Silver Surface-Assisted Dehydrobrominative Cross-Coupling between Identical Aryl Bromides.

Cross-coupling reactions represent an indispensable tool in chemical synthesis. An intriguing challenge in this field is to achieve selective cross-coupling between two precursors with similar reactivity or, to the limit, the identical molecules. Here we report an unexpected dehydrobrominative cross-coupling between 1,3,5-tris(2-bromophenyl)benzene molecules on silver surfaces. Using scanning tunneling microscopy, we examine the reaction process at the single-molecular level, quantify the selectivity of the dehydrobrominative cross-coupling, and reveal the modulation of selectivity by substrate lattice-related catalytic activity or molecular assembly effect. Theoretical calculations indicate that the dehydrobrominative cross-coupling proceeds via regioselective C-H bond activation of debrominated TBPB and subsequent highly selective C-C coupling of the radical-based intermediates. The reaction kinetics plays an important role in the selectivity for the cross-coupling. This work not only expands the toolbox for chemical synthesis but also provides important mechanistic insights into the selectivity of coupling reactions on the surface.

Integrated aerobic-anaerobic digestion of highly solids-loaded corn stover and swine manure under dynamic aeration: Temperature rise, physicochemical characteristics, and methane production.

This research aimed to design an integrated aerobic-anaerobic reactor with dynamic aeration that was automatically regulated based on real-time oxygen concentration and investigate the aerobic pretreatment and subsequent dry co-anaerobic digestion (co-AD) characteristics of highly solids-loaded corn stover and swine manure in terms of temperature rise, physiochemical characteristics, and methane production. The high-temperature feedstocks from the aerobic pretreatment phase rapidly entered the AD phase without transportation and effectively improved the start-up and methane production of the co-AD. Oxygen concentration range, aeration rate, and pretreatment time affected the cumulative aeration time, temperature rise, and organic matter removal interactively during aerobic pretreatment, and a low aeration rate was relatively preferable. Although the lignocellulose removal increased with the increase in pretreatment duration, the maximal lignin elimination efficiency only reached 1.30%. The inoculum injection in the transition phase from aerobic pretreatment to co-AD and the leachate reflux during co-AD were also critical for producing methane steadily apart from aerobic pretreatment. The cold air weakened the temperature rise of aerobic pretreatment, and the low-temperature leachate reduced the methane production in the co-AD process. An oxygen concentration range of 13%-17%, aeration rate of 0.10 m3/(min·m3), pretreatment time of 84 h, inoculum loading of 40%, leachate refluxing thrice per day, and double-layer inoculation were optimum for improving the integrated aerobic-anaerobic digestion system's ability to resist low temperatures and achieving high methane production. The maximal cumulative and volatile solids (VS) methane yields of corn stover and swine manure reached 444.58 L and 266.30 L/kg VS.

Quantification of Serum Metabolites in Early Colorectal Adenomas Using Isobaric Labeling Mass Spectrometry.

A major challenge in reducing the death rate of colorectal cancer is to screen patients using low-invasive testing. A blood test shows a high compliance rate with reduced invasiveness. In this work, a multiplex isobaric tag labeling strategy coupled with mass spectrometry is adopted to relatively quantify primary and secondary amine-containing metabolites in serum for the discovery of metabolite level changes of colorectal cancer. Serum samples from patients at different risk statuses and colorectal cancer growth statuses are studied. Metabolite identification is based on accurate mass matching and/or retention time of labeled metabolite standards. We quantify 40 metabolites across all the serum samples, including 18 metabolites validated with standards. We find significantly decreased levels of threonine and asparagine in the patients with growing adenomas or high-risk adenomas (p < 0.05). Glutamine levels decrease in patients with adenomas of unknown growth status or high-risk adenomas. In contrast, arginine levels are elevated in patients with low-risk adenoma. Receiver operating characteristic analysis shows high sensitivity and specificity of these metabolites for detecting growing adenomas. Based on these results, we conclude that a few metabolites identified here might contribute to distinguishing colorectal patients with growing adenomas from normal individuals and patients with unknown growth status of adenomas.

6-Plex mdSUGAR Isobaric-Labeling Guide Fingerprint Embedding for Glycomics Analysis.

Glycans are vital biomolecules with diverse functions in biological processes. Mass spectrometry (MS) has become the most widely employed technology for glycomics studies. However, in the traditional data-dependent acquisition mode, only a subset of the abundant ions during MS1 scans are isolated and fragmented in subsequent MS2 events, which reduces reproducibility and prevents the measurement of low-abundance glycan species. Here, we reported a new method termed 6-plex mdSUGAR isobaric-labeling guide fingerprint embedding (MAGNI), to achieve multiplexed, quantitative, and targeted glycan analysis. The glycan peak signature was embedded by a triplicate-labeling strategy with a 6-plex mdSUGAR tag, and using ultrahigh-resolution mass spectrometers, the low-abundance glycans that carry the mass fingerprints can be recognized on the MS1 spectra through an in-house developed software tool, MAGNIFinder. These embedded unique fingerprints can guide the selection and fragmentation of targeted precursor ions and further provide rich information on glycan structures. Quantitative analysis of two standard glycoproteins demonstrated the accuracy and precision of MAGNI. Using this approach, we identified 304 N-glycans in two ovarian cancer cell lines. Among them, 65 unique N-glycans were found differentially expressed, which indicates a distinct glycosylation pattern for each cell line. Remarkably, 31 N-glycans can be quantified in only 1 × 103 cells, demonstrating the high sensitivity of our method. Taken together, our MAGNI method offers a useful tool for low-abundance N-glycan characterization and is capable of determining small quantitative differences in N-glycan profiling. Therefore, it will be beneficial to the field of glycobiology and will expand our understanding of glycosylation.

CHRISTMAS: Chiral Pair Isobaric Labeling Strategy for Multiplexed Absolute Quantitation of Enantiomeric Amino Acids.

Amino acids (AAs) in the d-form are involved in multiple pivotal neurological processes, although their l-enantiomers are most commonly found. Mass spectrometry-based analysis of low-abundance d-AAs has been hindered by challenging enantiomeric separation from l-AAs, low sensitivity for detection, and lack of suitable internal standards for accurate quantification. To address these critical gaps, N,N-dimethyl-l-leucine (l-DiLeu) tags are first validated as novel chiral derivatization reagents for chromatographic separation of 20 pairs of d/l-AAs, allowing the construction of a 4-plex isobaric labeling strategy for enantiomer-resolved quantification through single step tagging. Additionally, the creative design of N,N-dimethyl-d-leucine (d-DiLeu) reagents offers an alternative approach to generate analytically equivalent internal references of d-AAs using d-DiLeu-labeled l-AAs. By labeling cost-effective l-AA standards using paired d- and l-DiLeu, this approach not only enables absolute quantitation of both d-AAs and l-AAs from complex biological matrices with enhanced precision but also significantly boosts the combined signal intensities from all isobaric channels, greatly improving the detection and quantitation of low-abundance AAs, particularly d-AAs. We term this quantitative strategy CHRISTMAS, which stands for chiral pair isobaric labeling strategy for multiplexed absolute quantitation. Leveraging the ion mobility collision cross section (CCS) alignment, interferences from coeluting isomers/isobars are effectively filtered out to provide improved quantitative accuracy. From wild-type and Alzheimer's disease (AD) mouse brains, we successfully quantified 20 l-AAs and 5 d-AAs. The significant presence and differential trends of certain d-AAs compared to those of their l-counterparts provide valuable insights into the involvement of d-AAs in aging, AD progression, and neurodegeneration.

Identification and clinical significance of tsRNAs and miRNAs in PBMCs of treatment-requiring retinopathy of prematurity.

The aim of the study is to reveal the expression profiling and clinical significance of peripheral blood mononuclear cell (PBMC) tRNA-derived small RNAs (tsRNAs) and microRNAs (miRNAs) of premature infants with treatment-requiring retinopathy of prematurity (ROP). Significantly altered tsRNAs and miRNAs were screened using small RNA sequencing. RT-qPCR was used to verify the altered RNAs identified by small RNA transcriptomics. The target genes, their enriched functions, and possibly involved signaling pathways were identified by bioinformatics analyses. According to the small RNA sequencing, 125 tsRNAs and 205 miRNAs were significantly altered in PBMCs obtained from infants with treatment-requiring ROP compared with the premature controls without retinopathy. We preliminarily validated the significant alterations of 6 tsRNAs and 9 miRNAs. The target genes for those tsRNAs were enriched for cellular macromolecule metabolic process, intracellular anatomical structure, transcription regulatory region nucleic acid binding, and Th17 cell differentiation; those of the altered miRNAs were enriched for the developmental process, cell junction, DNA-binding transcription activator activity, and FoxO signaling pathway. By verification with the extended sample size, we identified tsRNAs and miRNAs that could be potential biomarkers with clinical values. The study recognized the alterations and clinical significance of changed tsRNA/miRNA profiles in PBMCs from premature infants with ROP. These significantly altered tsRNAs and miRNAs might be useful as potential diagnostic biomarkers and molecular targets for treatment-requiring ROP.

m6A modifications of circular RNAs in ischemia-induced retinal neovascularization.

Ischemia-induced pathological neovascularization in the retina is a leading cause of blindness in various age groups. The purpose of the current study was to identify the involvement of circular RNAs (circRNAs) methylated by N6-methyladenosine (m6A), and predict their potential roles in oxygen-induced retinopathy (OIR) in mice. Methylation assessment via microarray analysis indicated that 88 circRNAs were differentially modified by m6A methylation, including 56 hyper-methylated circRNAs and 32 hypo-methylated circRNAs. Gene ontology enrichment analysis predicted that the enriched host genes of the hyper-methylated circRNAs were involved in cellular process, cellular anatomical entity, and protein binding. Host genes of the hypo-methylated circRNAs were enriched in the regulation of cellular biosynthetic process, the nucleus, and binding. According to the Kyoto Encyclopedia of Genes and Genomes analysis, those host genes were involved in the pathways of selenocompound metabolism, salivary secretion, and lysine degradation. MeRIP-qPCR verified significant alterations in m6A methylation levels of mmu_circRNA_33363, mmu_circRNA_002816, and mmu_circRNA_009692. In conclusion, the study revealed the m6A modification alterations in OIR retinas, and the findings above shed light on the potential roles of m6A methylation in circRNA regulatory functions in the pathogenesis of ischemia-induced pathological retinal neovascularization.

Boost-DiLeu: Enhanced Isobaric N,N-Dimethyl Leucine Tagging Strategy for a Comprehensive Quantitative Glycoproteomic Analysis.

Intact glycopeptide analysis has been of great interest because it can elucidate glycosylation site information and glycan structural composition at the same time. However, mass spectrometry (MS)-based glycoproteomic analysis is hindered by the low abundance and poor ionization efficiency of glycopeptides. Relatively large amounts of starting materials are needed for the enrichment, which makes the identification and quantification of intact glycopeptides from samples with limited quantity more challenging. To overcome these limitations, we developed an improved isobaric labeling strategy with an additional boosting channel to enhance N,N-dimethyl leucine (DiLeu) tagging-based quantitative glycoproteomic analysis, termed as Boost-DiLeu. With the integration of a one-tube sample processing workflow and high-pH fractionation, 3514 quantifiable N-glycopeptides were identified from 30 µg HeLa cell tryptic digests with reliable quantification performance. Furthermore, this strategy was applied to human cerebrospinal fluid (CSF) samples to differentiate N-glycosylation profiles between Alzheimer's disease (AD) patients and non-AD donors. The results revealed processes and pathways affected by dysregulated N-glycosylation in AD, including platelet degranulation, cell adhesion, and extracellular matrix, which highlighted the involvement of N-glycosylation aberrations in AD pathogenesis. Moreover, weighted gene coexpression network analysis (WGCNA) showed nine modules of glycopeptides, two of which were associated with the AD phenotype. Our results demonstrated the feasibility of using this strategy for in-depth glycoproteomic analysis of size-limited clinical samples. Taken together, we developed and optimized a strategy for the enhanced comprehensive quantitative intact glycopeptide analysis with DiLeu labeling, showing significant promise for identifying novel therapeutic targets or biomarkers in biological systems with a limited sample quantity.

N6-methyladenosine modifications of mRNAs and long noncoding RNAs in oxygen-induced retinopathy in mice.

Retinal neovascular diseases are major causes of blindness worldwide. As a common epitranscriptomic modification of eukaryotic RNAs, N6-methyladenosine (m6A) is associated with the pathogenesis of many diseases, including angiogenesis, through the regulation of RNA metabolism and functions. The aim of this study was to identify m6A modifications of mRNAs and long noncoding RNAs (lncRNAs) and determine their potential roles in retinal neovascularization. The transcriptome-wide m6A profiles of mRNAs and lncRNAs in the retinal tissues of mice with oxygen-induced retinopathy (OIR) and controls were identified by microarray analysis of immunoprecipitated methylated RNAs. The m6A methylation levels of mRNAs and lncRNAs identified in the microarray data were validated by MeRIP-qPCR. A total of 1321 mRNAs (151 hypermethylated and 1170 hypomethylated) and 192 lncRNAs (15 hypermethylated and 177 hypomethylated) were differentially methylated with the m6A modification in OIR and control mice. Gene ontology analysis showed that hypermethylated mRNAs were enriched in the regulation of multicellular organismal process, intracellular organelle, and protein binding, while hypomethylated mRNAs were enriched in cellular metabolic process, intracellular process, and binding. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that hypermethylated mRNAs were involved in dopaminergic synapses, glutamatergic synapse, and PI3K-Akt signaling pathway, while hypomethylated mRNAs were involved in autophagy, ubiquitin-mediated proteolysis, and spliceosome. Moreover, the altered levels of m6A methylation of ANGPT2, GNG12, ROBO4, and ENSMUST00000153785 were validated by MeRIP-qPCR. The results revealed an altered m6A epitranscriptome in OIR retinas. These methylated RNAs may act as novel modulators and targets in retinal neovascularization.

New insights into eutrophication management: Importance of temperature and water residence time.

Eutrophication and harmful cyanobacterial blooms threaten water resources all over the world. There is a great controversy about controlling only phosphorus or controlling both nitrogen and phosphorus in the management of lake eutrophication. The primary argument against the dual nutrients control of eutrophication is that nitrogen fixation can compensate the nitrogen deficits. Thus, it is of great necessary to study the factors that can significantly affect the nitrogen fixation. Due to the difference of climate and human influence, the water quality of different lakes (such as water temperature, N:P ratio and water residence time) is also quite different. Numerous studies have reported that the low N:P ratio can intensify the nitrogen fixation capacities. However, the effects of temperature and water residence time on the nitrogen fixation remain unclear. Thus, 30 shallows freshwater lakes in the eastern plain of China were selected to measure dissolved N2 and Ar concentrations through N2: Ar method using a membrane inlet mass spectrometer to quantify the nitrogen fixation capacities and investigate whether the temperature and water residence time have a great impact on nitrogen fixation. The results have shown that the short lake water residence time can severely inhibit the nitrogen fixation capacities through inhibiting the growth of nitrogen-fixing cyanobacteria, changing the N:P ratio and resuspending the solids from sediments. Similarly, lakes with low water temperature also have a low nitrogen fixation capacity, suggesting that controlling nitrogen in such lakes is feasible if the growth of cyanobacteria is limited by nitrogen.

Cognition effectiveness of continuous positive airway pressure treatment in obstructive sleep apnea syndrome patients with cognitive impairment: a meta-analysis.

Obstructive sleep apnea (OSA) is a common respiratory disorder characterized by recurrent pharyngeal collapses during sleep leading to intermittent hypoxia and sleep disruption. Cognitive challenges and high risks of cognitive impairment, including Alzheimer's disease (AD), are closely associated with OSA. Currently, continuous positive airway pressure (CPAP) is widely used in the treatment of OSA. However, whether CPAP benefits cognitive functions in patients with OSA remains elusive. Here, we identified published studies through a systematic review of PubMed, Cochrane Library, Embase, Wanfang Data, CBM, and CNKI from January 1, 1970, to July 1, 2020. 288 patients from 7 articles (one was excluded in the meta-analysis for it was a follow-up study) were included in the present study. It revealed that cognitive functions of OSA patients with mild cognitive impairment (MCI) or AD were mildly but significantly improved after CPAP treatment (SMD 0.49, 95% CI 0.11-0.86), especially long-term CPAP treatment (SMD 0.56, 95% CI 0.10-1.02, p = 0.02), as measured by Mini-Mental State Examination (MMSE) (SMD 0.49, 95%CI 0.11-0.86). However, no significant cognition benefits were detected by the Montreal Cognitive Assessment (SMD 0.43, 95% CI 0.85-1.72). In terms of heterogeneity, cognitive improvements by CPAP were detectable on OSA patients either at a younger age or over longer periods of CPAP treatment. Therefore, our findings highlight the partial efficiency of CPAP treatment in cognition improvement of OSA patients with MCI or AD.

The pathways from perceived discrimination to self-rated health among the Chinese diaspora during the COVID-19 pandemic: investigation of the roles of depression, anxiety, and social support.

BACKGROUND: Research indicates the adverse impacts of perceived discrimination on health, and discrimination inflamed by the COVID-19 pandemic, a type of social exclusion, could affect the well-being of the Chinese diaspora. We analyzed the relationship and pathways of perceived discrimination's effect on health among the Chinese diaspora in the context of the pandemic to contribute to the literature on discrimination in this population under the global public health crisis. METHODS: We analyzed data from 705 individuals of Chinese descent residing in countries outside of China who participated in a cross-sectional online survey between April 22 and May 9, 2020. This study utilized a structural equation model (SEM) to evaluate both direct and indirect effects of perceived discrimination on self-rated health (SRH) and to assess the mediating roles of psychological distress (namely, anxiety and depression) and social support from family and friends. RESULTS: This online sample comprised predominantly young adults and those of relatively high socioeconomic status. This study confirmed the total and direct effect of recently perceived discrimination on SRH and found the indirect effect was mainly mediated by depression. Mediating roles of anxiety and social support on the discrimination-health relationship were found insignificant in this SEM. CONCLUSIONS: Our findings suggest discrimination negatively affected the well-being of the Chinese diaspora, and depression acted as a major mediator between the discrimination-health relationship. Therefore, interventions for reducing discrimination to preserve the well-being of the Chinese diaspora are necessary. Prompt intervention to address depression may partially relieve the disease burden caused by the surge of discrimination.

[The impact of mood on the intrinsic functional connectivity].

Although a great number of studies have investigated the changes of resting-state functional connectivity (rsFC) in patients with mental disorders, such as depression and schizophrenia etc, little is known how stable the changes are, and whether temporal sad or happy mood can modulate the intrinsic rsFC. In our experiments, happy and sad video clips were used to induce temporally happy and sad mood states in 20 healthy young adults. We collected functional magnetic resonance imaging (fMRI) data while participants were watching happy or sad video clips, which were administrated in two consecutive days. Seed-based functional connectivity analyses were conducted using the anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), and amygdala as seeds to investigate neural network related to executive function, attention, and emotion. We also investigated the association of the rsFC changes with emotional arousability level to understand individual differences. There is significantly stronger functional connectivity between the left DLPFC and posterior cingulate cortex (PCC) under sad mood than that under happy mood. The increased connectivity strength was positively correlated with subjects' emotional arousability. The increased positive correlation between the left DLPFC and PCC under sad relative to happy mood might reflect an increased processing of negative emotion-relevant stimuli. The easier one was induced by strong negative emotion (higher emotional arousability), the greater the left DLPFC-PCC connectivity was indicated, the greater the instability of the intrinsic rsFC was shown.

N6-methyladenosine methylation in ophthalmic diseases: From mechanisms to potential applications.

N6-methyladenosine (m6A) modification, as the most common modification method in eukaryotes, is widely involved in numerous physiological and pathological processes, such as embryonic development, malignancy, immune regulation, and premature aging. Under pathological conditions of ocular diseases, changes in m6A modification and its metabolism can be detected in aqueous and vitreous humor. At the same time, an increasing number of studies showed that m6A modification is involved in the normal development of eye structures and the occurrence and progress of many ophthalmic diseases, especially ocular neovascular diseases, such as diabetic retinopathy, age-related macular degeneration, and melanoma. In this review, we summarized the latest progress regarding m6A modification in ophthalmic diseases, changes in m6A modification-related enzymes in various pathological states and their upstream and downstream regulatory networks, provided new prospects for m6A modification in ophthalmic diseases and new ideas for clinical diagnosis and treatment.

Aerobic composting characteristics of corn straw and pig manure under dynamic aeration.

The conventional aeration method is compulsorily continuous ventilation or aeration at equal intervals, and a uniform aeration rate does not vary during composting. A dynamic on-demand aeration approach based on the diverse oxygen consumption of microorganisms at different composting stages could solve the problems of insufficient oxygen supply or excessive aeration. This study aims to design an aerobic composting system with dynamic aeration, investigate the effects of dynamic aeration on the temperature rise and physicochemical characteristics during the aerobic composting of corn straw and pig manure, and optimise the control parameters of oxygen concentration. Higher temperatures and longer high-temperature durations were achieved under dynamic aeration, thereby accelerating the decomposition of organic compounds. Dynamic aeration effectively reduced the aeration frequency, the convective latent heat and moisture losses, and the power consumption in the middle and later stages of composting. The dynamic aeration regulated according to the oxygen concentration of 14%-17% in the exhaust was optimum. Under the optimal conditions, the period above 50 ℃ lasted 8.5 days, and the highest temperature, organic matter removal, and seed germination index reached 65.82 ℃, 37.59%, and 74.59%, respectively. The power consumption was decreased by 33.58% compared to the traditional intermittent aeration. Dynamic aeration would be a competitive approach for improving aerobic composting characteristics and reducing the power consumption and the hot exhaust gas emissions, especially in the cooling maturation stage, which was of great significance for realising the low-cost production of composting at scale and promoting the blossom of the organic fertiliser industry.

Bibliometric evaluation of global trends and characteristics of RNA methylation during angiogenesis.

Background: RNA methylation is involved in major life processes. Angiogenesis is a normal phenomenon that occurs constantly in the bodies of all mammals, once it is aberrant or something goes wrong, it may lead to pathological changes. The bibliometric analysis could produce a comprehensive overview of RNA methylation during angiogenesis. Methods: The Web of Science Core Collection (WoSCC) database was used to screen publications about RNA methylation during angiogenesis from Jan 1, 2000 to Nov 24, 2022. Bibliometric and visualization analyses were conducted to understand publication trends by CiteSpace and VOSviewer. Results: In total, 382 publications from 2000 to 2022 were included in the bibliometric and visualization analyses. On the whole, the number of publications had exponential growth. China was the country and Sun Yat-Sen University was the university associated with the largest number of publications, although publications from the United Kingdom and Soochow University were currently having the strongest impact. Cancer was the most studied topic in this field, and N6-methyladenosine is the most studied RNA methylation type. Conclusion: There is a continuously increasing trend in publications related to RNA methylation and angiogenesis, which has attracted much attention, particularly since 2011. RNA methylation might be a promising target in the investigation of pathological angiogenesis and related disorders, which deserves further investigation.

Progress and prospects of gene therapy in ophthalmology from 2000 to 2022: A bibliometric analysis.

Background: Gene therapy is a treatment approach at the genetic level, which brings great advances in many diseases and develops rapidly in recent years. Currently, its mechanism of action is mainly through the replacement of missing or defective genes, or the reduction of harmful gene products. However, the application of gene therapy in ophthalmology remains limited. Methods: A total of 1143 articles and reviews published in the field of ocular gene therapies were found in the Web of Science Core Collection database and used for the bibliometric analysis. CiteSpace was mainly applied to the network analysis of countries, institutions, keywords, and dual-map overlay of journals. The visual analysis of authors, journals, and references was used by VOSviewer. The geographical distribution of publications was conducted by R language. Results: The annual publications are increasing in general. Currently, the USA and the UK are two main sources of publications in this field. Switzerland, Denmark, and Finland are the top 3 countries that establish the most cooperation and exchanges with other countries or regions. The most cited and co-cited journal in this field is Investigative Ophthalmology & Visual Science. Gene therapy studies for eye diseases are mainly focused on retinal dysfunctions by the analysis of references, keywords, and counting of original research, including Leber's congenital amaurosis and retinitis pigmentosa. Conclusion: This study used bibliometrics to analyze overall characteristics and put forward prospects for the future in the field of gene therapy in ophthalmology. Ocular diseases, especially hereditary retinal diseases, will be the major focus of gene therapy in the future.

Exosomal non-coding RNAs in angiogenesis: Functions, mechanisms and potential clinical applications.

Exosomes are extracellular vesicles that can be produced by most cells. Exosomes act as important intermediaries in intercellular communication, and participate in a variety of biological activities between cells. Non-coding RNAs (ncRNAs) usually refer to RNAs that do not encode proteins. Although ncRNAs have no protein-coding capacity, they are able to regulate gene expression at multiple levels. Angiogenesis is the formation of new blood vessels from pre-existing vessels, which is an important physiological process. However, abnormal angiogenesis could induce many diseases such as atherosclerosis, diabetic retinopathy and cancer. Many studies have shown that ncRNAs can stably exist in exosomes and play a wide range of physiological and pathological roles including regulation of angiogenesis. In brief, some specific ncRNAs can be enriched in exosomes secreted by cells and absorbed by recipient cells through the exosome pathway, thus activating relevant signaling pathways in target cells and playing a role in regulating angiogenesis. In this review, we describe the physiological and pathological functions of exosomal ncRNAs in angiogenesis, summarize their role in angiogenesis-related diseases, and illustrate potential clinical applications like novel drug therapy strategies and diagnostic markers in exosome research as inspiration for future investigations.

Systematic Evaluation of the Application of Zebrafish in Toxicology (SEAZIT): Developing a Data Analysis Pipeline for the Assessment of Developmental Toxicity with an Interlaboratory Study.

The embryonic zebrafish is a useful vertebrate model for assessing the effects of substances on growth and development. However, cross-laboratory developmental toxicity outcomes can vary and reported developmental defects in zebrafish may not be directly comparable between laboratories. To address these limitations for gaining broader adoption of the zebrafish model for toxicological screening, we established the Systematic Evaluation of the Application of Zebrafish in Toxicology (SEAZIT) program to investigate how experimental protocol differences can influence chemical-mediated effects on developmental toxicity (i.e., mortality and the incidence of altered phenotypes). As part of SEAZIT, three laboratories were provided a common and blinded dataset (42 substances) to evaluate substance-mediated effects on developmental toxicity in the embryonic zebrafish model. To facilitate cross-laboratory comparisons, all the raw experimental data were collected, stored in a relational database, and analyzed with a uniform data analysis pipeline. Due to variances in laboratory-specific terminology for altered phenotypes, we utilized ontology terms available from the Ontology Lookup Service (OLS) for Zebrafish Phenotype to enable additional cross-laboratory comparisons. In this manuscript, we utilized data from the first phase of screening (dose range finding, DRF) to highlight the methodology associated with the development of the database and data analysis pipeline, as well as zebrafish phenotype ontology mapping.

Seasonal dynamics of odor compounds concentration driven by phytoplankton succession in a subtropical drinking water reservoir, southeast China.

Occurrences of odor compounds in drinking water reservoirs are considered as a nuisance by the water industry. Through the high-frequency monitoring of Tianmuhu Reservoir, a drinking water source for a city with a population of 700,000, we found that odor compounds seasonal dynamics were significantly related to phytoplankton succession, which was controlled by hydrometeorological process. 2-Methylisoborneol (2-MIB) was significantly related to Aphanizomenon sp. (r = 0.51). When the surface water temperature exceeded 12 â„ƒ, 2-MIB concentration may exceed the odor threshold concentration. With the proliferation of Aphanizomenon sp. in spring, 2-MIB concentration reached 87.22 ng/L. After late spring heavy rain, 2-MIB concentration sharply decreased to 3.19 ng/L. As the temperature increased at the end of the rainy season, Aphanizomenon sp. biomass increased to 2.09 mg/L, and 2-MIB concentration increased to 40.16 ng/L. These results showed that the concentration of odor compounds in shallow layer varied greatly because odor compounds mainly originated from phytoplankton and were susceptible to short-term hydrometeorological processes. However, the concentrations of odor compounds in deep layer were relatively insensitive to short-term weather processes. This study will improve the understanding of seasonal changes in odor compounds at different depths, and provide useful information for reservoir managers to prevent odor problems.