, RNA interference experiments in vitro and in vivo confirmed that H2A protein promotes JEV infection in mosquitoes. In summary, we found that mosquito H2A is a factor that supports JEV infection and can potentially facilitate cross-species transmission of JEV. [ABSTRACT FROM AUTHOR]

Fibrosis is a progressive pathological process participating in the progression of many diseases and can ultimately result in organ malfunction and failure. Around 45% of deaths in the United States are believed to be attributable to fibrotic disorders, and there are no favorable treatment regiments available to meet the need of blocking fibrogenesis, reversing established fibrosis, and curing diseases, especially in the terminal stage. Therefore, early detection and continuous monitoring provide valuable benefits for patients. Among all the advanced techniques developed in recent years for fibrosis evaluation, molecular imaging stands out with its distinct advantage of visualizing biochemical processes and patterns of target localization at the molecular and cellular level. In this review, we summarize the current state of the art in molecular imaging of benign fibrosis diseases. We will first introduce molecular pathways underlying fibrosis processes and potential targets. We will then elaborate on molecular probes that have been developed thus far, expounding on their mechanisms and current states of translational advancement. Finally, we will delineate the extant challenges impeding further progress in this area and the prospective benefits after overcoming these problems. [ABSTRACT FROM AUTHOR]

Water dissolved in nominally anhydrous minerals (NAMs) can be transported to deep regions of the Earth through subducting slabs, thereby significantly influencing the physicochemical properties of deep-Earth materials and impacting dynamic processes in the deep Earth. Stishovite, a prominent mineral present in subducting slabs, remains stable at mantle pressures of 9–50 GPa and can incorporate various amounts of water (H + , OH - , and H 2 O) in its crystal structure. Consequently, stishovite can play a crucial role in transporting water into the deep Earth through subducting slabs. This paper provides a comprehensive review of the research process concerning water (hydrogen) solubility in stishovite. The key factors that govern water solubility in stishovite are summarized as temperature, pressure, water fugacity, and aluminum content. Combined with published results on the dependence of water solubility on the aforementioned parameters, this paper proposes a new equation to describe the solubility of water in Al-bearing stishovite. Calculation results based on this equation suggest that stishovite may effectively accommodate water released from processes such as hydrous mineral breakdown, which could ultimately contribute to the presence of a water-rich transition zone. [ABSTRACT FROM AUTHOR]

Optical metasurfaces, planar subwavelength nanoantenna arrays with the singular ability to sculpt wavefront in almost arbitrary manners, are poised to become a powerful tool enabling compact and high-performance optics with novel functionalities. A particularly intriguing research direction within this field is active metasurfaces, whose optical response can be dynamically tuned postfabrication, thus allowing a plurality of applications unattainable with traditional bulk optics. Designing reconfigurable optics based on active metasurfaces is, however, presented with a unique challenge, since the optical quality of the devices must be optimized at multiple optical states. In this article, we provide a critical review on the active meta-optics design principles and algorithms that are applied across structural hierarchies ranging from single meta-atoms to full meta-optical devices. The discussed approaches are illustrated by specific examples of reconfigurable metasurfaces based on optical phase-change materials.

To discover new acetyl-CoA carboxylase (ACCase) inhibiting-based herbicides, twenty-nine novel quinazolin-4(3H)-one derivatives were designed and synthesized based on the aryloxyphenoxypropionate motif. The bioassay results showed that most of the target compounds showed better pre-emergent herbicidal activity against monocotyledonous weeds in a greenhouse. Especially, when applied at 375 g ha−1 under pre-emergence conditions, compound QPP-7 displayed excellent herbicidal activity against monocotyledonous weeds (i.e., E. crusgalli, D. sanguinalis, P. alopecuroides, S. viridis, E. indica, A. fatua, E. dahuricu, S. alterniflora) with inhibition rate >90%, and displayed excellent crop safety to O. sativa, T. aestivum, G. spp, and A. hypogaea. The study of structure-activity relationship (SAR) revealed that the herbicidal activity of target compounds is strongly influenced by the spatial position of R group and the bulk of R1 group on quinazolin-4(3H)-one, and the (R = 6-F, R1 = Me) pattern is confirmed as the optimal orientation. Furthermore, the molecular docking study and the good inhibitory activity of QPP-7 against E. crusgalli ACCase enzyme (IC50 = 54.65 nM) indicated that it may be a ACCase inhibitor. Taken together, the present work demonstrated that compound QPP-7 could serve as a potential lead structure for further developing novel ACCase inhibiting-based herbicide.

Non-alcoholic steatohepatitis (NASH) is an inflammatory disorder that is characterized by chronic activation of the hepatic inflammatory response and subsequent liver damage. The regulation of macrophage polarization in liver is closely related to the progression of NASH. The orphan nuclear receptor retinoic-acid-related orphan receptor α (RORα) and Krüppel-like factor 4 (KLF4) are key regulators which promote hepatic macrophages toward M2 phenotype and protect against NASH in mice. Nobiletin (NOB), a natural polymethoxylated flavone, is previously reported as a RORα regulator in diet-induced obese mice. However, it is still unclear whether NOB has the protective effect on NASH. In this study, we investigated the role of NOB in NASH using a methionine and choline deficient (MCD)-induced NASH mouse model. Our results showed that NOB ameliorated hepatic damage and fibrosis in MCD fed mice. NOB treatment reduced the infiltration of macrophages and neutrophils in the liver in MCD-fed mice. Of importance, NOB significantly increased the proportion of M2 macrophages and the expression of anti-inflammatory factors in vivo and in vitro. Meanwhile, NOB also decreased the population of M1 macrophages and the expression of proinflammatory cytokines. Mechanistically, NOB elevated KLF4 expression in macrophages. Inhibition of KLF4 abolished NOB regulated macrophage polarization. Furthermore, the regulation of NOB in KLF4 expression was dependent on RORα.