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Calmodulins (CaMs) and calmodulin-like proteins (CMLs) belong to families of calcium-sensors that act as calcium ion (Ca 2+ ) signal-decoding proteins and regulate downstream target proteins. As a tropical halophyte, Canavalia rosea shows great resistance to multiple abiotic stresses, including high salinity/alkalinity, extreme drought, heat, and intense sunlight. However, investigations of calcium ion signal transduction involved in the stress responses of C. rosea are limited. The CaM and CML gene families have been identified and characterized in many other plant species. Nevertheless, there is limited available information about these genes in C. rosea . In this study, a bioinformatic analysis, including the gene structures, conserved protein domains, phylogenetic relationships, chromosome distribution, and gene synteny, was comprehensively performed to identify and characterize CrCaMs and CrCMLs . A spatio-temporal expression assay in different organs and environmental conditions was then conducted using the RNA sequencing technique. Additionally, several CrCaM and CrCML members were then cloned and functionally characterized using the yeast heterogeneous expression system, and some of them were found to change the tolerance of yeast to heat, salt, alkalinity, and high osmotic stresses. The results of this study provide a foundation for understanding the possible roles of the CrCaM and CrCML genes, especially for halophyte C. rosea 's natural ecological adaptability for its native habitats. This study also provides a theoretical basis for further study of the physiological and biochemical functions of plant CaM s and CML s that are involved in tolerance to multiple abiotic stresses.

Dissolved organic matter (DOM) has a complex composition, which can interact with various pollutants and affect the removal of pollutants. Therefore, a thorough understanding of the interaction between the encccvironmental hormone nonylphenol (NP) and DOM is crucial for environmental impact and development. In this study, the interaction was investigated by means of excitation emission matrix (EEM) fluorescence spectroscopy, UV-Vis spectroscopy, FT-IR spectroscopy, nuclear magnetic resonance (NMR) and complex model analysis. The interaction between different MW DOM and NP was verified by the spectral characterization data. According to the characterization analysis, the main components of DOM in water samples were proteinoid (C1, C2, C4) with MW < 1 k Da, and their binding capacity (log K a value) and binding site number (n) showed the maximum values (3.37, 3.24, 3.26; 0.81, 1.22, 0.52). For the humus like substance (C3) with larger molecular weight, the log K a value and the number of binding points n increased with increasing molecular weight, and the maximum values were 3.13 and 0.31, respectively. It can be seen that low molecular weight proteins have strong binding ability and binding sites with NP, and high molecular weight humus also have strong binding ability. Overall, the interaction between DOM and NP has molecular weight dependence and heterogeneity. The purpose of this study is to deeply understand the interaction characteristics of different MW DOM with NP, and to provide theoretical support and reference for the study of the removal effects of NP pollutants., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:The authors declare no competing financial interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Thaumatin-like proteins (TLPs), including osmotins, are multifunctional proteins related to plant biotic and abiotic stress responses. TLP s are often present as large multigene families. Tetragonia tetragonoides (Pall.) Kuntze (Aizoaceae, 2 n = 2x = 32), a vegetable used in both food and medicine, is a halophyte that is widely distributed in the coastal areas of the tropics and subtropics. Saline-alkaline soils and drought are two major abiotic stress factors significantly affecting the distribution of tropical coastal plants. The expression of stress resistance genes would help to alleviate the cellular damage caused by abiotic stress factors such as high temperature, salinity-alkalinity, and drought. This study aimed to better understand the functions of TLP s in the natural ecological adaptability of T. tetragonoides to harsh habitats. In the present study, we used bioinformatics approaches to identify 37 TtTLP genes as gene family members in the T. tetragonoides genome, with the purpose of understanding their roles in different developmental processes and the adaptation to harsh growth conditions in tropical coral regions. All of the TtTLP s were irregularly distributed across 32 chromosomes, and these gene family members were examined for conserved motifs of their coding proteins and gene structure. Expression analysis based on RNA sequencing and subsequent qRT-PCR showed that the transcripts of some TtTLP s were decreased or accumulated with tissue specificity, and under environmental stress challenges, multiple TtTLP s exhibited changeable expression patterns at short (2 h), long (48 h), or both stages. The expression pattern changes in TtTLPs provided a more comprehensive overview of this gene family being involved in multiple abiotic stress responses. Furthermore, several TtTLP genes were cloned and functionally identified using the yeast expression system. These findings not only increase our understanding of the role that TLP s play in mediating halophyte adaptation to extreme environments but also improve our knowledge of plant TLP evolution. This study also provides a basis and reference for future research on the roles of plant TLP s in stress tolerance and ecological environment suitability.

Ionizing radiation (IR)-induced intestinal injury is usually accompanied by high lethality. Intestinal stem cells (ISCs) are critical and responsible for the regeneration of the damaged intestine. Astragalus polysaccharide (APS), one of the main active ingredients of Astragalus membranaceus (AM), has a variety of biological functions. This study was aimed to investigate the potential effects of APS on IR-induced intestine injury via promoting the regeneration of ISCs. We have established models of IR-induced intestinal injury and our results showed that APS played great radioprotective effects on the intestine. APS improved the survival rate of irradiated mice, reversed the radiation damage of intestinal tissue, increased the survival rate of intestinal crypts, the number of ISCs and the expression of intestinal tight junction-related proteins after IR. Moreover, APS promoted the cell viability while inhibited the apoptosis of MODE-K. Through organoid experiments, we found that APS promoted the regeneration of ISCs. Remarkably, the results of network pharmacology, RNA sequencing and RT-PCR assays showed that APS significantly upregulated the HIF-1 signalling pathway, and HIF-1 inhibitor destroyed the radioprotection of APS. Our findings suggested that APS promotes the regeneration of ISCs through HIF-1 signalling pathway, and it may be an effective radioprotective agent for IR-induced intestinal injury., (© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Bacopaside I (BSI) is a natural compound that is difficult to absorb orally but has been shown to have antidepressant effects. The microbiota-gut-brain axis is involved in the development of depression through the peripheral nervous system, endocrine system, and immune system and may be a key factor in the effect of BSI. Therefore, this study aimed to investigate the potential mechanism of BSI in the treatment of depression via the microbiota-gut-brain axis and to validate it in a fecal microbiota transplantation model. The antidepressant effect of BSI was established in CUMS-induced mice using behavioral tests and measurement of changes in hypothalamicpituitaryadrenal (HPA) axis-related hormones. The improvement of stress-induced gut-brain axis damage by BSI was observed by histopathological sections and enzyme-linked immunosorbent assay (ELISA). 16 S rDNA sequencing analysis indicated that BSI could modulate the abundance of gut microbiota and increase the abundance of probiotic bacteria. We also observed an increase in short-chain fatty acids, particularly acetic acid. In addition, BSI could modulate the disruption of lipid metabolism induced by CUMS. Fecal microbiota transplantation further confirmed that disruption of the microbiota-gut-brain axis is closely associated with the development of depression, and that the microbiota regulated by BSI exerts a partial antidepressant effect. In conclusion, BSI exerts antidepressant effects by remodeling gut microbiota, specifically through the Lactobacillus and Streptococcus-acetic acid-neurotrophin signaling pathways. Furthermore, BSI can repair damage to the gut-brain axis, regulate HPA axis dysfunction, and maintain immune homeostasis., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

In this study, we prepared porous Au-Ag alloy nanoparticle arrays with hydrophobic surfaces through the polystyrene colloidal crystal template combined with the chemical etching method to realize rapid SERS detection for biochemical molecules. In the preparation process, the pore size of Au-Ag alloy nanoparticles could be adjusted by changing the deposition time of the Ag element. Furthermore, after depositing the Au film on the surface of the porous nanoparticle arrays, their surface changed from hydrophilic to hydrophobic. The hydrophobic surface can drive target molecules to locally aggregate. Meanwhile, the hydrophobic surface also possessed a large number of active "hot spots" due to the porous structure. For these reasons, the porous Au-Ag alloy nanoparticle arrays can enable rapid and trace SERS detection, which provide the material basis for the subsequent construction of the high-quality SERS substrate., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Tetragonia tetragonoides (Pall.) Kuntze (Aizoaceae, 2n = 2x = 32), a vegetable used for both food and medicine, is a halophyte that is widely distributed in the coastal areas of the tropics and subtropics. Saline-alkaline soils and drought stress are two major abiotic stressors that significantly affect the distribution of tropical coastal plants. Abscisic acid-, stress-, and ripening-induced (ASR) proteins belong to a family of plant-specific, small, and hydrophilic proteins with important roles in plant development, growth, and abiotic stress responses. Here, we characterized the ASR gene family from T. tetragonoides , which contained 13 paralogous genes, and divided TtASRs into two subfamilies based on the phylogenetic tree. The TtASR genes were located on two chromosomes, and segmental duplication events were illustrated as the main duplication method. Additionally, the expression levels of TtASR s were induced by multiple abiotic stressors, indicating that this gene family could participate widely in the response to stress. Furthermore, several TtASR genes were cloned and functionally identified using a yeast expression system. Our results indicate that TtASR s play important roles in T. tetragonoides ' responses to saline-alkaline soils and drought stress. These findings not only increase our understanding of the role ASRs play in mediating halophyte adaptation to extreme environments but also improve our knowledge of plant ASR protein evolution.

Cryptotanshinone (CPT), a major biological active ingredient extracted from root of Salvia miltiorrhiza (Danshen), has shown several pharmacological activities. However, the effect of CPT on radiation-induced lung fibrosis (RILF) is unknown. In this study, we explored the protective effects of CPT on RILF from gut-lung axis angle, specifically focusing on the bile acid (BA)-gut microbiota axis. We found that CPT could inhibit the process of epithelial mesenchymal transformation (EMT) and suppress inflammation to reduce the deposition of extracellular matrix in lung fibrosis in mice induced by radiation. In addition, 16S rDNA gene sequencing and BAs-targeted metabolomics analysis demonstrated that CPT could improve the dysbiosis of gut microbiota and BA metabolites in RILF mice. CPT significantly enriched the proportion of the beneficial genera Enterorhabdus and Akkermansia, and depleted that of Erysipelatoclostridium, which were correlated with increased intestinal levels of several farnesoid X receptor (FXR) natural agonists, such as deoxycholic acid and lithocholic acid, activating the FXR pathway. Taken together, these results suggested that CPT can regulate radiation-induced disruption of gut microbiota and BAs metabolism of mice, and reduce the radiation-induced lung inflammation and fibrosis. Thus, CPT may be a promising drug candidate for treating RILF., (© 2023 John Wiley & Sons, Ltd.)

Leukopenia caused by radiation hinders the continuous treatment of cancers. Danggui Buxue Decoction (DBD) has been widely used in clinical owing to low toxicity and definite therapeutic effects to increase leukocytes. Meanwhile, icaritin (ICT) has also been proved to have the effect of boosting peripheral blood cells proliferation. However, there is no study to prove the efficacy of MDBD (Modified Danggui Buxue Decoction), a derivative herbal formula composed of DBD and ICT, in the treatment of radiation-induced leukopenia. In this study, we performed a model of 3.5 Gy whole-body radiation to induce leukopenia in mice. The results of pharmacodynamic studies demonstrated that MDBD could significantly increase the white blood cells in peripheral blood by improving the activity of bone marrow nuclear cells, reducing bone marrow damage, modulating spleen index, and regulating hematopoietic factors to alleviate leukopenia. We also analyzed the integrated results of metabolomics and transcriptomics and found that MDBD could relieve leukopenia and alleviate bone marrow damage by targeting steroid biosynthesis and IL-17 signaling pathway, in which the key genes are Jun, Cxcl2 and Egr1. Therefore, our study provides a basis for the effectiveness and compatibility in the combination of traditional Chinese medicine formula and small molecule drugs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Xin, Wei, Ding, Shen, Xu, Wei, Lv, Wang, Li, Zhang and Zu.)

Background: Patients with malignancy are at a higher risk of developing nosocomial infections. However, limited studies investigated the clinical features and prognostic factors of nosocomial infections due to fungi in cancer patients. Herein, this study aims to investigate the clinical characteristics of in-hospital fungal infections and develop a nomogram to predict the risk of in-hospital death during fungal infection of hospitalized cancer patients., Methods: This retrospective observational study enrolled cancer patients who experienced in-hospital fungal infections between September 2013 and September 2021. Univariate and multivariate logistic regression analyses were performed to identify independent predictors of in-hospital mortality. Variables demonstrating significant statistical differences in the multivariate analysis were utilized to construct a nomogram for personalized prediction of in-hospital death risk associated with nosocomial fungal infections. The predictive performance of the nomogram was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis., Results: A total of 216 participants were included in the study, of which 57 experienced in-hospital death. C.albicans was identified as the most prevalent fungal species (68.0%). Respiratory infection accounted for the highest proportion of fungal infections (59.0%), followed by intra-abdominal infection (8.8%). The multivariate regression analysis revealed that Eastern Cooperative Oncology Group Performance Status (ECOG-PS) 3-4 (odds ratio [OR] = 6.08, 95% confidence interval [CI]: 2.04-18.12), pulmonary metastases (OR = 2.76, 95%CI: 1.11-6.85), thrombocytopenia (OR = 2.58, 95%CI: 1.21-5.47), hypoalbuminemia (OR = 2.44, 95%CI: 1.22-4.90), and mechanical ventilation (OR = 2.64, 95%CI: 1.03-6.73) were independent risk factors of in-hospital death. A nomogram based on the identified risk factors was developed to predict the individual probability of in-hospital mortality. The nomogram demonstrated satisfactory performance in terms of classification ability (area under the curve [AUC]: 0.759), calibration ability, and net clinical benefit., Conclusions: Fungi-related nosocomial infections are prevalent among cancer patients and are associated with poor prognosis. The constructed nomogram provides an invaluable tool for oncologists, enabling them to make timely and informed clinical decisions that offer substantial net clinical benefit to patients., (© 2023. The Author(s).)

Ag dendrites have recently been widely reported due to their excellent surface-enhanced Raman scattering (SERS) properties. However, prepared pristine Ag dendrites are usually contaminated by organic impurities, which has a huge negative impact on their Raman detection and greatly limits their practical applications. In this paper, we reported a facile strategy to obtain clean Ag dendrites by high temperature decomposition of organic impurities. With the assistance of ultra-thin coating via atomic layer deposition (ALD), the nanostructure of Ag dendrites can be retained at high temperature. SERS activity can be recovered after etching ALD coating. Chemical composition tests indicate that the organic impurities can be effectively removed. As a result, the clean Ag dendrites can obtain more clearly discernible Raman peaks and lower limits of detection than the pristine Ag dendrites. Furthermore, it was demonstrated that this strategy is also applicable to clean other substrates, such as gold nanoparticles. Therefore, high temperature annealing with the help of ALD sacrifice coating is a promising and non-destructive strategy to clean the SERS substrates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Chronic fatigue syndrome (CFS) is a debilitating disease with no symptomatic treatment. Astragalus polysaccharide (APS), a component derived from the traditional Chinese medicine A. membranaceus, has significant anti-fatigue activity. However, the mechanisms underlying the potential beneficial effects of APS on CFS remain poorly understood. A CFS model of 6-week-old C57BL/6 male mice was established using the multiple-factor method. These mice underwent examinations for behavior, oxidative stress and inflammatory indicators in brain and intestinal tissues, and ileum histomorphology. 16 S rDNA sequencing analysis indicated that APS regulated the abundance of gut microbiota and increased production of short chain fatty acids (SCFAs) and anti-inflammatory bacteria. In addition, APS reversed the abnormal expression of Nrf2, NF-κB, and their downstream factors in the brain-gut axis and alleviated the reduction in SCFAs in the cecal content caused by CFS. Further, APS modulated the changes in serum metabolic pathways induced by CFS. Finally, it was verified that butyrate exerted antioxidant and anti-inflammatory effects in neuronal cells. In conclusion, APS could increase the SCFAs content by regulating the gut microbiota, and SCFAs (especially butyrate) can further regulate the oxidative stress and inflammation in the brain, thus alleviating CFS. This study explored the efficacy and mechanism of APS for CFS from the perspective of gut-brain axis and provides a reference to further explore the efficacy of APS and the role of SCFAs in the central nervous system., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Cysteine-rich transmembrane module (CYSTM) proteins constitute small molecular protein families and have been identified across eukaryotes, including yeast, humans, and several plant species. Plant CYSTMs play vital roles in growth regulation, development, phytohormone signal transduction, pathogen defense, environmental stress response, and even heavy metal binding and detoxification. Canavalia rosea (Sw.) DC is a perennial halophyte with great semi-arid and saline-alkali tolerance. In this study, the CrCYSTM family including 10 members were identified in the C. rosea genome, with the purpose of clarifying the possible roles of CrCYSTMs in C. rosea plants development and stress resistance. The phylogenetic relationships, exon-intron structure, domain structure, chromosomal localization, and putative cis-acting elements in promoter regions were predicted and analyzed. Transcriptome analysis combined with quantitative reverse transcription PCR showed that different CrCYSTM members exhibited varied expression patterns in different tissues and under different abiotic stress challenges. In addition, several CrCYSTMs were cloned and functionally characterized for their roles in abiotic stress tolerance with yeast expression system. Overall, these findings provide a foundation for functionally characterizing plant CYSTMs to unravel their possible roles in the adaptation of C. rosea to tropical coral reefs. Our results also lay the foundation for further research on the roles of plant CYSTM genes in abiotic stress signaling, especially for heavy metal detoxification., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

This paper proposes a speech recognition method based on a domain-specific language speech network (DSL-Net) and a confidence decision network (CD-Net). The method involves automatically training a domain-specific dataset, using pre-trained model parameters for migration learning, and obtaining a domain-specific speech model. Importance sampling weights were set for the trained domain-specific speech model, which was then integrated with the trained speech model from the benchmark dataset. This integration automatically expands the lexical content of the model to accommodate the input speech based on the lexicon and language model. The adaptation attempts to address the issue of out-of-vocabulary words that are likely to arise in most realistic scenarios and utilizes external knowledge sources to extend the existing language model. By doing so, the approach enhances the adaptability of the language model in new domains or scenarios and improves the prediction accuracy of the model. For domain-specific vocabulary recognition, a deep fully convolutional neural network (DFCNN) and a candidate temporal classification (CTC)-based approach were employed to achieve effective recognition of domain-specific vocabulary. Furthermore, a confidence-based classifier was added to enhance the accuracy and robustness of the overall approach. In the experiments, the method was tested on a proprietary domain audio dataset and compared with an automatic speech recognition (ASR) system trained on a large-scale dataset. Based on experimental verification, the model achieved an accuracy improvement from 82% to 91% in the medical domain. The inclusion of domain-specific datasets resulted in a 5% to 7% enhancement over the baseline, while the introduction of model confidence further improved the baseline by 3% to 5%. These findings demonstrate the significance of incorporating domain-specific datasets and model confidence in advancing speech recognition technology.

Heterochronic parabiosis has shown that aging individuals can be rejuvenated by a youthful circulatory system; however, the underlying mechanisms remain unclear. Here, we evaluated the effect of exosomes isolated from mouse induced pluripotent stem cells (iPSCs) on angiogenesis in naturally aged mice. To achieve this, the angiogenic capacity of aortic ring, the total antioxidant capacity (TAOC), p53 and p16 expression levels of major organs, the proliferation of adherent bone marrow cells, and the function and content of serum exosomes in aged mice administered iPSC-derived exosomes were examined. Additionally, the effect of iPSC-derived exosomes on injured human umbilical vein endothelial cells (HUVECs) was assessed. The angiogenic capacity of aortic rings and clonality of bone marrow cells from young mice were significantly higher than those from aged mice; moreover, the organs of aged mice had a higher expression of aging genes and lower total TAOC. However, in vitro and in vivo experiments showed that the administration of iPSC-derived exosomes significantly improved these parameters in aged mice. The synergistic effect of both in vivo and in vitro treatments of aortic rings with iPSC-derived exosomes improved the angiogenic capacity of aortic rings from aged mice to levels similar to that of young mice. Compared with untreated aged mice, serum exosomal protein content and their promoted effect on endothelial cell proliferation and angiogenesis were significantly higher in untreated young mice and aged mice treated with iPSC-derived exosomes. Overall, these results showed that iPSC-derived exosomes may rejuvenate the body by anti-aging the vascular system.

Background: Cardiomyocytes derived from pluripotent stem cells (PSC-CMs) have been widely accepted as a promising cell source for cardiac drug screening and heart regeneration therapies. However, unlike adult cardiomyocytes, the underdeveloped structure, the immature electrophysiological properties and metabolic phenotype of PSC-CMs limit their application. This project aimed to study the role of the transient receptor potential ankyrin 1 (TRPA1) channel in regulating the maturation of embryonic stem cell-derived cardiomyocytes (ESC-CMs)., Methods: The activity and expression of TRPA1 in ESC-CMs were modulated by pharmacological or molecular approaches. Knockdown or overexpression of genes was done by infection of cells with adenoviral vectors carrying the gene of interest as a gene delivery tool. Immunostaining followed by confocal microscopy was used to reveal cellular structure such as sarcomere. Staining of mitochondria was performed by MitoTracker staining followed by confocal microscopy. Calcium imaging was performed by fluo-4 staining followed by confocal microscopy. Electrophysiological measurement was performed by whole-cell patch clamping. Gene expression was measured at mRNA level by qPCR and at protein level by Western blot. Oxygen consumption rates were measured by a Seahorse Analyzer., Results: TRPA1 was found to positively regulate the maturation of CMs. TRPA1 knockdown caused nascent cell structure, impaired Ca 2+ handling and electrophysiological properties, and reduced metabolic capacity in ESC-CMs. The immaturity of ESC-CMs induced by TRPA1 knockdown was accompanied by reduced mitochondrial biogenesis and fusion. Mechanistically, we found that peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), the key transcriptional coactivator related to mitochondrial biogenesis and metabolism, was downregulated by TRPA1 knockdown. Interestingly, overexpression of PGC-1α ameliorated the halted maturation induced by TRPA1 knockdown. Notably, phosphorylated p38 MAPK was upregulated, while MAPK phosphatase-1 (MKP-1), a calcium-sensitive MAPK inhibitor, was downregulated in TRPA1 knockdown cells, suggesting that TRPA1 may regulate the maturation of ESC-CMs through MKP-1-p38 MAPK-PGC-1α pathway., Conclusions: Taken together, our study reveals the novel function of TRPA1 in promoting the maturation of CMs. As multiple stimuli have been known to activate TRPA1, and TRPA1-specific activators are also available, this study provides a novel and straightforward strategy for improving the maturation of PSC-CMs by activating TRPA1. Since a major limitation for the successful application of PSC-CMs for research and medicine lies in their immature phenotypes, the present study takes a big step closer to the practical use of PSC-CMs., (© 2023. The Author(s).)

Previous studies found that the reward effect is stronger in more difficult retrieval tasks of item memory. However, it remains unclear whether the effect of reward is influenced by the memory task difficulty level in the source memory. We investigated the effects and neural mechanisms of the processing depth during encoding and rewards at retrieval on the item and source memory using event-related potentials (ERPs). Participants were required to carry out the congruity-judgment (deep processing) and size-judgment (shallow processing) tasks during encoding, and they completed separate object and background tests (half presented with reward) immediately after encoding. The results revealed that congruity-judgment (compare to size-judgment) task had longer response time in encoding phase, and evoked significantly greater reward differences at Prs (the hit rate minus the false alarm rate) in item retrieval, and the reward (relative to no reward) significantly improved recognition accuracy in source retrieval. ERP results also showed that congruity-judgment (compare to size-judgment) task evoked the larger N170, P3a, LPP and a decreased P3b of the stimuli in encoding phase, and elicited the wider distribution of LPC and LPN reward effects (i.e., the average amplitudes under the reward condition were significantly more positive than under the non-reward condition) in item retrieval, and the reward effects at FN400, LPC, and LPN were found only in the congruity-judged items with optimal difficulty in source retrieval. The results suggest that reward at retrieval evoked a greater boost in the congruity-judged stimuli, whether in item or source retrieval, which maybe be related to their optimal retrieval difficulty (Pr is closer to medium 0.50). This meant that the reward is more effective in memory retrieval with optimal difficulty., Competing Interests: Declaration of competing interest The authors declared that they had no conflicts of interest with respect to their authorship or the publication of this article., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Concentrating a trace amount of molecules from liquids, solid objects, or the gas phase and delivering them to a localized area are crucial for almost any trace analyte detection device. Analytes within a liquid droplet resting on micro/nanostructured surfaces with liquid-repellent coatings can be concentrated during solvent evaporation. However, these coatings suffer from complex manufacturing procedures, poor versatility, and limited analyte enrichment efficiency. Here, we report on the use of an acoustic levitation platform to losslessly concentrate the analyte molecules dissolved in any volatile liquid, attached to solid objects, or spread in air. Gold nanoparticles can be simultaneously concentrated with the analytes in different phases, realizing sensitive, surface-enhanced Raman scattering detection even at attomolar (10 -18  mol/L) concentration levels. The acoustic levitation platform-enabled, lossless analyte enrichment can significantly increase the analytical performance of many conventional microsensing techniques., (© 2022. The Author(s).)

Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by MeCP2 mutations . Nonetheless, the pathophysiological roles of MeCP2 mutations in the etiology of intrinsic cardiac abnormality and sudden death remain unclear. In this study, we performed a detailed functional studies (calcium and electrophysiological analysis) and RNA-sequencing-based transcriptome analysis of a pair of isogenic RTT female patient-specific induced pluripotent stem-cell-derived cardiomyocytes (iPSC-CMs) that expressed either MeCP2 wildtype or MeCP2 mutant allele and iPSC-CMs from a non-affected female control. The observations were further confirmed by additional experiments, including Wnt signaling inhibitor treatment, siRNA-based gene silencing, and ion channel blockade. Compared with MeCP2 wildtype and control iPSC-CMs, MeCP2 mutant iPSC-CMs exhibited prolonged action potential and increased frequency of spontaneous early after polarization. RNA sequencing analysis revealed up-regulation of various Wnt family genes in MeCP2 mutant iPSC-CMs. Treatment of MeCP2 mutant iPSC-CMs with a Wnt inhibitor XAV939 significantly decreased the β-catenin protein level and CACN1AC expression and ameliorated their abnormal electrophysiological properties. In summary, our data provide novel insight into the contribution of activation of the Wnt/β-catenin signaling cascade to the cardiac abnormalities associated with MeCP2 mutations in RTT.

Previous studies have found differences in the cognitive and neural mechanisms between cognitive reappraisal and expression suppression in the regulation of various negative emotions and the recognition of regulated stimuli. However, whether these differences are valid for sadness remains unclear. As such, we investigated the effect of cognitive reappraisal and expression suppression on sadness regulation and the recognition of sad scenes adopting event-related potentials (ERPs). Twenty-eight healthy undergraduate and graduate students took part in this study. In the regulation phase, the participants were asked to down-regulation, expressive suppression, or maintain their sad emotion evoked by the sad images, and then to perform an immediately unexpected recognition task involving the regulated images. The behavioral results show that down-regulation reappraisal significantly diminished subjective feelings of sadness, but expressive suppression did not; both strategies impaired the participants' recognition of sad images, and expressive suppression had a greater damaging effect on the recognition of sad images than down-regulation reappraisal. The ERP results indicate that reappraisal (from 300 ms to 1,500 ms after image onset) and expressive suppression (during 300-600 ms) significantly reduced the late positive potential (LPP) induced by sadness. These findings suggest that down-regulation reappraisal and expression suppression can effectively decrease sadness, and that down-regulation reappraisal (relative to expression suppression) is a more effective regulation strategy for sadness. Both strategies impair the recognition of sad scenes, and expression suppression (compared to down-regulation reappraisal) leads to relatively greater impairment in the recognition of sad scenes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yan, Ding, Wang, Wu, Gao and Liu.)

Aims: Remdesivir is a prodrug of an adenosine triphosphate analogue and is currently the only drug formally approved for the treatment of hospitalized coronavirus disease of 2019 (COVID-19) patients. Nucleoside/nucleotide analogues have been shown to induce mitochondrial damage and cardiotoxicity, and this may be exacerbated by hypoxia, which frequently occurs in severe COVID-19 patients. Although there have been few reports of adverse cardiovascular events associated with remdesivir, clinical data are limited. Here, we investigated whether remdesivir induced cardiotoxicity using an in vitro human cardiac model., Methods and Results: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were exposed to remdesivir under normoxic and hypoxic conditions to simulate mild and severe COVID-19, respectively. Remdesivir induced mitochondrial fragmentation, reduced redox potential, and suppressed mitochondrial respiration at levels below the estimated plasma concentration under both normoxic and hypoxic conditions. Non-mitochondrial damage such as electrophysiological alterations and sarcomere disarray were also observed. Importantly, some of these changes persisted after the cessation of treatment, culminating in increased cell death. Mechanistically, we found that inhibition of DRP1, a regulator of mitochondrial fission, ameliorated the cardiotoxic effects of remdesivir, showing that remdesivir-induced cardiotoxicity was preventable and excessive mitochondrial fission might contribute to this phenotype., Conclusions: Using an in vitro model, we demonstrated that remdesivir can induce cardiotoxicity in hiPSC-CMs at clinically relevant concentrations. These results reveal previously unknown potential side-effects of remdesivir and highlight the importance of further investigations with in vivo animal models and active clinical monitoring to prevent lasting cardiac damage to patients., Competing Interests: Conflict of interest: none declared., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

In this article, a mixed finite element method for thermally coupled, stationary incompressible MHD problems with physical parameters dependent on temperature in the Lipschitz domain is considered. Due to the variable coefficients of the MHD model, the nonlinearity of the system is increased. A stationary discrete scheme based on the coefficients dependent temperature is proposed, in which the magnetic equation is approximated by Nédélec edge elements, and the thermal and Navier-Stokes equations are approximated by the mixed finite elements. We rigorously establish the optimal error estimates for velocity, pressure, temperature, magnetic induction and Lagrange multiplier with the hypothesis of a low regularity for the exact solution. Finally, a numerical experiment is provided to illustrate the performance and convergence rates of our numerical scheme.

Transforming levulinic acid (LA) to γ -valerolactone (GVL) is a significant route for converting biomass into valuable chemicals. The development of an efficient and robust heterogeneous catalyst for this reaction has aroused great interest. In this work, nitrogen-doped graphene (NG) supported nickel (Ni) based heterogeneous catalyst with excellent activities was successfully synthesized. The Ni/NG catalyst shows outstanding performance for hydrogenation of LA to GVL at a relatively low temperature of 140 °C, which is superior to most of reported heterogeneous catalysts. Further investigations indicate Ni nanoparticles are the active sites and the NG also plays an indispensable role. The catalytic performance is highly depended on the crystallinity, particles sizes and electronic structure of Ni in Ni/NG catalyst, which can be optimized by nitrogen doping. This work affords a new route for designing robust and excellent heterogeneous catalysts by doping method to optimize the support., (© 2022 IOP Publishing Ltd.)

Previous studies have explored the effects of retrieval reward and depth of processing in encoding on recognition, but it remains unclear whether and how reward and depth of processing during encoding influence recognition. We investigated the effect and neural mechanisms of encoding reward and processing depth on recognition using event-related potentials (ERPs) in this study. In the study phase, participants were asked to perform two encoding tasks: congruity-judgment (deep processing) and size-judgment (shallow processing) in reward and no-reward conditions. The test phases included object (item) and background (source) tests. The results of item retrieval showed that the accuracy of rewarded items was higher than that of unrewarded items only in the congruity-judgment task, and the reward effect (the average amplitudes in the reward condition were significantly more positive than those in the no-reward condition) in the 300-500 and 500-700 ms were greater in the congruity-judgment task than in the size-judgment task. The results of source retrieval showed that the accuracy of rewarded items was higher than that of unrewarded items, that the difference in the size-judgment task was significantly larger, and that the reward effect in the 300-500 and 500-700 ms were greater in the size-judgment task than in the congruity-judgment task. In conclusion, the encoding task moderated the reward effect in item and source memory., (© 2022. The Author(s).)

Structures with dense nanopores are desirable as surface-enhanced Raman scattering (SERS) sensing substrates because the nanopores can behave as both analyte containers and SERS-active sites (known as hot spots). Inspired by the dealloying process to prepare nanoporous structures through selectively removing active metals from their alloy, we developed a method to prepare nanoporous Ag nanorods through chemical reduction of the electrodeposited Ag 7 O 8 NO 3 nanorods using a strong reducing agent (e.g., NaBH 4 ). The length and the thickness of the Ag 7 O 8 NO 3 nanorods could be controlled by the electrodeposition voltage and time. Nitrogen and oxygen elements were immediately removed from Ag 7 O 8 NO 3 nanorods by the reducing agent, leaving behind a tremendous number of nanopores with a mean size of 20 nm, which can efficiently trap and enrich analytes. Meanwhile, the densely packed nanopores can behave as SERS hot spots to provide strong SERS enhancement. The nanoporous Ag nanorods as SERS substrates were used to sensitively detect adenine, spike glycoprotein, and polychlorinated biphenyls pollutants, as well as identify different types of bacteria. The simple fabrication process and the outstanding SERS performance of the nanoporous Ag nanorods make them promising candidates for SERS applications towards trace detection of pollutants, narcotics, food additives, and biomolecules., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Lipid metabolism plays a pivotal role in cancer progression and metastasis. This study aimed to investigate the prognostic value of lipid metabolism-related genes (LMRGs) in early-stage lung adenocarcinoma (LUAD) and develop a lipid metabolism-related gene prognostic index (LMRGPI) to predict their overall survival (OS) and treatment response. Methods: A total of 774 early-stage LUAD patients were identified from The Cancer Genome Atlas (TCGA, 403 patients) database and Gene Expression Omnibus (GEO, 371 patients) database. The non-negative Matrix Factorization (NMF) algorithm was used to identify different population subtypes based on LMRGs. The Least Absolute Shrinkage and Selection Operator (LASSO) and multivariate Cox regression analyses were used to develop the LMRGPI, with receiver operating characteristic (ROC) curves and concordance index being used to evaluate its performance. The characteristics of mutation landscape, enriched pathways, tumor microenvironment (TME), and treatment response between different LMRGPI groups were also investigated. Results: We identified two population subtypes based on LMRGs in the TCGA-LUAD cohort, with distinct prognosis, TME, and immune status being observed. LMRGPI was developed based on the expression levels of six LMRGs, including ANGPTL4 , NPAS2 , SLCO1B3 , ACOXL , ALOX15 , and B3GALNT1 . Higher LMRGPI was correlated with poor OS both in TCGA and GSE68465 cohorts. Two nomograms were established to predict the survival probability of early-stage LUAD, with higher consistencies being observed between the predicted and actual OS. Higher LMRGPI was significantly correlated with more frequent TP53 mutation, higher tumor mutation burden (TMB), and up-regulation of CD274. Besides, patients with higher LMRGPI presented unremarkable responses for gefitinib, erlotinib, cisplatin, and vinorelbine, while they tend to have a favorable response for immune checkpoint inhibitors (ICIs). The opposite results were observed in the low-LMRGPI group. Conclusions: We comprehensively investigated the prognostic value of LMRGs in early-stage LUAD. Given its good prognostic ability, LMRGPI could serve as a promising biomarker to predict the OS and treatment response of these patients., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Previous studies have found that reward effect is stronger for more difficult to retrieve items, but whether this effect holds true for the associative memory remains unclear too. We investigated the effects and neural mechanisms of the different unitization depths and reward sets on encoding associative memory using event-related potentials (ERPs), which were recorded through a Neuroscan system with a 64-channel electrode cap according to the international 10-20 system, and five electrodes (Fz, FCz, Cz, CPz, and Pz) were selected for analysis. Thirty healthy college students took part in this study. During encoding, participants were carried out two encoding tasks, a congruity-judgment task with high unitization and a color-judgment task with low unitization, with half of the items rewarded. The test phase was conducted immediately after the encoding phase. The results for false alarm rates and Prs (i.e., hit rates for old pairs minus false alarm rates for new pairs) in relational retrieval revealed that the reward differences in the color-judgment task were greater than those in the congruity-judgment task. The ERP results further showed significant reward effects (i.e., the reward significantly improved the average amplitudes compared to no reward) at P300 (300-500 ms) and LPP (500-800 ms) in the color-judgment task both for intact and rearranged items, and the reward effects at LPP (electrodes Fz, FCz, Cz, CPz, and Pz) were distributed more widely than the reward effects at P300 (electrodes Fz and FCz) in the color-judgment task. These results suggest that reward provided a greater boost when retrieving associative memory of low unitized items., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yan, Ding, Wu and Zhu.)

The Fe 3 O 4 @Au nanostars, whose anisotropic shape couples the plasmons focused on the magnetic core with the branches of the gold shell, hold promise for surface enhanced Raman spectroscopy (SERS) applications. Assembly of monodisperse Fe 3 O 4 @Au nanostars induced by a magnetic field could lead to highly ordered superstructures, providing distinctive SERS activity. In this study, a simplified fabrication technique was developed to assemble Fe 3 O 4 @Au nanostars on the inner walls of a glass capillary into a highly sensitive, reproducible and recyclable SERS active glass capillary under controlled magnetic alignment. The strong dipole-dipole interactions between the neighboring nanoparticles lead to a close-packed pattern as an energetically favorable configuration. The magnetic dipolar interaction between the particles can be further tuned by the controlled anisotropic shape of the gold shell. The interparticle plasmon couplings and lightning rod effects of the Fe 3 O 4 @Au nanostars contributed to Raman enhancement. Based on the capillary action, capillaries can act as a microreactor for the sampling tools. We further demonstrate SERS-based colorant detection in the capillary which the target molecule can easily detect by simple adsorption of the colorants by capillary action. The Fe3O4@Au nanostars in the capillary with a long shelf life, high sensitivity and low cost promote the application of SERS technology in widespread fields.

Pluripotent stem cells (PSCs) can undergo unlimited self-renewal and can differentiate into all the cell types present in our body, including cardiomyocytes. Therefore, PSCs can be an excellent source of cardiomyocytes for future regenerative medicine and medical research studies. However, cardiomyocytes obtained from PSC differentiation culture are regarded as immature structurally, electrophysiologically, metabolically, and functionally. Mitochondria are organelles responsible for various cellular functions such as energy metabolism, different catabolic and anabolic processes, calcium fluxes, and various signaling pathways. Cells can respond to cellular needs to increase the mitochondrial mass by mitochondrial biogenesis. On the other hand, cells can also degrade mitochondria through mitophagy. Mitochondria are also dynamic organelles that undergo continuous fusion and fission events. In this review, we aim to summarize previous findings on the changes of mitochondrial biogenesis, mitophagy, and mitochondrial dynamics during the maturation of cardiomyocytes. In addition, we intend to summarize whether changes in these processes would affect the maturation of cardiomyocytes. Lastly, we aim to discuss unanswered questions in the field and to provide insights for the possible strategies of enhancing the maturation of PSC-derived cardiomyocytes.

Angiotensin II (Ang II) plays an important role in regulating various physiological processes. However, little is known about the existence of intracellular Ang II (iAng II), whether iAng II would regulate the automaticity of early differentiating cardiomyocytes, and the underlying mechanism involved. Here, iAng II was detected by immunocytochemistry and ultra-high performance liquid chromatography combined with electrospray ionization triple quadrupole tandem mass spectrometry in mouse embryonic stem cell-derived cardiomyocytes (mESC-CMs) and neonatal rat ventricular myocytes. Expression of AT 1 R-YFP in mESC-CMs revealed that Ang II type 1 receptors were located on the surface membrane, while immunostaining of Ang II type 2 receptors (AT 2 R) revealed that AT 2 R were predominately located on the nucleus and the sarcoplasmic reticulum. While extracellular Ang II increased spontaneous action potentials (APs), dual patch clamping revealed that intracellular delivery of Ang II or AT 2 R activator C21 decreased spontaneous APs. Interestingly, iAng II was found to decrease the caffeine-induced increase in spontaneous APs and caffeine-induced calcium release, suggesting that iAng II decreased spontaneous APs via the AT 2 R- and ryanodine receptor-mediated pathways. This is the first study that provides evidence of the presence and function of iAng II in regulating the automaticity behavior of ESC-CMs and may therefore shed light on the role of iAng II in fate determination., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Qi, Wang, Chen, Wong, Ding, Sauer, Chen, Long, Yao, Cai and Tsang.)

Background: Biological pacemakers consisting of pluripotent stem cell-derived cardiomyocytes are potentially useful for treating bradycardia. However, tachyarrhythmia caused by derived cardiomyocytes themselves is one of main barriers hampering their clinical translation. An in-depth understanding of the mechanisms underlying the spontaneous action potential (a.k.a. automaticity) might provide potential approaches to solve this problem. The aim of this project is to study the role of canonical transient receptor potential isoform 7 (TRPC7) channels in regulating the automaticity of embryonic stem cell-derived cardiomyocytes (ESC-CMs)., Methods and Results: By Western blotting, the expression of TRPC7 was found to be increased during the differentiation of mouse ESC-CMs (mESC-CMs). Adenovirus-mediated TRPC7 knockdown decreased while overexpression increased the frequency of Ca 2+ transients (CaTs), local Ca 2+ releases (LCRs), and action potentials (APs) as detected by confocal microscopy and whole-cell patch-clamping. TRPC7 was found to be positively associated with the activity of ryanodine receptor 2 (RyR2), sarco/endoplasmic reticulum Ca 2+ -ATPase (SERCA), and sodium-calcium exchanger (NCX) but not hyperpolarization-activated, cyclic nucleotide-gated channel (HCN), and inositol trisphosphate receptor (IP3R). Knockdown or overexpression of TRPC7 did not alter the expression of HCN4, Cav1.3, Cav3.1, Cav3.2, IP3R1, RyR2, and SERCA but positively regulated the phosphorylation of RyR2 at S2814 and phospholamban (PLN) at T17. Moreover, the positive regulation of APs by TRPC7 was Ca 2+ -dependent, as overexpression of N-terminus of TRPC7 (dominant negative of TRPC7) which diminished the Ca 2+ permeability of TRPC7 decreased the AP frequency., Conclusions: TRPC7 regulates the automaticity of mESC-CMs through two mechanisms. On the one hand, TRPC7 positively regulates the intracellular Ca 2+ clock through the regulation of activities of both RyR2 and SERCA; on the other hand, TRPC7 also positively regulates the membrane clock via its influence on NCX activity. Altogether, our study reveals that TRPC7 is a potential drug target to manipulate the action potential firing rate of pluripotent stem cell-derived cardiomyocyte-based biological pacemakers to prevent tachyarrhythmia, a condition that might be encountered after transplantation.

Surface-enhanced Raman scattering (SERS) technique with naturally born analyte identification capability can achieve ultrahigh sensitivity. However, the sensitivity and quantification capability of SERS are assumed to be mutually exclusive. Here, we prohibit the formation of the ultrasensitive SERS sites to achieve a high quantification capability through separating the gold (Au) nanorods from approaching each other with thick metal organic framework (MOF) shells. The sensitivity decrease caused by the absence of the ultrasensitive SERS sites is compensated by the analyte enrichment function of a slippery surface. The porous MOF shell around the Au nanorod only allows analytes smaller than the pore size to approach the Au nanorods and contribute to the SERS spectrum within the complex sample, greatly enhancing the analyte identification capability. Overall, we have demonstrated an integrated SERS platform with analyte enrichment and analyte filtration function, realizing sensitive, quantitative, and size selective analyte identification in complex environments.

Developing low cost and highly robust electrocatalysts for oxygen evolution reaction, hydrogen evolution reaction (HER), and oxygen reduction reaction (ORR) is of great importance for the efficient conversion of sustainable energy sources. Herein, we report a facile pyrolysis strategy for the controllable synthesis of NiCo@NiS/S-CNTs with NiCo@NiS nanoparticles anchored on sulfur-doped carbon nanotubes (CNTs). The obtained NiCo@NiS/S-CNT electrocatalyst exhibits excellent dual-functional catalytic activities under an alkaline condition, an ORR performance with an onset potential of -30 mV, and a half-wave potential of -150 mV (versus Ag/AgCl) while the overpotential for the HER is -1.16 V (versus Ag/AgCl) at a current density of 10 mA cm -2 . It was found that the incorporation of sulfur can regulate the electronic structure of CNTs to accelerate the electron transfer performance and generate new catalytic sites, thus contributing to greatly enhancing both the activity and stability of the catalytic process. This work provides a promising way for the rational design of efficient and robust catalysts for sustainable energy conversion.

Background Pin2/TRF1-interacting protein, PinX1, was previously identified as a tumor suppressor. Here, we discovered a novel transcript variant of mPinX1 (mouse PinX1), mPinX1t (mouse PinX1t), in embryonic stem cells (ESCs). The aims of this investigation were (1) to detect the presence of mPinX1 and mPinX1t in ESCs and their differentiation derivatives; (2) to investigate the role of mPinX1 and mPinX1t on regulating the characteristics of undifferentiated ESCs and the cardiac differentiation of ESCs; (3) to elucidate the molecular mechanisms of how mPinX1 and mPinX1t regulate the cardiac differentiation of ESCs. Methods and Results By 5' rapid amplification of cDNA ends, 3' rapid amplification of cDNA ends, and polysome fractionation followed by reverse transcription-polymerase chain reaction, mPinX1t transcript was confirmed to be an intact mRNA that is actively translated. Western blot confirmed the existence of mPinX1t protein. Overexpression or knockdown of mPinX1 (both decreased mPinX1t expression) both decreased while overexpression of mPinX1t increased the cardiac differentiation of ESCs. Although both mPinX1 and mPinX1t proteins were found to bind to cardiac transcription factor mRNAs, only mPinX1t protein but not mPinX1 protein was found to bind to nucleoporin 133 protein, a nuclear pore complex component. In addition, mPinX1t-containing cells were found to have a higher cytosol-to-nucleus ratio of cardiac transcription factor mRNAs when compared with that in the control cells. Our data suggested that mPinX1t may positively regulate cardiac differentiation by enhancing export of cardiac transcription factor mRNAs through interacting with nucleoporin 133. Conclusions We discovered a novel transcript variant of mPinX1, the mPinX1t, which positively regulates the cardiac differentiation of ESCs.

Surface-enhanced Raman scattering (SERS) substrates capable of working under laser excitation in a broad wavelength range are highly desirable in diverse application fields. Here, we demonstrate that the bioinspired Ag brochosomes, hollow microscale particles with submicroscale pits, have broadband and omnidirectional SERS performance. The SERS performance of the Ag brochosomes under near-infrared laser excitation makes them promising for applications in biosensing fields, such as the sensitive detection of Staphylococcus aureus bacteria and bovine hemoglobin protein. Additionally, the SERS intensity was insensitive to the incident angle of the laser beam, resulting from the spherical structure of the Ag brochosomes. The omnidirectional SERS performance makes the Ag brochosomes have application potential for in-the-field analysis using a hand-held Raman spectrometer for which it is difficult to accurately control the laser beam normal to the SERS substrates. Overall, the broadband and omnidirectional brochosome SERS substrates will find applications in diverse fields, particularly in biomedicine and in-the-field analysis.

Nature of exosome-secreting cells determines exosome content and function. ALIX, involved in exosome biogenesis, promotes cell degeneration. Here, ALIX was knocked out (iPSC-ALIX -/- ) and overexpressed (iPSC-ALIX 3+ ) in induced pluripotent stem cells (iPSCs) using CRISPR-Cas9 and lentiviral transduction, respectively, and the secreted exosomes were analyzed. Exosomes from iPSC-ALIX -/- (exosome-KO), iPSC-ALIX 3+ (exosome-over), and their corresponding controls contained 176, 529, 431, and 351 proteins, respectively. Exosome-over showed increased protein levels, while exosome-KO contained fewer protein types without differing in total protein content. ALIX knockout did not affect exosome uptake by endothelial cells. Exosome-over more effectively promoted cell viability than exosome-GFP, in a dose-dependent manner. All exosomes were protective for endothelial cells injured by hydrogen peroxide or cisplatin, as demonstrated by promotion of cell viability, horizontal migration, angiogenic sprouting from aortic rings, and formation of capillary-like structures, inhibition of apoptosis, and maintenance of permeability of endothelial monolayer, although exosome-over and exosome-KO had stronger and weaker effects, respectively. SNX2 was important for ALIX-mediated exosomal function. Beneficial functions of the exosomes were independent of experimental models, targeted cell types, causes of injury, exosome-producing iPSC passages, clones of ALIX knockout, and transfection batches of ALIX overexpression. Thus, we present a novel strategy to manipulate iPSCs for production of exosomes with beneficial ALIX-regulated protein composition for varied exosome functions. KEY MESSAGES: ALIX knockout and overexpression regulate protein profile in iPSC-derived exosome. ALIX knockout decreases therapeutic function of iPSC-derived exosomes. ALIX overexpression increases therapeutic function of iPSC-derived exosomes. Manipulating iPSCs can produce exosomes with more beneficial protein content.

A growing number of epidemiological surveys show that PM 2.5 is an important promoter for the cardiovascular dysfunction induced by atmospheric pollution. PM 2.5 is a complex mixture of solid and liquid airborne particles and its components determine the health risk of PM 2.5 to a great extent. However, the individual cardiotoxicities of different PM 2.5 fractions are still unclear, especially in the cellular level. Here we used the neonatal rat cardiomyocytes (NRCMs) to evaluate the cardiac toxicity of PM 2.5 exposure. The cytotoxicities of Total-PM 2.5 , water soluble components of PM 2.5 (WS-PM 2.5 ) and water insoluble components of PM 2.5 (WIS-PM 2.5 ), which include the cell viability, cell membrane damage, reactive oxygen species (ROS) generation, were examined with NRCMs in vitro. The results indicated that Total-PM 2.5 or WIS-PM 2.5 exposure significantly decreased the cell viability, induced the cell membrane damage and increased the ROS level in NRCMs at concentrations above 50 µg/mL. However, WS-PM 2.5 exposure could induce the cytotoxicity on NRCMs until the concentration of WS-PM 2.5 was raised to a higher concentration (75 µg/mL). Furthermore, the DNA damage was detected in NRCMs after 48 h of exposure with Total-PM 2.5 , WS-PM 2.5 or WIS-PM 2.5 (75 µg/mL) and the adverse effects on mitochondrial function and action potentials of NRCMs were detected only both in the Total-PM 2.5 and WIS-PM 2.5 treatment group. In summary, our project not only estimates the risk of PM 2.5 on cardiac cells but also reveal that Total-PM 2.5 and WIS-PM 2.5 exposure were predominantly associated with the functional cardiotoxicities in NRCMs., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Surface-enhanced Raman scattering (SERS) has been recognized as a promising sensing technique in biomedical/biosensing applications and analytical chemistry. Silver (Ag) nanostructures have the strongest SERS enhancement, but suffer from severe enhancement degradation induced by oxidation. Here, we introduce electrochemical reduction of silver oxide to produce Ag SERS substrates on request to partially circumvent the SERS enhancement degradation problem of Ag SERS substrates. Silver oxide nanostructures were first prepared in pure silver citrate aqueous solutions with controllable morphologies depending on the electrodeposition parameters. The transition process from silver oxide to Ag was investigated by density functional theory calculations. Based on the understanding of the transition mechanism, heating treatment, applying reducing agent, and electrochemical reduction were adopted to transform silver oxide to Ag. Notably, no organic agents were introduced neither in the electrodeposition of silver oxide nor electrochemical transformation of silver oxide to Ag. The electrochemical reduction strategy could produce Ag SERS substrates with a 'clean' surface with outstanding SERS performance in a simple as well as cost and time effective manner. Ag SERS substrates can be used in biomedical/biosensing fields. The approach through electrochemical reduction of silver oxide to generate Ag SERS substrate may push forward practical application process of Ag SERS substrates.

A series of naphthalimide derivative gelators (G-o, G-m, and G-p) with three molecular isomers as their terminal groups were designed and synthesized. Only G-m and G-p could form stable organogels in some solvents including methanol, acetonitrile, n-hexane, toluene, ethanol, DMSO, DMF, and mixed solvents of acetonitrile/H 2 O (1/1, v/v). The different self-assembly structures were obtained from the self-assembly process of G-o, G-m, and G-p such as structures like a Chinese chestnut formed by irregular micrometer pieces, microbelts, and microbelt structures mingled with the bird's nest structures which exhibited different surface hydrophobicity with water contact angles of 121-139° due to their different intermolecular noncovalent interactions. To our surprise, G-p acetonitrile solution emitted 492 nm light with a red-shift of 72 nm compared with that emitted from G-o and G-m acetonitrile solution under 350 nm light excitation. Three gelators showed different detection abilities toward metal ions. G-o did not have any ability for sensitive and selective detection toward any ion. In contrast, G-m and G-p could sensitively and selectively detect Hg 2+ and Fe 3+ . The detection limits for Fe 3+ and Hg 2+ by G-m were 4.76 × 10 -5 M and 7.01 × 10 -6 M with the corresponding association constants ( K) of 1.64 × 10 4 and 3.79 × 10 4 M -1 , respectively. The detection limits for Fe 3+ and Hg 2+ by G-p were 3.26 × 10 -5 and 1.77 × 10 -6 M with the corresponding K of 1.44 × 10 5 and 1.99 × 10 4 M -1 , respectively. More interestingly, the back-titration of SCN - could distinguish Hg 2+ from Fe 3+ . At the same time, xerogels G-m and G-p also exhibited responsiveness toward Fe 3+ and Hg 2+ through fluorescence changes. The photophysical properties, gel formation, hierarchical structures, surface wettability, and their function in this self-assembly system could be tuned through the molecular isomer effect. This work provides a new research paradigm for molecular isomer tuned supramolecular self-assembly materials from noncovalent interaction to molecular function.

Exosomes are a family of extracellular vesicles that are secreted from almost all types of cells and are associated with cell-to-cell communication. The present study was performed to investigate the effects of human induced pluripotent stem cell-derived exosomes (hiPSC-exo) on cell viability, capillary-like structure formation and senescence in endothelial cells exposed to high glucose. Exosomes were isolated from the conditional medium of hiPSCs and confirmed by transmission electron microscopy, nanoparticle tracking analysis and western blot analysis using Alix and cluster of differentiation-63 as markers. hiPSC-exo were labeled with PKH26 for tracking, and it was determined that spherical exosomes, with a typical cup-shape, were absorbed by human umbilical vascular endothelial cells (HUVECs). Cultured HUVECs were treated with high glucose (33 mM) with or without hiPSC-exo (20 µg/ml) for 48 h, and cell viability, capillary tube formation and senescence were assessed. When exposed to high glucose, viability and tube formation in HUVECs was significantly reduced (P<0.0001), whereas the proportion of senescent cells was higher compared with that in control HUVECs (P<0.0001). Furthermore, hiPSC-exo restored cell viability and capillary-like structure formation, and reduced senescence in HUVECs exposed to high glucose (P<0.0001). However, hiPSC-exo had minimal effects on normal HUVECs. These findings suggest that stem cell-derived exosomes are able to promote cell proliferation, enhance capillary-like structure formation and reduce senescence in endothelial cells exposed to high glucose.

Acute respiratory distress syndrome (ARDS) is a disease that seriously threatens human life and health. The aim of the study was to investigate the effects of ulinastatin combined with mechanical ventilation on oxygen metabolism, inflammation and stress response, as well as the antioxidant capacity of ARDS. Eighty patients with ARDS treated in Yiwu Central Hospital from January, 2015 to December, 2016 were enrolled in the present study and divided into the observation (n=40) and control (n=40) groups, using a random number table. The control group was treated with mechanical ventilation, while the observation group, based on treatment of the control group, was treated with ulinastatin for 14 consecutive days as one course of treatment. The changes in the relevant indexes of oxygen metabolism, lung function, time of ventilator treatment, total hospital stay, and St. George's Respiratory Questionnaire (SGRQ) score of the two groups after intervention were compared, and the changes in inflammatory cytokine levels, dopamine receptor-related hormone levels, superoxide dismutase (SOD), malondialdehyde (MDA) and total antioxidant capacity of the two groups before intervention and at 1 and 4 weeks after intervention were compared. After intervention, the arterial blood lactate in the observation group was significantly lower than that in the control group (P<0.05), the oxygen uptake rate was significantly higher than that in the control group (P<0.05) and the arterial oxygen content was significantly higher than that in the control group (P<0.05). In the lung function indexes, the FEV 1 and FEV 1 /FVC levels in the observation group were smaller than those in the control group (P<0.05), the duration of ventilator treatment was significantly shorter than that in the control group (P<0.05), and the hospital stay was significantly less than that in the control group (P<0.05). Prior to intervention, SGRQ scores in the two groups were not statistically significant (P>0.05). At 1 and 4 weeks after intervention, the SGRQ scores of the observation group were significantly increased to those of the control group (P<0.05). The tumor levels of necrosis factor-α (TNF-α), interleukin-6 (IL-6) and CRP were significantly lower than those of the control group (P<0.05). The levels of adrenaline and norepinephrine were significantly lower than those of the control group (P<0.05). The levels of MDA, SOD and the total antioxidant capacity were significantly increased to those of control group (P<0.05). The application of ulinastatin combined with mechanical ventilation in ARDS patients is of great significance in improving the oxygen delivery-consumption balance of body, increasing the lung function, reducing the inflammatory and stress response, and improving the antioxidant capacity.

Herein, we report the synthesis of a 350 nm Cu nanoparticle array with different period combinations by a method based on a monolayer and have further investigated its surface-enhanced Raman scattering (SERS) properties experimentally. The SERS properties of the 350 nm Cu nanoparticle array were investigated, and the influence of the thickness of the Cu nanoshell was studied. The results demonstrated that the 18 min ion-sputtering deposition can improve the SERS activity in addition to good stability. This study can provide an optimized method for some inexpensive nanomaterials as highly active SERS substrates and a good solution to the interference caused by substrate impurity., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Two simple and novel gelators (G-P with pyridine and G-B with benzene) with different C-4 substitution groups on naphthalimide derivatives have been designed and characterized. Two gelators could form organogels in some solvents or mixed solvents. The self-assembly processes of G-P in a mixed solvent of acetonitrile/H 2 O (1/1, v/v) and G-B in acetonitrile were studied by means of electron microscopy and spectroscopy. The organogel of G-P in the mixed solvent of acetonitrile/H 2 O (1/1, v/v) formed an intertwined fiber network, and its emission spectrum had an obvious blue shift compared with that of solution. By contrast, the organogel of G-B in acetonitrile formed a straight fiber, and its emission had an obvious red shift compared with that of solution. G-P and G-B were employed in detecting nitroaromatic compounds because of their electron-rich property. G-P is more sensitive and selective toward 2,4,6-trinitrophenol (TNP) compared with G-B. The sensing mechanisms were investigated by 1 H NMR spectroscopic experiments and theoretical calculations. From these experimental results, it is proposed that electron transfer occurs from the electron-rich G-P molecule to the electron-deficient TNP because of the possibility of complex formation between G-P and TNP. The G-P molecule could detect TNP in water, organic solvent media, as well as using test strips. It is worth mentioning that the organogel G-P can not only detect TNP but also remove TNP from the solution into the organogel system.

A thiophene-based hybrid organogel system consisting of complex iridium (Ir) and EuCl 3 ·6H 2 O was designed and synthesized to realize dual responses to volatile acids and organic amine vapors. The photophysical properties and self-assembly of compound 1 and the hybrid organogel were also studied. Compound 1 could gelate some organic solvents and self-assemble into 3D nanofibers in the gels. The stable hybrid organogel 1-Ir-Eu could be obtained after addition of complex Ir and EuCl 3 ·6H 2 O. FTIR spectral results showed that the hydrogen bond still remained even upon addition of complex Ir, EuCl 3 ·6H 2 O, NaOH and CF 3 COOH to organogel 1. Interestingly, the emission properties of the hybrid organogel 1-Ir-Eu could undergo interconversion between cyan light and red light via addition of NaOH and CF 3 COOH. The emission properties of xerogel film 1-Ir-Eu obtained in the presence of NaOH could also undergo fast and reversible transition in response to volatile acids such as CF 3 COOH, formic acid, acetic acid, propionic acid and organic amine vapors such as ammonium hydroxide, Et 3 N, tripropylamine, and ethylenediamine. The emission spectral change of Ir-Eu in the organogel or xerogel in the presence of base and acid demonstrated the formation of a new complex between complex Ir and EuCl 3 ·6H 2 O. This dual-response process could be repeated many times. Contact angle experiment results further showed the morphology and internal components of the xerogel film surface in the process of response to gaseous CF 3 COOH and Et 3 N. This work provides a method for producing multifunctional supramolecular materials for sensing volatile acids and organic amine vapors.

A new serial of gelators with two cholesteryl groups based on o-phenylenediamine, m-phenylenediamine and p-phenylenediamine were synthesized, and their organogelation ability was evaluated. We found that G-o could form gels in DMF, DMSO and ethyl acetate, G-m and G-p could only gel DMF and 1,4-dioxane. The organogels were thoroughly characterized using various microscopic techniques including field-emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), UV-Vis spectrum, FT-IR spectrum and contact angle. The gelation ability, morphology, self-assembly mode and materials surface wettability all could be tuned via isomeride effect in self-assembly system. Interestingly, superhydrophobic surface was formed via the self-assembly of compound G-p in 1,4-dioxane and exhibited very high adsorption capacity for water. This gel system provided new method for modulation self-assembly process in supramolecular field., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Using the ultrafast pump-probe transient absorption spectroscopy, the femtosecond-resolved plasmon-exciton interaction of graphene-Ag nanowire hybrids is experimentally investigated, in the VIS-NIR region. The plasmonic lifetime of Ag nanowire is about 150 ± 7 femtosecond (fs). For a single layer of graphene, the fast dynamic process at 275 ± 77 fs is due to the excitation of graphene excitons, and the slow process at 1.4 ± 0.3 picosecond (ps) is due to the plasmonic hot electron interaction with phonons of graphene. For the graphene-Ag nanowire hybrids, the time scale of the plasmon-induced hot electron transferring to graphene is 534 ± 108 fs, and the metal plasmon enhanced graphene plasmon is about 3.2 ± 0.8 ps in the VIS region. The graphene-Ag nanowire hybrids can be used for plasmon-driven chemical reactions. This graphene-mediated surface-enhanced Raman scattering substrate significantly increases the probability and efficiency of surface catalytic reactions co-driven by graphene-Ag nanowire hybridization, in comparison with reactions individually driven by monolayer graphene or single Ag nanowire. This implies that the graphene-Ag nanowire hybrids can not only lead to a significant accumulation of high-density hot electrons, but also significantly increase the plasmon-to-electron conversion efficiency, due to strong plasmon-exciton coupling.

We successfully realised plasmon-driven selective reduction reactions of 2-amino-5-nitrobenzenethiol (2A-5-NBT) to 3,3'-dimercapto-4,4'-diaminoazobenzene , an azobenzene derivative, using surface-enhanced Raman scattering (SERS) spectroscopy, and supported by the theoretical calculations. The SERS spectra demonstrated that two 5-nitro groups of 2A-5-NBTs were selectively reduced to the -N=N- chemical bond of 3,3'-dimercapto-4,4'-diaminoazobenzene, whereas the 2-amine group of 2A-5-NBT remained unchanged. Our experimental results revealed that aqueous environments were preferable to ambient atmospheric environments for this selective reduction reaction. The product is very stable in aqueous environments. However, in ambient atmosphere environments, the product is not stable and can revert back to 2A-5-NBT, where the -N=N- chemical bond can be broken by plasmon scissors. The plasmon-induced catalytic reactions in aqueous environments could be used for the efficient synthesis of aromatic azobenzene derivative compounds, which are valuable chemicals that are widely used in the chemical industry as dyes, food additives and drugs.

Ag-coated sea-urchin-like Fe3O4@C core-shell particles can be synthesized by a facile one-step solvothermal method, followed by deposition of high-density Ag nanoparticles onto the carbon surface through an in situ growth process, respectively. The as-synthesized Ag-coated Fe3O4@C particles can be used as a surface-enhanced Raman scattering (SERS) substrate holding reproducible properties under an external magnetic force. The magnetic function of the particles allows concentrating the composite particles into small spatial regions, which can be exploited to decrease the amount of material per analysis while improving its SERS detection limit. In contrast to the traditional SERS substrates, the present Fe3O4@C@Ag particles hold the advantages of enrichment of organic pollutants for improving SERS detection limit and recycled utilization.