Specific Role Research Articles

Comparative analysis of the whole transcriptome landscapes of muscle and adipose tissue in Qinchuan beef cattle

BackgroundMuscle and adipose tissue are the most critical indicators of beef quality, and their development and function are regulated by noncoding RNAs (ncRNAs). However, the differential regulatory mechanisms of ncRNAs in muscle and adipose tissue remain unclear.ResultsIn this study, 2,343 differentially expressed mRNAs (DEMs), 235 differentially expressed lncRNAs (DELs), 95 differentially expressed circRNAs (DECs) and 54 differentially expressed miRNAs (DEmiRs) were identified in longissimus dorsi muscle (LD), subcutaneous fat (SF) and perirenal fat (VF) in Qinchuan beef cattle. The results of functional enrichment analysis showed that DEMs, DELs, DECs and DEmiRs were enriched in biological processes related to development and function of muscle and fat deposition, including skeletal muscle contraction, muscle organ development, PPAR signaling pathway, fatty acid metabolism and MAPK signaling pathway. Based on the competing endogenous RNA (ceRNA) regulatory mechanism, we constructed a lncRNA/circRNA-miRNA-mRNA network consisting of 6 circRNAs, 5 lncRNAs, 6 miRNAs and 27 mRNAs. Among them, 55 ceRNA axes were involved, including circRNA12990 - bta-miR-133a_L-1R + 1 - MYO6/ZEB2, circRNA2893/MSTRG.28538.1/MSTRG.11613.4 - pma-miR-145-5p_R + 2 - EYA4 and MSTRG.26982.1 - bta-let-7e_R + 1 - RBM40.ConclusionsThis study identified a group of differentially expressed mRNAs, lncRNAs, circRNAs and miRNAs between muscle and adipose tissue and constructed a potential ceRNA regulatory network, which may serve as a foundation for studying the differential regulatory roles of ncRNAs in the development and function of muscle and adipose tissue.

Irisin and Metastatic Melanoma: Selective Anti-Invasiveness Activity in BRAF Wild-Type Cells

Irisin is a newly discovered 12 kDa messenger protein involved in energy metabolism. Irisin affects signaling pathways in several types of cancer; however, the role of irisin in metastatic melanoma (MM) has not been described yet. We explored the biological effects of irisin in in vitro models of MM cells (HBLwt/wt, LND1wt/wt, Hmel1V600K/wt and M3V600E/V600E) capable of the oncogenic activation of BRAF. We treated MM cells with different concentrations of r-irisin (10 nM, 25 nM, 50 nM, 100 nM) for 24 h–48 h. An MTT assay highlighted that r-irisin did not affect the proliferation of MM cells. We subsequently treated MM cells with 10 nM r-irisin, corresponding to the dose exhibiting biological activity in vitro. Irisin reduced the invasive ability of only LND1wt/wt (p < 0.05), which highly expressed αv gene levels, but did not affect the invasion of BRAFmut cells. Gelatin zymography analysis showed a reduction in the enzymatic activity of MMP-2 and MMP-9 in BRAFwt/wt cells treated with 10 nM r-irisin. Moreover, gene expression analysis (qPCR) of MMP-2 and MMP-9 and of the fibrinolytic system (uPAR, uPA and PAI-1) highlighted a crucial role of 10 nM r-irisin treatment in the inhibition of pro-invasive systems in BRAFwt/wt. In conclusion, our results may suggest a possible differential role of irisin in melanoma cells.

Differential roles of human CD4+ and CD8+ regulatory T cells in controlling self-reactive immune responses.

Here we analyzed the relative contributions of CD4+ regulatory T cells expressing Forkhead box protein P3 (FOXP3) and CD8+ regulatory T cells expressing killer cell immunoglobulin-like receptors to the control of autoreactive T and B lymphocytes in human tonsil-derived immune organoids. FOXP3 and GZMB respectively encode proteins FOXP3 and granzyme B, which are critical to the suppressive functions of CD4+ and CD8+ regulatory T cells. Using CRISPR-Cas9 gene editing, we were able to achieve a reduction of ~90-95% in the expression of these genes. FOXP3 knockout in tonsil T cells led to production of antibodies against a variety of autoantigens and increased the affinity of influenza-specific antibodies. By contrast, GZMB knockout resulted in an increase in follicular helper T cells, consistent with the ablation of CD8+ regulatory T cells observed in mouse models, and a marked expansion of autoreactive CD8+ and CD4+ T cells. These findings highlight the distinct yet complementary roles of CD8+ and CD4+ regulatory T cells in regulating cellular and humoral responses to prevent autoimmunity.

Positive and negative affect differentially relate to alcohol and cannabis use in LGBTQ+ and cisgender-straight heavy-drinking adults: Results of an ambulatory assessment study.

Previous research has found that momentary positive affect precedes alcohol use, whereas results have been more mixed for negative affect. This study replicates and builds upon this literature by using a heavy drinking sample, half lesbian, gay, bisexual, trans, queer/questioning, and other minoritized sexual and gender identities (LGBTQ+) individuals. This study found that positive affect was related to subsequent alcohol use, but the relation was weaker for LGBTQ+ individuals compared to cisgender-straight individuals. Negative affect was negatively related to alcohol use in the overall sample, but LGBTQ+ individuals reported drinking more drinks following increased negative affect, and this effect was not significant for cisgender-straight individuals. Finally, positive affect was related to subsequent cannabis use, and negative affect was negatively related to cannabis use, which did not differ based on sexual orientation and gender identity. Future research should explore the impact of minority stress on the association between affect and drinking behaviors to understand the differential role of affect on LGBTQ+ individual's substance use. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

MicroRNA analysis reveals two modules that antagonistically regulate xylem tracheary element development in Arabidopsis.

Tracheary elements (TEs) are vital in the transport of various substances and contribute to plant growth. The differentiation of TEs is complex and regulated by a variety of microRNAs (miRNAs). However, the dynamic changes in miRNAs during each stage of TE differentiation remain unclear, and the miRNA regulatory network is not yet complete. This study employed Vascular cell Induction culture System Using Arabidopsis Leaves (VISUAL) to profile the miRNome during TE differentiation in Arabidopsis (Arabidopsis thaliana) and established comprehensive miRNA co-expression networks functioning at the different stages of TE differentiation. Two negatively correlated modules exist in the miRNA networks, each exhibiting strong intra-module positive correlation and strong inter-module negative correlation. Thus, the two modules may play opposite roles in TE differentiation and vascular development. Indeed, we found that miR408 promotes cambium formation and TE differentiation, consistent with miR408 as a key node in the networks of fate determination and the initiation of TE differentiation. Additionally, we found that miR163 inhibits secondary cell wall formation and TE differentiation, corresponding to miR163 as a key node in the TE maturation network. Moreover, we discovered that the miRNA co-expression network in poplar (Populus tomentosa) xylem development is also composed of two negatively correlated modules that contain miRNAs orthologous to those in Arabidopsis. Therefore, the two negatively correlated modules of the miRNA co-expression network are likely conserved and fundamental to xylem TE differentiation. These results provide insights into microRNA regulation in plant development.

Sonic Hedgehog signaling regulates the optimal differentiation pace from early-stage mesoderm to cardiogenic mesoderm in mice.

Sonic Hedgehog (Shh), encoding an extracellular signaling molecule, is vital for heart development. Shh null mutants show congenital heart disease due to left-right asymmetry defects stemming from functional anomaly in the midline structure in mice. Shh signaling is also known to affect cardiomyocyte differentiation, endocardium development, and heart morphogenesis, particularly in second heart field (SHF) cardiac progenitor cells that contribute to the right ventricle, outflow tract, and parts of the atrium. Despite extensive studies, our understanding remains incomplete. Notably, Shh signaling is suggested to promote cardiac differentiation, while paradoxically preventing premature differentiation of SHF progenitors. In this study, we elucidate the role of Shh signaling in the earliest phase of cardiac differentiation. Our meta-analysis of single-cell RNA sequencing suggests that cardiogenic nascent mesoderm cells expressing the bHLH transcription factor Mesp1 interact with axial mesoderm via Hh signaling. Activation of Hh signaling using a Smoothened agonist delayed or suppressed the differentiation of primitive streak cells expressing T-box transcription factor T to Mesp1+ nascent mesoderm cells both in vitro and ex vivo. Conversely, inhibition of Hh signaling by cyclopamine facilitated cardiac differentiation. The reduction of Eomes, an inducer of Mesp1, by Hh signaling appears to be the underlying mechanism of this phenomenon. Our data suggest that SHH secreted from axial mesoderm inhibits premature differentiation of T+ cells to Mesp1+ nascent mesoderm cells, thereby regulating the pace of cardiac differentiation. These findings enhance our comprehension of Shh signaling in cardiac development, underscoring its crucial role in early cardiac differentiation.

Emerging Combinatorial Drug Delivery Strategies for Breast Cancer: A Comprehensive Review.

Breast cancer remains the second most prevalent cancer among women in the United States. Despite advancements in surgical, radiological, and chemotherapeutic techniques, multidrug resistance continues to pose significant challenges in effective treatment. Combination chemotherapy has emerged as a promising approach to address these limitations, allowing multiple drugs to target malignancies via distinct mechanisms of action. Increasingly, the use of phytoconstituents alongside chemotherapeutic agents has shown promise in enhancing treatment outcomes. This combination therapy acts on key signaling pathways such as Hedgehog, Notch, Wnt/β- catenin, tyrosine kinases, and phosphatidylinositol 3-kinase (PI3K), which play critical roles in cellular proliferation, apoptosis, angiogenesis, differentiation, invasion, and metastasis. This review explores various signaling pathways involved in breast cancer progression, discusses conventional treatment methods like surgery, adjuvant radiotherapy, hormonal therapy, and chemotherapy, and highlights emerging nanocarrier-based drug delivery systems (DDS). Liposomes, dendrimers, exosomes, polymeric micelles, and nanoparticles (organic, inorganic, gold, magnetic, carbon-based, and quantum dots) are examined as innovative strategies for enhancing drug delivery efficacy. Furthermore, stimuli-responsive DDSs, including reactive oxygen species (ROS), enzyme-, and hypoxia- responsive systems, are presented as cutting-edge approaches to overcoming drug resistance. Special emphasis is placed on the co-delivery of chemotherapeutic agents and plant-based compounds, particularly in estrogen receptor-positive (ER+) breast cancer. This review aims to provide a comprehensive overview of novel combinatorial strategies and advanced nanocarriers for the effective and targeted treatment of breast cancer.

PKM2 controls cochlear development through lactate-dependent transcriptional regulation

Understanding the role of metabolic processes during inner ear development is essential for identifying targets for hair cell (HC) regeneration, as metabolic choices play a crucial role in cell proliferation and differentiation. Among the metabolic processes, growing evidence shows that glucose metabolism is closely related to organ development. However, the role of glucose metabolism in mammalian inner ear development and HC regeneration remains unclear. In this study, we found that glycolytic metabolism is highly active during mouse and human cochlear prosensory epithelium expansion. Using mouse cochlear organoids, we revealed that glycolytic activity in cochlear nonsensory epithelial cells was predominantly dominated by pyruvate kinase M2 (PKM2). Deletion of PKM2 induced a metabolic switch from glycolysis to oxidative phosphorylation, impairing cochlear organoid formation. Furthermore, conditional loss of PKM2 in cochlear progenitors hindered sensory epithelium morphogenesis, as demonstrated in PKM2 knockout mice. Mechanistically, pyruvate is generated by PKM2 catalysis and then converted into lactate, which then lactylates histone H3, regulating the transcription of key genes for cochlear development. Specifically, accumulated lactate causes histone H3 lactylation at lysine 9 (H3K9la), upregulating the expression of Sox family transcription factors through epigenetic modification. Moreover, overexpression of PKM2 in supporting cells (SCs) triggered metabolism reprogramming and enhanced HC generation in cultured mouse and human cochlear explants. Our findings uncover a molecular mechanism of sensory epithelium formation driven by glycolysis-lactate flow and suggest unique approaches for mammalian HC regeneration.

Functional analysis of conserved C. elegans bHLH family members uncovers lifespan control by a peptidergic hub neuron.

Throughout the animal kingdom, several members of the basic helix-loop-helix (bHLH) family act as proneural genes during early steps of nervous system development. Roles of bHLH genes in specifying terminal differentiation of postmitotic neurons have been less extensively studied. We analyze here the function of 5 Caenorhabditis elegans bHLH genes, falling into 3 phylogenetically conserved subfamilies, which are continuously expressed in a very small number of postmitotic neurons in the central nervous system. We show (a) that 2 orthologs of the vertebrate bHLHe22/e23 genes, called hlh-17 and hlh-32, function redundantly to specify the identity of a single head interneuron class (AUA), as well as an individual motor neuron (VB2); (b) that the PTF1a ortholog hlh-13 acts as a terminal selector to control terminal differentiation and function of the sole octopaminergic neuron class in C. elegans, RIC; and (c) that the NHLH1/2 ortholog hlh-15 controls terminal differentiation and function of the peptidergic AVK head interneuron class, a known neuropeptidergic signaling hub in the animal. Strikingly, through null mutant analysis and cell-specific rescue experiments, we find that loss of hlh-15/NHLH in the peptidergic AVK neurons and the resulting abrogation of neuropeptide secretion from these neurons causes a substantially extended lifespan of the animal, which we propose to be akin to hypothalamic control of lifespan in vertebrates. Our functional analysis reveals themes of bHLH gene function during terminal differentiation that are complementary to the earlier lineage specification roles of other bHLH family members. However, such late functions are much more sparsely employed by members of the bHLH transcription factor family, compared to the function of the much more broadly employed homeodomain transcription factor family.

TGFβ1 Restores Energy Homeostasis of Human Trophoblast Cells Under Hyperglycemia In Vitro by Inducing PPARγ Expression, AMPK Activation, and HIF1α Degradation.

Elevated glucose levels at the fetal-maternal interface are associated with placental trophoblast dysfunction and increased incidence of pregnancy complications. Trophoblast cells predominantly utilize glucose as an energy source, metabolizing it through glycolysis in the cytoplasm and oxidative respiration in the mitochondria to produce ATP. The TGFβ1/SMAD2 signaling pathway and the transcription factors PPARγ, HIF1α, and AMPK are key regulators of cell metabolism and are known to play critical roles in extravillous trophoblast cell differentiation and function. While HIF1α promotes glycolysis over mitochondrial respiration, PPARγ and AMPK encourage the opposite. However, the interplay between TGFβ1 and these energy-sensing regulators in trophoblast cell glucose metabolism remains unclear. This study aimed to investigate whether and how TGFβ1 regulates energy metabolism in trophoblast cells exposed to normal and high glucose conditions. The trophoblast JEG-3 cells were incubated in normal (5 mM) and high (25 mM) glucose conditions for 24 h in the absence and the presence of TGFβ1. The protein expression levels of phosphor (p)-SMAD2, GLUT1/3, HIF1α, PPARγ, p-AMPK, and specific OXPHOS protein subunits were determined by western blotting, and ATP and lactate production by bioluminescent assay kits. JEG-3 cells exposed to 25 mM glucose decreased ATP production but did not affect lactate production. These changes led to a reduction in the expression levels of GLUT1/3, mitochondrial respiratory chain proteins, and PPARγ, coinciding with an increase in HIF1α expression. Conversely, TGFβ1 treatment at 25 mM glucose reduced HIF1α expression while enhancing the expression levels of GLUT1/3, PPARγ, p-AMPK, and mitochondrial respiratory chain proteins, thereby rejuvenating ATP production. Our findings reveal that high glucose conditions disrupt cellular glucose metabolism in trophoblast cells by perturbing mitochondrial oxidative respiration and decreasing ATP production. Treatment with TGFβ1 appears to counteract this trend, probably by enhancing both glycolytic and mitochondrial metabolism, suggesting a potential regulatory role of TGFβ1 in placental trophoblast cell glucose metabolism.

The differential roles of transient and chronic loneliness in consumers’ variety­ seeking behavior

The differential roles of transient and chronic loneliness in consumers’ variety­ seeking behavior

Transcription factor 7-like 2 (TCF7l2) regulates CNS myelination separating from its role in upstream oligodendrocyte differentiation.

Oligodendrocyte progenitor cells (OPCs) differentiation into oligodendrocytes (OLs) and subsequent myelination are two closely coordinated yet differentially regulated steps for myelin formation and repair in the CNS. Previously thought as an inhibitory factor by activating Wnt/beta-catenin signaling, we and others have demonstrated that the Transcription factor 7-like 2 (TCF7l2) promotes OL differentiation independent of Wnt/beta-catenin signaling activation. However, it remains elusive if TCF7l2 directly controls CNS myelination separating from its role in upstream oligodendrocyte differentiation. This is partially because of the lack of genetic animal models that could tease out CNS myelination from upstream OL differentiation. Here, we report that constitutively depleting TCF7l2 transiently inhibited oligodendrocyte differentiation during early postnatal development, but it impaired CNS myelination in the long term in adult mice. Using time-conditional and developmental-stage-specific genetic approaches, we further showed that depleting TCF7l2 in already differentiated OLs did not impact myelin protein gene expression nor oligodendroglial populations, instead, it perturbed CNS myelination in the adult. Therefore, our data convincingly demonstrate the crucial role of TCF7l2 in regulating CNS myelination independent of its role in upstream oligodendrocyte differentiation.

The Transcription Factor SOX18 Inhibitor Small Molecule 4 Is a Potential Treatment of Cancer-Induced Lymphatic Metastasis and Lymphangiosarcoma.

Malignant tumors release growth factors, promoting lymphangiogenesis in primary tumors and draining sentinel lymph nodes, ultimately facilitating lymph node metastasis. As a malignant lymphatic tumor entity, lymphangiosarcomas are characterized by low survival rates and limited treatment options. The transcription factor SOX18 plays a crucial role in both lymphatic endothelial cell differentiation and cancer-induced lymphangiogenesis. In this invitro study, we investigated the potential therapeutic effect of a small molecule called Sm4, which inhibits SOX18, on lymphatic endothelial and lymphangiosarcoma cells invitro. Human dermal lymphatic endothelial cells (HDLECs), lymphangiosarcoma cells (MO-LAS), and other endothelial cell lines were cultured. We found that Sox18 exhibited high mRNA expression levels in both HDLEC and MO-LAS. Sm4 treatment decreased the Sox18 expression level at the mRNA and protein levels in both HDLEC and MO-LAS significantly, a phenomenon confirmed through immunofluorescence images. Additionally, Sm4 treatment suppressed the expression of key lymphatic phenotype markers (Prox1, Flt4, and Lyve1) and hindered migration in both HDLEC and MO-LAS, all while maintaining cell viability. These findings suggest that targeting SOX18 with Sm4 may hold potential as a therapeutic strategy for lymphangiosarcoma and cancer-induced lymphatic metastasis. Further invitro studies are warranted to investigate the mechanisms and conduct dose-response analyses to evaluate Sm4's potential as a targeted therapy for lymphangiosarcoma and cancer-induced lymphangiogenesis in the future.

Self-assembled peptide-based nanofibers for cardiovascular tissue regeneration.

Cardiovascular diseases are the leading cause of death worldwide, claiming millions of lives every year. Cardiac tissue engineering has emerged as a versatile option for repairing cardiac tissue and helping its regeneration. The use of nanomaterials, particularly nanofiber-based scaffolds combined with biomolecular cues like peptides, has significantly improved the compatibility and efficacy of the scaffolds for cardiac tissue regeneration. By utilising the self-assembly properties of peptides to create nanofiber scaffolds, we can achieve stability that closely mimics the natural components of cardiac tissue, making them perfect for cardiac tissue regeneration. In this review, we highlighted the dynamic process of self-assembly into nanofibers and the use of various self-assembled nanofibers for cardiovascular tissue regeneration, focusing on their roles in antithrombotic, angiogenic, differentiation, proliferation, and anti-atherosclerotic interventions.

SCPL48 regulates the vessel cell programmed cell death during xylem development in Arabidopsis thaliana.

Secondary cell wall (SCW) deposition is tightly coordinated with programmed cell death (PCD) during xylem development and plays a crucial role in plant stress responses. In this study, we characterized a serine carboxypeptidase-like gene, SCPL48, which exhibits xylem cell-specific expression patterns in stem xylem during vascular development. The scpl48 plants exhibited reduced stem xylem cell numbers, particularly vessel cells, accompanied by delayed organelle degradation during PCD and increased secondary wall thickness in xylem vessel cells. In contrast, SCPL48 overexpression resulted in increased vessel cell abundance and accelerated degradation of vessel cell contents, suggesting its critical role in xylem vessel cell differentiation. Notably, SCPL48 expression was significantly up-regulated in response to ABA treatment and drought stress, with SCPL48 overexpression lines demonstrating enhanced drought resistance. Further molecular analyses revealed that SCPL48 was directly targeted and transcriptionally activated by key SCW regulators VND6, and MYB46. Furthermore, the expression of PCD-related protease genes, including XCP1, XSP1, RNS3, MC9, γVPE, and CEP1, showed compensatory changes in both scpl48 mutants and SCPL48 overexpression lines. Collectively, our findings demonstrate that SCPL48 functions as a key regulator in xylem vessel cell differentiation, PCD and drought stress responses.

PTPA localized in the Golgi apparatus plays an important role in osteoblast differentiation

PTPA localized in the Golgi apparatus plays an important role in osteoblast differentiation

Impact of loyal and new customer segments on product upgrades: The role of quality differentiation through online reviews

Impact of loyal and new customer segments on product upgrades: The role of quality differentiation through online reviews

Differential roles of IL-6 and adrenomedullin in early diagnosis and mortality predictions in late-onset neonatal sepsis.

Diagnosing and predicting neonatal sepsis is challenging because of its nonspecific symptoms, lack of diagnostic criteria consensus, and absence of early, sensitive, and specific diagnostic laboratory tests. To evaluate the diagnostic and prognostic potential of adrenomedullin (ADM), interleukin-6 (IL-6), and C-reactive protein (CRP) in late-onset neonatal sepsis (LOS). We studied 53 neonates with culture-proven LOS by sampling at admission and on antibiotic treatment days 3 and 7. These data were compared with those of 22 healthy full-term controls sampled on day 3 before hospital discharge. Survivors and non-survivors in the sepsis group were analyzed separately. Coagulase-negative Staphylococcus was the most commonly detected pathogen. ADM (cutoff, 0.5 ng/mL) and CRP (cutoff, <5 mg/L) values aligned with manufacturer recommendations, while IL-6 levels (cutoff, 10 pg/mL) were higher than expected, likely due to labor stress. The median biomarker levels significantly distinguished neonates with sepsis from controls (p < 0.0001) at all time points with ADM and IL-6 levels elevated at admission, indicating their potential as early diagnostic markers. CRP level was diagnostically useful starting on day 3. Prognostically, IL-6 (p < 0.001) and ADM (p < 0.05) differentiated survivors from non-survivors; however, only IL-6 consistently predicted mortality at all time points (area under the curve [AUC] > 0.90). ADM and CRP levels showed poor prognostic value (AUC < 0.70). ADM and IL-6 demonstrated strong diagnostic utility in early LOS, whereas CRP became relevant later. IL-6 was the only reliable biomarker for predicting mortality, supporting its integration into clinical protocols. Combining IL-6 with CRP may enhance early detection and management, potentially improving neonatal outcomes. IL-6 is a robust biomarker for the early diagnosis and prognosis of LOS. Incorporating IL-6 into clinical practice with CRP could improve early neonatal LOS diagnosis and patient outcomes.

Melatonin Enhances the Low-Calcium Stress Tolerance by Regulating Brassinosteroids and Auxin Signals in Wax Gourd.

In plants, calcium (Ca) serves as an essential nutrient and signaling molecule. Melatonin is a biologically active and multi-functional hormone that plays an important role in improving nutrient use efficiency. However, its involvement in plant responses to Ca deficiency remains largely unexplored. This study aimed to assess the effects of melatonin on Ca absorption, the antioxidant system, and root morphology under low-Ca (LCa) stress conditions, as well as to identify key regulatory factors and signaling pathways involved in these processes using transcriptome analysis. Under LCa conditions, wax gourd seedling exhibited significant decreases in Ca accumulation, showed inhibition of root growth, and demonstrated the occurrence of oxidative damage. However, melatonin application significantly enhanced Ca content in wax gourd seedlings, and it enhanced the absorption of Ca2+ in roots by upregulating Ca2+ channels and transport genes, including BhiCNGC17, BhiCNGC20, BhiECA1, BhiACA1, and BhiCAX1. Furthermore, the application of exogenous melatonin mitigated the root growth inhibition and oxidative damage caused by LCa stress. This was evidenced by increases in the root branch numbers, root tips, root surface area, and root volume, as well as enhanced root vitality and antioxidant enzyme activities, as well as decreases in the reactive oxygen species content in melatonin treated plants. Transcriptome results revealed that melatonin mainly modulated the brassinosteroids (BRs) and auxin signaling pathway, which play essential roles in root differentiation, elongation, and stress adaptation. Specifically, melatonin increased the active BR levels by upregulating BR6ox (a BR biosynthesis gene) and downregulating BAS1 (BR degradation genes), thereby affecting the BR signaling pathway. Additionally, melatonin reduced IAA levels but activated the auxin signaling pathway, indicating that melatonin could directly stimulate the auxin signaling pathway via an IAA-independent mechanism. This study provides new insights into the role of melatonin in nutrient stress adaptation, offering a promising and sustainable approach to improve nutrient use efficiency in wax gourd and other crops.

Compression force promotes the osteogenic differentiation of periodontal ligament stem cells by regulating NAT10-mediated ac4C modification of BMP2

BackgroundOrthodontic treatment applies specific corrective forces to teeth, transmitting stress to periodontal tissue, thereby regulating the growth and development of periodontal ligament stem cells (PDLSCs). Recently, N-acetyltransferase 10 (NAT10) mediated N4-acetylcytidine (ac4C) modification is demonstrated to play a key role in the osteogenic differentiation of stem cells. Therefore, this study aimed explore the effects of Orthodontic treatment on the NAT10 mediated ac4C modification and osteogenic differentiation of PDLSCs.MethodsCompressive force was used to treat PDLSCs to simulate orthodontic force treatment. The ALP and ARS staining was performed to analyze the osteogenic differentiation of PDLSCs. Besides, ac4C dot blot and ac4C-RIP assays were performed to detect the global ac4C levels and BMP2 ac4C levels. The relationship between NAT10 and BMP2 was confirmed by RIP assay and immunofluorescence staining. The mRNA and protein levels of RUNX2, Oxterix and BMP2 were detected by RT-qPCR and western blot assays.ResultsCompressive force treatment promoted the osteogenic differentiation of PDLSCs, and enhanced the global ac4C levels and NAT10 levels in PDLSCs. NAT10 overexpression further promoted the osteogenic differentiation of compressive force treated PDLSCs. Besides, NAT10 overexpression increased ac4C levels of BMP2 and enhanced the mRNA stability of BMP2. Remodelin treatment significantly decreased the ac4C and mRNA levels of BMP2. Furthermore, BMP2 silencing reversed the role of NAT10 in the compressive force treated PDLSCs.ConclusionThis study demonstrated that compressive force promotes cell viability and osteogenic differentiation of PDLSCs by regulating BMP2 levels mediated by NAT10. NAT10 mediated ac4C levels of BMP2 is the key signaling axis of orthodontic stress in promoting cell growth and osteogenic differentiation of PDLSCs.Graphical abstract