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The mouse femur, particularly the distal femur, is commonly utilized in orthopedic research. Despite its significance, little is known about the key events involved in the postnatal development of the distal femur. Therefore, investigating the development process of the mouse distal femur is of great importance. In this study, distal femurs of CD-1 mice aged 1, 2, 4, 6, and 8 weeks were examined. We found that the width and height of the distal femur continued to increase till the 4th week, followed with stabilization. Notably, the width to height ratio remained relatively consistent with age. Micro computed tomography analysis demonstrated gradual increases in bone volume/tissue volume, trabecular number, and trabecular thickness from 1 to 6 weeks, alongside a gradual decrease in trabecular separation. Histological analysis further indicated the appearance of the secondary ossification center at approximately 2 weeks, with ossification mostly completed by 4 weeks, leading to the formation of a prototype epiphyseal plate. Subsequently, the epiphyseal plate gradually narrowed at 6 and 8 weeks. Moreover, the thickness and maturity of the bone cortex surrounding the epiphyseal plate increased over time, reaching peak cortical bone density at 8 weeks. In conclusion, to enhance model stability and operational ease, we recommend constructing conventional mouse models of the distal femur between 4 and 8 weeks old.
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Fêmur , Animais , Fêmur/metabolismo , Fêmur/diagnóstico por imagem , Fêmur/crescimento & desenvolvimento , Camundongos , Microtomografia por Raio-X , Lâmina de Crescimento/metabolismo , Lâmina de Crescimento/crescimento & desenvolvimento , Lâmina de Crescimento/diagnóstico por imagem , Densidade Óssea , Desenvolvimento Ósseo , Osteogênese , MasculinoRESUMO
Objective: To observe the effect of oral Quma Tongluo decoction on oxaliplatin-related chronic peripheral neuropathy. Methods: A total of 64 patients who met the inclusion criteria were randomly divided into an experimental group and a control group, with 32 cases in each group. The experimental group took Quma Tongluo decoction granules orally (2 times a day, 1 package each time, morning and evening after meals), and the control group took mecobalamin tablets orally (1 tablet each time, 3 times a day, after meals). After 4 weeks of treatment, the quantitative score of chronic peripheral neuropathy severity, a quantitative score of numbness, a quantitative score of pain, a chemotherapeutic peripheral neurotoxicity score, comprehensive neuropathy score, peripheral neurotoxicity grade, KPS score, and neuropathy area range score were compared between the two groups before and after treatment. Results: Before treatment, there were no significant differences between the two groups in the quantitative score of chronic peripheral neuropathy severity, quantitative score of numbness, chemotherapeutic peripheral neurotoxicity score, total neuropathy score, peripheral neurotoxicity grade, and chronic OIPN symptom range score (P > .05). After 4 weeks of treatment, there were significant differences in the quantitative score of chronic peripheral neuropathy severity, quantitative score of numbness, chemotherapeutic peripheral neurotoxicity score, total neuropathy score, peripheral neurotoxicity grade, and chronic OIPN symptom range score between the two groups (P < .05). There was no significant difference in pain quantification score and KPS score between the two groups before and after treatment (P > .05). The total effective rate of Quma Tongluo decoction in the treatment of oxaliplatin-related chronic peripheral neuropathy was higher than that of mecobalamin (87.1% > 20.6%), and no obvious adverse reactions such as Gastrointestinal reactions and allergic reactions were observed.One patient in the experimental group had diarrhea, the incidence of adverse reactions was about 3.2%, and the control group had no adverse reactions. Conclusions: Quma Tongluo decoction can effectively treat oxaliplatin-related chronic peripheral neuropathy, reduce the symptoms while reducing the scope of symptoms, and has no obvious adverse reactions in clinical practice, with good safety.
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This study aimed to develop a relatively natural and safe botanical insecticide for controlling the storage pest Tribolium castaneum in the egg and pupal stages. It examined how Elsholtzia densa Benth. essential oil (EO) and its primary components, ß-caryophyllene and limonene, affected T. castaneum eggs and pupae through contact and fumigation. Among th, the contact activities of ß-caryophyllene against T. castaneum eggs and pupae are LD50 (median lethal dose, 50%) = 0.156 mg/cm2 and ED50 (median effective dose, 50%) = 16.35 mg/pupa respectively. The study also investigated the effect of ß-caryophyllene and limonene on T. castaneum eggs and pupae through synergistic contact and fumigation. When the mixing ratio of ß-caryophyllene and limonene was 7:1, the LD50 value of contact activity against T. castaneum eggs was reduced to 0.100 mg/cm2, displaying an obvious synergistic effect. Experiments were conducted to investigate the antitoxic effect of ß-caryophyllene on T. castaneum eggs and pupae, as well as its effects on the enzymatic activity of acetylcholinesterase, succinate dehydrogenase, glutathione S-transferase and carboxylesterase in T. castaneum pupae. Finally, the molecular docking techniques were employed to confirm the aforementioned effects on enzyme function. The findings of this study might help improve storage pest control with T. castaneum and create eco-friendly insecticides using E. densa EO, ß-caryophyllene, and limonene.
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Inseticidas , Lamiaceae , Óleos Voláteis , Pupa , Tribolium , Animais , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Tribolium/efeitos dos fármacos , Lamiaceae/química , Inseticidas/farmacologia , Inseticidas/química , Pupa/efeitos dos fármacos , Óvulo/efeitos dos fármacos , Limoneno/farmacologia , Sesquiterpenos Policíclicos/farmacologia , Sesquiterpenos Policíclicos/químicaRESUMO
Investigations have shown that storage bugs seriously harm grains during storage. In the interim, essential oils (EOs) have been proven to be a good botanical pesticide. The anti-Lasioderma serricorne properties of Elsholtzia ciliata essential oil, which was obtained by steam distillation, were evaluated using DL-limonene, carvone, and their two optical isomer components using contact, repelling, and fumigation techniques. Simultaneously, the fumigation, contact, and repellent activities of carvone and its two optical isomers mixed with DL-limonene against L. serruricorne were evaluated. The results showed that E. ciliata, its main components (R-carvone, DL-limonene), and S-carvone exhibited both fumigations (LC50 = 14.47, 4.42, 20.9 and 3.78 mg/L) and contact (LD50 = 7.31, 4.03, 28.62 and 5.63 µg/adult) activity against L.serricorne. A binary mixture (1:1) of R-carvone and DL-limonene displayed an obvious synergistic effect. A binary mixture (1:1) of carvone and its two optical isomers exhibited an obvious synergistic effect, too. Furthermore, the repellent activity of the EO, carvone, and its two optical isomers, DL-limonene, and a combination of them varied. To stop insect damage during storage, E. ciliata and its components can be utilized as bio-insecticides.
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Inseticidas , Lamiaceae , Óleos Voláteis , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Lamiaceae/química , Animais , Inseticidas/química , Inseticidas/farmacologia , Limoneno/química , Limoneno/farmacologia , Repelentes de Insetos/química , Repelentes de Insetos/farmacologia , Monoterpenos Cicloexânicos/química , Monoterpenos Cicloexânicos/farmacologia , Sinergismo Farmacológico , FumigaçãoRESUMO
To assess bioequivalence of locally acting suspension-based nasal sprays, the U.S. FDA currently recommends a weight-of-evidence approach. In addition to in vitro and human pharmacokinetic (PK) studies, this includes a comparative clinical endpoint study to ensure equivalent bioavailability of the active pharmaceutical ingredient (API) at the site of action. The present study aimed to assess, within an in vitro/in vivo correlation paradigm, whether PK studies and dissolution kinetics are sensitive to differences in drug particle size for a locally acting suspension-based nasal spray product. Two investigational suspension-based nasal formulations of mometasone furoate (MF-I and MF-II; delivered dose: 180 µg) differed in API particle size and were compared in a single-center, double-blind, single-dose, randomized, two-way crossover PK study in 44 healthy subjects with oral charcoal block. Morphology-directed Raman spectroscopy yielded volume median diameters of 3.17 µm for MF-I and 5.50 µm for MF-II, and dissolution studies showed that MF-II had a slower dissolution profile than MF-I. The formulation with larger API particles (MF-II) showed a 45% smaller Cmax and 45% smaller AUC0-inf compared to those of MF-I. Systemic bioavailability of MF-I (2.20%) and MF-II (1.18%) correlated well with the dissolution kinetics, with the faster dissolving formulation yielding the higher bioavailability. This agreement between pharmacokinetics and dissolution kinetics cross-validated both methods and supported their use in assessing potential differences in slowly dissolving suspension-based nasal spray products.
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Sprays Nasais , Humanos , Disponibilidade Biológica , Furoato de Mometasona/farmacocinética , Tamanho da Partícula , Equivalência Terapêutica , Método Duplo-Cego , Estudos Cross-OverRESUMO
Chemoresistance of cancer cells is a major problem in treating cancer. Knowledge of how cancer cells may die or resist cancer drugs is critical to providing certain strategies to overcome tumour resistance to treatment. Paclitaxel is known as a chemotherapy drug that can suppress the proliferation of cancer cells by inducing cell cycle arrest and induction of mitotic catastrophe. However, today, it is well known that paclitaxel can induce multiple kinds of cell death in cancers. Besides the induction of mitotic catastrophe that occurs during mitosis, paclitaxel has been shown to induce the expression of several pro-apoptosis mediators. It also can modulate the activity of anti-apoptosis mediators. However, certain cell-killing mechanisms such as senescence and autophagy can increase resistance to paclitaxel. This review focuses on the mechanisms of cell death, including apoptosis, mitotic catastrophe, senescence, autophagic cell death, pyroptosis, etc., following paclitaxel treatment. In addition, mechanisms of resistance to cell death due to exposure to paclitaxel and the use of combinations to overcome drug resistance will be discussed.
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Antineoplásicos , Neoplasias , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Linhagem Celular Tumoral , Humanos , Mitose , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , Paclitaxel/farmacologiaRESUMO
Two-dimensional magnetic van der Waals materials provide a fertile platform for the design and control of topological spin textures such as skyrmions. However, despite studies reporting skyrmions in many 2D magnetic systems, those of the hosting van der Waals materials remain limited. Here, via first-principles calculations and Monte Carlo simulations, we propose BiCrX3 as a new family of materials for hosting skyrmions. Due to the large SOC of the X atom and intrinsic inversion asymmetry, an inherent large DMI occurs in all systems, enabling intriguing Néel-type skyrmions. Furthermore, upon applying a moderate magnetic field, isolated skyrmions and skyrmion lattices emerge in our systems, and are robust within a relatively wide temperature range.
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BACKGROUND: Nociceptin/orphanin FQ (N/OFQ) has been revealed to play bidirectional roles in orofacial pain modulation. Calcitonin gene-related peptide (CGRP) is a well-known pro-nociceptive molecule that participates in the modulation of orofacial pain. We aimed to determine the effects of N/OFQ on the modulation of orofacial pain and on the release of CGRP. METHODS: Orofacial pain model was established by ligating springs between incisors and molars in rats for the simulation of tooth movement. The expression level of N/OFQ was determined and pain level was scored in response to orofacial pain. Both agonist and antagonist of N/OFQ receptor were administered to examine their effects on pain and the expression of CGRP in trigeminal ganglia (TG). Moreover, gene therapy based on the overexpression of N/OFQ was delivered to validate the modulatory role of N/OFQ on pain and CGRP expression. RESULTS: Tooth movement elicited orofacial pain and an elevation in N/OFQ expression. N/OFQ exacerbated orofacial pain and upregulated CGRP expression in TG, while UFP-101 alleviated pain and downregulated CGRP expression. N/OFQ-based gene therapy was successful in overexpressing N/OFQ in TG, which resulted in pain exacerbation and elevation of CGRP expression in TG. CONCLUSIONS: N/OFQ exacerbated orofacial pain possibly through upregulating CGRP.
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Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Dor Facial/metabolismo , Peptídeos Opioides/metabolismo , Gânglio Trigeminal/metabolismo , Animais , Modelos Animais de Doenças , Dor Facial/etiologia , Masculino , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/fisiologia , Técnicas de Movimentação Dentária/efeitos adversos , NociceptinaRESUMO
MicroRNAs (miRNAs) are a class of small noncoding RNA molecules containing only 20-22 nucleotides. MiRNAs play a role in gene silencing and translation suppression by targeting and binding to mRNA. Proper control of miRNA expression is very important for maintaining a normal physiological environment because miRNAs can affect most cellular pathways, including cell cycle checkpoint, cell proliferation, and apoptosis pathways, and have a wide range of target genes. With these properties, miRNAs can modulate multiple signalling pathways involved in cancer development, such as cell proliferation, apoptosis, and migration pathways. MiRNAs that activate or inhibit the molecular pathway related to tumour angiogenesis are common topics of research. Angiogenesis promotes tumorigenesis and metastasis by providing oxygen and diffusible nutrients and releasing proangiogenic factors and is one of the hallmarks of tumour progression. CRC is one of the most common tumours, and metastasis has always been a difficult issue in its treatment. Although comprehensive treatments, such as surgery, radiotherapy, chemotherapy, and targeted therapy, have prolonged the survival of CRC patients, the overall response is not optimistic. Therefore, there is an urgent need to find new therapeutic targets to improve CRC treatment. In a series of recent reports, miRNAs have been shown to bidirectionally regulate angiogenesis in colorectal cancer. Many miRNAs can directly act on VEGF or inhibit angiogenesis through other pathways (HIF-1a, PI3K/AKT, etc.), while some miRNAs, specifically many exosomal miRNAs, are capable of promoting CRC angiogenesis. Understanding the mechanism of action of miRNAs in angiogenesis is of great significance for finding new targets for the treatment of tumour angiogenesis. Deciphering the exact role of specific miRNAs in angiogenesis is a challenge due to the high complexity of their actions. Here, we describe the latest advances in the understanding of miRNAs and their corresponding targets that play a role in CRC angiogenesis and discuss possible miRNA-based therapeutic strategies.
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Receptor activity-modifying protein 1 (RAMP1) might be a critical regulator during bone wound healing. However, the roles and mechanisms of RAMP1 in osteogenesis remain unclear. Here, we aimed to elucidate the role of RAMP1 and explore the effects of Yes-associated protein 1 (Yap1), an effector of the Hippo/Yap pathway, in this process. We used a RAMP1 overexpression lentiviral system in bone marrow mesenchymal stem cells (BMSCs), which enhanced RAMP1 expression in an effective, appropriate, and sustained manner. Alkaline phosphatase (ALP) activity assays and alizarin red staining showed that RAMP1 promoted osteogenic differentiation of BMSCs after calcitonin gene-related peptide (CGRP) treatment (10 -8 mol/L). Moreover, real-time polymerase chain reaction and Western blot analysis indicated that RAMP1 upregulated the expression of osteogenic phenotypic markers (ALP, runt-related transcription factor 2, osteopontin; p < 0.05). To further uncover the mechanism of RAMP1 in osteogenic differentiation, we used verteporfin (10 -7 mol/L) to block Yap1. Notably, verteporfin impaired RAMP1-induced osteogenesis. Taken together, our findings confirmed that RAMP1 is a key mediator of bone regeneration and indicate that RAMP1 promotes CGRP-induced osteogenic differentiation of BMSCs via regulation of the Hippo/Yap pathway.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Ciclo Celular/metabolismo , Células-Tronco Mesenquimais/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteína 1 Modificadora da Atividade de Receptores/metabolismo , Transdução de Sinais , Animais , Calcificação Fisiológica/genética , Diferenciação Celular , Proliferação de Células , Regulação da Expressão Gênica , Vetores Genéticos/metabolismo , Via de Sinalização Hippo , Lentivirus/metabolismo , Camundongos Endogâmicos C57BL , Osteogênese/genética , Fenótipo , Proteínas de Sinalização YAPRESUMO
It is well known that corpus callosotomy (CC) can bring a favorable seizure control outcome for disabling generalized seizures, but the complete remission rate achieved by CC is rarely reported, and the postoperative relapse pattern is still not clear. In this study, the authors reviewed patients with medically refractory epilepsy who were suffering disabling seizures, including drop attacks, generalized tonic-clonic seizures (GTCS), tonic seizures, atonic seizures, atypical absences, and complex partial seizures. The patients underwent anterior two third or complete CC in our hospital. Seizure control outcome was evaluated postoperatively at 2 weeks, 1 month, 3 months, 6 months, thereafter, at yearly intervals. Seizure-free or >90% reduction was considered to be satisfactory. There were 14 patients with mean age 11.00â±â6.34 at surgery. Of all the patients, 6 patients underwent anterior two third CC, and the other 8 patients underwent complete CC. All the patients were postoperatively followed up for at least 1 year. Four patients (28.57%) were free of all seizure types in the first year after surgery. Among the 9 patients with follow-up longer than 3 years, 2 patients (22.22%) were free of all seizure types. In the first 3 months after surgery, more than half of the seizure free patients (55.56%) relapsed with the same seizure types as preoperatively. Although after that, there was only 1 patient relapsed. Of all the seizure types, CC achieved the most favorable seizure outcome in drop attacks. In conclusion, CC could achieve complete seizure remission in a small portion of selected candidates. Exploration of the relapse mechanism will contribute to improve the seizure outcome following CC.
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Corpo Caloso/cirurgia , Epilepsia Resistente a Medicamentos/cirurgia , Complicações Pós-Operatórias/etiologia , Adolescente , Adulto , Criança , Pré-Escolar , China , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Estudos RetrospectivosRESUMO
Live attenuated vaccine is one of the efficient vaccine candidates in aquaculture, which can be easily delivered to fish via bath-vaccination. An outstanding advantage of bath-vaccination is that vaccine delivery is through the same route as that utilized by many fish pathogens, generating specific mucosal immune responses. In this work, we investigated the mucosal immune responses induced by a live attenuated Vibrio anguillarum vaccine in zebrafish via bath-vaccination. Bacteria proliferated rapidly in 3 h after vaccination and maintained at a high level until 6 h in the intestine. Besides, bacteria persisted in the intestine for a longer time whereas decreased rapidly in the skin and gills. Moreover, a significant up-regulation of TLR5 triggering a MyD88-dependent signaling pathway was observed in the intestine, which implied that flagella were the crucial antigenic component of the live attenuated vaccine. And macrophages and neutrophils showed active responses participating in antigen recognition and sampling after vaccination. Furthermore, an inflammation was observed with plenty of lymphocytes in the intestine at 24 h post vaccination but eliminated within 7 days. In conclusion, the live attenuated V. anguillarum vaccine induced notable mucosal immune responses in the intestine which could be used as a mucosal vaccine vector in the future.
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Antígenos de Bactérias/imunologia , Doenças dos Peixes/imunologia , Imunidade nas Mucosas , Vibrioses/veterinária , Vibrio/imunologia , Peixe-Zebra , Animais , Vacinas Bacterianas/administração & dosagem , Vacinas Bacterianas/farmacologia , Doenças dos Peixes/microbiologia , Microscopia Eletrônica de Transmissão/veterinária , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Regulação para Cima , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/farmacologia , Vibrioses/imunologia , Vibrioses/microbiologiaRESUMO
A highly sensitive and specific LC-MS/MS method for the quantitation of largazole thiol, the active species of the marine-derived preclinical histone deacetylase inhibitor, largazole (prodrug), was developed and validated. Largazole thiol was extracted with ethyl acetate from human or rat plasma along with the internal standard, harmine. Samples were separated on an Onyx Monolithic C18 column by a stepwise gradient elution with 0.1% formic acid in methanol and 0.1% aqueous formic acid employing multiple reaction monitoring (MRM) detection. Linear calibration curves were obtained in the range of 12.5-400 ng/mL with 200 µL of human plasma. The overall intra-day precision was from 3.87% to 12.6%, and the inter-day precision was from 7.12% to 9.8%. The accuracy at low, medium and high concentrations ranged from 101.55% to 105.84%. Plasma protein bindings of largazole thiol in human and rat plasma as determined by an ultrafiltration method were 90.13% and 77.14%, respectively. Plasma drug concentrations were measured by this LC-MS/MS method. The pharmacokinetics of largazole thiol in rats was studied following i.v. administration at 10 mg/kg and found to follow a two-compartment model. Largazole thiol was rapidly eliminated from systemic circulation within 2 h. The established LC-MS/MS method is suitable for the analysis of largazole thiol in human plasma, as well.
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Depsipeptídeos/farmacocinética , Inibidores de Histona Desacetilases/farmacocinética , Tiazóis/farmacocinética , Animais , Cromatografia Líquida de Alta Pressão , Meia-Vida , Humanos , Indicadores e Reagentes , Masculino , Espectrometria de Massas , Plasma/química , Ligação Proteica , Controle de Qualidade , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos TestesRESUMO
Graph neural networks (GNNs), a class of deep learning models designed for performing information interaction on non-Euclidean graph data, have been successfully applied to node classification tasks in various applications such as citation networks, recommender systems, and natural language processing. Graph node classification is an important research field for node-level tasks in graph data mining. Recently, due to the limitations of shallow GNNs, many researchers have focused on designing deep graph learning models. Previous GNN architecture search works only solve shallow networks (e.g., less than four layers). It is challenging and nonefficient to manually design deep GNNs for challenges like over-smoothing and information squeezing, which greatly limits their capabilities on large-scale graph data. In this article, we propose a novel neural architecture search (NAS) method for designing deep GNNs automatically and further exploit the application potential on various node classification tasks. Our innovations lie in two aspects, where we first redesign the deep GNNs search space for architecture search with a decoupled mode based on propagation and transformation processes, and we then formulate and solve the problem as a multiobjective optimization to balance accuracy and computational efficiency. Experiments on benchmark graph datasets show that our method performs very well on various node classification tasks, and exploiting large-scale graph datasets further validates that our proposed method is scalable.
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Titanium implants are widely used ; however, implantation occasionally fails due to infections during the surgery or poor osseointegration after the surgery. To solve the problem, an intelligent functional surface on titanium implant that can sequentially eradicate bacteria biofilm at the initial period and promote osseointegration at the late period of post-surgery time is designed. Such surfaces can be excited by near infrared light (NIR), with rare earth nanoparticles to upconvert the NIR light to visible range and adsorb by Au nanoparticles, supported by titanium oxide porous film on titanium implants. Under NIR irradiation, the implant converts the energy of phonon to hot electrons and lattice vibrations, while the former flows directly to the contact substance or partially reacts with the surrounding to generate reactive oxygen species, and the latter leads to the local temperature increase. The biofilm or microbes on the implant surface can be eradicated by NIR treatment in vitro and in vivo. Additionally, the surface exhibits superior biocompatibility for cell survival, adhesion, proliferation, and osteogenic differentiation, which provides the foundation for osseointegration. In vivo implantation experiments demonstrate osseointegration is also promoted. This work thus demonstrates NIR-generated electrons can sequentially eradicate biofilms and regulate the osteogenic process, providing new solutions to fabricate efficient implant surfaces.
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Nanopartículas Metálicas , Osseointegração , Osseointegração/fisiologia , Osteogênese , Titânio/farmacologia , Ouro/farmacologia , Antibacterianos/farmacologia , Propriedades de SuperfícieRESUMO
Dental implants are considered a superior option for the replacement of missing teeth. However, the invasive nature of the surgical procedure often results in significant postoperative inflammation, and the prolonged healing period of 3-6â¯months presents a notable disadvantage. High mobility group box 1 (HMGB1) is a critical mediator of acute inflammation following surgical injury, which can hinder the onset of osseointegration. This study aims to examine whether the inhibition of HMGB1 can mitigate acute inflammation and subsequently enhance osseointegration. The findings indicate that HMGB1 inhibition markedly reduces inflammation and promotes bone repair in murine models. Further in vitro investigations into the regulatory mechanisms of HMGB1 in macrophages reveal its role in increasing Yes-associated protein (YAP) activity, which contributes to pro-inflammatory polarization. Additionally, conditioned media derived from macrophages influenced by HMGB1 significantly impair the migratory and osteogenic capabilities of bone marrow-derived mesenchymal stem cells, which are essential for bone regeneration. In vivo experiments further validate that the administration of exogenous HMGB1 exacerbates postoperative acute inflammation and obstructs osseointegration. The study concludes that inhibiting HMGB1 fosters an anti-inflammatory polarization of macrophages, leading to diminished postoperative acute inflammation and expedited osseointegration around dental implants in mice.
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Antibacterial properties and osteogenic activity are considered as two crucial factors for the initial healing and long-term survivability of orthopedic implants. For decades, various drug-loaded implants to enhance biological activities have been investigated extensively. More importantly, to control the drug release timing is equally significant due to the sequential biological processes after implantation. Hence, developing a staged regulation system on the titanium surface is practically significant. Here, we prepared TiO2 nanotubes (TiO2 NTs) on the titanium surface by anodization, followed by the incorporation of zinc (Zn) and strontium (Sr) sequentially through a hydrothermal process. Surface characterization confirmed the successful fabrication of Zn and Sr-incorporated TiO2 NTs (Zn-Sr/TiO2) on the titanium surface. The ion release results exhibited the differential release characteristic of Zn and Sr, which meant the early-stage release of Zn and the long-term release of Sr. It was exactly in accord with the biological process after implantation, laying the basis of staged regulation after implantation. Zn-Sr/TiO2 showed favorable anti-early infection properties both in vitro and in vivo. Its inhibition effect on bacterial biofilm formation was attributed to the resistance against bacteria's initial adhesion and the killing effect on planktonic bacteria. Additionally, the release of Sr could alleviate infection-induced damage via immunoregulation. The biocompatibility and osteogenic activity mediated by M2 macrophage activation were confirmed with in vitro and in vivo studies. Therefore, it exhibited great potential in staged regulation for antibacterial activity in the early stage and the M2 activation-mediated osteogenic activity in the late stage. The staged regulation process was based on the differential release of Zn and Sr to achieve the early antibacterial effect and the long-term immune-induced osteogenic activity, to prevent implant-related infection and achieve better osseointegration. These two kinds of ions played their roles synergistically and complement mutually. This work is expected to provide an innovative idea for realizing sequential regulation after implantation.
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Osteogênese , Titânio , Titânio/farmacologia , Antibacterianos/farmacologia , Próteses e Implantes , Osseointegração , Bactérias , Íons , Propriedades de Superfície , Estrôncio/farmacologiaRESUMO
Biofilms on public devices and medical instruments are harmful. Hence, it is of great importance to fabricate antibacterial surfaces. In this work, we target the preparation of an antibacterial surface excited by near-infrared light via the coating of rare earth nanoparticles (RE NPs) on a titanium surface. The upconverted luminescence is absorbed by gold nanoparticles (Au NPs, absorber) to produce hot electrons and reactive oxygen species to eliminate the biofilms. The key parameters in tuning the upconversion effect to eliminate the biofilms are systematically investigated, which include the ratios of the sensitizer, activator, and matrix in the RE NPs, or the absorber Au NPs. The regulated RE NPs exhibit an upconversion quantum yield of 3.5%. Under illumination, photogenerated electrons flow through the surface to bacteria, such as E. coli, which disrupt the breath chain and eventually lead to the death of bacteria. The mild increase of the local temperature has an impact on the elimination of biofilms on the surface to a certain degree as well. Such a configuration on the surface of titanium exhibits a high reproducibility on the removal of biofilms and is functional after the penetration of light using soft tissue. This work thus provides a novel direction in the application of upconversion materials to be used in the fabrication of antibacterial surfaces.
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Nanopartículas Metálicas , Metais Terras Raras , Titânio , Ouro , Escherichia coli , Reprodutibilidade dos Testes , Antibacterianos/farmacologia , BiofilmesRESUMO
Low-dose computed tomography (LDCT) denoising tasks face significant challenges in practical imaging scenarios. Supervised methods encounter difficulties in real-world scenarios as there are no paired data for training. Moreover, when applied to datasets with varying noise patterns, these methods may experience decreased performance owing to the domain gap. Conversely, unsupervised methods do not require paired data and can be directly trained on real-world data. However, they often exhibit inferior performance compared to supervised methods. To address this issue, it is necessary to leverage the strengths of these supervised and unsupervised methods. In this paper, we propose a novel domain adaptive noise reduction framework (DANRF), which integrates both knowledge transfer and style generalization learning to effectively tackle the domain gap problem. Specifically, an iterative knowledge transfer method with knowledge distillation is selected to train the target model using unlabeled target data and a pre-trained source model trained with paired simulation data. Meanwhile, we introduce the mean teacher mechanism to update the source model, enabling it to adapt to the target domain. Furthermore, an iterative style generalization learning process is also designed to enrich the style diversity of the training dataset. We evaluate the performance of our approach through experiments conducted on multi-source datasets. The results demonstrate the feasibility and effectiveness of our proposed DANRF model in multi-source LDCT image processing tasks. Given its hybrid nature, which combines the advantages of supervised and unsupervised learning, and its ability to bridge domain gaps, our approach is well-suited for improving practical low-dose CT imaging in clinical settings. Code for our proposed approach is publicly available at https://github.com/tyfeiii/DANRF.
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Tomografia Computadorizada por Raios X , Humanos , Razão Sinal-Ruído , Algoritmos , Aprendizado de Máquina , Processamento de Imagem Assistida por Computador/métodosRESUMO
Ripening is one of the most important stages of fruit development and determines the fruit quality. Various factors play a role in this process, with epigenetic mechanisms emerging as important players. Epigenetic regulation encompasses DNA methylation, histone modifications and variants, chromatin remodeling, RNA modifications, and non-coding RNAs. Over the past decade, studies using tomato as a model have made considerable progress in understanding the impact of epigenetic regulation on fleshy fruit ripening and quality. In this paper, we provide an overview of recent advancements in the epigenetic regulation of tomato fruit ripening and quality regulation, focusing on three main mechanisms: DNA/RNA modifications, non-coding RNAs, and histone modifications. Furthermore, we highlight the unresolved issues and challenges within this research field, offering perspectives for future investigations to drive agricultural innovation.