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Oxidation of volatile organic compounds (VOCs) can lead to the formation of secondary organic aerosol (SOA), a significant component of atmospheric fine particles, which can affect air quality, human health, and climate change. However, the current understanding of the formation mechanism of SOA is still incomplete, which is not only due to the complexity of the chemistry but also relates to analytical challenges in SOA precursor detection and quantification. Recent instrumental advances, especially the development of high-resolution time-of-flight chemical ionization mass spectrometry (CIMS), greatly improved both the detection and quantification of low- and extremely low-volatility organic molecules (LVOCs/ELVOCs), which largely facilitated the investigation of SOA formation pathways. However, analyzing and interpreting complex mass spectrometric data remain a challenging task. This necessitates the use of dimension reduction techniques to simplify mass spectrometric data with the purpose of extracting chemical and kinetic information of the investigated system. Here we present an approach to apply fuzzy c -means clustering (FCM) to analyze CIMS data from a chamber experiment, aiming to investigate the gas phase chemistry of the nitrate-radical-initiated oxidation of isoprene. The performance of FCM was evaluated and validated. By applying FCM to measurements, various oxidation products were classified into different groups, based on their chemical and kinetic properties, and the common patterns of their time series were identified, which provided insight into the chemistry of the investigated system. The chemical properties of the clusters are described by elemental ratios and the average carbon oxidation state, and the kinetic behaviors are parameterized with a generation number and effective rate coefficient (describing the average reactivity of a species) using the gamma kinetic parameterization model. In addition, the fuzziness of FCM algorithm provides a possibility for the separation of isomers or different chemical processes that species are involved in, which could be useful for mechanism development. Overall, FCM is a technique that can be applied well to simplify complex mass spectrometric data, and the chemical and kinetic properties derived from clustering can be utilized to understand the reaction system of interest. [ABSTRACT FROM AUTHOR]

As the final stage of leaf development, leaf senescence is affected by a variety of internal and external signals including age and environmental stresses. Although significant progress has been made in elucidating the mechanisms of age-dependent leaf senescence, it is not clear how stress conditions induce a similar process. Here, we report the roles of a stress-responsive and senescence-induced gene, ERD7 (EARLY RESPONSIVE TO DEHYDRATION 7), in regulating both age-dependent and stress-induced leaf senescence in Arabidopsis. The results showed that the leaves of erd7 mutant exhibited a significant delay in both age-dependent and stress-induced senescence, while transgenic plants overexpressing the gene exhibited an obvious accelerated leaf senescence. Furthermore, based on the results of LC-MS/MS and PRM quantitative analyses, we selected two phosphorylation sites, Thr-225 and Ser-262, which have a higher abundance during senescence, and demonstrated that they play a key role in the function of ERD7 in regulating senescence. Transgenic plants overexpressing the phospho-mimetic mutant of the activation segment residues ERD7T225D and ERD7T262D exhibited a significantly early senescence, while the inactivation segment ERD7T225A and ERD7T262A displayed a delayed senescence. Moreover, we found that ERD7 regulates ROS accumulation by enhancing the expression of AtrbohD and AtrbohF, which is dependent on the critical residues, i.e., Thr-225 and Ser-262. Our findings suggest that ERD7 is a positive regulator of senescence, which might function as a crosstalk hub between age-dependent and stress-induced leaf senescence. [ABSTRACT FROM AUTHOR]

Ischemic heart diseases remain the leading cause of death globally, and stem cell-based therapy has been investigated as a potential approach for cardiac repair. Due to poor survival and engraftment in the cardiac ischemic milieu post transplantation, the predominant therapeutic effects of stem cells act via paracrine actions, by secreting extracellular vesicles (EVs) and/or other factors. Exosomes are nano-sized EVs of endosomal origin, and now viewed as a major contributor in facilitating myocardial repair and regeneration. However, EV/exosome therapy has major obstacles before entering clinical settings, such as limited production yield, unstable biological activity, poor homing efficiency, and low tissue retention. This review aims to provide an overview of the biogenesis and mechanisms of stem cell-derived EV/exosomes in the process of cardiac repair and discuss the current advancements in different optimized strategies to produce high-yield EV/exosomes with higher bioactivity, or engineer them with improved homing efficiency and therapeutic potency. In particular, we outline recent findings toward preclinical and clinical translation of EV/exosome therapy in ischemic heart diseases, and discuss the potential barriers in regard to clinical translation of EV/exosome therapy. • An overview of the biogenesis and mechanisms of EV/exosomes in cardiac repair. • Current advancements in different optimized strategies for EV/exosome therapy. • Finding and potential barriers toward clinical translation of EV/exosome therapy. [ABSTRACT FROM AUTHOR]

Aim: Spontaneous abortion (SA) is a multiple‐original syndrome with immune imbalance as one of its major risk factors. As Wharton's jelly‐mesenchymal stem cells (WJ‐MSCs) are considered to be able to prevent abortion, this study aims to explore the currently poorly understood underlining molecular signaling pathways and regulatory mechanisms of WJ‐MSCs in pregnancy maintenance. Methods: Abortion mode is established by subcutaneous injection of bromocriptine in rat on day 9 and abortion prevention is achieved by WJ‐MSCs injection via tail vein. WJ‐MSCs were cultured with/without the inhibitors of JAK/STAT or NF‐κB. The uterus was collected on the 14th day of gestation and the rate of embryo absorption was calculated. The expression of Th1/Th2/Th3 cytokines in decidual, placental tissue, and peripheral blood was analyzed. Results: WJ‐MSCs treatment significantly reduced the abortion rate in bromocriptine‐treated pregnancy such that it was not significantly different from a normal pregnancy. JAK/STAT inhibition abolished pregnancy preserving effects of WJ‐MSCs but NF‐κB inhibition did not. The levels of Th1‐related cytokines and mRNA levels in the bromocriptine abortion model were significantly higher than the normal pregnancy group and ethanol control group, while levels of the Th2‐related cytokines and mRNA levels significantly decreased. WJ‐MSCs transfusion into the abortion model restored cytokine profiles such that they were not significantly different from the normal pregnancy group and ethanol control group. JAK/STAT inhibition of WJ‐MSCs prevented their effect on cytokine and mRNA levels, but NF‐κB inhibition did not. Conclusions: WJ‐MSCs significantly lower the rate of embryo resorption of spontaneous abortion by reducing Th1‐related cytokines while increasing Th2 and Th3‐related cytokines in JAK/STAT‐dependent manner. [ABSTRACT FROM AUTHOR]

The NLRP3 inflammasome, estrogen and antimicrobial peptides have all been found to have a vital role in the protection of the bladder urothelium. However, the interdependence between these protective factors during a bladder infection is currently unknown. Our aim was to investigate the role of NLRP3 in the regulation of antimicrobial peptides and estrogen signaling in bladder epithelial cells during a UPEC infection. Human bladder epithelial cells and CRISPR/Cas9-generated NLRP3-deficient cells were stimulated with the UPEC strain CFT073 and estradiol. The gene and protein expression were evaluated with microarray, qRT-PCR, western blot and ELISA. Microarray results showed that the expression of most antimicrobial peptides was reduced in CFT073-infected NLRP3-deficient cells compared to Cas9 control cells. Conditioned medium from NLRP3-deficient cells also lost the ability to suppress CFT073 growth. Moreover, NLRP3-deficient cells had lower basal release of Beta-defensin-1, Beta-defensin-2 and RNase7. The ability of estradiol to induce an increased expression of antimicrobial peptides was also abrogated in NLRP3-deficient cells. The decreased antimicrobial peptide expression might be linked to the observed reduced expression and activity of estradiol receptor beta in NLRP3-deficient cells. This study suggests that NLRP3 may regulate the release and expression of antimicrobial peptides and affect estrogen signaling in bladder epithelial cells. [ABSTRACT FROM AUTHOR]

Lysophosphatidic acid receptors (LPARs) are six G-protein-coupled receptors that mediate LPA signaling to promote tumorigenesis and therapy resistance in many cancer subtypes, including breast cancer. Individual-receptor-targeted monotherapies are under investigation, but receptor agonism or antagonism effects within the tumor microenvironment following treatment are minimally understood. In this study, we used three large, independent breast cancer patient cohorts (TCGA, METABRIC, and GSE96058) and single-cell RNA-sequencing data to show that increased tumor LPAR1, LPAR4, and LPAR6 expression correlated with a less aggressive phenotype, while high LPAR2 expression was particularly associated with increased tumor grade and mutational burden and decreased survival. Through gene set enrichment analysis, it was determined that cell cycling pathways were enriched in tumors with low LPAR1, LPAR4, and LPAR6 expression and high LPAR2 expression. LPAR levels were lower in tumors over normal breast tissue for LPAR1, LPAR3, LPAR4, and LPAR6, while the opposite was observed for LPAR2 and LPAR5. LPAR1 and LPAR4 were highest in cancer-associated fibroblasts, while LPAR6 was highest in endothelial cells, and LPAR2 was highest in cancer epithelial cells. Tumors high in LPAR5 and LPAR6 had the highest cytolytic activity scores, indicating decreased immune system evasion. Overall, our findings suggest that potential compensatory signaling via competing receptors must be considered in LPAR inhibitor therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: The lipid phosphate phosphatases (LPPs) are a family of three enzymes that act at the cell surface and within the cell to modulate signaling. In many tumors, including breast cancers, LPP1 and LPP3 expression levels are decreased and LPP2 expression levels are increased relative to normal tissue, which stimulates a pro-cancerous phenotype by decreasing the turnover of bioactive lipids and promoting cell cycle progression. While most research has been conducted in the laboratory, validation in human tumors is lacking. We used three large independent patient cohorts and single-cell RNA-sequencing data to show that decreased LPP1/3 and increased LPP2 expression in cancers correlated to worse tumor biology, immune system evasion, and decreased survival. Most tumor LPP1/3 is produced by the stroma and LPP2 by cancer cells. Overall, our findings support pre-clinical evidence that restoring tumor LPP expression balance, particularly through LPP2 inhibition, could provide adjunct therapies for breast cancer patients. The LPP family is comprised of three enzymes that dephosphorylate bioactive lipid phosphates both intracellularly and extracellularly. Pre-clinical breast cancer models have demonstrated that decreased LPP1/3 with increased LPP2 expression correlates to tumorigenesis. This though has not been well verified in human specimens. In this study, we correlate LPP expression data to clinical outcomes in over 5000 breast cancers from three independent cohorts (TCGA, METABRIC, and GSE96058), investigate biological function using gene set enrichment analysis (GSEA) and the xCell cell-type enrichment analysis, and confirm sources of LPP production in the tumor microenvironment (TME) using single-cell RNA-sequencing (scRNAseq) data. Decreased LPP1/3 and increased LPP2 expression correlated to increased tumor grade, proliferation, and tumor mutational burden (all p < 0.001), as well as worse overall survival (hazard ratios 1.3–1.5). Further, cytolytic activity was decreased, consistent with immune system invasion. GSEA data demonstrated multiple increased inflammatory signaling, survival, stemness, and cell signaling pathways with this phenotype across all three cohorts. scRNAseq and the xCell algorithm demonstrated that most tumor LPP1/3 was expressed by endothelial cells and tumor-associated fibroblasts and LPP2 by cancer cells (all p < 0.01). Restoring the balance in LPP expression levels, particularly through LPP2 inhibition, could represent novel adjuvant therapeutic options in breast cancer treatment. [ABSTRACT FROM AUTHOR]

What Is Known and Objective. CYP2C19 is an important influencing factor for voriconazole trough plasma concentration (Cmin); however, it is not verified in Child–Pugh C (CP-C) cirrhosis patients, and no voriconazole dosage regimen is recommended for these patients in the package insert. This retrospective study identified CYP2C19 and other factors influencing voriconazole Cmin for CP-C cirrhosis, and obtained an appropriate method of application of voriconazole for them. Methods. A total of 66 patients with CP-C cirrhosis who accepted voriconazole therapy were involved. The voriconazole Cmin, clinical characteristics, CYP2C19 genotype, and adverse effects (AEs) were recorded and analyzed. Results. Unlike other research studies, voriconazole Cmin was not different among normal metabolizers (NMs), intermediate metabolizers (IMs), and poor metabolizers (PMs) of the CYP2C19 enzyme in CP-C cirrhosis (P > 0.05). The maintenance dose regimen for voriconazole was the only independent influencing factor for Cmin (P = 0.045; OR = 3.753; 95% CI, 1.029–13.694). At about 1/3 of the recommended maintenance dose, only 16.7% (8/48) had Cmin >5.5 μg/mL, 4.5% (3/48) had Cmin <1 μg/mL, and only one AE happened. There were four voriconazole-related AEs that happened in this study, and three AEs occurred (3/4, 75%) when the maintenance dose was not adjusted with therapeutic drug monitoring (TDM). What Is New and Conclusion. Voriconazole Cmin did not significantly vary according to CYP2C19 enzyme metabolization status (being an NM, IM, or PM) in CP-C cirrhosis. Reducing the maintenance dose of voriconazole to approximately 1/3 the standard maintenance dose and administering in combination with TDM in patients with CP-C cirrhosis are recommended. [ABSTRACT FROM AUTHOR]

Simple Summary: The gut microbiome has recently become a hot topic for researchers looking to understand colorectal cancer carcinogenesis and progression. Understanding the role of the microbiome on colorectal cancer will allow us to better understand how to apply various preventative measures and therapies, including newer treatments such as immunotherapy. The aim of this manuscript is to provide a comprehensive review of the topic and explore the most recent updates on microbial mechanisms associated with the pathogenesis and progression of colorectal cancer, as well as their implications for prevention, diagnosis, treatment, and future research. The gut microbiome has long been known to play a role in various aspects of health modulation, including the pathogenesis of colorectal cancer (CRC). With immunotherapy recently emerging as a successful treatment in microsatellite instability high (MSI-high) CRC, and with a newly demonstrated involvement of the gut microbiome in the modulation of therapeutic responses, there has been an explosion of research into the mechanisms of microbial effects on CRC. Harnessing and reprogramming the microbiome may allow for the expansion of these successes to broader categories of CRC, the prevention of CRC in high-risk patients, and the enhancement of standard treatments. In this review, we pull together both well-documented phenomena and recent discoveries that pertain to the microbiome and CRC. We explore the microbial mechanisms associated with CRC pathogenesis and progression, recent advancements in CRC systemic therapy, potential options for diagnosis and prevention, as well as directions for future research. [ABSTRACT FROM AUTHOR]

Gut microbial β-glucuronidases (GUSs) inhibition is a new approach for managing some diseases and medication therapy. However, the structural and functional complexity of GUSs have posed tremendous challenges to discover specific or broad-spectrum GUSs inhibitors using Escherichia coli GUS (Eco GUS) alone. This study first assessed the effects of twenty-one dietary flavones employing three Loop 1-type GUSs of different taxonomic origins, which were considered to be the main GUSs involved in deglucuronidation of small molecules, on p -nitrophenyl- β -D-glucuronide hydrolysis and a structure-activity relationship is preliminarily proposed based on both in vitro assays and a docking study with representative compounds. Eco GUS and Staphylococcus pasteuri GUS showed largely similar inhibition propensities with potencies positively correlating with the total hydroxyl groups and those at ring B of flavones, while docking results revealed strong interactions developed via ring A and/or C. Streptococcus agalactiae GUS (Saga GUS) exhibited distinct inhibition propensities, displaying late-onset inhibition and steep dose-response profiles with most tested compounds. The α-helix in loop 1 region of Saga GUS which causes spatial hindrance but offers a hydrophobic surface for contacting with the carbonyl group on ring C of flavones is believed to be essential for the allosteric inhibition of Saga GUS. Taken together, the study with a series of flavones revealed varied preferences for GUSs belonging to the same Loop 1-type, highlighting the necessity of adopting multi-GUSs instead of Eco GUS alone for screening broad-spectrum GUSs inhibitors or tailoring the inhibition based on specific GUS structure. • Three Loop 1 GUSs showed different inhibitory propensities via distinct mechanisms. • Eco GUS and Spas GUS inhibition correlates positively with B ring OH group of flavones. • Loop-1 α-helix of Saga GUS mainly accounts for steep-slope incomplete inhibition. • Docking study revealed primary interactions between GUSs and ring A/C of flavones. [ABSTRACT FROM AUTHOR]

Surface-enhanced Raman scattering (SERS) is a powerful label-free technique for the identification of molecules and molecular structures at extremely low concentrations. However, in most cases, the analytes will remain on SERS substrates, making the substrate a disposable consumable. Here, we propose a light erasable SERS substrate based on the metallic molybdenum dioxide (MoO 2) nanospheres. The MoO 2 nanospheres present a remarkable localized surface plasmon resonance (LSPR) absorption peak centered at 800 nm. Profiting from the local field magnification induced by the LSPR, MoO 2 exhibits excellent SERS detection sensitivity towards rhodamine 6 G (R6G), rhodamine B (RhB), methyl blue (MB), crystal violet (CV) and Malachite Green (MG), with a detection limit of 10−7 M and a maximum enhancement factor up to 5.4 × 104. Moreover, the metallic MoO 2 nanospheres possess a high photothermal conversion efficiency of 70.1% and good photothermal stability. The temperature of the MoO 2 surface can reach 438 °C under 808 nm laser irradiation with a power density of 2.5 W cm−2, exceeding the decomposition temperature of most organic molecules. Thus, the residual probe molecules can be completely removed from the MoO 2 substrate in less than 7.5 min under laser irradiation without compromising its SERS sensitivity and reproducibility. We anticipate our work will pave a new avenue for the development of reusable and highly sensitive SERS substrates. [Display omitted] • An in-situ light erasable MoO 2 SERS substrate was developed. • MoO 2 exhibits excellent sensitivity and universality in SERS detection. • MoO 2 can reach 438 °C under 808 nm laser irradiation at 2.5 W cm-2. • Residual molecules can be completely removed from MoO 2 substrate within 7.5 min. [ABSTRACT FROM AUTHOR]

Oxidation of isoprene by nitrate radicals (NO3) or by hydroxyl radicals (OH) under high NOx conditions forms a substantial amount of organonitrates (ONs). ONs impact NOx concentrations and consequently ozone formation while also contributing to secondary organic aerosol. Here we show that the ONs with the chemical formula C4H7NO5 are a significant fraction of isoprene‐derived ONs, based on chamber experiments and ambient measurements from different sites around the globe. From chamber experiments we found that C4H7NO5 isomers contribute 5%–17% of all measured ONs formed during nighttime and constitute more than 40% of the measured ONs after further daytime oxidation. In ambient measurements C4H7NO5 isomers usually dominate both nighttime and daytime, implying a long residence time compared to C5 ONs which are removed more rapidly. We propose potential nighttime sources and secondary formation pathways, and test them using a box model with an updated isoprene oxidation scheme. Plain Language Summary: Isoprene is the most abundant non‐methane trace gas emitted from vegetation in the atmosphere. Isoprene reacts with different oxidants forming numerous multifunctional products that affect both ozone and particulate matter concentrations via secondary organic aerosol formation. Day and nighttime isoprene oxidation under polluted conditions with high levels of nitrogen oxides (NOx) produces nitrogen containing species. Here, we used state‐of‐the‐art instrumentation to measure the isoprene‐derived nitrogen‐containing species, both in laboratory experiments and at six field sites around the globe. To support our interpretation, we apply a recently developed model for nighttime isoprene chemistry. We have identified a dominant nitrated product(s) in our experiments and with a significant ambient contribution both during day and nighttime. Key features of this species are its secondary formation from primary products and its relatively long lifetime under ambient conditions, explaining its accumulation in the atmosphere. Thus, it can be an important marker for the influence of NOx on isoprene oxidation. Key Points: The C4H7NO5 isomers are major secondary products of isoprene oxidation during nighttime and daytime in NOx‐influenced regionsThe C4H7NO5 isomers are multi‐generational products from several C5 compounds that accumulate in the atmosphereC4H7NO5 as a dominant isoprene‐derived species, can be important for the formation of ozone [ABSTRACT FROM AUTHOR]

Simple Summary: Tumor dormancy is a state in which some cancer cells are dormant by less cell proliferation, and are resistant to treatments, thus leading to late recurrence. As nuclear receptor subfamily 2 group F member 1 (NR2F1) is a biomarker of dormancy shown in experimental settings, we studied its clinical relevance by analyzing comprehensive gene expression profiles of approximately 7000 breast cancer patients using computational biological approaches. NR2F1 gene expression of bulk tumors correlated with the suppression of cell proliferation and metastasis-related pathways, but not with metastasis or survival. Using single-cell sequence cohorts, we found that NR2F1 was predominantly expressed in cancer-associated fibroblasts, particularly in inflammatory type, rather than in cancer cells. Further, NR2F1 expression in breast cancer cells did not consistently correlate with stem cell-like traits. Our findings suggest that the NR2F1 gene expression signal from a patient's bulk tumor is not from the cancer cells. Background: Tumor dormancy is a crucial mechanism responsible for the late recurrence of breast cancer. Thus, we investigated the clinical relevance of the expression of NR2F1, a known dormancy biomarker. Methods: A total of 6758 transcriptomes of bulk tumors from multiple breast cancer patient cohorts and two single-cell sequence cohorts were analyzed. Results: Breast cancer (BC) with high NR2F1 expression enriched TGFβ signaling, multiple metastases, and stem cell-related pathways. Cell proliferation-related gene sets were suppressed, and MKi67 expression was lower in high NR2F1 BC. In tumors with high Nottingham grade, NR2F1 expression was found to be lower. There was no consistent relationship between NR2F1 expression and metastasis or survival. Cancer mutation rates, immune responses, and immune cell infiltrations were lower in high NR2F1 tumors, whereas the infiltration of stromal cells including cancer-associated fibroblasts (CAFs) was higher. NR2F1 was predominantly expressed in CAFs, particularly inflammatory CAFs, rather than in cancer cells, consistently in the two single-cell sequence cohorts. Conclusions: NR2F1 expression in breast cancer is associated with tumor dormancy traits, and it is predominantly expressed in CAFs in the tumor microenvironment. [ABSTRACT FROM AUTHOR]

Herein, we have verified the interaction between the functional peptides from the SARS-CoV-2 and cell membrane, and we further proved that peptides exhibit little membrane disruption. The specific amino acids (Lys, Ile, Glu, Asn, Gln, etc.) with charge or hydrophobic residues play a significant role during the functional-peptide binding to membrane. The findings could provide the hints related to viral infection and also might pave the way for development of new materials based on peptides with membrane-binding activity, which would enable functional peptides further as peptide adjuvants, in order to help deliver the cancer drug into tumor cells for the efficient tumor therapy. [ABSTRACT FROM AUTHOR]

Herein, we synthesized green luminescent nitrogen (N) and sulfur (S) co-doped carbon dots (N, S-CDs) which could realize the monitor of 4-nitrophenol (4-NP) and pH. The N, S-CDs can be designed as a fluorescent probe for sensitive detection of 4-NP in water samples with linear ranges of 0–85 µM and a detection limit of 0.037 µM. Moreover, the fluorescence intensity of N, S-CDs is sensitive to pH and shows a linear relationship with pH values ranging from 3.50 to 7.25 and 7.25–12.00, accompanied with a significant color variation of the N, S-CDs solution from colorless to brown. Finally, the proposed N, S-CDs have also been applied to monitor the 4-NP in oocysts due to its low cytotoxicity. Scheme 1. Schematic diagram of the synthesis and application of the N, S-CDs. [Display omitted] • N, S-doped carbon dots (N, S-CDs) with green emission were synthesized by one-step hydrothermal method. • N, S-CDs can be used as a bifunctional sensing platform for the detection of pH and 4-nitrophenol (4-NP). • The detection of 4-nitrophenol (4-NP) in water samples were successfully realized by using N, S-CDs. • N, S-CDs can also be used for cell imaging. Using p-aminophenol and dithioacetamide as precursors, green luminescent nitrogen (N) and sulfur (S) co-doped carbon dots (N, S-CDs) are prepared by hydrothermal method with the quantum yield (QY) of 7.1 %. Superior properties of the N, S-CDs including high photostability, outstanding biocompatibility, and desirable biological penetration were found, which could realize the monitor of 4-nitrophenol (4-NP) and pH. The N, S-CDs can be designed as a fluorescent probe for sensitive detection of 4-NP in water samples with linear ranges of 0–85 µM and a detection limit of 0.037 µM. Moreover, the fluorescence intensity of N, S-CDs is sensitive to pH and shows a linear relationship with pH values ranging from 3.50 to 7.25 and 7.25–12.00, accompanied with a significant color variation of the N, S-CDs solution from colorless to brown. Finally, the proposed N, S-CDs have also been applied to monitor the 4-NP in oocysts due to its low cytotoxicity, providing a great capacity for various targets molecules detection. [ABSTRACT FROM AUTHOR]

Angiogenesis is essential for vascular development. The roles of regulatory long noncoding RNAs (lncRNAs) in mediating angiogenesis remain under‐explored. Human embryonic stem cell‐derived mesenchymal stem cells (hES‐MSCs) are shown to exert more potent cardioprotective effects against cardiac ischemia than human bone marrow‐derived MSCs (hBM‐MSCs), associated with enhanced neovascularization. The purpose of this study is to search for angiogenic lncRNAs enriched in hES‐MSCs, and investigate their roles and mechanisms. AC103746.1 is one of the most highly expressed intergenic lncRNAs detected in hES‐MSCs versus hBM‐MSCs, and named as SCDAL (stem cell‐derived angiogenic lncRNA). SCDAL knockdown significantly reduce the angiogenic potential and reparative effects of hES‐MSCs in the infarcted hearts, while overexpression of SCDAL in either hES‐MSCs or hBM‐MSCs exhibits augmented angiogenesis and cardiac function recovery. Mechanistically, SCDAL induces growth differentiation factor 6 (GDF6) expression via direct interaction with SNF5 at GDF6 promoter. Secreted GDF6 promotes endothelial angiogenesis via non‐canonical vascular endothelial growth factor receptor 2 activation. Furthermore, SCDAL‐GDF6 is expressed in human endothelial cells, and directly enhances endothelial angiogenesis in vitro and in vivo. Thus, these findings uncover a previously unknown lncRNA‐dependent regulatory circuit for angiogenesis. Targeted intervention of the SCDAL‐GDF6 pathway has potential as a therapy for ischemic heart diseases. [ABSTRACT FROM AUTHOR]

Autotaxin (ATX) and its product lysophosphatidic acid (LPA) have been implicated in lung fibrosis and cancer. We have studied their roles in DNA damage induced by carcinogenic crystalline silica particles (CSi). In an earlier study on bronchial epithelia, we concluded that ATX, via paracrine signaling, amplifies DNA damage. This effect was seen at 6–16 h. A succeeding study showed that CSi induced NLRP3 phosphorylation, mitochondrial depolarization, double strand breaks (DSBs), and NHEJ repair enzymes within minutes. In the current study we hypothesized a role for the ATX-LPA axis also in this rapid DNA damage. Using 16HBE human bronchial epithelial cells, we show ATX secretion at 3 min, and that ATX inhibitors (HA130 and PF8380) prevented both CSi-induced mitochondrial depolarization and DNA damage (detected by γH2AX and Comet assay analysis). Experiments with added LPA gave similar rapid effects as CSi. Furthermore, Rac1 was activated at 3 min, and a Rac1 inhibitor (NSC23766) prevented mitochondrial depolarization and genotoxicity. In mice the bronchial epithelia exhibited histological signs of ATX activation and signs of DSBs (53BP1 positive nuclei) minutes after a single inhalation of CSi. Our data indicate that CSi rapidly activate the ATX-LPA axis and within minutes this leads to DNA damage in bronchial epithelial cells. Thus, ATX mediates very rapid DNA damaging effects of inhaled particles. • Inhaled silica particles induce a rapid ATX response in bronchial epithelia. • Bronchial ATX secretion, LPA and Rac1 signaling cause DNA damage. • Our data indicate a novel mechanism for particle-induced DNA damage. [ABSTRACT FROM AUTHOR]

A 52-year-old woman with a strong family history of breast cancer was diagnosed as having triple-negative breast cancer (TNBC) in her right breast. Neoadjuvant chemotherapy (NAC; four cycles of epirubicin/cyclophosphamide/5-fluorouracil) was performed, followed by breast-conserving surgery and axillary lymph node dissection. Histopathological analysis of the surgical specimens demonstrated a few focal tumor cells remaining in the stroma, but not a pathological complete response (pCR). Weekly paclitaxel was subsequently added to the treatment regimen. A total of 17 months after the adjuvant treatments, TNBC recurred in her left breast with massive lymph node metastasis. Because of the early recurrence after standard treatment, NAC was administered together with carboplatin and paclitaxel. Histopathological analysis of the partially resected breast and axillary lymph nodes demonstrated a pCR. No recurrent disease was found 2 years after the second TNBC treatment. This case underlines the importance of platinum-based chemotherapy and prophylactic mastectomy for patients with BRCA dysfunction. [ABSTRACT FROM AUTHOR]

Calcific aortic valve disease (CAVD) is the most common valvular heart disease in adults. The cellular mechanisms of CAVD are still unknown, but accumulating evidence has revealed that osteogenic differentiation of human valve interstitial cells (hVICs) plays an important role in CAVD. Thus, we aimed to investigate the function of estrogen‐related receptor α (ERRα) in the osteogenic differentiation of hVICs. We found that the level of ERRα was significantly increased in CAVD samples compared to normal controls. In addition, ERRα was significantly upregulated during hVIC osteogenic differentiation in vitro. Gain‐ and loss‐of‐function experiments were performed to identify the function of ERRα in hVIC calcification in vitro. Inhibition of endogenous ERRα attenuated hVIC calcification, whereas overexpression of ERRα in hVICs promoted this process. RNA sequencing results suggested that heme oxygenase‐1 (Hmox1) was a downstream target of ERRα, which was further confirmed by western blotting. Additionally, we also found that downregulation of Hmox1 by shHmox1 efficiently reversed the inhibition of calcification induced by ERRα shRNA in hVICs. ChIP‐qPCR and luciferase assays indicated that Hmox1 was negatively regulated by ERRα. We found that overexpression of Hmox1 or its substrates significantly inhibited hVIC calcification in vitro. In conclusion, we found that knockdown of ERRα can inhibit hVIC calcification through upregulating Hmox1 and that ERRα and Hmox1 are potential targets for the treatment of CAVD. [ABSTRACT FROM AUTHOR]

Gut dysbiosis has been associated with inflammatory bowel disease (IBD), one of the most common gastrointestinal diseases. The microbial communities play essential roles in host physiology, with profound effects on immune homeostasis, directly or via their metabolites and/or components. There are increasing clinical trials applying fecal microbiota transplantation (FMT) with Crohn's disease (CD) and ulcerative colitis (UC). The restoration of dysbiotic gut microbiome is considered as one of the mechanisms of FMT therapy. In this work, latest advances in the alterations in gut microbiome and metabolome features in IBD patients and experimental mechanistic understanding on their contribution to the immune dysfunction were reviewed. Then, the therapeutic outcomes of FMT on IBD were summarized based on clinical remission, endoscopic remission and histological remission of 27 clinical trials retrieved from PubMed which have been registered on ClinicalTrials.gov with the results been published in the past 10 years. Although FMT is established as an effective therapy for both subtypes of IBD, the promising outcomes are not always achieved. Among the 27 studies, only 11 studies performed gut microbiome profiling, 5 reported immune response alterations and 3 carried out metabolome analysis. Generally, FMT partially restored typical changes in IBD, resulted in increased α-diversity and species richness in responders and similar but less pronounced shifts of patient microbial and metabolomics profiles toward donor profiles. Measurements of immune responses to FMT mainly focused on T cells and revealed divergent effects on pro-/anti-inflammatory functions. The very limited information and the extremely confounding factors in the designs of the FMT trials significantly hindered a reasonable conclusion on the mechanistic involvement of gut microbiota and metabolites in clinical outcomes and an analysis of the inconsistencies. • Gut microbes and their metabolites are key players in gut inflammation of IBD. • Gut microbiota-metabolite-human immunity axis in IBD was evidenced by existing data. • A summary of 27 FMT studies revealed promising results in a subset of IBD patients. • Data, albeit limited, support impact of FMT on microbiota-metabolite-immunity axis. • Microbiota-metabolite-immunity axis study drives mechanistic understanding of FMT. [ABSTRACT FROM AUTHOR]

Electric fields (EFs) in biological systems are well known, and their presence implies the activity of protein ion channels and pumps in various cells. The aggregation of islet amyloid polypeptides (IAPP) was recently found in human brain tissue, and this was related to the electrical activity of neurons and caused neuronal loss. However, the association between amyloid formation and the electric field is still unknown. Herein a direct method to stimulate the formation of the hIAPP peptide under an EF is reported. [ABSTRACT FROM AUTHOR]

The phenotype–genotype relationship is a key for personalized and precision medicine for complex diseases. To unravel the complexity of the clinical phenotype–genotype network, we used cardiovascular diseases (CVDs) and associated non-coding RNAs (ncRNAs) (i.e. miRNAs, long ncRNAs, etc.) as the case for the study of CVDs at a systems or network level. We first integrated a database of CVDs and ncRNAs (CVDncR, http://sysbio.org.cn/cvdncr/) to construct CVD–ncRNA networks and annotate their clinical associations. To characterize the networks, we then separated the miRNAs into two groups, i.e. universal miRNAs associated with at least two types of CVDs and specific miRNAs related only to one type of CVD. Our analyses indicated two interesting patterns in these CVD–ncRNA networks. First, scale-free features were present within both CVD–miRNA and CVD–lncRNA networks; second, universal miRNAs were more likely to be CVDs biomarkers. These results were confirmed by computational functional analyses. The findings offer theoretical guidance for decoding CVD–ncRNA associations and will facilitate the screening of CVD ncRNA biomarkers. Database URL : http://sysbio.org.cn/cvdncr/ [ABSTRACT FROM AUTHOR]

• A. actinomycetemcomitans induces IL-1β and IL-1RA release from gingival epithelial cells. • Caspase-1, Caspase-4 and NLRP3 are involved in A. actinomycetemcomitans -induced IL-1β release. • NLRP3 has a regulatory effect on several inflammatory proteins in gingival epithelial cells. Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) has myriads of virulence factors among which leukotoxin provides A. actinomycetemcomitans with the advantage to thrive in the surrounding hostile environment and evade host immune defences. The NLRP3 inflammasome has been associated with periodontal disease development. However, our understanding of the involvement of caspase-1, caspase-4, and NLRP3 in the release of IL-1β and other inflammatory mediators from gingival epithelial cells during a A. actinomycetemcomitans infection is limited. The aim of this study was to investigate how the inflammasome-associated proteins caspase-1, caspase-4 and NLRP3 regulate the immune response of gingival epithelial cells during a A. actinomycetemcomitans infection. Human gingival epithelial cells (Ca9-22) deficient in NLRP3, caspase-1 or caspase-4 were created using CRISPR/Cas9. Gingival epithelial cells were stimulated with the A. actinomycetemcomitans low-leukotoxic strain NCTC9710 or the highly leukotoxic JP2 strain HK 165 for 6, 12 and 24 h. The results showed that the JP2 strain HK1651 induced higher IL-1β and IL-1RA release and mediated more epithelial cell death compared to the NCTC9710 strain. These findings were found to be capsase-1, caspase-4 and NLRP3-dependant. A targeted protein analysis of inflammation-related proteins showed that the expression of 37 proteins were identified as being significantly altered after HK1651 infection compared to unstimulated Cas9 and NLRP3-deficient cells. Of the 37 proteins, 23 of these inflammation-related proteins released by NLRP3 - deficient cells differed significantly compared to Cas9 cells after infection. This suggests that NLRP3 has a broad effect on the inflammatory response in gingival epithelial cells. [ABSTRACT FROM AUTHOR]

• A simple method is utilized to produce N-doped carbon dots (N CDs) from o-aminophenol and ethylenediamine. • The N CDs possess quantum yield up to 38.4%. • Owing to the highly sensitive response to Ag+, the prepared N CDs can be developed as an effective sensing platform. • The N CDs are also used in bioimaging. N-doped carbon dots (N CDs) with green fluorescence is developed by the hydrothermal reaction with o-aminophenol and ethylenediamine as carbon and nitrogen sources, and the quantum yield (QY) is 38.4%. The N CDs are characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), Ultraviolet-visible absorption spectroscopy (UV–vis) and fluorescence spectroscopy. The results show that N CDs have good fluorescence properties and stability, and the N CDs are further utilized as a sensor for Ag+ via the static quenching effect (SQE) (λ ex =430 nm, λ em =510 nm). The linear range of Ag+ is 30–210 µmol/L with a limit of detection (LOD) of 4.7 µmol/L (S/ N = 3). On this basis, we quantitatively detect Ag+ in real samples. Furthermore, due to the excellent fluorescence performance, the N CDs are found to be an effective tool for Ag+ sensing in bioimaging. Herein, green-emission fluorescent N-doped carbon dots (N CDs) are developed by the hydrothermal reaction of o-aminophenol and ethylenediamine, and the quantum yield (QY) is 38.4%. The N CDs are utilized as a sensor for Ag+, and the linear range is 30–210 µM with a limit of detection (LOD) of 4.7 µM (S/ N = 3). On the other hand, the N CDs are further applied to biological imaging, constructing the fluorescence analysis method of Ag+ in biological samples. [Display omitted] [ABSTRACT FROM AUTHOR]

For capacitive biopotential measurement, a novel high input impedance front-end is proposed. The input impedance of the front-end can achieve more than 100 GΩ by matching the peripheral parameters. The front-end's noise model is provided, and noise optimization is given further. The analysis shows the proposed front-end can achieve at least two orders of input impedance more than the non-inverting amplifier circuit with the same peripheral parameters at the cost of only increasing twice input-referred noise. The final experimental results verify the analysis and show the front-end's feasibility of capacitive sensing electrocardiogram signal. Graphical abstract A novel high input impedance front-end is proposed, which impedance can achieve more than 100 GΩ by matching the peripheral parameters. The analysis and noise optimization results show the proposed front-end can achieve at least two orders of input impedance more than the non-inverting amplifier circuit with the same peripheral parameters at the cost of only increasing twice input-referred noise. The final experimental results verify the analysis and show its feasibility of capacitive sensing electrocardiogram signal. [ABSTRACT FROM AUTHOR]

Objectives: To analyze the prognosis and treatment decisions for patients with vaginal cancer through a large retrospective cohort study, in order to assist clinicians to evaluate the condition and choose treatment methods. Methods: This was a retrospective study analyzed with Cox regression, nomogram, and external validation. The Kaplan–Meier curve was used for comparative analysis of various treatment modalities. Results: A total of 6650 cases of vaginal cancer diagnosed between 2000 and 2018 from the Surveillance, Epidemiology, and End Results database and 106 cases diagnosed between 2006 and 2021 from Fujian Cancer Hospital were identified. Young age, early FIGO (the International Federation of Gynecology and Obstetrics) stage, well‐differentiated, squamous and adenocarcinoma, first primary malignancy, married, undergoing surgery, and chemoradiotherapy were good independent prognostic factors (P < 0.001). The internal and external validation concordance indices were 0.7102 and 0.7785, respectively. The Kaplan–Meier curves indicated that surgery, radiotherapy, and chemotherapy significantly improved survival in patients with vaginal cancer. Forest plots suggest that radiotherapy combined with surgery was superior to radiotherapy alone (P < 0.001). Conclusion: We established a specific nomogram to predict vaginal cancer prognosis. Surgery combined with external beam radiation plus brachytherapy may be the most recommended treatment option. Synopsis: A nomogram was established using the SEER database and validated using external data to predict the prognosis of patients with vaginal cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer (BC) in adolescents and young adults (AYA) has unique biological qualities, but the details of these features remain unclear, and treatment options are comparable to those of other age groups. In this study, we identified a gene that demonstrates a strong association with patient prognosis solely in AYA patients, despite the fact that its expression does not differ by age group. Although this gene, GALNT1, has no prognostic significance in whole BC, when examined in AYA BC, high GALNT1 was significantly associated with worse survival. Furthermore, high GALNT1 expression was found to be an independent factor for survival among several clinical features of AYA patients. Finally, high GALNT1 BC is associated with increased EMT, angiogenesis, and protein secretion in AYA patients, but not in the elderly. We report the clinical relevance of the GALNT1 gene in AYA BC. It is well established that genetic information differs amongst the adolescent and young adult population (AYA) and older patients. Although several studies on genetic information have been conducted, no current prognostic biomarker exists to help differentiate survival outcomes amongst AYA patients. The GALNT family of genes have been associated with several cancer etiologies, such as the Tn antigen and epithelial-mesenchymal transition (EMT); however, the clinical significance of GALNT1 expression in breast cancer (BC) remains unclear. We investigated the clinical relevance of GALNT1 expression in BC using two large independent cohorts. We found that, although triple-negative BC (TNBC) had the highest GALNT1 expression compared to ER-positive/HER2-negative BC, GALNT1 levels in BC were not associated with clinical aggressiveness, including histological grade, AJCC stage and N-category, and patient survival, consistently in both the METABRIC and GSE96058 cohorts. There was also no biological difference between low- and high-GALNT1 expression BC, as analyzed by hallmark gene sets via gene set enrichment analysis (GSEA). Further, no significant difference was found in GALNT1 expression levels among AYAs and older patients. However, high GALNT1 expression was associated with significantly worse survival in AYA patients, in both cohorts. Furthermore, high GALNT1 expression was found to be an independent factor among several clinical features, including subtype, histological grade, AJCC T and N-category, in AYA patients. In both cohorts, BC with high GALNT1 expression demonstrated low levels of CD8+ T-cell infiltration, but not other anti-cancerous or pro-cancerous immune cells. Finally, high levels of GALNT1 BC demonstrated increased EMT, angiogenesis, and protein secretion in the AYA population, but not in older patients. In conclusion, our findings demonstrate that GALNT1 expression was found to be associated with angiogenesis and EMT, and may have potential as prognostic biomarker, specifically in AYA patients. [ABSTRACT FROM AUTHOR]

Ozone (O3) pollution is becoming increasingly severe in China. In addition, our limited understanding of the relationship between O3 and volatile organic compounds (VOCs), is an obstacle to improving air quality. By developing an improved source-oriented speciated VOC emission inventory in 2013, we estimated the ozone formation potential (OFP) and investigated its characteristics in China. Besides, a comparison was made between our estimates and space-based observations from the ozone monitoring instrument (OMI) on the National Aeronautics and Space Administration (NASA)'s Aura satellite. According to our estimates, m-/p-xylene, ethylene, formaldehyde, toluene, and propene were the five species that had the largest potential to form ozone, and on-road vehicles, industrial processes, biofuel combustion, and surface coating were the key contributing sectors. Among different regions of China, the North China Plain, Yangtze River Delta, and Pearl River Delta had the highest OFP values. Our results suggest that O3 formation is VOC-limited in major urban areas of China. Additionally, considering the different photochemical reactivities of various VOC species and the disparate energy and industry structures in the different regions of China, more efficient OFP-based and localized VOC control measures should be implemented, instead of the current mass-based and nationally uniform policies. [ABSTRACT FROM AUTHOR]

In this work, a highly sensitive electrochemiluminescence (ECL) sensor for the detection of clenbuterol (CBT) in pork is reported. The fabrication of the sensor was carried out by modification of a glassy carbon electrode (GCE) with platinum nanoparticles (PtNPs)/silica nanoparticles doped with [Ru(bpy) 3 ] 2 + (RuSiNPs)/Nafion composite. The morphology, composition and electrochemical behavior of the PtNPs/RuSiNPs were characterized by scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy and electrochemical impedance spectroscopy, respectively. It was found that all the PtNPs are formed on the surface of RuSiNPs and the electron transfer resistance was obviously reduced on the PtNPs/RuSiNPs GCE. Taking the advantage of the Si-O-Si grid of RuSiNPs, the [Ru(bpy) 3 ] 2 + luminophore leaching from the modified electrode could largely be prevented, benefiting the ECL signal stability. Moreover, due to the enhanced electron transfer rate and electrocatalytical property of the PtNPs, the sensitivity of the PtNPs/RuSiNPs-based sensor was greatly improved. Under optimized conditions, the ECL peak intensity was linear with the concentration of CBT in the range of 5–100 ng mL − 1 , with a detection limit as low as 0.8 ng mL − 1 . The recoveries of the CBT obtained from spiked pork samples at PtNPs/RuSiNPs/Nafion GCE were between 89.5% and 106.3% and the RSDs were lower than 6.21%. The proposed ECL sensor based on PtNPs/RuSiNPs composite presented good characteristics for CBT determination in terms of rapid, high sensitivity and good stability, promising the applicability of this sensor in real samples. [ABSTRACT FROM AUTHOR]

108 ambient volatile organic compounds (VOCs) were measured continuously at a time resolution of an hour using an online gas chromatography–frame ionization detector/mass spectrometry (GC–FID/MS) in October 2014 in Beijing, and positive matrix factorization (PMF) was performed with online data. The evolution process and causes for high levels of VOCs during a haze event were investigated through comprehensive analysis. Results show that mixing ratios of VOCs during the haze event (89.29 ppbv) were 2 to 5 times as that in non-haze days, There was a distinct accumulation process of VOCs at the beginning of the haze event, and the mixing ratios of VOCs maintained at the high levels until to the end of pollution when the mixing ratios of ambient VOCs recovered to the normal concentration levels in a few hours. Some reactive and toxic species increased remarkably as well, which indicates a potential health risk to the public in terms of VOCs. Eight sources were resolved by PMF, and results revealed gasoline exhaust was the largest contributor (32–46%) to the ambient VOCs in Beijing. Emissions of gasoline exhaust surged from 13.46 to 40.36 ppbv, with a similar variation pattern to total VOCs, indicating that high levels of VOCs were largely driven to by expanded vehicular emissions. Emissions of biomass burning also increased noticeably (from 2.32 to 11.12 ppbv), and backward trajectories analysis indicated regional transport of biomass burning emissions. Our findings suggested that extremely high levels of VOCs during the haze event was primarily attributed to vehicular emissions, biomass burning and regional transport, as well as stationary synoptic conditions. [ABSTRACT FROM AUTHOR]

102 volatile organic compound (VOC) species were measured online using a gas chromatography–mass spectrometry/flame ionization detector (GC–MS/FID) at an urban site in Beijing in 11 August to 3 September 2015, when a series of rigorous air quality control measures were implemented in Beijing city and neighbouring provinces. Positive matrix factorization (PMF) was applied to identify emission sources from 1 h averaged values of VOC data. Based on the online VOC data and the PMF analysis results, the effectiveness of different control measures were investigated. The PMF results were compared with an emission inventory data. Results show that the rigorous air quality restrictions implemented were successful. The averaged ambient VOC mixing ratios during the emission control period and non-control period were 27.53 and 45.42 ppbv, respectively. The mixing ratios of total VOC during the control period were reduced by 40%. Alkanes were the most abundant chemical group in the two periods, followed by oxygenated volatile organic compounds (OVOCs). Almost all quantified VOC species decreased during the control period. Tracers of industrial sources and vehicle exhaust reduced most, including some halocarbons, esters and aromatics. Eight sources were resolved by online PMF analysis for ambient VOCs in Beijing. Contributions of those sources varied significantly during the control and non-control period. Compared with the values before control, contributions of vehicle-related sources were most reduced, followed by solvent utilization. Reductions of vehicle-related sources, solvent utilization, secondary formation, fuel combustion, and biogenic were responsible for 65%, 19%, 10%, 5%, and 1% of the reductions in ambient VOCs. Both PMF results and emission inventory data indicated that the control measure on traffic was very effective in reducing ambient VOCs in Beijing, with the emission reductions of about 50%. [ABSTRACT FROM AUTHOR]

[Display omitted] • The UPLC-QqQ-MS/MS (MRM) method was established for the first time for 14 coumarins in Suhuang antitussive capsule (SH). • A new ternary hybrid DESs (HDESs) system could improve the extraction rate of coumarins with different polarities. • Compared with conventional solvents, the HDESs could increase the extraction rate of total coumarins in SH by 53.9 %. Green solvents were emerged in recent years as potential extract-solvents to enhance the extract-efficiency of natural products. In this study, we reported a novel green extract-system, one of hybrid deep eutectic solvents (HDESs), which could simultaneously efficiently extract active ingredients with different polarities from herbal medicines. Initially, quantitative analyses of 14 coumarins in Suhuang antitussive capsule (SH) were performed by ultra-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UPLC-QqQ-MS/MS) under the multiple reaction monitoring (MRM) mode. After systematically optimizing the composition of HDESs, the composition of DL-menthol, decanoic acid, and 1-tetradecanol at a molar ratio of 6:0.5:1.5 exhibited the highest extract yields for target coumarins in SH. Then, response surface methodology (RSM) was employed to optimize the ultrasonic extraction conditions of this HDESs. The results showed that under the conditions of liquid to solid ratio of 496 mL/g, extract time of 30 min and water content of 35 %, the highest yield of total coumarins was obtained, and the extract efficiency was increased by 53.9 % compared with conventional organic solvents. Additionally, transmission electron microscopy (TEM) image showed the formation of HDESs-water micellar system during the ultrasonic-assisted extraction, which may promote the mass transfer process and improve the yield of target coumarins. This new ternary HDESs system could provide a green and effective extract technology for natural compounds with different polarities from complex plant materials. [ABSTRACT FROM AUTHOR]

A method was developed to establish a comprehensive anthropogenic VOC emission inventory in China, in which a four-level source categorization was proposed, and an emission factor determination system together with a reference database were developed. And this was applied to establish VOC emission inventories for the period 2008–2012. Results show China's anthropogenic VOC emissions increased from 22.45 Tg in 2008 to 29.85 Tg in 2012 at an annual average rate of 7.38%, with Shandong, Guangdong, Jiangsu, Zhejiang and Hebei provinces being the largest emitters. Industrial processes, transportation and solvent utilization were the key sources, accounting for 39.3%, 25.6%, and 14.9% of the total emissions in 2012, respectively. Passenger cars, biofuel combustion, coke production, field burning of biomass, and raw chemical manufacturing were the primary VOC sources nationwide. The key sources for each province were different because of the disparate industry and energy structure. China's VOC emissions displayed remarkable spatial variation, with emissions in the east and southeast regions being much larger than in the northwest, and the high emission areas mainly centered in the Bohai Economic Rim, the Yangtze River Delta, the Pearl River Delta and the Sichuan Basin. The size of high emission areas expanded over the period 2008–2012, with heavily polluted city clusters gradually emerging. [ABSTRACT FROM AUTHOR]

Metabolic reprogramming is essential for establishing the tumor microenvironment (TME). Glutamine has been implicated in cancer metabolism, but its role in clear cell renal carcinoma (ccRCC) remains unknown. Transcriptome data of patients with ccRCC and single-cell RNA sequencing (scRNA-seq) data were obtained from The Cancer Genome Atlas (TCGA, 539 ccRCC samples and 59 normal samples) database and GSE152938 (5 ccRCC samples). Differentially expressed genes related to glutamine metabolism (GRGs) were obtained from the MSigDB database. Consensus cluster analysis distinguished metabolism-related ccRCC subtypes. LASSO-Cox regression analysis was used to construct a metabolism-related prognostic model. The ssGSEA and ESTIMATE algorithms evaluated the level of immune cell infiltration in the TME, and the immunotherapy sensitivity score was obtained from TIDE. Cell–cell communication analysis was used to observe the distribution and effects of the target genes in the cell subsets. An image genomics model was constructed using imaging feature extraction and a machine learning algorithm. Results: Fourteen GRGs were identified. Overall survival and progression-free survival rates were lower in metabolic cluster 2, compared with those in cluster 1. The matrix/ESTIMATE/immune score in C1 decreased, but tumor purity in C2 increased. Immune cells were more active in the high-risk group, in which CD8 + T cells, follicular helper T cells, Th1 cells, and Th2 cells were significantly higher than those in the low-risk group. The expression levels of immune checkpoints were also significantly different between the two groups. RIMKL mainly appeared in epithelial cells in the single-cell analysis. ARHGAP11B was sparsely distributed. The imaging genomics model proved effective in aiding with clinical decisions. Glutamine metabolism plays a crucial role in the formation of immune TMEs in ccRCC. It is effective in differentiating the risk and predicting survival in patients with ccRCC. Imaging features can be used as new biomarkers for predicting ccRCC immunotherapy. [ABSTRACT FROM AUTHOR]

Heterogeneity within the same tumor type has been described to be complex and occur at multiple levels. Less is known about the heterogeneity at the level of metabolism, within a tumor set, yet metabolic pathways are highly relevant to survival signaling in tumors. In this study, we profiled the glucose metabolism of several non-small cell lung carcinoma (NSCLC) cell lines and could show that, NSCLC display distinct glycolytic metabolism. Genetic and pharmacological perturbation of glycolysis was selectively toxic to NSCLCs with high rates of glycolysis. Furthermore, high expression of hexokinase-2, localized at the mitochondria, was a feature of the NSCLCs dependent on glucose catabolism. Our study provides evidence for quantitative metabolic diversity in NSCLCs and indicates that glucose metabolism provide differential prosurvival benefits to NSCLCs. [ABSTRACT FROM AUTHOR]

Aims: Activation of cardiac fibroblasts into myofibroblasts constitutes a key step in cardiac remodeling after myocardial infarction (MI), due to interstitial fibrosis. Mesenchymal stem cells (MSCs) have been shown to improve post-MI remodeling an effect that is enhanced by hypoxia preconditioning (HPC). Leptin has been shown to promote cardiac fibrosis. The expression of leptin is significantly increased in MSCs after HPC but it is unknown whether leptin contributes to MSC therapy or the fibrosis process. The objective of this study was to determine whether leptin secreted from MSCs modulates cardiac fibrosis. Methods: Cardiac fibroblast (CF) activation was induced by hypoxia (0.5% O2). The effects of MSCs on fibroblast activation were analyzed by co-culturing MSCs with CFs, and detecting the expression of α-SMA, SM22α, and collagen IαI in CFs by western blot, immunofluorescence and Sirius red staining. In vivo MSCs antifibrotic effects on left ventricular remodeling were investigated using an acute MI model involving permanent ligation of the left anterior descending coronary artery. Results: Co-cultured MSCs decreased fibroblast activation and HPC enhanced the effects. Leptin deficit MSCs from Ob/Ob mice did not decrease fibroblast activation. Consistent with this, H-MSCs significantly inhibited cardiac fibrosis after MI and mediated decreased expression of TGF-β/Smad2 and MRTF-A in CFs. These effects were again absent in leptin-deficient MSCs. Conclusion: Our data demonstrate that activation of cardiac fibroblast was inhibited by MSCs in a manner that was leptin-dependent. The mechanism may involve blocking TGF-β/Smad2 and MRTF-A signal pathways. [ABSTRACT FROM AUTHOR]

Background: Episiotomy is a surgical solution to relieve perineal stress, resulting in an easily repairable incision, in comparison to the risks of serious vaginal trauma during delivery. The midwife typically adopts such a clinical decision, on experience and subjective judgment. However, the association between perineal stress and episiotomy is poorly characterized. Our aim was to identify a threshold value for perineal stress leading to episiotomy, which eventually may be employed as a clinical tool for assessing whether an episiotomy is required or not.Methods: In total, 245 nulliparous women were investigated for perineal stress during non-instrumental vaginal delivery in Ningbo Women & Children's Hospital. During the second stage of labor, a flexible membrane stress sensor was placed between the fetal head and perineal wall above the anal fissure. Once the entire fetal head pressed against the sensor, real-time perineal stress was measured, and the peak value was recorded. Cases were divided into non-episiotomy group (n = 173) and episiotomy group (n = 72). The correlations between perineal stress and episiotomy was assessed through logistic regression with adjustment for maternal age, estimated birthweight, duration of second stage of labor, maternal body mass index, and presence of analgesia. Midwives were blinded to all stress measurement values. The predictive value of perineal stress on performing episiotomy was evaluated, together with the ideal cut-off perineal stress value for performing episiotomy. A ROC analysis was also performed.Results: The episiotomy group had significantly higher levels of perineal stress in comparison to the non-episiotomy group (140.50 ± 16.03 N versus 118.37 ± 19.21 N, p < 0.01). The episiotomy group was linked to significantly higher perineal stress in comparison to the non-episiotomy group (140.50 ± 16.03 VS 118.37 ± 19.21 N, p < 0.01). ROC analysis between perineal stress and episiotomy revealed a high area under the curve (AUC 0.81, 95% CI 0.75-0.86) and a cut-off value for perineal stress of 124.49 N was identified for episiotomy decision.Conclusion: The level of perineal stress was an independent predictor of performing episiotomy in nulliparous women during non-instrumental vaginal delivery. Perineal stress exceeding 124.49 N was identified as the cut-off prompting midwives to perform episiotomy. [ABSTRACT FROM AUTHOR]

Abstract: Transcriptional regulators of the diphtheria toxin repressor (DtxR) family control the expression of genes involved in the uptake of iron and manganese, which is not only necessitous nutrients but also was suggested to be essential for intracellular redox cycling of microorganisms. We identified a unique DtxR homologue (DR2539) with special characteristics from Deinococcus radiodurans, which is known for its extreme resistance to radiation and oxidants. The dr2539 mutant showed higher resistance to hydrogen peroxide than the wild-type strain R1. Intracellular catalase activity assay and semiquantitative PCR analysis demonstrated that this DtxR is a negative regulator of catalase (katE). Furthermore, quantitative real-time PCR, global transcription profile and inductively coupled plasma–mass spectrometry analysis showed that the DtxR is involved in the regulation of antioxidant system by maintaining the intracellular Mn/Fe ion homeostasis of D. radiodurans. However, unlike the other DtxR homologues, the DtxR of D. radiodurans acts as a negative regulator of a Mn transporter gene (dr2283) and as a positive regulator of Fe-dependent transporter genes (dr1219, drb0125) in D. radiodurans. [Copyright &y& Elsevier]

Abstract: Mesenchymal stem cells (MSCs) have been induced to differentiate successfully from human embryonic stem cells (hES-MSCs), which could serve as an in vitro source of MSCs. However, the homing behaviors of such cells and their potential utility for liver regeneration in vivo have not been reported. We investigated factors that influenced early homing and the hepatic-directed differentiation potency of hES-MSCs in a mouse model of acute liver injury. The hES-MSCs could be detected 36h after cell infusion and this was unaffected by the number of cell passages in culture. Pretreatment of hES-MSCs with TNF-α resulted in higher rates of homing of these cells to the injured liver. Interestingly most of the cells homing at an early stage expressed alpha-fetoprotein (AFP), indicating hepatic differentiation. Thus, hES-MSCs can home to the acutely injured liver at high efficiency and undergo hepatic differentiation, suggesting that these cells could be useful for treating acute human liver injury. [Copyright &y& Elsevier]

Abstract: Embryonic stem cells (ESCs) often display high rates of apoptosis and spontaneous differentiation in routine culture, thus bring the proliferation of these cells highly inefficient. Moreover, little is known about the factors that are indispensable for sustaining self-renewal. To surmount these issues, we established transgenic mES cell lines expressing the enhanced green fluorescent protein (EGFP) under the control of the Rex1 promoter which is a key regulator of pluripotency in ES cells. In addition, we provided a simplified and improved protocol to derive transgenic mESCs from single cell. Finally, we showed that embryoid body (EB) development was faster than adherent differentiation in terms of differentiation ratio by real-time tracking of the EGFP expression. Therefore, these cell lines can be tracked and selected both in vitro and in vivo and should be invaluable for studying the factors that are indispensable for maintaining pluripotency. [Copyright &y& Elsevier]

Members of the CEP (C-terminally Encoded Peptide) gene family have been shown to be involved in various developmental processes and stress responses in plants. In order to understand the roles of CEP peptides in stress response, a comprehensive bioinformatics approach was employed to identify NtCEP genes in tobacco (Nicotiana tabacum L.) and to analyze their potential roles in stress responses. Totally 21 NtCEP proteins were identified and categorized into two subgroups based on their CEP domains. Expression changes of the NtCEP genes in response to various abiotic stresses were analyzed via qRT-PCR and the results showed that a number of NtCEPs were significant up-regulated under drought, salinity, or temperature stress conditions. Furthermore, application of synthesized peptides derived from NtCEP5, NtCEP13, NtCEP14, and NtCEP17 enhanced plant tolerance to different salt stress treatments. NtCEP5, NtCEP9 and NtCEP14, and NtCEP17 peptides were able to promote osmotic tolerance of tobacco plants. The results from this study suggest that NtCEP peptides may serve as important signaling molecules in tobacco's response to abiotic stresses. • Genome-wide analysis identified 21 CEP members in tobacco genome. • NtCEPs involved in multiple biotic and abiotic stresses response. • The peptides NtCEP5/13/14/17 enhanced plant tolerance to salt stress treatments. • The NtCEP5/9/14/17 peptides promoted osmotic tolerance in tobacco plants. [ABSTRACT FROM AUTHOR]

The microbiome is known to play a significant role in cancer biology; however, few studies have elucidated its relationship with Nonsmall Cell Lung Cancer (NSCLC) patient outcomes. We hypothesized that there are specific microorganisms that are closely related with NSCLC patient survival. Total of 647 NSCLC (Adenocarcinoma and Squamous Cell Carcinoma combined) patients in The Cancer Genome Atlas (TCGA) were analyzed using the R software. A Volcano Plot was analyzed with the patients divided into Short and Long Survivors by overall survival of 0.9 years, and we found that a bacterium Rothia was significantly abundant in Short Survivors, and Blastococcus, Leptospira, and Haematobacter in Long Survivors, but presence of Rothia alone was associated with overall survival. The age, race, subtype, and sex were not significantly different by the presence of Rothia in NSCLC. Unexpectedly, Rothia-positive NSCLC was associated with less cell proliferation by gene set enrichment analysis, Mki67 expression, proliferation score, with less fraction altered and homologous recombination deficiency, and with high infiltration of stromal cells, indicating favorable oncological characteristics. Further, Rothia-positive tumors were associated with significantly higher infiltration of CD8 T cells, CD4 T cells, Monocytes, and NK cells, and high interferon-gamma response, T-cell receptor richness, cytolytic activity, indicating favorable tumor immune microenvironment. NSCLC with Rothia was associated with worse survival but also with favorable oncological characteristics such as less cell proliferation and favorable tumor immune microenvironment. We cannot help but speculate that Rothia in NSCLC is associated with mortality unrelated to oncological characteristics. [ABSTRACT FROM AUTHOR]

• Rate constants of BrHg + NO 2 are measured versus temperature and pressure. • Formation of Hg(0) + BrNO 2 competes with addition to form BrHgONO. • Published calculations overestimated both reduction and oxidation rate constants. Atomic bromine is known to dominate the oxidation of Hg(0) to Hg(II) via a two-step process in the atmosphere– formation of BrHg and subsequent reactions of BrHg with atmospheric radicals, particularly NO 2. We report the first experimental determination of the rate constants for this reaction, which we measured versus temperature (313–373 K) and pressure (80–700 Torr) using laser photolysis-laser induced fluorescence (LP-LIF). Rate constants for addition are 3–11 times lower than those predicted by a previous computational study. We also confirm the existence of competing channel, which we assign to the predicted mercury reduction reaction. [ABSTRACT FROM AUTHOR]

Fruit softening, an irreversible process that occurs during fruit ripening, can lead to losses and waste during postharvest transportation and storage. Cell wall disassembly is the main factor leading to loss of fruit firmness, and several ripening-associated cell wall genes have been targeted for genetic modification, particularly pectin modifiers. However, individual knockdown of most cell wall–related genes has had minimal influence on cell wall integrity and fruit firmness, with the notable exception of pectate lyase. Compared to pectin disassembly, studies of the cell wall matrix, the xyloglucan–cellulose framework, and underlying mechanisms during fruit softening are limited. Here, a tomato (Solanum lycopersicum) fruit ripening–associated α-expansin (SlExpansin1/SlExp1) and an endoglucanase (SlCellulase2/SlCel2), which function in the cell wall matrix, were knocked out individually and together using clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9-mediated genome editing. Simultaneous knockout of SlExp1 and SlCel2 enhanced fruit firmness, reduced depolymerization of homogalacturonan-type pectin and xyloglucan, and increased cell adhesion. In contrast, single knockouts of either SlExp1 or SlCel2 did not substantially change fruit firmness, while simultaneous overexpression of SlExp1 and SlCel2 promoted early fruit softening. Collectively, our results demonstrate that SlExp1 and SlCel2 synergistically regulate cell wall disassembly and fruit softening in tomato. Knockout of SlExp1 and SlCel2, 2 coexpressed genes encoding potential cell wall–loosening agents, enhances fruit firmness and reduces cell wall disassembly in tomato (Solanum lycopersicum). [ABSTRACT FROM AUTHOR]

Ion-Selective Electrode (ISE) is an emerging technology for in situ monitoring of the chemical concentrations of an aqueous environment. In this work, we reported a novel all-solid-state silicate ISE, using an Ag/Pb/PbSiO3 electrode. This electrode responded to aqueous SiO32− with a reasonable slope of −31.34 mV/decade and a good reproductivity. The linear range covered from 10−5 M to 10−1 M, for the Na2SiO3 solutions and the response time was generally less than 5 s. Its potentiometric response to pH and silicate indicated that the prepared electrode was sensitive to silicate, rather than pH. Compared to the traditional liquid ISE, our all-solid-state silicate electrode was resistant to high pressure and could be used in situ, in deep water. In addition, the miniaturized electrodes (diameter of 0.4 mm and a length of 2–3 cm) could be easily integrated into a multi-modal sensor, which could simultaneously determine multiple parameters. Our prepared silicate ISE could potentially be used to determine the presence of silicate in a low-chloride aqueous environment, where the ISE exhibited better selectivity for silicate, over interfering ions such as, SO42−, NO3−, CH3COO−, CO32−, and PO43−. [ABSTRACT FROM AUTHOR]