The role of microbial metabolites in diabetic kidney disease.

Background: Growing evidence suggests a complex bidirectional interaction between gut microbes, gut-derived microbial metabolites, and diabetic kidney disease (DKD), known as the "gut-kidney axis" theory. The present study aimed to characterize the role of microbial metabolites in DKD. Methods: Six-week-old db/db and littermate db/m mice were raised to 20 weeks old. The serum, urine, feces, liver, perinephric fat, and kidney were analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS)-based metabolomic analyses. Results: The db/db mice showed obvious pathological changes and worse renal functions than db/m mice. Indoleacetaldehyde (IAld) and 5-hydroxy-l-tryptophan (5-HTP) in kidney samples, and serotonin (5-HT) in fecal samples were increased in the db/db group. Phosphatidylcholine (PC), phosphatidate (PA), and 1-acylglycerophosphocholine (lysoPC) were decreased in liver and serum samples of the db/db group, while PC and lysoPC were decreased in kidney and perinephric fat samples. Suggested metabolomic homeostasis was disrupted in DKD mice, especially glycerophospholipid and tryptophan metabolism, which are closely related to the gut microbiome. Conclusions: Our findings reveal the perturbation of gut microbial metabolism in db/db mice with DKD, which may be useful for building a bridge between the gut microbiota and the progression of DKD and provide a theoretical basis for the intestinal treatment of DKD.

The characteristics of extrachromosomal circular DNA in patients with end-stage renal disease.

BACKGROUND: End-stage renal disease (ESRD) is the final stage of chronic kidney disease (CKD). In addition to the structurally intact chromosome genomic DNA, there is a double-stranded circular DNA called extrachromosomal circular DNA (eccDNA), which is thought to be involved in the epigenetic regulation of human disease. However, the features of eccDNA in ESRD patients are barely known. In this study, we identified eccDNA from ESRD patients and healthy people, as well as revealed the characteristics of eccDNA in patients with ESRD. METHODS: Using the high-throughput Circle-Sequencing technique, we examined the eccDNA in peripheral blood mononuclear cells (PBMCs) from healthy people (NC) (n = 12) and ESRD patients (n = 16). We analyzed the length distribution, genome elements, and motifs feature of eccDNA in ESRD patients. Then, after identifying the specific eccDNA in ESRD patients, we explored the potential functions of the target genes of the specific eccDNA. Finally, we investigated the probable hub eccDNA using algorithms. RESULTS: In total, 14,431 and 11,324 eccDNAs were found in the ESRD and NC groups, respectively, with sizes ranging from 0.01 kb to 60 kb at most. Additionally, the ESRD group had a greater distribution of eccDNA on chromosomes 4, 11, 13, and 20. In two groups, we also discovered several motifs of specific eccDNAs. Furthermore, we identified 13,715 specific eccDNAs in the ESRD group and 10,585 specific eccDNAs in the NC group, both of which were largely annotated as mRNA catalog. Pathway studies using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) showed that the specific eccDNA in ESRD was markedly enriched in cell junction and communication pathways. Furthermore, we identified potentially 20 hub eccDNA-targeting genes from all ESRD-specific eccDNA-targeting genes. Also, we found that 39 eccDNA-targeting genes were associated with ESRD, and some of these eccDNAs may be related to the pathogenesis of ESRD. CONCLUSIONS: Our findings revealed the characteristics of eccDNA in ESRD patients and discovered potentially hub and ESRD-relevant eccDNA-targeting genes, suggesting a novel probable mechanism of ESRD.

Associations among teacher-child interaction, children's executive function and children's comprehensible vocabulary.

Objective: To understand the working mechanism and the relationships among the quality of teacher-child interaction (TCI), children's comprehensible vocabulary (CV) and executive function (EF). Methods: Using stratified sampling, 900 children (boys 50.2%) and 60 preschool teachers were recruited from 4 places in China for testing, and five measurement tools, including the Classroom Assessment Scoring System (CLASS), the Peabody Picture Vocabulary Test (PPVT-R), the Stroop test, a card sorting task, and the Wechsler Intelligence Scale for Children (WISC-IV), were used. Results: For every additional unit of TCI, EF increases by 0.55 units; For every additional unit of EF, CV increases by 0.55 units; For every additional unit of CV, EF increases by 0.55 units; For every additional unit of CV, TCI increases by 0.38 units; For every additional unit of TCI, CV increases by 0.38 units. In the Model of TCI-EF-CV, the estimated value of TCI and the total effect of comprehensible vocabulary is 0.18; Z = 9.84, which is significantly greater than 1.96 at the bias-corrected 95% confidence interval and at the percentile 95% confidence interval (0.15, 0.23), both of which do not contain 0. The direct effect of TCI and CV is significant and indirect effects account for 39%. In the Model of TCI-CV-EF, the total effect of TCI on executive function is 0.09 (Z = 6.14), the direct effect is not significant with bias-corrected 95% confidence interval and 95% confidence interval (-0.01, 0.03), both of which include 0. Conclusion: There are two-way effects among children's EF and CV, TCI and CV. EF plays a mediating role in the influence of TCI on CV. TCI positively predicts children's EF, but this mainly depends on CV. Therefore, TCI plays a positive role in the development of children's CV and EF.

Physical exercise can enhance meaning in life of college students: the chain mediating role of self-efficacy and life satisfaction.

Meaning in life refers to an individual's capacity to understand and grasp the meaning of their own existence, as well as being aware of the goals, tasks, or missions in their personal life. Previous studies have found that college students lack meaning in life, but physical exercise can enhance it. In this study, 3,196 college students completed self-report questionnaires to assess self-efficacy, life satisfaction, physical exercise, and meaning in life. The results revealed that the physical exercise not only influenced an individual's perceived meaning in life directly, but also influenced it through self-efficacy. Furthermore, it confirmed the chain mediating role of self-efficacy and life satisfaction, whereby engaging in physical exercise can ultimately impact meaning in life through self-efficacy and life satisfaction. This discovery can help educators create interventions to improve college students' physical exercise engagement and overall life satisfaction.

Vocational Identity Status in Chinese Emerging Adults with and without Hearing Impairment: Latent Profiles and Relationships with Self-Esteem and Subjective Well-Being.

This study aimed to (1) explore the configuration of vocational identity status among emerging adults with and without hearing impairment using latent profile analysis, and (2) investigate the relationships between vocational identity status and self-esteem and subjective well-being. In total, 408 students without disabilities and 432 with hearing impairments from two Chinese higher institutions participated in the study. The Vocational Identity Status Assessment, Rosenberg Self-Esteem scale, Satisfaction with Life Scale, and Positive and Negative Affect were used to assess the major variables. The results derived five latent profiles (achieved, foreclosed, searching moratorium, undifferentiated, and diffused) of vocational identity in the present sample. The students were over-represented in undifferentiated profiles and under-represented in achieved and foreclosed ones. Hearing impairment significantly affected vocational identity status profile membership. The results showed that emerging adults with achievement and foreclosure statuses displayed healthy psychological outcomes, having the highest self-esteem, life satisfaction, and positive affect, and the lowest negative affect. In contrast, the diffused group showed the most disturbing pattern with the lowest self-esteem, life satisfaction, and positive affect, and the highest negative affect. The research findings reveal some notable issues in vocational identity status for emerging Chinese adults, raising concerns about the influence of hearing impairment on vocational identity formation, and provide implications for Chinese society to facilitate college students' career development process to promote their vocational identity status and enhance their self-esteem and subjective well-being.

Integrated proteome and acetylome analyses unveil protein features of gestational diabetes mellitus and preeclampsia.

Gestational diabetes mellitus (GDM) and preeclampsia (PE) are associated with maternal and infant health. Although the pathogenesis of PE and GDM remains controversial, oxidative stress is involved in the underlying pathology of GDM and PE. Protein lysine acetylation (Kac) plays an important regulatory role in biological processes. There is little data regarding the association of the maternal acetylome with GDM and PE. This study aimed to assess the potential value of the proteome and acetylome for GDM and PE. In our study, we included placental tissues from healthy individuals (n = 6), GDM patients (n = 6), and PE patients (n = 6) to perform 4D-label free quantification proteomics analysis and PRM analysis. We identified 22 significantly regulated proteins and 192 significantly regulated acetylated proteins between the GDM and PE groups. Furthermore, 192 significantly regulated acetylated proteins were mainly enriched in endoplasmic reticulum stress (ERS) and ferroptosis pathways. Seventeen acetylated sites in these two pathways were verified by PRM analysis. Our comprehensive analysis revealed key features of GDM/PE-significantly regulated acetylated proteins in the placentas from GDM and PE. The results of signaling pathway analysis focused on ERS and ferroptosis. These findings may help explore the underlying pathology, new biomarkers, and therapeutic targets of GDM and PE.

Integrated proteome and malonylome analyses reveal the neutrophil extracellular trap formation pathway in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease of unknown etiology in which the posttranslational modifications (PTMs) of proteins play an important role. PTMs, such as those involved in the formation of neutrophil extracellular traps (NETs), have been well studied. The excessive formation and release of NETs can mediate inflammation and joint destruction in RA. It has been gradually recognized that lysine malonylation (Kmal) can regulate some biological processes in some prokaryotes and eukaryotes. However, less is known about the role of Kmal in RA. We therefore performed proteome and malonylome analyses to explore the proteomic characteristics of the peripheral blood mononuclear cells from 36 RA patients and 82 healthy subjects. In total, 938 differentially expressed proteins (DEPs) and 42 differentially malonylated proteins (DMPs) with 55 Kmal sites were detected through a liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based analysis. Functional analysis showed that two DEPs with four malonylated sites and one DMP with a malonylated site were identified in the neutrophil extracellular trap formation (NETosis) pathway. Altogether, this study not only describes the characteristics of the malonylome in RA for the first time, but it also reveals that malonylation may be involved in the NETosis pathway. SIGNIFICANCE: This is the first report that reveals the proteomic features of Kmal in RA through a LC-MS/MS-based method. In this study, we found that several key DMPs were associated with the NETosis pathway, which contributes to the development of RA. The present results provide an informative dataset for the future exploration of Kmal in RA.

The cytokine storm and COVID-19.

Coronavirus disease 2019 (COVID-19), which began in Wuhan, China, in December 2019, has caused a large global pandemic and poses a serious threat to public health. More than 4 million cases of COVID-19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have been confirmed as of 11 May 2020. SARS-CoV-2 is a highly pathogenic and transmissible coronavirus that primarily spreads through respiratory droplets and close contact. A growing body of clinical data suggests that a cytokine storm is associated with COVID-19 severity and is also a crucial cause of death from COVID-19. In the absence of antivirals and vaccines for COVID-19, there is an urgent need to understand the cytokine storm in COVID-19. Here, we have reviewed the current understanding of the features of SARS-CoV-2 and the pathological features, pathophysiological mechanisms, and treatments of the cytokine storm induced by COVID-19. In addition, we suggest that the identification and treatment of the cytokine storm are important components for rescuing patients with severe COVID-19.

Individual Differences in Negative Emotion Differentiation Predict Resting-State Spontaneous Emotional Regulatory Processes.

Negative emotion differentiation facilitates emotion regulation. However, whether individual differences in negative emotion differentiation is associated with resting-state spontaneous emotion regulation remains unclear. This study aimed to explore the effect of individual differences in negative emotion differentiation on spontaneous emotional regulatory processes as indexed by resting electroencephalogram (EEG) indicators (e.g., frontal alpha asymmetry and theta/beta ratio). Participants (n = 40, M age = 21.74 years, 62% women) completed a negative emotion differentiation task. Afterward, 4 min of resting EEG data were recorded. Multiple regression results showed that negative emotion differentiation significantly predicted the alpha asymmetry at electrode pairs (F4-F3 and FP2-FP1) and the theta/beta ratio at the F3 and FZ electrode sites. Individuals with high negative emotion differentiation presented more left-lateralized activations and a lower theta/beta ratio. Taken together, these results suggest that individuals with high negative emotion differentiation show enhanced spontaneous emotional regulatory functioning. Thus, we provided the first resting-state neural evidence on emotion differentiation of spontaneous emotional regulatory functioning.

Head and neck osteosarcoma: CT and MR imaging features.

OBJECTIVE: This study aims to assess the CT and MRI features of head and neck osteosarcoma (HNO). METHODS: 37 HNOs were identified, and the following imaging characteristics were reviewed on CT and MRI. RESULTS: A total of 37 patients(age 41.5 ± 15.0 years old; 16 males, 21 females) were included in the study. Tumours occurred in the maxilla (16, 43.2%), mandible (8, 21.6%), skull base (6, 16.2%), calvarium (5, 13.5%), paranasal sinuses (1, 2.7%) and cervical soft tissue (1, 2.7%). 16 patients received radiotherapy for nasopharyngeal carcinoma. Three patients (8.1%) developed osteosarcomas related to a primary bone disease. 16 of the (43.2%) tumours demonstrated lytic density on CT scans, followed by 13 (35.1%) showing mixed density and 7 (18.9%) with sclerotic density. Matrix mineralization was present in 32 (86.5%). 3 out of 24 (12.5%) tumours showed lamellar periosteal reactions, 21 out of 24 (87.5%) showed spiculated periosteal reactions. 12 tumours showed low signal intensities on T1WI, with 16 having heterogeneous signal intensities. 10 tumours showed high signal intensities on T2WI, and 18 showed heterogeneous signal intensities. With contrast-enhanced images, 3 tumours showed homogeneous enhancement (2 osteoblastic and 1 giant cell-rich), 18 tumours showed heterogeneous enhancement (13 osteoblastic, 4 fibroblastic and 1 giant cell-rich), and 7 tumours showed peripheral enhancement (6 chondroblastic and 1 osteoblastic). These tumours were characterized by soft tissue masses with a diameter of 5.6 ± 1.8 cm. CONCLUSIONS: HNO is a rare condition and is commonly associated with previous radiation exposure. This study provides age, sex distribution, location, CT and MRI features of HNO.

CT and MRI features of calvarium and skull base osteosarcoma (CSBO).

OBJECTIVE: This study aims to assess the CT and MRI features of calvarium and skull base osteosarcoma (CSBO). METHODS: The CT and MRI features and pathological characteristics of 12 cases of pathologically confirmed CSBO were analyzed retrospectively. RESULTS: 12 patients (age range 9-67 years; 3 male, 9 female) were included in the study. Tumours occurred in skull base (7, 58.3%), temporal (4, 33.3%) and frontal (1, 8.3%). Among all, six patients received radiotherapy for nasopharyngeal carcinoma. According to pathology, 11 out of 12 tumours were high-grade (91.7%). On CT, all the tumours had soft tissue mass penetrated into cortical bone with invasion of surrounding soft tissue. Six tumours were shown to have lytic density and six were mixed density. Matrix mineralization was present in 10 cases (83.3%). On MRI, tumours presented as soft-tissue masses measuring 5.9 ± 2.4 (3.9-8.0) cm. Five tumours showed low signal intensities on T1 weighted imaging with seven having heterogeneous signal intensities. One showed low signal intensity on T2 weighted imaging, two showed high signal intensities and nine heterogeneous signal intensities. All the tumours showed low signal intensities on diffusion-weighted imaging. On contrast enhanced images, seven cases showed heterogeneous enhancement, three showed peripheral enhancementand and two showed homogeneous enhancement. Dural tail sign were detected in nine cases. CONCLUSION: CSBO is rare, and is commonly associated with previous radiation exposure. A presumptive diagnosis for osteosarcoma should be considered when calvarium and skull base tumours with osteoid matrix and duraltail sign are found. ADVANCES IN KNOWLEDGE: CT and MR features of CSBO have not been reported. The study helps to identify CSBO and other sarcomas.

A Ratiometric and Colorimetric Hemicyanine Fluorescent Probe for Detection of SO2 Derivatives and Its Applications in Bioimaging.

Based upon the intramolecular charge transfer (ICT) mechanism, a novel ratiometric fluorescent probe EB was developed to detect SO32-/HSO3-. The probe displayed both colorimetric and ratiometric responses toward SO32-/HSO3-. It displayed a quick response (within 60 s), good selectivity and high sensitivity (a detection limit of 28 nM) towards SO32-/HSO3-. The SO32-/HSO3- sensing mechanism was confirmed as the Michael addition reaction by ESI-MS. Moreover, the probe could be applied to measure the level of sulfite in real samples, like sugar and chrysanthemum, and it could also be used to detect SO32-/HSO3- in HepG2 cells through confocal fluorescence microscopy, which proved its practical application in clinical diagnosis.

Mapping the frontal alpha asymmetry indicators of habitual emotion regulation: a data-driven approach.

Frontal alpha asymmetry (FAA) has been explored extensively in affective neuroscience. To determine which FAA indicators are linked with the habitual use of emotion regulation, we recorded the resting electroencephalogram alpha activity. First, we reduced all of the FAA indicators to four factors by exploratory factor analysis. Next, we carried out a multiple regression analysis to determine which factors could significantly predict the habitual use of emotion-regulation strategies. According to the results, greater left-asymmetric activation at the dorsolateral prefrontal cortex predicted increased use of reappraisal, whereas at the ventrolateral prefrontal cortex, it was predicted by right-asymmetric activation. Greater left-asymmetric frontal activity at the posterior dorsolateral prefrontal cortex was related to increased use of distraction and suppression. These results suggest that resting FAA in the prefrontal cortex region plays a significant role in the habitual use of emotion regulation.Video abstract: http://links.lww.com/WNR/A485.