Photoperiod critically regulates potato tuber development, with short days inducing the expression of the key tuberigen signal, SELF PRUNING 6A (StSP6A). To identify upstream regulators of StSP6A, we performed a transcriptome analysis of potato leaves in response to short days. Among the short day-responsive genes identified, ELONGATED HYPOCOTYL 5 (StHY5) emerged as a strong candidate regulator. We demonstrated that StHY5 expression is rapidly modulated in response to photoperiodic changes and that it directly activates StSP6A transcription by binding to multiple ACGT-containing element motifs within its promoter. Functional validation revealed that overexpression of StHY5 significantly promotes tuber formation and yield, mirroring the effect of elevated StSP6A. These findings establish StHY5 as a critical photoperiodic signal transducer in potato, acting upstream of StSP6A to initiate and enhance tuber formation in response to inductive short days. This molecular pathway presents a potential target for optimizing tuber yield in potato breeding programs.
INTRODUCTION AND AIMS:Female dentists make up a large proportion in China and often face heavy workloads and occupational pressure. This study aims to conduct a comprehensive analysis of the current situation, challenges and mental health conditions of female dentists in China. METHODS:A cross-sectional survey among female dentists in China was conducted using a structured questionnaire. The survey collected information on demographic characteristics, workload, income satisfaction, psychological status, occupational stress, and occupational attitudes. Logistic regression was used to analyse factors associated with income satisfaction, anxiety symptoms, depressive emotions, and professional commitment. RESULTS:A total of 3,504 valid responses from female dentists across China were collected. 27.22% participants reported income dissatisfaction, with 55.5% perceiving income not proportional to their effort and 45.32% believing they earned less than male colleagues of the same level. Age, practice status, clinical specialty, annual income and workload all affect income satisfaction. Family responsibilities substantially impacted careers, with 44.06% having given up opportunities for advancement due to family reasons. Mental health burdens were substantial, with 97.6% reporting occasional or frequent anxiety and 86.24% experiencing depressive moods. Work-family imbalance is the strongest positive predictor of anxiety and depression. A total of 78.48% participants expressed love for their profession, though only 40.83% would actively recommend it to others. Dissatisfaction with income, work intensity and promotion speed and work-family imbalance significantly reduces professional commitment. CONCLUSIONS:Female dentists in China constitute a highly qualified group yet facing multifaceted professional obstacles. Income satisfaction, psychological well-being, and occupational enthusiasm among female dentists are influenced by multiple factors. Systemic interventions are urgently needed to address pay equity, provide support for work-family balance and mental health to ensure a sustainable and healthy future for the dental workforce. CLINICAL RELEVANCE:This survey provides important insights into the current career landscape of female dentists in China and may inform strategies aimed at improving porfessional development and workforce equity.
Climate change-induced heat stress poses a significant threat to plant reproductive success and crop yields by disrupting both the floral transition and floral organ development. This review explores the complex thermosensory mechanisms that plants use to perceive and respond to elevated ambient temperatures, highlighting how environmental cues are integrated with developmental signaling pathways. Central to these responses is the thermosensory regulation of flowering time through conserved genetic networks that control key floral integrators such as FLOWERING LOCUS T (FT). Various temperature-sensitive regulators fine-tune flowering time through coordinated changes in gene expression, protein stability, and intracellular and intercellular trafficking. Beyond the floral transition, thermoresponsive pathways also influence meristem activity and floral organogenesis, with significant consequences for reproductive development and yield stability. A deeper understanding of these interconnected mechanisms will provide critical insights for developing climate-resilient crops that can sustain reproductive success under rising temperatures, thereby contributing to global food security.
Seasonal temperature fluctuations serve as crucial environmental cues that regulate plant reproductive timing, yet the mechanisms underlying thermoresponsive flowering regulation in tomato remain poorly understood. The study uncovers a temperature-sensing mechanism in the tomato shoot apical meristem coordinated through antagonistic interactions between a florigen-like protein FLOWERING LOCUS T-Like 2 (FTL2) and florigen protein SINGLE-FLOWER TRUSS (SFT). Under short day conditions, FTL2 expression is specifically upregulated at the shoot apex by high temperature and functions as a flowering repressor. FTL2 physically interacts with the floral inducer SFT, directly suppressing its transcriptional activity to delay floral transition. This FTL2-SFT regulatory circuit enables tomato precise integration of photoperiodic and thermal signals at the shoot apex, providing a molecular framework for seasonal flowering adaptation. The findings elucidate a fundamental mechanism of temperature perception in tomato flowering control and provide broader insights into how florigen-based networks contribute to adaptive flowering control across plant species.
The potato (Solanum tuberosum L.) is a vital global staple crop, and recent research has focused on elucidating the molecular mechanisms underlying tuber formation. MULTIPLE C2 DOMAIN AND TRANSMEMBRANE REGION PROTEINs (MCTPs) have emerged as essential regulators of macromolecule transport in plants; however, their roles in potato tuberization remain largely uncharacterized. In this study, we conduct a comprehensive genome-wide analysis of the MCTP family in potato, identifying 17 StMCTP members. Expression profiling reveals tissue-specific and hormone-responsive expression patterns, with dynamic regulation observed during the stolon-to-tuber transition. Subcellular localization assays indicate that StMCTP proteins are distributed in distinct or overlapping patterns in Nicotiana benthamiana leaf epidermal cells. StMCTP9, a homolog of Arabidopsis QUIRKY, is highly expressed in leaves and stolons and interacts with StSP6A, a key tuberigen signal. Knocking down StMCTP9 delays tuber initiation, indicating its role in tuber development. Heterologous expression of StSP6A in Arabidopsis promotes flowering, revealing divergent outcomes of the mobile signal pathway in potato and Arabidopsis. Together, our findings reveal a previously unrecognized role of StMCTP9 in mediating tuber formation, providing a foundation for understanding the broader functional landscape of MCTPs in potato development.
Senescent mandibular bone repair poses a formidable challenge without a completely satisfactory strategy. Endogenous cell recruitment and osteogenic differentiation are two sequential stages in bone regeneration, and disruptions in these two processes present significant obstacles to senescent bone repair. To address these issues, engineered extracellular vesicles (EV) with sequential stem cell recruitment and osteogenic functions were developed. This study demonstrated that Apt19s-engineered extracellular vesicles (Apt19s-EV) recognize and recruit bone marrow mesenchymal stem cells derived from old rats (O-BMSCs) specifically and effectively. MiR-376b-5p, identified by RNA sequencing and transfection, was significantly decreased in O-BMSCs, and it was selected to construct miR-376b-5p-engineered extracellular vesicles (376b-EV). 376b-EV could promote osteogenesis and alleviate senescence of O-BMSCs by targeting Camsap1. To combine the advantages of Apt19s and miR-376b-5p, dual engineered extracellular vesicles (Apt-376b-EV) comprising both Apt19s and miR-376b-5p modifications were constructed. To further validate its function, Gelatin methacryloyl (GelMA) hydrogel was used as a carrier to construct the Apt-376b-EV@GelMA delivery system. The in vitro results have demonstrated that Apt-376b-EV@GelMA could recruit O-BMSCs, alleviate senescence and promote osteogenic differentiation sequentially. Notably, the in vivo study also showed that Apt-376b-EV@GelMA could sequentially recruit endogenous stem cells and enhance new bone formation in senescent bone fracture and critical-sized defect models. In summary, the dual engineered extracellular vesicles, Apt-376b-EV, offer an appealing solution for recruiting endogenous stem cells and promoting bone repair sequentially in the senescent microenvironment, which may broaden the clinical applications of engineered EV and provide valuable strategies for treating senescent bone-related diseases in the future clinical work.
Abscisic acid (ABA), a pivotal plant hormone once primarily associated with stress response, is now increasingly acknowledged for its indispensable role in plant development. This comprehensive review delves into the multifaceted functions of ABA in regulating various aspects of plant growth and development. From inhibiting germination to orchestrating seedling establishment, flowering time, and dormancy induction, ABA emerges as a central player in shaping plant developmental transitions. Unraveling the intricate regulatory mechanisms governing the ABA signaling pathway provides valuable insights into how plants adapt to environmental challenges while effectively managing their growth and reproductive strategies. This expanding knowledge not only highlights the significance of ABA in plant biology but also has profound implications for enhancing agricultural practices.
Potatoes are valued as reliable crops due to their high carbohydrate content and relatively low farming demands. Consequently, significant attention has been directed towards understanding and controlling the life cycle of potato tubers in recent years. Notably, recent studies have identified self-pruning 6A (StSP6A) as a key component of the tuberigen, the mobile signal for tuber formation, produced in leaves and then transported underground to induce tuber formation in potatoes. Recent progress in comprehending the signaling mechanisms that regulate StSP6A by photoperiod and ambient temperature components, its long-distance transport into underground tissue, and its involvement in regulating stolon tuberization has advanced significantly. Consequently, the modulation of StSP6A and other possible tuberigen signals, along with their regulatory pathways, significantly impacts potato domestication and crop yield. This progress highlights the differential regulation of tuberigen signals and their potential functions in promoting tuber formation.
Seed dormancy and germination are dynamically regulated by abscisic acid (ABA), with transcription factor ABA INSENSITIVE 5 (ABI5) serving as a key repressor of germination under stress. Here, we identify QUIRKY (QKY), a MULTIPLE C2 DOMAIN AND TRANSMEMBRANE REGION PROTEIN (MCTP) in Arabidopsis, as a critical regulator of ABA signaling through posttranslational control of ABI5. QKY interacts with ABI5 and facilitates its cytoplasmic degradation via the E3 ubiquitin ligase KEEP ON GOING (KEG), promoting the recruitment of ABI5 into phase-separated condensates. Loss of QKY function enhances ABA hypersensitivity, reducing seed germination rates and impairing seedling establishment. These findings highlight QKY as a scaffold that integrates phase separation and targeted ubiquitination to fine-tune ABA responses, balancing dormancy and germination. Our study expands the understanding of posttranslational ABI5 regulation and reveals MCTPs as central players in coordinating growth-stress trade-offs during early plant development.
Multiple C2 domain and transmembrane region proteins (MCTPs) are an evolutionarily conserved family involved in protein trafficking and signal transduction. Although several investigations have demonstrated that MCTPs play crucial roles in plant growth and development, their specific biological functions within tomatoes (Solanum lycopersicum L.) remain predominantly mysterious. In this study, we identify and characterize 14 SlMCTP genes derived from tomatoes. Chromosome mapping, gene structure, phylogenetic connections, and subcellular localization are presented herein. Meanwhile, the varied expression patterns of SlMCTPs within different tissues and under diverse hormonal and NaCl treatment conditions are revealed. Moreover, we find that SlMCTP10, SlMCTP11, and SlMCTP12, which belong to the same clade, display high expression levels at the main stem apex, suggesting their potential functions in shoot development. Furthermore, we knock out the SlMCTP10 gene in tomato using CRISPR-Cas9. The Slmctp10 seedlings exhibit defects in shoot meristem development, manifested by abnormal cotyledons and shorter internodes. Together, our findings offer fundamental insights into the SlMCTP family and uncover the role of SlMCTP proteins in regulating shoot meristem development in tomato plants.
The close spatial and temporal connection between osteogenesis and angiogenesis around type H vasculature is referred as "osteogenesis-angiogenesis coupling", which is one of the basic mechanisms of osteogenesis. Endothelial cells (ECs), bone marrow mesenchymal stem cells (BMSCs), and their specific lineage constitute important cluster that participate in the regulation of osteogenesis and angiogenesis in bone microenvironment. However, the regulatory mechanism of osteogenesis-angiogenesis coupling under the condition of bone healing has not been unveiled. In this study, we demonstrated that the exosome derived from ECs (EC-exo) is an initiator of type H blood vessels formation, and EC-exo acts as a mediator in orchestrating osteogenesis-angiogenesis coupling by enhancing BMSC osteogenic differentiation and EC angiogenesis both in monolayer and stereoscopic co-culture system of primary human cells. The transcriptome array indicated that zinc finger and BTB domain containing 16 (ZBTB16) is a key gene in EC-exo-mediated osteogenesis, and ZBTB16 is indispensable in EC-exo-initiated osteogenesis-angiogenesis coupling. Mechanistically, EC-exo up-regulated the expression of ZBTB16 in BMSCs, thereby promoting osteoprogenitor phenotype transformation; the osteoprogenitors further promote ECs which constitute type H vessel (H-ECs) generation by activating HIF-1α pathway; and the H-ECs conversely promotes osteogenic differentiation of BMSCs. The crosstalk between BMSCs and ECs triggered by EC-exo constitutes a positive feedback loop that enhances osteogenesis-angiogenesis coupling. This study demonstrates that EC-exo can become an effective therapeutic tool to promote bone regeneration and repair.
The plant hormone auxin orchestrates almost all aspects of plant growth and development. AUXIN RESPONSE FACTORs (ARFs) control the transcription of auxin-responsive genes, forming cytoplasmic condensates to modulate auxin sensitivity and diversify auxin response regulation. However, the dynamic control of ARF distribution across different subcellular compartments remains largely obscure. Here, we show that three MULTIPLE C2 DOMAIN AND TRANSMEMBRANE REGION PROTEINs (MCTPs), MCTP3, MCTP4, and MCTP6, control ARF nucleocytoplasmic partitioning and determine lateral root development. MCTP3/4/6 are highly expressed in lateral roots and specifically interact with ARF7 and ARF19 to dissolve their cytoplasmic condensates. This promotes ARF nuclear localization in lateral root primordia and enhances auxin signaling during lateral root formation. Our findings confer MCTP as a key switch to modulate auxin responses and outline an MCTP-ARF signaling cascade that is crucial for the establishment of the plant root system.
Bone repair in elderly patients poses a huge challenge due to the age-related progressive decline in regenerative abilities attributed to the senescence of bone marrow stem cells (BMSCs). Bioactive scaffolds have been applied in bone regeneration due to their various biological functions. In this study, we aimed to fabricate functionalized bioactive scaffolds through loading osteoinductive extracellular vesicles (OI-EVs) based on mesoporous bioactive glass (MBG) scaffolds (1010 particles/scaffold) and to investigate its effects on osteogenesis and senescence of BMSCs. The results suggested that OI-EVs upregulate the proliferative and osteogenic capacities of senescent BMSCs. More importantly, The results showed that loading OI-EVs into MBG scaffolds achieved better bone regeneration. Furthermore, OI-EVs and BMSCs RNAs bioinformatics analysis indicated that OI-EVs play roles through transporting pivotal lncRNA acting as a "sponge" to compete with Mob3a for miR-1843a-5p to promote YAP dephosphorylation and nuclear translocation, ultimately resulting in elevated proliferation and osteogenic differentiation and reduced senescence-related phenotypes. Collectively, these results suggested that the OI-EVs lncRNA ceRNA regulatory networks might be the key point for senescent osteogenesis. More importantly, the study indicated the feasibility of loading OI-EVs into scaffolds and provided novel insights into biomaterial design for facilitating bone regeneration in the treatment of senescent bone defects. STATEMENT OF SIGNIFICANCE: Constructing OI-EVs/MBG delivering system and verification of its bone regeneration enhancement in senescent defect repair. Aging bone repair poses a huge challenge due to the age-related progressive degenerative decline in regenerative abilities attributed to the senescence of BMSCs. OI-EVs/MBG delivering system were expected as promising treatment for senescent bone repair, which could provide an effective strategy for bone regeneration in elderly patients. Clarification of potential OI-EVs lncRNA ceRNA regulatory mechanism in senescent bone regeneration OI-EVs play important roles through transferring lncRNA-ENSRNOG00000056625 sponging miR-1843a-5p that targeted Mob3a to activate YAP translocation into nucleus, ultimately alleviate senescence, promote proliferation and osteogenic differentiation in O-BMSCs, which provides theoretical basis for EVs-mediated therapy in future clinical works.
Silicon (Si)-based biomaterials have been widely applied for bone regeneration. However, the underlying mechanisms remain unknown. T lymphocyte-mediated adaptive immune response plays a vital role in the process of bone regeneration. In the present study, mesoporous silica (MS) was used as a model material of Si-based biomaterials. It showed that the supernatant of CD4 + T cells pretreated with MS extract significantly promoted the vascularized bone regeneration. The potential mechanism is closely related to the fact that MS extract could reduce the expression of regulatory factor X-1 (RFX-1) in CD4 + T cells, which could lead to interleukin-17A (IL-17A) overexpression through increased histone H3 acetylation and decreased DNA methylation and H3K9 trimethylation. Importantly, the in vivo experiments further revealed that MS particles dramatically stimulated bone regeneration with improved angiogenesis in the critical-sized calvarial defect mouse model accompanied by upregulation of IL-17A in peripheral blood and the proportion of Th17 cells.
PURPOSE:To compare the treatment effects of clear aligners and customized lingual appliance on treating bimaxillary dentoalveolar protrusion patients with first premolar extractions.METHODS:Fifty-four patients with bimaxillary dentoalveolar protrusion treated in Shanghai Ninth People Hospital were involved in the retrospective study. Twenty-five cases used clear aligners and 29 cases used customized lingual appliance. All of them were treated by extracting 4 first premolars and retracting anterior teeth with strong anchorage. The changes of anterior tooth and soft tissue adduction before and after treatment were compared by lateral cephalometric measurements. SPSS 26.0 software package was used for data analysis.RESULTS:The total course of treatment in the clear aligners group (46.32±7.37 months) was about 10.8 months longer than that in the customized lingual appliance group (35.55±5.90 months) (P<0.05). There was no significant difference in upper incisor retraction, lower incisor inclination and overjet reduction between the two groups(P>0.05). There were significant differences in upper lip retraction, lower lip retraction, upper incisor torque reduction, and overbite reduction between the two groups(P<0.05). Customized lingual appliance group showed a significant improvement of lips retraction and overbite reduction in orthodontic treatment. For the correction of overjet, there was no significant difference between the two groups (P=0.337). The data of U1-OP (the distance between edge of the upper central incisor and the functional occlusal plane) was not in normal distribution, and there was no significant difference between the two groups(P=0.184).CONCLUSIONS:The two techniques can both retract the anterior teeth and lips to improve the profile. However, the customized lingual appliance was more effective in improving the soft tissue profile of patients with bimaxillary dentoalveolar protrusion, with shorter treatment course.
The repair of damaged cartilage still remains a great challenge in clinic. It is demonstrated that bone marrow stromal cells (BMSCs)-chondrocytes communication is of great significance for cartilage repair. Moreover, BMSCs have been confirmed to enhance biological function of chondrocytes via exosome-mediated paracrine pathway. Lithium-containing scaffolds have been reported to effectively promote cartilage regeneration; however, whether lithium-containing biomaterial could facilitate cartilage regeneration through regulating BMSCs-derived exosomes has not been illustrated. In the study, the model lithium-substituted bioglass ceramic (Li-BGC) is selected and regulatory effects of BMSCs-derived exosomes after Li-BGC treatment (Li-BGC-Exo) are systemically evaluated. The data reveal that Li-BGC-Exo notably promotes chondrogenesis, which attributes to the upregulated exosomal miR-455-3p transfer, consequently leads to suppression of histone deacetylase 2 (HDAC2) and enhanced histone H3 acetylation in chondrocytes. Notably, BMSCs-derived exosomes after LiCl treatment (LiCl-Exo) exhibits the similar regulatory effect with Li-BGC-Exo, indicating that the pro-chondrogenesis capability of them is mainly owing to the lithium ions. Furthermore, the in vivo study proves that LiCl-Exo remarkably facilitates cartilage regeneration. The research may provide novel possibility for the intrinsic mechanism of chondrogenesis trigged by lithium-containing biomaterials, and suggests that application of lithium-containing scaffolds may be a promising strategy for cartilage regeneration.
In the new power system, the viability of planning scheme depends largely on the suitability of the wind and photovoltaic (WP) output scenario. A scenario reconstruction model for wind and photovoltaic power considering the spatio-temporal correlation and credibility is proposed in this paper. The probability density of scenario about each moment is obtained by kernel density estimation. The Copula function is used to obtain the WP output correlation and generate the reconstructed scenario in each season. The credibility of WP output from historical data and reconstructed data are calculated respectively. It can be obtained from the credibility comparison results that the scenario reconstruction model can fully reflect the real situation.
BackgroundMany scholars have proven cervical vertebral maturation (CVM) method can predict the growth and development and assist in choosing the best time for treatment. However, assessing CVM is a complex process. The experience and seniority of the clinicians have an enormous impact on judgment. This study aims to establish a fully automated, high-accuracy CVM assessment system called the psc-CVM assessment system, based on deep learning, to provide valuable reference information for the growth period determination.MethodsThis study used 10,200 lateral cephalograms as the data set (7111 in train set, 1544 in validation set and 1545 in test set) to train the system. The psc-CVM assessment system is designed as three parts with different roles, each operating in a specific order. 1) Position Network for locating the position of cervical vertebrae; 2) Shape Recognition Network for recognizing and extracting the shapes of cervical vertebrae; and 3) CVM Assessment Network for assessing CVM according to the shapes of cervical vertebrae. Statistical analysis was conducted to detect the performance of the system and the agreement of CVM assessment between the system and the expert panel. Heat maps were analyzed to understand better what the system had learned. The area of the third (C3), fourth (C4) cervical vertebrae and the lower edge of second (C2) cervical vertebrae were activated when the system was assessing the images.ResultsThe system has achieved good performance for CVM assessment with an average AUC (the area under the curve) of 0.94 and total accuracy of 70.42%, as evaluated on the test set. The Cohen's Kappa between the system and the expert panel is 0.645. The weighted Kappa between the system and the expert panel is 0.844. The overall ICC between the psc-CVM assessment system and the expert panel was 0.946. The F1 score rank for the psc-CVM assessment system was: CVS (cervical vertebral maturation stage) 6 > CVS1 > CVS4 > CVS5 > CVS3 > CVS2.ConclusionsThe results showed that the psc-CVM assessment system achieved high accuracy in CVM assessment. The system in this study was significantly consistent with expert panels in CVM assessment, indicating that the system can be used as an efficient, accurate, and stable diagnostic aid to provide a clinical aid for determining growth and developmental stages by CVM.
PURPOSE:To observe the regulatory effect of lithium-doped hydroxyapatite nanowires on bone metabolism in osteoporotic zebrafish induced by dexamethasone.METHODS:Pure hydroxyapatite nanowires(nHA) and hydroxyapatite nanowires doped with 10% lithium ions (Li-nHA) were prepared by using hydrothermal method, and then material characterization was performed. The juvenile zebrafish cultured for 3 days(3dpf) were selected and co-cultured with nHA and Li-nHA extracts up to 7dpf. A negative(0.1% DMSO) control group was set up and transgenic zebrafish Tg(ola.sp7:nlsGFP) was used to select the best concentration for promoting bone formation. The osteoporotic zebrafish were induced by dexamethasone and incubated with nHA and Li-nHA extracts. The wild-type zebrafish was stained with alizarin red and the osteogenic differentiation was observed in transgenic zebrafish. Real-time quantitative PCR was adopted to detect osteogenic maker genes, such as zinc finger transcription factor (SP7), alkaline phosphatase (ALP), osteoprotegerin (OPG), Runt related transcription factor 2(Runx2) and osteocalcin (OCN). Statistical analysis was performed with GraphPad Prism 9.3 software.RESULTS:nHA and Li-nHA promoted bone formation and up-regulated expression levels of ALP, OCN, Runx2, SP7 and OPG of osteoporotic zebrafish. Compared with nHA, Li-nHA significantly increased the mineralization specific staining area and cumulative optical density of zebrafish bone, and the expression of osteogenic maker genes was also significantly increased.CONCLUSIONS:Doping lithium ions in nano hydroxyapatite can enhance its osteoinductive properties, and Li-nHA can effectively improve bone formation of osteoporotic zebrafish.