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Chronic fatigue syndrome (CFS) severely impact patients' quality of life and lacks well-acknowledged drug therapy. Sijunzi decoction (SJZD), a classical Chinese herbal formula, has been widely used for spleen deficiency syndrome like fatigue in China. However, there is a lack of evidence on the efficacy of SJZD in treating CFS. To evaluate the efficacy and safety of SJZD for CFS. A multi-center, double-blinded, randomized controlled trial. Participants with definite diagnoses of CFS and spleen deficiency syndrome were randomly assigned in 1:1 ratio to receive SJZD or placebo granules for 2 months. The primary outcome was the change of Chalder fatigue questionnaire (CFQ) scoring after treatment. Other outcomes included changes in short form-36 physical function (SF36-PF) score, spleen deficiency scale score, Euroqol Questionnaire-Visual Analogue Scale (ED-VAS) score, and clinical global impression (CGI) evaluating by corresponding questionnaires. Fecal metagenome sequencing was conducted to explore the potential mechanism of SJZD effect. From June 2020 to July 2021, 105 of 127 participants completed the study at four hospitals in China. After a 2-month treatment, intention-to-treat (ITT) analysis found participants who received SJZD had larger reduction than placebo control (mean change 6.65 [standard deviation (SD) 6.11] points vs. 5.31 [SD 5.19] points; difference 1.34, 95 % confidence interval [CI] -0.65 to 3.33). Per-protocol (PP) analysis reported confirmative results with a significant difference between SJZD and placebo groups (2.24, 95 % CI 0.10 to 4.39). SJZD also significantly improved overall health status compared with placebo in per-protocol population (p = 0.009). No significant difference was found between groups in changes of SF36-PF, spleen deficiency scale scoring, and CGI. Fecal metagenome sequencing and correlation analyses indicated that the beneficial effect of SJZD may be related to the abundance change of Pediococcus acidilactici. No serious adverse event or abnormal laboratory test was found during the whole study. Our results indicated that SJZD can improve fatigue symptom and overall health status in patients with CFS under good medication adherence. Potential therapeutic effects may be related to the regulation of gut microbiota. Large-scale trials with longer intervention period are encouraged to further support SJZD's application. (ID, ISRCTN23930966, URL = https://www.isrctn.com/ISRCTN23930966). [Display omitted] [ABSTRACT FROM AUTHOR]

Black carbon (BC) can combine with organic matter and form secondary pollutants known as aged BC. BC and aged BC can cause respiratory system inflammation and induce lesions at relevant sites, but the underlying mechanism has remained unknown. To gain insight into the potential mechanisms, we focused on macrophages and transforming growth factor β-activated kinase 1 (TAK1) which are a crucial factor in inflammation. Our research aims to determine the role of TAK1 in macrophages in pulmonary inflammation induced by particulate matter. In this study, BC and 1,4-naphthoquinone were mixed to model aged BC (1,4NQ-BC) in atmosphere. BC induced mice lung inflammation model, lung macrophage knock-down TAK1 animal model and primary macrophage knock-down TAK1 model were used to explore whether TAK1 in macrophage is a critical role in the process of inflammation. The results showed that the expressions of inflammatory cytokines (IL-1β, IL-6, IL-33) mRNA were significantly increased and the phosphorylation of MAPK and NF-κB signaling pathway related proteins were enhanced in RAW 264.7 cell lines. In vivo studies revealed that the indicators of pulmonary inflammation (pathology, inflammatory cell numbers) and related cytokines (IL-1β, IL-6, IL-33) mRNA expressions in CD11c-Map3k7−/− animals were significantly lower than wild-type animals after mice were instilled particles. In mice primary macrophages, the expressions of IL-6, IL-33 mRNA were inhibited after TAK1 gene was knock-down. These results unequivocally demonstrated that TAK1 plays a crucial role in BC induced lung inflammation in mice, and we can infer that BC and 1,4NQ-BC cause these inflammatory responses by stimulating pulmonary macrophages. • BC has different physico-chemical properties compared with 1,4NQ-BC. • TAK1 knock-down in macrophages could alleviate mice lung inflammation induced by BC and 1,4NQ-BC. • TAK1 plays a key role in the production of IL-33 by macrophages. [ABSTRACT FROM AUTHOR]

Objectives To systematically review the current dental literature regarding clinical accuracy of guided implant surgery and to analyze the involved clinical factors. Material and Methods PubMed and Cochrane Central Register of Controlled Trials were searched. Meta-analysis and meta-regression analysis were performed. Clinical studies with the following outcome measurements were included: (1) angle deviation, (2) deviation at the entry point, and (3) deviation at the apex. The involved clinical factors were further evaluated. Results Fourteen clinical studies from 1951 articles initially identified met the inclusion criteria. Meta-regression analysis revealed a mean deviation at the entry point of 1.25 mm (95% confidence interval [CI]: 1.22-1.29), 1.57 mm (95% CI: 1.53-1.62) at the apex, and 4.1° in angle (95% CI: 3.97-4.23). A statistically significant difference ( P < .001) was observed in angular deviations between the maxilla and mandible. Partially guided surgery showed a statistically significant greater deviation in angle ( P < .001), at the entry point ( P < .001), and at the apex ( P < .001) compared with totally guided surgery. The outcome of guided surgery with flapless approach indicated significantly more accuracy in angle ( P < .001), at the entry point ( P < .001), and at apex ( P < .001). Significant differences were observed in angular deviation based on the use of fixation screw ( P < .001). Conclusions The position of guide, guide fixation, type of guide, and flap approach could influence the accuracy of computer-aided implant surgery. A totally guided system using fixation screws with a flapless protocol demonstrated the greatest accuracy. Future clinical research should use a standardized measurement technique for improved accuracy. [ABSTRACT FROM AUTHOR]

Unmanned aerial vehicle (UAV) path planning plays an important role in the flight process of an UAV, which needs an effective algorithm to deal with UAV path planning problem. The search and rescue optimization algorithm (SAR) is easy to implement and has the characteristics of flexible, but it has slow convergence speed and has not been applied to UAV path planning. To address these problems, a heuristic crossing search and rescue optimization algorithm (HC-SAR) is proposed. HC-SAR combines a heuristic crossover strategy with the basic SAR to improve the convergence speed and maintain the population diversity in the optimization process. Furthermore, a real-time path adjustment strategy is proposed to straighten the UAV flight path. In addition, cubic B-spline interpolation is used to smooth the generated path. Comprehensive experiments including two-dimensional and three-dimensional environments for different threat zone are conducted to validate the performance of HC-SAR. The results show that HC-SAR has a high convergence speed and can successfully obtain a safe and efficient path, and it significantly outperforms SAR, differential evolution (DE), ant lion optimizer (ALO), squirrel search algorithm (SSA) and salp swarm algorithm (SSA) in all the cases. These results suggest that the proposed algorithm can effectively serve as an alternative for solving UAV path planning problem. • A hybrid algorithm named HC-SAR is proposed for UAV path planning. • A heuristic crossover strategy is combined with SAR to greatly improve SAR. • A real-time path adjustment strategy is proposed to straighten the UAV flight path. • HC-SAR outperforms the competitors in convergence speed and solution quality. [ABSTRACT FROM AUTHOR]

In this paper, I argue that only dialogue that links science, aesthetics, and axiology can solve the ecological crisis' moral concerns. Serious consideration can thus be given to raising bio-ecological awareness (Section 1). The paper traces three global waves in the emerging field of ecolinguistics (Section 2). Their divergences and disharmony have hindered awareness of the bio-ecology and the benign development of the discipline (Section 3). To bring clarity to the field, it is therefore proposed that the roots of disharmony tap into the moral and ethical harmony of Chinese worldview (Section 4). By adopting a harmonious view of language, mind and the world, a future harmonious ecolinguistics can be realized to become a life science (Section 5). In short, a synthesis of science, axiology and aesthetics can bring new harmony to European and Chinese ecolinguistics. Such an outcome would be a significant step in improving human bio-ecological awareness and resolving the ecological crisis (Section 6). [ABSTRACT FROM AUTHOR]

[Display omitted] • ASB improves postnatal immune activation (PIA)-induced cognitive impairment. • ASB exerts neuroprotection by inhibiting neuronal apoptosis and promoting neurogenesis. • ASB regulates BCL2 expression via H3K27me3 in neurons. Postnatal immune activation (PIA) often induces neuroinflammation and disrupts neural functions, ultimately causing cognitive impairment. Among them, neuronal dysfunction is one of the key causes of many neurological diseases. It is particularly important to develop effective neuroprotectants to prevent inflammatory brain diseases. Recently, the protective effect of astilbin (ASB) on nervous system diseases has attracted much attention. However, whether ASB can resolve neuronal dysfunction and cognitive decline triggered by PIA remains unclear. In this study, we used the lipopolysaccharide (LPS)-induced PIA model and found that ASB improved PIA-induced cognitive impairment and neuronal dysfunction in adult mice. Moreover, ASB inhibited PIA-induced neurogenesis deficits and synaptic damage. Finally, we found that ASB treatment inhibited the levels of EZH2/H3K27me3 and decreased the enrichment level of H3K27me3 at the promoter of BCL2 and BDNF. Together, our results demonstrated that ASB may protect against PIA-induced cognitive impairment through EZH2-mediated histone methylation. This study established the role of ASB and epigenetic factor EZH2 regulatory network on the PIA model, which provided new clues and theoretical guidance for the clinical treatment of PIA-induced cognitive impairment. [ABSTRACT FROM AUTHOR]

The ongoing pandemic created by COVID-19 has co-existed with humans for some time now, thus resulting in unprecedented disease burden. Previous studies have demonstrated the non-linear and single effects of meteorological factors on viral transmission and have a question of how to exclude the influence of unrelated confounding factors on the relationship. However, the interactions involved in such relationships remain unclear under complex weather conditions. Here, we used a panel smooth transition regression (PSTR) model to investigate the non-linear interactive impact of meteorological factors on daily new cases of COVID-19 based on a panel dataset of 58 global cities observed between Jul 1, 2020 and Jan 13, 2022. This new approach offers a possibility of assessing interactive effects of meteorological factors on daily new cases and uses fixed effects to control other unrelated confounding factors in a panel of cities. Our findings revealed that an optimal temperature range (0°C–20 °C) for the spread of COVID-19. The effect of RH (relative humidity) and DTR (diurnal temperature range) on infection became less positive (coefficient: 0.0427 to −0.0142; p < 0.05) and negative (coefficient: −0.0496 to −0.0248; p < 0.05) with increasing average temperature(T). The highest risk of infection occurred when the temperature was −10 °C and RH was >80% or when the temperature was 10 °C and DTR was 1 °C. Our findings highlight useful implications for policymakers and the general public. [Display omitted] • Using panel smooth transition regression to assess interactive effects of meteorological factors on spread of COVID-19. • We control the human mobility, population density, GDP and other unrelated confounding factors. • The effect of RH on spread of COVID-19 becomes less positive with the increasing temperature. • The subzero temperature and high RH associated with high fraction of aerosol to support the spread of the virus. • A mild temperature and DTR associated with a fast spread of COVID-19. [ABSTRACT FROM AUTHOR]

Our aim was to investigate the impact of diabetes mellitus and different durations of glycaemic control on early osseointegration of dental implants, and to explore possible mechanisms by measuring the expression of integrin α5β1 and fibronectin in bone around the implant. We divided 33 male Zucker diabetic fatty (ZDF) rats aged 3 months into 3 groups. The first group comprised diabetic rats with dental implants (controls); the second group was treated with insulin and implants were placed simultaneously (exenatide alone group); and the third group was treated with insulin until the serum glucose was at a constant concentration ( < 16 mmol/L), and implants were then inserted (exenatide+normal glucose group). Rats were killed 7, 14, 30, and 60 days after implants had been inserted. The expression of integrin α5β1 and fibronectin in bone around the implants was detected by immunohistochemical analysis in each group. The expression in the exenatide+normal glucose group was stronger than in the other 2 groups. Fourteen days after implantation, expression of integrin α5β1 in the exenatide alone group was significantly stronger than that in the control group (p=0.027), and 60 days after implantation the expression of fibronectin in the exenatide alone group was also significantly stronger than that among the controls (p=0.001). Both fibronectin and integrin α5β1 participate in the adhesion of osteoblasts and act as signals at the bone/implant interface. Diabetes interferes with the osseointegration of implants by deferring expression of fibronectin and integrin α5β1. [ABSTRACT FROM AUTHOR]

Polyurethane elastomer nanocomposites are strategically important due to their indispensable applications in daily life and high-tech fields. Herein, a series of nanocomposites with extraordinary strength, toughness and energy dissipation are reported, which are enabled by multiple dynamic moieties including dynamic boronic ester covalent bonds, boron-nitrogen coordination bonds in the matrix and on the interface. The surface-modified silica nanoparticles with amino-silane coupling agent (D-SiO 2) were added to the polyurethane matrix that contains boron-nitrogen coordination. The presence of interfacial coordination significantly improves the dispersion of D-SiO 2 and enhances the interface interaction of polyurethane composites (SPU/D-SiO 2), which is evidenced by scanning electron microscopy, transmission electron microscopy and rheological investigation. Through mechanical experiment analysis, these modified polyurethane composites exhibit high tensile strength and toughness. The tensile strength of SPU/10D-SiO 2 increases to 19.5 ± 0.2 MPa and its tensile toughness achieves 216.9 MJ/m3, which is 35% of increase as compared with the pristine SPU that had a record-high toughness. In addition, the coordination bonds in the matrix and interface in the composites provide versatile and efficient energy dissipation during the tensile process. This work offers a facile method to improve the mechanical robustness of the newly developed supramolecular polyurethane elastomers. [Display omitted] • The interfacial coordination significantly improves the dispersion of D-SiO 2 and enhances the interfacial interaction. • The tensile toughness of SPU/10D-SiO 2 achieves 216.9 MJ/m3, which is 35% of increase as compared with the pristine SPU. • The extraordinary strength, toughness and energy dissipation are enabled by multiple dynamic moieties. [ABSTRACT FROM AUTHOR]

Defective in cullin neddylation 1(DCN1) is a co-E3 ligase that is important for cullin neddylation. Dysregulation of DCN1 highly correlates with the development of various cancers. Herein, from the initial high-throughput screening, a novel hit compound 5a containing a phenyltriazole thiol core (IC 50 value of 0.95 μM for DCN1-UBC12 interaction) was discovered. Further structure-based optimization leads to the development of SK-464 (IC 50 value of 26 nM). We found that SK-464 not only directly bound to DCN1 in vitro , but also engaged cellular DCN1, suppressed the neddylation of cullin3, and hindered the migration and invasion of two DCN1-overexpressed squamous carcinoma cell lines (KYSE70 and H2170). These findings indicate that SK-464 may be a novel lead compound targeting DCN1-UBC12 interaction. [Display omitted] • A hit compound 5a containing a phenyltriazole thiol core was discovered as DCN1-UBC12 interaction inhibitor in initial HTS. • 38 phenyltriazole thiol derivatives were further designed, synthesized and evaluated. • SK-464 could significantly inhibit DCN1-UBC12 interaction at both protein and cellular levels. • SK-464 effectively inhibits the migration and invasion of two DCN1-overexpressed squamous cell carcinoma cell lines. [ABSTRACT FROM AUTHOR]

• The self-compacting road concrete incorporating nano-silica was prepared. • The optimum content of nano-silica is 1% based on grey relational analysis. • Incorporation of nano-silica improves the flexural fatigue performance of samples. • Nano-silica can promote the secondary hydration reaction and fill the micropores. In this study, the mix proportion of self-compacting road concrete with ternary cementitious materials was optimized by incorporating nano-silica particles to improve its flexural fatigue performance. The filling property and compressive strength were selected as evaluating indicators to design L 9 (33) orthogonal test, and then four kinds of mix proportions were selected to prepare the nano-modified self-compacting concrete (SCC) according to the results of grey relational analysis and comprehensive weighting method. The four-point flexural fatigue tests were conducted to establish the probabilistic fatigue equations of nano-modified SCC based on the two-parameter Weibull distribution with survival rates of 50% and 95%, respectively. The modification mechanism was revealed with the help of scanning electron microscopy and X-ray diffraction phase analysis. The results indicate that the optimal mix proportion of self-compacting road concrete could be obtained when nano-silica accounts for 1% of the mass of cementitious materials. The specimens with 1% nano-silica particles showed the best flexural fatigue performance, with the reduction factor of flexural strength increased by 1.5%–5.0% and the sensitivity of fatigue life to the stress levels decreased by 2.1%–9.7% at survival rate of 50%. The nanoparticles provided a physical filling effect and facilitated the formation of low-density calcium silicate hydrate gel, filling the internal micro-pores to make the structure more compact. Nano-silica improved the flexural fatigue performance of self-compacting road concrete to a certain extent. [ABSTRACT FROM AUTHOR]

Hydrazone and their derivatives are a series of highly active molecules, which are widely used as lead compounds for the research and development of new anti-cancer drugs. In this study, 20 compounds were synthesized, based on this scaffold and their in vitro cytotoxicity against 6 cancer cell lines, including EC9706, SMMC-7721, MCF7, PC3, MGC-803 and EC109 was tested. Among them, compound 6p , showed strong anti-proliferative activities on esophageal carcinoma cells: EC9706 and EC109 with IC 50 values of 1.09 ± 0.03 and 2.79 ± 0.45 μM, respectively. 6p also significantly induces both EC9706 and EC109 cell cycle arrest at G0/G1 phase and cell apoptosis, as well as intracellular ROS accumulation, which could be markedly reversed caspase or ROS inhibitor: NAC. Meanwhile, treatment of compound 6p results in significant declined mitochondria membrane potential, increases in the expression of P53 and bax, as well as decrease in Bcl-2. 6p also activates caspase-8/9/3, PARP and Bid, indicating that 6p induces cancer cell apoptosis via the death receptor-mediated extrinsic pathway and the mitochondria-mediated intrinsic pathway. Further studies also proved that 6p does not show obvious side effects at cellular and in vivo levels. Our findings suggested that hydrazone derivative: compound 6p may serve as a lead compound for further optimization against esophageal cancer cells. [ABSTRACT FROM AUTHOR]

The transition from multipotent neural stem cells (NSCs) to terminally differentiated neurons is a multistep process, and the transition is finely regulated by transcription factors with basic helix-loop-helix (bHLH) motifs. Melatonin is an endogenous neurohormone with profound neurotrophic and neuroprotective effects both during the embryonic developmental stage and adulthood. The effects of melatonin on the differentiation of NSCs have been reported, and these effects may be responsible for its neuroprotective properties. However, the mechanisms underlying the effects of melatonin are not well understood. It is unclear whether melatonin affects the expression of bHLH factors at the onset of neuronal differentiation, and the molecular mechanisms involved still need to be further explored. Using mouse NSCs, we identified a novel role for melatonin in the epigenetic regulation of bHLH factors during neuronal differentiation. Our data showed that melatonin promoted neuronal differentiation by specifically increasing the acetylation of histone H3 lysine14 (H3K14). Increased H3K14 acetylation altered the chromatin state of the promoters of bHLH factors Neurogenin1 and NeuroD1 and activated their transcription; then, Neurogenin1 and NeuroD1 initiated and sustained the commitment to neuronal fates. As we know, CBP/p300 is an important class of histone acetyltransferases that acetylate histone H3K14, we found that melatonin activated the histone acetyltransferase activity of CREB-binding protein (CBP)/p300 via ERK signaling pathways. For the first time, we systematically showed the molecular mechanism of action of melatonin, which suggested that melatonin functions as a regulator of the acetylation-dependent gene expression network. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To study the effects of group reminiscence therapy on depressive symptoms, self-esteem, and affect balance among community dwelling elderly. Methods: Eight communities were randomly selected from 372 eligible communities in Changsha city. They were randomly divided into four experimental groups and four control group. Geriatric Depression Scale (GDS) was used to screen entire 478 older adults living in these 8 communities. One hundred and sixty five of them had a GDS score between 11 and 25; among them, 125 participated in the study finally. The elderly group who were in the control group received health education, while the intervention group received both health education and group reminiscence therapy for 6 weeks. Both groups were assessed with the GDS, Self-Esteem Scale (SES), and Affect Balance Scale (ABS) before and after the 6-week-intervention. The results were analyzed using a mixed effect model with fixed effect of the intervention and random effect of the community, incorporating the structured randomness at the community level. Results: After 6 weeks’ therapy, the GDS scores in the intervention group decreased significantly compared to those in the control group (p <0.001). Scores on the positive affect subscale and affect balance in the intervention group increased significantly higher than control group, and scores on the negative affect subscale decreased significantly lower than control group (p <0.01). After the intervention, there were no statistically significant differences in self-esteem scores between intervention and control groups. Conclusions: Group reminiscence therapy was effective in reducing symptoms of depression, improving affect balance, and promoting mental health of community-dwelling elderly. [Copyright &y& Elsevier]

The current chemiluminescence (CL) probes for hydroxyl radical (•OH) are poorly selective owing to a non-specific redox reaction. To the best of our knowledge, there have not been established on the CL probes for •OH using the strong electrophilicity of •OH. In this work, an ultrastrong CL emission is initiated by electrophilic attack of •OH towards rhodamine B (RhB) on the surface of montomorillonite (MMT). The improved CL emissions are attributed to the oriented H-type aggregation of RhB molecules on the surface of MMT by π–π stacking interactions, resulting in an increase in π-electron density of aromatic ring of RhB. The high π-electron density of benzene ring could facilitate the attack of electrophilic •OH towards RhB. In addition, a novel CL probe for •OH with high selectivity and high sensitivity has been established using the electrophilic properties of •OH rather than its common redox properties. The applicability of the proposed CL probe is evaluated by detecting •OH in untreated and gentamicin treated mouse fresh plasma samples. Our findings provide a new strategy to improve the selectivity of CL sensor of •OH. [ABSTRACT FROM AUTHOR]

Postnatal immune activation (PIA) can affect normal brain development and increase the risk of behavioral abnormalities in later life, including depressive-like behavior. Therefore, there is an urgent need to find safe and effective clinical medications for PIA. Recently, the protective effect of astilbin (ASB) in nervous system diseases has attracted much attention. However, the effect of ASB on neurodevelopmental diseases remains unclear. In this study, we used a lipopolysaccharide (LPS)-induced PIA mouse model and found that ASB specifically improved PIA-induced depressive-like behavior but not anxiety-like behavior in adult mice. Astrocytes play an essential role in regulating neuroinflammation, and are the most abundant cell type in the brain. In the PIA model, we found that ASB selectively inhibited astrocyte activation but not microglial activation in the cortex and hippocampus. Moreover, our results showed that ASB specifically upregulated the expression of menin protein in astrocytes and blocked the entry of P65 protein into the nucleus, thus inhibiting the secretion of IL-1β and TNF-α by astrocytes. Taken together, ASB reduced the occurrence of astrocyte-mediated neuroinflammation by targeting menin, thereby attenuating the PIA-induced depressive-like behavior. Our results reveal that ASB may be an attractive antidepressant drug and exert an antidepressant effect in PIA. In terms of drug selection, ASB may be a specific drug for patients with depressive symptoms. [ABSTRACT FROM AUTHOR]

Steel slag is considered to improve the road performance of cold mixed asphalt (CMA) due to its superior physicochemical characteristics. To realize the potential application of steel slag in CMA pavement, the alkalinity, hydration activity, pore characteristics, and three-dimensional (3D) morphology were quantitatively characterized and evaluated based on the X-ray fluorescence (XRF), mercury intrusion porosimetry (MIP), 3D laser scanning, and 3D structured light measurement, respectively. The results show that the alkalinity of steel slag can not fully reflect its hydration activity. Most steel slag has high alkalinity with an alkalinity value greater than 2.5, while the activity index (AI) is generally less than 1.0. The pores of steel slag are mostly "ink-bottle" shaped, in which macropores are the most developed, and small pores and micropores are the least developed. The total pore volume of macropores is the largest, while the total pore area of small pores is the largest. The porosity of porous, less porous, and dense steel slag is 12.05%, 6.88%, and 1.28%, respectively. The adsorption and accommodation capacity of porous steel slag for fluids is the largest, followed by less porous and dense steel slag. All three steel slags have good 3D shapes, and their shape factor (SF), sphericity (S), needle degree (ND), and flake degree (FD) have distribution intervals of 0.81–1.19, 0.70–0.99, 1.01–1.90, and 1.01–1.51, respectively. Porous steel slag shows richer apparent morphology than less porous and dense steel slag. Their apparent morphology characterization indicators R a , R q , R p , R v , and R t show a good linear positive correlation with porosity, which can be regarded as the classification criterion for apparent morphology. This study will help enrich the theoretical basis and control indicator system for applying steel slag in CMA pavement. [Display omitted] • The alkalinity and hydration activity of steel slag and their relationship were clarified. • The pore characteristics of steel slag and its effect on fluid adsorption were elucidated. • The 3D morphology of steel slag and its classification criteria were determined. [ABSTRACT FROM AUTHOR]

In this study, self-luminescent cement-based composite materials (SCCM) were prepared by doping luminescent powder and reflective powder into cement-based materials, and then self-luminescent and self-cleaning cement-based composite materials (SSCCM) were obtained by hydrophobic treatment on the surface of the SCCM, afterwards their mechanical properties, luminous properties, hydrophobicity and mechanism were evaluated. The results indicated that doping luminescent powder and reflective powder could enhance the brightness and afterglow time of the SCCM specimen. Compared with the control group, the initial and 10 min brightness increased by 4.7–45.79% and 14.63–59.09%, respectively. The 8 h luminous brightness was in range of 0.02–0.2 cd/m2. The addition of luminescent powder and reflective powder improved the mechanical strength of the SCCM specimen, while the super-hydrophobic materials had little effect on its strength and luminous properties. The luminescent powder and reflective powder not only reacted with cement hydration products to produce a large number of hexagonal plates CH and cluster AFm crystal, but also promoted the hydration reaction of the un-hydrated cement particles. Moreover, due to its smaller particle size, it could fill the tiny pores among hydration products, thereby improved the micro-distribution of the hardened cement matrix and enhanced the strength. The hydration products of cement could absorb short wave ultraviolet light, thus reducing the excitation wavelength range and intensity of the specimen, the emission spectrum was yellowish green with a peak value of 520 nm. The SSCCM had excellent hydrophobicity, the contact angle and surface energy of the specimen coated with fluorosilane materials is 159.8° and −19.11 mJ/m2, respectively. Due to the fluorination, the surface roughness of the SSCCM was larger, where exists a large number of hierarchical micro- and nano-structure. Image 10615 • The self-luminescent cement-based composite materials (SCCM) were prepared. • The self-luminescent and self-cleaning cement-based composite materials (SSCCM) were obtained. • The properties and mechanism of the SCCM were studied. • The properties and mechanism of the SSCCM were analyzed. [ABSTRACT FROM AUTHOR]

Abstract Black carbon (BC) is a key component of atmospheric particles which has adverse effects on human health. Oxidation could lead to chemical property and toxicity potency changes of BC. The key cytokines participating in lung damage in mice induced by BC and ozone-oxidized BC (oBC) particles have been investigated in this study. It was concluded that oBC has stronger potency of inducing lung damage in mice comparing to BC. IL-6 and IL-33 were hypothesized to play important roles in this damage. Accordingly, IL-6 and IL-33 neutralizing antibodies were used to explore which cytokine might play a key role in lung inflammation induced by BC and oBC. As a result, IL-6 neutralizing antibody did not alleviate the lung damage induced by BC and oBC. However, IL-33 neutralizing antibody prevented BC and oBC induced lung damage. Furthermore, IL-33 neutralizing antibody treatment reduced IL-6 mRNA expression. It is hypothesized that MAPK and PI3K-AKT pathways might be involved in the oBC particles caused lung damage. It was concluded that IL-33 plays a key role in BC and oBC induced lung damage in mice. Graphical abstract Unlabelled Image Highlights • oBC has stronger potency in inducing lung inflammation in mice than BC. • IL-33 neutralizing antibody prevented BC and oBC induced lung damage. • IL-33 neutralizing antibody prevented BC and oBC induced lung damage through MAPK and PI3K/AKT pathways. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Qingkailing injection (QKLI) is prepared from eight traditional Chinese medicinal materials or their extracts, which is widely used in clinical practice to treat the upper respiratory inflammation, pneumonia, high fever and viral encephalitis, nonetheless, suffering from serious anaphylaxis. Aim of study This study aims to develop an integrative metabolomics approach for deciphering the biochemical basis of QKLI induced anaphylaxis (QKLI-IA). Materials and methods The accuracy of animal modeling, the coverage of detected metabolites and the timeliness of pathological reaction are three key factors for revealing the biochemical basis of disease with untargeted metabolomics. In this study, firstly, the allergic rats (responders) were first screened by passive cutaneous anaphylaxis experiment and then were utilized for modeling. To cover a wider range of metabolites, a large-scale untargeted metabolomics based on metabolites polarity-oriented analysis was performed using ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Then, to evaluate the timeliness of QKLI-IA, a time-dependent metabolomic profiling including the early, mid and late anaphylaxis stages of QKLI-IA, was performed. Results Corresponding to early, mid and late anaphylaxis stages of QKLI-IA, 14, 9 and 4 potential biomarkers were identified, respectively. Metabolism pathway analysis revealed that QKLI-IA resulted in dynamic changes in serum amino acid, fatty acid, glycerolipid, and phospholipid metabolisms. Twenty-four metabolites were found with identical fluctuating trends across the three stages of QKLI-IA. The results indicate that the pathogenesis of QKLI-IA is closely related to arachidonic acid metabolism. Conclusion This research provides a methodology reference for revealing the biochemical basis of disease using metabolomic profiling and offers a new insight to understand the pathogenesis of QKLI-IA. [ABSTRACT FROM AUTHOR]

Background Dimethyl sulfoxide (DMSO) is a widely used solvent and vehicle for in vivo and in vitro administration of test compounds. Effects of DMSO independent of the test compound, such as in studies examining morphological plasticity or neurotoxic responses, may lead to spurious results. Aim To investigate effects of DMSO concentration ([DMSO]) on morphology and survival of primary cultured neurons and astrocytes. Methods Primary cultured neurons and astrocytes were treated with 0.25%–10.00% [DMSO] for 12–48 h. Viable cell number and morphology were compared to untreated cultures using the CCK-8 assay and phase-contrast microscopy. Expression levels of the neuronal marker NeuN and astrocyte marker glial fibrillary acidic protein (GFAP) were determined by immunofluorescence and western blotting. Results A [DMSO] ≤ 0.50% had no effect on neuronal number or NeuN expression up to 24 h, while ≥1.00% induced a progressive and dramatic loss of both viability and NeuN expression even after 12 h. Brief (12 h) exposure to ≤1.00% DMSO had no effect on astrocytes survival or GFAP expression, while ≥5.00% significantly reduced both at all exposure durations. In contrast to neurons, exposure to 0.50% and 1.00% DMSO for 24 or 48 h enhanced astrocytes proliferation and GFAP expression. Astrocytic processes were maintained at 0.50% and 1.00% DMSO, while neurons exhibited marked neurite retraction at ≥0.50%. Conclusion A [DMSO] ≥ 0.5% markedly disrupts neuronal morphology and reduces viability, even after brief exposure. In astrocytes, 0.50% and 1.00% DMSO appear to induce reactive gliosis. For treatment of neural cells, [DMSO] should be ≤0.25% to obviate spurious vehicle effects. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality around the world. The physiological or pathological processes of CVDs can be well indicated by timely and accurate diagnosis of relevant biomarkers and function parameters. Nanosensors integrating the advantages of nanomaterials and sensing platforms have shown good potential for rapid diagnosis of CVDs, especially for early prediction. In this review, recent advances in nanosensors for the detection of CVDs are summarized, including electrochemical, optical, pressure, and paper-based nanosensors. Design strategies for different nanosensors and the corresponding sensing nanomaterials, mechanisms, and properties are briefly discussed. This review also offered a preliminary analysis of the obstacles and prospects for using nanosensors to diagnose CVDs. [Display omitted] [ABSTRACT FROM AUTHOR]

Road construction is the primary method for high-value utilization of construction and demolition wastes (CDWs), but the research on its application to the asphalt pavement surface layer is still in the early stages of development. The service life of recycled asphalt concrete (RAC) has become a "troublesome issue," so in-depth research on the fatigue properties of RAC is needed. This paper gives a detailed review of the fatigue properties of RAC. First, the properties of recycled aggregates (RAs) are summarized, noting that the properties of RAs and natural aggregates (NAs) vary widely. Recycled concrete coarse aggregates (RCCAs) are most appropriate for the application. Second, the design points of RAC are discussed, and it is concluded that in the design process of RAC, gradation correction is needed. The optimal asphalt content should be calculated by volume index. Third, the fatigue properties test plan and the influence of RAs on it are analyzed, finding that it ignores the applicability of different test methods and the impacts of regional temperature and climate conditions. The existing research mainly focuses on the correlation between recycled aggregate (RA) content and fatigue properties. There is insufficient research on the influence of RA properties on fatigue properties. Finally, future research directions and recommendations for a test plan regarding the fatigue properties of RAC are proposed. Research should focus on the effect of RA properties on fatigue properties. It should be carried out with reasonable test methods, service life characterization models, and climate identical test conditions to clarify the durability index. The evaluation system of fatigue properties of RAC should be established, and solid theoretical supports for the application of CDWs should be provided, thereby accelerating the application of recycled asphalt pavement containing CDWs. [ABSTRACT FROM AUTHOR]

In this paper, a polarization-controlled multifunctional coding metasurface is presented by integrating reflection and transmission coding metasurfaces, where a filter layer is inserted between them to ensure good performances of reflection and transmission modes. A cross-type pattern as reflection element and two double-G patterns as transmission elements are respectively encoded based on propagation phase and geometrical phase principles for independently manipulating the reflected and transmitted waves. By configuring the organized phase profile on the presented coding metasurface, the functions of beam splitting, radar cross section (RCS) reduction and vortex beam generator can be achieved at different frequencies by changing the polarization state of incident waves. Such design can perform three separate functions and simultaneous controls of transmitted and reflected wavefronts on a metasurface. Both numerical and theoretical calculated results verify the outstanding properties of the presented multifunctional coding metasurface. This scheme provides an efficient method to realize multi-function metadevices, which may have potential applications in highly integrated electromagnetic (EM) systems. [ABSTRACT FROM AUTHOR]

Whole-cell amino acid biosensors can sense the concentrations of certain amino acids and output easily detectable signals, which are important for construction of microbial producers. However, many reported biosensors have poor specificity because they also sense non-target amino acids. Besides, biosensors for many amino acids are still unavailable. In this study, we proposed a new strategy for constructing whole-cell biosensors based on aminoacyl-tRNA synthetases (aaRSs), which take the advantage of their universality and intrinsically specific binding ability to corresponding amino acids. Taking isoleucine biosensor as an example, we first mutated the isoleucyl-tRNA synthetase in Escherichia coli to dramatically decrease its affinity to isoleucine. The engineered cells specifically sensed isoleucine and output isoleucine dose-dependent cell growth as an easily detectable signal. To further expand the sensing range, an isoleucine exporter was overexpressed to enhance excretion of intracellular isoleucine. Since cells equipped with the optimized whole-cell biosensor showed accelerated growth when cells produced higher concentrations of isoleucine, the biosensor was successfully applied in high-throughput selection of isoleucine overproducers from random mutation libraries. This work demonstrates the feasibility of engineering aaRSs to construct a new kind of whole-cell biosensors for amino acids. Considering all twenty proteinogenic and many non-canonical amino acids have their specific aaRSs, this strategy should be useful for developing biosensors for various amino acids. • A sensitive and specific whole-cell biosensor based on isoleucyl-tRNA synthetase mutant was developed. •Overexpression of the isoleucine exporter enlarged the sensing range of the biosensor. •The biosensor was used for high-throughput screening of isoleucine overproducers. •The universality of aminoacyl-tRNA synthetases for proteinogenic amino acids provides a new strategy for constructing amino acid biosensors. [ABSTRACT FROM AUTHOR]

Studies on the third-generation of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) targeting EGFRL858R/T790M mutant remain hotspots, specifically for non-small cell lung cancer (NSCLC). In the current study, a new series of EGFR-TKIs with thieno[3,2- d pyrimidine derivatives(6a - 6r) bearing quinolin-2(1 H)-ones were designed and synthesized, through conformational constrained strategy from the third generation of EGFR-TKI olmutinib. In vitro structure-activity relationship (SAR) studies indicated that compounds 6a , 6l , 6m , 6n and 6o exhibited good selective inhibition to EGFRL858R/T790M (IC 50 ≤ 250 nM) over wild type EGFR (IC 50 > 10000 nM). The observed selectivity of compounds 6l and 6o was also proved by the computational molecular docking and the cellular thermal shift assay. These compounds had good growth inhibitory effect on the four tested cancer cell lines. Specifically, 6o could significantly inhibit the colony formation, wound healing and the expression of p-EGFR and its downstream p-ERK in EGFRL858R/T790M H1975 lung cancer cells. Our findings suggest that the thieno[3,2-d]pyrimidine compounds, especially 6l and 6o , can selectively target the mutant EGFRL858R/T790M in vitro and at cellular level and may serve as the lead compounds for generating new series of the third-generation EGFR-TKIs. The new thieno[3,2-d]pyrimidine compounds, especially 6l and 6o , can efficiently and selectively target the mutant EGFRL858R/T790M in vitro and at cellular level and may serve as the lead compounds for generating new series of the third-generation EGFR-TKIs. Image 1 • Half of thieno[3,2-d]pyrimidine derivatives showed potent selective inhibition on EGFRL858R/T790M in vitro. • Compounds 6l and 6o were specifically targeted to EGFRL858R/T790M. • 6o exhibited good and selective inhibition for H1975, bearing EGFRL858R/T790M than those in A549s, bearing EGFRWT. • 6o remarkably down-regulated the expression of p-EGFR and p-ERK in H1975 cells. [ABSTRACT FROM AUTHOR]

• Pre-cracking degree of static compaction specimen changed significantly. • Indirect tensile strength performance of static compaction specimen was the worst. • Pre-cracking both reduced shrinkage of two kinds of specimen effectively. • Crack resistance of vibration compaction specimen was better. The cement-stabilized macadam formed by static (SC) and vibration compaction (VC) were pre-cracked and their properties comparison were conducted. It indicated that the lowest self-healing rate of VC and SC at 7 days were 57.1% and 54.2%, respectively, with the pre-cracking time of 3 days and degree of 40%. It proved that the shrinkage strains of VC and SC were reduced at most by 35.8% and 35.3%, respectively, with the pre-cracking time of 2 days and degree of 40%, respectively, and the corresponding crack resistance were improved by nearly 300%, with the time of 2 days and degree of 30%. The results showed that VC had a better performance. [ABSTRACT FROM AUTHOR]

Potent and safe anticancer drugs research and development are still on the way to human health. In this report, a series of novel thiosemicarbazone derivatives containing indole fragment were designed and synthesized. Most compounds exhibited excellent antiproliferative activity against PC3, MGC803 and EC109 cell lines with low micromolar IC 50 (0.14–12μM). Especially, compound 5j can selectively inhibit PC3 cells in three tested tumor cells with IC 50 value of 0.14 μM, which may be attributed to a synergistic effect after introducing indole fragment into the TSC structure. Meanwhile, compound 5j displayed more selectivity in PC3 cells toward two normal WPMY-1 and GES-1 cell lines, compared to those of 3-AP and DPC. We also found that 5j can effectively inhibit PC3 cell proliferation, colonization and induce apoptosis. What's more, 5j may significantly suppress migration and invasion by blocking the EMT process but had no effect on cell cycle. Collectively, our findings indicate that 5j with structure of thiosemicarbazone containing indole may serve as a useful anticancer lead for further optimization and development. Image 1 • Thiosemicarbazone derivatives containing indole were designed and synthesized. • 5j displayed more selectivity in PC3 toward WPMY-1, compared to those of 3-AP. • 5j can effectively inhibit PC3 proliferation, colonization and induce apoptosis. • 5j could suppress migration and had no effect on cell cycle arrest. [ABSTRACT FROM AUTHOR]