Regeneration Pathways Research Articles

Decoding lung complexity: single-cell sequencing in lung diseases, regeneration, and drug discovery

The lung is constantly exposed to the external environment, making it highly susceptible to infections and injuries caused by airborne pollutants and pathogens. Understanding the cellular players and molecular mechanisms underlying post-injury lung repair is essential for elucidating the repair processes following injury. Single-Cell Sequencing (sc-seq) offers unprecedented single-cell resolution, enabling researchers to dissect the complex biological profiles that drive diverse lung pathologies and to uncover the signaling pathways crucial for lung regeneration. This review will explore the latest findings in lung diseases and regeneration revealed by sc-seq. Additionally, we will highlight how continuous advancements in sc-seq technology are paving the way for the development of novel drugs aimed at targeting pathways involved in lung regeneration and treating lung diseases. By offering single-cell resolution, recent advancements in sc-seq have enabled researchers to dissect multiple layers of biological profiles underlying diverse lung pathogenesis and uncover signaling pathways critical for lung regeneration. In this review, we will discuss recent sc-seq findings in lung diseases and regeneration. Continuous advancements in sc-seq technology hold great promise for facilitating the development of novel drugs targeting lung regeneration pathways and lung diseases. These repair processes are mediated by resident epithelial stem cells and their niche cells.

Land covers associated with forest expansion hot spots in the Nepal Himalaya

Abstract Many regions of the Himalaya are experiencing forest expansion, signifying a widespread forest transition across this fragile mountain system. In the Nepal Himalaya, forest expansion is increasingly attributed to the narrative of cropland abandonment driven by rural outmigration. Understanding forest change dynamics as consequences of land use changes is critical in the context of rural mountain societies such as Nepal, which exhibit complex interactions between forest, agriculture, and livelihoods. We analysed forest gain in Nepal from 2000–2019 to inquire where and when forests have expanded and what land covers transitioned into forests. We integrated spatiotemporal analysis of national land cover maps and photointerpretation of very high resolution (VHR) imagery to improve analytical estimates. The Middle Mountain physiographic region experienced the strongest hot spots of forest gains relative to the high mountains or lowlands. Visual interpretation of VHR showed that 68.8% of forest gains since 2000 occurred on shrubland, and 26.5% on cropland. The dominance of shrubland-forest transitions implied that shrubland is an intermediate stage in a multi-decadal succession process, or a semi-permanent state such as arrested succession. Notably however, we also detected cropland-forest transitions occurring as fast as 6–10 years, indicating the potential for rapid forest succession if biophysical conditions permit. Thus, variations in land cover transitions to forests in the hills implicated multiple pathways of forest regeneration, reflecting a variety of spatiotemporally explicit drivers. Our results differ from previous studies because VHR image analysis accounted for land cover classification errors and improved land cover quantification. Further research on spatially explicit mechanisms and drivers of forest gain are needed to understand the synergies of forest, agriculture, and livelihoods to inform land use land cover policies that could be leveraged to enhance rural mountain livelihoods.

MiRNA-519e promotes cardiomyocyte cell division accompanied by pro-angiogenic and anti-apoptotic effects

Abstract Background MicroRNAs have the therapeutic potential for heart repair after myocardial infarction(MI). Using a functional high-throughput screening approach, we identified microRNA-519e(miR-519e) as an inducer of cell-cycling in human-derived iPSC-cardiomyocytes(hiPSC-­CM). Purpose This study examines miR-519e for cell division in hiPSC-­CM, additional beneficial functions in heart-related non-CMs, and direct target identification and validation in vitro and in vivo. Methods MiR-519e-mimics or miR-scrambled(miR-scr) were transfected into hiPSC-­CM, human aortic endothelial cells(HAEC) and human cardiac fibroblasts(cFB). Proliferative markers (EdU(5-Ethynyl-2'- deoxyuridine), H3P(Phospho-Histone H3) and AURKB(Aurora B-kinase)) and apoptotic response using MTT assay after exposure to doxorubicin were assessed in hiPSC­-CMs. Angiogenic capacity of HAEC was evaluated by tube formation assay and fibrotic response of cFBs using EdU and α-SMA(smooth muscle actin) staining. In vivo, a mouse MI model with ligation of the left anterior descending followed by intramyocardial injection of miR-519e or miR-scr was used. Direct target identification of miR-519e was assessed using in silico analysis combined with RNA-Seq of miR-519e-mimic treated hiPSC-CMs and validated using Ago2-RNA immunoprecipitation(RIP) followed by qPCR. Results After transfection of miR-519e-mimics in hiPSC-­CM, a significant proliferative response indicative of cell division was observed in immunofluorescence staining and on protein level as compared with miR-scr treated hiPSC-CMs (EdU, H3P and AURKB, p<0.01). Apoptosis was blunted in miR-519e-treated hiPSC-CMs (p<0.05). MiR-519e-treatment of HAEC resulted in more meshes (p<0.01) and longer tube length (p<0.05), indicating enhanced pro-angiogenic capacity. Importantly, EdU-uptake and α-SMA were similar in miR-519e-treated cFB as compared to miR-scr, suggesting neutral effects of miR-519e on myofibroblast transition. In mice undergoing MI, injection of miR-519e-mimics significantly downregulated CDKN1A/P21(Cyclin dependent kinase inhibitor 1A) (p<0.05 vs. miR-scr), a direct target of miR-519e and negative master regulator of cell-cycling. For further novel target identification of miR-519e, we performed in silico analysis combined with RNA-Seq data from miR-519e-treated hiPSC-CM and validation using Ago2-RIP followed by qPCR. Herein, we identified PTEN(Phosphatase and tensin homolog) and TGFBR2(Transforming growth factor β receptor 2) that are involved in cardiomyocyte proliferation and hypoxic response, as direct targets of miR-519e. Conclusion Collectively, miR-519e is a potent inducer of cell division in human cardiomyocytes, with anti-apoptotic and pro-angiogenic capacity in the absence of pro-fibrotic effects. We show that miR-519e treatment downregulates key negative cell-cycle regulators in vivo and we identified novel direct targets of miR-519e that are involved in regulatory pathways for heart regeneration.

Dendrite injury triggers neuroprotection in Drosophila models of neurodegenerative disease.

Dendrite defects and loss are early cellular alterations observed across neurodegenerative diseases that play a role in early disease pathogenesis. Dendrite degeneration can be modeled by expressing pathogenic polyglutamine disease transgenes in Drosophila neurons in vivo. Here, we show that we can protect against dendrite loss in neurons modeling neurodegenerative polyglutamine diseases through injury to a single primary dendrite branch. We find that this neuroprotection is specific to injury-induced activation of dendrite regeneration: neither injury to the axon nor injury just to surrounding tissues induces this response. We show that the mechanism of this regenerative response is stabilization of the actin (but not microtubule) cytoskeleton. We also demonstrate that this regenerative response may extend to other neurodegenerative diseases. Together, we provide evidence that activating dendrite regeneration pathways has the potential to slow-or even reverse-dendrite loss in neurodegenerative disease.

Current advances in the development of microRNA-integrated tissue engineering strategies: a cornerstone of regenerative medicine.

Regenerative medicine is an innovative scientific field focused on repairing, replacing, or regenerating damaged tissues and organs to restore their normal functions. A central aspect of this research arena relies on the use of tissue-engineered scaffolds, which serve as structural supports that mimic the extracellular matrix, providing an environment that orchestrates cell growth and tissue formation. Remarkably, the therapeutic efficacy of these scaffolds can be improved by harnessing the properties of other molecules or compounds that have crucial roles in healing and regeneration pathways, such as phytochemicals, enzymes, transcription factors, and non-coding RNAs (ncRNAs). In particular, microRNAs (miRNAs) are a class of tiny (20-24nt), highly conserved ncRNAs that play a critical role in the regulation of gene expression at the post-transcriptional level. Accordingly, miRNAs are involved in a myriad of biological processes, including cell differentiation, proliferation, and apoptosis, as well as tissue regeneration, angiogenesis, and osteogenesis. On this basis, over the past years, a number of research studies have demonstrated that miRNAs can be integrated into tissue-engineered scaffolds to create advanced therapeutic platforms that precisely modulate cellular behavior and offer a controlled and targeted release of miRNAs to optimize tissue repair and regeneration. Therefore, in this current review, we discuss the most recent advances in the development of miRNA-loaded tissue-engineered scaffolds and provide an overview of the future outlooks that should be aborded in this area of study in order to lay the groundwork for the clinical translation of these tissue engineering approaches.

Map3k1 suppresses terminal differentiation of migratory eye progenitors in planarian regeneration.

Proper stem cell targeting and differentiation is necessary for regeneration to succeed. In organisms capable of whole body regeneration, considerable progress has been made identifying wound signals initiating this process, but the mechanisms that control the differentiation of progenitors into mature organs are not fully understood. Using the planarian as a model system, we identify a novel function for map3k1, a MAP3K family member possessing both kinase and ubiquitin ligase domains, to negatively regulate terminal differentiation of stem cells during eye regeneration. Inhibition of map3k1 caused the formation of multiple ectopic eyes within the head, but without controlling overall head, brain, or body patterning. By contrast, other known regulators of planarian eye patterning like WntA and notum also regulate head regionalization, suggesting map3k1 acts distinctly. Eye resection and regeneration experiments suggest that unlike Wnt signaling perturbation, map3k1 inhibition did not shift the target destination of eye formation in the animal. Instead, map3k1(RNAi) ectopic eyes emerge in the regions normally occupied by migratory eye progenitors, and the onset of ectopic eyes after map3k1 inhibition coincides with a reduction to eye progenitor numbers. Furthermore, RNAi dosing experiments indicate that progenitors closer to their normal target are relatively more sensitive to the effects of map3k1, implicating this factors in controlling the site of terminal differentiation. Eye phenotypes were also observed after inhibition of map2k4, map2k7, jnk, and p38, identifying a putative pathway through which map3k1 prevents differentiation. Together, these results suggest that map3k1 regulates a novel control point in the eye regeneration pathway which suppresses the terminal differentiation of progenitors during their migration to target destinations.

Calcium Hydroxylapatite in Regenerative Aesthetics: Mechanistic Insights and Mode of Action.

Calcium Hydroxylapatite-Carboxymethylcellulose (CaHA-CMC) is a widely used soft-tissue filler known for its compatibility with human tissue and for its effective volumizing properties. The biodegradable CaHA microspheres function as a scaffold for the formation of new tissue by stimulating a variety of cellular responses leading to the production of collagen, elastin, vasculature and proteoglycans and thereby enhancing skin quality. Despite the promising regenerative effects of CaHA-CMC, substantial gaps remain in understanding its precise underlying mechanisms, and addressing these gaps is crucial for optimizing its clinical applications. A literature search was conducted using PubMed, google scholar and web of science for key words including "calcium hydroxylapatite", " tissue regeneration", "macrophages", "fibroblasts" and "calcium". This review elucidates the novel mechanisms of CaHA-CMC action within aesthetic medicine, with a focus on the dynamic interactions between macrophages and fibroblasts. The key role of calcium ions as critical biocues in directing skin regeneration pathways is explored alongside an examination of the distinct physicochemical properties of CaHA-CMC. CaHA-CMC helps in tissue regeneration by providing calcium ions that act as key biological cues, promoting fibroblast activity and collagen production.

The Regulatory Role of miRNAs in Zebrafish Fin Regeneration

Since Teleostei fins have a strong regenerative capacity, further research was conducted on the regulation of gene expression during fin regeneration. This research focuses on miRNA, which is a key post-transcriptional regulatory molecule. In this study, a miRNA library for the fin regeneration of zebrafish was constructed to reveal the differential expression of miRNA during fin regeneration and to explore the regulatory pathway for fin regeneration. Following the injection of miRNA agomir into zebrafish, the proliferation of blastema cells and the overall fin regeneration area were significantly reduced. It was observed that the miRNAs impaired blastocyte formation by affecting fin regeneration through the inhibition of the expressions of genes and proteins associated with blastocyte formation (including yap1 and Smad1/5/9), which is an effect associated with the Hippo pathway. Furthermore, it has been demonstrated that miRNAs can impair the patterns and mineralization of newly formed fin rays. The miRNAs influenced fin regeneration by inhibiting the expression of a range of bone-related genes and proteins in osteoblast lineages, including sp7, runx2a, and runx2b. This study provides a valuable reference for the further exploration of morphological bone reconstruction in aquatic vertebrates.

Exosomes, peptides and peri-procedure management – comparative investigations

Introduction: Exosome technology is a promising new advancement in therapeutic options but is still in its early stages, leading to uncertainties. A small pilot study compared traditional peptide technology (Regenerating Skin Nectar with TriHex Technology® and TriHex Technology® peptide + Octapeptide) to two leading exosome products (Stem cell derived Lyophilized exosomes and Platelet derived exosomes) for post-procedure use. These studies were carried out on pre-clinical (ex vivo) and clinical front to investigate effects on the extracellular matrix, dermo-epidermal junction, and skin tolerance as post-procedure outcomes. Methods and materials: The ex vivo model study was conducted by 3D Genomics using photodamaged skin from facelift patients. The skin was divided, processed under BSL2 conditions and cultured in transwells with specific media. Treatments, including peptides and platelet-derived products, were applied daily for 7 days, while stem cell-derived exosomes were applied as a single application as per the described usage. One set was left untreated as a control. Skin samples were treated and analyzed using immunohistochemistry staining for tropoelastin and CD44. RNA was isolated after treatments and sequenced to assess changes in gene expression. The study aimed to compare the effects of different treatments on skin regeneration and tolerance. Clinically, the participants underwent microneedling of the face and applied exosomes and peptides on each side of the face as comparisons. Participants completed questionnaires on Day 0. On Days 0,1,2,3 and 4 participants completed their self-healing ratings and were also assessed by an assessor on their healing rating on a 5-point scale. Results: The plated exosome products exhibited significant toxicity in the ex vivo model and neither of the exosome products produced relevant changes in gene expression or regenerative effects in this model. Participants in the small clinical series experienced unpleasant burning and stinging in keeping with the effects seen in the ex vivo model. In contrast, the peptide technology showed favorable gene expression upregulation and histological changes in the extracellular matrix and was well-tolerated and comfortable for post-procedure use, as has been demonstrated in multiple clinical trials. Conclusion: The overall impression from these pilot studies suggests that peptide formulations are better tolerated and more effectively target ECM regenerative effects. Conversely, exosome preparations appear to be prone to skin reactions and lack clear targeting of skin regenerative pathways.

Scaling Up Stability: Navigating from Lab Insights to Robust Oxygen Evolution Electrocatalysts for Industrial Water Electrolysis

AbstractIn the pursuit of sustainable hydrogen production via water electrolysis, paramount importance of electrocatalyst stability emerges as a defining factor for long‐term industrial viability. A thorough understanding and enhancement of stability not only ensure extended catalyst lifetimes but also pave the way for consistent and efficient hydrogen generation. This review focuses on the pivotal role of stability in determining the practical viability of oxygen evolution electrocatalysts (OECs) for large‐scale applications in water electrolysis for hydrogen production. The paper explores the pivotal role of stability over initial activity, citing examples and hypothetical scenarios. First, figures of merits for stability evaluation of the electrocatalyst are explained along with the available benchmarking protocols for stability evaluation. Further, the text delves into various strategies that can enhance the stability of the electrocatalyst which include self‐healing/regeneration pathway, oxygen evolution reaction (OER) mechanism optimization to achieve highly stable OER and stabilization of active metals atoms within the electrocatalyst to inhibit dissolution as a way forward for industrial application. The interplay of stability, activity, and cost is also explained to suit the industrial application of the electrocatalyst. Lastly, it outlines challenges, prospects, and future directions, presenting a guide for advancing OECs in the hydrogen generation landscape.

Unveiling axolotl transcriptome for tissue regeneration with high-resolution annotation via long-read sequencing

Axolotls are known for their remarkable regeneration ability. Exploring their transcriptome provides insight into regenerative mechanisms. However, the current annotation of the axolotl transcriptome is limited, leaving the role of unannotated transcripts in regeneration unknown. To discourse this challenge, we exploited long-read sequencing technology, which enables direct observation of full-length RNA transcripts, greatly enhancing the coverage and accuracy of axolotl transcriptome annotation. By utilizing this method, we identified 222 novel gene loci and 4775 novel transcripts, which were quantified using short-read sequencing data. Through the inclusive analysis, we discovered novel homologs, potential functional proteins, noncoding RNAs, and alternative splicing events in key regeneration pathways. In particular, we identified novel transcripts with high protein-coding potential implicated in cell cycle regulation and musculoskeletal development, and regeneration were identified. Interestingly, alternative splice variants were also detected across diverse pathways critical to regeneration. This specifies that these novel transcripts potentially play vital roles underpinning the robust regenerative capacities of axolotls. Single-cell transcriptomic analysis further revealed these isoforms to predominantly exist in axolotl limb chondrocytes and mature tissue cell populations. Overall, the findings significantly advanced consideration of the axolotl transcriptome and provided a new perspective for understanding the mechanisms of regenerative abilities of axolotls.

C286, an orally available retinoic acid receptor β agonist drug, regulates multiple pathways to achieve spinal cord injury repair.

Retinoic acid receptor β2 (RARβ2) is an emerging therapeutic target for spinal cord injuries (SCIs) with a unique multimodal regenerative effect. We have developed a first-in-class RARβ agonist drug, C286, that modulates neuron-glial pathways to induce functional recovery in a rodent model of sensory root avulsion. Here, using genome-wide and pathway enrichment analysis of avulsed rats' spinal cords, we show that C286 also influences the extracellular milieu (ECM). Protein expression studies showed that C286 upregulates tenascin-C, integrin-α9, and osteopontin in the injured cord. Similarly, C286 remodulates these ECM molecules, hampers inflammation and prevents tissue loss in a rodent model of spinal cord contusion C286. We further demonstrate C286's efficacy in human iPSC-derived neurons, with treatment resulting in a significant increase in neurite outgrowth. Additionally, we identify a putative efficacy biomarker, S100B, which plasma levels correlated with axonal regeneration in nerve-injured rats. We also found that other clinically available retinoids, that are not RARβ specific agonists, did not lead to functional recovery in avulsed rats, demonstrating the requirement for RARβ specific pathways in regeneration. In a Phase 1 trial, the single ascending dose (SAD) cohorts showed increases in expression of RARβ2 in white blood cells correlative to increased doses and at the highest dose administered, the pharmacokinetics were similar to the rat proof of concept (POC) studies. Collectively, our data suggests that C286 signalling in neurite/axonal outgrowth is conserved between species and across nerve injuries. This warrants further clinical testing of C286 to ascertain POC in a broad spectrum of neurodegenerative conditions.

Examining the liver-pancreas crosstalk reveals a role for the molybdenum cofactor in β-cell regeneration.

Regeneration of insulin-producing β-cells is an alternative avenue to manage diabetes, and it is crucial to unravel this process in vivo during physiological responses to the lack of β-cells. Here, we aimed to characterize how hepatocytes can contribute to β-cell regeneration, either directly or indirectly via secreted proteins or metabolites, in a zebrafish model of β-cell loss. Using lineage tracing, we show that hepatocytes do not directly convert into β-cells even under extreme β-cell ablation conditions. A transcriptomic analysis of isolated hepatocytes after β-cell ablation displayed altered lipid- and glucose-related processes. Based on the transcriptomics, we performed a genetic screen that uncovers a potential role of the molybdenum cofactor (Moco) biosynthetic pathway in β-cell regeneration and glucose metabolism in zebrafish. Consistently, molybdenum cofactor synthesis 2 (Mocs2) haploinsufficiency in mice indicated dysregulated glucose metabolism and liver function. Together, our study sheds light on the liver-pancreas crosstalk and suggests that the molybdenum cofactor biosynthesis pathway should be further studied in relation to glucose metabolism and diabetes.

Recent Research Advances on the Hippo‐Yki Pathway of Crustaceans: Current Knowledge and Potential Applications in Crustacean Aquaculture

ABSTRACTThe Hippo‐YAP/Yki pathway is critical for the regulation of physiological responses in various biological processes from invertebrates to mammals. Crustaceans, in particular shrimp and crabs, are important food sources worldwide. In response to the needs of crustacean aquaculture and disease control, the regulatory mechanisms of crustacean life activities, especially immunity, have been increasingly emphasized. Emerging clues suggest that Hippo‐Yki pathway is important for immunity and regeneration in crustaceans. In this review, the structure, activation pattern, response mechanism to pathogen invasion, and crosstalk with other signaling cascades of the Hippo‐Yki pathway in aquaculture crustaceans are summarized and its similarities and differences with those in mammals and Drosophila are investigated. Based on this, the roles of the Hippo‐Yki pathway in crustacean immune response and limb regeneration are further discussed, and the application potential of strategies pharmacologically or biologically targeting this pathway for crustacean disease control and breeding is theoretically explored.

Metabolic Engineering of High L-Lysine-Producing Escherichia coli for de Novo Production of L-Lysine-Derived Compounds.

5-Aminovalerate (5-AVA), 5-hydroxyvalerate (5-HV), and 1,5-pentanediol (1,5-PDO) are l-lysine derivatives with extensive applications in the production of materials such as polyesters, polyurethane, plasticizers, inks, and coatings. However, their large-scale production is limited by the lack of efficient synthetic pathways. Here, we aimed to construct multiple synthetic pathways by screening the key enzymes involved in the synthesis of these compounds in Escherichia coli. The engineered pathway utilizing RaiP demonstrated a superior catalytic efficiency. The LER strain that overexpressed only raiP successfully synthesized 9.70 g/L 5-HV and 8.31 g/L 5-AVA, whereas the strain LERGY that overexpressed raiP, gabT, and yahK accumulated 9.72 g/L 5-HV and 7.95 g/L 5-AVA from 20 g/L glucose. The introduction of exogenous transaminases and dehydrogenases enhanced cell growth and fermentation efficiency with respect to 5-HV synthesis, albeit without significantly impacting the yield. Strain LE05, incorporating only two exogenous enzymes, RaiP and CaR, produced 1.87 g/L 1,5-PDO, 3.85 g/L 5-HV, and 4.78 g/L 5-hydroxyglutaraldehyde from 20 g/L glucose after 6 days. The strain LE02G, fortified with transaminase, dehydrogenase, and NADPH regeneration system, accumulated 7.82 g/L 1,5-PDO, whereas the aldp-knock out LE02G2 synthesized 10.98 g/L 1,5-PDO from 50 g/L glucose in fed-batch fermentation after 6 days, yielding 0.22 g/g glucose (0.37 mol/mol). Introducing the NADPH regeneration pathway and deleting the NADPH-consuming pathways increased the 1,5-PDO yield and decreased the precursor concentration. The proposed pathways and engineering strategies presented in this study can prove instrumental in developing biological routes for the practical production of 5-AVA, 5-HV, and 1,5-PDO.

The integrated analysis of gut microbiota and metabolome revealed steroid hormone biosynthesis is a critical pathway in liver regeneration after 2/3 partial hepatectomy.

Introduction: The liver is the only organ capable of full regeneration in mammals. However, the exact mechanism of gut microbiota and metabolites derived from them relating to liver regeneration has not been fully elucidated. Methods: To demonstrate how the gut-liver axis contributes to liver regeneration, using an LC-QTOF/MS-based metabolomics technique, we examine the gut microbiota-derived metabolites in the gut content of C57BL/6J mice at various points after 2/3 partial hepatectomy (PHx). Compound identification, multivariate/univariate data analysis and pathway analysis were performed subsequently. The diversity of the bacterial communities in the gastrointestinal content was measured using 16S rRNA gene sequencing. Then, the integration analysis of gut microbiota and metabolome was performed. Results: After 2/3 PHx, the residual liver proliferated quickly in the first 3days and had about 90% of its initial weight by the seventh day. The results of PLS-DA showed that a significant metabolic shift occurred at 6h and 36h after 2/3 PHx that was reversed at the late phase of liver regeneration. The α and β-diversity of the gut microbiota significantly changed at the early stage of liver regeneration. Specifically, Escherichia Shigella, Lactobacillus, Akkermansia, and Muribaculaceae were the bacteria that changed the most considerably during liver regeneration. Further pathway analysis found the most influenced co-metabolized pathways between the host and gut bacteria including glycolysis, the TCA cycle, arginine metabolism, glutathione metabolism, tryptophan metabolism, and purine and pyrimidine metabolism. Specifically, steroid hormone biosynthesis is the most significant pathway of the host during liver regeneration. Discussion: These findings revealed that during liver regeneration, there was a broad modification of gut microbiota and systemic metabolism and they were strongly correlated. Targeting specific gut bacterial strains, especially increasing the abundance of Akkermansia and decreasing the abundance of Enterobacteriaceae, may be a promising beneficial strategy to modulate systemic metabolism such as amino acid and nucleotide metabolism and promote liver regeneration.

Sustainable Electrochemical Recycling of Spent Lithium-Ion Batteries: Selective Extraction of Lithium and Direct Regeneration of De-Lithiated Material

The recycling of spent lithium-ion batteries has become an urgent imperative. In recent years, the rising demand for lithium has sparked interest in the selective extraction of lithium from spent LIBs cathode materials. This process is of interest as it can streamline processes, improve lithium recovery efficiency, and reduce processing costs. Electrochemical methods for selectively extracting lithium from spent cathode materials have gained significant attention among various selective extraction methods due to their advantages, such as low energy consumption and environmental friendliness. Despite substantial progress in improving the efficiency of lithium recovery through electrochemical methods, the economic returns from lithium salt products, to some extent, are still insufficient to offset the processing costs of the entire process, thereby limiting the further development of this technology. Therefore, it is necessary to develop reasonable strategies for the utilization of such de-lithiated materials to further enhance product yields. One promising strategy among these approaches is direct regeneration of fresh cathode materials from the de-lithiated material. However, due to a lack of clear understanding of the structural evolution of transition metal oxides during the lithium extraction process, and the lithiation mechanisms of lithium-depleted materials, there is currently no research report on the direct regeneration of such de-lithiated materials into battery materials.Herein, an electrochemical method using LiCl aqueous as electrolyte is developed to realize the selective extraction of lithium from spent polycrystal LiNi0.55Co0.15Mn0.3O2 (NCM) cathode materials, with a maximum de-lithiation rate approaching 90%. Thorough characterizations were conducted to monitor the morphological, structural, and compositional evolution of NCM during the electrochemical de-lithiation process. These findings contribute to a profound understanding of the characteristics of the de-lithiated material and inform the rational design of regeneration pathways tailored to such materials. The results reveal that the deep de-lithiation of NCM in lithium-aqueous electrolyte triggers water-molecule intercalation, leading to an unusual phase transformation beyond H1→H2→H3. This phase transformation causes substantial lattice expansion along c-axis and introduces severe lattice distortion in de-lithiated material. The over-expanded lattice and the presence of bulk defects resulted in an unstable structure, posing huge challenge for the subsequent direct regeneration of de-lithiated material using conventional calcination methods. To address this, we employ a hydrothermal re-lithiation process, characterized by a milder, lithium-rich and water-based environment. This process is able to create a “lithium-water-balance” structure for de-lithiated materials by promoting the lithium diffusion into the lithium-deficiency structure and facilitating the exchange between lithium ions and water molecules. This process effectively enhances structural stability of the de-lithiated material. As a result, subsequent calcination successfully converts the degraded structure back into the original lithium-conductive layer structure by further eliminating the remaining lattice defects in material and promoting the cation rearrangement. The regenerated material exhibits decent electrochemical performances, which delivers a capacity of 153.2 mAh g−1 at 1C and 132.5 mAh g− 1 at 5C. This work provides insights into the electrochemical de-lithiation method and fills a gap in the utilization of de-lithiated NCM, paving the way for the sustainable recycling of spent LIBs.

Age-related epithelial defects limit thymic function and regeneration

The thymus is essential for establishing adaptive immunity yet undergoes age-related involution that leads to compromised immune responsiveness. The thymus is also extremely sensitive to acute insult and although capable of regeneration, this capacity declines with age for unknown reasons. We applied single-cell and spatial transcriptomics, lineage-tracing and advanced imaging to define age-related changes in nonhematopoietic stromal cells and discovered the emergence of two atypical thymic epithelial cell (TEC) states. These age-associated TECs (aaTECs) formed high-density peri-medullary epithelial clusters that were devoid of thymocytes; an accretion of nonproductive thymic tissue that worsened with age, exhibited features of epithelial-to-mesenchymal transition and was associated with downregulation of FOXN1. Interaction analysis revealed that the emergence of aaTECs drew tonic signals from other functional TEC populations at baseline acting as a sink for TEC growth factors. Following acute injury, aaTECs expanded substantially, further perturbing trophic regeneration pathways and correlating with defective repair of the involuted thymus. These findings therefore define a unique feature of thymic involution linked to immune aging and could have implications for developing immune-boosting therapies in older individuals.

Vision: A specialized pathway for pigment regeneration in cones

Vision relies on two types of photoreceptor cells, rods and cones. Rods outnumber cones in the retinas of humans and most other vertebrate species, yet the contribution of cones to our vision is far more impactful than rods. A new study reveals an elegant enzymatic mechanism that favors light perception by cones under daylight conditions when rods are saturated by light and contribute little to useful vision.

Macro-Calcium Carbonate-Hydrogel Hybrid Spheroids: Design and Biomedical Applications.

In advancing tissue engineering, we introduce a particle system combining the strength of calcium carbonate with the flexibility of hydrogels enhanced with alkaline phosphatase (ALP) for improved bone regeneration. Our innovation lies in creating large hybrid macrospheroids by bonding mineral nanostructured microparticles loaded with ALP through hydrogel polymerization. These composite macrospheroids address critical challenges in cell seeding, growth, and handling within three-dimensional (3D) environments. We conducted extensive characterization of these particles using scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), mechanical property assessment, and fluorescence microscopy. The results demonstrate that the hybrid macrospheroids significantly enhance cell manipulation and growth in three-dimensional structures. Specifically, ALP-loaded macrospheroids showed a marked improvement in osteogenic activity, promoting effective bone tissue regeneration. This study not only showcases a unique approach to overcoming the limitations of traditional hydrogels in tissue engineering but also opens pathways for bone tissue regeneration. Our findings offer a promising tool for cell seeding and growth in 3D structures, potentially revolutionizing practices in tissue engineering and regenerative medicine.