Prevalence and plasma exosome-derive microRNA diagnostic biomarker screening of adolescent idiopathic scoliosis in Yunnan Province, China.

Background: Idiopathic scoliosis significantly affects the physical and mental health of children and adolescents, with varying prevalence rates in different regions. The occurrence of idiopathic scoliosis is associated with genetic regulation and biochemical factors, but the changes in exosome-derived miRNA profiles among idiopathic scoliosis patients remain unclear. This study aimed to determine the prevalence of idiopathic scoliosis in Yunnan Province, China, and identify key exosome-derived miRNAs in idiopathic scoliosis through a cohort study. Methods: From January 2018 to December 2020, a cross-sectional study on idiopathic scoliosis in children and adolescents was conducted in Yunnan Province. A total of 84,460 students from 13 cities and counties in Yunnan Province participated in a scoliosis screening program, with ages ranging from 7 to 19 years. After confirmation through screening and imaging results, patients with severe idiopathic scoliosis and normal control individuals were selected using propensity matching. Subsequently, plasma exosome-derived miRNA sequencing and RT-qPCR validation were performed separately. Based on the validation results, diagnostic performance analysis and target gene prediction were conducted for differential plasma exosome-derived miRNAs. Results: The overall prevalence of idiopathic scoliosis in children and adolescents in Yunnan Province was 1.10%, with a prevalence of 0.87% in males and 1.32% in females. The peak prevalence was observed at age 13. Among patients diagnosed with idiopathic scoliosis, approximately 12.8% had severe cases, and there were more cases of double curvature than of single curvature, with thoracolumbar curvature being the most common in the single-curvature group. Sequencing of plasma exosome-derived miRNAs associated with idiopathic scoliosis revealed 56 upregulated and 153 downregulated miRNAs. Further validation analysis confirmed that hsa-miR-27a-5p, hsa-miR-539-5p, and hsa-miR-1246 have potential diagnostic value. Conclusions: We gained insights into the epidemiological characteristics of idiopathic scoliosis in Yunnan Province and conducted further analysis of plasma exosome-derived miRNA changes in patients with severe idiopathic scoliosis. This study has provided new insights for the prevention and diagnosis of idiopathic scoliosis, paving the way for exploring clinical biomarkers and molecular regulatory mechanisms. However, further validation and elucidation of the detailed biological mechanisms underlying these findings will be required in the future.

Environmentally relevant concentrations of benzophenones exposure disrupt intestinal homeostasis, impair the intestinal barrier, and induce inflammation in mice.

The aim of this study is to investigate the adverse effects of benzophenones (BPs) on the intestinal tract of mice and the potential mechanism. F1-generation ICR mice were exposed to BPs (benzophenone-1, benzophenone-2, and benzophenone-3) by breastfeeding from birth until weaning, and by drinking water after weaning until maturity. The offspring mice were executed on postnatal day 56, then their distal colons were sampled. AB-PAS staining, HE staining, immunofluorescence, Transmission Electron Microscope, immunohistochemistry, Western Blot and RT-qPCR were used to study the effects of BPs exposure on the colonic tissues of offspring mice. The results showed that colonic microvilli appeared significantly deficient in the high-dose group, and the expression of tight junction markers Zo-1 and Occludin was significantly down-regulated and the number of goblet cells and secretions were reduced in all dose groups, and the expression of secretory cell markers MUC2 and KI67 were decreased, as well as the expression of intestinal stem cell markers Lgr5 and Bmi1, suggesting that BPs exposure caused disruption of intestinal barrier and imbalance in the composition of the intestinal stem cell pool. Besides, the expression of cellular inflammatory factors such as macrophage marker F4/80 and tumor necrosis factor TNF-α was elevated in the colonic tissues of all dose groups, and the inflammatory infiltration was observed, which means the exposure of BPs caused inflammatory effects in the intestinal tract of F1-generation mice. In addition, the contents of Notch/Wnt signaling pathway-related genes, such as Dll-4, Notch1, Hes1, Ctnnb1and Sfrp2 were significantly decreased in each high-dose group (P < 0.05), suggesting that BPs may inhibit the regulation of Notch/Wnt signaling pathway. In conclusion, exposure to BPs was able to imbalance colonic homeostasis, disrupt the intestinal barrier, and trigger inflammation in the offspring mice, which might be realized through interfering with the Notch/Wnt signaling pathway.

Specific long-term changes in anti-SARS-CoV-2 IgG modifications and antibody functions in mRNA, adenovector, and protein subunit vaccines.

Various vaccine platforms were developed and deployed against the COVID-19 disease. The Fc-mediated functions of IgG antibodies are essential in the adaptive immune response elicited by vaccines. However, the long-term changes of protein subunit vaccines and their combinations with mRNA vaccines are unknown. A total of 272 serum and plasma samples were collected from individuals who received first to third doses of the protein subunit Medigen, the mRNA (BNT), or the adenovector AstraZeneca vaccines. The IgG subclass level was measured using enzyme-linked immunosorbent assay, and Fc-N glycosylation was measured using LC-MS/MS. Antibody-dependent phagocytosis (ADCP) and complement deposition (ADCD) of anti-spike (S) IgG antibodies were measured. IgG1 and 3 reached the highest anti-S IgG subclass level. IgG1, 2, and 4 subclass levels significantly increased in mRNA- and Medigen-vaccinated individuals. Fc-glycosylation was stable, except in female BNT vaccinees, who showed increased bisection and decreased galactosylation. Female BNT vaccinees had a higher anti-S IgG titer than that of males. ADCP declined in all groups. ADCD increased in Medigen-vaccinated individuals after the third dose. Each vaccine produced specific long-term changes in Fc structure and function. This finding is critical when selecting a vaccine platform or combination to achieve the desired immune response.

Tanshinone IIA improves Alzheimer's disease via RNA nuclear-enriched abundant transcript 1/microRNA-291a-3p/member RAS oncogene family Rab22a axis.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative condition characterized by oxidative stress and neuroinflammation. Tanshinone IIA (Tan-IIA), a bioactive compound isolated from Salvia miltiorrhiza plants, has shown potential neuroprotective effects; however, the mechanisms underlying such a function remain unclear. AIM: To investigate potential Tan-IIA neuroprotective effects in AD and to elucidate their underlying mechanisms. METHODS: Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology. To assess changes in oxidative stress and neuroinflammation, we performed enzyme-linked immunosorbent assay and western blotting. Additionally, the effect of Tan-IIA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Genetic changes related to the long non-coding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1)/microRNA (miRNA, miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction. RESULTS: In vivo, Tan-IIA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice. In vitro experiments showed that Tan-IIA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability, apoptosis, oxidative stress, and neuroinflammation. In this process, the lncRNA NEAT1 - a potential therapeutic target - is highly expressed in AD mice and downregulated via Tan-IIA treatment. Mechanistically, NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p, which activates nuclear factor kappa-B (NF-κB) signaling, leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein, which exacerbates AD. Tan-IIA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling. CONCLUSION: This study demonstrates that Tan-IIA exerts neuroprotective effects in AD by modulating the NEAT1/miR-291a-3p/Rab22a/NF-κB signaling pathway, serving as a foundation for the development of innovative approaches for AD therapy.

Social network and related factors in older people with sensory impairment in the community: Using principal component analysis.

AIM: Older people with sensory impairment are more likely to have smaller and weaker social network due to their reduced ability, which lowers their quality of life. However, there is little research on the social network in older people with sensory impairment, especially the related factors. The aim of the study was to explore the related factors of social network and to provide evidence for the improvement of social network to promote successful aging in older people with sensory impairment. METHODS: A cross-sectional study was conducted among 374 participants for hearing and vision assessment and questionnaire survey in a community, Beijing. Data were collected and analyzed by principal component analysis (PCA) and multiple logistic regression using IBM SPSS 25.0 software. RESULTS: PCA showed that there were six risk factors whose eigenvalues >1 were extracted, with a total variance of 56.555%. Multiple logistic regression analysis of principal component indicated that five factors including physical health factor, social interaction factor, psychological status factor, lifestyle factor, and family condition factor, were statistically significant (p < 0.05). CONCLUSIONS: The social network of older people with sensory impairment is relatively poor. Physical health factor, social interaction factor, psychological status factor, lifestyle factor, and family condition factor may be related factors. Medical staff should pay attention to physical, psychological and social characteristics of older people, especially with sensory impairment, to carry out necessary measures to improve social network and avoid social isolation.

Effect of Zinc and Severe Plastic Deformation on Mechanical Properties of AZ61 Magnesium Alloy.

This study investigates the effects of zinc (4 wt.%) and severe plastic deformation on the mechanical properties of AZ61 magnesium alloy through the stir-casting process. Severe plastic deformation (Equal Channel Angular Pressing (ECAP)) has been performed followed by T4 heat treatment. The microstructural examinations revealed that the addition of 4 wt.% Zn enhances the uniform distribution of ß-phase, contributing to a more uniformly corroded surface in corrosive environments. Additionally, dynamic recrystallization (DRX) significantly reduces the grain size of as-cast alloys after undergoing ECAP. The attained mechanical properties demonstrate that after a single ECAP pass, AZ61 + 4 wt.% Zn alloy exhibits the highest yield strength (YS), ultimate compression strength (UCS), and hardness. This research highlights the promising potential of AZ61 + 4 wt.% Zn alloy for enhanced mechanical and corrosion-resistant properties, offering valuable insights for applications in diverse engineering fields.

[ADAMTS13-Mediated Proteolytic Cleavage of Unusually Large von Willebrand Factor Polymers on Endothelial Cells in the Absence of Fluid Shear Stress].

OBJECTIVE: To investigate the molecular mechanism of proteolytic cleavage of unusually large von Willebrand Factor(ULVWF) on endothelial cells by ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats-13) in the absence of fluid shear stress, so as to provide a theoretical basis for the pathogenesis of thrombotic thrombocytopenic purpura (TTP) and other thrombotic disorders. METHODS: The ADAMTS13-mediated proteolysis of ULVWF on the surface of endothelial cells in the absence of fluid shear stress was observed through immunofluorescence microscopy. The variation in VWF antigen levels in the conditioned media were determined by ELISA assay. The levels of VWF and the proteolytic fragments released into the conditioned media were determined by ELISA assay and Western blot in the absence and presence of fluid shear stress or FVIII. The effect of ADAMTS13-mediated ULVWF cleavage on the normal distribution of plasma VWF multimers was evaluated by multimer analysis. Histamine stimulated human umbilical vein endothelial cells (HUVECs) were incubated with ADAMTS13 and various N- and C-terminally truncated mutants. Then the ULVWF that maintained binding to the cells were observed through immunofluorescence microscopy and the soluble ULVWF released from endothelial cells was determined by ELISA, so as to demonstrate the domains of ADAMTS13 required for proteolysis of ULVWF on endothelial cells. RESULTS: The ULVWF strings on the endothelial cell surface were rapidly proteolyzed by recombinant and plasma ADAMTS13 in the absence of fluid shear stress. This proteolytic processing of ULVWF depended on incubation time and ADAMTS13 concentration, but not shear stress and FVIII. The distribution of VWF releaseded by ADAMTS13-mediated proteolysis was quite similar to that secreted by endothelial cells under histamine stimulation, suggesting the ULVWF cleavage occured at the cell surface. The proteolysis of the ULVWF on endothelial cells required the Cys-rich(CysR) and spacer domains, but not the TSP1 2-8 and CUB domains of ADAMTS13. CONCLUSION: The ULVWF polymers on endothelial cells are sensitive to ADAMTS13-mediated cleavage even in the absence of fluid shear stress. The findings provide novel insight into the molecular mechanism of ADAMTS13-mediated ULVWF cleavage at the cellular level and may contribute to understanding of the pathogenesis of TTP and other thrombotic disorders.

Unveiling the Impact of Light-Induced Acceptor-Generated ROS on Device Stability in Organic Photovoltaics.

The intrinsic stability of the acceptor is a crucial component of the photovoltaic device stability. In this study, we investigated the efficiency and stability of the nonfused-ring acceptors LC8 and BC8 under indoor light conditions. Interestingly, we found that devices based on BC8 with terminal side chains exhibited a higher indoor efficiency and stability. Through accelerated aging experiments, we discovered that the acceptors generate singlet oxygen under light exposure with BC8 demonstrating lower levels of ROS compared to LC8. We attribute this difference to the modulation of the acceptor aggregation orientation. Furthermore, the generated reactive oxygen species (ROS) further deteriorate the acceptor structure, and this phenomenon is also observed in high-efficiency acceptor structures, such as Y6. Our research reveals important mechanisms of acceptor photo-oxidation processes, providing a theoretical basis for enhancing the intrinsic stability of acceptors.

Acanthopanax senticosus cultures fermented by Lactobacillus rhamnosus enhanced immune response through improvement of antioxidant activity and inflammation in crucian carp (Carassius auratus).

Lactic acid bacteria (LAB) have been recognized as safe microorganism that improve micro-flora disturbances and enhance immune response. A well-know traditional herbal medicine, Acanthopanax senticosus (As) was extensively utilized in aquaculture to improve growth performance and disease resistance. Particularly, the septicemia, skin wound and gastroenteritis caused by Aeromonas hydrophila threaten the health of aquatic animals and human. However, the effects of probiotic fermented with A. senticosus product on the immune regulation and pathogen prevention in fish remain unclear. Here, the aim of the present study was to elucidate whether the A. senticosus fermentation by Lactobacillus rhamnosus improve immune barrier function. The crucian carp were fed with basal diet supplemented with L. rhamnosus fermented A. senticosus cultures at 2 %, 4 %, 6 % and 8 % bacterial inoculum for 8 weeks. After trials, the weight gain rate (WGR), specific growth rate (SGR) were significantly increased, especially in LGG-6 group. The results confirmed that the level of the CAT, GSH-PX, SOD, lysozyme, and MDA was enhanced in fish received with probiotic fermented product. Moreover, the L. rhamnosus fermented A. senticosus cultures could trigger innate and adaptive immunity, including the up-regulation of the C3, C4, and IgM concentration. The results of qRT-PCR revealed that stronger mRNA transcription of IL-1ß, IL-10, IFN-γ, TNF-α, and MyD88 genes in the liver, spleen, kidney, intestine and gills tissues of fish treated with probiotic fermented with A. senticosus product. After infected with A. hydrophila, the survival rate of the LGG-2 (40 %), LGG-4 (50 %), LGG-6 (60 %), LGG-8 (50 %) groups was higher than the control group. Meanwhile, the pathological damage of the liver, spleen, head-kidney, and intestine tissues of probiotic fermentation-fed fish could be alleviated after pathogen infection. Therefore, the present work indicated that L. rhamnosus fermented A. senticosus could be regard as a potential intestine-target therapy strategy to protecting fish from pathogenic bacteria infection.

A Dataset on Population Activity Patterns in Typical Regions of North China.

This data article describes the "Typical Regional Activity Patterns" (TRAP) dataset, which is based on the Tackling Key Problems in Air Pollution Control Program. In order to explore the interaction between air pollution and physical activity, we collected activity patterns of 9,221 residents with different occupations and lifestyles for three consecutive days in typical regions (Jinan and Baoding) where air pollutant concentrations were higher than those in neighboring areas. The TRAP dataset consists of two aspects of information: demographic indicators (personal information, occupation, personal habits, and living situation) and physical activity pattern data (activity location and intensity); additionally, the exposure measures of physical activity patterns are included, which data users can match to various endpoints for their specific purpose. This dataset provides evidence for exploring the attributes of activity patterns of residents in northern China and for interdisciplinary researchers to develop strategies and measures for health education and health promotion.

Hemorrhagic bronchitis caused by carbapenem-resistant Acinetobacter baumannii infection: A case report.

Carbapenem-resistant Acinetobacter baumannii (CR-AB) is rarely found in community respiratory infections, and there are currently no reports of hemorrhagic bronchitis caused by its infection. This work presents a case of bronchial bleeding in a diabetic patient who acquired a community-acquired infection of CR-AB. Treatment with levofloxacin was unsuccessful, as the patient's hemoptysis symptoms recur. The patient was treated with minocycline based on the drug sensitivity test, resulting in the disappearance of hemoptysis symptoms. The patient was subjected to follow-up by phone for three months and did not experience any further hemoptysis symptoms. This case highlights that CR-AB infection causes hemorrhagic bronchitis, and the antimicrobial treatment should be based on drug sensitivity results.

Construction and validation of m6A-related diagnostic model for psoriasis.

Background: Psoriasis is a chronic immune-mediated inflammatory disease. N6-methyladenosine (m6A) is involved in numerous biological processes in both normal and diseased states. Herein, we aimed to explore the potential role of m6A regulators in the diagnosis of psoriasis and predict molecular mechanisms by which m6A regulators impact psoriasis. Methods: GSE30999 (170 human skin tissue samples) and GSE13355 (180 human skin tissue samples) were downloaded as the training analysis dataset and validation dataset respectively. M6A-related genes were obtained from the literature and their expression levels in GSE30999 samples were measured to identify M6A-related DEGs between psoriasis lesions (LS) and non-lesional lesions (NL). We identified m6A-related DEGs using differential expression analysis and assessed their interactions through correlation analysis and network construction. A logistic regression analysis followed by LASSO optimization was employed to select m6A-related DEGs for the construction of a diagnostic model. The performance of the model was validated using support vector machine (SVM) methodology with sigmoid kernel function and extensive cross-validation. Additionally, the correlation between m6A-related DEGs and immune cell infiltration was analyzed, as well as the association of these DEGs with psoriasis subtypes. Functional analysis of the m6A-related DEGs included the construction of regulatory networks involving miRNAs, transcription factors (TFs), and small-molecule drugs. The m6A modification patterns were also explored by examining the gene expression differences between psoriasis subtypes and their enriched biological pathways. Finally, the expression of significant m6A regulators involved in the diagnostic model was examined by RT-qPCR. Results: In this study, ten optimal m6A-related DEGs were identified, including FTO, IGF2BP2, METTL3, YTHDC1, ZC3H13, HNRNPC, IGF2BP3, LRPPRC, YTHDC2, and HNRNPA2B1. A diagnostic model based on these m6A-related DEGs was constructed, demonstrating high diagnostic accuracy with an area under the curve (AUC) in GSE30999 and GSE13355 of 0.974 and 0.730, respectively. Meanwhile, the expression level of m6A regulators verified by RT-qPCR was consistent with the results in GSE30999. The infiltration of activated mast cells and NK cells was significantly associated with all ten m6A-related DEGs in psoriasis. Among them, YTHDC1, HNRNPC, and FTO were targeted by most miRNAs and were regulated by nine related TFs. Therefore, patients may benefit from dorsomorphin and cyclosporine therapy. Between the two subgroups, 1,592 DEGs were identified, including LRPPRC and METTL3. These DEGs were predicted to be involved in neutrophil activation, cytokine-cytokine receptor interactions, and chemokine signaling pathways. Conclusions: A diagnostic model based on ten m6A-related DEGs in patients with psoriasis was constructed, which may provide early diagnostic biomarkers and therapeutic targets for psoriasis.

Nanodrug delivery systems for regulating microglial polarization in ischemic stroke treatment: A review.

The incidence of ischemic stroke (IS) is rising in tandem with the global aging population. There is an urgent need to delve deeper into the pathological mechanisms and develop new neuroprotective strategies. In the present review, we discuss the latest advancements and research on various nanodrug delivery systems (NDDSs) for targeting microglial polarization in IS treatment. Furthermore, we critically discuss the different strategies. NDDSs have demonstrated exceptional qualities to effectively permeate the blood-brain barrier, aggregate at the site of ischemic injury, and target specific cell types within the brain when appropriately modified. Consequently, NDDSs have considerable potential for reshaping the polarization phenotype of microglia and could be a prospective therapeutic strategy for IS. The treatment of IS remains a challenge. However, this review provides a new perspective on neuro-nanomedicine for IS therapies centered on microglial polarization, thereby inspiring new research ideas and directions.

Social support as a mediator between mental health and stigma among newly HIV-positive men who have sex with men.

OBJECTIVES: The sociocultural context of China gives rise to unique experiences of HIV-related stigma and adverse impacts on mental health among men who have sex with men (MSM) living with HIV. However, few studies have explored the stigma among families in the cultural context of China and the role of social support as a mediator to explain how HIV-related stigma results in poor psychological well-being. This study aims to test the mediating effect of social support between HIV-related stigma and family stigma on the mental health of MSM. METHODS: This cross-sectional study recruited newly MSM with HIV in two cities (Beijing and Wuhan) in China as participants from February 2021 to August 2022. A total of 257 MSM with HIV were recruited for the study. The mediating effects were examined using mediation models (SAS PROC CAUSALMED). RESULTS: The overall total effect of HIV-related stigma on mental health was ß = -1.483 (bootstrap 95% CI = -1.881, -1.104 p < 0.001), and the mediating effect of social support was ß = -0.321 (bootstrap 95% CI = -0.571, -0.167 p = .001). A higher level of stigma from family predicts lower mental health with an overall total effect of ß = -1.487 (bootstrap 95% CI = -1.823, -1.101 p < 0.001), while the indirect effect (mediation effect) of social support on mental health is ß = -0.281 (bootstrap 95% CI = -0.477, -0.142 p = .003). CONCLUSIONS: Given the mediating effect of social support on mental health, programs enhancing social support and decreasing stigmatization should be designed to improve the mental health of MSM with HIV, the interventions are needed at both the family and community levels. Public health campaigns in China that frame HIV and same-sex behavior as chronic issues and normal phenomena can correct misinformation related to HIV and MSM that leads to stigma and negative emotional reactions.

Lineage-specific canonical and non-canonical activity of EZH2 in advanced prostate cancer subtypes.

Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase and emerging therapeutic target that is overexpressed in most castration-resistant prostate cancers and implicated as a driver of disease progression and resistance to hormonal therapies. Here we define the lineage-specific action and differential activity of EZH2 in both prostate adenocarcinoma (PRAD) and neuroendocrine prostate cancer (NEPC) subtypes of advanced prostate cancer to better understand the role of EZH2 in modulating differentiation, lineage plasticity, and to identify mediators of response and resistance to EZH2 inhibitor therapy. Mechanistically, EZH2 modulates bivalent genes that results in upregulation of NEPC-associated transcriptional drivers (e.g., ASCL1) and neuronal gene programs, and leads to forward differentiation after targeting EZH2 in NEPC. Subtype-specific downstream effects of EZH2 inhibition on cell cycle genes support the potential rationale for co-targeting cyclin/CDK to overcome resistance to EZH2 inhibition.

Neural Network Dynamics and Brain Oscillations Underlying Aberrant Inhibitory Control in Internet Addiction.

Previous studies have reported a role of alterations in the brain's inhibitory control mechanism in addiction. Mounting evidence from neuroimaging studies indicates that its key components can be evaluated with brain oscillations and connectivity during inhibitory control. In this study, we developed an internet-related stop-signal task with electroencephalography (EEG) signal recorded to investigate inhibitory control. Healthy controls and participants with Internet addiction were recruited to participate in the internet-related stop-signal task with 19-channel EEG signal recording, and the corresponding event-related potentials and spectral perturbations were analyzed. Brain effective connections were also evaluated using direct directed transfer function. The results showed that, relative to the healthy controls, participants with Internet addiction had increased Stop-P3 during inhibitory control, suggesting that they have an altered neural mechanism in impulsive control. Furthermore, participants with Internet addiction showed increased low-frequency synchronization and decreased alpha and beta desynchronization in the middle and right frontal regions compared to healthy controls. Aberrant brain effective connectivity was also observed, with increased occipital-parietal and intra-occipital connections, as well as decreased frontal-paracentral connection in participants with Internet addiction. These results suggest that physiological signals are essential in future implementations of cognitive assessment of Internet addiction to further investigate the underlying mechanisms and effective biomarkers.

Human transcriptome array analysis and diffusion tensor imaging in attention-deficit/hyperactivity disorder.

The mRNA markers identified using microarray assay and diffusion tensor magnetic resonance imaging (DTI) were applied to elucidate the pathophysiology of attention-deficit hyperactivity disorder (ADHD). First, we obtained total RNA from leukocytes from three children with ADHD and three healthy controls for analysis with microarray assays. Subsequently, we applied real-time quantitative polymerase chain reaction (qRT‒PCR) assays to validate the differential expression of 7 genes (COX7B, CYCS, TFAM, UTP14A, ZNF280C, IFT57 and NDUFB5) between 130 ADHD patients and 70 controls, and we built an ADHD prediction model based on the ΔCt values of aforementioned seven genes (AUROC = 0.98). Finally, in a validation group (28 patients with ADHD and 27 healthy controls), mRNA expression of the above seven genes also significantly differentiated ADHD patients from controls (AUROC value = 0.91). The DTI analysis showed increased fractional anisotropy (FA) of the forceps minor, superior corona radiata, posterior corona radiata and anterior corona radiata in ADHD patients. Moreover, the FA of the right superior corona radiata tract was positively correlated with ΔCt levels of the COX7B gene and the IFT57 gene. The results shed a new light on a genetic profile of ADHD that may help in deciphering the white matter microstructural features in disease pathogenesis.

Correlation of potential diagnostic biomarkers (circulating miRNA and protein) of bipolar II disorder.

OBJECTIVES: We previously identified certain peripheral biomarkers of bipolar II disorder (BD-II) including circulating miRNAs (miR-7-5p, miR-142-3p, miR-221-5p, and miR-370-3p) and proteins (Matrix metallopeptidase 9 (MMP9), phenylalanyl-tRNA synthetase subunit beta (FARSB), peroxiredoxin 2 (PRDX2), carbonic anhydrase 1 (CA-1), and proprotein convertase subtilisin/kexin type 9 (PCSK9)). We try to explore the connection between these biomarkers. METHODS: We explored correlations between the peripheral levels of above circulating miRNAs and proteins in our previously collected BD-II (N = 96) patients and control (N = 115) groups. We further searched TargetScan and BioGrid websites to identify direct and indirect interactions between these protein-coding genes and circulating miRNAs. RESULTS: In the BD-II group, we identified significant correlations between the miR-221-5p and CA-1 (rho = -0.323, P = 0.001), FARSB (rho = 0.251, P = 0.014), MMP-9 (rho = 0.313, P = 0.002) and PCSK9 (rho = 0.252, P = 0.014). The miR-370-3p also significantly correlated with FARSB expression (rho = 0.330, P = 0.001) and PCSK9 expression (rho = 0.221, P = 0.031) in the BD-II group. Our findings were in line with the modulating axis identified from TargetScan and BioGrid, miR-221-5p/CA-1/MMP9 and miR-370-3p/FARSB/PCSK9, suggesting their association with BD-II. CONCLUSION: Our result supported that peripheral candidate miRNA and protein biomarkers may interact in BD-II. We concluded that miR-221-5p/CA-1/MMP9 and miR-370-3p/FARSB/PCSK9 axes might act a critical role in the pathomechanism of BD-II.

Hidden diversity of Pestalotiopsis and Neopestalotiopsis (Amphisphaeriales, Sporocadaceae) species allied with the stromata of entomopathogenic fungi in Taiwan.

Pestalotiopsissensu lato, commonly referred to as pestalotiopsis-like fungi, exhibit a broad distribution and are frequently found as endophytes, saprobes and pathogens across various plant hosts. The taxa within pestalotiopsis-like fungi are classified into three genera viz. Pestalotiopsis, Pseudopestalotiopsis and Neopestalotiopsis, based on the conidial colour of their median cells and multi-locus molecular phylogenies. In the course of a biodiversity investigation focusing on pestalotiopsis-like fungi, a total of 12 fungal strains were identified. These strains were found to be associated with stromata of Beauveria, Ophiocordyceps and Tolypocladium in various regions of Taiwan from 2018 to 2021. These strains were evaluated morphologically and multi-locus phylogenetic analyses of the ITS (internal transcribed spacer), tef1-α (translation elongation factor 1-α) and tub2 (beta-tubulin) gene regions were conducted for genotyping. The results revealed seven well-classified taxa and one tentative clade in Pestalotiopsis and Neopestalotiopsis. One novel species, Pestalotiopsismanyueyuanani and four new records, N.camelliae-oleiferae, N.haikouensis, P.chamaeropis and P.hispanica, were reported for the first time in Taiwan. In addition, P.formosana and an unclassified strain of Neopestalotiopsis were identified, based on similarities of phylogeny and morphology. However, the data obtained in the present study suggest that the currently recommended loci for species delimitation of pestalotiopsis-like fungi do not deliver reliable or adequate resolution of tree topologies. The in-vitro mycelial growth rates of selected strains from these taxa had an optimum temperature of 25 °C, but growth ceased at 5 °C and 35 °C, while all the strains grew faster under alkaline than acidic or neutral pH conditions. This study provides the first assessment of pestalotiopsis-like fungi, associated with entomopathogenic taxa.

Integrated analysis of differentially expressed genes and miRNA expression profiles in dilated cardiomyopathy.

Background: Although dilated cardiomyopathy (DCM) is a prevalent form of cardiomyopathy, the molecular mechanisms underlying its pathogenesis and progression remain poorly understood. It is possible to identify and validate DCM-associated genes, pathways, and miRNAs using bioinformatics analysis coupled with clinical validation methods. Methods: Our analysis was performed using 3 mRNA datasets and 1 miRNA database. We employed several approaches, including gene ontology (GO) analysis, KEGG pathway enrichment analysis, protein-protein interaction networks analysis, and analysis of hub genes to identify critical genes and pathways linked to DCM. We constructed a regulatory network for DCM that involves interactions between miRNAs and mRNAs. We also validated the differently expressed miRNAs in clinical samples (87 DCM ，83 Normal) using qRT-PCR.The miRNAs' clinical value was evaluated by receiver operating characteristic curves (ROCs). Results: 78 differentially expressed genes (DEGs) and 170 differentially expressed miRNAs (DEMs) were associated with DCM. The top five GO annotations were collagen-containing extracellular matrix, cell substrate adhesion, negative regulation of cell differentiation, and inflammatory response. The most enriched KEGG pathways were the Neurotrophin signaling pathway, Thyroid hormone signaling pathway, Wnt signaling pathway, and Axon guidance. In the PPI network, we identified 10 hub genes, and in the miRNA-mRNA regulatory network, we identified 8 hub genes and 15 miRNAs. In the clinical validation, we found 13 miRNAs with an AUC value greater than 0.9. Conclusion: Our research offers novel insights into the underlying mechanisms of DCM and has implications for identifying potential targets for diagnosis and treatment of this condition.