Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depressionlike behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer’s disease and depression.Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.

Background: Collaborative robots have emerged as a solution for complex and precision-driven tasks. However, there is no comprehensive risk assessment model for collaborative robotic work in the Republic of Korea. Thus, we aim to develop a risk assessment model tailored to the unique characteristics of human-robot collaboration. Methods: In this study, we examine the risk assessment factors in three key fields: worker, robotic systems, and work environment. The items adopted in the existing models of HFACS, USUS, and human–robot trust were initially selected to extract items for the risk assessment model. The analytic hierarchy process methodology was applied to refine and prioritize the evaluation items. Score scales were constructed for the six checklists. A five-level score ranging from one to five was given to each question in the checklist, and the average score was used to quantitatively evaluate each area. Results: The six evaluation checklists coalesced to constitute a comprehensive risk assessment model was adjusted for collaborative robot operations. Implementing the proposed model in six robot-operated workplaces yielded consistent results. Companies involved in previous robot-related accidents exhibited deficiencies in these risks than accident-free robot workplaces. Thus, comprehensive risk assessments encompassing the necessary factors are crucial to prevent accidents in robot-related work environments. Conclusion The proposed risk assessment model can offer a robust foundation for guiding the future development of diverse risk assessment models for collaborative robot environments and facilitate the safe coexistence of humans and robots in the Industry 4.0 era.

BACKGROUND: Current tendon and ligament reconstruction surgeries rely on scar tissue healing which differs from native bone-to-tendon interface (BTI) tissue. We aimed to engineer Synovium-derived mesenchymal stem cells (Sy-MSCs) based scaffold-free fibrocartilage constructs and investigate in vivo bone–tendon interface (BTI) healing efficacy in a rat anterior cruciate ligament (ACL) reconstruction model. METHODS: Sy-MSCs were isolated from knee joint of rats. Scaffold-free sy-MSC constructs were fabricated and cultured in differentiation media including TGF-b-only, CTGF-only, and TGF-b + CTGF. Collagenase treatment on tendon grafts was optimized to improve cell-to-graft integration. The effects of fibrocartilage differentiation and collagenase treatment on BTI integration was assessed by conducting histological staining, cell adhesion assay, and tensile testing. Finally, histological and biomechanical analyses were used to evaluate in vivo efficacy of fibrocartilage construct in a rat ACL reconstruction model. RESULTS: Fibrocartilage-like features were observed with in the scaffold-free sy-MSC constructs when applying TGF-band CTGF concurrently. Fifteen minutes collagenase treatment increased cellular attachment 1.9-fold compared to the Control group without affecting tensile strength. The failure stress was highest in the Col + D + group (22.494 ± 13.74 Kpa) compared to other groups at integration analysis in vitro. The ACL Recon + FC group exhibited a significant 88% increase in estimated stiffness (p = 0.0102) compared to the ACL Recon group at the 4-week postoperative period. CONCLUSION Scaffold-free, fibrocartilage engineering together with tendon collagenase treatment enhanced fibrocartilaginous BTI healing in ACL reconstruction.

BACKGROUND: Poly(L-lactic acid) (PLLA) is a biodegradable polymer (BP) that replaces conventional petroleumbased polymers. The hydrophobicity of biodegradable PLLA periodontal barrier membrane in wet state can be solved by alloying it with natural polymers. Alloying PLLA with gelatin imparts wet mechanical properties, hydrophilicity, shrinkage, degradability and biocompatibility to the polymeric matrix. METHODS: To investigate membrane performance in the wet state, PLLA/gelatin membranes were synthesized by varying the gelatin concentration from 0 to 80 wt%. The membrane was prepared by electrospinning. RESULTS: At the macroscopic scale, PLLA containing gelatin can tune the wet mechanical properties, hydrophilicity, water uptake capacity (WUC), degradability and biocompatibility of PLLA/gelatin membranes. As the gelatin content increased from 0 to 80 wt%, the dry tensile strength of the membranes increased from 6.4 to 38.9 MPa and the dry strain at break decreased from 1.7 to 0.19. PLLA/gelatin membranes with a gelatin content exceeding 40% showed excellent biocompatibility and hydrophilicity. However, dimensional change (37.5% after 7 days of soaking), poor tensile stress in wet state (3.48 MPa) and rapid degradation rate (73.7%) were observed. The highest WUC, hydrophilicity, porosity, suitable mechanical properties and biocompatibility were observed for the PLLA/40% gelatin membrane. CONCLUSION PLLA/gelatin membranes with gelatin content less than 40% are suitable as barrier membranes for absorbable periodontal tissue regeneration due to their tunable wet mechanical properties, degradability, biocompatibility and lack of dimensional changes.

Objective: The purpose of this study was to identify prognostic factors related to outcomes of out-of-hospital cardiac arrest caused by pesticide poisoning. Methods: This retrospective observational study used countrywide population-based data from the Out-of-Hospital Cardiac Arrest Surveillance of the Korean Centers for Disease Control and Prevention from January 2008 to December 2018. Adult out-of-hospital cardiac arrest (OHCA) patients (over the age of 18) poisoned by a pesticide who experienced cardiac arrest and a subsequent return of spontaneous circulation (ROSC) were included in the study. The primary outcome variables were prognostic factors related to survival at hospital discharge, and the secondary outcome variable was good neurological outcome (Cerebral Performance Categories 1 or 2) at hospital discharge. Results: Three hundred and three patients were enrolled in the study, and 48 (15.8%) survived until hospital discharge (the hospital discharge group), and 255 (84.2%) died in hospital (the in-hospital death group). Fifteen (4.9%) of the 303 study subjects had a good neurological outcome, and 288 (95.1%) had a poor neurological outcome. Multivariate logistic regression showed that sustained pre-hospital ROSC was significantly associated with survival to discharge (adjusted odds ratio [AOR]=3.186; 95% confidence interval [CI], 1.436-7.068; P=0.004) and good neurological outcome (AOR=8.945; 95% CI, 2.974-26.907; P≤0.001). Conclusion Sustained pre-hospital ROSC is associated with a favorable outcome in cases of OHCA induced by pesticide poisoning.