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Monitoring peroxynitrite (ONOO–) fluctuations is particularly important for assessing pathological progression and oxidative damage due to their crucial role in maintaining the redox balance of organisms. However, due to the lack of efficient tools for differentially monitoring ONOO–fluctuations at different concentration ranges in vivo, the precise detection of endogenous ONOO–fluctuations under pathological conditions in living systems remains challenging. Herein, we rationally designed a double-enhanced emission cascade activatable near-infrared (NIR) fluorescent probe (B-TCF) for the measurement of ONOO–, which consists of a borate ester response group and a malononitrile hemicyanine fluorophore. Especially, after sequential oxidative hydrolysis of the borate ester group and xanthene skeleton, B-TCFexhibited a sequentially double-enhanced NIR emission response at 776 and 625 nm for different ONOO–concentration ranges. Moreover, B-TCFrevealed excellent and promising performance for ONOO–in terms of high selectivity, sensitivity, and reaction rate (k= 28.2 M–1s–1). Motivated by the two-step emission signal enhancement and large wavelength shift in the NIR region, B-TCFenabled discriminative imaging of ONOO–with the low and high concentrations in living cells. Importantly, B-TCFwas successfully applied for assessing the pathological progression of isoniazid and acetaminophen-induced liver damage in vivo by detecting the endogenous different ONOO–levels. Overall, this study not only demonstrates the first double-enhanced emission cascade activatable NIR fluorescent probe for measuring the dynamic variation of ONOO–in related diseases but also shows great potential as an effective molecular tool for evaluating the various stages of drug-induced liver damage.

Bipolar membranes (BPMs) enable the operation of electrochemical reactors with electrode compartments in different chemical environments or pH. The transport properties at the microscopic scale are dictated by the composition and morphology of the interfacial junctions as well as the specific chemistry of the ion-exchange layers that support the current of protons and hydroxide ions. This work elucidates the relation between water-dissociation efficiency and the physicochemical properties of the individual ion-exchange membrane layers in the poly(styrene-b-poly(ethylene-ran-butylene)-b-polystyrene) (SEBS)-based BPM. The optimal water dissociation performance of three previously reported water-dissociation catalysts in the SEBS-based BPM was examined, with junction thickness of graphene oxide > TiO2> SnO2, resulting in disparate junction morphologies at the BPM’s interface. A hybrid junction system, which included both the effective water dissociation catalyst SnO2and direct contacting of the ion-exchange membrane layer, exhibited high water dissociation efficiency. This was likely due to the immediate ion transport pathway provided by direct membrane contact around the catalyst, which also improved the interfacial adhesion. A higher ion exchange capacity (IEC) in BPMs substantially enhanced the water dissociation performance in BPMs without water-dissociation catalysts. However, the incorporation of the effective SnO2catalyst into the BPMs with a lower IEC significantly improved performance, an effect attributed to the hybrid junction system. Additionally, the increase in water uptake and ion conductivity of the cation exchange layer with higher IEC suggested that the cation exchange layer and its interface to the water-dissociation catalyst layer may play a key role in water dissociation. This study identifies the key parameters of individual BPM components and their interactions to water dissociation performance, offering new insights to guide in the construction of future BPMs optimized for enhanced water dissociation efficiency at high current densities.

Cobalt-catalyzed enantioconvergent cross-coupling of C(sp3)–H bonds with in situ-generated sulfenate anions is achieved to access chiral sulfoxides, which are found in the structures of many biologically active agents. The more challenging aliphatic C–H bonds as well as sterically hindered substrates containing tertiary C–H bonds could also be tolerated well. Mechanistic studies indicate that the transformation could undergo a CoIIS(O)R-mediated single-electron transfer with N-fluorocarboxamides, followed by a 1,5-hydrogen atom transfer and then a pivotal organocobalt(IV)-controlled enantioselective cross-coupling process. This novel asymmetric radical reaction for C–S bond construction could open a new door for the synthesis of sulfur-centered chiral compounds.

Cardiac fibrosis is a detrimental pathological process, which constitutes the key factor for adverse cardiac structural remodeling leading to heart failure and other critical conditions. Circular RNAs (circRNAs) have emerged as important regulators of various cardiovascular diseases. It is known that several circRNAs regulate gene expression and pathological processes by binding miRNAs. In this study we investigated whether a novel circRNA, named circNSD1, and miR-429-3p formed an axis that controls cardiac fibrosis. We established a mouse model of myocardial infarction (MI) for in vivo studies and a cellular model of cardiac fibrogenesis in primary cultured mouse cardiac fibroblasts treated with TGF-β1. We showed that miR-429-3p was markedly downregulated in the cardiac fibrosis models. Through gain- and loss-of-function studies we confirmed miR-429-3p as a negative regulator of cardiac fibrosis. In searching for the upstream regulator of miR-429-3p, we identified circNSD1 that we subsequently demonstrated as an endogenous sponge of miR-429-3p. In MI mice, knockdown of circNSD1 alleviated cardiac fibrosis. Moreover, silence of human circNSD1 suppressed the proliferation and collagen production in human cardiac fibroblasts in vitro. We revealed that circNSD1 directly bound miR-429-3p, thereby upregulating SULF1 expression and activating the Wnt/β-catenin pathway. Collectively, circNSD1 may be a novel target for the treatment of cardiac fibrosis and associated cardiac disease.

The spatial constraints imposed by the DNA structure have significant implications for the walking efficiency of three-dimensional DNA walkers. However, accurately quantifying and manipulating steric hindrance remains a challenging task. This study presents a steric hindrance-controlled DNA walker utilizing an enzymatic strand displacement amplification (ESDA) strategy for detecting microRNA-21 (miR-21) with tunable dynamic range and sensitivity. The steric hindrance of the DNA walker was precisely manipulated by varying the length of empty bases from 6.5 Å to 27.4 Å at the end of the track strand and adjusting the volumetric dimensions of the hairpin structure from 9.13 nm3to 26.2 nm3at the terminus of the single-foot DNA walking strand. This method demonstrated a tunable limit of detection for miR-21 ranging from 3.6 aM to 35.6 nM, along with a dynamic range from ∼100-fold to ∼166 000-fold. Impressively, it exhibited successful identification of cancer cells and clinical serum samples with high miR-21 expression. The proposed novel strategy not only enables tunable detection of miRNA through the regulation of steric hindrance but also achieves accurate and quantitative analysis of the steric hindrance effect, promising broader applications in personalized medicine, early disease detection, and drug development.

Pyrrolocarbazole skeletons are well known to possess a variety of biological activities that might be therapeutically useful in the treatment of cancers. Herein, an acid-catalyzed stereoselective hydroarylation/Diels–Alder cycloaddition/aromatization of ynamide–indoles is described. We newly designed and synthesized a variety of piperazine-fused pyrrolocarbazole derivatives that could be further applied to the synthesis of potent Wee1 inhibitors.

To clarify the precipitation of silica hydrate from the real desilication solutions of aluminosilicate solid wastes by adding seeds and improve integrated waste utilization, the seeded precipitation was studied using synthesized sodium silicate solution containing different inorganic salt impurities. The results show that sodium chloride, sodium sulfate, sodium carbonate, or calcium chloride can change the siloxy group structure. The number of high-polymeric siloxy groups decreases with increasing sodium chloride or sodium sulfate concentration, which is detrimental to seeded precipitation. Calcium chloride favors the polymerization of silicate ions, and even the chain groups precipitate with the precipitation of high-polymeric sheet and cage-like siloxy groups. The introduced sodium cations in sodium carbonate render a more open network structure of high-polymeric siloxy groups, although the carbonate ions favor the polymerization of siloxy groups. No matter how the four impurities affect the siloxy group structure, the precipitates are always amorphous opal-A silica hydrate.

A single-layer and wideband antenna with a small footprint and a good filtering response is developed based on the nonuniform grid array. First, the advantages of the conventional grid array antenna (GAA) in terms of miniaturization and closer multiresonances are demonstrated through comparison with a conventional microstrip patch antenna (MPA). Then, based on the analysis of these resonances in GAA, two evolution processes are implemented to improve the performance. On the one hand, the grid units are adjusted, i.e., the GAA turns into a nonuniform GAA (NUGAA). On the other hand, a coplanar L-probe and two pairs of short slots are integrated into the NUGAA. The former evolution makes the three resonance modes in GAA aligned, and thus the bandwidth is extended; meanwhile, this step introduces the radiation null (RN) at the lower operational band edge. The latter evolution generates the RN at the upper operational band-edge, which, together with the lower RN, leads to a skirt selectivity and preferable out-of-band rejection level; meanwhile, this step modifies the resonant mode in the higher band, and ensures a broadside radiation pattern with a consistent polarization. Finally, the optimized NUGAA with a compact size of $0.45\times 0.28\times 0.055\lambda _{0}^{3}$ is fabricated and measured, demonstrating excellent agreement with the simulation results. The proposed design achieves a bandwidth of 3.08–3.71 GHz (18.8%) with more than 21.5 dB out-of-band suppression level. Moreover, the bandwidth-to-volume ratio (BVR) reaches $0.027\times 10^{3}$ / $\lambda _{0}^{3}$ .

In this study, we aim to explore the application of a resonant cavity structure in quantum dot full-color display technology, with a specific focus on the impact of black matrix (BM) width on display performance. We propose two theoretical calculation methods to evaluate how BM width influences the image performance of displays. Through systematic investigation, we observed that increasing the BM width from 0 nm to 25 nm can decrease the cross talk between subpixels from 48.65% to 0%. Additionally, improvements can be made to reduce the Aliasing Effect between subpixels. The color gamut of the images can be enhanced across all three display structures examined in this research. Notably, the display featuring the Ag/ZnO/Ag sandwich structure achieves a color gamut ratio of 100.65% Adobe RGB, with a color gamut coverage of 87.17% Adobe RGB.

The vaginal epithelium plays pivotal roles in host defense against pathogen invasion, contributing to the maintenance of an acidic microenvironment within the vaginal lumen through the activity of acid-base transport proteins. However, the precise defense mechanisms of the vaginal epithelium after a bacterial infection remain incompletely understood. This study showed that bacterial lipopolysaccharide (LPS) potentiated net proton efflux by up-regulating the expression of Na+-H+exchanger 1 (NHE1) in vaginal epithelial cells. Pharmacologic inhibition or genetic knockdown of Toll-like receptor-4 and the extracellular signal–regulated protein kinase signaling pathway effectively counteracted the up-regulation of NHE1 and the enhanced proton efflux triggered by LPS in vaginal epithelial cells. In vivostudies revealed that LPS administration led to luminal acidification through the up-regulation of NHE1 expression in the rat vagina. Moreover, inhibition of NHE exhibited an impaired defense against acute bacterial infection in the rat vagina. These findings collectively indicate the active involvement of vaginal epithelial cells in facilitating luminal acidification during acute bacterial infection, offering potential insights into the treatment of bacterial vaginosis.

Epithelial–myoepithelial carcinoma (EMC) is a rare tumor that occurs mainly in the major salivary glands. Cases occurring in the nasal cavity are rarely reported. The patient was a 48-year-old woman with a postoperative pathological diagnosis of EMC. The patient recovered well after surgery. We consulted and summarized all previous cases of nasal EMC. We also discuss the clinical presentation, treatment, and prognosis of EMC of the nasal cavity and paranasal sinuses.

Disclosed herein is a rhodium(III)-catalyzed intramolecular cyclization of ynamides with propargyl esters. A variety of highly functionalized 2,5-dihydropyrroles were obtained in moderate to good yields with high E/Zselectivities. Subsequent oxidation of the products gave valuable pyrrole derivatives. Additionally, scale-up reactions and late-stage derivatizations highlight the potential synthetic utility of this methodology.

Boron neutron capture therapy (BNCT) targets invasive, radioresistant cancers but requires a selective and high B-10 loading boron drug. This manuscript investigates boron-rich poly(ethylene glycol)-block-(poly(4-vinylphenyl boronate ester)) polymer micelles synthesized via atom transfer radical polymerization for their potential application in BNCT. Transmission electron microscopy (TEM) revealed spherical micelles with a uniform size of 43 ± 10 nm, ideal for drug delivery. Additionally, probe sonication proved effective in maintaining the micelles’ size and morphology postlyophilization and reconstitution. In vitro studies with B16–F10 melanoma cells demonstrated a 38-fold increase in boron accumulation compared to the borophenylalanine drug for BNCT. In vivo studies in a B16–F10 tumor-bearing mouse model confirmed enhanced tumor selectivity and accumulation, with a tumor-to-blood (T/B) ratio of 2.5, surpassing BPA’s T/B ratio of 1.8. As a result, mice treated with these micelles experienced a significant delay in tumor growth, highlighting their potential for BNCT and warranting further research.

Comprehensive evaluation of reservoirs is an important link in gas reservoir exploration and development. The evaluation of tight carbonate reservoirs often focuses on the characteristics of porosity and permeability, ignoring the important factor of fractures, also the quantitative evaluation of reservoirs is relatively few. It is difficult to identify fractures and evaluate the reservoir factors qualitatively and quantitatively. Herein, the sedimentary microfacies and microporosity of the tight carbonate reservoir of the Ma55 submember in the eastern Sulige area are comprehensively studied by casting thin section, rock physical property, and capillary pressure test data. The backpropagation (BP) neural network algorithm is used to identify and predict fractures. Finally, through the analytic hierarchy process, the above reservoir influencing factors are modeled and quantitatively analyzed for reservoir evaluation. The results show that the highest probability of fracture development in the central and northwest areas of the study area can reach 0.92. The accuracy of the BP neural network model in identifying cracks can reach 80%, which is reliable and effective compared with the conventional logging identification method. Reservoirs can be classified into four types according to their quality. The synthetic weights of porosity, permeability and fracture development probability are 0.2, 0.2 and 0.216 respectively, which are the three most important evaluation parameters. This study improves the accuracy of fracture identification and prediction of tight reservoirs in comprehensive reservoir evaluation, which provides guidance and scheme for more detailed exploration and development of tight carbonate reservoirs.

The economical removal of organics from sodium aluminate solutions has been required for decades. Based on security filtration using tricalcium aluminate hexahydrate (TCA) as a filter aid, a novel short process to eliminate impurity particles and remove organics simultaneously was presented. Ultrafine TCA samples with poor crystallization, high TCA content, high surface free energy, and large lattice distortion were prepared in the concentrated sodium aluminate solution. The zeta potential of the TCA binary mixture in alkaline solutions was linearly depended on the TCA content, suggesting the additivity of the zeta potential in the binary mixture. The variation in the electrical double layer of the TCA binary mixture was demonstrated in the alkaline solution. Furthermore, the ultrafine TCA exhibited a high adsorption capacity for organics with long alkyl chains and high relative-molecular-mass. The adsorption capacity of 69.69 mg/g organic carbon for sodium humate was achieved, whereas the digestion at a high temperature remarkably reduced the adsorption capacity of TCA.

A chemical activation followed by a high-temperature self-healing strategy is employed to create abundant interconnected closed pores in lignin-derived hard carbon, and the mechanism of closed pore formation during carbonization is revealed.

Catalytic decomposition of NO by Cu-ZSM-5 has potential application. In order to reveal the mechanism of the process, the adsorption of NO over short-range Cu+pairs in Cu-ZSM-5 was simulated based on density functional theory. The reaction pathways of NO decomposition assisted by the by-products N2O and NO2were also proposed. The results showed that the double nuclear copper-oxygen species was an important active centre. During the reaction, the highest activation energy (171.39 kJ/mol) was required for the decomposition of the by-product NO2on the binuclear copper-oxygen species. While that for the decomposition of N2O was 86.92 kJ/mol, suggesting that the decomposition of NO2was more difficult. The desorption energy of N2and O2were 28.43 and 100.78 kJ/mol, respectively. The rate determining step was O2desorption. NO acted both as a reactant and a key reductant for the redox cycle of the active centre of Cu-ZSM-5 during the process.

Fixed‐dose combination (FDC) therapies can enhance patient convenience and adherence to prescribed treatment regimens. Elagolix is a novel oral gonadotropin‐releasing hormone receptor antagonist approved for management of moderate to severe pain associated with endometriosis and heavy menstrual bleeding associated with uterine fibroids. Hormonal add‐back therapy can attenuate the reversible hypoestrogenic effects of elagolix. An FDC formulation containing elagolix/estradiol (E2)/norethindrone acetate (NETA) 300/1/0.5 mg as the morning dose and an elagolix 300 mg capsule as the evening dose, were evaluated in 2 bioequivalence studies including the effects of food. Study 1 in premenopausal women assessed the bioavailability of the elagolix 300‐mg capsule relative to the commercially available elagolix 300‐mg tablet. Study 2 in postmenopausal women, elagolix/E2/NETA (300 mg/1 mg/0.5 mg) FDC capsule was assessed relative to the elagolix 300‐mg tablet coadministered with E2/NETA 1‐mg/0.5‐mg tablet, the regimen that was studied in Phase 3 uterine fibroid studies. Under fasting conditions, the test elagolix 300‐mg capsule was bioequivalent to the reference elagolix 300‐mg tablet. Under fasting conditions, the elagolix/E2/NETA FDC capsule was bioequivalent to the coadministered elagolix 300‐mg tablet and E2/NETA 1/0.5‐mg tablet. Following administration of elagolix/E2/NETA FDC capsule after a high‐fat breakfast, elagolix mean maximum concentration (Cmax) and area under the plasma concentration‐time curve (AUC) were 38% and 28% lower, relative to fasting conditions. NETA mean Cmaxwas 51% lower and AUC from time 0 to infinity was 20% higher, while baseline‐adjusted total estrone mean Cmaxand AUC were 46% and 14% lower, respectively. No safety concerns were identified. These results enabled bridging the elagolix/E2/NETA FDC capsule.

Electron-coupled-proton buffers (ECPBs) store and deliver protons and electrons in a reversible fashion. We have recently reported an ECPB based on Cu and a redox-active ligand that promoted 4H+/4e–reversible transformations (J. Am. Chem. Soc.2022, 144, 16905). Herein, we report a series of Cu-based ECPBs in which the ability of these to accept and/or donate H•equivalents can be tuned via ligand modification. The thermochemistry of the 4H+/4e–ECPB equilibrium was determined using open-circuit potential measurements. The reactivity of the ECPBs against proton-coupled electron transfer (PCET) reagents was also analyzed, and the results obtained were rationalized based on the thermochemical parameters. Experimental and computational analysis of the thermochemistry of the H+/e–transfers involved in the 4H+/4e–ECPB transformations found substantial differences between the stepwise (namely, BDFE1, BDFE2, BDFE3, and BDFE4) and average bond dissociation free energy values (BDFEavg.). Our analysis suggests that this “redox unleveling” is critical to promoting the disproportionation and ligand-exchange reactions involved in the 4H+/4e–ECPB equilibria. The difference in BDFEavg.within the series of Cu-based ECPBs was found to arise from a substantial change in the redox potential (E1/2) upon modification of the ligand scaffold, which is not fully compensated for by a change in the acidity/basicity (pKa), suggesting “thermochemical decompensation”.

Evaluating the heterogeneity of extracellular vesicles (EVs) is crucial for unraveling their complex actions and biodistribution. Here, we identify consistent architectural heterogeneity of EVs using cryogenic transmission electron microscopy (cryo-TEM), which has an inherent ability to image biological samples without harsh labeling methods while preserving their native conformation. Imaging EVs isolated using different methodologies from distinct sources, such as cancer cells, normal cells, immortalized cells, and body fluids, we identify a structural atlas of their dominantly consistent shapes. We identify EV architectural attributes by utilizing a segmentation neural network model. In total, 7,576 individual EVs were imaged and quantified by our computational pipeline. Across all 7,576 independent EVs, the average eccentricity was 0.5366 ± 0.2, and the average equivalent diameter was 132.43 ± 67 nm. The architectural heterogeneity was consistent across all sources of EVs, independent of purification techniques, and compromised of single spherical, rod-like or tubular, and double shapes. This study will serve as a reference foundation for high-resolution images of EVs and offer insights into their potential biological impact.

Excipients are important components of pharmaceutical preparations that affect their quality, safety, and efficacy. Macrocyclic receptors are a family of supramolecular excipients with several advantages, including molecular-level protection, small sizes, fast kinetics of host-guest recognition, and modular construction. With the continuous advances in the medical field, personalized and precision medicine requires the development of excipients with low dosages, integrated modifying effects, universality, and controlled release. To meet these requirements, we have developed a new family of macrocyclic excipients based on calixarenes by integrating their covalent (broad chemical design space) and noncovalent (wide range of substrates) advantages. Accordingly, azocalixarenes (AzoCAs) were designed, showing high binding affinities to a broad spectrum of active pharmaceutical ingredients (APIs), selectivity to interferents, and responsiveness to hypoxic microenvironments. Due to their highly efficient and controllable recognition, AzoCAs serve as low-dose excipients for 30 APIs. Molecular encapsulation by AzoCAs results in the integrated modification of the physicochemical properties of APIs, including solubility, stability, bioavailability, and biocompatibility. Moreover, AzoCAs can be reduced by azoreductases overexpressed in hypoxic microenvironments, leading to the controlled release of APIs. Collectively, AzoCA excipients have broad application prospects for a series of diseases such as enteritis, arthritis, stroke, cancer, bacterial infection and kidney injury, with diverse therapeutic modalities, including chemotherapy, photodynamic therapy, photothermal therapy, immunotherapy, boron neutron capture therapy, radiotherapy, fluorescence imaging, and their combinations.

A photocatalytic annulation cascade of unactivated N-alkene-linked indoles with Langlois’ reagent by a radical relay is developed at room temperature under blue LED irradiation. The reaction afforded a series of tri/difluoromethylated pyrrolo[1,2-a]indoles in moderate to good yields. The DFT study suggests that the reaction is ascribed to a rhodamine 6G-induced cyclization cascade involving vinyl addition-radical relay and hydrogen-atom-abstraction (HAA) processes, and interestingly, pyrrolo[1,2-a]indoles are applied as fluorescent dyes into the fluorescence spectrum and live-cell imaging. This paper represents an initial example on photocatalytic cyclization cascades by radical relay and the HAA process.

In pursuit of potent pharmaceutical candidates and to further improve their chemical traits, small ring systems can serve as a potential starting point. Small ring units have the additional merit of loaded strain at their core, making them suitable reactants as they can capitalize on this intrinsic driving force. With the introduction of cyclobutenone as a strained precursor to ketene, the photocycloaddition with another strained unit, bicyclo[1.1.0]butane (BCB), enables the reactivity of both π-units in the transient ketene. This double strain-release driven [2π+2σ]-photocycloaddition promotes the synthesis of diverse heterobicyclo[2.1.1]hexane units, a pharmaceutically relevant bioisostere. The effective reactivity under catalyst-free conditions with a high functional group tolerance defines its synthetic utility. Experimental mechanistic studies and density functional theory (DFT) calculations suggest that the [2π+2σ]-photocycloaddition takes place via a triplet mechanism.

In this study, we reported the synthesis and structural characterization of a triphos-CoIIcomplex [(κ3-triphos)CoII(CH3CN)2]2+(1) and a triphos-CoI-H complex [(κ2-triphos)HCoI(CO)2] (4). The facile synthetic pathways from 1to [(κ3-triphos)CoII(κ2-O2CH)]+(1′) and [(κ3-triphos)CoI(CH3CN)]+(2), respectively, as well as the interconversion between [(κ3-triphos)CoI(CO)2]+(3) and 4have been established. The activation energy barrier, associated with the dehydrogenation of a coordinated formate fragment in 1′yielding the corresponding 2accompanied by the formation of H2and CO2, was experimentally determined as 23.9 kcal/mol. With 0.01 mol % loading of 1, a maximum TON ∼ 1735 within 18 h and TOF ∼ 483 h–1for the first 3 h could be achieved. Kinetic isotope effect (KIE) values of 2.25 (kHCOOH/kDCOOH) and 1.36 (kHCOOH/kHCOOD) for the dehydrogenation of formic acid and its deuterated derivatives, respectively, implicate that the H–COOH bond cleavage is likely the rate-determining step. The catalytic mechanism proposed by density functional theory (DFT) calculations coupled with experimental 1H NMR and gas chromatography-mass spectrometry (GC-MS) analysis unveils two competing pathways for H2production; specifically, deprotonating a HCOO–H bond by a proposed Co–H intermediate Cand homolytic cleavage of the CoII–H moiety of C, presumably via a dimeric Co intermediate Dcontaining a [Co2(μ-H)2]2+core, to yield the corresponding 2and H2.

Background: Hericium erinaceus is a versatile mushroom with potential therapeutic benefits. A variety of bioactive compounds have been found in this mushroom that have anti-ulcer, antiinflammatory, immunomodulatory, and blood sugar and lipid regulating effects.Objectives: The aim is to isolate and characterize compounds from the rice medium of H. erinaceus and evaluate their potential therapeutic effects on oxidative stress-associated diseases.Methods: Fifteen compounds were isolated and characterized using NMR spectra and ESI-MS. The effects of compounds 3 and 7 on LPS-induced nitric oxide (NO) generation in BV2 cells and H2O2- induced cytotoxicity in SH-SY5Y cells were investigated. The regulation of nitric oxide production and apoptosis-associated proteins Bcl-2 and Bax were also examined.Results: Compounds 3 and 7 exhibited potent inhibitory effects on LPS-induced NO generation in microglial cells and significant resistance to H2O2-induced cytotoxicity in neuronal cells. Molecular docking simulations demonstrated the interaction of compounds 3 and 7 with iNOS and Bax, respectively. Western blot analysis revealed that 7 inhibited NO production and regulated the expression of Bax and Bcl-2, suggesting a protective effect against H2O2-induced apoptosis.Conclusion: Compounds 3 and 7 isolated from H. erinaceus are potential therapeutic candidates for oxidative stress-associated diseases, possibly through their regulation of nitric oxide production and apoptosis-related proteins. Further investigations are warranted to elucidate their mechanisms of action and therapeutic potential.

With the maturity and development of digital and intelligent technologies, the traditional construction industry is undergoing changes. However, most construction enterprises in China still lack comprehensive understanding of intelligent construction technologies (Minoli et al. IEEE Internet Things J 4:269–283, Minoli et al., IEEE Internet Things J 4:269–283, 2017). Therefore, research on the application and promotion of ICT is needed. This study aims to identify the factors hindering expressway construction enterprises from adopting ICT. Expert interviews and scoring were used to collect data from 32 experts. The TOSE framework identified fourteen influencing factors. The Fuzzy-DEMATEL-ISM method analyzed the expert scoring results. The results determined that the fourteen hypotheses were established, and the factors had hindering effects on enterprises adopting ICT. This study enhances research rigor by using empirical methods. The TOSE framework allows comprehensive identification of factors. And this study focuses on expressway construction enterprises, an under-researched area.

There exist a variety of resource conflicts due to resource constraints in production lines during the period of renewal of sophisticated products manufacturing, probably leading to production delays and resource wastage. With respect to the resource conflicts of the resource-constrained multiproject scheduling problem in sophisticated product lines, we construct a multiproject production line resource conflict resolution model, design a feedback regulation, and a hybrid genetic algorithm based on the cooperative game negotiation mechanism, which covers four stages starting from the manufacturer receiving the orders of original and upgraded products, taking into account of resource reallocation, resource sharing, and seeking help from emergency suppliers, to respond highly to the dynamics of customer orders and optimize production systems, achieving intelligent advances. The case results show that the proposed method can save up to 77.84% of the delay and scheduling cost, and these savings can allow the manufacturer to increase profits by 10.82% due to shortening the production delay. The current work not only helps manufacturers of sophisticated products to improve their production efficiencies and reduce delay cost but also provides a certain basis for future managers to make production management decisions.

Paclitaxel resistance is associated with a poor prognosis in non-small cell lung cancer (NSCLC) patients, and currently, there is no promising drug for paclitaxel resistance. In this study, we investigated the molecular mechanisms underlying the chemoresistance in human NSCLC-derived cell lines. We constructed paclitaxel-resistant NSCLC cell lines (A549/PR and H460/PR) by long-term exposure to paclitaxel. We found that triptolide, a diterpenoid epoxide isolated from the Chinese medicinal herb Tripterygium wilfordiiHook F, effectively enhanced the sensitivity of paclitaxel-resistant cells to paclitaxel by reducing ABCB1 expression in vivo and in vitro. Through high-throughput sequencing, we identified the SHH-initiated Hedgehog signaling pathway playing an important role in this process. We demonstrated that triptolide directly bound to HNF1A, one of the transcription factors of SHH, and inhibited HNF1A/SHH expression, ensuing in attenuation of Hedgehog signaling. In NSCLC tumor tissue microarrays and cancer network databases, we found a positive correlation between HNF1A and SHH expression. Our results illuminate a novel molecular mechanism through which triptolide targets and inhibits HNF1A, thereby impeding the activation of the Hedgehog signaling pathway and reducing the expression of ABCB1. This study suggests the potential clinical application of triptolide and provides promising prospects in targeting the HNF1A/SHH pathway as a therapeutic strategy for NSCLC patients with paclitaxel resistance.

Dynamic assessment with an intelligent agent can differentiate the capabilities and proficiency of students. It can therefore be advocated as an interactive approach to conduct assessments on students in learning systems. Facebook AI Research proposed ELF OpenGo, an open-source reimplementation of the AlphaZero algorithm. They also developed Darkforest, which displays the competence and skills of high-level amateur Go players. To enable these open-source AI bots to assist humans at different levels in learning Go, this paper proposes an intelligent agent for real-world applications in robotic edutainment and humanized co-learning. To achieve this, we successfully constructed an OpenGo Darkforest (OGD) cloud platform using these AI bots and further combined the brain computer interface with the OGD cloud platform to observe the relationship between the brainwaves and win rates of human Go players. The intelligent agent also converted human brainwaves into physiological indices and reflected these in the robot to express human feelings or emotions in real-time. For future educational applications, this paper also presents intelligent robot teachers learning together with students in Taiwan and Japan. More than 200 students have been co-learning with intelligent robot teachers in Tainan, Kaohsiung, Taipei, and Tokyo from 2018 to 2019. The learning performance and feedback from students and teachers has been extremely positive, especially from remedial students.

This article presents a dual-polarized wide-angle scanning phased array antenna for 5G application. This antenna has the properties of compact structure, orthogonal polarization, and low elevation coverage. The parasitic metal columns are used to suppress the abnormal resonance and improve the beamwidth of the elements. Bent frame metal arms are applied to make a compact element size of $0.37\times 0.37\times 0.33\lambda _{0}^{3}$ (where $\lambda _{0}$ represents the center frequency wavelength), which further broadens the beamwidth of the antenna element and optimizes the active reflection coefficients for large-angle scanning within the operating frequency band. Subsequently, a $6\times 6$ antenna array prototype based on the proposed element is designed and fabricated. The measured results indicate that the operational frequency band of the array spans from 3.0 to 3.8 GHz, and a wide scanning angle of ±80° can be achieved with a gain fluctuation below 7 dB. The measured results are closely correlated with the simulated ones, which confirms the effectiveness of the proposed design for wide-angle scanning.

Hypertension is a prominent contributor to vascular injury. Deubiquinatase has been implicated in the regulation of hypertension-induced vascular injury. In the present study we investigated the specific role of deubiquinatase YOD1 in hypertension-induced vascular injury. Vascular endothelial endothelial-mesenchymal transition (EndMT) was induced in male WT and YOD1−/−mice by administration of Ang II (1 μg/kg per minute) via osmotic pump for four weeks. We showed a significantly increased expression of YOD1 in mouse vascular endothelial cells upon Ang II stimulation. Knockout of YOD1 resulted in a notable reduction in EndMT in vascular endothelial cells of Ang II-treated mouse; a similar result was observed in Ang II-treated human umbilical vein endothelial cells (HUVECs). We then conducted LC-MS/MS and co-immunoprecipitation (Co-IP) analyses to verify the binding between YOD1 and EndMT-related proteins, and found that YOD1 directly bound to β-catenin in HUVECs via its ovarian tumor-associated protease (OTU) domain, and histidine at 262 performing deubiquitination to maintain β-catenin protein stability by removing the K48 ubiquitin chain from β-catenin and preventing its proteasome degradation, thereby promoting EndMT of vascular endothelial cells. Oral administration of β-catenin inhibitor MSAB (20 mg/kg, every other day for four weeks) eliminated the protective effect of YOD1 deletion on vascular endothelial injury. In conclusion, we demonstrate a new YOD1-β-catenin axis in regulating Ang II-induced vascular endothelial injury and reveal YOD1 as a deubiquitinating enzyme for β-catenin, suggesting that targeting YOD1 holds promise as a potential therapeutic strategy for treating β-catenin-mediated vascular diseases.

This article constructs a multiobjective super conflict grey target negotiation consensus approach to possibly solve problems of multiobjective group consensus. This approach considers relationships and behaviors of decision-makers (DMs), and the influence and constraint of the objectives by maximizing the satisfaction of DMs and the moderator and by minimizing the coordination cost. It first defines DMs’ initial bull’s-eye and consensus bull’s-eye, develops a multiobjective super conflict grey target negotiation consensus system, and constructs a multiobjective super conflict grey target negotiation consensus approach. Second, by making use of the theory and methods of grey target decision-making, grey relational analysis, super conflict, and group consensus, this article establishes a multiobjective super conflict grey target negotiation consensus approach for two situations: with or without any objective constraint. Third, by considering limited compromises and tolerance behaviors where DMs have compromise limits and cost-free thresholds toward the consensus bull’s-eye, we further optimize the consensus approach by employing parabolic utility functions in compromise intervals to reflect DMs’ risk-appetite attitude and then discussing how to reasonably allocate the consensus budgets based on tolerance intervals. In the end, we use the challenge of the transboundary pollution of the Taihu Lake Basin to confirm the validity and rationality of our proposed model.

IntroductionClinical exposure to paediatrics increases student interest in the specialty. However, the paediatric placement is relatively short and usually falls towards the end of medical school in the UK. A student-led shadowing scheme was developed to provide opportunities for medical students, including those at an early stage, to experience clinical paediatrics.MethodsPaediatric society members could apply for a shadowing day in the scheme run in 2022 and 2023. Feedback was collected following the day. Free text answers on learning points and the impact of shadowing on views of paediatrics were analysed using a framework approach. Knowledge of the role of a paediatrician and consideration of a career in paediatrics were rated on a 5-point Likert scale before and after the shadowing day.Results66 and 37 students completed shadowing days in cycles 1 and 2, respectively. Students’ knowledge of the role of the paediatrician and consideration of a career in paediatrics increased significantly after the shadowing scheme. The key themes that participating year 1–2 students gained from the scheme were: increased interest in paediatrics, increased knowledge about the specialty, challenges and decision-making in paediatrics, variety within paediatrics, communication skills, working with families, improving practical skills and some overwhelming first clinical experiences.DiscussionA student-run shadowing scheme is a novel and sustainable way to provide early exposure to paediatrics in medical school. This will help to develop interest in paediatrics from the start of medical school, as clinical exposure is a key factor in choosing paediatrics once qualified.

By assembling a tetradentate N-donor ligand tetra(pyridine-4-yl)benzene-1,4-diamine (TBD) with a copper ion, three novel Cu(I)-based coordination frameworks, bearing one-, two-, and three-dimensional (3D) architectures, namely, [Cu2Br2(TBD)·H2O] (1), [Cu2Br2(TBD)] (2), and [CuI(TBD)] (3), have been synthesized and characterized. Owing to the different coordination modes of [Cu2Br2] dinuclear units, compounds 1and 2display distinct structures with double-stranded chains for 1and 4-connected layers for 2. Compound 3presents a (3,4)-connected 3D network, which is fabricated from neutral Cu-TBD layers with the bridging organic ligands. Solid-state photoluminescence test implies that the three compounds exhibit bright yellow emissions with the luminescence lifetime at a microsecond scale. Interestingly, through the alternation of the ratios with compound 3and blue phosphor, tunable luminescence emissions from yellow to white light have been achieved. Moreover, the luminescence sensing ability toward various metal cations was examined on 1. The compound could be competent to serve as a selective fluorescent probe for the recognition of Fe3+despite the existence of other interferences.

The concept of convexity plays an important role in the study of economics and consumer theory. For the most part, such studies have been conducted on the assumption that consumer preferences are a binary relation that is complete, reflexive and transitive on the set Xof consumption choices. However, each consumer is a biological being with multidimensional physiological needs so that possible consumptions from different dimensions cannot be compared by using preferences. By removing that unrealistic assumption, this paper examines how the various concepts of convex preferences and relevant properties can be re-established. We derive a series of 10 formal propositions and construct 6 examples to show that (a) a weighted combination of two possible consumptions is not necessarily comparable with any of the consumptions; (b) not every convergent sequence of a consumer’s preferred consumptions asymptotically preserves that consumer’s preference preordering; (c) not all preferences satisfy either positive multiplicativity or additive conservation; (d) three types of preference convexities – weak convexity, convexity and strong convexity – can all be introduced into general convex spaces. This paper concludes with some research topics of expected significance for future works.

ABSTRACT Geosynthetics are an effective method to increase the seismic level of reinforcement soil structures. In this paper, sensor-enabled geobelts (SEGB) that performed self-measurement and reinforcement functions were developed on [...]

ABSTRACT The durability of geosynthetics is important for their service life, transportation and long-term storage. This paper presents the effects of three accelerating degradation tests (thermal oxidation, UV radiation and [...]

A photocatalyzed oxidative dehydrogenative annulation between 2-(1H-indol-2-yl)phenols and alkenylphenols is presented. Various indole-fused benzoxepines can be obtained at room temperature using atom-efficient strategies. This method not only avoids the use of stoichiometric amounts of oxidants but also exhibits excellent atom economy by generating H2O as the only theoretical byproduct.

The development of safe and versatile functional agents for nutritional fortification and plant health defense is highly needed. This paper reports a triazole selenourea that enables the nutritional fortification of Chinese flowering cabbage (Brassica campestrisL. ssp. chinensisvar. utilizTsen et Lee) microgreens and defense against Colletotrichum higginsianumand diamondback moth (Plutella xylostella). It can significantly increase the content of nutrients (such as soluble proteins, soluble sugars, total flavonoids, total phenolics, and glucosinolates) in microgreens, promote the absorption of mineral elements, and improve the composition of amino acids. It can also effectively control the incidence of anthracnose rot and P. xylostellain vivo.

A strategy for the synthesis of dibenz[a,j]anthracenes (DBAs) from cyclohexa-2,5-diene-1-carboxylic acids is presented. Our approach involves sequential C–H olefination, cycloaddition, and decarboxylative aromatization. In the key step for DBA skeleton construction, the bis-C–H olefination products, 1,3-dienes, are utilized as substrates for [4 + 2] cycloaddition with benzyne. This concise synthetic route allows for regioselective ring formation and functional group introduction. The structural features and photophysical properties of the resulting DBA molecules are discussed.

Solvothermal reaction of cadmium nitrate with a polypyridine-containing ligand tetra(pyridine-4-yl)benzene-1,4-diamine (TBD) gives rise to a novel Cd(II)-organic framework with the 3D interpenetrated architecture [Cd(TBD) (NO3)2·DMA](1) (DMA = N,N-dimethylacetamide). The stability test is performed on compound 1, which shows that the Cd-MOF can be quite stable in water and even harsh conditions. A photoluminescence study has been investigated on 1. Remarkably, nitrofurantoin, as a kind of antibiotic, has a great quenching effect on the luminescent performance of the prepared hybrid, suggesting that compound 1can be regarded as an effective chemical sensor to detect specific analytes. The anti-interference test, recyclability examination, and sensing mechanism have been further conducted. Moreover, in virtue of the electron transfer from oxygen of NO3–to nitrogen atoms of TBD, photochromism behavior can be easily realized in compound 1.

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Background and objectives: Migraine is a major public health problem owing to its long disease duration and disease relapse. Non-invasive brain stimulation treatments were reported effective for the management of migraine, but the comparative effectiveness of three main NIBSs, rTMS, nVNS, and tDCS, has not been studied. We aimed to explore the relative efficacy of rTMS, tDCS, and nVNS in migraine prophylaxis by using network meta-analysis (NMA). Methods: We searched OVID Medline, Embase, Cochrane Controlled Register of Trials, and Web of Science from inception to 1 January 2022. Randomized controlled trials that reported the efficacy of rTMS, tDCS or nVNS in the prophylactic treatment of migraine were included. The primary outcome was monthly migraine frequency, and secondary outcomes were headache intensity and the impact of headaches on daily life. The relative effects of the treatments in contrast to the others were measured by using standard mean difference (SMD). Results: We included 31 trials with 1659 participants. Fourteen trials were rated as low risk of bias. The results showed that tDCS (SMD − 1.58; 95%CI, − 2.38 to  − 0.79; P-score = 0.92) had the largest effect on migraine frequency when compared with sham interventions in reducing monthly migraine frequency, and tDCS had a larger effect than rTMS (SMD − 0.62; 95%CI, − 1.81 to 0.57) and nVNS (SMD − 1.39; 95%CI, − 3.27 to 0.49). tDCS had also the largest effect in reducing pain intensity when compared with sham intervention (SMD − 1.49; 95%CI, − 2.46 to  − 0.52) and rTMS (SMD − 0.48; 95%CI, − 2.06 to 1.09). Conclusions: For the prophylactic treatment of migraine, tDCS was relatively more effective than rTMS and nVNS. Head-to-head comparison trials are needed to confirm the findings.

[2 + 2]-Cycloaddition is the most straightforward approach to the construction of cyclobutanes. In this paper, the intermolecular [2 + 2]-cycloaddition reaction of 3-alkylideneindolin-2-ones with alkenes was achieved. This reaction can be used in the synthesis of 3-spirocyclobutyl oxindoles, polycyclic oxindoles, and late stage modification of some drug molecules.

The elongation of photosynthesis, or functional staygreen, represents a feasible strategy to propel metabolite flux towards cereal kernels. However, achieving this goal remains a challenge in food crops. Here we report the cloning of wheat CO2assimilation and kernel enhanced 2(cake2), the mechanism underlying the photosynthesis advantages and natural alleles amenable to breeding elite varieties. A premature stop mutation in the A-genome copy of the ASPARTIC PROTEASE 1(APP-A1) gene increased the photosynthesis rate and yield. APP1 bound and degraded PsbO, the protective extrinsic member of photosystem II critical for increasing photosynthesis and yield. Furthermore, a natural polymorphism of the APP-A1gene in common wheat reduced APP-A1’s activity and promoted photosynthesis and grain size and weight. This work demonstrates that the modification of APP1increases photosynthesis, grain size and yield potentials. The genetic resources could propel photosynthesis and high-yield potentials in elite varieties of tetraploid and hexaploid wheat.

Graphical abstract: In this study, we selected four cardiovascular stent materials of high clinical interest to evaluate their biomechanical effects on PTCA to provide vascular surgeons with additional tools for selecting cardiovascular stents.

• High mass-loading (∼7 mg cm−2) and binder-free MCV@CC flexible cathode was fabricated through the hydrothermal process under the assistance of MXene bridge. • The MXene bridge induces the growth of vanadium oxide on CC, achieving improved conductivity of the flexible electrode. • The MCV@CC flexible cathode exhibits large areal capacity (2.36 mAh cm−2) and excellent cycling stability (capacity retention of 86.1% after 1200 cycles). • Assembled quasi-solid-state MCV@CC//Zn flexible battery delivers potentially practical application in electronic products. Flexible zinc-ion batteries (ZIBs) are promising power sources for portable devices due to their high safety and low production cost. However, the low mass-loading and limited areal capacity of cathode materials are the major problems blocking the practicability of ZIBs. Herein, a high mass-loading and binder-free flexible vanadium oxide (MCV@CC) cathode with a large areal capacity was fabricated via the bridge effect of MXene. The functional MXene bridge induces the growth of the vanadium oxide active layer on the carbon cloth (CC) flexible substrate. The binder-free cathode can reduce the electrochemically inactive weight of the whole electrode, which enhances the energy density of ZIBs. Consequently, the MCV@CC cathode (mass-loading of ∼7 mg cm−2) delivers a desirable areal capacity (2.36 mAh cm−2) and good cycling stability (capacity retention of 86.1% after 1200 cycles at 10 mA cm−2). Moreover, several ex-situ characterization results indicate that the reaction mechanism upon battery cycling is based on the reversible Zn2+/H+ (de)intercalation in the vanadium oxide interlayer. Furthermore, the assembled quasi-solid-state MCV@CC//Zn flexible battery exhibits decent performance at different bending states. Such a bridge effect strategy sheds light on the construction of high mass-loading flexible electrodes for ZIBs applications. [ABSTRACT FROM AUTHOR]

In this paper, we propose a brain–computer interface(BCI)-based Human-in-the-Loop(Hit-Loop) agent for human and artificial intelligence(AI) colearning in music listening and appreciation with an Artificial Intelligence of Things(AIoT) application. The novel BCI-based Hit-Loop agentcontains human intelligencewith BCI-based AIoT-Fuzzy Markup Language(FML) and BCI-FML agents, as well as machine intelligencewith AI-FML Hit-Loopand AIoT-FML agents. We used FML to facilitate communication between humans and the AI-FML robotsthrough an AIoT-FML Learning Tool(AIoT-FML-LT), which was the core technology of the AI-FML Hit-Loop agentfor the BCI-based music listening and appreciation application. Furthermore, the novel AIoT-FML-LTin conjunction with the BCI-FMLand AIoT-FML agentswas developed and presented for music listening and student learning. Moreover, the BCI-based AIoT-FMLand AI-FML Hit-Loop agentswere applied in English language learning, and the AIoT-FML-LTassisted in measuring student learning performance in Taiwan and Japan. The human-like high-level knowledge base and rule base were constructed by various domain experts, as well as the personalized electroencephalography (EEG) and student English learning data sets collected using the BCI device and AIoT-FML-LT, respectively, and were applied to machine learning models such as deep learning and particle swarm optimization. Additionally, the AIoT-FML-LTwas connected to the AIoT-FML Hit-Loop agentfor human and robot colearning. The relationship between human perceptions and the AIoT-FML Hit-Loop agentin terms of eyes, ears, nose, tongue, body, and braincorresponding to sights, sounds, smells, tastes, objects of touch, and mindare discussed. Finally, the students learned human language and AI language by using the AI-FML robotsand AIoT-FML-LTtogether with the human English learning and AI-FML machine learning models, respectively. The experimental results reveal that the BCI-based Hit-Loop agentfor human and AI-FML robotcolearning in conjunction with AIoT applications can effectively facilitate music listening and appreciation application as well as English listening in Taiwan and Japan. The learning behavior and performance of the students also improved after incorporation of the human and robot colearning model.

Background and Objective: The aim of this study was to investigate the factors affecting extrusion time in both children and adults with ventilation tube (VT) insertion, providing useful information for clinicians for better decision-making, follow strategy, and potentially improve clinical outcomes for these patients.Methods: Data from patients receiving myringotomy with VT insertion from January 1, 2007, to June 30, 2012, were retrospectively collected and analyzed by the end of 2018. Various factors, including age, gender, history of VT insertion, tympanogram, size of VT used, local finding of tympanic membrane, hypertension, diabetes mellitus, hyperlipidemia, and postoperative ear infection, were included and analyzed to examine the effects of these factors on extrusion time.Results: A total of 447 patients were included in this study (Child group–Adult group = 237:210). The overall average extrusion time was 225.85 days. In the subgroup analysis, the average time was 221.3 days and 231.0 days for children and adults, respectively. The results showed that the VT extrusion time was significantly longer in participants without a history of VT insertion and in those where larger sized VTs were inserted in both age-groups. Male gender had an influence on extrusion time in children. In addition, a history of VT insertion and VT size were determined to be factors related to extrusion before 12 months in children.Conclusion: History of VT insertion and VT size were significantly related to VT extrusion time in both children and adults and defined as factors associated with extrusion before 12 months in children. The findings suggest avoiding VT with a diameter < 1 mm and considering an appropriately larger size in patients with a history of VT insertion to optimize VT retention.