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Decellularized extracellular matrix (dECM) offers a three‐dimensional, non‐immunogenic scaffold, enriched with bioactive components, making it a suitable candidate for tissue regeneration. Although dECM‐based scaffolds have been successfully implemented in preclinical and clinical settings within tissue engineering and regenerative medicine, the mechanisms of tissue remodeling and functional restoration are not fully understood. This review critically assesses the state‐of‐the‐art in dECM scaffolds, including decellularization techniques for various tissues, quality control and cross‐linking. It highlights the functional properties of dECM components and their latest applications in multiorgan tissue engineering and biomedicine. Additionally, the review addresses current challenges and limitations of decellularized scaffolds and offers perspectives on future directions in the field. We conducted a critical evaluation of decellularization techniques, quality control, cross‐linking, and modification methods for dECM scaffolds derived from different sources. The functional properties of dECM components as well as their recent applications in multi‐organ tissue engineering and biomedicine were thoroughly reviewed. This work aims to discuss and summarize the current challenges and limitations of acellular scaffolds while also outlining future directions.

This paper addresses a serial-batching scheduling problem where the jobs with arbitrary release times are scheduled on parallel machines with the objective to minimize the makespan. The effects of learning and deterioration are considered simultaneously, and each job’s actual processing time depends on the sum of previous jobs’ processing times and the position of the current job. Each machine can process up to c jobs in the manner of serial batch, i.e., one after another with a setup time for each batch. Structural properties are identified for the special cases of the studied problem. Based on these derived structural properties, we propose a novel hybrid SC-VNS algorithm to solve the studied problem, which combines Society and Civilization (SC) algorithm with Variable Neighborhood Search (VNS). Computational experiments are conducted to evaluate the performance of the proposed hybrid algorithm and some other well-known algorithms. The results demonstrate that the proposed hybrid SC-VNS algorithm performs quite better than the compared algorithms in terms of the solution quality and the required running time.

Over the past decade, organoids have emerged as a prevalent and promising research tool, mirroring the physiological architecture of the human body. However, as the field advances, the traditional use of animal or tumor-derived extracellular matrix (ECM) as scaffolds has become increasingly inadequate. This shift has led to a focus on developing synthetic scaffolds, particularly hydrogels, that more accurately mimic three-dimensional (3D) tissue structures and dynamics in vitro. The ECM–cell interaction is crucial for organoid growth, necessitating hydrogels that meet organoid-specific requirements through modifiable physical and compositional properties. Advanced composite hydrogels have been engineered to more effectively replicate in vivo conditions, offering a more accurate representation of human organs compared to traditional matrices. This review explores the evolution and current uses of decellularized ECM scaffolds, emphasizing the application of decellularized ECM hydrogels in organoid culture. It also explores the fabrication of composite hydrogels and the prospects for their future use in organoid systems.

This paper investigates a parallel-machine group scheduling problem where non-identical jobs with arbitrary sizes and inclusive processing set restrictions can be either processed on in-house parallel machines in the form of serial batch or outsourced with cost. The objective of our study is aimed at minimizing the weighted sum of the in-house makespan and the total outsourcing cost for a platform manufacturing enterprise. Some structural properties are identified for the optimal solution in some special cases of the studied problem, which contribute to the optimal solution for the studied problem. Further, based on these properties, a novel hybrid algorithm VNS–NKEA is proposed to solve the studied problem, which integrates neighborhood knowledge-based evolutionary algorithm (NKEA) and variable neighborhood search (VNS). To demonstrate the better performance including solution quality and the convergence speed of the proposed algorithm, computational experiments are conducted to evaluate its performance by comparing with other proposed algorithms. The experiment results show that the hybrid algorithm performs quite better than other compared algorithms for each instance, which reflect that the hybrid algorithm can solve the studied problem effectively.

Mitochondria Sirtuins including SIRT4 erase a variety of posttranslational modifications from mitochondria proteins, leading to metabolic reprogramming that acts as a tumor suppressor, oncogenic promotor, or both. However, the factors and the underlying mechanisms that stimulate and relay such a signaling cascade are poorly understood. Here, we reveal that the voltage‐gated calcium channel subunit α2δ1‐mediated calcium signaling can upregulate the expression of SIRT4, which is highly expressed in α2δ1‐positive pancreatic tumor‐initiating cells (TICs). Furthermore, SIRT4 is functionally sufficient and indispensable to promote TIC properties of pancreatic cancer cells by directly deacetylating ENO1 at K358, leading to attenuated ENO1's RNA‐binding capacity, enhanced glycolytic substrate 2‐PG affinity, and subsequently robust catalytic activity with boosted glycolytic ability and increased production of lactate acid. Interestingly, both SIRT4 and deacetylated mimetic of ENO1‐K358 can increase the lactylation of histones at multiple sites including H3K9 and H3K18 sites, which resulted in epigenetic reprogramming to directly activate a variety of pathways that are essential for stemness. Hence, the study links α2δ1‐mediated calcium signaling to SIRT4‐mediated histone lactylation epigenetic reprogramming in promoting the stem cell‐like properties of pancreatic cancer, which holds significant potential for the development of novel therapeutic strategies by targeting TICs of pancreatic cancer. As a downstream target of α2δ1‐mediated calcium signaling, SIRT4 serves as an oncogene to promote the stemness of pancreatic cancer via deacetylating ENO1 directly at K358, leading to attenuated ENO1's RNA‐binding capacity, enhanced glycolytic substrate 2‐PG binding and robust glycolytic activity to increase the level of lactate that induce histone lactylation to epigenetically regulate signaling pathways essential for stemness.

SIRT4 is well-known as a tumor suppressor by controlling several metabolic pathways, although it is highly expressed in certain cancers including hepatocellular carcinoma (HCC). Here, we reported that SIRT4 was highly expressed in the voltage-gated calcium channel α2δ1 subunit-positive HCC tumor-initiating cells (TIC), and was upregulated by α2δ1-mediated calcium signaling. Moreover, the expression of SIRT4 in HCC tissues was predictive of poor prognosis of the patients. Interestingly, SIRT4 was functionally sufficient and indispensable to promote TIC properties and invasiveness of HCC cells by directly deacetylating the leucine catabolism pathway enzyme-3-methylcrotonyl-CoA carboxylase 2 (MCCC2) at K269, leading to the formation of a stable MCCC1/MCCC2 complex with robust MCCC enzymatic activity to produce more acetyl-CoA, which resulted in increased H3K27 acetylation and stem cell-like properties at doses≤2 µM. However, 10 µM acetyl-CoA was neither able to enhance H3K27 acetylation, nor to promote stem cell-like properties, while forced expression of SIRT4 in α2δ1 cells resulted in retardation of tumor growth . Thus, SIRT4 serves as an oncogene to promote stemness and invasiveness by controlling the production of acetyl-CoA, linking α2δ1-mediated calcium signaling to SIRT4-mediated epigenetic reprogramming of HCC TICs which hold significant potential for the development of novel therapeutic strategies targeting TICs, and the dual roles of SIRT4 in HCC might be dependent on the production levels of acetyl-CoA.

Aging is characterised by progressive structural and functional changes in the liver, with the extracellular matrix (ECM) playing a key role in modulating these changes. Our study presents a comprehensive proteomic analysis of the liver ECM across different age stages, uncovering significant age‐related changes. Through the identification of 158 ECM proteins in decellularised rat liver scaffolds, we reveal the intricate relationship between ECM composition and liver maturation, as well as the decrease in regenerative capacity. Lumican was identified as a critical regulator with heightened expression in neonatal livers, which is associated with enhanced hepatocyte proliferation and maintenance of stem cell characteristics. Temporal expression analysis distinguished four distinct clusters of ECM proteins, each reflecting the liver's functional evolution from early development to old age. Early developmental stages were marked by proteins essential for liver growth, while adulthood was characterised by a robust ECM supporting metabolic functions. Middle age showed a regulatory shift towards protease balance, and later life was associated with haemostasis‐related processes. Our findings underscore the multifaceted role of the ECM in liver health and aging, offering potential opportunities for therapeutic intervention to counteract age‐induced liver dysfunction. This study provides a foundational understanding of ECM dynamics in liver aging and sets the stage for the development of innovative strategies to mitigate the effects of age‐related liver decline. This study reveals age‐dependent remodelling of the liver extracellular matrix (ECM), identifying Lumican as a key regulator of hepatocyte proliferation and stemness in foetal development. Dynamic ECM shifts influence liver function, offering insights into therapeutic strategies for aging‐related hepatic decline.

The cover image is based on the article Deciphering Age‐Dependent ECM Remodelling in Liver: Proteomic Profiling and Its Implications for Aging and Therapeutic Targets by Juan Liu et al., https://doi.org/10.1111/cpr.70087 . image

Post-stroke depression (PSD) affects millions of patients who suffer cerebral stroke. However, the molecular mechanisms and pathophysiology are poorly understood. Previous studies have shown that exosomes have been proven to be involved in neuropsychiatric disorders such as stroke and post-stroke depression in neurotransmitter release, neuronal remodeling, and neuron angiogenesis. Here we extracted and purified hippocampal exosomes from stroke mouse model to investigate mechanisms of hippocampal exocytosis in PSD assessed by using behavioral tests and biochemical methods. Aiming at the effect of hippocampal exosomes from stroke on the development of PSD, behavioral test was compared including sugar water preference experiment, open fields, forced swimming test, to explore it in depth. Further, the expression of depression-related protein (proBDNF and p75NTR) and synapse-associated proteins (Synaptotagmin and PSD95) was evaluated by Western blotting, RT-qPCR or immunofluorescence staining. Density of dendritic protrusions of neurons was assessed by Golgi staining to measure changes in spine density after the treatment of hippocampal exosomes from stroke. Our results revealed that injection of exosomes from stroke models significantly aggravated depressive-like behaviors, increase of depression-related protein (proBDNF and p75NTR) expression and deficiency of synapse-associated proteins (Synaptotagmin and PSD95) expression, and the decreased number of spin density. Our findings together suggest that hippocampal exosomes from stroke cause exacerbation of depressive-like behavior in mice, possibly resulting from the regulation of neurogenesis by its depression-associated proteins (proBDNF and p75NTR). Therefore, hippocampal exosomes from stroke are promising targets for the diagnosis and treatment of PSD.

Background Nitrate (represented by NN or NO 3 − -N) and ammonium (represented by AN or NH 4 + -N) are the two predominant nitrogen (N) forms utilized by plants; however, the physiological mechanisms underlying citrus response to different N forms are still poorly understood. In this study, seedlings of two citrus varieties ( Citrus reticulata Blanco cv. Lugan and Citrus sinensis (L.) Osbeck cv. Xuegan) were cultivated under two N forms (NN and AN, at 4 mmol L − 1 ) to investigate their ultrastructural, physiological, and biochemical characteristics. Results Compared with AN treatment, NN treatment significantly promoted plant growth by regulating the physiological and morphological characteristics of roots and leaves. Under AN conditions, there was an excessive accumulation of free amino acids and soluble proteins in both leaves and roots, which suppressed the activity of N assimilation enzymes and consequently reduced plant N uptake. Furthermore, AN treatment inhibited photosynthetic performance by decreasing chlorophyll content, damaging chloroplast structure, and disrupting photosynthetic electron transport chain. Consequently, this led to the accumulation of non-structural carbohydrates in both leaves and roots, ultimately affecting the morphogenesis of citrus plants. Additionally, AN treatment induced an oxidative stress response, increasing malondialdehyde (MDA) levels and eliciting an antioxidant response in citrus seedlings. Moreover, based on measured physiological parameters, principal component analysis showed an obvious separation between AN and NN treatments. Conclusions Our findings demonstrated that NN supply enhanced plant growth owing to the improved coordination of carbon and N metabolism in citrus plants, thereby providing a basis for optimizing N management strategies in sustainable citrus production. Highlights 1. N source effects on plant growth and N metabolism in two citrus varieties were investigated. 2. The process of citrus N assimilation was improved by nitrate fed. 3. Ammonium inhibits photosynthetic performance by disturbing chloroplast structure and assimilates production. 4. Unused light energy induced photo-oxidative stress under ammonium conditions. 5. Nitrate promotes plant growth by regulating N metabolism and photosynthesis physiology.