Background: Toll-like receptors (TLRs) are recognized as important contributors to the initiation and modulation of the inflammatory response in the eye. This study investigated the precise expression patterns and functionality of TLRs in human corneal epithelial cells (HCE) and in conjunctival fibroblasts (HCF). Methods: The cell surface expression of TLRs 2-4, TLR7 and TLR9 in HCE and HCF was examined by flow cytometry with or without stimulation with lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (poly I:C). The mRNA expression of the TLRs was determined by real-time PCR. The protein content levels of interleukin (IL)-6, IL-8, IL-1β and tumor necrosis factor-α (TNF-α) were measured in HCE and HCF using multiplex fluorescent bead immunoassay (FBI). Results: The surface expression of TLR3 and TLR4 was detected on both HCE and HCF. Following incubation with LPS, the percentage of HCE cells staining for TLR4 decreased from 10.18% to 0.62% (P < 0.001). Incubation with poly I:C lowered the percentage of HCE cells positive for TLR3 from 10.44% to 2.84% (P < 0.001). The mRNA expression of TLRs2, 4, 7 and 9 was detected in HCE only. Activation of HCE with LPS complex elicited protein secretion up to 4.51 ± 0.85-fold higher levels of IL-6 (P < 0.05), 2.5 ± 0.36-fold IL-8 (P > 0.05), 4.35 ± 1.12-fold IL-1β (P > 0.05) and 29.35 ± 2.3-fold TNFα (P < 0.05) compared to cells incubated in medium. Conclusions: HCF and HCE both express TLRs that respond to specific ligands by increasing cytokine expression. Following activation, the surface expression of TLR3 and TLR4 on HCE is decreased, thus creating a negative feedback loop, mitigating the effect of TLR activation.

Biofabricating 3D cardiac tissues that mimic the native myocardial tissue is a pivotal challenge in tissue engineering. In this study, we fabricate 3D cardiac tissues with controlled, multidirectional cellular alignment and directed or twisting contractility. We show that multidirectional filamented light can be used to biofabricate high‐density (up to 60 × 10 ⁶ cells mL ⁻¹ ) tissues, with directed uniaxial contractility (3.8x) and improved cell‐to‐cell connectivity (1.6x gap junction expression). Furthermore, by using multidirectional light projection, we can partially overcome cell‐induced light attenuation, and fabricate larger tissues with multidirectional cellular alignment. For example, we fabricate a tri‐layered myocardium‐like tissue and a bi‐layered tissue with torsional contractility. The approach provides a new strategy to rapidly fabricate aligned cardiac tissues relevant to regenerative medicine and biohybrid robotics.

Objectives: Lung neuroendocrine tumors (LNETs) are rare, comprising 1–2% of lung cancers. This study aimed to compare overall survival (OS) and recurrence-free survival (RFS) after lobar resection versus sublobar resection for LNETs and to identify factors associated with prognosis and resection extent. Methods: We retrospectively analyzed patients with clinical stage I (T ≤ 4 cm, N0M0) typical or atypical carcinoid who underwent curative resection at Hadassah Medical Center and Kaplan medical Center between 2010 and 2024. Results: Seventy patients (mean age 56.8 ± 16 years; 63% female) were included. Lobar resection was performed in 40 (57%) and sublobar resection in 30 (43%; 15 segmentectomies, 15 wedge resections). Pathology revealed 50 typical carcinoid (71.43%) and 20 atypical carcinoid (28.57%). Final pathological stage was I in 57 patients (81.42%), II in 9 (12.86%), and III in 4 (5.71%), reflecting surgical upstaging in 13 patients (18.57%), all due to nodal involvement. Atypical carcinoid was associated with worse RFS, nodal upstaging, and adjuvant therapy (all p < 0.01). Patients undergoing sublobar resection were older, had higher comorbidity scores, more frequently presented with peripheral tumors, and underwent less frequent lymph node assessment (all p < 0.01). At a median follow-up of 3.8 years for OS and 2.0 years for RFS, survival rates were 95.7% for both. Neither OS, RFS, nor postoperative normalization of plasma pro-gastrin-releasing peptide (ProGRPp) levels differed significantly between lobar resection and sublobar resection (p = 0.94, p = 0.42, and p = 0.205, respectively). Conclusions: Sublobar resection may represent an acceptable surgical option for selected patients with clinical stage I LNETs, particularly for peripheral tumors ≤ 2 cm in older or comorbid patients. The high rate of nodal upstaging underscores the need for lymph node assessment, irrespective of resection extent.

Introduction: Lung neuroendocrine tumors (LNETs) are rare, with surgical resection as the mainstay of treatment, although the optimal extent remains uncertain. Herein, we present the first meta‐analysis to assess the effect of resection extent (lobar vs. sub‐lobar) on overall survival. Methods: We conducted a systematic review of the literature to identify studies comparing overall survival following lobectomy versus sub‐lobar resection in LNETs. An inverse‐variance meta‐analysis was performed, and a Cox regression model was applied to reconstructed time‐to‐event data estimated from published Kaplan–Meier curves to generate pooled survival estimates. Results: Six studies encompassing 3,700 patients (lobectomy, n = 2,409; sub‐lobar resection, n = 1,291) were included in the final analysis. The pooled 5‐year overall survival for the entire cohort was 78.8% (95% CI, 76.6–81.1). No statistically significant difference in overall survival was observed between lobectomy and sub‐lobar resection (HR = 1.21; 95% CI, 0.80–1.83; I ² = 0%). Segmentectomy and lobectomy demonstrated comparable survival ( p = 0.38), whereas wedge resection was associated with higher mortality (HR = 2.02; 95% CI, 1.64–2.49; I ² = 0%). Sampling of >10 lymph nodes was more frequent in lobectomy than sub‐lobar resection (29.1% [95% CI, 0.8–95.3] vs 7.4% [95% CI, 0.01–98], respectively), likely contributing to the higher rate of nodal pathologic upstaging observed in the lobectomy group (6.2% [95% CI, 0.2–64.9] vs 2.2% [95% CI, 0–99]). Conclusion: In this first meta‐analysis of surgical resection for LNETs, sub‐lobar resection and lobectomy showed no clear difference in overall survival. Adequate lymph node assessment remains essential, irrespective of the surgical approach.