Radiomic profiling for insular diffuse glioma stratification with distinct biologic pathway activities.

Current literature emphasizes surgical complexities and customized resection for managing insular gliomas; however, radiogenomic investigations into prognostic radiomic traits remain limited. We aimed to develop and validate a radiomic model using multiparametric magnetic resonance imaging (MRI) for prognostic prediction and to reveal the underlying biological mechanisms. Radiomic features from preoperative MRI were utilized to develop and validate a radiomic risk signature (RRS) for insular gliomas, validated through paired MRI and RNA-seq data (N = 39), to identify core pathways underlying the RRS and individual prognostic radiomic features. An 18-feature-based RRS was established for overall survival (OS) prediction. Gene set enrichment analysis (GSEA) and weighted gene coexpression network analysis (WGCNA) were used to identify intersectional pathways. In total, 364 patients with insular gliomas (training set, N = 295; validation set, N = 69) were enrolled. RRS was significantly associated with insular glioma OS (log-rank p = 0.00058; HR = 3.595, 95% CI:1.636-7.898) in the validation set. The radiomic-pathological-clinical model (R-P-CM) displayed enhanced reliability and accuracy in prognostic prediction. The radiogenomic analysis revealed 322 intersectional pathways through GSEA and WGCNA fusion; 13 prognostic radiomic features were significantly correlated with these intersectional pathways. The RRS demonstrated independent predictive value for insular glioma prognosis compared with established clinical and pathological profiles. The biological basis for prognostic radiomic indicators includes immune, proliferative, migratory, metabolic, and cellular biological function-related pathways.

Hepatoprotective effects and mechanisms of l-theanine and epigallocatechin gallate combined intervention in alcoholic fatty liver rats.

BACKGROUND: Chronic excessive alcohol consumption can lead to alcoholic fatty liver, posing substantial health risks. l-Theanine (LTA) and epigallocatechin gallate (EGCG) in tea exert antioxidant and hepatoprotective effects. However, the combined effects of LTA and EGCG on rats with alcoholic fatty liver, and the underlying mechanisms of such effects, remain unclear. In this study, Sprague Dawley (SD) rats were fed with alcohol for 6 weeks to induce alcoholic fatty liver. Subsequently, for another 6 weeks, the rats were administered LTA (200 mg kg-1 day-1), EGCG (200 mg kg-1 day-1), or a combination of LTA with EGCG (40 mg kg-1 day-1 l-Thea +160 mg kg-1 day-1 EGCG), respectively. RESULTS: The combined use of LTA and EGCG for alcoholic fatty liver disease had more significant effects than their individual administration. This combination reduced the activity of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as well as the levels of hepatic triglyceride (TG), malondialdehyde (MDA), and reactive oxygen species (ROS) in the rats. The combined intervention also increased hepatic superoxide dismutase (SOD) and glutathione peroxidase activity. Reductions in hepatic fat accumulation and inflammatory responses were observed. The mechanism underlying these effects primarily involved the inhibition of fatty acid synthesis and the alleviation of lipid peroxidation through the downregulation of the mRNA and protein expression of TNF-α, SREBP1c, and CYP2E1 and the upregulation of the mRNA and protein expression of ADH1, ALDH2, Lipin-1, PPARαPPARα, AMPK, and PGC-1α, thereby promoting the oxidative decomposition of fatty acids and reducing the synthesis of cholesterol and glucose. CONCLUSION: l-Theanine and EGCG appear to be able to alleviate alcoholic fatty liver by modulating lipid metabolism and ameliorating oxidative stress, indicating their potential as natural active ingredients in anti-alcoholic fatty liver food products. © 2024 Society of Chemical Industry.

A survey study on early detection of young children with disabilities in urban and rural areas of China.

AIM: This study aimed to understand how children and families access early intervention in China. BACKGROUND: Timely identification and high-quality intervention is expected to prevent and reduce the occurrence and severity of chronic functional impairment for children with disability and is of great significance to individuals and the society. The current study recruited 1129 caregivers of children with disabilities from rural and urban areas of China were recruited to participate in a survey. RESULTS: (a) The first concern about development was raised, usually by the parents, when a child with disabilities was 26 months of age, (b) developmental screening took place 4 months after the first concern and diagnostic evaluation happened 7 months after, (c) the types of early intervention programme varied across urban and rural areas and (d) child and family factors were found associating with age of detection. CONCLUSIONS: Findings highlight the concerningly late age of children being identified for early intervention and disparities in services between urban and rural areas in China. Implications are provided for practitioners, policy makers and future research.

Differentiation of Diffuse Infiltration Pattern in Multiple Myeloma From Hyperplastic Hematopoietic Bone Marrow: Qualitative and Quantitative Analysis Using Whole-Body MRI.

BACKGROUND: The visual assessment used for diffuse infiltration of multiple myeloma (MM) is inadequate. It can be difficult to differentiate MM from hyperplastic hematopoietic bone marrow (HHBM) because the MRI signal characteristics overlap. PURPOSE: To analyze the bone marrow diffuse signal changes on whole-body MRI caused by MM and HHBM. STUDY TYPE: Retrospective. SUBJECTS: Thirty Four patients with MM (21 men and 13 women), 22 patients with HHBM (9 men and 13 women), and 15 healthy controls (9 men and 6 women). FIELD STRENGTH/SEQUENCE: A 3.0 T MRI; diffusion-weighted whole-body imaging with background body signal suppression (DWIBS), modified Dixon T1 fast field echo, and T2 STIR. ASSESSMENT: Three radiologists analyzed the whole-body MRI alone and in combination with apparent diffusion coefficient (ADC) and fat fraction (FF) with qualitative and quantitative analysis. Normalized T1 and T2 signal intensities (nT1 and nT2) and signal-to-noise ratio (SNR) were obtained. STATISTICAL TESTS: Kruskal-Wallis and chi-square tests. RESULTS: The MM group had significantly higher ADC and significantly lower FF than HHBM and control groups. There was no significant difference in nT1, nT2 or SNR between MM and HHBM (P = 0.932, P = 0.097, and P = 0.110, respectively). Receiver operating characteristic (ROC) analysis using ADC and FF cut-off values of 0.47 × 10-3  mm2 /sec and 20.63%, respectively. The AUC was 0.866 for ADC and 0.886 for FF. The quantitative analysis yielded better specificity (observer 1: 81.8% vs. 27.3%; observer 2: 68.2% vs. 22.7%; and observer 3: 72.7% vs. 18.2%) and a higher diagnostic accuracy (observer 1: 82.1% vs. 51.8%; observer 2: 80.4% vs. 50.0%; observer 3: 76.8% vs. 44.6%) than the qualitative analysis. DATA CONCLUSION: Whole-body MRI combined with DWIBS and mDIXON could be used to differentiate between MM and HHBM. Combining the quantitative ADC and FF with the whole-body MRI improved the specificity and accuracy in differentiating these conditions. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Assessment of the Utility of Physiologically-based Pharmacokinetic Model for prediction of Pharmacokinetics in Chinese and Japanese Populations.

The objective for the present analyses was to evaluate the utility of physiologically-based pharmacokinetic (PBPK) modeling for prediction of the pharmacokinetics (PK) in Chinese and Japanese populations with a panel of Pfizer internal compounds. Twelve compounds from Pfizer internal development pipeline with available Westerner PK data and available PK data in at least one of the subpopulations of Japanese and Chinese populations were identified and included in the current analysis. These selected compounds represent various elimination pathways across different therapeutic areas. The Simcyp® PBPK simulator was used to develop and verify the PBPK models of individual compounds. The developed models for these compounds were verified by using the clinical PK data in Westerners. The verified PBPK models were further used to predict the PK of these compounds in Chinese and Japanese populations and the predicted PK parameters were compared with the observed PK parameters. Ten of the 12 compounds had PK data in Chinese, and all the 12 compounds had PK data in Japanese. In general, the PBPK models performed well in predicting PK in Chinese and Japanese, with 8 of 10 drugs in Chinese and 7 of 12 drugs in Japanese has AAFE values less than 1.25-fold. PBPK-guided predictions of the relative PK difference were successful for 75% and 50%, respectively, between Chinese and Western and between Japanese and Western of the tested drugs using 0.8-1.25 as criteria. In conclusion, well verified PBPK models developed using data from Westerners can be used to predict the PK in Chinese and Japanese populations.

Test-retest multisite reproducibility of neurovascular 4D flow MRI.

BACKGROUND: 4D flow MRI shows great potential in neurovascular disorders such as stenosis, atherosclerotic disease, aneurysms, and vascular malformations. Its widespread application in the neurovascular system requires evidence of good test-retest multicenter reproducibility. PURPOSE: To assess the multicenter reproducibility, test-retest reliability and interobserver dependence of 4D flow MRI in measurements of cerebral blood flow/velocity in main intracranial vessels. STUDY TYPE: Prospective study. SUBJECTS: Ten healthy subjects underwent 4D flow scans at three different centers. All subjects were scanned twice at 2 different days at each center. FIELD STRENGTH/SEQUENCE: 3.0 T; 4D flow sequence. ASSESSMENT: Multicenter reproducibility, test-retest reliability and interobserver agreement for measurements of the blood flow and peak velocity from five regions of interest were assessed (bilateral internal carotid arteries, bilateral medial cerebral arteries, and sagittal sinus). STATISTICAL TEST: A Shapiro-Wilks test was conducted to assess normality of measurements in each scan. Coefficient of variances (CVs) was computed to evaluate intra- and intersite variances of all measurements. The multicenter reproducibility was assessed by two-way mixed intraclass correlation coefficient (ICC). A Bland-Altman plot and Pearson correlation were used to evaluate test-retest reliability. ICC was calculated to assess interobserver agreements. RESULTS: All P-values for Shapiro-Wilks tests were greater than 0.05, which indicated the normality of all measurements. Both intra- and intersite CVs were lower than 12%. There was good test-retest reliability for both blood flow and peak velocity of all ROIs (r = 0.75-0.94). In addition, high multicenter reproducibility was detected (ICC = 0.77-0.96, all P < 0.001). The results of these measurements also showed great interobserver agreement (all ICC > 0.9 and all P < 0.001). DATA CONCLUSION: High multicenter reproducibility and test-retest reliability was shown for 4D flow in the measurements of blood flow and peak velocity of intracranial vessels. In addition, these measurements showed great interobserver agreement. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:1543-1552.

Antibiotics-induced perturbations in gut microbial diversity influence metabolic phenotypes in a murine model of high-fat diet-induced obesity.

Gut microbiota play a key role in the regulation of obesity and associated metabolic disorders. To study the relationship between them, antibiotics have been widely used to generate pseudo-germ-free rodents as control models. However, it is not clear whether antibiotics impact an animal's metabolic phenotype. Therefore, the effect of antibiotics-induced gut microbial perturbations on metabolic phenotypes in high-fat diet (HFD) fed mice was investigated. The results showed that antibiotics perturbed gut microbial composition and structure. Community diversity and richness were reduced, and the phyla Firmicutes/Bacteroidetes (F/B) ratio was decreased by antibiotics. Visualization of Unifrac distance data using principal component analysis (PCA) and unweighted pair-group method with arithmetic mean (UPGAM) demonstrated that fecal samples of HFD-fed mice separated from those of chow diet (CD) fed mice. Fecal samples from antibiotics-treated and non-treated mice were clustered into two different microbial populations. Moreover, antibiotics suppressed HFD-induced metabolic features, including body weight gain (BWG), liver weight (LW), epididymal fat weight (EFW), and serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), fasting blood glucose (FBG), and insulin (INS) significantly (P < 0.05). Lachnospiraceae, Ruminiclostridium and Helicobacter, biomarkers of mouse gut microbiota before treatment by antibiotics, were positively correlated with obesity phenotypes significantly (P < 0.05) and were decreased by (92.95 ± 5.09) %, (97.73 ± 2.09) % and (99.48 ± 0.21) % respectively after 30 days of treatment by antibiotics. However, Bacteroidia were enriched in HFD-fed antibiotics-treated mice and were negatively correlated with obesity phenotypes significantly (P < 0.05). We suggested that the antibiotics-induced depletion of Lachnospiraceae, Ruminiclostridium, and Helicobacter, and the decrease in F/B ratio in gut microbiota played a role in the prevention of HFD-induced obesity in mice.

Pharmacokinetics and exploratory efficacy biomarkers of bococizumab, an anti-PCSK9 monoclonal antibody, in hypercholesterolemic Japanese subjects
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OBJECTIVE: Bococizumab, a monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9, has been shown to reduce low-density lipoprotein cholesterol (LDL-C). Here, we describe the pharmacokinetics and pharmacodynamics of bococizumab and its effect on lipoprotein particle composition and other biomarkers, based on a double-blind, placebo-controlled, randomized, dose-ranging study. MATERIALS AND METHODS: The study consisted of two populations: Japanese subjects with uncontrolled LDL-C (LDL-C ≥ 100 mg/dL) despite treatment with atorvastatin (n = 121) and Japanese subjects naïve to lipid-lowering agents with LDL-C ≥ 130 mg/dL (n = 97). Subjects were randomized to receive either bococizumab 50, 100, or 150 mg or placebo, every 2 weeks. One arm of subjects in the ator-vastatin-treated population received ezetimibe 10 mg instead of bococizumab. RESULTS: In both populations, bococizumab exposure increased with increasing dose, and subjects with lower body weights tended to have higher exposures. Bococizumab treatment was associated with a dose-dependent reduction in LDL particles and a small increase in total high-density lipoprotein (HDL) particles. Significant reductions in lipoprotein-associated phospholipase A2 (Lp-PLA2) were observed for bococizumab-treated subjects but not for subjects treated with placebo or ezetimibe. CONCLUSION: Increased bococizumab dosage resulted in increased exposure. Levels of LDL and HDL particles and biomarkers such as Lp-PLA2 were also altered with bococizumab treatment. (ClinicalTrials.gov identifier: NCT02055976).
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Development and Validation of an Analytical Method Based on HPLC-ELSD for the Simultaneous Determination of Rosmarinic Acid, Carnosol, Carnosic Acid, Oleanolic Acid and Ursolic Acid in Rosemary.

The safety, efficacy and stability of natural antioxidants have been the focus of research in the food industry, with the aim of rapidly analyzing and controlling the quality of rosemary and its extracts, a novel analytical method involving high-performance liquid chromatography with evaporative light scattering detection (HPLC-ELSD) was developed for the simultaneous determination of rosmarinic acid, carnosol, carnosic acid, oleanolic acid and ursolic acid in rosemary. Chromatographic separation was conducted with gradient elution mode by using a Zorbax SB-C18 column (4.6 mm × 250 mm, 5 µm) with mobile phases of methanol and 0.6% acetic acid. The drift tube temperature of ELSD was 70 °C, and the pressure of nebulizer nitrogen gas was 40 Psi. The method developed has high sensitivity (with limits of detection from 1.3 to 8.6 µg/mL), acceptable linearity over the tested concentrations (with correlation coefficients from 0.991 to 0.999), good repeatability (with intra- and inter-day CV less than 3.1% for all analytes) and satisfactory accuracy (with recovery between 95.5% and 100.8%). The method has been demonstrated as a powerful tool for the functional ingredients analysis and quality control of rosemary and its extracts in a cost- and time-effective manner.

Design and synthesis of reversible solid-state photochromic pyrazolones by introducing a pyridine ring.

We demonstrate a new strategy for designing reversibility, fatigue resistance and fluorescence switching materials, which are based on pyrazolone derivatives by introducing a pyridine ring. The reversible "on" and "off" modulation of fluorescence emission was up to 95% in the solid state.

Pharmacokinetics and Safety of Intramuscular Injectable Benzathine Penicillin G in Japanese Healthy Participants.

An intramuscular (IM) suspension of benzathine penicillin G (BPG) has been used as first-line therapy for the treatment of syphilis worldwide since its approval in the 1950s. However, there are limited reports about the pharmacokinetics of BPG. A Phase 1 study was conducted on eight Japanese healthy participants to investigate the pharmacokinetics (samples collected predose to 648 h post-dose) and safety of 2.4 million units of BPG after a single IM injection. Following administration, penicillin G, the active moiety of BPG, was absorbed slowly from the injection site with a median time to Cmax (tmax) of 48 h post-dose. After the achievement of Cmax, concentrations of penicillin G declined slowly in a monophasic fashion with a mean apparent terminal half-life of 189 h. Geometric mean AUCinf and Cmax were 50770 ng•h/mL and 259 ng/mL, respectively. Median time (range) above the well-accepted therapeutic concentration (18 ng/mL) for syphilis treatment was 561 h (439-608 h [18-25 days]), which reached and exceeded the necessary duration of 7-10 days for syphilis treatment. Two participants were underdosed with residual drug left in the syringe due to the high viscosity of the drug product. Only one (12.5%) participant reported a mild adverse event of nasopharyngitis, which was considered not related to the study treatment. The study results supported BPG approval in Japan as an option for syphilis treatment.

A comparative assessment of age-related nicotinamide adenine dinucleotide phosphate-diaphorase positivity in the spinal cord and medulla oblongata of pigeons, rats, and mice.

Nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase (N-d) positive neurons have been extensively studied across various animals, and N-d neurodegenerative neurites have been detected in some aged animal models. However, detailed knowledge on N-d positivity and aging-related alterations in the spinal cord and medulla oblongata of pigeons is limited. In this study, we investigated N-d positivity and age-related changes in the pigeon's spinal cord and medulla oblongata and compared them to those in rats and mice. Pigeons, had more N-d neurons in the dorsal horn, around the central canal, and in the column of Terni in the thoracic and lumbar segments, with scattered neurons found in the ventral horn of the spinal segments. N-d neurons were also present in the white matter of the spinal cord. Morphometric analysis revealed that the size of N-d soma in the lumbosacral, cervical, and thoracic regions was substantially altered in aged pigeons compared to young birds. Furthermore, the lumbar to sacral segments underwent significant morphological alterations. The main findings of this study were the presence of age-related N-d positive bodies (ANB) in aged pigeons, predominantly in the external cuneate nucleus (CuE) and occasionally in the gracilis and CuEs. ANBs were also identified in the gracile nuclei and spinal cord in the aged rats and mice, whereas in aged rats, ANBs were detected in the CuE spinal nucleus. Immunohistochemistry showed that the age-related alterations occurred in the cell types and neuropeptides in old animals. The results suggest weak inflammatory response and neuronal dysfunction in the spinal cord in aged pigeons. Our results suggested that the ANB could be a potential aging marker for the central nervous system.

MRI-guided cell membrane-camouflaged bimetallic coordination nanoplatform for combined tumor phototherapy.

Nanotechnology for tumor diagnosis and optical therapy has attracted widespread interest due to its low toxicity and convenience but is severely limited due to uncontrollable tumor targeting. In this work, homologous cancer cell membrane-camouflaged multifunctional hybrid metal coordination nanoparticles (DRu/Gd@CM) were prepared for MRI-guided photodynamic therapy (PDT) and photothermal therapy (PTT) of tumors. Bimetallic coordination nanoparticles are composed of three functional modules: dopamine, Ru(dcbpy)3Cl2 and GdCl3, which are connected through 1,4-Bis[(1H-imidazole-1-yl)methyl]benzene (BIX). Their morphology can be easily controlled by adjusting the ratio of precursors. Optimistically, the intrinsic properties of the precursors, including the photothermal properties of polydopamine (PDA), the magnetic resonance (MR) response of Gd3+, and the singlet oxygen generation of Ru(dcbpy)3Cl2, are well preserved in the hybrid metal nanoparticles. Furthermore, the targeting of homologous cancer cell membranes enables these coordinated nanoparticles to precisely target tumor cells. The MR imaging capabilities and the combination of PDT and PTT were demonstrated in in vitro experiments. In addition, in vivo experiments indicated that the nanoplatform showed excellent tumor accumulation and therapeutic effects on mice with subcutaneous tumors, and could effectively eliminate tumors within 14 days. Therefore, it expanded the new horizon for the preparation of modular nanoplatform and imaging-guided optical therapy of tumors.

Rapid visual detection of sulfur dioxide residues in food using acid-sensitive CdTe quantum dots-loaded alginate hydrogel beads.

Acid-sensitive CdTe quantum dots-loaded alginate hydrogel (CdTe QDs-AH) beads were designed for the visual detection of SO2 residues. As proof of concept, two types of CdTe QDs were selected as model probes and embedded in AH beads. The entire test was performed within 25 min in a modified double-layer test tube with one bead fixed above the sample solution. Adding citric acid and heating at 70 ℃ for 20 min transformed the sulfites in the solution into SO2 gas, which then quenched the fluorescence of the CdTe QDs-AH beads. Using this assay, qualitative, naked-eye detection of SO2 residues was achieved in the concentration range of 25-300 ppm, as well as precise quantification was possible based on the difference in the average fluorescence brightness of the beads before and after the reaction. Five food types were successfully analysed using this method, which is simpler and more economical than existing methods, and does not require complex pretreatment.

Added value of zoomed-echo-planar imaging diffusion-weighted imaging for evaluation of periampullary carcinomas.

BACKGROUND: To assess the image quality feasibility and diagnostic value of zoomed diffusion-weighted imaging (z-EPI DWI) using echo-planar imaging (EPI) compared with conventional DWI (c-EPI DWI) in patients with periampullary disease. METHODS: Thirty-six patients with periampullary carcinomas and fifteen with benign periampullary disease were included in this study. All the subjects underwent MR cholangiopancreatography (MRCP), c-EPI DWI, and z-EPI DWI. Two radiologists independently assessed image quality of the two image sets, including overall image quality and lesion conspicuity. In addition, signal intensity and ADC measurements of DWIs in the periampullary lesions were conducted. Diagnostic accuracies of the combined image sets of MRCP and z-EPI DWI were compared with those of a combined set of MRCP and c-EPI DWI. RESULTS: z-EPI DWI showed significantly better image quality scores (anatomic structure visualization, 2.94 ± 0.24; overall image quality, 2.96 ± 0.17) compared to that with c-EPI DWI (anatomic structure visualization, 2.02 ± 0.22; overall image quality, 2.04 ± 0.24) (both P < 0.01). For all the periampullary malignant lesions and small lesions (≤ 20 mm), there was better delineation of lesion conspicuity and the lesion margin, as well as diagnostic confidence with z-EPI DWI (all P < 0.05). The rate of periampullary malignancy's hyperintense signal on z-EPI DWI was increased to 91.7% (33/36) compared to c-EPI DWI (69.4% (25/36)) (P = 0.023). For all malignant lesions and small lesions, the diagnostic accuracy scores were increased using the MRCP and z-EPI DWI combined set, compared to the MRCP and c-EPI DWI combined set (P < 0.05). Diagnostic accuracy for detection and differentiation of malignant lesions from benign lesions significantly improved for the MRCP and z-EPI DWI combined set compared with MRCP and c-EPI DWI combined set (P < 0.05). There were no significant differences between c-EPI DWI and z-EPI DWI in the ADC values of periampullary malignant and benign lesions (P > 0.05). CONCLUSIONS: z-EPI DWI has an advantage that could lead to remarkable image quality improvements and enhanced lesion visualization of periampullary carcinomas. z-EPI DWI was superior to c-EPI DWI for detecting, delineating, and diagnosing the lesions, particularly for small challenging lesions.

Bibliometric study of neuroinflammation in autism spectrum disorder.

Background: Neuroinflammation is closely associated with the occurrence and development of autism spectrum disorder (ASD). This study aims to describe the global development history and current status of neuroinflammation in ASD from 2004 to 2021 and reveal the research hotspots and frontiers to provide a reference for scholars in related fields to carry out further research. Methods: Journal articles on ASD and neuroinflammation-related research were obtained from the Web of Science Core Collection (WOSCC) database from its inception to 2021. Literature was analyzed visually by VOSviewer, CiteSpace, and R language, including publication analysis, author, institution, national/regional cooperative network analysis, and keyword analysis. We screened the most accumulatively cited 10 experimental papers in the field and the most cited 10 experimental papers in the last 2 years (2020 and 2021) for combing. Results: A total of 620 publications were included in this study, and the number of publications has increased in recent years. The United States (256, 41.29%) was the country with the largest number of publications. King Saud University (40, 6.45%) was the most published institution; Laila Al-Ayadhi Yousef was the most published researcher; the Brain Behavior and Immunity was the main journal for the study of neuroinflammation in autism, having published 22 related articles. Keyword co-occurrence analysis showed that short chain fatty acid, mast cells, and glial cells have been the focus of recent attention. Burst keywords show that gut microbiota and immune system are the future research trends. Conclusion: This bibliometric study describes the basic framework for the development in the field of neuroinflammation and ASD through an exploration of key indicators (countries, institutions, journals, authors, and keywords). We found that the key role of neuroinflammation in the development of ASD is attracting more and more researchers' attention. Future studies can investigate the changes in cytokines and glial cells and their related pathways in ASD neuroinflammation. Immunotherapy to inhibit neuroinflammation may be intensively studied as a direction for ASD treatment or intervention.

The association of coagulation indicators with in-hospital acute kidney injury and malignant events of patients with acute aortic dissection: a retrospective cohort study.

Background: Acute kidney injury (AKI) is a prevalent complication of acute aortic dissection (AAD) and is associated with poor outcomes. The onset of AAD may result in endothelial injury due to the formation of the false lumen, which can activate the coagulation pathway and lead to coagulation dysfunction. It serves as a valuable diagnostic and prognostic marker for AAD, but also plays a role in the pathological mechanisms underlying AKI. We aimed to investigate the potential value of coagulation indicators at admission for assessing in-hospital AKI and malignant events after AAD. Methods: We identified patients with AAD admitted to the First Affiliated Hospital of Shantou University Medical College from January 2015 to October 2020 and divided them into two groups according to coagulation function. Univariable and multivariable analyses were used to analyze the association between coagulation indicators and AKI and malignant events in patients with AAD. Chi-squared or Fisher exact test and receiver operating characteristic (ROC) curve analysis was conducted to assess the value of coagulation indicators in predicting in-hospital AKI and malignant events. Results: A total of 487 patients were enrolled in this study, including 309 cases with normal coagulation. After the multivariable adjustment, the incidence of in-hospital AKI in the abnormal coagulation group was significantly higher [model 1: 2.061 (1.214-3.501), P=0.007; model 2: 1.833 (1.058-3.177), P=0.031; model 3: 1.836 (1.048-3.216), P=0.034]. The incidence of malignant events was higher in the abnormal prothrombin time (PT) group [model 1: 4.283 (0.983-18.665), P=0.053; model 2: 7.342 (1.467-36.749), P=0.015; model 3: 6.996 (1.377-35.537), P=0.019]. Chi-squared and Fisher exact test showed that PT and abnormal coagulation score (ACS) were statistically different among the AKI groups and malignant event groups. Under ROC analysis, coagulation indicators were helpful to predict AKI (AUC =0.668; P<0.001). Conclusions: Our study confirmed the presence of coagulation dysfunction is associated with an increased risk of AKI and malignant events. It suggested the severity of coagulation dysfunction is positively correlated with the incidence of in-hospital AKI in AAD patients. These results highlight the importance of considering coagulation dysfunction as a potential mechanism underlying AKI and malignant events after AAD.

Associations between dysbiosis gut microbiota and changes of neurotransmitters and short-chain fatty acids in valproic acid model rats.

Introduction: The microbiota-gut-brain axis plays an important role in the pathophysiology of autism spectrum disorder, but its specific mechanisms remain unclear. This study aimed to explore the associations of changes in neurotransmitters and short-chain fatty acids with alterations in gut microbiota in valproic acid model rats. Methods: The autism model rats were established by prenatal exposure to valproic acid (VPA). The Morris water maze test, open field test, and three-chamber test were conducted to assess the behaviors of rats. 16S rRNA gene sequences extracted from fecal samples were used to assess the gut microbial composition. Gas and liquid chromatography-mass spectroscopy was used to identify short-chain fatty acids in fecal samples and neurotransmitters in the prefrontal cortex (PFC). Results: The results showed that 28 bacterial taxa between valproic acid model rats and control rats were identified, and the most differential bacterial taxa in valproic acid model rats and control rats belonged to metagenomic species and Lactobacillus intestinalis. Acetic acid, butyric acid, valeric acid, isobutyric acid, and isovaleric acid were significantly decreased in the valproic acid model rats compared to those in control rats. Five neurotransmitters (threonine, kynurenine, tryptophan, 5-hydroxyindoleacetic acid, denoted as 5-HIAA, and betaine aldehyde chloride, denoted as BAC) were significantly decreased, whereas betaine was increased in the prefrontal cortex of valproic acid model rats compared to control rats. A variety of neurotransmitters (≥4) were correlated with Pseudomonas, Collisella, and Streptococcus at the genus level, and they were also related to the decrease of short-chain fatty acids. Discussion: According to this study, we can preliminarily infer that gut microbiota or their metabolic productions (such as SCFAs) may influence central neurotransmitter metabolism through related pathways of the gut-brain axis. These results provide microbial and short-chain fatty acid (SCFA) frameworks for understanding the role of the microbiota-gut-brain axis in autism spectrum disorder and shed new light on autism spectrum disorder treatment.

De novo aging-related NADPH diaphorase positive megaloneurites in the sacral spinal cord of aged dogs.

We investigated aging-related changes in nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) in the spinal cord of aged dogs. At all levels of the spinal cord examined, NADPH-d activities were observed in neurons and fibers in the superficial dorsal horn (DH), dorsal gray commissure (DGC) and around the central canal (CC). A significant number of NADPH-d positive macro-diameter fibers, termed megaloneurites, were discovered in the sacral spinal cord (S1-S3) segments of aged dogs. The distribution of megaloneurites was characterized from the dorsal root entry zone (DREZ) into the superficial dorsal horn, along the lateral collateral pathway (LCP) to the region of sacral parasympathetic nucleus (SPN), DGC and around the CC, but not in the cervical, thoracic and lumbar segments. Double staining of NADPH-d histochemistry and immunofluorescence showed that NADPH-d positive megaloneurites co-localized with vasoactive intestinal peptide (VIP) immunoreactivity. We believed that megaloneurites may in part represent visceral afferent projections to the SPN and/or DGC. The NADPH-d megaloneurites in the aged sacral spinal cord indicated some anomalous changes in the neurites, which might account for a disturbance in the aging pathway of the autonomic and sensory nerve in the pelvic visceral organs.

Characterization of curli A production on living bacterial surfaces by scanning probe microscopy.

Curli are adhesive surface fibers produced by many Enterobacteriaceae, such as Escherichia coli and Salmonella enterica. They are implicated in bacterial attachment and invasion to epithelial cells. In this study, atomic force microscopy was used to determine the effects of curli on topology and mechanical properties of live E. coli cells. Young's moduli of both curli-deficient and curli-overproducing mutants were significantly lower than that of their wild-type (WT) strain, while decay lengths of the former strains were higher than that of the latter strain. Surprisingly, topological images showed that, unlike the WT and curli-overproducing mutant, the curli-deficient mutant produced a large number of flagella-like fibers, which may explain why the strain had a lower Young's modulus than the WT. These results suggest that the mechanical properties of bacterial surfaces are greatly affected by the presence of filamentous structures such as curli and flagella.