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Introduction: Scleroderma bovista can form symbiotic ectomycorrhizal fungi with hazel roots. The mechanism through which S. bovista promotes hazelnut growth remains unclear. Methods: This study aimed to evaluate the effect of ectomycorrhizal fungus S. bovista on the growth and development of hazel roots and gene expression changes through comparative transcriptome analysis. Results: After inoculation with S. bovista, the fungus symbiotically formed ectomycorrhiza with hazel roots. The fresh weights of the aboveground and underground parts of My treatment (inoculated with S. bovista and formed mycorrhiza) were much higher than those of the control, respectively. The length, project area, surface area, volume, forks, and diameter of the inoculated seedlings root were 1.13 to 2.48 times higher than those of the control. In the paired comparison, 3,265 upregulated and 1,916 downregulated genes were identified. The most significantly enriched Gene Ontology term for the upregulated Differentially Expressed Genes was GO:0005215 (transporter activity). Immunohistochemical analysis suggested that the expression levels of auxin and Auxin Response Factor9 were significantly increased by S. bovista after the formation of mycorrhizal fungi in hazelnut root tips. Discussion: These results indicate that genes related to auxin biosynthesis, transport and signaling, and transport of nutrients may contribute to root development regulation in hazel ectomycorrhiza.
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Understanding the mechanical characteristics of rocks when subjected to direct tension is crucial for assessing the stability of rock formations. Within the scope of this research, a series of tests was conducted using Tage tuff to assess the deformation behavior and crack extension of rock under direct tension. The axial, lateral, and shear strain fields as well as crack propagation, localized deformation behavior, and failure mode of the rocks were analyzed using three-dimensional digital image correlation method. The results showed that the axial strain fields on the specimen surface were heterogeneous, with different locations and localization occurring in the pre-peak stage, which was similar to the evolution of shear strain, whereas the lateral strain only showed slight changes. The crack extension direction was inferred, indicating that both tensile and shear stress occurred in the tests. Furthermore, different stress-strain responses were observed for the inside and outside of the localized bands. Then, the surface patterns of specimen failure were scanned and analyzed to assess the failure mode and residual strength of the specimen under direct tensile stress. Finally, the results of direct tension, uniaxial compression, and Brazilian split tests for Tage tuff were compared, and the complete stress-strain curve of uniaxial tension (UT) was simulated using a nonlinear-variable-compliance constitutive equation. This study provides a deeper understanding into the damage behavior of rocks under direct tension.
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Plants NADP-malic enzymes (NADP-MEs) act as a class of oxidative decarboxylase to mediate malic acid metabolism in organisms. Despite NADP-MEs have been demonstrated to play pivotal roles in regulating diverse biological processes, the role of NADP-MEs involving in plant growth and development remains rarely known. Here, we characterized the function of rice cytosolic OsNADP-ME2 in regulating plant height. The results showed that RNAi silencing and knock-out of OsNADP-ME2 in rice results in a dwarf plant structure, associating with significant expression inhibition of genes involving in phytohormone Gibberellin (GA) biosynthesis and signaling transduction, but with up-regulation for the expression of GA signaling suppressor SLR1. The accumulation of major bioactive GA1, GA4 and GA7 are evidently altered in RNAi lines, and exogenous GA treatment compromises the dwarf phenotype of OsNADP-ME2 RNAi lines. RNAi silencing of OsNADP-ME2 also causes the reduction of NADP-ME activity associating with decreased production of pyruvate. Thus, our data revealed a novel function of plant NADP-MEs in modulation of rice plant height through regulating bioactive GAs accumulation and GA signaling, and provided a valuable gene resource for rice plant architecture improvement.
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Self-assembled peptides have been among the important biomaterials due to its excellent biocompatibility and diverse functions. Over the past decades, substantial progress and breakthroughs have been made in designing self-assembled peptides with multifaceted biomedical applications. The techniques for quantitative analysis, including imaging-based quantitative techniques, chromatographic technique and computational approach (molecular dynamics simulation), are becoming powerful tools for exploring the structure, properties, biomedical applications, and even supramolecular assembly processes of self-assembled peptides. However, a comprehensive review concerning these quantitative techniques remains scarce. In this review, recent progress in techniques for quantitative investigation of biostability, cellular uptake, biodistribution, self-assembly behaviors of self-assembled peptide etc., are summarized. Specific applications and roles of these techniques are highlighted in detail. Finally, challenges and outlook in this field are concluded. It is believed that this review will provide technical guidance for researchers in the field of peptide-based materials and pharmaceuticals, and facilitate related research for newcomers in this field.
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According to the synaptic homeostasis hypothesis (SHY), sleep serves to renormalize synaptic connections that have been potentiated during the prior wake phase due to ongoing encoding of information. SHY focuses on glutamatergic synaptic strength and has been supported by numerous studies examining synaptic structure and function in neocortical and hippocampal networks. However, it is unknown whether synaptic down-regulation during sleep occurs in the hypothalamus, i.e., a pivotal center of homeostatic regulation of bodily functions including sleep itself. We show that sleep, in parallel with the synaptic down-regulation in neocortical networks, down-regulates the levels of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) in the hypothalamus of rats. Most robust decreases after sleep were observed at both sites for AMPARs containing the GluA1 subunit. Comparing the effects of selective rapid eye movement (REM) sleep and total sleep deprivation, we moreover provide experimental evidence that slow-wave sleep (SWS) is the driving force of the down-regulation of AMPARs in hypothalamus and neocortex, with no additional contributions of REM sleep or the circadian rhythm. SWS-dependent synaptic down-regulation was not linked to EEG slow-wave activity. However, spindle density during SWS predicted relatively increased GluA1 subunit levels in hypothalamic synapses, which is consistent with the role of spindles in the consolidation of memory. Our findings identify SWS as the main driver of the renormalization of synaptic strength during sleep and suggest that SWS-dependent synaptic renormalization is also implicated in homeostatic control processes in the hypothalamus.
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The radiation-induced skin injury (RISI) remains a great challenge for clinical wound management and care after radiotherapy, as patients will suffer from the acute radiation injury and long-term chronic inflammatory damage during the treatment. The excessive ROS in the early acute stage and prolonged inflammatory response in the late healing process always hinder therapeutic efficiency. Herein, we developed an extracellular matrix (ECM)-mimetic multifunctional glycopeptide hydrogel (oCP@As) to promote and accelerate RISI repair via a dual-modulation strategy in different healing stages. The oCP@As hydrogel not only can form an ECM-like nanofiber structure through the Schiff base reaction but also exhibits ROS scavenging and DNA double-strand break repair abilities, which can effectively reduce the acute radiation damage. Meanwhile, the introduction of oxidized chondroitin sulfate, which is the ECM polysaccharide-like component, enables regulation of the inflammatory response by adsorption of inflammatory factors, accelerating the repair of chronic inflammatory injury. The animal experiments demonstrated that oCP@As can significantly weaken RISI symptoms, promote epidermal tissue regeneration and angiogenesis, and reduce pro-inflammatory cytokine expression. Therefore, this multifunctional glycopeptide hydrogel dressing can effectively attenuate RISI symptoms and promote RISI healing, showing great potential for clinical applications in radiotherapy protection and repair.
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Glicopéptidos , Hidrogeles , Traumatismos por Radiación , Piel , Cicatrización de Heridas , Animales , Hidrogeles/química , Hidrogeles/farmacología , Glicopéptidos/química , Glicopéptidos/farmacología , Glicopéptidos/uso terapéutico , Piel/efectos de los fármacos , Piel/efectos de la radiación , Piel/patología , Traumatismos por Radiación/tratamiento farmacológico , Traumatismos por Radiación/prevención & control , Cicatrización de Heridas/efectos de los fármacos , Ratones , Humanos , Matriz Extracelular/metabolismo , Matriz Extracelular/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , MasculinoRESUMEN
Anoplophora glabripennis (ALB) is one of the most devastating wood boring insects of poplars. Populus deltoides 'Shalinyang (PdS), a new poplar variety, shows strong resistance to ALB infestation. However, the molecular mechanism of insect resistance in PdS is unclear. Here, we found that lignan content was much higher in PdS phloem after ALB infestation than in healthy trees, and that adding lignan to artificial diet significantly reduced: larval weight; digestive enzyme activity (cellulase [CL], polygalacturonase [PG]); detoxification enzyme activity (carboxylesterase [CarE], glutathione S-transferase [GSH-ST]); and defense enzyme activity (Catalase [CAT]). We further identified the lignan biosynthesis-related PdPLR1 gene (Pinoresinol-lariciresinol reductase, PLR) based on transcriptome analysis, and it was significantly up-regulated in the PdS phloem attacked by ALB. Overexpression of PdPLR1 in Arabidopsis increased th lignan content. In contrast, silencing PdPLR1 in PdS significantly decreased expression levels of PdPLR1 and lignan content by 82.45% and 56.85%. However, silencing PdPLR1 increased the number of adults ovipositions and eggs hatching. The activity of CL, PG, CarE, GSH-ST and CAT and the biomass of larvae fed on phloem of PdS with silenced PdPLR1 were significantly higher than in the control. Taken together, up regulation of PdPLR1 enhanced PdS resistance to ALB by regulating lignan synthesis. Our findings provide in-depth insights into the molecular mechanisms of PdS-ALB interactions, which lay the foundation for understanding of defense in poplars to pest infection.
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Lignanos , Proteínas de Plantas , Populus , Lignanos/biosíntesis , Lignanos/metabolismo , Populus/genética , Populus/metabolismo , Animales , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Regulación de la Expresión Génica de las Plantas , Arabidopsis/genética , Arabidopsis/metabolismo , Larva , Plantas Modificadas Genéticamente , Escarabajos/metabolismoRESUMEN
Using computer vision technology to estimate pig live weight is an important method to realize pig welfare. But there are two key issues that affect pigs' weight estimation: one is the uneven illumination, which leads to unclear contour extraction of pigs, and the other is the bending of the pig body, which leads to incorrect pig body information. For the first one, Mask R-CNN was used to extract the contour of the pig, and the obtained mask image was converted into a binary image from which we were able to obtain a more accurate contour image. For the second one, the body length, hip width and the distance from the camera to the pig back were corrected by XGBoost and actual measured information. Then we analyzed the rationality of the extracted features. Three feature combination strategies were used to predict pig weight. In total, 1505 back images of 39 pigs obtained using Azure kinect DK were used in the numerical experiments. The highest prediction accuracy is XGBoost, with an MAE of 0.389, RMSE of 0.576, MAPE of 0.318% and R2 of 0.995. We also recommend using the Mask R-CNN + RFR method because it has fairly high precision in each strategy. The experimental results show that our proposed method has excellent performance in live weight estimation of pigs.
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Pharmacokinetic changes induced by radiation following radiotherapy ("RT-PK" phenomenon) are of great significance to the effectiveness and safety of chemotherapeutic agents in clinical settings. The aims of this study were to clarify the organic anion transporters (Oats) involved in the "RT-PK" phenomenon of bestatin in rats following X-ray irradiation and to elucidate its potential mechanism via vitamin D signalling. Pharmacokinetic studies, uptake assays using rat kidney slices and primary proximal tubule cells, and molecular biological studies were performed. Significantly increased plasma concentrations and systemic exposure to bestatin were observed at 24 and 48 h following abdominal X-ray irradiation, regardless of oral or intravenous administration of the drugs in rats. Reduced renal clearance and cumulative urinary excretion of bestatin were observed at 24 and 48 h post-irradiation in rats following intravenous administration. The uptake of the probe substrates p-aminohippuric acid and oestrone 3-sulfate sodium in vitro and the expression of Oat1 and Oat3 in vivo were reduced in the corresponding models following irradiation. Moreover, the upregulation of the vitamin D receptor (Vdr) in mRNA and protein levels negatively correlated with the expressions and functions of Oat1 and Oat3 following irradiation. Additionally, elevated plasma urea nitrogen levels and histopathological changes were observed in rats after exposure to irradiation. The "RT-PK" phenomenon of bestatin occurs in rats after exposure to irradiation, possibly resulting in the regulation of the expressions and activities of renal Oats via activation of the Vdr signalling pathway.
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Regulación hacia Abajo , Riñón , Receptores de Calcitriol , Animales , Ratas , Receptores de Calcitriol/metabolismo , Masculino , Riñón/metabolismo , Riñón/efectos de la radiación , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/efectos de la radiación , Ratas Sprague-Dawley , Rayos X , Proteína 1 de Transporte de Anión Orgánico/metabolismo , Proteína 1 de Transporte de Anión Orgánico/genética , Transportadores de Anión Orgánico/metabolismo , Túbulos Renales Proximales/metabolismo , Túbulos Renales Proximales/efectos de la radiación , Túbulos Renales Proximales/efectos de los fármacos , Leucina/análogos & derivadosRESUMEN
Although seminal plasma extracellular vesicles (SPEVs) play important roles in sperm function, little is known about their metabolite compositions and roles in sperm motility. Here, we performed metabolomics and proteomics analysis of boar SPEVs with high or low sperm motility to investigate specific biomarkers affecting sperm motility. In total, 140 proteins and 32 metabolites were obtained through differentially expressed analysis and weighted gene coexpression network analysis (WGCNA). Seven differentially expressed proteins (DEPs) (ADIRF, EPS8L1, PRCP, CD81, PTPRD, CSK, LOC100736569) and six differentially expressed metabolites (DEMs) (adenosine, beclomethasone, 1,2-benzenedicarboxylic acid, urea, 1-methyl-l-histidine, and palmitic acid) were also identified in WGCNA significant modules. Joint pathway analysis revealed that three DEPs (GART, ADCY7, and NTPCR) and two DEMs (urea and adenosine) were involved in purine metabolism. Our results suggested that there was significant correlation between proteins and metabolites, such as IL4I1 and urea (r = 0.86). Furthermore, we detected the expression level of GART, ADCY7, and CDC42 in sperm of two groups, which further verified the experimental results. This study revealed that several proteins and metabolites in SPEVs play important roles in sperm motility. Our results offered new insights into the complex mechanism of sperm motility and identified potential biomarkers for male reproductive diseases.
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In order to address this gap in knowledge, the present study utilized both in vivo and in vitro models to investigate the role of the m6A demethylase ALKBH5 in protecting against cerebral I/R injury by inhibiting PANoptosis (Pytoptosis, Ppoptosis, and Necroptosis) in an m6A-dependent manner. They observed that ALKBH5, the predominant m6A demethylase, was downregulated in these models, while SNHG3 and PANoptosis-related proteins (ZBP1, AIM2, Cappase-3, Caspase-8, cleaved Caspase-1, GSDMD-N, and p-MLKL) were elevated. Additionally, both ALKBH5 overexpression and SNHG3-deficiency were found to ameliorate PANoptosis and injury induced by OGD/reperfusion and OGD/RX in both mice tissues and astrocyte cells. Further experiments demonstrated that ALKBH5 induced m6A-demethylation in SNHG3, leading to its degradation. Low expression of SNHG3, on the other hand, prevented the formation of the SNHG3-ELAVL1-ZBP1/AIM2 complex, which in turn destabilized ZBP1 and AIM2 mRNA, resulting in the downregulation of these PANoptosis-related genes. Ultimately, the rescue experiments provided evidence that ALKBH5 protected against PANoptosis in cerebral I/R injury models through the inhibition of SNHG3.This study sheds light on the intricate molecular mechanisms involved in the pathogenesis of cerebral I/R injury and highlights the potential of m6A-related genes as therapeutic targets in this condition.
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Desmetilasa de ARN, Homólogo 5 de AlkB , Daño por Reperfusión , Animales , Desmetilasa de ARN, Homólogo 5 de AlkB/metabolismo , Desmetilasa de ARN, Homólogo 5 de AlkB/genética , Ratones , Daño por Reperfusión/genética , Daño por Reperfusión/metabolismo , Daño por Reperfusión/prevención & control , Adenosina/análogos & derivados , Adenosina/metabolismo , Masculino , ARN Largo no Codificante/genética , Humanos , Apoptosis , Modelos Animales de EnfermedadRESUMEN
NUT Carcinomaï¼NCï¼ is a rare malignant tumor of unknown origin, which is highly aggressive. It is characterized by chromosome rearrangement accompanied by NUTM1 gene. The pathological manifestations were sudden and focal squamous in poorly differentiated or undifferentiated carcinoma. NUTM1gene rearrangement can be used to diagnose NC. The prognosis of NUT cancer is poor. Clinically, there is no established treatment plan. treatment options mainly comprise surgery, radiotherapy and chemotherapy. A 74-year-old patient with NC of the nasal cavity and sinuses was reported. Her clinical presentation was right nasal congestion with facial swelling. Sinus CT and MRI showed soft tissue density in the right nasal cavity and maxillary sinus with bone destruction. After admission, the patient underwent nasal endoscopic biopsy, and the postoperative pathological FISH staining showed BRD4/NUT fusion tï¼15, 19ï¼. The tumor was significantly reduced after two courses of sequential chemoradiotherapy. Two months later, the patient underwent a partial maxillary resection due to the rapid regrowth of sinusoidal mass, invading the hard palate. The patient died 2 months after surgery due to multiple organ failure resulted from tumor metastasis, with a survival time of 11 months. The clinical characteristics, diagnosis and treatment of this case were reported and related literature was reviewed.
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Cavidad Nasal , Neoplasias Nasales , Humanos , Anciano , Femenino , Cavidad Nasal/patología , Neoplasias Nasales/terapia , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Proteínas de Fusión Oncogénica/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Resultado Fatal , CarcinomaRESUMEN
Thyroid cancer is the most common type of endocrine cancer, and most patients have a good prognosis. However, the thyroid cancer differentiation status strongly affects patient response to conventional treatment and prognosis. Therefore, exploring the molecular mechanisms that influence the differentiation of thyroid cancer is very important for understanding the progression of this disease and improving therapeutic options. In this study, SETMAR as a key gene that affects thyroid cancer differentiation is identified. SETMAR significantly regulates the proliferation, epithelial-mesenchymal transformation (EMT), thyroid differentiation-related gene expression, radioactive iodine uptake, and sensitivity to MAPK inhibitor-based redifferentiation therapies of thyroid cancer cells. Mechanistically, SETMAR methylates dimethylated H3K36 in the SMARCA2 promoter region to promote SMARCA2 transcription. SMARCA2 can bind to enhancers of the thyroid differentiation transcription factors (TTFs) PAX8, and FOXE1 to promote their expression by enhancing chromatin accessibility. Moreover, METTL3-mediated m6A methylation of SETAMR mRNA is observed and showed that this medication can affect SETMAR expression in an IGF2BP3-dependent manner. Finally, the METTL3-14-WTAP activator effectively facilitates the redifferentiation of thyroid cancer cells via the SETMAR-SMARCA2-TTF axis utilized. The research provides novel insights into the molecular mechanisms underlying thyroid cancer dedifferentiation and provides a new approach for therapeutically promoting redifferentiation.
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Diferenciación Celular , Ensamble y Desensamble de Cromatina , Neoplasias de la Tiroides , Factores de Transcripción , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/patología , Humanos , Diferenciación Celular/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Ensamble y Desensamble de Cromatina/genética , Ratones , Animales , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/genética , Transición Epitelial-Mesenquimal/genética , Proliferación Celular/genética , Modelos Animales de EnfermedadRESUMEN
PURPOSE: This study aimed to investigate the effectiveness and safety of endovascular revascularisation of intracranial artery occlusion and stenosis in moyamoya disease using stent angioplasty. MATERIALS AND METHODS: We recruited 12 patients (8 women and 4 men) with occlusion and stenosis of intracranial arteries in the context of moyamoya disease who underwent endovascular stent angioplasty. Clinical data, baseline conditions, lesion location, treatment outcomes, periprocedural complications, and follow-up outcomes were analysed. RESULTS: The occlusion was located at the M1 segment of the middle cerebral artery in 8 patients, at both the M1 and A2 segments in one patient, and at the C7 segment of the internal carotid artery in 3. Thirteen stents were deployed at the occlusion site, including the low-profile visualized intraluminal support (LVIS) device in 8 patients, an LVIS device and a Solitaire AB stent in one, and a Leo stent in 3, with a success rate of 100% and no intraprocedural complications. Plain CT imaging after stenting revealed leakage of contrast agent, which disappeared on the second day, resulting in no clinical symptoms or neurological sequelae. Follow-up angiography studies were performed in all patients for 6-12 months (mean, 8.8). Slight asymptomatic in-stent stenosis was observed in 2 patients (16.7%), and no neurological deficits were observed in the other patients. All preoperative ischaemic symptoms completely disappeared at follow-up. CONCLUSION: Stent angioplasty is a safe and effective treatment for occlusion and stenosis of intracranial arteries in moyamoya disease.
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Procedimientos Endovasculares , Enfermedad de Moyamoya , Stents , Humanos , Enfermedad de Moyamoya/cirugía , Femenino , Masculino , Adulto , Resultado del Tratamiento , Persona de Mediana Edad , Angioplastia , Adulto Joven , AdolescenteRESUMEN
G protein-coupled receptors (GPCRs) are a large family of cell membrane proteins that are important targets for drug discovery. Nanobodies, also known as VHH (variable domains of heavy chain-only antibodies, HcAbs) antibodies, are small antibody fragments derived from camelids that have gained significant attention as potential therapeutics for targeting GPCRs due to their advantages over conventional antibodies. However, there are challenges in developing nanobodies targeting GPCRs, among which epitope accessibility is the most significant because the cell membrane partially shields the GPCR surface. We developed a universal protocol for making nanobodies targeting GPCRs using the cell membrane extract of GPCR-overexpressing HEK293 cells as the llama/alpaca immunization antigen. We constructed an immune VHH library and identified nanobodies by phage display bio-panning. The monoclonal nanobodies were recombinantly expressed in Escherichia coli (E. coli) and purified to characterize their binding potency.
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Background: The claustrum (CLA), a subcortical area between the insular cortex and striatum, innervates almost all cortical regions of the mammalian brain. There is growing evidence that CLA participates in many brain functions, including memory, cognition, and stress response. It is proposed that dysfunction or malfunction of the CLA might be the pathology of some brain diseases, including stress-induced depression and anxiety. However, the role of the CLA in fear memory and anxiety disorders remains largely understudied. Methods: We evaluated the influences of neurotoxic lesions of the CLA using auditory-cued fear memory and anxiety-like behaviors in rats. Results: We found that lesions of anterior CLA (aCLA) but not posterior CLA (pCLA) before fear conditioning attenuated fear retrieval, facilitated extinction, and reduced freezing levels during the extinction retention test. Post-learning lesions of aCLA but not pCLA facilitated fear extinction and attenuated freezing behavior during the extinction retention test. Lesions of aCLA or pCLA did not affect anxiety-like behaviors evaluated by the open field test and elevated plus-maze test. Conclusion: These data suggested that aCLA but not pCLA was involved in fear memory and extinction. Future studies are needed to further investigate the anatomical and functional connections of aCLA subareas that are involved in fear conditioning, which will deepen our understanding of CLA functions.
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Autologous nerve transplantation (ANT) is currently considered the gold standard for treating long-distance peripheral nerve defects. However, several challenges associated with ANT, such as limited availability of donors, donor site injury, mismatched nerve diameters, and local neuroma formation, remain unresolved. To address these issues comprehensively, we have developed porous poly(lactic-co-glycolic acid) (PLGA) electrospinning fiber nerve guide conduits (NGCs) that are optimized in terms of alignment and conductive coating to facilitate peripheral nerve regeneration (PNR) under electrical stimulation (ES). The physicochemical and biological properties of aligned porous PLGA fibers and poly(3,4-ethylenedioxythiophene):polystyrene sodium sulfonate (PEDOT:PSS) coatings were characterized through assessments of electrical conductivity, surface morphology, mechanical properties, hydrophilicity, and cell proliferation. Material degradation experiments demonstrated the biocompatibility in vivo of electrospinning fiber films with conductive coatings. The conductive NGCs combined with ES effectively facilitated nerve regeneration. The designed porous aligned NGCs with conductive coatings exhibited suitable physicochemical properties and excellent biocompatibility, thereby significantly enhancing PNR when combined with ES. This combination of porous aligned NGCs with conductive coatings and ES holds great promise for applications in the field of PNR.