Search

Cell implantation offers an appealing avenue for heart repair after myocardial infarction (MI). Nevertheless, the implanted cells are subjected to the aberrant myocardial niche, which inhibits cell survival and maturation, posing significant challenges to the ultimate therapeutic outcome. The functional cardiac patches (CPs) have been proved to construct an elastic conductive, antioxidative, and angiogenic microenvironment for rectifying the aberrant microenvironment of the infarcted myocardium. More importantly, inducing implanted cardiomyocytes (CMs) adapted to the anisotropic arrangement of myocardial tissue by bioengineered structural cues within CPs are more conducive to MI repair. Herein, a functional Cig/(TA-Cu) CP served as biomimetic cardiac niche was fabricated based on structural anisotropic cigarette filter by modifying with tannic acid (TA)-chelated Cu2+ (TA-Cu complex) via a green method. This CP possessed microstructural anisotropy, electrical conductivity and mechanical properties similar to natural myocardium, which could promote elongation, orientation, maturation, and functionalization of CMs. Besides, the Cig/(TA-Cu) CP could efficiently scavenge reactive oxygen species, reduce CM apoptosis, ultimately facilitating myocardial electrical integration, promoting vascular regeneration and improving cardiac function. Together, our study introduces a functional CP that integrates multimodal cues to create a biomimetic cardiac niche and provides an effective strategy for cardiac repair.

Abstract Treatment response and prognosis estimation in advanced pulmonary adenocarcinoma are challenged by the significant heterogeneity of the disease. The current Response Evaluation Criteria in Solid Tumors (RECIST) criteria, despite providing a basis for solid tumor response evaluation, do not fully encompass this heterogeneity. To better represent these nuances, we introduce the intertumoral heterogeneity response score (THRscore), a measure built upon and expanding the RECIST criteria. This retrospective study included patients with 3–10 measurable advanced lung adenocarcinoma lesions who underwent first‐line chemotherapy or targeted therapy. The THRscore, derived from the coefficient of variation in size for each measurable tumor before and 4–6 weeks posttreatment, unveiled a correlation with patient outcomes. Specifically, a high THRscore was associated with shorter progression‐free survival, lower tumor response rate, and a higher tumor mutation burden. These associations were further validated in an external cohort, confirming THRscore's effectiveness in stratifying patients based on progression risk and treatment response, and enhancing the utility of RECIST in capturing complex tumor behaviors in lung adenocarcinoma. These findings affirm the promise of THRscore as an enhanced tool for tumor response assessment in advanced lung adenocarcinoma, extending the RECIST criteria's utility.

The paper aims to establish the related backward stochastic dynamic equations on time scales, BS ∇ Es for short, concerning to ∇-integral on time scales. We present the martingale decomposition theorem on time scales and prove the existence and uniqueness theorem of solutions to BS ∇ Es. This work can be considered as a unification and a generalization of similar results in backward stochastic difference equations and backward stochastic differential equations.

The interaction of a hybrid transshipment policy and customer switching behaviour will exacerbate the complexity of the structure of a hybrid transshipment policy. To cope with this problem, a discrete-time dynamic programming model framework with customer switching behaviour is developed. Based on this framework, we demonstrate that the retailer can obtain more profits with a hybrid transshipment than without one. Next, the existence of a reactive and preventive transshipment policy is shown, respectively. We further analyse the structural property of the holdback policy of reactive transshipment and give the threshold of customer switching rate when always rejecting the request. Meanwhile, a dominant preventive transshipment policy is formulated by which the retailer can control the inventory regardless of the influence of the preventive transshipment policy of the other as long as the inventory is observed by developing an easy-to-implement optimal hybrid transshipment strategy. In addition, the existence of an ordering Nash equilibrium of two retailers is proven. Then, we also illustrate the existence of a transshipment area and analyse the impact of the transshipment cost and switching rate on ordering, the hybrid transshipment policy, and profit by using numerical examples. Finally, we find that the retailer is more willing to adjust inventory by ordering when there is a lower transshipment price and adjust inventory by hybrid transshipment when there is a higher transshipment price.