Divergent electroencephalogram resting-state functional network alterations in subgroups of autism spectrum disorder: a symptom-based clustering analysis.

Autism spectrum disorder (ASD) is characterized by etiological and phenotypic heterogeneity. Despite efforts to categorize ASD into subtypes, research on specific functional connectivity changes within ASD subgroups based on clinical presentations is limited. This study proposed a symptom-based clustering approach to identify subgroups of ASD based on multiple clinical rating scales and investigate their distinct Electroencephalogram (EEG) functional connectivity patterns. Eyes-opened resting-state EEG data were collected from 72 children with ASD and 63 typically developing (TD) children. A data-driven clustering approach based on Social Responsiveness Scales-Second Edition and Vinland-3 scores was used to identify subgroups. EEG functional connectivity and topological characteristics in four frequency bands were assessed. Two subgroups were identified: mild ASD (mASD, n = 37) and severe ASD (sASD, n = 35). Compared to TD, mASD showed increased functional connectivity in the beta band, while sASD exhibited decreased connectivity in the alpha band. Significant between-group differences in global and regional topological abnormalities were found in both alpha and beta bands. The proposed symptom-based clustering approach revealed the divergent functional connectivity patterns in the ASD subgroups that was not observed in typical ASD studies. Our study thus provides a new perspective to address the heterogeneity in ASD research.

Multimodal investigation of dynamic brain network alterations in autism spectrum disorder: Linking connectivity dynamics to symptoms and developmental trajectories.

BACKGROUND: Autism spectrum disorder (ASD) has been associated with disrupted brain connectivity, yet a comprehensive understanding of the dynamic neural underpinnings remains lacking. This study employed concurrent electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) techniques to investigate dynamic functional connectivity (dFC) patterns and neurovascular characteristics in children with ASD. We also explored associations between neurovascular characteristics and the developmental trajectory of adaptive behavior in individuals with ASD. METHODS: Resting-state EEG and fNIRS data were simultaneously recorded from 58 ASD and 63 TD children. We implemented a k-means clustering approach to extract the dFC states for each modality. In addition, a multimodal covariance network (MCN) was constructed from the EEG and fNIRS dFC features to capture the neurovascular characteristics linked to ASD. RESULTS: EEG analyses revealed atypical properties of dFC states in the beta and gamma bands in children with ASD compared to TD children. For fNIRS, the ASD group exhibited atypical properties of dFC states such as duration and transitions relative to the TD group. The MCN analysis revealed significantly suppressed functional covariance between right superior temporal and left Broca's areas, alongside enhanced right dorsolateral prefrontal-left Broca covariance in ASD. Notably, we found that early neurovascular characteristics can predict the developmental progress of adaptive functioning in ASD. CONCLUSION: The multimodal investigation revealed distinct dFC patterns and neurovascular characteristics associated with ASD, elucidating potential neural mechanisms underlying core symptoms and their developmental trajectories. Our study highlights that integrating complementary neuroimaging modalities may aid in unraveling the complex neurobiology of ASD.

Semi-rational design based on the interaction between SmFMO and FAD isoalloxazine ring to enhance the enzyme activity.

Flavin monooxygenases (FMOs) have been widely used in the biosynthesis of natural compounds due to their excellent stereoselectivity, regioselectivity and chemoselectivity. Stenotrophomonas maltophilia flavin monooxygenase (SmFMO) has been reported to catalyze the oxidation of various thiols to corresponding sulfoxides, but its activity is relatively low. Herein, we obtained a mutant SmFMOF52G which showed 4.35-fold increase in kcat/Km (4.96 mM-1s-1) and 6.84-fold increase in enzyme activity (81.76 U/g) compared to the SmFMOWT (1.14 mM-1s-1 and 11.95 U/g) through semi-rational design guided by structural analysis and catalytic mechanism combined with high-throughput screening. By forming hydrogen bond with O4 atom of FAD isoalloxazine ring and reducing steric hindrance, the conformation of FAD isoalloxazine ring in SmFMOF52G is more stable, and NADPH and substrate are closer to FAD isoalloxazine ring, shortening the distances of hydrogen transfer and substrate oxygenation, thereby increasing the rate of reduction and oxidation reactions and enhancing enzyme activity. Additionally, the overall structural stability and substrate binding capacity of the SmFMOF52G have significant improved than that of SmFMOWT. The strategy used in this study to improve the enzyme activity of FMOs may have generality, providing important references for the rational and semi-rational engineering of FMOs.

USP47 deficiency in mice modulates tumor infiltrating immune cells and enhances antitumor immune responses in prostate cancer.

This study investigates the role of USP47, a deubiquitinating enzyme, in the tumor microenvironment and its impact on antitumor immune responses. Analysis of TCGA database revealed distinct expression patterns of USP47 in various tumor tissues and normal tissues. Prostate adenocarcinoma showed significant downregulation of USP47 compared to normal tissue. Correlation analysis demonstrated a positive association between USP47 expression levels and infiltrating CD8+ T cells, neutrophils, and macrophages, while showing a negative correlation with NKT cells. Furthermore, using Usp47 knockout mice, we observed a slower tumor growth rate and reduced tumor burden. The absence of USP47 led to increased infiltration of immune cells, including neutrophils, macrophages, NK cells, NKT cells, and T cells. Additionally, USP47 deficiency resulted in enhanced activation of cytotoxic T lymphocytes (CTLs) and altered T cell subsets within the tumor microenvironment. These findings suggest that USP47 plays a critical role in modulating the tumor microenvironment and promoting antitumor immune responses, highlighting its potential as a therapeutic target in prostate cancer.

A rapid bacterial pathogen and antimicrobial resistance diagnosis workflow using Oxford nanopore adaptive sequencing method.

Metagenomic sequencing analysis (mNGS) has been implemented as an alternative approach for pathogen diagnosis in recent years, which is independent of cultivation and is able to identify all potential antibiotic resistance genes (ARGs). However, current mNGS methods have to deal with low amounts of prokaryotic deoxyribonucleic acid (DNA) and high amounts of host DNA in clinical samples, which significantly decrease the overall microbial detection resolution. The recently released nanopore adaptive sampling (NAS) technology facilitates immediate mapping of individual nucleotides to a given reference as each molecule is sequenced. User-defined thresholds allow for the retention or rejection of specific molecules, informed by the real-time reference mapping results, as they are physically passing through a given sequencing nanopore. We developed a metagenomics workflow for ultra-sensitive diagnosis of bacterial pathogens and ARGs from clinical samples, which is based on the efficient selective 'human host depletion' NAS sequencing, real-time species identification and species-specific resistance gene prediction. Our method increased the microbial sequence yield at least 8-fold in all 21 sequenced clinical Bronchoalveolar Lavage Fluid (BALF) samples (4.5 h from sample to result) and accurately detected the ARGs at species level. The species-level positive percent agreement between metagenomic sequencing and laboratory culturing was 100% (16/16) and negative percent agreement was 100% (5/5) in our approach. Further work is required for a more robust validation of our approach with large sample size to allow its application to other infection types.

An RNA aptamer photoelectrochemical biosensor based on the exciton energy transfer constructed for theophylline detection.

A novel photoelectrochemical (PEC) biosensor was developed incorporating a specifically designed RNA aptamer for the detection of theophylline (TP). This involved utilizing two nucleotide base aptamers with tailored sequences designed to target TP. The 3' end of a single-stranded RNA sequence (5'-GGAUACCA-(CH2)6-SH-3') and the 5' end of a complementary stranded RNA sequence (5'-HS-(CH2)6-CCUUGGAAGCC-3') were linked to gold nanoparticles (AuNPs) and CdS quantum dots (QDs), respectively. These two single-stranded RNAs (ssRNA) formed a double-stranded RNA (dsRNA) capable of recognizing TP. This major structural change altered the spacing between QDs and NPs, which signaled the presence and concentration of TP. TP was photoelectrochemical catalytic oxidation by the hole of CdS QDs under illumination, then anode photocurrent was generated. Due to the increase in surface impedance and the effect of exciton energy transfer (EET) between QDs and AuNPs, the photocurrent would undergo varying degrees of change. TP was detected by changes in photocurrent. PEC detection of TP was achieved in the range of 0.1 µM-200 µM. The detection limit was 0.033 µM. The method exhibited commendable reproducibility and remarkable selectivity. The biosensor was used to measure TP content in tea, beverages and blood samples, resulting in satisfactory recovery rates.

Is atezolizumab plus bevacizumab as first-line therapy for unresectable hepatocellular carcinoma superior to lenvatinib? a systematic review and meta­analysis.

BACKGROUND: This meta-analysis was dedicated to evaluating the effectiveness and safety of Atezolizumab plus Bevacizumab (Atez/Bev) and Lenvatinib (LEN) as first-line systematic therapy for unresectable hepatocellular carcinoma (u-HCC). METHODS: The prospective protocol for this study was registered with the PROSPERO (Registration number: CRD42022356874). Literature searches were conducted in PubMed, EMBASE database Cochrane Library, and Web Science to determine all clinical controlled studies that reported Atez/Bev and LEN for treating u-HCC. We. evaluated as primary end-point overall survival (OS) and progression-free survival (PFS), as well as other outcomes such as tumor response and adverse events (AEs).Quality assessment and data extraction of studies were conducted independently by three reviewers. Mean difference (MD) and odds ratio (OR) with 95% confidence interval (CI) were calculated using a fixed-effects or random-effects model. The meta-analysis was performed with RevMan 5.3 software. RESULTS: 12 retrospective cohort studies (RCSs) involving a total of 4948 patients were finally included. The results showed that compared with LEN, Atez/Bev can improve the patient's PFS (HR = 0.80, 95% CI: 0.72 ~ 0.88; p < 0.0001) and reduce the rate of overall AEs (OR = 0.46 95% CI: 0.38 ~ 0.55, p < 0.00001) and grade ≥ 3 AEs (OR = 0.43; 95% CI: 0.36 ~ 0.51, p < 0.00001), while there is no difference between OS and treatment responses rate (objective response rate, disease control rate, complete response, partial response, progressive disease, and stable disease) between two groups. In addition, the subgroup analysis shows that Atez/Bev can promote the OS of patients with viral hepatitis. (HR = 0.79, 95% CI: 0.67 ~ 0.95; p = 0.01), while LEN has an advantage in improving OS in patients with Child-Pugh grade B liver function (HR = 1.98, 95% CI: 1.50 ~ 2.63; p < 0.00001). CONCLUSION: Current evidence shows that compared with LEN, Atez/Bev has more advantages in PFS and safety in treating u-HCC and can improve the OS of patients with viral. LEN has advantages in improving the OS of patients with grade B liver function. However, more multicenter randomized controlled experiments are needed in the future to verify our results.

Sex Differences in Outcome of Aneurysmal Subarachnoid Hemorrhage and Its Relation to Postoperative Cerebral Ischemia.

BACKGROUND: Whether there is a sex difference in the outcome of aneurysmal subarachnoid hemorrhage (aSAH) remains controversial, and clarifying the role of women in postoperative cerebral ischemic events can help us to understand its relationship with poor prognosis. Therefore, the purpose of this study was to elucidate the relationship between the three aspects of sex differences, postoperative cerebral ischemia, and poor prognosis after aSAH. METHODS: A total of 472 patients admitted within 72 h after aSAH between January 2018 and December 2022 were included. We systematically analyzed the characteristics of sex differences in aSAH and explored the relationship between delayed cerebral ischemia (DCI), surgery-related cerebral infarction (SRCI), and poor prognosis (modified Rankin Scale > 2). RESULTS: Compared with women, men were in worse condition and had more intracerebral hematoma (p = 0.001) on admission, whereas women were older (p < 0.001) and had more multiple aneurysms (p = 0.002). During hospitalization, men were more likely to experience emergency intubation (p = 0.036) and tracheotomy (p = 0.013). Women achieved functional independence at discharge at a similar rate to men (p = 0.394). Among postoperative complications, the incidence of DCI (22% vs. 12%, p = 0.01) and urinary tract infection (p = 0.022) was significantly higher in women. After adjusting for age, multivariable regression analysis showed that hypertension (odds ratio [OR] 2.139, 95% confidence interval [CI] 1.027-4.457), preoperative rerupture (OR 12.240, 95% CI 1.491-100.458), pulmonary infection (OR 2.297, 95% CI 1.070-4.930), external ventricular drainage placement (OR 4.382, 95% CI 1.550-12.390), bacteremia (OR 14.943, 95% CI 1.412-158.117), SRCI (OR 8.588, 95% CI 4.092-18.023), venous thrombosis (OR 5.283, 95% CI 1.859-15.013), higher modified Fisher grades (p = 0.003), and Hunt-Hess grades (p = 0.035) were associated with poor prognosis, whereas DCI (OR 1.394, 95% CI 0.591-3.292) was not an independent risk factor for poor prognosis. The proportion of patients who fully recovered from cerebral ischemia was higher in the DCI group (p < 0.001) compared with the SRCI group, and more patients were discharged with modified Rankin Scale > 2 in the SRCI group (p = 0.005). CONCLUSIONS: Women have a higher incidence of DCI, but there is no sex difference in outcomes after aSAH, and poor prognosis is associated with worse admission condition and perioperative complications. SRCI is a strong independent risk factor for poor prognosis, whereas DCI is not.

Prostate Health Index Density Outperforms Prostate-specific Antigen Density in the Diagnosis of Clinically Significant Prostate Cancer in Equivocal Magnetic Resonance Imaging of the Prostate: A Multicenter Evaluation.

PURPOSE: We compare Prostate Health Index, Prostate Health Index density, and PSA density in predicting clinically significant prostate cancer in MRI-guided prostate biopsy. MATERIALS AND METHODS: This is a multicenter evaluation of prospectively maintained prostate biopsy databases at 10 urology centers. Men with Prostate Health Index and MRI-guided targeted and systematic prostate biopsy performed and without prior prostate cancer diagnosis were included. The additional value of PSA density, Prostate Health Index, and Prostate Health Index density to MRI PI-RADS (Prostate Imaging Reporting & Data System) score was evaluated with multivariable analyses, area under the curve, and decision curve analyses. The proportion of unnecessary biopsies that can be avoided are estimated for clinically significant prostate cancer (International Society of Urological Pathology group ≥2 prostate cancer). RESULTS: A total of 1,215 men were analyzed. Prostate cancer and clinically significant prostate cancer were diagnosed in 51% (617/1,215) and 35% (422/1,215) of men, respectively. Clinically significant prostate cancer was diagnosed in 4.4% (3/68), 15% (72/470), 39% (176/446), and 74% (171/231) of highest PI-RADS score of 2, 3, 4, and 5 lesions, respectively. In multivariable analyses, independent predictors for clinically significant prostate cancer detection included Prostate Health Index (OR 1.04), prostate volume (OR 0.97), and PI-RADS score 4 (OR 2.81) and 5 (OR 8.34). Area under the curve for clinically significant prostate cancer of PI-RADS + Prostate Health Index density (0.85) was superior to PI-RADS + PSA density (0.81), Prostate Health Index density (0.81), Prostate Health Index (0.78), PI-RADS (0.76), PSA density (0.72), and PSA (0.60) in the whole cohort, and the superiority of Prostate Health Index density was also observed in PI-RADS 3 lesions. Decision curve analysis showed Prostate Health Index density achieving the best net clinical benefit in PI-RADS 3 or 4 cases. Among PI-RADS 3 lesions, using cutoffs of PSA density 0.15, Prostate Health Index 38.0, and Prostate Health Index density 0.83 could reduce 58%, 67%, and 72% of unnecessary biopsies, respectively. CONCLUSIONS: Prostate Health Index density outperformed Prostate Health Index or PSA density in clinically significant prostate cancer detection in men with multiparametric MRI performed, and further reduced unnecessary biopsies in PI-RADS 3 lesions.

Impact of the uniaxial strain on terahertz modulation characteristics in flexible epitaxial VO2 film across the phase transition.

Exploring flexible electronics is on the verge of innovative breakthroughs in terahertz (THz) communication technology. Vanadium dioxide (VO2) with insulator-metal transition (IMT) has excellent application potential in various THz smart devices, but the associated THz modulation properties in the flexible state have rarely been reported. Herein, we deposited an epitaxial VO2 film on a flexible mica substrate via pulsed-laser deposition and investigated its THz modulation properties under different uniaxial strains across the phase transition. It was observed that the THz modulation depth increases under compressive strain and decreases under tensile strain. Moreover, the phase-transition threshold depends on the uniaxial strain. Particularly, the rate of the phase transition temperature depends on the uniaxial strain and reaches approximately 6 °C/% in the temperature-induced phase transition. The optical trigger threshold in laser-induced phase transition decreased by 38.9% under compressive strain but increased by 36.7% under tensile strain, compared to the initial state without uniaxial strain. These findings demonstrate the uniaxial strain-induced low-power triggered THz modulation and provide new insights for applying phase transition oxide films in THz flexible electronics.

Fibroblast growth factor 13 is involved in the pathogenesis of temporal lobe epilepsy.

BACKGROUND: Temporal lobe epilepsy (TLE) is the most common drug-resistant epilepsy in adults, with pathological mechanisms remaining to be fully elucidated. Fibroblast Growth Factor 13 (FGF13) encodes an intracellular protein involved in microtubule stabilization and regulation of voltage-gated sodium channels (VGSCs) function. FGF13 mutation has been identified in patients with inherent seizure, suggesting a potential association between FGF13 and the etiology of TLE. Here, we set to explore the pathological role of FGF13 in the etiology of TLE. RESULTS: We found that the expression of FGF13 was increased in the cortical lesions and CA1 region of sclerotic hippocampus and correlated with the seizure frequency in TLE patients. Also, Fgf13 expression was increased in the hippocampus of chronic TLE mice generated by kainic acid (KA) injection. Furthermore, Fgf13 knockdown or overexpression was respectively found to attenuate or potentiate the effects of KA on axonal length, somatic area and the VGSCs-mediated current in the hippocampal neurons. CONCLUSIONS: Taken together, these findings suggest that FGF13 is involved in the pathogenesis of TLE by modulating microtubule activity and neuronal excitability.

A new abietane diterpenoid from Lycopodium complanatum.

A new abietane diterpenoid, 1ß, 11-epoxyabieta-12-hydroxy-8, 11, 13-triene-7-one (1), along with three known compounds (2-4), was isolated from Lycopodium complanatum. Their structures were confirmed by the analysis of 1D, 2D NMR and HRESIMS data, and comparison with previous spectral data. All compounds were tested for inhibitory activities against A549, HepG2 and MCF-7 tumor cell lines. [Figure: see text].

Prognostic significance of fibrinogen and neutrophil/lymphocyte ratio score and D-dimer/Albumin ratio for prognosis in patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND: Recent research indicates that systemic inflammation significantly affects the overall prognosis of individuals with aneurysmal subarachnoid hemorrhage. To delve deeper into this issue, a retrospective study was undertaken. The study aimed to investigate the relationship between fibrinogen and neutrophil/lymphocyte ratio scores, D-dimer/Albumin ratios, and the Glasgow Outcome Scale at 6 months post-discharge for patients with aSAH. METHODS: A retrospective analysis was conducted on 321 patients who experienced aneurysmal subarachnoid hemorrhage. These patients were monitored using the Glasgow Outcome Scale six months after being discharged from Huizhou Central People's Hospital. Patients with GOS scores between 1 and 3 were classified as having a poor prognosis, while those with scores ranging from 4 to 5 were considered to have a good prognosis. To create distinct sets, patients were randomly divided into both training and validation groups. The best cut-off value for the D-dimer/Albumin ratio was established through ROC curves, and the scores for fibrinogen and the neutrophil/lymphocyte ratio were calculated. Utilizing multivariate logistic regression analysis, independent risk factors linked to an unfavorable prognosis in aSAH patients were identified. A nomogram model was developed and validated based on these findings, providing an improved approach for evaluating the prognostic influence of risk factors. To gauge the model's predictive performance, several analytical tools such as ROC curves, calibration curves, and decision curve analysis were employed. This comprehensive approach ensured a thorough assessment of the prognostic prediction capabilities of the model. RESULTS: Multivariate regression analysis revealed that Age (OR=3.87, 95%CI=1.54-9.73, p=0.004), Pneumonia (OR=3.54, 95%CI=1.41-8.86, p=0.007), WFNS (OR=3.24, 95%CI=1.23-8.54, p=0.017), DAR (OR=2.88, 95%CI=1.13-7.34, p=0.027), and F-NLR (OR=3.12, 95%CI=1.22-7.97, p=0.017) were identified as independent risk factors influencing the prognosis of patients with aSAH. Additionally, the area under the ROC curve was 0.866 (95%CI=0.805-0.927) for the training set and 0.924 (95%CI=0.849-0.999) for the validation set. The calibration curve analysis demonstrated a minor error of 0.02 for the training set and 0.051 for the validation set. Furthermore, both the training set and validation set displayed significant clinical benefits according to the DCA curves, underscoring the meaningful utility of the developed nomogram. CONCLUSIONS: Fibrinogen and neutrophil/lymphocyte ratio scores, and the D-dimer/Albumin ratio emerged as significant independent risk factors for prognosticating the outcomes of patients with aSAH. Leveraging these factors, a robust nomogram model was meticulously developed, showcasing its impressive precision in prognostic predictions. These results underscore the promising clinical applicability of these biomarkers as effective prognostic indicators for individuals afflicted by aSAH.

Childhood adversity, adulthood adversity and suicidal ideation in Chinese patients with major depressive disorder: in line with stress sensitization.

The stress sensitization model indicates that early adversity (e.g., childhood stress) sensitizes individuals to subsequent proximal stress (e.g., stressful life events in adult life), thereby increasing their vulnerability to psychiatric disorders. However, the effect of stress sensitization on suicidality in patients with major depressive disorder (MDD) has not been previously investigated. Data for the present study were derived from the Objective Diagnostic Markers and Personalized Intervention in MDD Patients (ODMPIM) study. The psychiatric diagnosis and suicidal ideation were evaluated by the Mini-International Neuropsychiatric Interview (M.I.N.I.). We used a multiple logistic analysis to examine the association among childhood adversity (CA), adulthood adversity (AA) and suicidal ideation. Among 1084 MDD patients, 48.6% had suicidal ideation and 65.6% experienced life adversity during their childhood or adulthood. Patients who reported suicidal ideation were more likely to report CA (46.7% vs. 38.7%, P = 0.008) or AA (49.5% vs. 40.9%, P = 0.004) than patients without suicidal ideation. Patients who experienced two waves of adversity (both CA and AA) were associated with higher rates of suicidal ideation (odds ratio = 1.68, 95% CI = 1.19-2.37, P = 0.003); however, neither CA nor AA alone was associated with suicidal ideation. This study first verifies the hypothesis of stress sensitization on suicidal ideation in patients with MDD. Focusing on stress sensitization may enhance the early identification of MDD patients at suicidal risk and the ability to provide timely and appropriate intervention. Clinicaltrials.gov identifier: NCT02023567.

Comparison of Mirabegron plus Tamsulosin and Tamsulosin Monotherapy for the Treatment of Ureteral Stent-Related Symptoms: A Prospective Randomized Study.

INTRODUCTION: The aim of this study was to compare the efficacy of mirabegron plus tamsulosin to tamsulosin monotherapy in terms of ureteral stent-related discomfort after ureteroscopic lithotripsy. METHODS: A total of 102 patients undergoing ureteroscopic lithotripsy and silicone ureteral stent placement were enrolled in this study. Patients were randomized 1:1 to receive either tamsulosin 0.4 mg once daily or mirabegron 50 mg + tamsulosin 0.4 mg once daily during the stenting period. Before the operation, the IPSS, QOL, and pain score were collected. On the day of ureteral stent removal, the USSQ, analgesic usage amount was collected and recorded. RESULTS: The median USSQ-body pain score in the tamsulosin group and tamsulosin + mirabegron group was 15 and 16, respectively (p = 0.530). The median analgesic usage in the two groups was 3 and 2, respectively (p = 0.170). The median USSQ-urinary symptoms, USSQ-general health, USSQ-work performance, USSQ-sexual matters, and USSQ-additional problems in the two groups were 26 and 26 (p = 0.194), 11 and 12 (p = 0.068), 12 and 13 (p = 0.105), 2 and 2 (p = 0.437), 9 and 9 (p = 0.533), respectively. The international patients used more analgesics than Chinese patients (6 vs. 1, p = 0.015). CONCLUSION: Compared to tamsulosin alone, tamsulosin + mirabegron showed no additional benefit on the ureteral stent-related pain control after ureteroscopic lithotripsy and silicone stent placement. There was no significant difference on the analgesic usage and USSQ scores between the two groups. Chinese patients request fewer analgesics than international patients.

Regulation of FOXO3 on neuronal ferroptosis after intracerebral hemorrhage via modulating NOX4 transcription.

INTRODUCTION: Intracerebral hemorrhage (ICH) is known to trigger neuronal ferroptosis while forkhead box O3 (FOXO3) is implicated in ICH. This study aimed to determine the specific effect of FOXO3 on neuronal ferroptosis after ICH. METHODS: The ICH mouse model was established through the injection of bacterial collagenase type IV and the cell model was established in Hemin-induced HT-22 cells. Subsequently, neurological functions, brain water content, and histopathological changes in mice were assessed. HT-22 cell activity was examined via cell counting kit-8 (CCK-8) method, and the levels of FOXO3, NADPH oxidase 4 (NOX4), and glutathione peroxidase 4 (GPX4) in brain tissues and HT-22 cells were measured. Fe2+ concentration and the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) in the tissues and cells were examined. The binding relationship between FOXO3 and the NOX4 promoter region was determined via chromatin-immunoprecipitation (Ch-IP). Rescue experiments were designed to probe the role of NOX4 in the regulation of FOXO3 on neuronal ferroptosis. RESULTS: FOXO3 was highly-expressed in ICH models while silencing FOXO3 alleviated brain damage, edema, and inflammatory infiltration in ICH mice. Meanwhile, silencing FOXO3 enhanced cell activity, diminished ROS and MDA activities and Fe2+ concentration, and elevated GSH and GPX4 levels in the tissues or cells. FOXO3 could bind to the NOX4 promoter and upregulate NOX4 transcription. NOX4 overexpression partially neutralized the repressive role of silencing FOXO3 in neuronal ferroptosis. CONCLUSION: Silencing FOXO3 attenuated ICH-induced neuronal ferroptosis via down-regulating NOX4 transcription levels, thus ameliorating post-ICH brain damage.

Application of a three-dimensional visualization model in intraoperative guidance of percutaneous nephrolithotomy.

OBJECTIVES: To establish a three-dimensional visualization model of percutaneous nephrolithotomy, apply it to guiding intraoperative puncture in a mixed reality environment, and evaluate its accuracy and clinical value. METHODS: Patients with percutaneous nephrolithotomy indications were prospectively divided into three-dimensional group and control group with a ratio of 1:2. For patients in three-dimensional group, positioning markers were pasted on the skin and enhanced computed tomography scanning was performed in the prone position. Holographic three-dimensional models were made and puncture routes were planned before operation. During the operation, the three-dimensional model was displayed through HoloLens glass and visually registered with the patient's body. Puncture of the target renal calyx was performed under three-dimensional-image guiding and ultrasonic monitoring. Patients in the control group underwent routine percutaneous nephrolithotomy in the prone position under the monitoring of B-ultrasound. Deviation distance of the kidney, puncture time, puncture attempts, channel coincidence rate, stone clearance rate, and postoperative complications were assessed. RESULTS: Twenty-one and 40 patients were enrolled in three-dimensional and control group, respectively. For three-dimensional group, the average deviation between virtual and real kidney was 3.1 ± 2.9 mm. All punctures were performed according to preoperative planning. Compared with the control group, the three-dimensional group had shorter puncture time (8.9 ± 3.3 vs 14.5 ± 6.1 min, P < 0.001), fewer puncture attempts (1.4 ± 0.6 vs 2.2 ± 1.5, P = 0.009), and might also have a better performance in stone clearance rate (90.5% vs 72.5%, P = 0.19) and postoperative complications (P = 0.074). CONCLUSIONS: The percutaneous nephrolithotomy three-dimensional model manifested acceptable accuracy and good value for guiding puncture in a mixed reality environment.

Two New C21 Steroidal Glycosides from Selaginella Braunii Baker.

Two new C21 steroidal glycosides, brapreguanes A and B (1-2) were isolated from 75 % aqueous ethanol extract of Selaginella braunii Baker. Their structures were established by spectroscopic analyses (1D/2D NMR spectra and HR-ESI-MS). The absolute configurations of sugar were elucidated by enzymatic hydrolysis and GCMS analysis. In addition, all compounds were evaluated for the anti-proliferative activities against various human cancer cells in vitro. Compounds exhibited no inhibition to various human cancer cells.

Computed tomographic parameters correlate with coagulation disorders in isolated traumatic brain injury.

BACKGROUND AND OBJECTIVE: The imbalanced hemostatic equilibrium caused by brain tissue or vessel damage underlies the pathophysiology of traumatic brain injury (TBI)-induced coagulopathy, and cranial computed tomography (CT) is the gold standard for evaluating brain injury. The present study aimed to explore the correlation between quantitative cranial CT parameters and coagulopathy after TBI. METHODS: We retrospectively collected the medical records of TBI patients with extracranial abbreviated injury scale (AIS) scores <3 who were admitted to our institution. The quantitative cranial CT parameters of patients with and without coagulopathy were compared, and univariate correlation analysis between CT parameters and coagulation subtest values and platelet counts was performed. The predictors for each subtest of coagulation function were probed by multivariate regression. RESULTS: TBI patients with coagulopathy had a larger intracerebral haematoma/contusion (ICH/C) volume (p < 0.001), a higher incidence of compressed basal cisterns (p = 0.015), a higher Graeb score (p < 0.001) and subarachnoid haematoma (Fisher's scaling score) (p = 0.019) than those without coagulopathy. IH/C volume was identified as an independent risk factor for predicting coagulopathy. ICH/C volume showed a significantly positive correlation with APTT (Pearson's correlation = 0.333, p < 0.001), while a significant negative correlation with PLT (Pearson's correlation = - 0.312, p < 0.001). CONCLUSION: ICH/C volume was a main quantitative cranial CT parameter for predicting coagulopathy, suggesting that parenchymal brain damage and vessel injury were closely associated with coagulopathy after TBI.

Urchin-Type Architecture Assembled by Cobalt Phosphide Nanorods Encapsulated in Graphene Framework as an Advanced Anode for Alkali Metal Ion Batteries.

Urchin-type cobalt phosphide microparticles assembled by nanorod were encapsulated in a graphene framework membrane (CoP@GF), and used as a binder-free electrode for alkali metal ion batteries. Electrochemical measurements indicate that this membrane exhibits enhanced reversible lithium, sodium, and potassium storage capabilities. Moreover, the energy storage properties of CoP@GF electrodes in alkali metal ion batteries display an order of Li>Na>K. DFT calculations on adsorption energy of CoP surfaces for Li, Na, and K indicated that CoP surfaces were more favorable to transfer electrons to Li atoms than Na and K, and the surface reactivity can be ordered as Li-CoP>Na-CoP>K-CoP; thus, CoP@GF exhibits better storage capacity for lithium. This work provides experimental and theoretical basis for understanding the electrochemical performance of cobalt phosphide-based membranes for alkali metal ion batteries.