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GPR126 is a member of the adhesion G protein-coupled receptors (aGPCRs) that is essential for the normal development of diverse tissues, and its mutations are implicated in various pathological processes. Here, through screening 34 steroid hormones and their derivatives for cAMP production, we found that progesterone (P4) and 17-hydroxyprogesterone (17OHP) could specifically activate GPR126 and trigger its downstream Gi signaling by binding to the ligand pocket in the seven-transmembrane domain of the C-terminal fragment of GPR126. A detailed mutagenesis screening according to a computational simulated structure model indicated that K1001ECL2 and F1012ECL2 are key residues that specifically recognize 17OHP but not progesterone. Finally, functional analysis revealed that progesterone-triggered GPR126 activation promoted cell growth in vitro and tumorigenesis in vivo, which involved Gi-SRC pathways in a triple-negative breast cancer model. Collectively, our work identified a membrane receptor for progesterone/17OHP and delineated the mechanisms by which GPR126 participated in potential tumor progression in triple-negative breast cancer, which will enrich our understanding of the functions and working mechanisms of both the aGPCR member GPR126 and the steroid hormone progesterone.
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Progesterona , Receptores Acoplados a Proteínas G , Receptores de Progesterona , Neoplasias de la Mama Triple Negativas , 17-alfa-Hidroxiprogesterona/metabolismo , Línea Celular Tumoral , Humanos , Progesterona/metabolismo , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Transducción de Señal , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/metabolismoRESUMEN
The inherent zero-band gap nature of graphene and its fast photocarrier recombination rate result in poor optical gain and responsivity when graphene is used as the light absorption medium in photodetectors. Here, semiconducting graphene nanoribbons with a direct bandgap of 1.8 eV are synthesized and employed to construct a vertical heterojunction photodetector. At a bias voltage of -5 V, the photodetector exhibits a responsivity of 1052 A/W, outperforming previous graphene-based heterojunction photodetectors by several orders of magnitude. The achieved detectivity of 3.13 × 1013 Jones and response time of 310 µs are also among the best values for graphene-based heterojunction photodetectors reported until date. Furthermore, even under zero bias, the photodetector demonstrates a high responsivity and detectivity of 1.04 A/W and 2.45 × 1012 Jones, respectively. The work shows a great potential of graphene nanoribbon-based photodetection technology.
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Currently, the construction of anti-ambipolar transistors (AATs) is primarily based on asymmetric heterostructures, which are challenging to fabricate. AATs used for photodetection are accompanied by dark currents that prove difficult to suppress, resulting in reduced sensitivity. This work presents light-triggered AATs based on an in-plane lateral WSe2 homojunction without van der Waals heterostructures. In this device, the WSe2 channel is partially electrically controlled by the back gate due to the screening effect of the bottom electrode, resulting in a homojunction that is dynamically modulated with gate voltage, exhibiting electrostatically reconfigurable and light-triggered anti-ambipolar behaviors. It exhibits high responsivity (188 A/W) and detectivity (8.94 × 1014 Jones) under 635 nm illumination with a low power density of 0.23 µW/cm2, promising a new approach to low-power, high-performance photodetectors. Moreover, the device demonstrates efficient self-driven photodetection. Furthermore, ternary inverters are realized using monolithic WSe2, simplifying the manufacturing of multivalued logic devices.
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Plant embryogenic calli (ECs) can undergo somatic embryogenesis to regenerate plants. This process is mediated by regulatory factors, such as transcription factors and specifically expressed genes, but the precise molecular mechanisms underlying somatic embryogenesis at the single-cell level remain unclear. In this study, we performed high-resolution single-cell RNA sequencing analysis to determine the cellular changes in the EC of the woody plant species Dimocarpus longan (longan) and clarify the continuous cell differentiation trajectories at the transcriptome level. The highly heterogeneous cells in the EC were divided into 12 putative clusters (e.g., proliferating, meristematic, vascular, and epidermal cell clusters). We determined cluster-enriched expression marker genes and found that overexpression of the epidermal cell marker gene GDSL ESTERASE/LIPASE-1 inhibited the hydrolysis of triacylglycerol. In addition, the stability of autophagy was critical for the somatic embryogenesis of longan. The pseudo-timeline analysis elucidated the continuous cell differentiation trajectories from early embryonic cell division to vascular and epidermal cell differentiation during the somatic embryogenesis of longan. Moreover, key transcriptional regulators associated with cell fates were revealed. We found that ETHYLENE RESPONSIVE FACTOR 6 was characterized as a heat-sensitive factor that negatively regulates longan somatic embryogenesis under high-temperature stress conditions. The results of this study provide new spatiotemporal insights into cell division and differentiation during longan somatic embryogenesis at single-cell resolution.
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Sapindaceae , Transcriptoma , Transcriptoma/genética , Sapindaceae/genética , Perfilación de la Expresión Génica , Análisis de Secuencia de ARN , Desarrollo Embrionario , Técnicas de Embriogénesis Somática de Plantas , Regulación de la Expresión Génica de las Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMEN
In photoelectrochemical (PEC) cells, selective oxidation of organic substrates coupled with hydrogen evolution represents a promising approach for value-added chemical production and solar energy conversion. In this study, we report on PEC epoxidation of alkenes at a ruthenium dye-sensitized photoanode in a CH3CN/H2O mixed solvent with LiBr as a mediator and water as the oxygen source. The dye-sensitized photoanode was found to exhibit significant advantages in the simultaneous improvement of charge separation and suppression of charge recombination. First, LiBr as a redox mediator plays a critical role in charge separation, leading to an excellent excited electron injection efficiency of 95% and a high dye regeneration efficiency of 87%. Second, the predominant charge recombination pathway on the dye-sensitized photoanode is efficiently blocked by the reaction between alkene and the in situ generated bromine oxidant. As a result, the current system achieved a remarkable photocurrent density of over 4 mA cm-2 with a record-high incident photo-to-current efficiency (IPCE) of 51% and extraordinary selectivity of up to 99% for the epoxidation of a wide range of alkenes. Meanwhile, nearly 100% Faradaic efficiency for hydrogen evolution was obtained. The performance shown here exceeds that obtained by metal oxide-based semiconductor photoanodes under comparable conditions, demonstrating the great potential of dye-sensitized photoelectrodes for organic synthesis owing to their diversity and tunability.
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The synthesis of photocatalysts with both broad light absorption and efficient charge separation is significant for a high solar energy conversion, which still remains to be a challenge. Herein, a narrow-bandgap Y2Ti2O5S2 (YTOS) oxysulfide nanosheet coexposed with defined {101} and {001} facets synthesized by a flux-assisted solid-state reaction was revealed to display the character of an anisotropic charge migration. The selective photodeposition of cocatalysts demonstrated that the {101} and {001} surfaces of YTOS nanosheets were the reduction and oxidation regions during photocatalysis, respectively. Density functional theory (DFT) calculations indicated a band energy level difference between the {101} and {001} facets of YTOS, which contributes to the anisotropic charge migration between them. The exposed Ti atoms on the {101} surface and S atoms on the {001} surface were identified, respectively, as reducing and oxidizing centers of YTOS nanosheets. This anisotropic charge migration generated a built-in electric field between these two facets, quantified by spatially resolved surface photovoltage microscopy, the intensity of which was found to be highly correlated with photocatalytic H2 production activity of YTOS, especially exhibiting a high apparent quantum yield of 18.2% (420 nm) after on-site modification of a Pt@Au cocatalyst assisted by Na2S-Na2SO3 hole scavengers. In conjunction with an oxygen-production photocatalyst and a [Co(bpy)3]2+/3+ redox shuttle, the YTOS nanosheets achieved a solar-to-hydrogen conversion efficiency of 0.15% via a Z-scheme overall water splitting. Our work is the first to confirm anisotropic charge migration in a perovskite oxysulfide photocatalyst, which is crucial for enhancing charge separation and surface catalytic efficiency in this material.
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Plant somatic embryogenesis (SE) is an in vitro biological process wherein bipolar structures are induced to form somatic cells and regenerate into whole plants. MicroRNA (miRNA) is an essential player in plant SE. However, the mechanism of microRNA408 (miR408) in SE remains elusive. Here, we used stable transgenic technology in longan (Dimocarpus longan) embryogenic calli to verify the mechanism by which miR408 promotes cell division and differentiation of longan early SE. dlo-miR408-3p regulated riboflavin biosynthesis by targeting nudix hydrolase 23 (DlNUDT23), a previously unidentified gene mediating N6-methyladenosine (m6A) modification and influencing RNA homeostasis and cell cycle gene expression during longan early SE. We showed that DlMIR408 overexpression (DlMIR408-OE) promoted 21-nt miRNA biosynthesis. In DlMIR408-OE cell lines, dlo-miR408-3p targeted and downregulated DlNUDT23, promoted riboflavin biosynthesis, decreased flavin mononucleotide (FMN) accumulation, promoted m6A level, and influenced miRNA homeostasis. DNA replication, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, the pentose phosphate pathway, and taurine and hypotaurine metabolism were also closely associated with riboflavin metabolism. In a riboflavin feeding assay, dlo-miR408-3p and pre-miR408 were upregulated and DlNUDT23 was downregulated, increasing the m6A level and cell division and differentiation in longan globular embryos. When riboflavin biosynthesis was inhibited, dlo-miR408-3p was downregulated and DlNUDT23 was upregulated, which decreased m6A modification and inhibited cell division but did not inhibit cell differentiation. FMN artificial demethylated m6A modification affected the homeostasis of precursor miRNA and miRNA. Our results revealed a mechanism underlying dlo-miR408-3p-activated riboflavin biosynthesis in which DlNUDT23 is targeted, m6A modification is dynamically mediated, and cell division is affected, promoting early SE in plants.
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MicroARNs , Sapindaceae , Perfilación de la Expresión Génica , Sapindaceae/genética , Sapindaceae/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Riboflavina/metabolismoRESUMEN
Somatic embryogenesis (SE), like zygotic embryo development, is a progressive process. Early SE is the beginning of a switch from a somatic to an embryogenic state and is an important stage for initiating chromatin reprogramming of SE. Previous studies suggest that changes in chromatin accessibility occur during early SE, although information on the 3D structure of chromatin is not yet available. Here, we present a chromosome-level genome assembly of longan (Dimocarpus longan) using PacBio combined with high-through chromosome conformation capture scaffolding, which resulted in a 446 Mb genome assembly anchored onto 15 scaffolds. During early SE, chromatin was concentrated and then decondensed, and a large number of long terminal repeat retrotransposons (LTR-RTs) were enriched in the local chromatin interaction region, suggesting LTR-RTs were involved in chromatin reorganization. Early SE was accompanied by the transformation from A to B compartments, and the interactions between B compartments were enhanced. Results from chromatin accessibility, monomethylation of histone H3 at lysine 4 (H3K4me1) modification, and transcription analyses further revealed a gene regulatory network for cell wall thickening during SE. Particularly, we found that the H3K4me1 differential peak binding motif showed abnormal activation of ethylene response factor transcription factors and participation in SE. The chromosome-level genomic and multiomics analyses revealed the 3D conformation of chromatin during early SE, providing insight into the molecular mechanisms underlying cell wall thickening and the potential regulatory networks of TFs during early SE in D. longan. These results provide additional clues for revealing the molecular mechanisms of plant SE.
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Cromosomas de las Plantas , Técnicas de Embriogénesis Somática de Plantas , Sapindaceae , Biomarcadores/metabolismo , Pared Celular , Cromatina , Redes Reguladoras de Genes , Genoma de Planta , Código de Histonas , Anotación de Secuencia Molecular , Sapindaceae/citología , Sapindaceae/crecimiento & desarrollo , Sapindaceae/metabolismo , TranscriptomaRESUMEN
A novel, to the best of our knowledge, noise-immune cavity-enhanced optical heterodyne molecular spectrometry (NICE-OHMS) has been developed, utilizing optical feedback for laser-to-cavity locking with a common distributed-feedback diode laser. The system incorporates active control of the feedback phase and feedforward control of the laser current, allowing for consecutive laser frequency detuning by scanning a piezoelectric transducer (PZT) attached to the cavity. To enhance the fidelity of the spectroscopic signal, wavelength-modulated (wm) NICE-OHMS is implemented. Benefiting from the optical feedback, a modulation frequency of 15â kHz is achieved, surpassing the frequencies typically used in traditional NICE-OHMS setups. Then, the sub-Doppler-broadened wm-NICE-OHMS signal of acetylene at 1.53â µm is observed. A seven-fold improvement in signal to noise ratio has been demonstrated compared to NICE-OHMS alone and a limit of detection of 6.1 × 10-10cm-1 is achieved.
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This publisher's note contains a correction to Opt. Lett.49, 202 (2024)10.1364/OL.507004.
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BACKGROUND AND PURPOSE: Deep brain stimulation (DBS) has emerged as a promising treatment for movement disorders. This prospective study aims to evaluate the effects of bilateral subthalamic nucleus DBS (STN-DBS) on motor and non-motor symptoms in patients with primary Meige syndrome. METHODS: Thirty patients who underwent bilateral STN-DBS between April 2017 and June 2020 were included. Standardized and validated scales were utilized to assess the severity of dystonia, health-related quality of life, sleep, cognitive function and mental status at baseline and at 1 year and 3 years after neurostimulation. RESULTS: The Burke-Fahn-Marsden Dystonia Rating Scale movement scores showed a mean improvement of 63.0% and 66.8% at 1 year and 3 years, respectively, after neurostimulation. Similarly, the Burke-Fahn-Marsden Dystonia Rating Scale disability scores improved by 60.8% and 63.3% at the same time points. Postoperative quality of life demonstrated a significant and sustained improvement throughout the follow-up period. However, cognitive function, mental status, sleep quality and other neuropsychological functions did not change after 3 years of neurostimulation. Eight adverse events occurred in six patients, but no deaths or permanent sequelae were reported. CONCLUSIONS: Bilateral STN-DBS is a safe and effective alternative treatment for primary Meige syndrome, leading to improvements in motor function and quality of life. Nevertheless, it did not yield significant amelioration in cognitive, mental, sleep status and other neuropsychological functions after 3 years of neurostimulation.
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Estimulación Encefálica Profunda , Distonía , Trastornos Distónicos , Síndrome de Meige , Núcleo Subtalámico , Humanos , Síndrome de Meige/terapia , Síndrome de Meige/etiología , Distonía/terapia , Calidad de Vida , Estimulación Encefálica Profunda/efectos adversos , Estudios Prospectivos , Trastornos Distónicos/terapia , Resultado del Tratamiento , Globo PálidoRESUMEN
BACKGROUND: Construct deep learning models for colonoscopy quality control using different architectures and explore their decision-making mechanisms. METHODS: A total of 4,189 colonoscopy images were collected from two medical centers, covering different levels of bowel cleanliness, the presence of polyps, and the cecum. Using these data, eight pre-trained models based on CNN and Transformer architectures underwent transfer learning and fine-tuning. The models' performance was evaluated using metrics such as AUC, Precision, and F1 score. Perceptual hash functions were employed to detect image changes, enabling real-time monitoring of colonoscopy withdrawal speed. Model interpretability was analyzed using techniques such as Grad-CAM and SHAP. Finally, the best-performing model was converted to ONNX format and deployed on device terminals. RESULTS: The EfficientNetB2 model outperformed other architectures on the validation set, achieving an accuracy of 0.992. It surpassed models based on other CNN and Transformer architectures. The model's precision, recall, and F1 score were 0.991, 0.989, and 0.990, respectively. On the test set, the EfficientNetB2 model achieved an average AUC of 0.996, with a precision of 0.948 and a recall of 0.952. Interpretability analysis showed the specific image regions the model used for decision-making. The model was converted to ONNX format and deployed on device terminals, achieving an average inference speed of over 60 frames per second. CONCLUSIONS: The AI-assisted quality system, based on the EfficientNetB2 model, integrates four key quality control indicators for colonoscopy. This integration enables medical institutions to comprehensively manage and enhance these indicators using a single model, showcasing promising potential for clinical applications.
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Colonoscopía , Aprendizaje Profundo , Control de Calidad , Colonoscopía/normas , Humanos , Pólipos del Colon/diagnóstico por imagen , Pólipos del Colon/diagnósticoRESUMEN
This paper systematically studied the composition-controlled nonlinear optical properties and pulse modulation of ternary ReS2(1-x)Se2xalloys for the first time. The compositionally modulated characteristics of ReS2(1-x)Se2xon the band gap were simulated based on the first principles. We investigated the effect of the band gap on the saturable absorption properties. In addition, we demonstrated the modulation characteristics of different components ReS2(1-x)Se2xon 1.5µm Q-switched pulse performance. The Q-switched threshold, repetition rate, and pulse duration increase as the S(sulfur)-element composition rise. And pulse energy also was affected by the S(sulfur)-element composition. The ReS0.8Se1.2SA was selected to realize a conventional soliton with high energy in the all-fiber mode-locked laser. The pulse was centered at 1562.9 nm with a pulse duration of 2.26 ps, a repetition rate of 3.88 MHz, and maximum pulse energy of 1.95 nJ. This work suggests that ReS2(1-x)Se2xhas great potential in laser technology and nonlinear optics, and widely extends the material applications in ultrafast photonics.
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The temperature-dependent bend and twist elasticities of dsDNA, as well as their couplings, were explored through all-atom molecular dynamics simulations. Three rotational parameters, tilt, roll, and twist, were employed to assess the bend and twist elasticities through their stiffness matrix. Our analysis indicates that the bend and twist stiffnesses decrease as the temperature rises, primarily owing to entropic influences stemming from thermodynamic fluctuations. Furthermore, the couplings between these rotational parameters also exhibit a decline with increasing temperature, although the roll-twist coupling displays greater strength than the tilt-roll and tilt-twist couplings, attributed to its more robust correction component. We elucidated the influence of temperature on bend and twist elasticities based on the comparisons between various models and existing data.
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Hematopoietic toxicity due to ionizing radiation (IR) is a leading cause of death in nuclear incidents, occupational hazards, and cancer therapy. Oxymatrine (OM), an extract originating from the root of Sophora flavescens (Kushen), possesses extensive pharmacological properties. In this study, we demonstrate that OM treatment accelerates hematological recovery and increases the survival rate of mice subjected to irradiation. This outcome is accompanied by an increase in functional hematopoietic stem cells (HSCs), resulting in enhanced hematopoietic reconstitution abilities. Mechanistically, we observed significant activation of the MAPK signaling pathway, accelerated cellular proliferation, and decreased cell apoptosis. Notably, we identified marked increases in the cell cycle transcriptional regulator Cyclin D1 (Ccnd1) and the anti-apoptotic protein BCL2 in HSCs after OM treatment. Further investigation revealed that the expression of Ccnd1 transcript and BCL2 levels were reversed upon specific inhibition of ERK1/2 phosphorylation, effectively negating the rescuing effect of OM. Moreover, we determined that targeted inhibition of ERK1/2 activation significantly counteracted the regenerative effect of OM on human HSCs. Taken together, our results suggest a crucial role for OM in hematopoietic reconstitution following IR via MAPK signaling pathway-mediated mechanisms, providing theoretical support for innovative therapeutic applications of OM in addressing IR-induced injuries in humans.
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Alcaloides , Ratones , Humanos , Animales , Fosforilación , Alcaloides/farmacología , Transducción de Señal , Apoptosis , Proteínas Proto-Oncogénicas c-bcl-2/genéticaRESUMEN
Folic acid deficiency is common worldwide and is linked to an imbalance in gut microbiota. However, based on model animals used to study the utilization of folic acid by gut microbes, there are challenges of reproducibility and individual differences. In this study, an in vitro fecal slurry culture model of folic acid deficiency was established to investigate the effects of supplementation with 5-methyltetrahydrofolate (MTHF) and non-reduced folic acid (FA) on the modulation of gut microbiota. 16S rRNA sequencing results revealed that both FA (29.7%) and MTHF (27.9%) supplementation significantly reduced the relative abundance of Bacteroidetes compared with control case (34.3%). MTHF supplementation significantly improved the relative abundance of Firmicutes by 4.49%. Notably, compared with the control case, FA and MTHF supplementation promoted an increase in fecal levels of Lactobacillus, Bifidobacterium, and Pediococcus. Short-chain fatty acid (SCFA) analysis showed that folic acid supplementation decreased acetate levels and increased fermentative production of isobutyric acid. The in vitro fecal slurry culture model developed in this study can be utilized as a model of folic acid deficiency in humans to study the gut microbiota and demonstrate that exogenous folic acid affects the composition of the gut microbiota and the level of SCFAs. KEY POINTS: ⢠Establishment of folic acid deficiency in an in vitro culture model. ⢠Folic acid supplementation regulates intestinal microbes and SCFAs. ⢠Connections between microbes and SCFAs after adding folic acid are built.
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Deficiencia de Ácido Fólico , Microbioma Gastrointestinal , Animales , Humanos , Ácido Fólico , Fermentación , ARN Ribosómico 16S/genética , Reproducibilidad de los Resultados , Ácidos Grasos VolátilesRESUMEN
OBJECTIVE: The aim of this study was to develop and validate an interpretable and highly generalizable multimodal radiomics model for predicting the prognosis of patients with cerebral hemorrhage. METHODS: This retrospective study involved 237 patients with cerebral hemorrhage from 3 medical centers, of which a training cohort of 186 patients (medical center 1) was selected and 51 patients from medical center 2 and medical center 3 were used as an external testing cohort. A total of 1762 radiomics features were extracted from nonenhanced computed tomography using Pyradiomics, and the relevant macroscopic imaging features and clinical factors were evaluated by 2 experienced radiologists. A radiomics model was established based on radiomics features using the random forest algorithm, and a radiomics-clinical model was further trained by combining radiomics features, clinical factors, and macroscopic imaging features. The performance of the models was evaluated using area under the curve (AUC), sensitivity, specificity, and calibration curves. Additionally, a novel SHAP (SHAPley Additive exPlanations) method was used to provide quantitative interpretability analysis for the optimal model. RESULTS: The radiomics-clinical model demonstrated superior predictive performance overall, with an AUC of 0.88 (95% confidence interval, 0.76-0.95; P < 0.01). Compared with the radiomics model (AUC, 0.85; 95% confidence interval, 0.72-0.94; P < 0.01), there was a 0.03 improvement in AUC. Furthermore, SHAP analysis revealed that the fusion features, rad score and clinical rad score, made significant contributions to the model's decision-making process. CONCLUSION: Both proposed prognostic models for cerebral hemorrhage demonstrated high predictive levels, and the addition of macroscopic imaging features effectively improved the prognostic ability of the radiomics-clinical model. The radiomics-clinical model provides a higher level of predictive performance and model decision-making basis for the risk prognosis of cerebral hemorrhage.
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Three new neutral and ionic phosphorescent iridium(III) complexes were successfully prepared using 1-(6-methoxynaphthalen-2-yl)isoquinoline as the main ligand, while the auxiliary ligand was 2-(2-1H-imidazolyl)pyridine. Three complexes (Ir1, Ir2, Ir3) showed red emission, peaking at 610, 609, and 615 nm, respectively, and they exhibited good solubility and excellent photophysical properties in different solvents, which is suitable to prepare organic light-emitting diodes (OLEDs) by solution method. Among the three OLEDs prepared by iridium(III) complexes using the solution method, the device based on Ir2 possessed better electroluminescent properties, and its maximum brightness, current efficiency (CE), power efficiency (PE), and the maximum external quantum efficiency (EQE) were 507.2 cd m-2 , 0.14 cd A-1 , 0.06 lm W-1 , and 0.14%. respectively, proving that the three complexes have a certain of potential for OLEDs applications and are expected to expand the applications of iridium(III) complexes for OLEDs.
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Iridio , Ligandos , Iones , Solubilidad , SolventesRESUMEN
Calycosin (Caly), a flavonoid compound, demonstrates a variety of beneficial properties. However, the specific mechanisms behind Caly's anticancer effects remain largely unexplored. Network pharmacology was used to explore the potential targets of Caly in renal cancer. Additionally, RNA-seq sequencing was used to detect changes in genes in renal cancer cells after Caly treatment. Validation was carried out through quantitative reverse transcription-PCR and Western blot analysis. The luciferase reporter assay was applied to pinpoint the interaction site between MAZ and HAS2. Furthermore, the immunoprecipitation assay was utilized to examine the ubiquitination and degradation of MAZ. In vivo experiments using cell line-derived xenograft mouse models were performed to assess Calycosin's impact on cancer growth. Network pharmacology research suggests Caly plays a role in promoting apoptosis and inhibiting cell adhesion in renal cancer. In vitro, Caly has been observed to suppress proliferation, colony formation, and metastasis of renal cancer cells while also triggering apoptosis. Additionally, it appears to diminish hyaluronic acid synthesis by downregulating HAS2 expression. MAZ is identified as a transcriptional regulator of HAS2 expression. Calycosin further facilitates the degradation of MAZ via the ubiquitin-proteasome pathway. Notably, Caly demonstrates efficacy in reducing the growth of renal cell carcinoma xenograft tumors in vivo. Our findings indicate that Caly suppresses the proliferation, metastasis, and progression of renal cell carcinoma through its action on the MAZ/HAS2 signaling pathway. Thus, Caly represents a promising therapeutic candidate for the treatment of renal cell carcinoma.
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Non-coding RNAs (ncRNAs) induced competing endogenous RNAs (ceRNA) play crucial roles in various biological process by regulating target gene expression. However, the studies of ceRNA networks in the regulation of ovarian ovulation processing of chicken remains deficient compared to that in mammals. Our present study revealed that circEML1 was differential expressed in hen's ovarian tissues at different ages (15 W/20 W/30 W/68 W) and identified as a loop structure from EML1 pre-mRNA, which promoted the expressions of CYP19A1/StAR and E2/P4 secretion in follicular granulosa cells (GCs). Furthermore, circEML1 could serve as a sponge of gga-miR-449a and also found that IGF2BP3 was targeted by gga-miR-449a to co-participate in the steroidogenesis, which possibly act the regulatory role via mTOR/p38MAPK pathways. Meanwhile, in the rescue experiment, gga-miR-449a could reverse the promoting role of circEML1 to IGF2BP3 and steroidogenesis. Eventually, this study suggested that circEML1/gga-miR-449a/IGF2BP3 axis exerted an important role in the steroidogenesis in GCs of chicken.