Application of stem cells in the study of developmental and functional toxicity of endodermal-derived organs caused by nanoparticles.

Nanoparticles have unique properties that make them useful in biomedicine. However, their extensive use raises concerns about potential hazards to the body. Therefore, it is crucial to establish effective and robust toxicology models to evaluate the developmental and functional toxicity of nanoparticles on the body. This article discusses the use of stem cells to study the developmental and functional toxicity of organs of endodermal origin due to nanoparticles. The study discovered that various types of nanoparticles have varying effects on stem cells. The application of stem cell models can provide a possibility for studying the effects of nanoparticles on organ development and function, as they can more accurately reflect the toxic mechanisms of different types of nanoparticles. However, stem cell toxicology systems currently cannot fully reflect the effects of nanoparticles on entire organs. Therefore, the establishment of organoid models and other advanced assessment models is expected to address this issue.

Pediatric incarcerated inguinal hernia: Traditional open or laparoscopic-assisted approach?

The objective of this study was to compare the safety and efficacy of laparoscopic-assisted surgery and traditional open surgery for pediatric incarcerated inguinal hernia. A total of 58 pediatric patients with indirect incarcerated inguinal hernia between January 2014 and January 2020 were included in this study. The patients were divided into 2 groups; observational group who underwent laparoscopic-assisted surgery (n = 36), and a control group who underwent traditional open surgery (n = 22). The overall operation time, intraoperative blood loss, postoperative recovery time, length of hospital stay, occurrence of postoperative scrotal or vulvar hematomas, incidence of postoperative surgical site infection, and hernia recurrence were analyzed and compared between the 2 groups. Compared with the control group, the operation time (38.28 ±â€…5.90) minutes, intraoperative blood loss (1.15 ±â€…0.54 mL), postoperative recovery time (8.39 ±â€…1.42 h), and length of hospital stay (1.64 ±â€…0.59) were significantly lower in the observational group (P < .05). There was no incidence of scrotal or vulvar hematoma or surgical site infection in the observation group, which was significantly lower than that in the control group (P < .05). However, no statistically significant difference was found in the rate of postoperative hernia recurrence between the 2 groups (P > .05). In conclusion, laparoscopic-assisted surgery appears to be a safe and effective alternative approach to traditional open surgery for the treatment of pediatric incarcerated inguinal hernia. Its advantages include reduced trauma, faster recovery, shorter hospital stays, and fewer complications.

Integrative analyses of genetic characteristics associated with skeletal endothelial cells.

The osseous vascular endothelium encompasses a vast intricate framework that regulates bone remodeling. Osteoporosis, an age-associated systemic bone disease, is characterized by the degeneration of the vascular architecture. Nevertheless, the precise mechanisms underpinning the metamorphosis of endothelial cells (ECs) with advancing age remain predominantly enigmatic. In this study, we conducted a systematic analysis of differentially expressed genes (DEGs) and the associated pathways in juvenile and mature femoral ECs, utilizing data sourced from the Gene Expression Omnibus (GEO) repositories (GSE148804) and employing bioinformatics tools. Through this approach, we successfully discerned six pivotal genes, namely Adamts1, Adamts2, Adamts4, Adamts14, Col5a1, and Col5a2. Subsequently, we constructed a miRNA-mRNA network based on miRNAs displaying differential expression between CD31hiEMCNhi and CD31lowEMCNlow ECs, utilizing online repositories for prediction. The expression of miR-466i-3p and miR-466i-5p in bone marrow ECs exhibited an inverse correlation with age. Our in vivo experiments additionally unveiled miR-466i-5p as a pivotal regulator in osseous ECs and a promising therapeutic target for age-related osteoporosis.

The impact of past temporal discounting on mental health: Opposite effects of positive and negative event aftertastes over time: Aftertaste and time.

Background: Time frees people from bereavement, but also fades childhood happiness, these dynamics can be understood through the framework of past temporal discounting (PTD), which refers to the gradual decrease in affect intensity elicited by recalling positive or negative events over time. Despite its importance, measuring PTD has been challenging, and its impact on real-life outcomes, such as mental health remains unknown. Method: Here, we employed a longitudinal tracking approach to measure PTD in healthy participants (N = 210) across eight time points. We recorded changes in affect intensity for positive and negative events and examined the impact of PTD on mental health outcomes, including general mental well-being, depression, stress sensitivity, and etc. Results: The results of Bayesian multilevel modeling indicated that the affect intensity for positive and negative events discounted over time at a gradually decelerating rate. Furthermore, we found that maintaining good mental health heavily depended on rapid PTD of negative events and slow PTD of positive events. Conclusions: These results provide a comprehensive characterization PTD and demonstrate its importance in maintaining mental health.

Cortical gradient perturbation in attention deficit hyperactivity disorder correlates with neurotransmitter-, cell type-specific and chromosome- transcriptomic signatures.

AIMS: This study aimed to illuminate the neuropathological landscape of attention deficit hyperactivity disorder (ADHD) by a multiscale macro-micro-molecular perspective from in vivo neuroimaging data. METHODS: The "ADHD-200 initiative" repository provided multi-site high-quality resting-state functional connectivity (rsfc-) neuroimaging for ADHD children and matched typically developing (TD) cohort. Diffusion mapping embedding model to derive the functional connectome gradient detecting biologically plausible neural pattern was built, and the multivariate partial least square method to uncover the enrichment of neurotransmitomic, cellular and chromosomal gradient-transcriptional signatures of AHBA enrichment and meta-analytic decoding. RESULTS: Compared to TD, ADHD children presented connectopic cortical gradient perturbations in almost all the cognition-involved brain macroscale networks (all pBH <0.001), but not in the brain global topology. As an intermediate phenotypic variant, such gradient perturbation was spatially enriched into distributions of GABAA/BZ and 5-HT2A receptors (all pBH <0.01) and co-varied with genetic transcriptional expressions (e.g. DYDC2, ATOH7, all pBH <0.01), associated with phenotypic variants in episodic memory and emotional regulations. Enrichment models demonstrated such gradient-transcriptional variants indicated the risk of both cell-specific and chromosome- dysfunctions, especially in enriched expression of oligodendrocyte precursors and endothelial cells (all pperm <0.05) as well enrichment into chromosome 18, 19 and X (pperm <0.05). CONCLUSIONS: Our findings bridged brain macroscale neuropathological patterns to microscale/cellular biological architectures for ADHD children, demonstrating the neurobiologically pathological mechanism of ADHD into the genetic and molecular variants in GABA and 5-HT systems as well brain-derived enrichment of specific cellular/chromosomal expressions.

Comprehensive analysis of single cell and bulk data develops a promising prognostic signature for improving immunotherapy responses in ovarian cancer.

The tumor heterogeneity is an important cause of clinical therapy failure and yields distinct prognosis in ovarian cancer (OV). Using the advantages of integrated single cell RNA sequencing (scRNA-seq) and bulk data to decode tumor heterogeneity remains largely unexplored. Four public datasets were enrolled in this study, including E-MTAB-8107, TCGA-OV, GSE63885, and GSE26193 cohorts. Random forest algorithm was employed to construct a multi-gene prognostic panel and further evaluated by receiver operator characteristic (ROC), calibration curve, and Cox regression. Subsequently, molecular characteristics were deciphered, and treatments strategies were explored to deliver precise therapy. The landscape of cell subpopulations and functional characteristics, as well as the dynamic of macrophage cells were detailly depicted at single cell level, and then screened prognostic candidate genes. Based on the expression of candidate genes, a stable and robust cell characterized gene associated prognosis signature (CCIS) was developed, which harbored excellent performance at prognosis assessment and patient stratification. The ROC and calibration curves, and Cox regression analysis elucidated CCIS could serve as serve as an independent factor for predicting prognosis. Moreover, a promising clinical tool nomogram was also constructed according to stage and CCIS. Through comprehensive investigations, patients in low-risk group were charactered by favorable prognosis, elevated genomic variations, higher immune cell infiltrations, and superior antigen presentation. For individualized treatment, patients in low-risk group were inclined to better immunotherapy responses. This study dissected tumor heterogeneity and afforded a promising prognostic signature, which was conducive to facilitating clinical outcomes for patients with OV.

Protein-based bioactive coatings: from nanoarchitectonics to applications.

Protein-based bioactive coatings have emerged as a versatile and promising strategy for enhancing the performance and biocompatibility of diverse biomedical materials and devices. Through surface modification, these coatings confer novel biofunctional attributes, rendering the material highly bioactive. Their widespread adoption across various domains in recent years underscores their importance. This review systematically elucidates the behavior of protein-based bioactive coatings in organisms and expounds on their underlying mechanisms. Furthermore, it highlights notable advancements in artificial synthesis methodologies and their functional applications in vitro. A focal point is the delineation of assembly strategies employed in crafting protein-based bioactive coatings, which provides a guide for their expansion and sustained implementation. Finally, the current trends, challenges, and future directions of protein-based bioactive coatings are discussed.

Association between platelet­to­lymphocyte ratio and serum prostate specific antigen.

There is evidence that the systemic inflammatory response may have an impact on prostate-specific antigen (PSA) levels. However, the relationship between the platelet-to-lymphocyte ratio (PLR) and PSA remains unclear. As a result, the relationship between PLR and PSA using the National Health and Nutrition Examination Survey (NHANES) database was examined. After the screening, 6,638 participants out of 52,186 in the NHANES survey conducted between 2001 to 2010 were suitable for the present study. The PLR was the independent variable in the present study, and PSA was the dependent variable. The selected subjects in the present study had an average age of 58.563±11.848 years. After controlling for covariates, the results showed that with every increase in PLR, the PSA concentration increased by 0.004 ng/ml (0.001, 0.007). This difference was statistically significant. Furthermore, a smoothing curve based on a fully adjusted model was created to investigate the possibility of a linear relationship between PLR and PSA concentration in men from USA. In men from USA, an independent and positive correlation between PLR and PSA was identified, which could potentially result in overdiagnosis of asymptomatic prostate cancer in populations with higher PLR levels.

AARS2 as a novel biomarker for prognosis and its molecular characterization in pan-cancer.

INTRODUCTION: The mitochondrial alanyl-tRNA synthetase 2 (AARS2) as one of aminoacyl-tRNA synthases (ARSs) performs amino acid transportation and involves protein synthesis. However, its role in cancer remains largely unexplored. METHODS: In this study, more than 10,000 samples were enrolled to explore genomic alterations, biological function, prognosis, and clinical treatment based on AARS2 across pan-cancer. The molecular characterization of AARS2 was confirmed in hepatocellular carcinoma (HCC) using proteomics analysis, quantitative real-time PCR, western blotting, immunohistochemical staining, and cell experiments. RESULTS: For genomic landscape, the AARS2 was dramatically upregulated in multiple cancers, which might be mainly caused by copy number alteration rather than mutation and methylation. The abnormal expression of AARS2 was prominently associated with activity of cancer pathways and performed oncogenic roles in most cancers. Systematic experiments in vitro substantiated the elevated expression of AARS2, and the deficiency of it inhibited cell proliferation and cell migration in HCC. Meanwhile, our findings suggested that AARS2 could serve as a novel promising and stable biomarker for assessing prognosis and immunotherapy. Moreover, a variety of therapeutic drugs and targeted pathways were proposed for cancer treatment, which might enhance clinical efficacy. CONCLUSION: The AARS2 could serve as a new oncogenic gene that promotes cell proliferation and migration in HCC. The comprehensive investigations increased the understanding of AARS2 across human cancers and generated beginning insights of AARS2 in genomic landscape, molecular biological function, prognosis, and clinical treatment.

Posterior concave reconstruction with cage in the surgical treatment of complex lumbar deformity caused by lumbosacral hemivertebrae.

PURPOSE: To identify the clinical and radiological outcomes in the coronal and sagittal planes after treatment of congenital complex lumbosacral hemivertebrae (LSHV) with or without posterior concave reconstruction. METHODS: We retrospectively reviewed a consecutive series of patients with congenital LSHV deformities treated by posterior-only hemivertebra resection. The minimum follow-up was 2 years. The patients were divided into a concave-cage group and a non-cage group. The radiographic and clinical results were compared between the two groups. RESULTS: Forty patients were categorized into the cage group (n = 14) and non-cage group (n = 26). At the end of the propensity score matching analysis, 14 patients from the cage group were matched to 14 patients in the non-cage group. The lumbosacral curve and thoracolumbar/lumbar curve improved significantly in both groups at the final postoperative follow-up (P < 0.001), and the lumbosacral curve at the final follow-up was remarkably lower in the cage than non-cage group. The correction rates of the lumbosacral curve and thoracolumbar/lumbar curve were significantly higher in the cage than non-cage group. The lower lumbar lordosis improved significantly in both groups at the final postoperative follow-up (P < 0.05), and the lower lumbar lordosis at the final follow-up and its correction were remarkably higher in the cage than non-cage group (both P < 0.05). CONCLUSIONS: Posterior column reconstruction with insertion of a concave cage may achieve a higher correction rate of large lower lumbar lordosis and lumbosacral coronal deformity, attain better sagittal balance, and have fewer complications related to implant failure than posterior-only hemivertebra resection in patients with congenital LSHV.

Expression of TXLNA in brain gliomas and its clinical significance: a bioinformatics analysis.

BACKGROUND: To analyze the expression of TXLNA in brain gliomas and its clinical significance. METHODS: Gene Expression Profiling Interactive Analysis（GEPIA）and Chinese Glioma Genome Atlas（CGGA）databases were retrieved as the methods. To assess the disparity between TXLNA expression in glioma and normal brain tissue. The Kaplan-Meier survival curve was employed to preliminarily evaluate the survival curves of the high and low expression groups, this was done for investigate the correlation between TXLNA expression level and the survival and prognosis of glioma. A Cox proportional regression risk model of multivariate nature was employed to evaluate the elements impacting the survival and prognosis of glioma. Gene pool enrichment analysis（GSEA）was used to investigate the related function of TXLNA in glioma. A Pearson correlation test and co-expression analysis were employed to identify the genes most associated with TXLNA expression. RESULT: The enrichment analysis results were observably enriched in signal pathways for instance the cell cycle and completion and coordination cascade pathways, and it is evident that high expression of TXLNA in gliomas is related to a poor survival and a bad patient prognosis, thus making it an independent prognostic factor for gliomas. Genes such as STK40 and R1MS1 are significantly correlated with TXLNA, playing a synergistic or antagonistic role. CONCLUSIONS: The prognosis of GBM patients is strongly linked to the high expression of TXLNA, which may be a viable therapeutic target for curbing cancer progression and creating new immunotherapies for GBM.

A Comparison of Corpectomy ACDF Hybrid Procedures with Nano-Hydroxyapatite/Polyamide 66 Cage and Titanium Mesh Cage for Multi-level Degenerative Cervical Myelopathy: A Stepwise Propensity Score Matching Analysis.

OBJECTIVE: Previous studies have found satisfactory clinical results with the nano-hydroxyapatite/polyamide 66 (n-HA/PA66) cage to reconstruct the stability of anterior cervical column. However, studies evaluating the long-term outcomes of the n-HA/PA66 cage in multi-level degenerative cervical myelopathy (MDCM) have not been reported. This study aims to compare the outcomes of corpectomy anterior cervical discectomy and fusion (ACDF) hybrid procedures between the n-HA/PA66 cage and titanium mesh cage (TMC) to treat MDCM. METHODS: After the screening for eligibility, this retrospective study involved 90 patients who underwent corpectomy ACDF hybrid (CACDFH) procedure from June 2013 to June 2018. The CACDFH procedure is the combination of ACDF and anterior cervical corpectomy and fusion (ACCF). According to the cage utilized, we categorized patients into a n-HA/PA66 cage group and a TMC group. Then, stepwise propensity score matching (PSM) was performed to maintain comparable clinical data between groups. All the patients were followed up ≥4 years and the longest follow-up time was 65.43 (±11.49) months. Cage subsidence, adjacent segment degeneration (ASD), segmental height (SH), segmental angle (SA), cervical lordosis (CL), and clinical data (visual analogue scale [VAS] and Japanese Orthopaedic Association [JOA] score) was evaluated preoperatively, at 1 week, and at the final surgery follow-up. The independent student's t test and chi-square test were applied to compare the differences between groups. RESULTS: Through PSM analysis, 25 patients from the n-HA/PA66 group were matched to 25 patients in the TMC group. The occurrence of ASD was 16.0% (4/25) in the n-HA/PA 66 group, which was significantly less than in the TMC group at 44.0% (11/25) (p = 0.031). Moreover, the cage subsidence rate was significantly higher in the TMC group as compared to the n-HA/PA 66 group (40.0% vs. 12.0%, p = 0.024). But there was no significant difference in SH, SA, and CL at any time after surgery as determined through follow-up. The VAS and JOA scores significantly improved in both groups at 3 months postoperative and at final follow-up. However, there were no significant differences in the VAS and JOA score at any time between the two groups in preoperative (p > 0.05). CONCLUSION: The n-HA/PA66 cage is associated with lower rate of cage subsidence and ASD than the TMC in the treatment of MDCM. The n-HA/PA66 cage could be superior to the TMC in corpectomy ACDF hybrid procedures.

Genomes of cultivated and wild Capsicum species provide insights into pepper domestication and population differentiation.

Pepper (Capsicum spp.) is one of the earliest cultivated crops and includes five domesticated species, C. annuum var. annuum, C. chinense, C. frutescens, C. baccatum var. pendulum and C. pubescens. Here, we report a pepper graph pan-genome and a genome variation map of 500 accessions from the five domesticated Capsicum species and close wild relatives. We identify highly differentiated genomic regions among the domesticated peppers that underlie their natural variations in flowering time, characteristic flavors, and unique resistances to biotic and abiotic stresses. Domestication sweeps detected in C. annuum var. annuum and C. baccatum var. pendulum are mostly different, and the common domestication traits, including fruit size, shape and pungency, are achieved mainly through the selection of distinct genomic regions between these two cultivated species. Introgressions from C. baccatum into C. chinense and C. frutescens are detected, including those providing genetic sources for various biotic and abiotic stress tolerances.

Clinical Outcomes of Isobar TTL System with Isthmic Bone Grafting and Pedicle Screw-Vertebral Plate Hook with Direct Repair of Defect for Lumbar Spondylolysis: A Matched-Pair Case Control Study.

OBJECTIVE: Although direct isthmic repair, such as PSVPH, did not affect the mobility of the fixed segment and adjacent segment, it has a relatively low rate of isthmic fusion compared with conventional fusion. The Isobar TTL dynamic internal fixation system has been widely used in clinical practice and has achieved satisfactory clinical results. However, the use of the Isobar TTL system in combination with direct isthmic repair for lumbar spondylolysis has rarely been reported. The aim of this study was to compare the clinical and radiologic outcomes between patients who underwent Isobar TTL system and PSVPH with direct repair of defect for lumbar spondylolysis. METHODS: Stepwise propensity score matching (PSM) for age and sex were performed to keep comparable clinical data between groups in this retrospective and matched-pair case control study. A total of 50 patients diagnosed with lumbar spondylolysis underwent surgical implantation of the Isobar TTL group (n = 25) or PSVPH group (n = 25) from June 2009 to June 2016. Clinical outcomes were assessed using the Oswestry disability index (ODI), and visual analog score (VAS). Radiographic evaluations included range of motion (ROM) and the disc heights of stabilized segment and adjacent segment, adjacent segment degeneration (ASD) and bony fusion. Three-dimensional reconstruction of lumbar CT scan was obtained to evaluate bone fusion of the isthmic at final follow-up. The independent Student's t test and chi-square test were applied to compare the differences between groups. RESULTS: A total of 25 patients from TTL group were matched to 25 patients in PSVPH group for age, sex, body mass index (BMI), defect side, spondylolisthesis meyerding, and follow-up duration. The intervertebral space height (IH) of stabilized segment at postoperative 1 week and final follow-up in the TTL group was higher than those in the PSVPH group, respectively (P = 0.030; P = 0.013). The ROM of stabilized segment at final follow-up in the TTL group was significantly lower than that in the PSVPH group (P < 0.001). The bony fusion rate at the final follow-up was 88.0% (22/25 cages) in the TTL group and 80.0% (20/25 cages) in the PSVPH group. The ODI score at final follow-up in the TTL group was significantly lower than that in the PSVPH group (P = 0.007). CONCLUSION: Overall, our data suggest that the Isobar TTL system outcomes are comparable to those in the PSVPH, with a similar high bony fusion rate as PSVPH, especially its wider indications as a new surgery.

Long-term outcomes of the nano-hydroxyapatite/polyamide-66 cage versus the titanium mesh cage for anterior reconstruction of thoracic and lumbar corpectomy: a retrospective study with at least 7 years of follow-up.

BACKGROUND: The nano-hydroxyapatite/polyamide-66 (n-HA/PA66) cage is a biomimetic cage with a lower elastic modulus than the titanium mesh cage (TMC). This study aimed to compare the long-term outcomes of the n-HA/PA66 cage and TMC in the anterior reconstruction of thoracic and lumbar fractures. METHODS: We retrospectively studied 113 patients with acute traumatic thoracic or lumbar burst fractures, comprising 60 patients treated with the TMC and 53 treated with the n-HA/PA66 cage for anterior reconstruction following single-level corpectomy. The radiographic data (cage subsidence, fusion status, segmental sagittal alignment) and clinical data (visual analogue scale (VAS) for pain and Oswestry Disability Index (ODI) for function) were evaluated preoperatively, postoperatively, and at final follow-up after a minimum 7-year period. RESULTS: The n-HA/PA66 and TMC groups had similar final fusion rates (96.2% vs. 95.0%). The cage subsidence at final follow-up was 2.3 ± 1.6 mm with subsidence of more than 3 mm occurring in 24.5% in the n-HA/PA66 group, which was significantly lower than the respective values of 3.9 ± 2.5 mm and 58.3% in the TMC group. The n-HA/PA66 group also had better correction of the bisegmental kyphotic angle than the TMC group (7.1° ± 7.5° vs 1.9° ± 8.6°, p < 0.01), with lower loss of correction (2.9° ± 2.5° vs 5.2° ± 4.1°, p < 0.01). The mean ODI steadily decreased after surgery in both groups. At final follow-up, the ODI and VAS were similar in the TMC and n-HA/PA66 groups. CONCLUSIONS: The n-HA/PA66 cage is associated with excellent radiographic fusion, better maintenance of the height of the fused segment, and better correction of kyphosis than the TMC during 7 years of follow-up after one-level anterior corpectomy. With the added benefit of radiolucency, the n-HA/PA66 cage may be superior to the TMC in anterior reconstruction of thoracic or lumbar fractures.