Mesenchymal condensation in tooth development and regeneration: a focus on translational aspects of organogenesis.

The teeth are vertebrate-specific, highly specialized organs performing fundamental functions of mastication and speech, the maintenance of which is crucial for orofacial homeostasis and is further linked to systemic health and human psychosocial well-being. However, with limited ability for self-repair, the teeth can often be impaired by traumatic, inflammatory, and progressive insults, leading to high prevalence of tooth loss and defects worldwide. Regenerative medicine holds the promise to achieve physiological restoration of lost or damaged organs, and in particular an evolving framework of developmental engineering has pioneered functional tooth regeneration by harnessing the odontogenic program. As a key event of tooth morphogenesis, mesenchymal condensation dictates dental tissue formation and patterning through cellular self-organization and signaling interaction with the epithelium, which provides a representative to decipher organogenetic mechanisms and can be leveraged for regenerative purposes. In this review, we summarize how mesenchymal condensation spatiotemporally assembles from dental stem cells (DSCs) and sequentially mediates tooth development. We highlight condensation-mimetic engineering efforts and mechanisms based on ex vivo aggregation of DSCs, which have achieved functionally robust and physiologically relevant tooth regeneration after implantation in animals and in humans. The discussion of this aspect will add to the knowledge of development-inspired tissue engineering strategies and will offer benefits to propel clinical organ regeneration.

AMPK, a hub for the microenvironmental regulation of bone homeostasis and diseases.

AMP-activated protein kinase (AMPK), a crucial regulatory kinase, monitors energy levels, conserving ATP and boosting synthesis in low-nutrition, low-energy states. Its sensitivity links microenvironmental changes to cellular responses. As the primary support structure and endocrine organ, the maintenance, and repair of bones are closely associated with the microenvironment. While a series of studies have explored the effects of specific microenvironments on bone, there is lack of angles to comprehensively evaluate the interactions between microenvironment and bone cells, especially for bone marrow mesenchymal stem cells (BMMSCs) which mediate the differentiation of osteogenic lineage. It is noteworthy that accumulating evidence has indicated that AMPK may serve as a hub between BMMSCs and microenvironment factors, thus providing a new perspective for us to understand the biology and pathophysiology of stem cells and bone. In this review, we emphasize AMPK's pivotal role in bone microenvironment modulation via ATP, inflammation, reactive oxygen species (ROS), calcium, and glucose, particularly in BMMSCs. We further explore the use of AMPK-activating drugs in the context of osteoarthritis and osteoporosis. Moreover, building upon the foundation of AMPK, we elucidate a viewpoint that facilitates a comprehensive understanding of the dynamic relationship between the microenvironment and bone homeostasis, offering valuable insights for prospective investigations into stem cell biology and the treatment of bone diseases.

Molecular Design of Solid Polymer Electrolytes with Enthalpy-Entropy Manipulation for Li Metal Batteries with Aggressive Cathode Chemistry.

Solid polymer electrolytes (SPEs) with high ion conductivity, high Li+ transference number, and a wide electrochemical window are promising for the next-generation high-energy Li metal batteries (LMBs). Here we describe an enthalpy-entropy manipulation strategy enabling a class of polycarbonate-based copolymeric electrolytes (PCCEs) with regulated cation/anion solvation via a molecular design of the polymer backbone. By integrating a weakly solvating linear carbonate with another strongly solvating cyclic carbonate segment in the polymer backbone, the cation-dipole coordination for Li+ ions (with two types of carbonyl groups) is weakened (low enthalpy penalty) and nondirectional (high entropy penalty), which enables a weak solvation and rapid diffusion of Li+. We further introduce a bis-acrylamide-based cross-linking segment which, other than imparting high mechanical strength, exhibits dihydrogen bonding with the difluoro(oxalate) borate anions, which is strong (high enthalpy penalty) and directional (low entropy penalty), thus restricting the migration of anions. As a result, the PCCE delivers a high ionic conductivity of 0.66 mS cm-1 with a high Li+ transference number (0.76) at 25 °C, as well as high oxidation stability. By an in situ polymerization approach, the PCCE enables LMBs using high-nikel LiNi0.8Co0.1Mn0.1O2 cathodes with a high capacity retention of 82.2% over 800 cycles with a cutoff voltage of 4.5 V and further LMBs using aggressive LiNi0.5Mn1.5O4 cathodes with a 96.4% capacity retention over 300 cycles with a cutoff voltage of 5.0 V. The described enthalpy-entropy manipulation approach offers a unique perspective for the molecular design of high-performance SPEs for high-energy Li metal batteries.

Neutrophils suppress osteogenic differentiation of Gli1+ stem cells via neutrophil extracellular traps and contribute to bone loss in periodontitis.

Periodontitis is a severe and chronic oral inflammatory disease that leads to the progressive and irreversible destruction of periodontal tissues, ultimately resulting in tooth loss. Among the immune cell subtypes involved, neutrophils play a crucial role in the initiation and progression of periodontitis. Mesenchymal stem cells (MSCs) are essential components of periodontal tissue, contributing to tissue development, homeostasis, and regeneration. Recent studies have demonstrated that neutrophils significantly affect the function of MSCs by changing the inflammatory environment. However, the specific effects of neutrophils on periodontal MSCs during periodontitis remain unclear, highlighting a gap in our understanding of the disease mechanisms. In this study, we utilized the Gli1-CreERT2;mT/mG transgenic mouse model to specifically mark Gli1+ cells, a critical and representative subset of MSCs in the periodontal tissues responsible for maintaining tissue homeostasis. We reveal that neutrophils inhibit the osteogenic differentiation of Gli1+ cells and exacerbate alveolar bone destruction by secreting neutrophil extracellular traps (NETs), which induce endoplasmic reticulum stress in Gli1+ cells. These findings highlight the pivotal impact of neutrophils on distinct subpopulations of periodontal MSCs in the pathogenesis of periodontitis, offering valuable insights into the underlying mechanisms of the disease and suggesting potential future therapeutic strategies aimed at modulating the interactions between neutrophils and MSCs.

Integrating network pharmacology and experimental validation reveals therapeutic effects of D-mannose on NAFLD through mTOR suppression.

Non-alcoholic fatty liver disease (NAFLD), a chronic liver condition and metabolic disorder, has emerged as a significant health issue worldwide. D-mannose, a natural monosaccharide widely existing in plants and animals, has demonstrated metabolic regulatory properties. However, the effect and mechanism by which D-mannose may counteract NAFLD have not been studied. In this study, network pharmacology followed by molecular docking analysis was utilized to identify potential targets of mannose against NAFLD, and the leptin receptor-deficient, genetically obese db/db mice was employed as an animal model of NAFLD to validate the regulation of D-mannose on core targets. As a result, 67 targets of mannose are predicted associated with NAFLD, which are surprisingly centered on the mechanistic target of rapamycin (mTOR). Further analyses suggest that mTOR signaling is functionally enriched in potential targets of mannose treating NAFLD, and that mannose putatively binds to mTOR as a core mechanism. Expectedly, repeated oral gavage of supraphysiological D-mannose ameliorates liver steatosis of db/db mice, which is based on suppression of hepatic mTOR signaling. Moreover, daily D-mannose administration reduced hepatic expression of lipogenic regulatory genes in counteracting NAFLD. Together, these findings reveal D-mannose as an effective and potential NAFLD therapeutic through mTOR suppression, which holds translational promise.

Odontogenesis-Empowered Extracellular Vesicles Safeguard Donor-Recipient Stem Cell Interplay to Support Tooth Regeneration.

Harnessing the developmental events of mesenchymal condensation to direct postnatal dental stem cell aggregation represents a cutting-edge and promising approach to tooth regeneration. Tooth avulsion is among the most prevalent and serious dental injuries, and odontogenic aggregates assembled by stem cells from human exfoliated deciduous teeth (SHED) have proven effective in revitalizing avulsed teeth after replantation in the clinical trial. However, whether and how SHED aggregates (SA) communicate with recipient components and promote synergistic tissue regeneration to support replanted teeth remains elusive. Here, it is shown that SA-mediated avulsed tooth regeneration involves periodontal restoration and recovery of recipient Gli1+ stem cells, which are mobilized and necessarily contribute to the reestablishment of the tooth-periodontal ligament-bone interface. Mechanistically, the release of extracellular vesicles (EVs) is revealed indispensable for the implanted SA to mobilize recipient Gli1+ cells and regenerate avulsed teeth. Furthermore, SHED aggregates-released EVs (SA-EVs) are featured with odontogenic properties linked to tissue regeneration, which enhance migration, proliferation, and differentiation of Gli1+ cells. Importantly, local application of SA-EVs per se empowers recipient Gli1+ cells and safeguards regeneration of avulsed teeth. Collectively, the findings establish a paradigm in which odontogenesis-featured EVs govern donor-recipient stem cell interplay to achieve tooth regeneration, inspiring cell-free translational regenerative strategies.

Hepatocyte-derived tissue extracellular vesicles safeguard liver regeneration and support regenerative therapy.

Tissue-derived extracellular vesicles (EVs) are emerging as pivotal players to maintain organ homeostasis, which show promise as a next-generation candidate for medical use with extensive source. However, the detailed function and therapeutic potential of tissue EVs remain insufficiently studied. Here, through bulk and single-cell RNA sequencing analyses combined with ultrastructural tissue examinations, we first reveal that in situ liver tissue EVs (LT-EVs) contribute to the intricate liver regenerative process after partial hepatectomy (PHx), and that hepatocytes are the primary source of tissue EVs in the regenerating liver. Nanoscale and proteomic profiling further identify that the hepatocyte-specific tissue EVs (Hep-EVs) are strengthened to release with carrying proliferative messages after PHx. Moreover, targeted inhibition of Hep-EV release via AAV-shRab27a in vivo confirms that Hep-EVs are required to orchestrate liver regeneration. Mechanistically, Hep-EVs from the regenerating liver reciprocally stimulate hepatocyte proliferation by promoting cell cycle progression through Cyclin-dependent kinase 1 (Cdk1) activity. Notably, supplementing with Hep-EVs from the regenerating liver demonstrates translational potential and ameliorates insufficient liver regeneration. This study provides a functional and mechanistic framework showing that the release of regenerative Hep-EVs governs rapid liver regeneration, thereby enriching our understanding of physiological and endogenous tissue EVs in organ regeneration and therapy.

Mesenchymal stromal cell-mediated immune regulation: A promising remedy in the therapy of type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a major threat to global public health, with increasing prevalence as well as high morbidity and mortality, to which immune dysfunction has been recognized as a crucial contributor. Mesenchymal stromal cells (MSCs), obtained from various sources and possessing potent immunomodulatory abilities, have displayed great therapeutic potential for T2DM. Interestingly, the immunomodulatory capabilities of MSCs are endowed and plastic. Among the multiple mechanisms involved in MSC-mediated immune regulation, the paracrine effects of MSCs have attracted much attention. Of note, extracellular vesicles (EVs), an important component of MSC secretome, have emerged as pivotal mediators of their immunoregulatory effects. Particularly, the necrobiology of MSCs, especially apoptosis, has recently been revealed to affect their immunomodulatory functions in vivo. In specific, a variety of preclinical studies have demonstrated the beneficial effects of MSCs on improving islet function and ameliorating insulin resistance. More importantly, clinical trials have further uncovered the therapeutic potential of MSCs for T2DM. In this review, we outline current knowledge regarding the plasticity and underlying mechanisms of MSC-mediated immune modulation, focusing on the paracrine effects. We also summarize the applications of MSC-based therapies for T2DM in both preclinical studies and clinical trials, with particular emphasis on the modulation of immune system.

Tc-99m-MIBI SPECT/CT imaging to diagnose secondary hyperparathyroidism after parathyroid forearm transplantation.

This article report a 40-year-old male patient who underwent total thyroidectomy and forearm auto-transplantation in another hospital for secondary hyperparathyroidism. After 4 years of follow-up, the level of parathyroid hormone continued to increase, and ultrasound showed nodules in the neck and right forearm, which were considered to be of parathyroid origin. Technetium 99m sestamibi single photon emission computed tomography and computed tomography (Tc-99m-MIBI SPECT/CT) imaging showed increased radioactive uptake in the submuscular soft tissue nodule of the right medial forearm, maximum standardized uptake value (SUVmax) is 0.98, which was identified as transplanted functioning parathyroid tissue. No parathyroid imaging activity was found in the neck. The patient then underwent partial removal of ectopic parathyroid tissue from the right forearm. Pathological examination confirmed parathyroid tissue, and removal was followed by a rapid decline in serum parathyroid hormone levels.

Enhancing preoperative diagnosis of pancreatic ductal adenocarcinoma and mass-forming chronic pancreatitis: a study on normalized conventional MR imaging parameters.

PURPOSE: To assess the utility of signal intensity ratio (SIR) in distinguishing between mass-forming chronic pancreatitis (MFCP) and pancreatic ductal adenocarcinoma (PDAC), thereby reducing unnecessary pancreatectomies or delayed diagnosis brought by misdiagnosis. MATERIALS AND METHODS: This retrospective study included 170 participants (34 with MFCP and 136 with PDAC) who underwent radical pancreatic surgery and were diagnosed via specimen pathology. The study group was carefully selected with a 1:4 ratio matching for sex, age, and operation time between two entities. T1 SIR, T2 SIR, arterial phase (AP) SIR, portal venous phase (VP) SIR, delay phase (DP) SIR, DWI0-50 SIR, and DWI500-1000 SIR, were calculated by dividing the signal intensity of lesions by that of the paraspinal muscle, serving as a reference organ. Intraclass Correlation Coefficient (ICC) was estimated to evaluate the intraobserver and interobserver reliability. Wilcoxon tests were employed for univariate analysis, and receiver operating characteristic (ROC) curves were generated to determine optimal cutoff points and AUC values for selected predictors. A tenfold cross-validation method was applied to validate the robustness of the results. RESULTS: The ICC demonstrated excellent correlation for both intraobserver and interobserver(ICCs > 0.8). T1 SIR, AP SIR, VP SIR, and DP SIR were significantly lower in the PDAC group compared to the MFCP group, and exhibited good independent predictive properties with the sensitivities of 61.8, 61.8, 70.6, and 73.5%, specificities of 66.2, 68.4, 59.6, and 55.9%, and AUCs of 0.620, 0.659, 0.670, and 0.668, respectively, hovering around 0.7. The tenfold cross-validation confirmed the reliability and robustness of our findings, with consistent AUC, sensitivity, specificity, and 95% confidence intervals over 1000 iterations. CONCLUSION: T1 SIR, AP SIR, VP SIR, and DP SIR show promise as potential imaging biomarkers for distinguishing between MFCP and PDAC.

Learning an Interpretable Stylized Subspace for 3D-aware Animatable Artforms.

Throughout history, static paintings have captivated viewers within display frames, yet the possibility of making these masterpieces vividly interactive remains intriguing. This research paper introduces 3DArtmator, a novel approach that aims to represent artforms in a highly interpretable stylized space, enabling 3D-aware animatable reconstruction and editing. Our rationale is to transfer the interpretability and 3D controllability of the latent space in a 3D-aware GAN to a stylized sub-space of a customized GAN, revitalizing the original artforms. To this end, the proposed two-stage optimization framework of 3DArtmator begins with discovering an anchor in the original latent space that accurately mimics the pose and content of a given art painting. This anchor serves as a reliable indicator of the original latent space local structure, therefore sharing the same editable predefined expression vectors. In the second stage, we train a customized 3D-aware GAN specific to the input artform, while enforcing the preservation of the original latent local structure through a meticulous style-directional difference loss. This approach ensures the creation of a stylized sub-space that remains interpretable and retains 3D control. The effectiveness and versatility of 3DArtmator are validated through extensive experiments across a diverse range of art styles. With the ability to generate 3D reconstruction and editing for artforms while maintaining interpretability, 3DArtmator opens up new possibilities for artistic exploration and engagement.

A Senescence-Associated Secretory Phenotype of Bone Marrow Mesenchymal Stem Cells Inhibits the Viability of Breast Cancer Cells.

Breast cancer, the most prevalent malignancy in women, often progresses to bone metastases, especially in older individuals. Dormancy, a critical aspect of bone-metastasized breast cancer cells (BCCs), enables them to evade treatment and recur. This dormant state is regulated by bone marrow mesenchymal stem cells (BMMSCs) through the secretion of various factors, including those associated with senescence. However, the specific mechanisms by which BMMSCs induce dormancy in BCCs remain unclear. To address this gap, a bone-specific senescence-accelerated murine model, SAMP6, was utilized to minimize confounding systemic age-related factors. Confirming senescence-accelerated osteoporosis, distinct BMMSC phenotypes were observed in SAMP6 mice compared to SAMR1 counterparts. Notably, SAMP6-BMMSCs exhibited premature senescence primarily due to telomerase activity loss and activation of the p21 signaling pathway. Furthermore, the effects of conditioned medium (CM) derived from SAMP6-BMMSCs versus SAMR1-BMMSCs on BCC proliferation were examined. Intriguingly, only CM from SAMP6-BMMSCs inhibited BCC proliferation by upregulating p21 expression in both MCF-7 and MDA-MB-231 cells. These findings suggest that the senescence-associated secretory phenotype (SASP) of BMMSCs suppresses BCC viability by inducing p21, a pivotal cell cycle inhibitor and tumor suppressor. This highlights a heightened susceptibility of BCCs to dormancy in a senescent microenvironment, potentially contributing to the increased incidence of breast cancer bone metastasis and recurrence observed with aging.

Liver-based inter-organ communication: A disease perspective.

Inter-organ communication through hormones, cytokines and extracellular vesicles (EVs) has emerged to contribute to the physiological states and pathological processes of the human body. Notably, the liver coordinates multiple tissues and organs to maintain homeostasis and maximize energy utilization, with the underlying mechanisms being unraveled in recent studies. Particularly, liver-derived EVs have been found to play a key role in regulating health and disease. As an endocrine organ, the liver has also been found to perform functions via the secretion of hepatokines. Investigating the multi-organ communication centered on the liver, especially in the manner of EVs and hepatokines, is of great importance to the diagnosis and treatment of liver-related diseases. This review summarizes the crosstalk between the liver and distant organs, including the brain, the bone, the adipose tissue and the intestine in noticeable situations. The discussion of these contents will add to a new dimension of organismal homeostasis and shed light on novel theranostics of pathologies.

Ptip safeguards the epigenetic control of skeletal stem cell quiescence and potency in skeletogenesis.

Stem cells remain in a quiescent state for long-term maintenance and preservation of potency; this process requires fine-tuning regulatory mechanisms. In this study, we identified the epigenetic landscape along the developmental trajectory of skeletal stem cells (SSCs) in skeletogenesis governed by a key regulator, Ptip (also known as Paxip1, Pax interaction with transcription-activation domain protein-1). Our results showed that Ptip is required for maintaining the quiescence and potency of SSCs, and loss of Ptip in type II collagen (Col2)+ progenitors causes abnormal activation and differentiation of SSCs, impaired growth plate morphogenesis, and long bone dysplasia. We also found that Ptip suppressed the glycolysis of SSCs through downregulation of phosphoglycerate kinase 1 (Pgk1) by repressing histone H3 lysine 27 acetylation (H3K27ac) at the promoter region. Notably, inhibition of glycolysis improved the function of SSCs despite Ptip deficiency. To the best of our knowledge, this is the first study to establish an epigenetic framework based on Ptip, which safeguards skeletal stem cell quiescence and potency through metabolic control. This framework is expected to improve SSC-based treatments of bone developmental disorders.

Symmetrical Design of Biphenazine Derivative Anode for Proton Ion Batteries with High Voltage and Long-Term Cycle Stability.

Organic anodes have emerged as a promising energy storage medium in proton ion batteries (PrIBs) due to their ability to reversibly accommodate non-metallic proton ions. Nevertheless, the currently available organic electrodes often encounter dissolution issues, leading to a decrease in long-cycle stability. In addition, the inherent potential of the organic anode is generally relatively high, resulting in low cell voltage of assembled PrIBs (<1.0 V). To address these challenges, a novel long-period stable, low redox potential biphenylzine derivative, [2,2'-biphenazine]-7,7'-tetraol (BPZT) is explored, from the perspective of molecular symmetry and solubility, in conjunction with the effect of the molecular frontier orbital energy levels on its redox potential. Specifically, BPZT exhibited a low potential of 0.29 V (vs SHE) and is virtually insoluble in 2 m H2SO4 electrolyte during cycling. When paired with MnO2@GF or PbO2 cathodes, the resulting PrIBs achieve cell voltages of 1.07 V or 1.44 V, respectively, and maintain a high capacity retention of 90% over 20000 cycles. Additionally, these full batteries can operate stably at a high mass loading of 10 mgBPZT cm-2, highlighting their potential toward long-term energy storage applications.

Microenvironment-responsive nano-bioconjugated vesicles for the multi-pronged treatment of liver fibrosis.

Liver fibrosis represents an inevitable stage of various chronic liver diseases. The activated hepatic stellate cells (aHSCs) are the main drivers for promoting the development of liver fibrosis. Meanwhile, liver macrophages can secrete pro-inflammatory cytokines, thus accelerating the deterioration of the liver. Regulating both aHSCs and the inflammatory microenvironment in the liver simultaneously may be an effective strategy for treating liver fibrosis. A multi-pronged nano-bioconjugated system, HNP-B-aEV, was developed according to the above strategy. Based on cell aggregate-derived extracellular vesicles (aEVs) and hydroxychloroquine (HCQ)-loaded nanoparticles (HNP) modified with retinol, HNP-B-aEV is prepared via a reactive oxygen species (ROS)-responsive boronate linker. In the ROS-rich microenvironment of liver fibrosis, aEVs and HNP are released, eliminating ROS, and targeting aHSCs and macrophages respectively to inhibit the activation of HSCs. Both in vitro and in vivo studies demonstrated that HNP-B-aEV can significantly inhibit the release of inflammatory factors from M1 macrophages, remodeling the microenvironment and preventing the activation of HSCs, offering a multi-pronged treatment for liver fibrosis. This strategy can inhibit the progression of liver fibrosis at its source, providing a new perspective for the clinical treatment of liver fibrosis.

Understanding the role of mitochondria in the pathogenesis of chronic pain.

Chronic pain is a major public health problem. Mitochondria play important roles in a myriad of cellular processes and mitochondrial dysfunction has been implicated in multiple neurological disorders. This review aims to provide an insight into advances in understanding of the role of mitochondrial dysfunction in the pathogenesis of chronic pain. The results show that the five major mitochondrial functions (the mitochondrial energy generating system, reactive oxygen species generation, mitochondrial permeability transition pore, apoptotic pathways and intracellular calcium mobilisation) may play critical roles in neuropathic and inflammatory pain. Therefore, protecting mitochondrial function would be a promising strategy to alleviate or prevent chronic pain states. Related chronic inflammatory and neuropathic pain models, as well as the spectral characteristics of current fluorescent probes to detect mitochondria in pain studies, are also discussed.

Polyvinylpyrrolidone-Intercalated Mn0.07 VOx toward High Rate and Long-Life Aqueous Zinc-Ion Batteries.

Aqueous zinc-ion batteries (AZIBs) are expected to be an attractive alternative in advanced energy storage devices due to large abundance and dependable security. Nevertheless, the undesirable energy density and operating voltage still hinder the development of AZIBs, which is intimately associated with the fundamental properties of the cathode. In this work, polyvinylpyrrolidone (PVP) intercalated Mn0.07 VOx (PVP-MnVO) with a large interlayer spacing of 13.5 Å (against 12.5 Å for MnVO) synthesized by a facile hydrothermal method is adopted for the cathode in AZIBs. The experimental results demonstrate that PVP-MnVO with expanded interlayer spacing provides beneficial channels for the rapid diffusion of Zn2+ , resulting in a high discharge capacity of 402 mAh g-1 at 0.1 A g-1 , superior to that of MnVO (275 mAh g-1 at 0.1 A g-1 ). Meanwhile, the PVP molecule remains in the layer structure as a binder/pillar, which can maintain its structural integrity well during the charging/discharging process. Consequently, PVP-MnVO cathode exhibits superior rate capability and cycling stability (89% retention after 4300 cycles at 10 A g-1 ) compared to that of MnVO (≈51% retention over 500 cycles at 2 A g-1 ). This work proposes a new approach to optimize the performance of vanadium-based electrode materials in AZIBs.

Geometric Wheat Modeling and Quantitative Plant Architecture Analysis Using Three-Dimensional Phytomers.

The characterization, analysis, and evaluation of morphology and structure are crucial in wheat research. Quantitative and fine characterization of wheat morphology and structure from a three-dimensional (3D) perspective has great theoretical significance and application value in plant architecture identification, high light efficiency breeding, and cultivation. This study proposes a geometric modeling method of wheat plants based on the 3D phytomer concept. Specifically, 3D plant architecture parameters at the organ, phytomer, single stem, and individual plant scales were extracted based on the geometric models. Furthermore, plant architecture vector (PA) was proposed to comprehensively evaluate wheat plant architecture, including convergence index (C), leaf structure index (L), phytomer structure index (PHY), and stem structure index (S). The proposed method could quickly and efficiently achieve 3D wheat plant modeling by assembling 3D phytomers. In addition, the extracted PA quantifies the plant architecture differences in multi-scales among different cultivars, thus, realizing a shift from the traditional qualitative to quantitative analysis of plant architecture. Overall, this study promotes the application of the 3D phytomer concept to multi-tiller crops, thereby providing a theoretical and technical basis for 3D plant modeling and plant architecture quantification in wheat.

Construction, Characterization, and Regenerative Application of Self-Assembled Human Mesenchymal Stem Cell Aggregates.

Mesenchymal stem cells (MSCs), characterized by their self-renewal ability and multilineage differentiation potential, can be derived from various sources and are emerging as promising candidates for regenerative medicine, especially for regeneration of the tooth, bone, cartilage, and skin. The self-assembled approach of MSC aggregation, which notably constructs cell clusters mimicking the developing mesenchymal condensation, allows high-density stem cell delivery along with preserved cell-cell interactions and extracellular matrix (ECM) as the microenvironment niche. This method has been shown to enable efficient cell engraftment and survival, thus promoting the optimized application of exogenous MSCs in tissue engineering and safeguarding clinical organ regeneration. This paper provides a detailed protocol for the construction and characterization of self-assembled aggregates based on umbilical cord mesenchymal stem cells (UCMSCs), as well as an example of the cranial bone regenerative application. The implementation of this procedure will help guide the establishment of an efficient MSC transplantation strategy for tissue engineering and regenerative medicine.