Downregulation of hsa_circ_0006620 inhibits the malignant progression of prostate cancer by regulation of the miR-502-3p/HK2 axis mediated by aerobic glycolysis.

Circular RNAs (circRNA) are a class of covalently-closed, single-stranded RNAs that have been implicated in cancer progression due to their regulation of metabolism. However, the roles of circRNA in prostate cancer remain largely unknown. In this study, fluorescence in situ hybridization and RT-qPCR were used to investigate hsa_circ_0006620 expressions in both prostate cancer cells and tissues, after high-throughput sequencing. The luciferase reporter assay was used to identify hsa_circ_0006620 downstream targets. Transwell migration assays, 5-ethynyl-20-deoxyuridine assays, and Cell Counting Kit-8assays were used to investigate both proliferation and migration. In vivo tumorigenesis and metastasis assays were performed to investigate the role of hsa_circ_0006620 in prostate cancer. The results showed that hsa_circ_0006620 expression increased in prostate cancer cells and tissues. Hsa_circ_0006620 downregulation inhibited prostate cancer cell proliferation as well as in vivo and in vitro migrations. The luciferase results validated that miR-502-3p and hexokinase 2 (HK2) were hsa_circ_0006620 downstream targets. HK2 overexpression or miR-502-3p inhibition reversed prostate cancer cell migration after hsa_circ_0006620 silencing. The study also found that overexpression of HK2 or inhibition of prostate cancer reversed aerobic glycolysis after hsa_circ_0006620 silencing. In summary, the results showed thathsa_circ_0006620 downregulation inhibited prostate cancerby regulation of the miR-502-3p/HK2 axis mediated by aerobic glycolysis.

Directional Characteristic Enhancement of an Omnidirectional Detection Sensor Enabled by Strain Partitioning Effects in a Periodic Composite Hole Substrate.

An omnidirectional stretchable strain sensor with high resolution is a critical component for motion detection and human-machine interaction. It is the current dominant solution to integrate several consistent units into the omnidirectional sensor based on a certain geometric structure. However, the excessive similarity in orientation characteristics among sensing units restricts orientation recognition due to their closely matched strain sensitivity. In this study, based on strain partition modulation (SPM), a sensitivity anisotropic amplification strategy is proposed for resistive strain sensors. The stress distribution of a sensitive conductive network is modulated by structural parameters of the customized periodic hole array introduced underneath the elastomer substrate. Meanwhile, the strain isolation structures are designed on both sides of the sensing unit for stress interference immune. The optimized sensors exhibit excellent sensitivity (19 for 0-80%; 109 for 80%-140%; 368 for 140%-200%), with nearly a 7-fold improvement in the 140%-200% interval compared to bare elastomer sensors. More importantly, a sensing array composed of multiple units with different hole configurations can highlight orientation characteristics with amplitude difference between channels reaching up to 29 times. For the 48-class strain-orientation decoupling task, the recognition rate of the sensitivity-differentiated layout sensor with the lightweight deep learning network is as high as 96.01%, superior to that of 85.7% for the sensitivity-consistent layout. Furthermore, the application of the sensor to the fitness field demonstrates an accurate recognition of the wrist flexion direction (98.4%) and spinal bending angle (83.4%). Looking forward, this methodology provides unique prospects for broader applications such as tactile sensors, soft robotics, and health monitoring technologies.

Perceptual representations in L1 and L2 spatial and abstract language processing: applying an innovative sentence-diagram verification paradigm.

Introduction: Perceptual representations in language comprehension were examined using sentence-picture verification tasks. However, concerns have been raised regarding the suitability of concrete pictures for representing abstract concepts compared to image-schematic diagrams. To assess the perceptual representations of spatial and abstract domains in both first language (L1) and second language (L2) processing, the study tests bilingual speakers' mental imagery on the basis of the simulation-based L1 comprehension model and proposes a simulation-based L2 comprehension model, supported by empirical evidence from an innovative sentence-diagram verification paradigm. Methods: 41 adult L1 Mandarin Chinese speakers participated in the study. 21 participants completed the Chinese sentence-diagram verification task (Experiment 1), while 20 participants completed the translation-equivalent version in L2 English (Experiment 2). Participants read a sentence [e.g., A diligent worker walked into the office (spatial sense); A strong team headed into the final (abstract sense)] at their self-paced speed, followed by a congruent (e.g., into diagram) or incongruent diagram (e.g., out-of diagram), and made binary judgments to verify spatial configurations between the sentence and diagram. Semantic rating tasks in both Chinese and English were also conducted to validate congruency between diagrams and sentences in both languages. Results and discussion: Results from Experiment 1 indicate overall compatibility effects on L1 Chinese processing, unaffected by directional verbs or abstractness of sense. Results from Experiment 2 reveal interference effects on L2 English processing, with interference observed only after reading sentences encoding spatial senses, not abstract senses. Aligning with previous findings using sentence-picture verification tasks, the current findings confirm the weaker mental simulation effects in L2 processing compared to L1 processing. These findings extend the existing simulation-based L1 comprehension model, provide empirical support for the proposed simulation-based L2 comprehension model, and validate the innovative sentence-diagram verification paradigm for examining image-schematic representations in spatial and abstract language processing among Chinese-English bilinguals. The paradigm holds significant potential for research on perceptual representations in processing a broader range of grammatical and semantic properties during both online and offline L1 and L2 comprehension.

Identification of a potential sialylation-related pattern for the prediction of prognosis and immunotherapy response in small cell lung cancer.

Our study aimed to establish a novel system for quantifying sialylation patterns and comprehensively analyze their relationship with immune cell infiltration (ICI) characterization, prognosis, and therapeutic sensitivity in small cell lung cancer (SCLC). We conducted a thorough assessment of the sialylation patterns in 100 patients diagnosed with SCLC. Our primary focus was on analyzing the expression levels of 7 prognostic sialylation-related genes. To evaluate and quantify these sialylation patterns, we devised a sialylation score (SS) using principal component analysis algorithms. Prognostic value and therapeutic sensitivities were then evaluated using multiple methods. The GSE176307 was used to verify the predictive ability of SS for immunotherapy. Our study identified 2 distinct clusters based on sialylation patterns. Sialylation cluster B exhibited a lower level of induced ICI therapy and immune-related signaling enrichment, which was associated with a poorer prognosis. Furthermore, there were significant differences in prognosis, response to targeted inhibitors, and immunotherapy between the high and low SS groups. Patients with high SS were characterized by decreased immune cell infiltration, chemokine and immune checkpoint expression, and poorer response to immunotherapy, while the low SS group was more likely to benefit from immunotherapy. This work showed that the evaluation of sialylation subtypes will help to gain insight into the heterogeneity of SCLC. The quantification of sialylation patterns played a non-negligible role in the prediction of ICI characterization, prognosis and individualized therapy strategies.

Combination of arsenic trioxide and apatinib synergistically inhibits small cell lung cancer by down-regulating VEGFR2/mTOR and Akt/c-Myc signaling pathway via GRB10.

BACKGROUND: Small cell lung carcinoma (SCLC) is characterized by -poor prognosis, -high predilection for -metastasis, -proliferation, and -absence of newer therapeutic options. Elucidation of newer pathways characterizing the disease may allow for development of targeted therapies and consequently favorable outcomes. METHODS: The current study explored the combinatorial action of arsenic trioxide (ATO) and apatinib (APA) in vitro and in vivo. In vitro models were tested using -H446 and -H196 SCLC cell lines. The ability of drugs to reduce -metastasis, -cell proliferation, and -migration were assessed. Using bioinformatic analysis, differentially expressed genes were determined. Gene regulation was assessed using gene knock down models and confirmed using Western blots. The in vivo models were used to confirm the resolution of pathognomic features in the presence of the drugs. Growth factor receptor bound protein (GRB) 10 expression levels of human small cell lung cancer tissues and adjacent tissues were detected by IHC. RESULTS: In combination, ATO and APA were found to significantly reduce -cell proliferation, -migration, and -metastasis in both the cell lines. Cell proliferation was found to be inhibited by activation of Caspase-3, -7 pathway. In the presence of drugs, it was found that expression of GRB10 was stabilized. The silencing of GRB10 was found to negatively regulate the VEGFR2/Akt/mTOR and Akt/GSK-3ß/c-Myc signaling pathway. Concurrently, absence of metastasis and reduction of tumor volume were confirmed in vivo. The immunohistochemical results confirmed that the expression level of GRB10 in adjacent tissues was significantly higher than that in human small cell lung cancer tissues. CONCLUSIONS: Synergistically, ATO and APA have a more significant impact on inhibiting cell proliferation than each drug independently. ATO and APA may be mediating its action through the stabilization of GRB10 thus acting as a tumor suppressor. We thus, preliminarily report the impact of GRB10 stability as a target for SCLC treatment.

Investigating cortical complexity and connectivity in rats with schizophrenia.

Background: The above studies indicate that the SCZ animal model has abnormal gamma oscillations and abnormal functional coupling ability of brain regions at the cortical level. However, few researchers have focused on the correlation between brain complexity and connectivity at the cortical level. In order to provide a more accurate representation of brain activity, we studied the complexity of electrocorticogram (ECoG) signals and the information interaction between brain regions in schizophrenic rats, and explored the correlation between brain complexity and connectivity. Methods: We collected ECoG signal from SCZ rats. The frequency domain and time domain functional connectivity of SCZ rats were evaluated by magnitude square coherence and mutual information (MI). Permutation entropy (PE) and permutation Lempel-Ziv complexity (PLZC) were used to analyze the complexity of ECoG, and the relationship between them was evaluated. In addition, in order to further understand the causal structure of directional information flow among brain regions, we used phase transfer entropy (PTE) to analyze the effective connectivity of the brain. Results: Firstly, in the high gamma band, the complexity of brain regions in SCZ rats is higher than that in normal rats, and the neuronal activity is irregularity. Secondly, the information integration ability of SCZ rats decreased and the communication of brain network information was hindered at the cortical level. Finally, compared with normal rats, the causal relationship between brain regions of SCZ rats was closer, but the information interaction center was not clear. Conclusion: The above findings suggest that at the cortical level, complexity and connectivity are valid biomarkers for identifying SCZ. This bridges the gap between peak potentials and EEG. This may help to understand the pathophysiological mechanisms at the cortical level in schizophrenics.

Preparation and Adsorption Photocatalytic Properties of PVA/TiO2 Colloidal Photonic Crystal Films.

Polyvinyl alcohol (PVA)/TiO2/colloidal photonic crystal (CPC) films with photocatalytic properties are presented, where TiO2 nanoparticles were introduced into the PVA gel network. Such PVA/TiO2/CPC films possess three-dimensional periodic structures that are supported with a PVA/TiO2 composite gel. The unique structural color of CPCs can indicate the process of material preparation, adsorption, and desorption. The shift of diffraction peaks of CPCs can be more accurately determined using fiber-optic spectroscopy. The effect of the PVA/TiO2/CPC catalyst films showed better properties as the degradation of methylene blue (MB) by the PVA/TiO2/CPC film catalyst in 4 h was 77~90%, while the degradation of MB by the PVA/TiO2 film was 33% in 4 h, indicating that the photonic crystal structure was 2.3~2.7 times more effective than that of the bulk structure.

A Probabilistic Approach to Estimate the Temporal Order of Pathway Mutations Accounting for Intra-Tumor Heterogeneity.

The development of cancer involves the accumulation of somatic mutations in several essential biological pathways. Delineating the temporal order of pathway mutations during tumorigenesis is crucial for comprehending the biological mechanisms underlying cancer development and identifying potential targets for therapeutic intervention. Several computational and statistical methods have been introduced for estimating the order of somatic mutations based on mutation profile data from a cohort of patients. However, one major issue of current methods is that they do not take into account intra-tumor heterogeneity (ITH), which limits their ability to accurately discern the order of pathway mutations. To address this problem, we propose PATOPAI, a probabilistic approach to estimate the temporal order of mutations at the pathway level by incorporating ITH information as well as pathway and functional annotation information of mutations. PATOPAI uses a maximum likelihood approach to estimate the probability of pathway mutational events occurring in a specific sequence, wherein it focuses on the orders that are consistent with the phylogenetic structure of the tumors. Applications to whole exome sequencing data from The Cancer Genome Atlas (TCGA) illustrate our method's ability to recover the temporal order of pathway mutations in several cancer types.

Lamivudine protects mice from gastric ulcer by activating PGK1 to suppress ferroptosis.

Gastric ulcer is a highly prevalent digestive tract disease across the world, which is recurrent and hard to cure, sometimes transforming into gastric cancer if left untreated, posing great threat to human health. To develop new medicines for gastric ulcer, we ran a series of screens with ethanol stress model in GES-1 cells, and we uncovered that lamivudine rescued cells from ethanol toxicity. Then, we confirmed this discovery using the well-established ethanol-induced gastric ulcer model in mice and our findings suggest that lamivudine can directly activate phosphoglycerate kinase 1 (PGK1, EC 2.7.2.3), which binds and stimulates superoxide dismutase 1 (SOD1, EC 1.15.1.1) to inhibit ferroptosis and ultimately improve gastric ulcer. Moreover, AAV-PGK1 exhibited comparable gastroprotective effects to lamivudine. The findings are expected to offer novel therapeutic strategies for gastric ulcer, encompassing both lamivudine and AAV-PGK1.

Novel insights into causal effects of serum lipids, lipid metabolites, and lipid-modifying targets on the risk of intracerebral aneurysm.

INTRODUCTION: Different serum lipid and lipid-lowering agents are reported to be related to the occurrence of intracerebral aneurysm (IA). However, the causal relationship between them requires further investigation. PATIENTS AND METHODS: Mendelian randomization (MR) analysis was performed on IA and its subtypes by using instrumental variants associated with six serum lipids, 249 lipid metabolic traits, and 10 lipid-lowering agents that were extracted from the largest genome-wide association study. Phenome-wide MR analyses were conducted to identify potential phenotypes associated with significant lipid-lowering agents. RESULTS: After multiple comparison adjustments (p < 0.0083), genetically proxied triglyceride (TG) (odds ratio [OR] 1.25, 95% confidence interval [CI] 1.07-1.47, p = 0.005) and high-density lipoprotein cholesterol (HDL-C) levels (OR 0.93, 95% CI 0.89-0.98, p = 0.008) showed causal relationships with the risk of IA. Four lipid metabolic traits showed a causal relationship with the risk of IA (p < 0.0002). As confirmed by drug target MR, the causal relationship between the HMGCR target and IA, HMGCR target and subarachnoid hemorrhage (SAH), ANGPTL3 target and SAH, CETP target, and SAH remained statistically significant after multiple adjustments (p < 0.005). Additionally, phenome-wide MR did not identify other diseases linked to the significant lipid-lowering agent (p < 6.39 × 10-5). DISCUSSION AND CONCLUSION: This study not only supports that serum lipids (TG and HDL-C) are associated with IA but also confirms the positive effect and absence of safety concerns of intervening HMGCR, ANGPTL3, and CETP targets in IA and its subtypes, opening new avenues for IA treatment.

Combining blood pressure variability and heart rate variability to analyze the autonomic nervous function of rotenone induced Parkinson's rat model.

BACKGROUND: Parkinson's patients have significant autonomic dysfunction, early detect the disorder is a major challenge. To assess the autonomic function in the rat model of rotenone induced Parkinson's disease (PD), Blood pressure and ECG signal acquisition are very important. NEW METHOD: We used telemetry to record the electrocardiogram and blood pressure signals from awake rats, with linear and nonlinear analysis techniques calculate the heart rate variability (HRV) and blood pressure variability (BPV). we applied nonlinear analysis methods like sample entropy and detrended fluctuation analysis to analyze blood pressure signals. Particularly, this is the first attempt to apply nonlinear analysis to the blood pressure evaluate in rotenone induced PD model rat. RESULTS: HRV in the time and frequency domains indicated sympathetic-parasympathetic imbalance in PD model rats. Linear BPV analysis didn't reflect changes in vascular function and blood pressure regulation in PD model rats. Nonlinear analysis revealed differences in BPV, with lower sample entropy results and increased detrended fluctuation analysis results in the PD group rats. COMPARISON WITH EXISTING METHODS AND CONCLUSIONS: our experiments demonstrate the ability to evaluate autonomic dysfunction in models of Parkinson's disease by combining the analysis of BPV with HRV, consistent with autonomic impairment in PD patients. Nonlinear analysis by blood pressure signal may help in early detection of the PD. It indicates that the fluctuation of blood pressure in the rats in the rotenone model group tends to be regular and predictable, contributes to understand the PD pathophysiological mechanisms and to find strategies for early diagnosis.

Correction of plasma fat-soluble vitamin levels by blood lipids in elderly patients with coronary heart disease.

This study aims to investigate the correlation between plasma fat-soluble vitamin levels and blood lipid in elderly patients with coronary heart disease (CHD). A total of 120 participants were enrolled, including 60 CHD patients and 60 controls without CHD. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to quantify plasma levels of vitamins A, D3, E, and K. Data analysis was conducted using the statistical analysis system module of MetaboAnalyst 5.0. The CHD group showed significantly higher levels of plasma total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) but not high-density lipoprotein cholesterol (HDL-C) compared to controls. The CHD group exhibited significantly higher plasma levels of VA and VE, positively correlating with TC, TG, and LDL-C. After adjusted by TG levels, the CHD group had significantly lower plasma levels of VA and VE, negatively correlating with TC, TG, and LDL-C. The CHD group also had significantly lower concentrations of VD3, independent of TG modification, compared to controls. VD3 negatively correlated with TC, TG, and LDL-C. Elderly individuals with CHD display abnormal blood lipid metabolism, and fat-soluble vitamins adjusted by TG levels can more accurately and timely response to implicit fat-soluble vitamins deficiency in CHD patients.

Metabolome-Wide Mendelian Randomization Assessing the Causal Role of Serum and Cerebrospinal Metabolites in Traumatic Brain Injury.

Previous studies have identified metabolites as biomarkers or potential therapeutic targets for traumatic brain injury (TBI). However, the causal association between them remains unknown. Therefore, we investigated the causal effect of serum metabolites and cerebrospinal fluid (CSF) metabolites on TBI susceptibility through Mendelian randomization (MR). Genetic variants related to metabolites and TBI were extracted from a corresponding genome-wide association study (GWAS). Causal effects were estimated through the inverse variance weighted approach, supplemented by a weighted median, weight mode, and the MR-Egger test. In addition, sensitivity analyses were further performed to evaluate the stability of the MR results, including the MR-Egger intercept, leave-one-out analysis, Cochrane's Q-test, and the MR-PRESSO global test. Metabolic pathway analysis was applied to uncover the underlying pathways of the significant metabolites in TBI. In blood metabolites, substances such as 4-acetaminophen sulfate and kynurenine showed positive links, whereas beta-hydroxyisovalerate and creatinine exhibited negative correlations. CSF metabolites such as N-formylanthranilic acid were positively related, while kynurenate showed negative associations. The metabolic pathway analysis highlighted the potential biological pathways involved in TBI. Of these 16 serum metabolites, 11 CSF metabolites and metabolic pathways may serve as useful circulating biomarkers in clinical screening and prevention, and may be candidate molecules for the exploration of mechanisms and drug targets.

Causal links between gut microbiomes, cytokines and risk of different subtypes of epilepsy: a Mendelian randomization study.

Objective: Recent research suggests a potential link between the gut microbiome (GM) and epilepsy. We undertook a Mendelian randomization (MR) study to determine the possible causal influence of GM on epilepsy and its various subtypes, and explore whether cytokines act as mediators. Methods: We utilized Genome-Wide Association Study (GWAS) summary statistics to examine the causal relationships between GM, cytokines, and four epilepsy subtypes. Furthermore, we assessed whether cytokines mediate the relationship between GM and epilepsy. Significant GMs were further investigated using transcriptomic MR analysis with genes mapped from the FUMA GWAS. Sensitivity analyses and reverse MR were conducted for validation, and false discovery rate (FDR) correction was applied for multiple comparisons. Results: We pinpointed causal relationships between 30 GMs and various epilepsy subtypes. Notably, the Family Veillonellaceae (OR:1.03, 95%CI:1.02-1.05, p = 0.0003) consistently showed a strong positive association with child absence epilepsy, and this causal association endured even after FDR correction (p-FDR < 0.05). Seven cytokines were significantly associated with epilepsy and its subtypes. A mediating role for cytokines has not been demonstrated. Sensitivity tests validated the primary MR analysis outcomes. Additionally, no reverse causality was detected between significant GMs and epilepsy. Of the mapped genes of notable GMs, genes like BLK, FDFT1, DOK2, FAM167A, ZSCAN9, RNGTT, RBM47, DNAJC21, SUMF1, TCF20, GLO1, TMTC1, VAV2, and RNF14 exhibited a profound correlation with the risk factors of epilepsy subtypes. Conclusion: Our research validates the causal role of GMs and cytokines in various epilepsy subtypes, and there has been no evidence that cytokines play a mediating role between GM and epilepsy. This could provide fresh perspectives for the prevention and treatment of epilepsy.

Translatome and transcriptome profiling of neonatal mice hippocampus exposed to sevoflurane anesthesia.

Exposure to anesthesia in early life may cause severe damage to the brain and lead to cognitive impairment. The underlying mechanisms, which have only been investigated in a limited scale, remains largely elusive. We performed translatome and transcriptome sequencing together for the first time in hippocampus of neonatal mice that were exposed to sevoflurane. We treated a group of neonatal mice with 2.5 % sevoflurane for 2 h on day 6, 7, 8, 9 and treated another group on day 6, 7. We performed behavioral study after day 30 for both groups and the control to evaluate the cognitive impairment. On day 36, we collected translatome and transcriptome from the hippocampus in the two groups, compared the gene expression levels between the groups and the control, and validated the results with RT-qPCR. We identified 1750 differentially expressed genes (DEGs) from translatome comparison and 1109 DEGs from transcriptome comparison. As expected, translatome-based DEGs significantly overlapped with transcriptome-based DEGs, and functional enrichment analysis generated similar enriched cognition-related GO terms and KEGG pathways. However, for many genes like Hspa5, their alterations in translatome differed remarkably from those in transcriptome, and Western blot results were largely concordant with the former, suggesting that translational regulation plays a significant role in cellular response to sevoflurane. Our study revealed global alterations in translatome and transcriptome of mice hippocampus after neonatal exposure to sevoflurane anesthesia and highlighted the importance of translatome analysis in understanding the mechanisms responsible for anesthesia-induced cognitive impairment.

Design and synthesis of N-aryl-2-trifluoromethyl-quinazoline-4-amine derivatives as potential Werner-dependent antiproliferative agents.

To discover new Werner (WRN) helicase inhibitors, a series of N-aryl-2-trifluoromethyl-quinazoline-4-amine derivatives were designed and synthesized through a structural optimization strategy, and the anticancer activities of 25 new target compounds against PC3, K562, and HeLa cell lines were evaluated by the MTT assay. Some of these compounds exhibited excellent inhibitory activity against three different cancer cell lines. Compounds 6a, 8i, and 13a showed better antiproliferative activity against K562 cells, with IC50 values of 3871.5, 613.6 and 134.7 nM, respectively, than did paclitaxel (35.6 nM), doxorubicin (2689.0 nM), and NSC 617145 (20.3 nM). To further verify whether the antiproliferative activity of these compounds is dependent on WRN, PC3 cells overexpressing WRN (PC3-WRN) were constructed to further study their antiproliferative potency in vitro, and the inhibition ratio and IC20 values showed that compounds 6a, 8i, and 13a were more sensitive to PC3-WRN than were the control group cells (PC3-NC). The IC20 ratios of compounds 6a, 8i, and 13a to PC3-NC and PC3-WRN were 94.3, 153.4 and 505.5, respectively. According to the docking results, the compounds 6a, 8i, and 13a overlapped well with the binding pocket of 6YHR. Further study demonstrated that among the tested compounds, 13a was the most sensitive to PC3-WRN. In summary, our research identified a series of N-aryl-2-trifluoromethyl-quinazoline-4-amine derivatives as potential WRN-dependent anticancer agents.

RND3 modulates microglial polarization and alleviates neuroinflammation in Parkinson's disease by suppressing NLRP3 inflammasome activation.

Neuroinflammation mediated by microglia plays an important role in the etiology of Parkinson's disease (PD). Rho family GTPase 3 (RND3) exerts anti-inflammatory effects and may act as a potential new inducer of neuroprotective phenotypes in microglia. However, whether RND3 can be used to regulate microglia activation or reduce neuroinflammation in PD remains elusive. The study investigated the microglia modulating effects and potential anti-inflammatory effects of RND3 in vivo and in vitro, using animal models of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD and cell models of BV-2 cells stimulated by LPS plus IFN-γ with or without RND3-overexpression. The results showed that RND3 was highly expressed in the MPTP-induced PD mouse model and BV-2 cells treated with LPS and IFN-γ. In vivo experiments confirmed that RND3 overexpression could modulate microglia phenotype and ameliorate MPTP-induced neuroinflammation through inhibiting activation of the NLRP3 inflammasome in substantia nigra pars compacta (SNpc). In vitro study showed that RND3 overexpression could attenuate the production of pro-inflammatory factors in BV2 cells stimulated by LPS and IFN-γ. Mechanistically, RND3 reduced the activation of the NLRP3 inflammasome upon LPS and IFN-γ stimulation. Taken together, these findings suggest that RND3 modulates microglial polarization and alleviates neuroinflammation in Parkinson's disease by suppressing NLRP3 inflammasome activation.

Causal association between gut microbiomes and different types of aneurysms: a Mendelian randomization study.

Background: Previous studies suggests that gut microbiomes are associated with the formation and progression of aneurysms. However, the causal association between them remains unclear. Methods: A two-sample Mendelian randomization was conducted to investigate whether gut microbiomes have a causal effect on the risk of intracerebral aneurysm (IA), thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA), and aortic aneurysm (AA). Single nucleotide polymorphisms (SNPs) smaller than the locus-wide significance level (1 × 10-5) were selected as instrumental variables. We used inverse-variance weighted (IVW) test as the primary method for the evaluation of causal association. MR-Egger, weighted median, weighted mode, and MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) methods were conducted for sensitive analysis. The p-value was adjusted by the false discovery rate (FDR) which adjust the results of multiple comparisons, a p < 0.05 and q < 0.1 was considered a significant causal association. Additionally, a p < 0.05 and q > 0.1 was considered a suggestive causal effect. Additionally, reverse MR was also performed to exclude the possibility of reverse causality. Results: The phylum Firmicutes (OR = 0.62; 95% CI, 0.48-0.81), class Lentisphaeria (OR = 0.75; 95% CI, 0.62-0.89), and order Victivallales (OR = 0.75; 95% CI, 0.62-0.89) have a causal protective effect on the risk of AAA. Additionally, class Verrucomicrobia, class Deltaproteobacteria, order Verrucomicrobiale, family Verrucomicrobiacea, genus Eubacterium rectale group, genus Akkermansia, and genus Clostridium innocuum group were negatively associated with the risk of different types of aneurysms, whereas class Negativicutes, order Selenomonadales, and genus Roseburia had positive causal association with different types of aneurysms (p < 0.05; q > 0.1). Further sensitivity analysis validated the robustness of our MR results, and no reverse causality was found with these gut microbiomes (p > 0.05). Conclusion: Our MR analysis confirmed the causal association of specific gut microbiomes with AAA, and these microbiomes were considered as protective factors. Our result may provide novel insights and theoretical basis for the prevention of aneurysms through regulation of gut microbiomes.

Correlation research on visual behavior and cognition of impression against localized church facades in China.

Churches in China are material witnesses of cultural dissemination, and their architectural forms are in the process of localization. In order to determine the optimal degree of localization of church facades as well as to study the correlation between visual behavior and subjective cognition, five church facades with different degrees of localization were selected in present study, and the questionnaire survey as well as eye-tracking technology were used to collect data from two aspects: subjective cognition (the impression and acceptance levels) and objective eye movement (the first fixation duration, total fixation duration, fixation count, and visit count). The results showed the differences in public perceptions of church facades, and the impression of participants was continuously enhanced with the increasing of localization degree of church facade, while the acceptance level showed a U-shaped change. What's more, the correlation between the impression level and the first fixation duration was found to be 0.910, the Pearson coefficient between the acceptance level and the total fixation duration was found to be 0.928, indicating that eye-tracking indicators could accurately reflect the subjective cognition of the public. Performed analyses demonstrated that eye-tracking technology would provides an important technical mean for the design, conservation, and renewal of building facades.

Observation on the tilt and decentration of multifocal intraocular lens with optic capture in Berger space for pediatric cataract.

PURPOSE: This study aimed to observe the tilt and decentration of multifocal intraocular lens (IOL) with optic capture in Berger space within 2 years after pediatric cataract surgery. METHODS: This is a prospective observational study. The implantation of multifocal IOL (Tecnis ZMB00) with optic capture in Berger space was performed on 33 patients (48 eyes) with pediatric cataract at Qingdao Eye Hospital. Tilt and decentration of IOL was measured using Scheimpflug system (Pentacam) at 1 month and 2 years postoperatively. RESULTS: All the multifocal IOLs were successfully implanted in Berger space with optic capture and no visually significant complications were detected during the follow-up. The mean tilt of IOLs was 2.779° ± 0.950° in the vertical plane and 2.399° ± 0.898° in the horizontal plane at 1 month postoperatively, and the mean length of the decentration was 0.207 ± 0.081 mm in vertical plane and 0.211 ± 0.090 mm in the horizontal plane. Compared with 1 month after surgery, the angle of tilt decreased by a mean of 0.192° and decentration increased by a mean of 0.014 mm at the vertical meridian at 2 years postoperatively (P = 0.37 and P = 0.27, respectively), meanwhile, tilt increased by 0.265° and decentration increased by 0.012 mm at the horizontal meridian (P = 0.11 and P = 0.22, respectively). CONCLUSIONS: The follow-up results suggest the tilt and decentration of multifocal IOL implantation with optic capture in Berger space remain stable in an acceptable range within 2 years after cataract surgery in children above the age of 5. TRIAL REGISTRATION: The study was approved by the Ethics Committee of Qingdao Eye Hospital, and registered on Chinese Clinical Trial Registry (ChiCTR identifier: 1900023155).