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Background: Glioblastoma represents the most frequently diagnosed malignant neoplasm within the central nervous system. Human glioblastoma cells can be phenotypically reprogrammed into neuron‐like cells through the forced expression of NEUROG2 and SOXC factors. NEUROG2 serves as a pioneer factor, establishing an initial framework for this transformation. However, the specific role of SOXC factors has not been fully elucidated. Methods: In this study, we used ChIP‐seq to determine the potential target gene of NGN2. RNA‐seq has been used to evaluate the transcriptional change during NGN2‐SOX11‐mediated neuron reprogramming. Immunofluorescence was used to determine the neuron reprogramming efficacy and cell proliferation ability. ChIP‐qPCR, Co‐IP, and Western Blot were performed to investigate the mechanism. Results: Our findings reveal that SOXC factors, in contrast to their previously identified function as transcriptional activators, act as transcriptional repressors. They achieve this by recruiting TRIM28 to suppress the expression of ECT2, a RhoGEF. This suppression results in the differential regulation of RhoA, RAC1, and CDC42 activities throughout the reprogramming process. We further establish that small molecules targeting RhoA and its effectors can substitute for SOXC factors in facilitating the neuronal reprogramming of glioblastoma cells. Conclusion: These results underscore the pivotal role of SOXC factors' transcriptional repression and illuminate one of their specific downstream targets. [ABSTRACT FROM AUTHOR]

In this study, peptide‐based self‐assembled nanosheets with a thickness of approximately 1 nm were prepared using a hierarchical covalent physical fabrication strategy. The covalent alternating polymerization of helical peptide E3 with an azobenzene (AZO) structure yielded copolymers CoP(E3‐AZO), which physically self‐assembled into ultrathin nanosheets in an unanticipated two‐dimensional horizontal monolayer arrangement. This special monolayer arrangement enabled the thickness of the nanosheets to be equal to the cross‐sectional diameter of a single linear copolymer, which is a rare phenomenon. Molecular dynamics simulations suggested that the synergistic effect of multiple molecular interactions drives the self‐assembly of CoP(E3‐AZO) into nanosheets and that various methods, including phototreatment, pH adjustment, the addition of additives, and introduction of cosolvents, can alter the molecular interactions and modulate the self‐assembly of CoP(E3‐AZO), yielding diverse nanostructures. Remarkably, the ultrathin nanosheets selectively inhibited cancer cells at certain concentrations. [ABSTRACT FROM AUTHOR]

In this study, peptide‐based self‐assembled nanosheets with a thickness of approximately 1 nm were prepared using a hierarchical covalent physical fabrication strategy. The covalent alternating polymerization of helical peptide E3 with an azobenzene (AZO) structure yielded copolymers CoP(E3‐AZO), which physically self‐assembled into ultrathin nanosheets in an unanticipated two‐dimensional horizontal monolayer arrangement. This special monolayer arrangement enabled the thickness of the nanosheets to be equal to the cross‐sectional diameter of a single linear copolymer, which is a rare phenomenon. Molecular dynamics simulations suggested that the synergistic effect of multiple molecular interactions drives the self‐assembly of CoP(E3‐AZO) into nanosheets and that various methods, including phototreatment, pH adjustment, the addition of additives, and introduction of cosolvents, can alter the molecular interactions and modulate the self‐assembly of CoP(E3‐AZO), yielding diverse nanostructures. Remarkably, the ultrathin nanosheets selectively inhibited cancer cells at certain concentrations. [ABSTRACT FROM AUTHOR]

SUMMARY: The cytosol‐facing outer membrane (OM) of organelles communicates with other cellular compartments to exchange proteins, metabolites, and signaling molecules. Cellular surveillance systems also target OM‐resident proteins to control organellar homeostasis and ensure cell survival under stress. However, the OM proximity proteomes have never been mapped in plant cells since using traditional approaches to discover OM proteins and identify their dynamically interacting partners remains challenging. In this study, we developed an OM proximity labeling (OMPL) system using biotin ligase‐mediated proximity biotinylation to identify the proximity proteins of the OMs of mitochondria, chloroplasts, and peroxisomes in living Arabidopsis (Arabidopsis thaliana) cells. Using this approach, we mapped the OM proximity proteome of these three organelles under normal conditions and examined the effects of the ultraviolet‐B (UV‐B) or high light (HL) stress on the abundances of OM proximity proteins. We demonstrate the power of this system with the discovery of cytosolic factors and OM receptor candidates potentially involved in local protein translation and translocation. The candidate proteins that are involved in mitochondrion–peroxisome, mitochondrion–chloroplast, or peroxisome–chloroplast contacts, and in the organellar quality control system are also proposed based on OMPL analysis. OMPL‐generated OM proximity proteomes are valuable sources of candidates for functional validation and suggest directions for further investigation of important questions in cell biology. [ABSTRACT FROM AUTHOR]

The hydrophilicity of carbon cloth was improved through pretreatment using an oxidation process resulting in activated carbon cloth with microscopically pronounced grooved cracks. This activated carbon cloth served as a highly hydrophilic substrate suitable for electrode material loading while also possessing attractive electrochemical properties. Polypyrrole/reduced graphene oxide (PPy/rGO) composites were subsequently polymerized and chemically reduced in situ on the pretreated carbon cloth (HCC), introducing nitrogen atoms of different valences into the composite. Contact angle and electrochemical tests demonstrate that the prepared electrode material displayed enhanced hydrophilicity and low impedance. Based on HCC/PPy/rGO, the symmetrical flexible quasi-solid supercapacitor exhibited a high energy density of 0.60 mWh cm−3 at a power density of 6.25 mW cm−3, as well as a great power density of 62.5 mW cm−3 at 0.34 mWh cm−3 and good flexibility. Moreover, three fabricated supercapacitor devices connected in series illuminated a white LED for about 4 min, demonstrating the potential use of pretreated-carbon cloth/polypyrrole/rGO materials for flexible wearable devices. [ABSTRACT FROM AUTHOR]

Due to their higher safety, stability and energy density, all-solid-state batteries will be promising candidates for the next generation of lithium battery systems. The acquisition of high-performance solid-state electrolytes is pivotal in the actualization of all-solid-state batteries. By uniformly dispersing nanoscale Li1.3Al0.3Ti1.7(PO4)3 (LATP) powders into polyethylene oxide (PEO)-LiClO4 at varying mass ratios, a composite electrolyte membrane of approximately 50 μm thickness was prepared using the casting method. Subsequent characterization of these materials, accomplished through X-ray diffraction, scanning electron microscopy, electrochemical impedance spectroscopy, and cyclic charge–discharge tests, unveiled intriguing findings. Although the beneficial effect of LATP on the conductivity of PEO is somewhat limited, it demonstrates a capability to reduce the interface impedance between polyethylene oxide and lithium metal, thereby enhancing interface stability. This research provides constructive insights and prompts for designing composite electrolytes for future all-solid-state batteries. [ABSTRACT FROM AUTHOR]

Background: Acral lentiginous melanoma (ALM) is a highly malignant and invasive type of melanoma with unique locations of onset. Its incidence is increasing and early diagnosis is challenging. Reflectance confocal microscopy (RCM) is a non‐invasive technique that provides an accurate image of tissue pathology. There are few reports on the use of RCM for the assessment of ALM. Materials and methods: In this retrospective study, data from 31 patients with a clinical diagnosis of ALM were collected. RCM image features were compared with histopathological findings to determine the concordance between the two methods. The sensitivity, specificity, positive predictive value, and negative predictive value of RCM for the diagnosis of ALM were evaluated. Results: RCM and histopathology findings were concordant in 29 of 31 patients (93.5%). There were no false‐negative results, although there were two false positives in RCM diagnosis. The sensitivity of RCM for diagnosing ALM was 100%, specificity was 50%, positive predictive value was 93.1%, and negative predictive value was 100%. Conclusions: RCM showed substantial concordance with histopathology in the diagnosis of ALM. It is a reliable and valuable non‐invasive diagnostic tool that holds promise for the early diagnosis of ALM. [ABSTRACT FROM AUTHOR]

Simple Summary: Gastric cancer (GC) has a poor prognosis, as it has often grown into an advanced stage when diagnosed. Genetic testing is crucial for establishing a treatment plan. In this study, next-generation sequencing (NGS) was performed to discover that LRP1B mutation was associated with a poor prognosis in GC. Through layer-by-layer research, it was found that LRP1B expression in GC was accompanied by a higher-level infiltration of CD4+ T, CD8+ T cells, and CD86/CD163. It is concluded that LRP1B expression can stimulate tumor immune cell infiltration, thus bringing clinical benefits to GC patients. Background: Recent studies have shown that low-density lipoprotein receptor-related protein 1b (LRP1B), as a potential tumor suppressor, is implicated in the response to immunotherapy. The frequency of LRP1B mutation gene is high in many cancers, but its role in gastric cancer (GC) has not been determined. Methods: The prognostic value of LRP1B mutation in a cohort containing 100 patients having received radical gastrectomy for stage II–III GC was explored. By analyzing the data of LRP1B mRNA, the risk score of differentially expressed genes (DEGs) between LRP1B mutation-type and wild-type was constructed based on the TCGA-STAD cohort. The infiltration of tumor immune cells was evaluated by the CYBERSORT algorithm and verified by immunohistochemistry. Results: LRP1B gene mutation was an independent risk factor for disease-free survival (DFS) in GC patients (HR = 2.57, 95% CI: 1.28–5.14, p = 0.008). The Kaplan–Meier curve demonstrated a shorter survival time in high-risk patients stratified according to risk score (p < 0.0001). CYBERSORT analysis showed that the DEGs were mainly concentrated in CD4+ T cells and macrophages. TIMER analysis suggested that LRP1B expression was associated with the infiltration of CD4+ T cells and macrophages. Immunohistochemistry demonstrated that LRP1B was expressed in the tumor cells (TCs) and immune cells in 16/89 and 26/89 of the cohort, respectively. LRP1B-positive TCs were associated with higher levels of CD4+ T cells, CD8+ T cells, and CD86/CD163 (p < 0.05). Multivariate analysis showed that LRP1B-positive TCs represented an independent protective factor of DFS in GC patients (HR = 0.43, 95% CI: 0.10–0.93, p = 0.042). Conclusions: LRP1B has a high prognostic value in GC. LRP1B may stimulate tumor immune cell infiltration to provide GC patients with survival benefits. [ABSTRACT FROM AUTHOR]

The post-pandemic era has transformed work-life boundaries, driven by factors such as working hours, an increased number of working women and single parents, the implementation of various ICTs, and the rise of flexible work arrangements. This study examines the role of female workers and entrepreneurs in establishing and managing coworking spaces (CSs) designed to improve work-life balance through flexible scheduling and location options. The challenges faced by female entrepreneurs in promoting an inclusive society and economic system are also explored, as well as the benefits experienced by independent workers and teleworkers in terms of networking, social interaction, knowledge exchange, and community building. The "She Economy" is analyzed in three stages: germination, growth, and maturity, considering challenges from both family and workplaces. This paper investigates the background of female identity and the ideological transformation of female identity in the consumption process after the pandemic, using mass media, especially female-focused media, as a lens. Finally, the paper proposes recommendations for the future development of the "She Economy" from the perspectives of communicators, women, and the social environment. [ABSTRACT FROM AUTHOR]

Candida albicans (C. albicans), the most common fungal pathogen, has the ability to form a biofilm, leading to enhanced virulence and antibiotic resistance. Cocultimycin A, a novel antifungal antibiotic isolated from the co-culture of two marine fungi, exhibited a potent inhibitory effect on planktonic C. albicans cells. This study aimed to evaluate the anti-biofilm activity of cocultimycin A against C. albicans and explore its underlying mechanism. Crystal violet staining showed that cocultimycin A remarkably inhibited biofilm formation in a dose-dependent manner and disrupted mature biofilms at higher concentrations. However, the metabolic activity of mature biofilms treated with lower concentrations of cocultimycin A significantly decreased when using the XTT reduction method. Cocultimycin A could inhibit yeast-to-hypha transition and mycelium formation of C. albicans colonies, which was observed through the use of a light microscope. Scanning electron microscopy revealed that biofilms treated with cocultimycin A were disrupted, yeast cells increased, and hypha cells decreased and significantly shortened. The adhesive ability of C. albicans cells treated with cocultimycin A to the medium and HOEC cells significantly decreased. Through the use of a qRT-PCR assay, the expression of multiple genes related to adhesion, hyphal formation and cell membrane changes in relation to biofilm cells treated with cocultimycin A. All these results suggested that cocultimycin A may be considered a potential novel molecule for treating and preventing biofilm-related C. albicans infections. [ABSTRACT FROM AUTHOR]

In this study, we report the development of a porous activated carbon electrode (PACE) material for supercapacitors, derived from anthracite carbonized at high temperatures in an argon atmosphere. Our approach involves a facile air pre-oxidation process, followed by KOH activation, to significantly enhance the material's specific surface area and porosity. The pre-oxidation treatment effectively increased the specific surface area to 1555.1 m2 g−1, resulting in a large number of micropores and mesopores. Moreover, this treatment effectively modulated the structure of small-to-medium-sized pores (2–4 nm) in the PACE samples, ensuring sufficient charge storage capacity and rapid electrolyte ion transport. The optimal sample, C-Pre-2h, demonstrated remarkable cycling stability, with 100% capacitance retention after 10,000 cycles, and a high specific capacitance of 272.1 F g−1 at 1 A g−1. A symmetric supercapacitor based on C-Pre-2h exhibited a substantial energy density of 10.11 Wh kg−1 at 256 W kg−1, alongside a high power density of 25,641 W kg−1 at 3.16 Wh kg−1. This work presents a cost-effective porous carbon material with exceptional cycling stability and superior performance for supercapacitor applications. [ABSTRACT FROM AUTHOR]

Lead-free BaTiO3 (BTO) film was fabricated by pulsed laser deposition on LaAlO3/SrTiO3 (LAO/STO) heterostructure in oxygen pressure of 2 × 10−3 Pa, which is experimentally required for ensuring the two-dimensional electron gas at LAO/STO heterointerface. Modulation of back-gate voltage on the superconductivity of LAO/STO and BTO/LAO/STO heterointerfaces was studied. The results indicate that the back-gate voltage can adjust the resistance at high temperatures around 300 mK, while it does not modulate the superconducting transition temperature of LAO/STO, which occurs at 160 mK. As for BTO/LAO/STO, it still shows a superconducting transition-like behavior at 110 mK. However, when a negative back-gate voltage is applied, the superconducting transition-like behavior disappears, and after removing the voltage, unlike what was observed for LAO/STO, the superconductivity cannot be recovered. Given this, some underlying mechanisms are proposed. [ABSTRACT FROM AUTHOR]

Manganese oxides (MnOx) have become an increasingly popular electrode material for supercapacitors due to their low cost, abundance, and environmentally-friendly nature. One important factor that enhances their electrochemical properties is the manganese valence. Mn3+ is particularly useful as it exhibits two redox couples (Mn2+/Mn3+ and Mn3+/Mn4+), which maximize the redox reaction and result in excellent electrochemical performance. This study focused on regulating the manganese valence using a facile pyrolysis method, resulting in a Mn3+-rich MnOx/rGO composite (rGO denotes reduced graphene oxide) at a pyrolysis temperature of 400 °C. The composite demonstrated a high specific capacitance of 304 F g−1. Additionally, asymmetric supercapacitors (MnOx/rGO//activated carbon) were assembled with aqueous and quasi-solid electrolytes respectively, and they demonstrated similar performance. The supercapacitor device also showed good capacitance retention of 82% after 10,000 charge/discharge cycles at a current density of 10 A g−1. Furthermore, the variation of the energy storage mechanism for MnOx/rGO with the change of manganese valence was discussed. Overall, this work highlights the importance of controllable synthesis of MnOx-based electrode materials for high-performance supercapacitors, and could pave the way for future developments in the field. [ABSTRACT FROM AUTHOR]

The drivers of fire regimes prior to the European occupation of Australia are still contentious, with some advocating regimes dominated by anthropogenic ignitions and others advocating a climate source or mixture of these elements. Here, we examine an 850-year history of fire regimes at Lake Werri Berri in south-east Australia, prior to and following European occupation. Macroscopic charcoal and FTIR spectroscopy were used to infer broad changes of the fire regime in proximity to the lake. We found little change through much of the 850-year period and most interesting, no apparent change following the initial displacement of Indigenous peoples and the introduction of farming and woodcutting to the region by Europeans. From the mid-20th Century onwards, there was an increase in both area burnt and fire severity or intensity, likely the result of increased fuel load and connectivity following an extended period of increased precipitation and heavier recreational land usage, which likely led to an increase in anthropogenic ignitions. [ABSTRACT FROM AUTHOR]

Ethnographic observations suggest that Indigenous peoples employed a distinct regime of frequent, low-intensity fires in the Australian landscape in the past. However, the timing of this behaviour and its ecological impact remain uncertain. Here, we present detailed analysis of charcoal, including a novel measure of fire severity using Fourier transform infrared (FTIR) spectroscopy, at a site in eastern Australia that spans the last two glacial/interglacial transitions between 135–104 ka and 18–0.5 ka BP (broadly equivalent to Marine Isotope Stage (MIS) 6-5 and 2-1, respectively). The accumulation of charcoal and vegetation composition was similar across both periods, correlating closely with Antarctic ice core records, and suggesting that climate is the main driver of fire regimes. Fire severity was lower over the past 18,000 years compared to the penultimate glacial/interglacial period and suggests increasing anthropogenic influence over the landscape during this time. Together with local archaeological records, our data therefore imply that Indigenous peoples have been undertaking cultural burning since the beginning of the Holocene, and potentially the end of the Last Glacial Maximum. We highlight the fact that this signal is not easily discernible in the other proxies examined, including widely used charcoal techniques, and propose that any anthropogenic signal will be subtle in the palaeo-environmental record. While early Indigenous people's reasons for landscape burning were different from those today, our findings nonetheless suggest that the current land management directions are based on a substantive history and could result in a reduction in extreme fire events. [ABSTRACT FROM AUTHOR]

Mitochondria are the center of energy metabolism in eukaryotic cells and play a central role in the metabolism of living organisms. Mitochondrial diseases characterized by defects in oxidative phosphorylation are the most common congenital diseases. Meanwhile, mitochondrial dysfunction caused by secondary factors such as non-inherited genetic mutations can affect normal physiological functions of human cells, induce apoptosis, and lead to the development of various diseases. This paper reviewed several major factors and mechanisms that contribute to mitochondrial dysfunction and discussed the development of diseases closely related to mitochondrial dysfunction and drug treatment strategies discovered in recent years. [ABSTRACT FROM AUTHOR]

Abdominal aortic aneurysm (AAA) is a vascular disorder greatly threatening life of the elderly population. Dexmedetomidine (DEX), an α2-adrenergic receptor agonist, has been shown to suppress AAA development. Nevertheless, the signaling pathways that might be mediated by DEX in AAA has not been clarified. Vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) were treated with Angiotensin II (Ang II) to mimic AAA in vitro. BrdU, wound healing, and Transwell assays were utilized for measuring VSMC proliferation and migration. Western blotting was used for evaluating protein levels of contractile VSMC markers, collagens and matrix metalloproteinases (MMPs) in VSMCs as well as apoptosis- and HMGB1/TLR4/NF-κB signaling-related markers in ECs. Cell adhesion molecule expression and monocyte-endothelial adhesion were assessed by immunofluorescence staining and adhesion assays. Flow cytometry was implemented for analyzing EC apoptosis. Hematoxylin-eosin staining and ELISA were used to detect the effect of DEX in vivo. In this study, DEX inhibited Ang II-evoked VSMC phenotype switch and extracellular matrix degradation. DEX suppressed the inflammatory response and apoptosis of ECs induced by Ang II. DEX inhibited HMGB1/TLR4/NF-κB signaling pathway in Ang II-treated ECs. DEX attenuated Ang II-induced AAA and inflammation in mice. Overall, DEX ameliorates Ang II-induced VSMC phenotype switch, and inactivates HMGB1/TLR4/NF-κB signaling pathway to alleviate Ang II-induced EC dysfunction. [ABSTRACT FROM AUTHOR]

This study examined the effects of commonly used oxidants in sedimentary macroscopic charcoal analysis on two sediment cores from Thirlmere Lakes National Park, Southeast Australia. The cores, from Lake Werri Berri (WB3) and Lake Couridjah (LC2), span ~900 years and 135,000 years, respectively. The Charcoal Accumulation Rate (CHAR) for both charcoal area and count was quantified using four different chemical treatments and compared to a control using only water. We also quantified the Charring Intensity (CI) of isolated charcoal fragments, a proxy for the severity/intensity of fire, determined using the FTIR spectral characteristics of the remaining charcoal after each treatment. We found significant differences in both the area and number of particles across all treatments in both cores. Significantly, we found substantial differences in CI between treatments, with few charcoal particles formed in low-severity fire (e.g., below ~400 °C or 3.0 °C.s.106) in groups treated with an oxidant. In contrast, the control group displayed a wider range of CI values and contained lightly pyrolyzed particles. This suggests that methods using an oxidant to concentrate sedimentary charcoal are potentially biasing records towards high-intensity or -severity fires. We suggest that consideration should be used when choosing laboratory methods based on the hypotheses being tested. [ABSTRACT FROM AUTHOR]

Airline crew scheduling is a very important part of the operational planning of commercial airlines, but it is a linear integer programming problem with multi-constraints. Traditionally, the airline crew scheduling problem is determined by solving the crew pairing problem (CPP) and the crew rostering problem (CRP), sequentially. In this paper, we propose a new heuristic solver based on the parallel genetic algorithm and an innovative crew scheduling algorithm, which improves traditional crew scheduling by integrating CPP and CRP into a single problem. The innovative scheduling method includes a global heuristic search and an adjustment for flights and crew so as to realize crew scheduling. The parallel genetic algorithm is used to divide the population into multiple threads for parallel calculation and to optimize the randomly generated flight sequence to maximize the number of flights that meet the crew configuration. Compared with the genetic algorithm, CPLEX and Gurobi, it shows high optimization efficiency, with a time reduction of 16.57–85.82%. The experiment shows that our crew utilization ratio is higher than that for traditional solvers, achieving almost 44 flights per month, with good scalability and stability in both 206 and 13,954 flight datasets, and can better manage airline crew scheduling in times of crew scarcity. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular Carcinoma (HCC) is a common malignant neoplasm with limited treatment options and poor outcomes. Thus, there is an urgent need to find sensitive biomarkers for HCC. Methods: Gene expression and clinicopathological information were obtained from public databases, based on which a pyroptosis-related gene signature was constructed by the least absolute shrinkage and selection operator Cox regression. The applicability of the signature was evaluated via Kaplan–Meier curve and time-dependent ROC curve. TIMER, QUANTISEQ, MCPCOUNTER, EPIC, CIBERSORT, ssGSEA, and ESTIMATE were employed to assess the immune status. Comparisons between groups were analyzed with Wilcoxon test. Pearson and Spearman correlation analyses were adopted for linear correlation analysis. Genetic knockdown was conducted using siRNA transfection and the mRNA expression levels of interest genes were measured using quantitative reverse transcription PCR. Finally, protein levels in 10 paired tumor tissues and adjacent non-tumor tissues from HCC patients were measured using immunohistochemistry. Results: A pyroptosis-related gene signature was established successfully to calculate independent prognostic risk scores. It was found that survival outcomes varied significantly between different risk groups. In addition, an attenuated antitumor immune response was found in the high-risk group. Meanwhile, multiple immune checkpoints were up-regulated in high-risk score patients. Cell cycle-related genes, angiogenesis-related genes and tumor drug resistance genes were also markedly elevated. Knockdown of prognostic genes in the signature significantly inhibited the expression of immune checkpoint genes and angiogenesis-related genes. Besides, each prognostic gene was expressed at a higher level in HCC tissues than in adjacent normal tissues. Conclusions: We successfully established a novel pyroptosis-related gene signature which could help predict the overall survival and assess the immune status of HCC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: The sequence–structure–function paradigm, which emphasizes the relationship between the 3D structure and functions of a protein, is a core concept in biology. The relationship further determines the functional specificity of proteins. By studying G-protein-coupled receptors (GPCRs), we investigated how the 3D structures of proteins are related to the activation mechanisms and functions. The activation of GPCRs involves many events, such as conformational changes, agonist binding, G-protein binding, nucleotide binding/release, etc. By exploring the coupled free-energy landscape of these events, we offer a possible explanation for the functional differences between the three families of GPCRs and how they are related to their signal responding specificities. G-protein-coupled receptors (GPCRs) are a critical family in the human proteome and are involved in various physiological processes. They are also the most important drug target, with approximately 30% of approved drugs acting on such receptors. The members of the family are divided into six classes based on their structural and functional characteristics. Understanding their structural–functional relationships will benefit us in future drug development. In this article, we investigate the features of protein function, structure, and energy that describe the dynamics of the GPCR activation process between different families. GPCRs straddle the cell membrane and transduce signals from outside the membrane into the cell. During the process, the conformational change in GPCRs that is activated by the binding of signal molecules is essential. During the binding process, different types of signal molecules result in different signal transfer efficiencies. Therefore, the GPCR classes show a variety of structures and activation processes. Based on the experimental crystal structures, we modeled the activation process of the β2 adrenergic receptor (β2AR), glucagon receptor (GCGR), and metabotropic glutamate receptor 2 (mGluR2), which represent class A, B, and C GPCRs, respectively. We calculated their activation free-energy landscapes and analyzed the structure–energy–function relationship. The results show a consistent picture of the activation mechanisms between different types of GPCRs. This could also provide us a way to understand other signal transduction proteins. [ABSTRACT FROM AUTHOR]

Garnet-type Li7La3Zr2O12 (LLZO) is considered as a promising solid electrolyte. However, the synthesis of LLZO often requires a high temperature, which may lead to the evaporation of the lithium and result in a decrease in ionic conductivity. Therefore, it is an important issue how to reduce the synthesis temperature of LLZO and simultaneously increase its ionic conductivity. Herein, we synthesized garnet-type solid electrolytes of Li6.1Ga0.3La3Zr2O12 (LLZO-Ga) with x wt% CuO (x = 0, 0.2, 0.5, 1, 2) by the traditional solid-state reaction method, in which CuO was introduced as a sintering aid to reduce the sintering temperature of LLZO-Ga and increase its Li-ion conductivity. It is found that adding a small amount of CuO as an additive can reduce the sintering temperature from 1100 ℃ to about 1000 ℃. As a result, when the amount of CuO is 0.5 wt%, LLZO-Ga shows the highest room-temperature ionic conductivity and the lowest activation energy, which are 1.111 mS/cm and 0.27 eV, respectively. [ABSTRACT FROM AUTHOR]

Background: Metastasis and/or recurrence can decrease the survival time of gastric cancer patients undergoing radical operation. Among them, those with stage IIIb and IIIc are especially at a high risk of metastasis and recurrence. The traditional Chinese medicine collaborative model (TCMCM) has been used in the treatment of cancer; however, its effects have not been systematically evaluated. This study is designed to evaluate whether TCMCM can decrease adverse effects after chemotherapy and reduce the recurrence and metastasis of stage IIIb and IIIc gastric cancer. Methods/design: This prospective, multicenter, randomized, open-label trial will recruit 260 patients with stage IIIb and IIIc gastric cancer who undergo radical surgery for D2 lymphadenectomy. The patients will be randomly assigned to receive usual adjuvant chemotherapy and TCMCM (intervention group) in a 1:1 ratio. Patients in the intervention group will receive an oral traditional Chinese formula, auricular acupressure, and acupoint therapy. All participants will receive usual adjuvant chemotherapy. The primary outcome is a 3-year disease-free survival rate. Secondary outcomes include quality of life, side effects caused by chemotherapy, and safety-related measures. Assessments will be performed during the screening period, at 4 and 8 cycles after adjuvant chemotherapy, and 9, 12, 18, 24, 30, and 36 months after randomization. Adverse events will be recorded. In addition, biological samples will be collected for mechanism analysis. Discussion: This will be the first clinical trial to evaluate the effects of TCMCM on disease-free survival (DFS) and quality of life in patients with stage IIIb and IIIc gastric cancer. Our results may be used to standardize TCMCM. We will also perform a larger-scale clinical trial in the future. Trial registration: ClinicalTrials.govNCT03607656. Registered on 1 July 2018. The final protocol version is V1.1. [ABSTRACT FROM AUTHOR]

The need for novel antibiotics has become imperative with the increasing prevalence of antibiotic resistance in Gram-negative bacteria in clinics. Acting as a permeability barrier, lipopolysaccharide (LPS) protects Gram-negative bacteria against drugs. LPS is synthesized in cells and transported to the outer membrane (OM) via seven lipopolysaccharide transport (Lpt) proteins (LptA–LptG). Of these seven Lpt proteins, LptC interacts with LptA to transfer LPS from the inner membrane (IM) to the OM, and assembly is aided by LptD/LptE. This interaction among the Lpt proteins is important for the biosynthesis of LPS; therefore, the Lpt proteins, which are significant in the assembly process of LPS, can be a potential target for new antibiotics. In this study, a yeast two-hybrid (Y2H) system was used to screen compounds that could block LPS transport by inhibiting LptA/LptC interaction, which finally disrupts the biosynthesis of the OM. We selected the compound IMB-0042 for this study. Our results suggest that IMB-0042 disrupts LptA/LptC interaction by binding to both LptA and LptC. Escherichia coli cells, when treated with IMB-0042, showed filament morphology, impaired OM integrity, and an accumulation of LPS in the periplasm. IMB-0042 inhibited the growth of Gram-negative bacteria and showed synergistic sensitization to other antibiotics, with low cytotoxicity. Thus, we successfully identified a potential antibacterial agent by using a Y2H system, which blocks the transport of LPS by targeting LptA/LptC interaction in Escherichia coli. [ABSTRACT FROM AUTHOR]

Objective Abnormal expression of CUT-like homeobox 2 gene (CUX2) has been highlighted as potential clinical biomarkers in human cancers. Notably, the function of CUX2 has been less elucidated in breast cancer (BC). We focused on the role of the CUX2 in tumorigenesis and progression of BC with the involvement of the lysine demethylase 5B (KDM5B)/sex determining region Y-box 17 (SOX17) axis. Methods CUX2, KDM5B, and SOX17 expression levels in BC tissues and cells were tested by reverse transcription quantitative PCR and Western blotting. Later, the effects of CUX2, KDM5B, and SOX17 on the malignant behaviors of MDA-MB-231 and MCF-7 cells were analyzed by CCK-8, colony formation, and Transwell assays in vitro. The interactions of CUX2, KDM5B, and SOX17 were validated by online website prediction, ChIP assay, and dual luciferase reporter gene assay. The subcutaneous tumorigenesis in nude mice was conducted to observe the roles of CUX2, KDM5B, and SOX17 in BC tumor growth in vivo. Results CUX2 and KDM5B were highly expressed while SOX17 had low expression in BC. Inhibition of CUX2 suppressed BC cell malignant phenotypes. CUX2 promoted KDM5B expression through transcriptional activation, enabling its high expression in BC. KDM5B inhibited SOX17 expression through histone demethylation. Overexpression of KDM5B or downregulation of SOX17 reversed the inhibitory effect of CUX2 downregulation on the malignant behaviors of BC cells. Inhibition of CUX2 impeded BC cell growth in vivo through the KDM5B/SOX17 axis. Conclusion This study highlights that suppression of CUX2 inhibits KDM5B to repress tumorigenesis and progression of BC through overexpressing SOX17. [ABSTRACT FROM AUTHOR]

Background: Metastasis and/or recurrence can decrease the survival time of gastric cancer patients undergoing radical operation. Among them, those with stage IIIb and IIIc are especially at a high risk of metastasis and recurrence. The traditional Chinese medicine collaborative model (TCMCM) has been used in the treatment of cancer; however, its effects have not been systematically evaluated. This study is designed to evaluate whether TCMCM can decrease adverse effects after chemotherapy and reduce the recurrence and metastasis of stage IIIb and IIIc gastric cancer. Methods/design: This prospective, multicenter, randomized, open-label trial will recruit 260 patients with stage IIIb and IIIc gastric cancer who undergo radical surgery for D2 lymphadenectomy. The patients will be randomly assigned to receive usual adjuvant chemotherapy and TCMCM (intervention group) in a 1:1 ratio. Patients in the intervention group will receive an oral traditional Chinese formula, auricular acupressure, and acupoint therapy. All participants will receive usual adjuvant chemotherapy. The primary outcome is a 3-year disease-free survival rate. Secondary outcomes include quality of life, side effects caused by chemotherapy, and safety-related measures. Assessments will be performed during the screening period, at 4 and 8 cycles after adjuvant chemotherapy, and 9, 12, 18, 24, 30, and 36 months after randomization. Adverse events will be recorded. In addition, biological samples will be collected for mechanism analysis. Discussion: This will be the first clinical trial to evaluate the effects of TCMCM on disease-free survival (DFS) and quality of life in patients with stage IIIb and IIIc gastric cancer. Our results may be used to standardize TCMCM. We will also perform a larger-scale clinical trial in the future. Trial registration: ClinicalTrials.govNCT03607656. Registered on 1 July 2018. The final protocol version is V1.1. [ABSTRACT FROM AUTHOR]

Chemically reduced graphene oxide (RGO) samples prepared with three different reducing agents, such as sodium borohydride (NaBH4), hydrazine hydrate (N2H4·H2O), and N, S dual-doped thiourea (CS(NH2)2), were prepared (respectively labeled as B-RGO, N-RGO, N/S-RGO) and compared with commercial RGO samples (represented as C-RGO). The changes of their structures and properties over time have been studied to explore the stability of electrochemical performance. Samples preserved for 0 day (fresh sample), 7 days, 30 days, and 90 days were obtained by storing the prepared RGO powder for different times under natural conditions and characterized by means of analytical methods. The results suggested that even though the phase structures and electrochemical performance of the samples were relatively stable, their surface morphology and oxidation degree varied slightly, and the electrical conductivity even changed dramatically, which decreased significantly at the initial stage of storage. It is found that among different reducing agents, N-RGO samples prepared in this work have similar stability in performance and approximate specific capacitance of around 150.0 F/g at 1 A/g compared to that of C-RGO. As for N/S-RGO, it shows the highest conductivity of 107 S/m, but its decline rate is faster than that of N-RGO, which possesses the conductivity of 76 S/m. In this work, we compared the electrochemical performance of different chemically reduced RGO at different storage times and tried to explain the principles of their performance changes over time. This work has focused on investigating the performance stability of RGO during a long preservation period of up to 90 days, complemented extensive relevant test data of various performance changes over time, and especially, filled in the remarkable data gaps in the less-reported conductivity test of different storage time. [ABSTRACT FROM AUTHOR]

This study examines the potential of using calcium‐rich precursors to improve the strength of alkali‐activated slag (AAS) cement at low temperature. To achieve this target, the effect of calcium‐rich precursors on the early strength development of AAS mortars cured at 5°C was assessed. The strength development was investigated along with its internal temperature, microstructure and reaction products. It is found that the calcium‐rich precursors can improve the early strength of AAS around 35% and the group with Portland cement clinker gave the highest strength. Calcium oxide can also increase the compressive strength of AAS cement, but its effectiveness is not as good as the sample with clinker. Adding calcium sulfoaluminate can increase the early strength, while no significant contribution to 28‐day strength could be found. The results highlight that compressive strength of modified AAS mortar can reach 15 MPa at 6 h and 20 MPa at 24 h at 5°C, suggesting that this binder could be a valuable alternative for low temperature construction. [ABSTRACT FROM AUTHOR]

Aims: We aimed to investigate the effect of omeprazole on the pharmacokinetics (PK) of pyrotinib and determine the safety of this combination in healthy Chinese volunteers. Methods: Eighteen healthy volunteers were enrolled in this single‐dose and self‐controlled study. Pyrotinib (400 mg per oral) was administered 30 minutes after the standard meal. Omeprazole was administered from day 6 (D6) to D10 (40 mg, per oral). On D10, the subjects took omeprazole under fasting conditions, followed by pyrotinib 30 minutes after the standard meal. Blood samples for PK analyses in each phase were collected for analysing the drug concentration. Safety was assessed via clinical laboratory tests and physical examinations. Results: Compared with a single dose of pyrotinib, pyrotinib coadministered with omeprazole showed no significant difference in exposure, elimination, half‐life and apparent clearance rate. The mixed‐effects model revealed that the least‐squares geometric mean ratios of area under the concentration–time curve (AUC)0‐t, AUC0‐∞ and maximum plasma concentration (Cmax,90% confidence intervals) of pyrotinib alone and pyrotinib coadministered with omeprazole were 0.94 (0.82, 1.08), 0.94 (0.83, 1.08) and 0.91 (0.806, 1.038), respectively, indicating the absence of significant differences in AUC0‐t, AUC0‐∞ and Cmax. During the treatment period, 6 subjects (33.3%) reported 8 adverse events during pyrotinib monotherapy and omeprazole administration, respectively; 10 subjects (55.6%) reported 34 adverse events in the combined administration phase. Conclusion: Omeprazole, a proton‐pump inhibitor, did not significantly impact the PK properties of pyrotinib, and a good safety profile was observed on coadministration. [ABSTRACT FROM AUTHOR]

Aims: The pharmacokinetics (PK) of hetrombopag were found to be nonlinear across evaluated dose ranges. The aim of this study was to develop a mechanism‐based population pharmacokinetic/pharmacodynamic (PopPK/PD) model and to provide a reasonable expected therapeutic dose for a future confirmatory clinical study of hetrombopag. Methods: Nonlinear mixed‐effects modelling was performed using pooled 2168 hetrombopag concentrations and 1526 platelet counts from 72 healthy subjects and 32 chronic idiopathic thrombocytopenic purpura (ITP) patients from two phase I studies and one phase II study. The final model was evaluated via goodness‐of‐fit plots, visual predictive check and nonparametric bootstrap. Simulations from the validated PopPK/PD model were used to devise an expected therapeutic dose for later confirmatory clinical study. Results: The pharmacokinetic data of hetrombopag were well described by a modified target‐mediated drug disposition (TMDD) model with dual sequential first‐order absorption. Mean parameter estimates (interindividual variability) were CL/F 7.66 L/h (63.5%), Vc/F 30.0 L (77.2%) and Kdeg 0.693/h (87.1%). The pharmacodynamic profile was well described by a five‐compartment lifespan model with four‐transit and one‐platelet compartments. Simulation results suggested that chronic ITP patients following 10 mg once‐daily hetrombopag would able to achieve an ideal platelet count level (50‐200 × 109/L). Conclusion: TMDD was the primary reason leading to nonlinear PK profile of hetrombopag. Our PK/PD modelling and simulation results support 10 mg once‐daily as the recommended therapeutic dose for chronic ITP patients in subsequent confirmatory clinical study of hetrombopag. [ABSTRACT FROM AUTHOR]

By modifying the preparation process of Pechini method, we can improve the structure of Li0.33La0.55TiO3 (LLTO) crystalline powder, so as to obtain high-density LLTO solid electrolyte. Through optimizing the sintering process, LLTO powder with good dispersion and uniform particle size was calcined at 800 °C; afterwards, the LLTO solid electrolyte samples with excellent properties were prepared by sintering at 1250 °C. The LLTO samples showed a low activation energy of 0.32 eV, a high relative density of 91.2%, and a high ionic conductivity of 2.7 × 10−5 S/cm. By adding three different aluminum salts, the ionic conductivity of Al3+-doped LLTO (A-LLTO) was further improved significantly. Especially in this case, with 30-nm Al2O3 doped, the conductivity of A-LLTO was increased to 4.7 × 10−5 S/cm, the activation energy was reduced to 0.30 eV, and the relative density was increased to 92.8%. [ABSTRACT FROM AUTHOR]

Graphene has been widely studied and applied in the electrode materials of supercapacitors due to its good electrical stability and high theoretical capacitance. In this study, graphene oxide (GO) is prepared by a modified Hummer's method and then reduced to obtain reduced graphene oxide (rGO). However, due to the incomplete reduction, the existence of oxygen-containing groups or defects on graphene layers may lead to poor electrical conductivity. Meanwhile, for thermodynamic stability, the graphene layers tend to agglomerate when kept for long time, resulting in the degradation of electrochemical properties. Multi-walled carbon nanotubes (MWCNTs) are one-dimensional materials with high aspect ratio and high electrical conductivity. Nevertheless, due to their insufficient hydrophilicity, their electrochemical properties such as capacitance are limited, which hinders their further development in supercapacitors. In this work, rGO/MWCNTs composite was synthesized without any surfactants and analyzed by means of structural and electrochemical tests. The variations on microstructure, surface chemical states, defects, and electrochemical properties of rGO/MWCNTs composite at different preservation times were investigated, which were also compared with those of the pure rGO under the same preservation conditions. The results show that, for long-time preservation, the addition of MWCNTs can inhibit the agglomeration of rGO and improve the rate capability and cyclic stability as the electrode material of supercapacitor. This study is of great guiding significance for understanding the time failure of rGO and rGO/MWCNTs composite in practical applications. [ABSTRACT FROM AUTHOR]

Electrode materials for supercapacitors are extensively studied at present; however, their structural and electrochemcial properties still require further improvement. Hence, a series of polyaniline/reduced graphene oxide binary composites (PANI/RGO, PG-i, i = 1–5) and polyaniline/multi-walled carbon nanotubes/reduced graphene oxide ternary composites (PANI/MWCNT/RGO, PCG-i, i = 1–6) were prepared by a facile hydrothermal method. The morphology, structure and electrochemical performance of these samples are systematically analyzed and discussed. Analysis shows that all the samples have abundant pore structure. By changing the ratio of components, PCG-5 shows superior comprehensive electrochemical performance, including a high specific capacitance of 478 F g−1 at 1 A g−1, a considerable capacitance retention (63.56%, from 1 A g−1 to 20 A g−1, and 55.33%, from 1 A g−1 to 50 A g−1) and an extraordinary cycling stability (64% after 3500 cycles, at 2 A g−1) in 1 M H2SO4. The results prove that the PANI/MWCNT/RGO ternary composites have great potential as supercapacitor electrodes. [ABSTRACT FROM AUTHOR]

A new perspective on the hydration process of graphene oxide (GO)/cement composites is provided in this paper. The quantitative evaluation of GO on the hydration of four minerals and the dissolution sequence of the four minerals were determined through thermodynamic calculation and quantitative results of solid phases. GO promoted the driving force for dissolution of C3S , C2S , C3A , and C4AF , evidenced from thermodynamic calculations. Quantitative X-ray diffraction analysis proved that GO tended to preferentially affect the hydration of C3A and C4AF rather than C3S and C2S before 2 h of hydration. The amounts of the phase consumption and formation of hydration products increased with the addition of GO. The nitrogen adsorption/desorption test confirmed that the gel pore volume was increased in the presence of GO. The improvement of hydration degree was confirmed by Si29 magic-angle spinning nuclear magnetic resonance (MAS NMR). A slight increase of Q2/Q1 ratio and the main chain length in calcium silicate hydrate (C-S-H) gel can be found in GO-containing systems, which is different from that in pure C3S systems, and needs further study. [ABSTRACT FROM AUTHOR]

Background: Metastasis and/or recurrence can decrease the survival time of gastric cancer patients undergoing radical operation. Among them, those with stage IIIb and IIIc are especially at a high risk of metastasis and recurrence. The traditional Chinese medicine collaborative model (TCMCM) has been used in the treatment of cancer; however, its effects have not been systematically evaluated. This study is designed to evaluate whether TCMCM can decrease adverse effects after chemotherapy and reduce the recurrence and metastasis of stage IIIb and IIIc gastric cancer.Methods/design: This prospective, multicenter, randomized, open-label trial will recruit 260 patients with stage IIIb and IIIc gastric cancer who undergo radical surgery for D2 lymphadenectomy. The patients will be randomly assigned to receive usual adjuvant chemotherapy and TCMCM (intervention group) in a 1:1 ratio. Patients in the intervention group will receive an oral traditional Chinese formula, auricular acupressure, and acupoint therapy. All participants will receive usual adjuvant chemotherapy. The primary outcome is a 3-year disease-free survival rate. Secondary outcomes include quality of life, side effects caused by chemotherapy, and safety-related measures. Assessments will be performed during the screening period, at 4 and 8 cycles after adjuvant chemotherapy, and 9, 12, 18, 24, 30, and 36 months after randomization. Adverse events will be recorded. In addition, biological samples will be collected for mechanism analysis.Discussion: This will be the first clinical trial to evaluate the effects of TCMCM on disease-free survival (DFS) and quality of life in patients with stage IIIb and IIIc gastric cancer. Our results may be used to standardize TCMCM. We will also perform a larger-scale clinical trial in the future.Trial Registration: ClinicalTrials.gov NCT03607656 . Registered on 1 July 2018. The final protocol version is V1.1. [ABSTRACT FROM AUTHOR]

Background: Epithelial-to-mesenchymal transition (EMT) is a pivotal cellular phenomenon involved in tumour metastasis and progression. In gastric cancer (GC), EMT is the main reason for recurrence and metastasis in postoperative patients. Acacetin exhibits various biological activities. However, the inhibitory effect of acacetin on EMT in GC is still unknown. Herein, we explored the possible mechanism of acacetin on EMT in GC in vitro and in vivo. Methods: In vitro, MKN45 and MGC803 cells were treated with acacetin, after which cell viability was detected by CCK-8 assays, cell migration and invasion were detected by using Transwell and wound healing assays, and protein expression was analysed by western blots and immunofluorescence staining. In vivo, a peritoneal metastasis model of MKN45 GC cells was used to investigate the effects of acacetin. Results: Acacetin inhibited the proliferation, invasion and migration of MKN45 and MGC803 human GC cells by regulating the expression of EMT-related proteins. In TGF-β1-induced EMT models, acacetin reversed the morphological changes from epithelial to mesenchymal cells, and invasion and migration were limited by regulating EMT. In addition, acacetin suppressed the activation of PI3K/Akt signalling and decreased the phosphorylation levels of TGF-β1-treated GC cells. The in vivo experiments demonstrated that acacetin delayed the development of peritoneal metastasis of GC in nude mice. Liver metastasis was restricted by altering the expression of EMT-related proteins. Conclusion: Our study showed that the invasion, metastasis and TGF-β1-induced EMT of GC are inhibited by acacetin, and the mechanism may involve the suppression of the PI3K/Akt/Snail signalling pathway. Therefore, acacetin is a potential therapeutic reagent for the treatment of GC patients with recurrence and metastasis. [ABSTRACT FROM AUTHOR]

In order to study the fracture ability classification of rock mass under the cracking action of supercritical CO2 phase transition, based on the classification theory of rock mass in blasting engineering, an analytic hierarchy process (AHP)-entropy weight method (EWM) and the cloud model classification method for rock mass cracking under CO2 phase transformation are proposed. In this method, rock density, rock tensile strength, rock wave impedance, and rock mass integrity coefficient are used as the factors to determine the level of rock mass fracturing, and the evaluation index system of rock mass fracturing is established. Through this evaluation method, the rock mass in a reconstruction project section of Nyingchi, Tibet, is classified and evaluated. The results present that this new classification method of rock mass fracture ability uses AHP–EWM to carry out the weight distribution of the classification index. In addition, it is combined with the cloud model for the classification division, overcoming the traditional classification method fixed with appraisal pattern flaw. Therefore, it has validity and feasibility. According to the characteristics of fracture ability, the rock masses in the area to be rebuilt on the Tibet Highway are divided into grade II, grade III, and grade IV, which provides scientific guidance for the construction of the project. [ABSTRACT FROM AUTHOR]

With the advantages of high power density, long cycle life, and fast charging, supercapacitor has become a research hotspot in recent decades. Graphene is considered as an ideal electrode material for supercapacitors because of its special electrical and mechanical properties. In order to prepare graphene that can be used as supercapacitor electrode materials, various methods are proposed, among which hydrothermal method is mostly used, but graphene prepared using this method always agglomerates seriously and rarely have pores that might be helpful for the increase of electrochemical performance. Therefore, sodium alginate, which has strong hydrogen bonding with graphene oxide and might be helpful to optimize the structure of graphene in the reduction process, should be considered. In this paper, by optimizing the ratio of reducing agent and graphene oxide in hydrothermal reaction, two samples that exhibit better performance were obtained. On this basis, sodium alginate was added in the process of hydrothermal reduction of graphene oxide, and the effect of it on the structure and properties of graphene was explored. The results demonstrate that pore structure is formed and the rate performance is improved obviously by adding sodium alginate. [ABSTRACT FROM AUTHOR]

Introduction: The effects of continuous infusions of ciprofol on its pharmacodynamic and pharmacokinetic properties and safety profiles in healthy Chinese subjects were evaluated.Methods: In this open-label, randomized, two-way cross-over study, subjects received initial doses of continuous ciprofol/propofol as an infusion for 30 min in part 1 (n = 8) and a bolus dose in part 2 (n = 8) followed by maintenance infusions for a total of 4 h in part 1 and 12 h in part 2. Each subject participated in both parts with a washout time of at least 40 h.Results: The safety and tolerability parameters of ciprofol were similar to those of propofol, and all treatment-emergent adverse events were mild. The incidences of injection pain and respiratory depression in subjects given ciprofol were lower than those receiving propofol. The pharmacokinetic parameters Cmax, tmax, t1/2, λz and MRT for ciprofol and propofol were similar, while CL, Vd and Vss were statistically significantly different. Pharmacodynamic parameters including the Richmond Agitation Sedation Scale and bispectral index profiles of ciprofol were similar to those of propofol.Conclusion: Ciprofol has potential for clinical application for continuous intravenous infusion to maintain sedation for 12 h with the same safety, tolerability and efficacy as propofol. [ABSTRACT FROM AUTHOR]

Use of graphene oxide (GO) and graphene nanoplatelets (GNPs) has shown some promising potential to boost the performance of Portland cement (PC). Their influence and working mechanisms in other binding systems, e.g. alkali-activated slag (AAS), are still unclear, although some encouraging results have been reported. This study aims at characterising and quantifying roles of GO and GNPs on shrinkage of AAS mortars. A comprehensive experimental programme was carried out to assess the drying shrinkage and autogenous shrinkage of GO/GNPs-added AAS cements along with hydration process and microstructural changes in order to explain the reasons. The results indicate that the shrinkage of AAS is further increased by GO/GNPs due to refined microstructure and higher degree of hydration of GGBS. That is, the main drawback of AAS, high shrinkage, cannot be mitigated by using these two nano materials. Against these backgrounds, it is early to recommend to directly use GO or GNPs in AAS mixes. [ABSTRACT FROM AUTHOR]