Testing the accuracy of a four serum microRNA panel for the detection of primary bladder cancer: a discovery and validation study.

BACKGROUND: Bladder cancer (BC) is one of the ten most common cancers worldwide with late detection and early age of diagnosis. There is abundant evidence that early detection and timely intervention can lead to a better prognosis of BC. Substantial evidence has indicated that microRNAs (miRNAs) are specific to different tumour types and are remarkably stable, indicating that serum miRNAs may serve as potential cancer diagnostic markers. This study aimed to identify suitable serum miRNAs to create a panel that can be used to diagnose primary BC. METHODS: In this study, 18 miRNAs that were differentially expressed in BC were obtained from the PubMed or Gene Expression Omnibus database. Then, 18 BC-related-miRNAs were verified in screening and validation sets created using 56 (28 primary BC vs. 28 NCs) and 168 (84 primary BC vs. 84 NCs) serum samples, respectively. Quantitative reverse transcription-PCR (qRT-PCR) was performed to verify the identity of the differential miRNAs. A multi-miRNA panel with superior diagnostic performance was constructed. TCGA and KEGG databases were used to conduct the survival analysis and bioinformatics analysis, respectively. RESULTS: Six serum miRNAs (miR-221-5p, miR-181a-5p, miR-98-5p, miR-15a-5p, miR-222-3p, and miR-197-3p) were significantly aberrantly expressed in the BC patients, while four miRNAs from among them (miR-221-5p, miR-181a-5p, miR-15a-5p, miR-222-3p) were assembled into a panel that showed high diagnostic value (AUC = 0.875, 95% CI: 0.815 - 0.921; sensitivity: 82.14%; and specificity: 85.71%) based on the logistic regression analysis. The survival analysis showed that miR-181a-5p was closely associated with BC prognosis (Log-rank p-value < 0.05). CONCLUSION: The combination of the four miRNAs (miR-221-5p, miR-181a-5p, miR-15a-5p and miR-222-3p) may be a novel non-invasive serological biomarker for BC screening.

Early detection and timely intervention can lead to a better prognosis of bladder cancer.This study aimed to identify suitable serum miRNAs to create a panel that can be used to diagnose primary bladder cancer.

Integrating Self-Partitioned Pore Space and Amine Functionality into an Aromatic-Rich Coordination Framework with Ph Stability for Effective Purification of C2 Hydrocarbons.

A great demand for high-purity C2 hydrocarbons calls for the development of chemically stable porous materials for the effective isolation of C2 hydrocarbons from CH4 and CO2. However, such separations are challenged by their similar physiochemical parameters and have not been systematically studied to date. In this work, we reported a cadmium-based rod-packing coordination framework compound ZJNU-140 of a new 5,6,7-c topology built up from a custom-designed tricarboxylate ligand. The metal-organic framework (MOF) features an aromatic-abundant pore surface, uncoordinated amine functionality, and self-partitioned pore space of suitable size. These structural characteristics act synergistically to provide the MOF with both selective recognition ability and the confinement effect toward C2 hydrocarbons. As a result, the MOF displays promising potential for adsorptive separation of C2-CH4 and C2-CO2 mixtures. The IAST-predicted C2/CH4 and C2/CO2 adsorption selectivities, respectively, fall in the ranges of 7.3-10.2 and 2.1-2.9 at 298 K and 109 kPa. The real separation performance was also confirmed by dynamic breakthrough experiments. In addition, the MOF can maintain skeleton intactness in aqueous solutions with a wide pH range of 3-11, as confirmed by powder X-ray diffraction (PXRD) and isotherm measurements, showing no loss of framework integrity and porosity. The excellent hydrostability, considerable uptake capacity, impressive adsorption selectivity, and mild regeneration make ZJNU-140 a promising adsorbent material applied for the separation and purification of C2 hydrocarbons.

Ligand Conformation Fixation Strategy for Expanding the Structural Diversity of Copper-Tricarboxylate Frameworks and C2H2 Purification Performance Studies.

Structural and functional expansion of metal-organic frameworks (MOFs) is fundamentally important because it not only enriches the structural chemistry of MOFs but also facilitates the full exploration of their application potentials. In this work, by employing a dual-site functionalization strategy to lock the ligand conformation, we designed and synthesized a pair of biphenyl tricarboxylate ligands bearing dimethyl and dimethoxy groups and fabricated their corresponding framework compounds through coordination with copper(II) ions. Compared to the monofunctionalized version, introduction of two side groups can significantly fix the ligand conformation, and as a result, the dual-methoxy compound exhibited a different network structure from the mono-methoxy counterpart. Although only one almost orthogonal conformation was observed for the two ligands, their coordination framework compounds displayed distinct topological structures probably due to different solvothermal conditions. Significantly, with a hierarchical cage-type structure and good hydrostability, the dimethyl compound exhibited promising practical application value for industrially important C2H2 separation and purification, which was comprehensively demonstrated by equilibrium/dynamic adsorption measurements and the corresponding Clausius-Clapeyron/IAST/DFT theoretical analyses.

The full-length genome sequence of a novel amalgavirus in Lilium spp. in China.

We report for the first time the complete genome sequence of a novel amalgavirus, tentatively designated as 'lily amalgavirus 1' (LAV-1), isolated from Lilium spp. in China. LAV-1 is a 3448-nt double-stranded RNA virus that encodes two putative proteins. Open reading frame 1 (ORF1) encodes a 394-aa protein with unknown function. ORF2 encodes a putative RNA-dependent RNA polymerase (RdRp) of 895 aa. The two ORFs putatively encode a '1 + 2' fusion protein generated by a '+1' programmed ribosomal frameshift (PRF). BLASTp analysis revealed that the complete genome sequence of LAV-1 shares 48.23-59.80% sequence identity (query sequence coverage > 77%) with those of members of the genus Amalgavirus, with the highest nucleotide sequence identity of 59.80% with that of Allium cepa amalgavirus 1 (query sequence coverage, 87%). The genome structure, phylogenetic relationships, and sequence similarities to other plant amalgaviruses suggest that LAV-1 is a new member of the genus Amalgavirus.

Volatile organic compounds from second-hand smoke may increase susceptibility of children through oxidative stress damage.

Although humans are generally exposed to second-hand smoke (SHS), volatile organic compounds (VOCs) exposure derived from SHS and its health hazard to non-smokers are rarely investigated. Thus, we examined the effects of SHS on VOCs exposure and oxidative stress damage via a passive smoking simulation experiment in 6 children and 7 adults. To further validate the studied urinary VOC metabolites as biomarkers for passive smoking, 259 children were recruited. The levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), malonaldehyde (MDA), trans-3'-hydroxycotinine (OH-Cot) and 31 VOC metabolites in urine were determined. The results showed that the geomean concentrations of 17 VOC metabolites in urine of children were 26.5%-138% higher than those of adults after passive smoking. The levels of urinary 8-OHdG, MDA and OH-Cot increased by 24.6%, 18.8% and 600% in children, but only 1.25%, 10.3% and 116% in adults, respectively. Therefore, children are more vulnerable to SHS than adults. After exposure to SHS, the levels of 8 urinary VOC metabolites of benzene, acrylonitrile, 1-bromopropane, propylene oxide, toluene, methyl methacrylate and cyanide increased by 60.9%-538% within 23 h. These 8 VOC metabolites were also significantly associated with 8-OHdG or MDA in urine (p < 0.01). Therefore, exposure to VOCs caused by SHS increases body oxidative stress damage. OH-Cot level higher than 2.00 µg/g Cr can be used as a threshold of passive smoking. The levels of urinary s-benzylmercapturic acid (BMA) and s-phenylmercapturic acid (PMA) in children increased by 494% and 728% within 6 h after passive smoking, respectively. Population validation study indicated that BMA and PMA levels were significantly elevated in children exposed to SHS. Therefore, in addition to OH-Cot, urinary BMA and PMA are potentially useful short-term biomarkers of passive smoking. Future studies should focus on the differences in VOC metabolism and detoxification mechanisms between children and adults.

A Series of Metal-Organic Framework Isomers Based on Pyridinedicarboxylate Ligands: Diversified Selective Gas Adsorption and the Positional Effect of Methyl Functionality.

Solvothermal assembly of copper(II) cations and 5-(pyridine-3-yl)isophthalate linkers bearing different position-substituted methyl groups afforded four ligand-induced metal-organic framework (MOF) isomers as a platform for investigating diverse selective gas adsorption properties and understanding the positional effect of methyl functionality. Single-crystal X-ray diffraction (SCXRD) analyses showed that, when the methyl substituent is at the para position with respect to the pyridinic N atom, the resultant framework compound ZJNU-27 features an eea-type topology, while the other three solids possess an isoreticular structure with an rtl-type topology when the methyl group is situated at the other positions. As revealed by N2 physi-adsorption measurements at 77 K, they exhibit moderate specific surface areas ranging from 584 to 1182 m2 g-1 and distinct degrees of framework flexibility, which are heavily dependent on the methyl position. Comprehensive gas adsorption studies show that they are capable of effectively separating three pairs of binary gas mixtures including C2H2-CH4, CO2-CH4, and CO2-N2 couples. Moreover, their uptake capacities and adsorption selectivities can be tailored by altering the methyl position. In addition, their framework hydro-stability is also influenced by the methyl position. Compared to ZJNU-27 and ZJNU-28, ZJNU-26 and ZJNU-29 exhibit poorer stability against H2O, although the methyl group is more close to inorganic secondary building units (SBUs), which are believed to originate from the steric effect of the methyl group. Overall, the four MOFs display the methyl position-dependent network architectures, framework flexibilities, and selective gas adsorption properties as well as hydrostabilities. The findings observed in this work not only demonstrate the importance of the positional effect of the functional group but also highlight that engineering the substituent position is a potential strategy for achieving the modulation of MOF structures and properties.

Modulation of Topological Structures and Adsorption Properties of Copper-Tricarboxylate Frameworks Enabled by the Effect of the Functional Group and Its Position.

To push forward the structural development and fully explore the potential utility, it is highly desired but challenging to regulate in a controllable manner the structures and properties of MOFs. In this work, we reported the structural and functional modulation of Cu(II)-tricarboxylate frameworks by employing a strategy of engineering the functionalities and their positions. Two pairs of unsymmetrical biaryl tricarboxylate ligands modified with a methyl group and a pyridinic-N atom at distinct positions were logically designed and synthesized, and their corresponding Cu(II)-based MOFs were solvothermally constructed. Diffraction analyses revealed that the variation of functionalities and their positions furnished three different types of topological structures, which we ascribed to the steric effect exerted by the methyl group and the chelating effect involving the pyridinic-N atom. Furthermore, gas adsorption studies showed that three of them are potential candidates as solid separation media for acetylene (C2H2) purification, with the separation potential tailorable by altering functionalities and their locations. At 106.7 kPa and 298 K, the C2H2 uptake capacity varies from 64.1 to 132.4 cm3 (STP) g-1, while the adsorption selectivities of C2H2 over its coexisting components of CO2 and CH4 fall in the ranges of 3.28-4.60 and 14.1-21.9, respectively.

Effect of air-drying and oven-drying treatment on Cr(VI) content and Cr bond forms in soil.

Air-drying and oven-drying are pretreatment processes often used before testing and analyzing various soil characteristics in the laboratory. This study selected three kinds of soil, including red soil, entisol, and alluvial soil, and examined the variation of the Cr(VI) content and Cr bond forms in these soils during air-drying and oven-drying. The results show that when the soil is air-dried in natural environment, the Cr(VI) content decreases with air-drying time. On day 10 of air-drying, the Cr(VI) content in these soils is 22.8∼47.9 % of the initial value. When the soil is oven-dried, the Cr(VI) concentration decays faster; on day 8, the Cr(VI) is no longer detected in these soil samples. When the Cr(VI)-contaminated soil is treated by air-drying and oven-drying, the Cr bond form converts into a more stable form. After oven-drying, the Cr mainly exists in Fe-Mn oxide form, organic bond form, and residual form. The air-drying and oven-drying pretreatment processes of soil reduce the Cr(VI) content and stabilize the Cr bond form. If the laboratory analytic results are applied to risk analysis or remediation strategy planning for chromium-contaminated soil, the toxicity, bioavailability, and mobility of Cr in soil may be underrated.

Measurement Invariance of the Children's Social Desirability Scale-Short Version (CSD-S) Across Gender, Grade Level, and Race/Ethnicity.

Social desirability bias is a methodological challenge with participant self-reports. Social desirability measures are often used to control the potential effects of social desirability bias on participant self-reports, but whether these measures are interpreted similarly across different demographic groups remains unclear. This study examines the factor structure and measurement invariance of the Children's Social Desirability Scale-Short version (CSD-S) across gender, grade level, and race/ethnicity with a large sample of children and adolescents in the United States. Results indicate a close fit to a one-factor model. Tests of measurement invariance show partial strong invariance across gender (male vs. female) and grade level (elementary vs. middle vs. high schoolers) as well as strong invariance across race/ethnicity (Asian vs. Black/African American vs. Hispanic/Latine vs. White vs. Bi/Multiracial). Latent mean differences were found across grade level and race/ethnicity but not gender, with lower grades reporting higher social desirability than upper grades and Bi/Multiracials reporting lower social desirability than Asians and Hispanics/Latines. Findings provide preliminary evidence for the use of CSD-S in detecting social desirability bias and assessing meaningful social desirability differences in diverse children and adolescents.

The value of a three-microRNA panel in serum for prostate cancer screening.

BACKGROUND: Globally, prostate cancer is the second most common malignancy in males. Serum microRNAs (miRNAs) may function as non-invasive and innovative biomarkers for various cancers. Our study aimed to determine potential miRNAs for prostate cancer screening. METHODS: A three-stage study was accomplished to ascertain crucial miRNAs as markers. In the screening stage, we searched PubMed for aberrantly expressed miRNAs relevant to prostate cancer and selected them as candidate miRNAs. In training and validation stages, with serum specimens from 112 prostate cancer patients and 112 healthy controls, expressions of candidate miRNAs were identified through quantitative reverse transcription-polymerase chain reaction. The diagnostic capabilities of miRNAs were determined by receiver operating characteristic curves. Bioinformatic analysis was utilized to explore the function of the critical miRNAs. RESULTS: Expression of six serum miRNAs (miR-34b-3p, miR-556-5p, miR-200c-3p, miR-361-5p, miR-369-3p, miR-485-3p) were significantly altered in prostate cancer patients contrasted with healthy controls. The optimal combination of critical miRNAs is a three-miRNA panel (miR-34b-3p, miR-200c-3p, and miR-361-5p) with good diagnostic capability. FLRT2, KIAA1755, LDB3, and NTRK3 were identified as the potential genes targeted by the three-miRNA panel. CONCLUSIONS: The three-miRNA panel may perform as an innovative and promising serum marker for prostate cancer screening.

Intra-arterial chemotherapy plus BCG, a promising combination adjuvant treatment for high-risk NMIBC.

PURPOSE: To develop a novel combination therapy for high-risk nonmuscle-invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor (TURBT), namely, intra-arterial chemotherapy (IAC) plus BCG immunotherapy, and to compare the feasibility and safety of the 2 therapies. MATERIALS AND METHODS: A retrospective study was conducted on the data of 119 patients who were diagnosed with high-risk NMIBC and underwent TURBT in the past 5 years. Those who did not complete the treatment were excluded, and the remaining 98 patients were divided into 2 groups: both groups received intravesical BCG immunotherapy, while the BCG+IAC group received 4 courses of extra intra-arterial chemotherapy. Clinical and follow-up data were processed using statistical software. RESULTS: The recurrence rate was 22.2% in the BCG+IAC group and 35.8% in the BCG group, whereas the progression rates were 8.9% and 24.5%, respectively. In the Kaplan-Meier plot, a statistically significant difference was observed with respect to recurrence-free survival (p = 0.025), as well as the progression-free survival of the two groups was similar (p = 0.019). A total of 22.2% of the patients with adverse effects of IAC and 79.6% of patients suffered from adverse reactions to BCG immunotherapy, and most of the adverse effects were mild and tolerable. Univariate and multivariate analysis indicated that multifocal and treatment were independent risk factors for recurrence, while the history of recurrence and treatment were independent risk factors for progression. CONCLUSION: IAC could be a promising auxiliary treatment for BCG immunotherapy in decreasing the recurrence and progression rate of high-risk NMIBC with little additional toxicity.

A panel based on three-miRNAs as diagnostic biomarker for prostate cancer.

Background: Prostate cancer (PCa) is one of the most prevalent malignancies affecting the male life cycle. The incidence and mortality of prostate cancer are also increasing every year. Detection of MicroRNA expression in serum to diagnose prostate cancer and determine prognosis is a very promising non-invasive modality. Materials and method: A total of 224 study participants were included in our study, including 112 prostate cancer patients and 112 healthy adults. The experiment consisted of three main phases, namely, the screening phase, the testing phase, and the validation phase. The expression levels of serum miRNAs in patients and healthy adults were detected using quantitative reverse transcription-polymerase chain reaction. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to evaluate the diagnostic ability, specificity, and sensitivity of the candidate miRNAs. Result: Eventually, three miRNAs most relevant to prostate cancer diagnosis were selected, namely, miR-106b-5p, miR-129-1-3p and miR-381-3p. We used these three miRNAs to construct a diagnostic panel with very high diagnostic potential for prostate cancer, which had an AUC of 0.912 [95% confidence interval (CI): 0.858 to 0.950; p < 0.001; sensitivity = 91.67%; specificity = 79.76%]. In addition, the three target genes (DTNA, GJB1, and TRPC4) we searched for are also expected to be used for prostate cancer diagnosis and treatment in the future.

Overcoming small-bandgap charge recombination in visible and NIR-light-driven hydrogen evolution by engineering the polymer photocatalyst structure.

Designing an organic polymer photocatalyst for efficient hydrogen evolution with visible and near-infrared (NIR) light activity is still a major challenge. Unlike the common behavior of gradually increasing the charge recombination while shrinking the bandgap, we present here a series of polymer nanoparticles (Pdots) based on ITIC and BTIC units with different π-linkers between the acceptor-donor-acceptor (A-D-A) repeated moieties of the polymer. These polymers act as an efficient single polymer photocatalyst for H2 evolution under both visible and NIR light, without combining or hybridizing with other materials. Importantly, the difluorothiophene (ThF) π-linker facilitates the charge transfer between acceptors of different repeated moieties (A-D-A-(π-Linker)-A-D-A), leading to the enhancement of charge separation between D and A. As a result, the PITIC-ThF Pdots exhibit superior hydrogen evolution rates of 279 µmol/h and 20.5 µmol/h with visible (>420 nm) and NIR (>780 nm) light irradiation, respectively. Furthermore, PITIC-ThF Pdots exhibit a promising apparent quantum yield (AQY) at 700 nm (4.76%).

Evaluative Skill in the Creative Process: A Cross-cultural Study.

Evaluative skill is the ability to accurately judge ideas on creativity (or originality), which is a critical component of creativity. Various aspects of creativity have been examined cross-culturally, but little research has focused on evaluative skill. The first goal of this study was to examine the measurement invariance of evaluative skill assessments, which were based on two types of divergent thinking tests (Line Meanings and Uses), between American (n = 341) and Chinese (n = 345) college students. Multi-group confirmatory factor analyses supported a two-factor model based on two types of evaluation tasks, and this model satisfied configural and weak invariance. However, partial strong invariance was satisfied only for the Uses evaluation task. Based on this evidence, our second goal was to explore the differences in evaluative skill between these two groups. Via latent mean comparisons, we found that American participants had better performance on evaluative skill based on the Uses evaluation task than their Chinese counterparts. Taken together, this study is one of the first to examine the cross-cultural differences in evaluative skill between American and Chinese adults. This study offered preliminary results showing some invariance in evaluative skill assessments across cultures and indicating cross-cultural differences in this ability.

Rapid Screening of Microalgae as Potential Sources of Natural Antioxidants.

In order to rapidly screen microalgae species as feedstocks for antioxidants, extracts were obtained from 16 microalgae strains (under 11 genera, 7 classes) using two methods: a one-step extraction with ethanol/water and a three-step fractionating procedure using hexane, ethylacetate, and water successively. Measuring the total phenol content (TPC), total carotenoid content (TCC), and antioxidant activity of the extracts, indicating TPC and TCC, played an important role in determining the antioxidant activity of the microalgae. A weighted scoring system was used to evaluate the antioxidant activity, and the scores of microalgal samples from two extraction methods were calculated using the same system. Among the investigated microalgae, Euglena gracilis SCSIO-46781 had the highest antioxidant score, contributing to high TPC and TCC, followed by Arthrospira platensis SCSIO-44012, Nannochloropsis sp. SCSIO-45224, Phaeodactylum tricornutum SCSIO-45120, and Nannochloropsis sp. SCSIO-45006, respectively. Additionally, the above-mentioned five strains are currently being applied in commercial production, indicating this system could be effective not only for screening microalgal antioxidants, but also for screening microalgal species/strains with strong adaptation to environmental stress, which is a critical trait for their commercial cultivation.

Daily positive and negative affect during the COVID-19 pandemic.

The COVID-19 pandemic influenced emotional experiences globally. We examined daily positive and negative affect between May/June 2020 and February 2021 (N = 151,049; 3,509,982 observations) using a convenience sample from a national mobile application-based survey that asked for daily affect reports. Four questions were examined: (1) How did people in the United States feel from May/June 2020 to February 2021?; (2) What demographic variables are related to positive and negative affect?; (3) What is the relationship between experienced stressors and daily affect?; and (4) What is the relationship between daily affect and preventive behavior? Positive affect increased, and negative decreased over time. Demographic differences mirrored those from before the pandemic (e.g., younger participants reported more negative and less positive affect). Stressors such as feeling unwell, experiencing COVID-19 symptoms, exposure to COVID-19, and lack of sleep were associated with less positive and more negative affect. Exercising protective behaviors predicted future affect, and affect also predicted future protective behaviors (e.g., less protective behavior when happy but more when grateful and thoughtful). The implications for public health communication were discussed.

Sibling absence and body mass index: From adolescence to adulthood.

OBJECTIVES: To examine if sibling absence is associated with higher BMI and to identify potential lifestyle factors underlying this effect; to determine if sibling effects on BMI persist into adulthood. METHODS: We used data from all five waves of the National Longitudinal Study of Adolescent to Adult Health to study the sibling factors and BMI of 3,563 participants who were in grades 7-12 at first wave (1994-95). These participants were measured again in the second wave (1996), the third wave (2001-2002), the fourth wave (2008-2009), and most recently, the fifth wave (2016-2018). We identified categories of siblings, comparing the BMI of those without siblings either to birth order or sibship size. BMI was calculated based on direct measurements of height and weight; underlying mechanisms were self-reported. RESULTS: Participants without siblings had significantly higher BMI than those with siblings, across waves, regardless of sibship size. Those without siblings had consistently higher BMI than middle-born, but not last-born participants. Adolescents without siblings reported eating fast food more frequently and spending more screen time. CONCLUSIONS: Sibling absence is associated with higher BMI in adolescence and this difference persists into adulthood.

Dose makes poison: Insights into the neurotoxicity of perinatal and juvenile exposure to environmental doses of 16 priority-controlled PAHs.

Whether chronic exposure to environmental doses of polycyclic aromatic hydrocarbons (PAHs) can lead to neurotoxic effects is still unclear. Hence, the neurotoxic effects of perinatal and juvenile exposure to 16 priority-controlled PAHs were investigated. The mice were treated with 0, 0.5, 18.75, 50, 1875 µg/kg/day of PAHs corresponding to various population exposure concentrations from gestation to postnatal day 60. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and hippocampal and cortical neurotransmitter levels were determined using liquid chromatography-tandem mass spectrometry. Typical indicators or outcome of neurotoxicity, including, spatial learning and memory ability, hippocampal long-term potentiation (LTP) and dendritic spine density were evaluated via Morris water maze tests, electrophysiological experiments and Golgi-Cox assays, respectively. The results showed that exposure to different levels of PAH could not increase oxidative DNA damage level. Mice exposed to 0.5, 50 and 1875 µg/kg/day PAHs had significantly longer escape latency than the control group only on the 1st day (p < 0.05). The number of platform crossings and the time spent in target quadrant were similar between the control and the PAHs-exposed mice. Compared with the control mice, only those exposed to 50 µg/kg/day PAHs had significantly lower LTP in hippocampal CA1 region and dendritic spine density in hippocampal DG region (p < 0.05). Except for serotonin, no significant difference in hippocampal and cortical neurotransmitter concentrations was observed between the control and PAHs-exposed groups. Taken together, perinatal and juvenile exposure to environmental doses of PAHs had no profound effect on spatial learning and memory abilities, hippocampal LTP, dendritic spines density, and neurotransmitter levels. These unexpected findings were quite different from previous in vivo studies which commonly used 2-3 orders of magnitude higher PAHs doses to treat animals. Thus, the environmental dose is a crucial reference for future toxicological research to reveal the actual toxic mechanisms and human health effects of PAHs exposure.

A BERT-based ensemble learning approach for the BioCreative VII challenges: full-text chemical identification and multi-label classification in PubMed articles.

In this research, we explored various state-of-the-art biomedical-specific pre-trained Bidirectional Encoder Representations from Transformers (BERT) models for the National Library of Medicine - Chemistry (NLM CHEM) and LitCovid tracks in the BioCreative VII Challenge, and propose a BERT-based ensemble learning approach to integrate the advantages of various models to improve the system's performance. The experimental results of the NLM-CHEM track demonstrate that our method can achieve remarkable performance, with F1-scores of 85% and 91.8% in strict and approximate evaluations, respectively. Moreover, the proposed Medical Subject Headings identifier (MeSH ID) normalization algorithm is effective in entity normalization, which achieved a F1-score of about 80% in both strict and approximate evaluations. For the LitCovid track, the proposed method is also effective in detecting topics in the Coronavirus disease 2019 (COVID-19) literature, which outperformed the compared methods and achieve state-of-the-art performance in the LitCovid corpus. Database URL: https://www.ncbi.nlm.nih.gov/research/coronavirus/.

Single-Cell RNA Sequencing Identifies Intra-Graft Population Heterogeneity in Acute Heart Allograft Rejection in Mouse.

Transplant rejection remains a major barrier to graft survival and involves a diversity of cell types. However, the heterogeneity of each cell type in the allograft remains poorly defined. In the present study, we used single-cell RNA sequencing technology to analyze graft-infiltrating cells to describe cell types and states associated with acute rejection in a mouse heart transplant model. Unsupervised clustering analysis revealed 21 distinct cell populations. Macrophages formed five cell clusters: two resident macrophage groups, two infiltrating macrophage groups and one dendritic cell-like monocyte group. Infiltrating macrophages were predominantly from allogeneic grafts. Nevertheless, only one infiltrating macrophage cluster was in an active state with the upregulation of CD40, Fam26f and Pira2, while the other was metabolically silent. Re-clustering of endothelial cells identified five subclusters. Interestingly, one of the endothelial cell populations was almost exclusively from allogeneic grafts. Further analysis of this population showed activation of antigen processing and presentation pathway and upregulation of MHC class II molecules. In addition, Ubiquitin D was specifically expressed in such endothelial cell population. The upregulation of Ubiquitin D in rejection was validated by staining of mouse heart grafts and human kidney biopsy specimens. Our findings present a comprehensive analysis of intra-graft cell heterogeneity, describe specific macrophage and endothelial cell populations which mediate rejection, and provide a potential predictive biomarker for rejection in the clinic.