Anionic cardiolipin stabilizes the transmembrane region of hyaluronan synthase and promotes catalysis-relevant dynamics.

Hyaluronic acid (HA) is a glycosaminoglycan essential for cellular processes and finding increasingly applications in medicine, pharmaceuticals, and cosmetics. While membrane-integrated Class I hyaluronan synthase (HAS) catalyzes HA synthesis in most organisms, the molecular mechanisms by which HAS-lipid interactions impact HAS catalysis remain unclear. This study employed coarse-grained molecular dynamics simulation combined with dimensionality reduction to uncover the interplay between lipids and Streptococcus equisimilis HAS (SeHAS). A minimum of 67 % cardiolipin is necessary for HA synthesis, as determined through simulations using gradient-composed membranes. The anionic cardiolipin stabilizes the cationic transmembrane regions of SeHAS and thereby maintains its conformation. Moreover, the highly dynamic cardiolipin is required to modulate the catalysis-relevant motions in HAS and thus facilitate HA synthesis. These findings provide molecular insights essential not only for understanding the physiological functions of HAS, but also for the development of cell factories and enzyme catalysts for HA production.

Advances in Functionalized Hydrogels in the Treatment of Myocardial Infarction and Drug-Delivery Strategies.

Myocardial infarction (MI) is a serious cardiovascular disease with high morbidity and mortality rates, posing a significant threat to patient's health and quality of life. Following a MI, the damaged myocardial tissue is typically not fully repaired, leading to permanent impairment of myocardial function. While traditional treatments can alleviate symptoms and reduce pain, their ability to repair damaged heart muscle tissue is limited. Functionalized hydrogels, a broad category of materials with diverse functionalities, can enhance the properties of hydrogels to cater to the needs of tissue engineering, drug delivery, medical dressings, and other applications. Recently, functionalized hydrogels have emerged as a promising new therapeutic approach for the treatment of MI. Functionalized hydrogels possess outstanding biocompatibility, customizable mechanical properties, and drug-release capabilities. These properties enable them to offer scaffold support, drug release, and tissue regeneration promotion, making them a promising approach for treating MI. This paper aims to evaluate the advancements and delivery methods of functionalized hydrogels for treating MI, while also discussing their potential and the challenges they may pose for future clinical use.

Shock Wave Therapy Alleviates Hypoxia/Reoxygenation-Induced Cardiomyocyte Injury by Inhibiting Both Apoptosis and Ferroptosis.

Shock wave therapy (SWT) is a new alternative therapy for patients with severe coronary artery disease that improves myocardial ischemic symptoms by delivering low-energy shock wave stimulation to ischaemic myocardium with low-energy pulsed waves. However, the specific mechanism of its protective effect is not fully understood, especially for the protective mechanism in cardiomyocytes after hypoxia/reoxygenation (H/R). We selected a rat H9c2 cardiomyocyte cell line to establish a stable H/R cardiomyocyte injury model by hypoxia/reoxygenation, and then used SWT for therapeutic intervention to explore its cardiomyocyte protective mechanisms. The results showed that SWT significantly increased cell viability and GSH levels while decreasing LDH levels, ROS levels, and MDA levels. SWT also improved mitochondrial morphology and function of cells after H/R. Meanwhile, we found that SWT could increase the expression of GPX4, xCT, and Bcl-2, while decreasing the expression of Bax and cleaved caspase-3, and inhibiting cardiomyocyte apoptosis and ferroptosis. Moreover, this protective effect of SWT on cardiomyocytes could be significantly reversed by knockdown of xCT, a key regulator protein of ferroptosis. In conclusion, our study shows that SWT can attenuate hypoxia-reoxygenation-induced myocardial injury and protect cardiomyocyte function by inhibiting H/R-induced apoptosis and ferroptosis, and this therapy may have important applications in the treatment of clinical myocardial ischemic diseases.

The Predictive Value of Atherogenic Index of Plasma, Non- High Density Lipoprotein Cholesterol (Non-HDL-C), Non-HDL-C/HDL-C, and Lipoprotein Combine Index for Stroke Incidence and Prognosis in Maintenance Hemodialysis Patients.

Purpose: The serum lipid level is strongly associated with atherosclerosis. However, research on the relationship between lipid-derived indices and acute ischemic stroke (AIS) occurrence in hemodialysis populations is limited. This study aimed to explore the predictive value of lipid-derived indices, including atherogenic index of plasma (AIP), Non- high density lipoprotein cholesterol (Non-HDL-C), Non-HDL-C/HDL-C, and lipoprotein combine index (LCI) in clinical practice for the occurrence and prognosis of AIS in hemodialysis patients. Methods: A total of 451 patients undergoing maintenance hemodialysis were screened and 350 were enrolled in this study. The lipid parameters exhibit a progressive increase across the tertiles, with values rising from Q1 through Q3. Enrolled patients were divided into three groups (Q1, Q2, and Q3) based on tertiles of AIP, Non-HDL-C, Non-HDL-C/HDL-C, and LCI values. Kaplan-Meier curves were performed to investigate the association between the AIP, Non-HDL-C, Non-HDL-C/HDL-C, LCI and AIS-free survival in hemodialysis patients. Chi-square analysis was used to explore the association between the AIP, Non-HDL-C, Non-HDL-C/HDL-C, LCI and AIS outcomes in hemodialysis patients. AIS outcomes were assessed using the modified Rankin Scale (mRS). Results: Kaplan-Meier analysis revealed that the AIS-free survival rates were significantly higher in the Q1 group compared to Q2 and Q3 groups for AIP, Non-HDL-C, Non-HDL-C/HDL-C, and LCI. Log rank tests showed statistically significant differences between the Q1 group and the Q2 and Q3 groups (p < 0.05 for all). The proportion of patients with a good outcome mRS was higher in the Q1 group compared to the Q2-Q3 groups (AIP: 0.818 vs 0.792; Non- HDL-C: 0.866 vs 0.767; Non- HDL-C/HDL-C: 0.867 vs 0.767; LCI: 0.938 vs 0.750). Conclusion: The four lipid-derived parameters are effective predictors of AIS in patients undergoing hemodialysis, and AIP has a strongest correlation with the risk of AIS. Hemodialysis patients with elevated levels of the four lipid-derived indices had a higher incidence of AIS and poorer functional outcomes compared to those with lower levels. Our conclusions may require confirmation by further research in the future.

Crowd-sourced benchmarking of single-sample tumor subclonal reconstruction.

Subclonal reconstruction algorithms use bulk DNA sequencing data to quantify parameters of tumor evolution, allowing an assessment of how cancers initiate, progress and respond to selective pressures. We launched the ICGC-TCGA (International Cancer Genome Consortium-The Cancer Genome Atlas) DREAM Somatic Mutation Calling Tumor Heterogeneity and Evolution Challenge to benchmark existing subclonal reconstruction algorithms. This 7-year community effort used cloud computing to benchmark 31 subclonal reconstruction algorithms on 51 simulated tumors. Algorithms were scored on seven independent tasks, leading to 12,061 total runs. Algorithm choice influenced performance substantially more than tumor features but purity-adjusted read depth, copy-number state and read mappability were associated with the performance of most algorithms on most tasks. No single algorithm was a top performer for all seven tasks and existing ensemble strategies were unable to outperform the best individual methods, highlighting a key research need. All containerized methods, evaluation code and datasets are available to support further assessment of the determinants of subclonal reconstruction accuracy and development of improved methods to understand tumor evolution.

GPR168 functions as a tumor suppressor in mouse melanoma by restraining Akt signaling pathway.

Malignant melanoma (MM) is a malignant tumor associated with high mortality rates and propensity for metastasis. Despite advancement in treatment, the incidence of MM continue to rise globally. GPR168, also known as MrgprF, is a MAS related GPR family member. The low expression of GPR168 has also been reported in many malignant tumors including MM. In the study, the statistical analysis from The Cancer Genome Atlas (TCGA) revealed a significant down regulation of GPR168 in melanoma compared to normal melanocytes, underscoring its importance in MM. The aim of the present study is to investigate the affect of GPR168 overexpression and elucidate its molecular mechanisms in MM cells. In addition, we used mouse melanoma B16-F10 cell line and xenograph tumor model to explore the function of GPR168 in melanoma. Our findings demonstrate that GPR168 overexpression could inhibit B16-F10 cell proliferation, migration, and xenografts tumor growth. Further, mechanistic studies revealed that GPR168 affected B16-F10 progress through Akt signal pathway with the decreased expression of p-Akt, p-GSK-3ß, ß-catenin, Myc, CyclinD1 and CDK4. In order to validate these findings, a rescue experiment was formulated employing GPR168 polyclonal antibody (Anti-GPR168 pAbs) to block GPR168 functionality. The addition of Anti-GPR168 pAbs into the culture medium restored both cell proliferation and migration. In conclusion, the overexpression of GPR168 in mouse melanoma B16-F10 cells suppressed proliferation and migration through the Akt signaling pathway. These findings collectively propose GPR168 as a promising novel tumor suppressor in MM, suggesting its potential as a therapeutic target in future interventions.

Analysis of m6A-regulated genes and subtype classification in lupus nephritis.

BACKGROUND: Lupus nephritis (LN) is the most common and severe clinical manifestation of systemic lupus erythematosus (SLE). N6-methyladenosine (m6A) is a reversible RNA modification and has been implicated in various biological processes. However, the roles of m6A regulators in LN are not fully demonstrated. METHODS: We downloaded the kidney tissue transcriptome dataset of LN patients and normal controls from the GEO database and extracted the expression levels of m6A regulators. We constructed and compared Random Forest (RF) and Support Vector Machine (SVM) models, and subsequently selected featured genes to develop nomogram models. The m6A subtypes were identified based on significantly differentially expressed m6A regulators, and the m6A gene subtypes were identified based on m6A-associated differential genes, and the two m6A modification patterns were comprehensively evaluated. RESULTS: We obtained the GSE32591 and GSE112943 datasets from the GEO database, including 78 LN samples and 36 normal control samples. We extracted the expression levels of 20 m6A regulators. By RF analysis we identified 7 characteristic m6A regulators and constructed nomogramh models with these 7 genes. We identified two m6A subtypes based on these seven important m6A regulators, and the immune cell infiltration levels of the two subtype clusters were significantly different. We identified two more m6A gene subtypes based on m6A-associated DEGs. We calculated the m6A scores using the principal component analysis (PCA) algorithm and found that the m6A scores of m6A cluster A and gene cluster A were lower than those of m6A cluster B and gene cluster B. In addition, we found that the levels of inflammatory factors were also significantly different between m6A clusters and gene clusters. CONCLUSION: This study confirms that m6A regulators are involved in the LN process through different modes of action and provide new diagnostic and therapeutic targets for LN.

The effect of corneal power on the accuracy of 14 IOL power formulas.

BACKGROUND: This study evaluates the impact of corneal power on the accuracy of 14 newer intraocular lens (IOL) calculation formulas in cataract surgery. The aim is to assess how these formulas perform across different corneal curvature ranges, thereby guiding more precise IOL selection. METHODS: In this retrospective case series, 336 eyes from 336 patients who underwent cataract surgery were studied. The cohort was divided into three groups according to preoperative corneal power. Key metrics analyzed included mean prediction error (PE), standard deviation of PE (SD), mean absolute prediction error (MAE), median absolute error (MedAE), and the percentage of eyes with PE within ± 0.25 D, 0.50 D, ± 0.75 D, ± 1.00 D and ± 2.00 D. RESULTS: In the flat K group (Km < 43 D), VRF-G, Emmetropia Verifying Optical Version 2.0 (EVO2.0), Kane, and Hoffer QST demonstrated lower SDs (± 0.373D, ± 0.379D, ± 0.380D, ± 0.418D, respectively) compared to the VRF formula (all P < 0.05). EVO2.0 and K6 showed significantly different SDs compared to Barrett Universal II (BUII) (all P < 0.02). In the medium K group (43 D ≤ Km < 46 D), VRF-G, BUII, Karmona, K6, EVO2.0, Kane, and Pearl-DGS recorded lower MAEs (0.307D to 0.320D) than Olsen (OLCR) and Castrop (all P < 0.03), with RBF3.0 having the second lowest MAE (0.309D), significantly lower than VRF and Olsen (OLCR) (all P < 0.05). In the steep K group (Km ≥ 46D), RBF3.0, K6, and Kane achieved significantly lower MAEs (0.279D, 0.290D, 0.291D, respectively) than Castrop (all P < 0.001). CONCLUSIONS: The study highlights the varying accuracy of newer IOL formulas based on corneal power. VRF-G, EVO2.0, Kane, K6, and Hoffer QST are highly accurate for flat corneas, while VRF-G, RBF3.0, BUII, Karmona, K6, EVO2.0, Kane, and Pearl-DGS are recommended for medium K corneas. In steep corneas, RBF3.0, K6, and Kane show superior performance.

Glycyrrhizin attenuates myocardial ischemia reperfusion injury by suppressing Inflammation, oxidative stress, and ferroptosis via the HMGB1-TLR4-GPX4 pathway.

Ferroptosis, a form of regulated cell death process, play an important role in myocardial ischemia‒reperfusion (I/R) injury. Glycyrrhizin (GL), a natural glycoconjugate triterpene, has the property to improve growth rate, immune regulation, antioxidant, anti-inflammatory. However, whether GL can attenuate myocardial I/R injury by modulating ferroptosis or other mechanisms are still unclear. In this study, SD rats underwent in vivo myocardial ischemia/reperfusion (I/R) surgery, while H9C2 cells were subjected to the hypoxia/reoxygenation (H/R) model for in vitro experiments. In addition, TAK-242, a TLR4-specific antagonist, and GL were also used to evaluate the effect and mechanisms of GL on the cardiac function and expression of ferroptosis-related gene and protein in vivo and vitro. The results show that GL decreased not only the expression of the inflammation-related factors (HMGB1, TNF-α, IL-6, IL-18 and IL-1ß), but also reduced the number of TUNEL-positive cardiomyocytes, and mitigated pathological alterations in I/R injury. In addition, GL decreased the levels of MDA, promoted antioxidant capacity such as GSH, CAT, Cu/Zn-SOD, Mn-SOD, and SOD in vivo and vitro. More importantly, GL and TAK-242 regulate ferroptosis-related protein and gene expression in I/R and H/R model. Surprisingly, GL may ameliorate cardiomyocyte ferroptosis and ultimately improves cardiac function induced by H/R via the HMGB1-TLR4-GPX4 axis. Therefore, we have highlighted a novel mechanism by which GL regulates inflammation, oxidative stress, and ferroptosis via the HMGB1-TLR4-GPX4 pathway to prevent myocardial I/R injury. GL appears to be a potentially applicable drug for the treatment of myocardial I/R injury.

Factors associated with progressive anisometropia after bilateral intraocular lens implantation in patients with pediatric cataract.

OBJECTIVES: To identify factors associated with progressive anisometropia after bilateral intraocular lens (IOL) implantation in patients with pediatric cataract. METHODS: Clinical and standardized questionnaire data were collected for Sixty-eight patients with pediatric cataract (136 eyes) who underwent bilateral IOL implantation and at least 1 year of follow-up. Univariate and multivariate linear regression models were used to identify factors associated with postoperative anisometropia. RESULTS: The median age at IOL implantation was 3.2 years (range: 1-12.4 years), and median follow-up time was 5.7 years (range: 1.1-14 years). At 1 month postoperatively and at the last follow-up, there were 19 (27%) and 31 (46%) cases of anisometropia ≥1 D, 9 (13%) and 15 (22%) cases of anisometropia ≥2 D, and 2 (3%) and 9 (13%) cases of anisometropia ≥3 D, respectively. Compared with 1 month postoperatively, the amount of anisometropia increased in 45 (67%) patients. Greater anisometropia one year or more after bilateral IOL implantation was associated with larger intereye difference in IOL power (P = 0.032, 95%CI 0.013 to 0.285), intereye difference in preoperative axial length (P = 0.018, 95%CI -1.247 to -0.123), presence of strabismus (P = 0.017, 95%CI 0.063-0.601), anisometropia at 1 month postoperatively (P = 0.001, 95%CI 0.126-0.478), and intereye difference in axial length at the last follow-up (P = 0.047, 95%CI 0.005-0.627). CONCLUSION: Anisometropia might progress after bilateral IOL implantation in patients with pediatric cataract. Greater intereye difference in IOL power, presence of strabismus might increase the potential of progressive anisometropia.

Multi-omic profiling of the developing human cerebral cortex at the single-cell level.

The cellular complexity of the human brain is established via dynamic changes in gene expression throughout development that is mediated, in part, by the spatiotemporal activity of cis-regulatory elements (CREs). We simultaneously profiled gene expression and chromatin accessibility in 45,549 cortical nuclei across six broad developmental time points from fetus to adult. We identified cell type-specific domains in which chromatin accessibility is highly correlated with gene expression. Differentiation pseudotime trajectory analysis indicates that chromatin accessibility at CREs precedes transcription and that dynamic changes in chromatin structure play a critical role in neuronal lineage commitment. In addition, we mapped cell type-specific and temporally specific genetic loci implicated in neuropsychiatric traits, including schizophrenia and bipolar disorder. Together, our results describe the complex regulation of cell composition at critical stages in lineage determination and shed light on the impact of spatiotemporal alterations in gene expression on neuropsychiatric disease.

Mean Platelet Volume/Platelet Count Ratio as a Predictor of Both Incidence and Prognosis of Acute Ischemic Stroke in Hemodialysis Patients.

Purpose: This study aimed to explore whether the mean platelet volume/platelet count ratio (MPR) has predictive value for the occurrence and prognosis of acute ischemic stroke (AIS) in hemodialysis patients. Patients and Methods: A total of 402 patients undergoing maintenance hemodialysis were screened and 259 were enrolled in this study. The receiver operating characteristic curve and area under the curve (AUC) were used to evaluate the predictive power of the models. The patients enrolled in this study were divided into three groups based on the tertiles of the MPR value (Q1, Q2, and Q3). Kaplan-Meier curves were used to investigate the association between the MPR and AIS-free survival in hemodialysis patients. Chi-square analysis was performed to explore the association between the MPR and AIS outcomes in hemodialysis patients. And the AIS outcome was assessed using the modified Rankin Scale (mRS). Results: MPR had a predictive value for the occurrence of AIS (AUC=0.814) in hemodialysis patients with a high sensitivity and specificity. AIS-free survival rates in the MPR Q1, MPR Q2, and MPR Q3 groups were 0.930, 0.701, and 0.360, respectively. The proportion of patients with good outcomes (mRS 0-2) was significantly greater among patients in the MPR Q1-Q2 group than in the MPR Q3 group (0.844 vs 0.745, p <0.001). Conclusion: The MPR can be used as a good predictor of AIS in patients undergoing hemodialysis. Patients on hemodialysis with increased MPR levels had a higher incidence of AIS and poorer functional outcomes than those with low MPR levels.

Effects of HMGB1/RAGE/cathespin B inhibitors on alleviating hippocampal injury by regulating microglial pyroptosis and caspase activation in neonatal hypoxic-ischemic brain damage.

Microglia play a crucial role in regulating neuroinflammation in the pathogenesis of neonatal hypoxic-ischemic brain damage (HIBD). Pyroptosis, an inflammatory form of programmed cell death, has been implicated in HIBD; however, its underlying mechanism remains unclear. We previously demonstrated that high-mobility group box 1 protein (HMGB1) mediates neuroinflammation and microglial damage in HIBD. In this study, we aimed to investigate the association between HMGB1 and microglial pyroptosis and elucidate the mechanism involved in rats with HIBD (both sexes were included) and in BV2 microglia subjected to oxygen-glucose deprivation. Our results showed that HMGB1 inhibition by glycyrrhizin (20 mg/kg) reduced the expression of microglial pyroptosis-related proteins, including caspase-1, the N-terminus fragment of gasdermin D (N-GSDMD), and pyroptosis-related inflammatory factors, such as interleukin (IL) -1ß and IL-18. Moreover, HMGB1 inhibition resulted in reduced neuronal damage in the hippocampus 72 h after HIBD and ultimately improved neurobehavior during adulthood, as evidenced by reduced escape latency and path length, as well as increased time and distance spent in the target quadrant during the Morris water maze test. These results revealed that HIBD-induced pyroptosis is mediated by HMGB1/receptor for advanced glycation end products (RAGE) signaling (inhibition by FPS-ZM1, 1 mg/kg) and the activation of cathespin B (cat B). Notably, cat B inhibition by CA074-Me (5 mg/kg) also reduced hippocampal neuronal damage by suppressing microglial pyroptosis, thereby ameliorating learning and memory impairments caused by HIBD. Lastly, we demonstrated that microglial pyroptosis may contribute to neuronal damage through the HMGB1/RAGE/cat B signaling pathway in vitro. In conclusion, these results suggest that HMGB1/RAGE/cat B inhibitors can alleviate hippocampal injury by regulating microglial pyroptosis and caspase activation in HIBD, thereby reducing the release of proinflammatory mediators that destroy hippocampal neurons and induce spatial memory impairments.

Cardioprotective effects of Schisantherin A against isoproterenol-induced acute myocardial infarction through amelioration of oxidative stress and inflammation via modulation of PI3K-AKT/Nrf2/ARE and TLR4/MAPK/NF-κB pathways in rats.

BACKGROUND AND AIMS: The scientific community is concerned about cardiovascular disease mortality and morbidity, especially myocardial infarction (MI). Schisantherin A (SCA), a dibenzocyclooctadiene lignan monomer found in S. chinensis fruits has cardiovascular advantages such as increasing NO production in isolated rat thoracic aorta and reducing heart damage caused by ischemia-reperfusion (I/R) through decreasing apoptosis. The present study was undertaken to explore the potential effects of SCA on ISO-induced myocardial infarction in rats. METHODS: Rats were randomly allocated to four groups: control; ISO-treated, and two additional groups of ISO + SCA (5 or 10 mg/kg body weight). All SCA-treated groups were administered with SCA for 20 days and all ISO groups were challenged with ISO on days 19 and 20. RESULTS: SCA significantly attenuated ISO-induced rise in heart/body weight ratio, myocardial infarct size, and cardiac functional biomarkers (CK-MB, cTnI and BNP). SCA pre- and co-treatment resulted in a significant reduction in oxidative stress (via MDA, NO and GSH and increased activities of SOD, CAT and GPx) and inflammation (via decreased levels of TNF-α, IL-6 and IL-1ß) markers when compared to the same levels in cardiac tissue of ISO-treated rats. This study also showed that SCA protects ISO-induced oxidative stress and inflammation by activating the PI3K-AKT/Nrf2/ARE pathway and suppressing TLR4/MAPK/NF-κB pathways. Furthermore, SCA treatment protected histopathological alterations observed in only ISO-treated cardiac transverse sections of rats. CONCLUSION: In conclusion, the findings of this study suggest that SCA protects against cardiac injury in the ISO-induced MI model of rats.

Presurgical MRI-Based Radiomics Models for Predicting Cerebellar Mutism Syndrome in Children With Posterior Fossa Tumors.

BACKGROUND: Current studies have indicated that tumoral morphologic features are associated with cerebellar mutism syndrome (CMS), but the radiomics application in CMS is scarce. PURPOSE: To develop a model for CMS discrimination based on multiparametric MRI radiomics in patients with posterior fossa tumors. STUDY TYPE: Retrospective. POPULATION: A total of 218 patients (males 132, females 86) with posterior fossa tumors, 169 of which were included in the MRI radiomics analysis. The MRI radiomics study cohort (169) was split into training (119) and testing (50) sets with a ratio of 7:3. FIELD/SEQUENCE: All the MRI were acquired under 1.5/3.0 T scanners. T2-weighted image (T2W), T1-weighted (T1W), fluid attenuated inversion recovery (FLAIR), diffusion-weighted imaging (DWI). ASSESSMENT: Apparent diffusion coefficient (ADC) maps were generated from DWI. Each MRI dataset generated 1561 radiomics characteristics. Feature selection was performed with univariable logistic analysis, correlation analysis, and least absolute shrinkage and selection operator (LASSO) penalized logistic regression. Significant clinical features were selected with multivariable logistic analysis and used to constructed the clinical model. Radiomics models (based on T1W, T2W, FLAIR, DWI, ADC) were constructed with selected radiomics features. The mix model was based on the multiparametric MRI radiomics features. STATISTICAL TEST: Multivariable logistic analysis was utilized during clinical features selection. Models' performance was evaluated using the area under the receiver operating characteristic (AUC) curve. Interobserver variability was assessed using Cohen's kappa. Significant threshold was set as P < 0.05. RESULTS: Sex (aOR = 3.72), tumor location (aOR = 2.81), hydrocephalus (aOR = 2.14), and tumor texture (aOR = 5.08) were significant features in the multivariable analysis and were used to construct the clinical model (AUC = 0.79); totally, 33 radiomics features were selected to construct radiomics models (AUC = 0.63-0.93). Seven of the 33 radiomics features were selected for the mix model (AUC = 0.93). DATA CONCLUSION: Multiparametric MRI radiomics may be better at predicting CMS than single-parameter MRI models and clinical model. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: 2.

Single-cell RNA sequencing reveals new subtypes of lens superficial tissue in humans.

Although the cell atlas of the human ocular anterior segment of the human eye was revealed by single-nucleus RNA sequencing, whether subtypes of lens stem/progenitor cells exist among epithelial cells and the molecular characteristics of cell differentiation of the human lens remain unclear. Single-cell RNA sequencing is a powerful tool to analyse the heterogeneity of tissues at the single cell level, leading to a better understanding of the processes of cell differentiation. By profiling 18,596 cells in human lens superficial tissue through single-cell sequencing, we identified two subtypes of lens epithelial cells that specifically expressed C8orf4 and ADAMTSL4 with distinct spatial localization, a new type of fibre cells located directly adjacent to the epithelium, and a subpopulation of ADAMTSL4+ cells that might be lens epithelial stem/progenitor cells. We also found two trajectories of lens epithelial cell differentiation and changes of some important genes during differentiation.

Long-term postoperative quality of life in childhood survivors with cerebellar mutism syndrome.

Background: To investigate the long-term quality of life (QoL) of children with cerebellar mutism syndrome (CMS) and explore the risk factors for a low QoL. Procedure: This cross-sectional study investigated children who underwent posterior fossa surgery using an online Pediatric Quality of Life Inventory questionnaire. CMS and non-CMS patients were included to identify QoL predictors. Results: Sixty-nine patients were included (male, 62.3%), 22 of whom had CMS. The mean follow-up time was 45.2 months. Children with CMS had a significantly lower mean QoL score (65.3 vs. 83.7, p < 0.001) and subdomain mean scores (physical; 57.8 vs. 85.3, p < 0.001; social: 69.5 vs. 85.1, p = 0.001; academic: p = 0.001) than those without CMS, except for the emotional domain (78.0 vs. 83.7, p = 0.062). Multivariable analysis revealed that CMS (coefficient = -14.748.61, p = 0.043), chemotherapy (coefficient = -7.629.82, p = 0.013), ventriculoperitoneal (VP) shunt placement (coefficient = -10.14, p = 0.024), and older age at surgery (coefficient = -1.1830, p = 0.007) were independent predictors of low total QoL scores. Physical scores were independently associated with CMS (coefficient = -27.4815.31, p = 0.005), VP shunt placement (coefficient = -12.86, p = 0.025), and radiotherapy (coefficient = -13.62, p = 0.007). Emotional score was negatively associated with age at surgery (coefficient = -1.92, p = 0.0337) and chemotherapy (coefficient = -9.11, p = 0.003). Social scores were negatively associated with male sex (coefficient = -13.68, p = 0.001) and VP shunt placement (coefficient = -1.36, p = 0.005), whereas academic scores were negatively correlated with chemotherapy (coefficient = -17.45, p < 0.001) and age at surgery (coefficient = -1.92, p = 0.002). Extent of resection (coefficient = 13.16, p = 0.021) was a good predictor of higher academic scores. Conclusion: CMS results in long-term neurological and neuropsychological deficits, negatively affecting QoL, and warranting early rehabilitation.

Acetyl-CoA carboxylase inhibitor increases LDL-apoB production rate in NASH with cirrhosis: prevention by fenofibrate.

Treatment with acetyl-CoA carboxylase inhibitors (ACCi) in nonalcoholic steatohepatitis (NASH) may increase plasma triglycerides (TGs), with variable changes in apoB concentrations. ACC is rate limiting in de novo lipogenesis and regulates fatty acid oxidation, making it an attractive therapeutic target in NASH. Our objectives were to determine the effects of the ACCi, firsocostat, on production rates of plasma LDL-apoB in NASH and the effects of combined therapy with fenofibrate. Metabolic labeling with heavy water and tandem mass spectrometric analysis of LDL-apoB enrichments was performed in 16 NASH patients treated with firsocostat for 12 weeks and in 29 NASH subjects treated with firsocostat and fenofibrate for 12 weeks. In NASH on firsocostat, plasma TG increased significantly by 17% from baseline to week 12 (P = 0.0056). Significant increases were also observed in LDL-apoB fractional replacement rate (baseline to week 12: 31 ± 20.2 to 46 ± 22.6%/day, P = 0.03) and absolute synthesis rate (ASR) (30.4-45.2 mg/dl/day, P = 0.016) but not plasma apoB concentrations. The effect of firsocostat on LDL-apoB ASR was restricted to patients with cirrhosis (21.0 ± 9.6 at baseline and 44.2 ± 17 mg/dl/day at week 12, P = 0.002, N = 8); noncirrhotic patients did not change (39.8 ± 20.8 and 46.3 ± 14.8 mg/dl/day, respectively, P = 0.51, N = 8). Combination treatment with fenofibrate and firsocostat prevented increases in plasma TG, LDL-apoB fractional replacement rate, and ASR. In summary, in NASH with cirrhosis, ACCi treatment increases LDL-apoB100 production rate and this effect can be prevented by concurrent fenofibrate therapy.

Epidemiological characteristics, clinical presentations, and prognoses of pediatric brain tumors: Experiences of national center for children's health.

Background: We aimed to describe the epidemiological characteristics, clinical presentations, and prognoses in a national health center for children. Methods: From January 2015 to December 2020, 484 patients aged 0-16 years, who were diagnosed with brain tumors and received neurosurgery treatment, were enrolled in the study. Pathology was based on the World Health Organization 2021 nervous system tumor classification, and tumor behaviors were classified according to the International Classification of Diseases for Oncology, third edition. Results: Among the 484 patients with brain tumors, the median age at diagnosis was 4.62 [2.19, 8.17] years (benign tumors 4.07 [1.64, 7.13] vs. malignant tumors 5.36 [2.78, 8.84], p=0.008). The overall male-to-female ratio was 1.33:1(benign 1.09:1 vs. malignant 1.62:1, p=0.029). Nausea, vomiting, and headache were the most frequent initial symptoms. The three most frequent tumor types were embryonal tumors (ET, 22.8%), circumscribed astrocytic gliomas (20.0%), and pediatric-type diffuse gliomas (11.0%). The most common tumor locations were the cerebellum and fourth ventricle (38.67%), the sellar region (22.9%) and ventricles (10.6%). Males took up a higher proportion than females in choroid plexus tumors (63.6%), ET (61.1%), ependymal tumors (68.6%), and germ cell tumors (GCTs, 78.1%). Patients were followed for 1 to 82 months. The overall 5-year survival rate was 77.5%, with survival rates of 91.0% for benign tumors and 64.6% for malignant tumors. Conclusion: Brain tumors presented particularly sex-, age-, and regional-dependent epidemiological characteristics. Our results were consistent with previous reports and might reflect the real epidemiological status in China.

Apigenin alleviates oxidative stress-induced myocardial injury by regulating SIRT1 signaling pathway.

Apigenin is a natural flavonoid which is widely found in vegetables and fruits. However, the mechanism of apigenin in oxidative stress-induced myocardial injury has not been fully elucidated. We established an isoproterenol (Iso)-induced myocardial injury mouse model and a hypoxia/reoxygenation (H/R)-induced H9c2 cell injury model, followed by pretreatment with apigenin to explore its protective effects. Apigenin can significantly alleviate isoproterenol-induced oxidative stress, cell apoptosis and myocardial remodeling in vivo. Apigenin pretreatment can also significantly improve cardiomyocyte morphology, decrease H/R induced oxidative stress, and attenuate cell apoptosis and inflammation in vitro. Further mechanism study revealed that apigenin treatment reversed isoprenaline and H/R-induced decrease of Sirtuin1 (SIRT1). Molecular docking results proved that apigenin can form hydrogen bond with 230 Glu, a key site of SIRT1 activation, indicating that apigenin is an agonist of SIRT1. Moreover, SIRT1 knockdown by siRNA significantly reversed the protective effect of apigenin in H/R-induced myocardial injury. In conclusion, apigenin protects cardiomyocyte function from oxidative stress-induced myocardial injury by modulating SIRT1 signaling pathway, which provides a new potential therapeutic natural compound for the clinical treatment of cardiovascular diseases.