RESUMEN
Cutaneous wound healing is associated with the unpleasant sensation of itching. Here we investigated the mechanisms underlying this type of itch, focusing on the contribution of soluble factors released during healing. We found high amounts of interleukin 31 (IL-31) in skin wound tissue during the peak of itch responses. Il31-/- mice lacked wound-induced itch responses. IL-31 was released by dermal conventional type 2 dendritic cells (cDC2s) recruited to wounds and increased itch sensory neuron sensitivity. Transfer of cDC2s isolated from late-stage wounds into healthy skin was sufficient to induce itching in a manner dependent on IL-31 expression. Addition of the cytokine TGF-ß1, which promotes wound healing, to dermal DCs in vitro was sufficient to induce Il31 expression, and Tgfbr1f/f CD11c-Cre mice exhibited reduced scratching and decreased Il31 expression in wounds in vivo. Thus, cDC2s promote itching during skin would healing via a TGF-ß-IL-31 axis with implications for treatment of wound itching.
Asunto(s)
Interleucinas/metabolismo , Células de Langerhans/fisiología , Prurito/patología , Células Receptoras Sensoriales/fisiología , Factor de Crecimiento Transformador beta1/metabolismo , Animales , Femenino , Humanos , Interleucinas/genética , Células de Langerhans/trasplante , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Persona de Mediana Edad , Receptores de Interleucina/metabolismo , Piel/citología , Piel/crecimiento & desarrollo , Piel/lesiones , Canales Catiónicos TRPV/metabolismo , Cicatrización de Heridas/fisiologíaRESUMEN
Regulatory T cells (Treg cells) perform suppressive functions in disparate tissue environments and against many inflammatory insults, yet the tissue-enriched factor(s) that influence Treg cell phenotype and function remain largely unknown. We have shown a vital role for transforming growth factor-ß (TGF-ß) signals in safe-guarding specific Treg cell functions. TGF-ß signals were dispensable for steady-state Treg cell homeostasis and for Treg cell suppression of T cell proliferation and T helper-1 (Th1) cell differentiation. However, Treg cells require TGF-ß signals to appropriately dampen Th17 cells and regulate responses in the gastrointestinal tract. TGF-ß signaling maintains CD103 expression, promotes expression of the colon-specific trafficking molecule GPR15, and inhibits expression of GPR174, a receptor for lysophosphatidylserine, on Treg cells, collectively supporting the accumulation and retention of Treg cells in the colon and control of colitogenic responses. Thus, we reveal an unrecognized function for TGF-ß signaling as an upstream factor controlling Treg cell activity in specific tissue environments.
Asunto(s)
Especificidad de Órganos/inmunología , Transducción de Señal/inmunología , Linfocitos T Reguladores/inmunología , Células Th17/inmunología , Factor de Crecimiento Transformador beta/inmunología , Animales , Antígenos CD/inmunología , Antígenos CD/metabolismo , Proliferación Celular , Encefalomielitis Autoinmune Experimental/genética , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/metabolismo , Citometría de Flujo , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/inmunología , Factores de Transcripción Forkhead/metabolismo , Tracto Gastrointestinal/inmunología , Tracto Gastrointestinal/metabolismo , Tracto Gastrointestinal/patología , Homeostasis/inmunología , Cadenas alfa de Integrinas/inmunología , Cadenas alfa de Integrinas/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/inmunología , Proteínas Serina-Treonina Quinasas/metabolismo , Receptor Tipo I de Factor de Crecimiento Transformador beta , Receptores Acoplados a Proteínas G/inmunología , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Factores de Crecimiento Transformadores beta/genética , Receptores de Factores de Crecimiento Transformadores beta/inmunología , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Linfocitos T Reguladores/metabolismo , Células Th17/metabolismo , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
BACKGROUND: Sunitinib has emerged as the primary treatment for advanced or metastatic clear cell renal cell carcinoma (ccRCC) due to its significant improvement in patients' average survival time. However, drug resistance and adverse effects of sunitinib pose challenges to its clinical benefits. METHODS: The differentially expressed genes (DEGs) associated with sunitinib sensitivity and resistance in ccRCC were investigated. Cell counting kit-8, plate colony formation, flow cytometry and subcutaneous xenograft tumor model assays were employed to explore the effects of PDZK1 on ccRCC. Further research on the molecular mechanism was conducted through western blot, co-immunoprecipitation, immunofluorescence co-localization and immunohistochemical staining. RESULTS: We elucidated that PDZK1 is significantly downregulated in sunitinib-resistant ccRCC specimens, and PDZK1 negatively regulates the phosphorylation of PDGFR-ß and the activation of its downstream pathways through interaction with PDGFR-ß. The dysregulated low levels of PDZK1 contribute to inadequate inhibition of cell proliferation, tumor growth, and insensitivity to sunitinib treatment. Notably, our preclinical investigations showed that miR-15b antagomirs enhance sunitinib cytotoxic effects against ccRCC cells by upregulating PDZK1 levels, suggesting their potential in overcoming sunitinib resistance. CONCLUSIONS: Our findings establish the miR-15b/PDZK1/PDGFR-ß axis as a promising therapeutic target and a novel predictor for ccRCC patients' response to sunitinib treatment.
Asunto(s)
Carcinoma de Células Renales , Resistencia a Antineoplásicos , Neoplasias Renales , Receptor beta de Factor de Crecimiento Derivado de Plaquetas , Sunitinib , Sunitinib/farmacología , Sunitinib/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/metabolismo , Humanos , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/genética , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , Animales , Resistencia a Antineoplásicos/genética , Ratones , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , MicroARNs/genética , Transducción de Señal/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Masculino , Ratones Desnudos , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismoRESUMEN
Renewal of integumentary organs occurs cyclically throughout an organism's lifetime, but the mechanism that initiates each cycle remains largely unknown. In a miniature pig model of tooth development that resembles tooth development in humans, the permanent tooth did not begin transitioning from the resting to the initiation stage until the deciduous tooth began to erupt. This eruption released the accumulated mechanical stress inside the mandible. Mechanical stress prevented permanent tooth development by regulating expression and activity of the integrin ß1-ERK1-RUNX2 axis in the surrounding mesenchyme. We observed similar molecular expression patterns in human tooth germs. Importantly, the release of biomechanical stress induced downregulation of RUNX2-wingless/integrated (Wnt) signaling in the mesenchyme between the deciduous and permanent tooth and upregulation of Wnt signaling in the epithelium of the permanent tooth, triggering initiation of its development. Consequently, our findings identified biomechanical stress-associated Wnt modulation as a critical initiator of organ renewal, possibly shedding light on the mechanisms of integumentary organ regeneration.
Asunto(s)
Regulación hacia Abajo , Odontogénesis , Vía de Señalización Wnt , Animales , Fenómenos Biomecánicos , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Saco Dental/citología , Saco Dental/metabolismo , Humanos , Integrina beta1/metabolismo , Modelos Biológicos , Cultivo Primario de Células , Porcinos , Porcinos EnanosRESUMEN
The intestinal tract, which is the primary site of digestion and absorption of nutrients, is one of the most vulnerable organs during aging. Dietary nitrate, which is mainly derived from the diet and absorbed in the intestinal tract, is a key messenger that connecting oral and general health. However, whether dietary nitrate regulates intestinal tract homeostasis remains unclear. Our data revealed that the serum and salivary nitrate levels decreased during mice aging. The functional proteins of the epithelial barrier (E-cadherin, Claudin-1 and Zonula Occludens-1) in the colon tissues decreased during the aging process. Long-term nitrate supplement in drinking water restored the serum and salivary nitrate levels and increased the functional proteins expression of the colon epithelial barrier. Dietary nitrates increase the relative abundance of some intestinal probiotics, particularly those associated with the production of short-chain fatty acids, such as Blautia, Alloprevotella, Butyricicoccus, and Ruminococcaceae, while promoting the butyric acid production in the colon. Moreover, the expression of Sialin (encoded by Slc17a5), which is a nitrate transporter, increased in the colon epithelial cells by nitrate supplementation. The epithelial cell-conditional Slc17a5-knockout mutant mice (K14-cre; Slc17a5fl/fl) revealed that the functional proteins expression of the colon epithelial barrier and the proliferation of PCNA-positive intestinal epithelial cells in the colon crypts was significantly decreased compared with those of the K14-cre; Slc17a5fl/+ mice. Taken together, our findings suggested that nitrate supplementations were associated with the increased expression of colonic epithelial barriers-related proteins and the increased Sialin expression. Nitrate may serve as a potential therapeutic approach in maintaining aged colonic homeostasis.
RESUMEN
Epithelial-mesenchymal interactions occur during tooth development. The dental epithelium (DE) is regarded as the signal center that regulates tooth morphology. However, the mechanism by which DE regulates the differentiation of mesenchyme-derived dental papilla (DP) into odontoblasts remains unclear. Using miniature pigs as a model, we analyzed the expression profiles of the DE and DP during odontoblast differentiation using high-throughput RNA sequencing. The phosphatidylinositol-3-kinase (PI3K)/AKT pathway is one of the most enriched pathways in both DE and DP. The PI3K/AKT pathway was first activated in the inner enamel epithelium but not in the DP on embryonic day 50. This pathway was then activated in the odontoblast layer on embryonic day 60. We showed that AKT activation promoted odontoblast differentiation of DP cells. We further demonstrated that activation of PI3K/AKT signaling in the DE effectively increased the expression levels of AKT and dentin sialophosphoprotein in DP cells. Additionally, we found that DE cells secreted collagen type IV alpha 6 chain (COL4A6) downstream of epithelial AKT signaling to positively regulate mesenchymal AKT levels. Therefore, our data suggest that PI3K/AKT signaling from the DE to the DP promotes odontoblast differentiation via COL4A6 secretion.
Asunto(s)
Odontoblastos , Proteínas Proto-Oncogénicas c-akt , Animales , Porcinos , Odontoblastos/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Diferenciación Celular/genética , EpitelioRESUMEN
OBJECTIVES: Prevention of atherosclerotic cardiovascular disease (ASCVD) is important in individuals with metabolic syndrome components (MetS), and periodontitis may play an important role in this process. This study aims to evaluate the association between periodontitis and ASCVD in participants with the components of MetS, including obesity, dysglycemia, hypertension, and dyslipidemia. MATERIALS AND METHODS: This study conducted followed the MOOSE reporting guidelines and the PRISMA 2020 guidelines. EMBASE, MEDLINE, Web of Science, Cochrane Library, PubMed and OpenGrey were searched for observational studies about the linkage of periodontitis to ASCVD in people with MetS components up to April 9, 2023. Cohort, case-control and cross-sectional studies were included after study selection. Quality evaluation was carried out using the original and modified Newcastle-Ottawa Scale as appropriate. Random-effects model was employed for meta-analysis. RESULTS: Nineteen studies were finally included in the quality analysis, and all of them were assessed as moderate to high quality. Meta-analyses among fifteen studies revealed that the participants with periodontitis were more likely to develop ASCVD in those who have dysglycemia (RR = 1.25, 95% CI = 1.13-1.37; p < 0.05), obesity (RR = 1.13, 95% CI = 1.02-1.24; p < 0.05), dyslipidemia (RR = 1.36, 95% CI = 1.13-1.65; p < 0.05), or hypertension (1.20, 95% CI = 1.05-1.36; p < 0.05). CONCLUSIONS: Periodontitis promotes the development of ASCVD in participants with one MetS component (obesity, dysglycemia, hypertension or dyslipidemia). CLINICAL RELEVANCE: In people with MetS components, periodontitis may contribute to the ASCVD incidence.
Asunto(s)
Aterosclerosis , Síndrome Metabólico , Periodontitis , Síndrome Metabólico/complicaciones , Humanos , Periodontitis/complicaciones , Factores de Riesgo , Hipertensión/complicaciones , Dislipidemias/epidemiología , Enfermedades CardiovascularesRESUMEN
Parkinson's disease (PD) is a common neurodegenerative disease. Here, the purpose of the study was to explore the function of long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) in PD and its underlying mechanism. An in vivo 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-hydrochloride (MPTP)-induced mouse model of PD was generated and the SH-SY5Y cells were treated with MPP + to induce neuronal damage in vitro. Quantitative real-time polymerase chain reaction (QRT-PCR) and Western blot were used to detect the expression of HOTAIR, miR-221-3p, α-synuclein and apoptosis-related genes. MTT, flow cytometry and TUNEL assay was used to detect cell viability and apoptosis, respectively. The levels of inflammatory cytokines TNF-α,IL-1ß and IL-6 were detected by ELISA assay. The levels of lactate dehydrogenase (LDH), reactive oxygen species (ROS), and superoxide dismutase (SOD) were determined using the appropriate assay kits. The interactions between miR-221-3p and HOTAIR or α-synuclein were determined by dual luciferase assay and RNA binding protein immunoprecipitation (RIP). Co-localization of HOTAIR and miR-221-3p was also proved by immunofluorescence staining. The results showed that HOTAIR was highly expressed, while miR-221-3p expression was decreased in PD model in vivo and in vitro. In SH-SY5Y cells treated with MPP+, the knockdown of HOTAIR increased cell viability and reduced cell apoptosis, the secretion of inflammatory cytokines and oxidative stress reaction, while HOTAIR overexpression led to opposite effects. Furthermore, HOTAIR sponged miR-221-3p which directly targeted α-synuclein and thus regulated the expression of α-synuclein. Meanwhile, inhibiting miR-221-3p could partially reverse the neuroprotective effects of HOTAIR knockdown. In conclusion, HOTAIR attenuated the injury of SH-SY5Y cells induced by MPP+ via miR-221-3p/α-synuclein axis, suggesting the potential therapeutic value of HOTAIR in PD.
Asunto(s)
MicroARNs , Enfermedades Neurodegenerativas , Enfermedad de Parkinson , ARN Largo no Codificante/metabolismo , alfa-Sinucleína/metabolismo , Animales , Apoptosis , Línea Celular Tumoral , Humanos , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patologíaRESUMEN
Periodontitis is an irreversible inflammatory response that occurs in periodontal tissues. Given the size and diversity of natural flora in the oral mucosa, host immunity must strike a balance between pathogen identification and a complicated system of tolerance. The innate immune system, which includes innate lymphoid cells (ILCs), certainly plays a crucial role in regulating this homeostasis because pathogens are quickly recognized and responded to. ILCs are a recently discovered category of tissue-resident lymphocytes that lack adaptive antigen receptors. ILCs are found in both lymphoid and non-lymphoid organs and are particularly prevalent at mucosal barrier surfaces, where they control inflammatory response and homeostasis. Recent studies have shown that ILCs are important players in periodontitis; however, the mechanisms that govern the innate immune response in periodontitis still require further investigation. This review focuses on the intricate crosstalk between ILCs and the microenvironment in periodontal tissue homeostasis, with the purpose of regulating or improving immune responses in periodontitis prevention and therapy.
Asunto(s)
Linfocitos , Periodontitis , Humanos , Inmunidad Innata , HomeostasisRESUMEN
Non-alcoholic fatty liver disease (NAFLD) leads to hippocampal damage and causes a variety of physiopathological responses, including the induction of endoplasmic reticulum stress (ERS), neuroinflammation, and alterations in synaptic plasticity. As an important trace element, strontium (Sr) has been reported to have antioxidant effects, to have anti-inflammatory effects, and to cause the inhibition of adipogenesis. The present study was undertaken to investigate the protective effects of Sr on hippocampal damage in NAFLD mice in order to elucidate the underlying mechanism of Sr in NAFLD. The mouse model of NAFLD was established by feeding mice a high-fat diet (HFD), and the mice were treated with Sr. In the NAFLD mice, we found that treatment with Sr significantly increased the density of c-Fos+ cells in the hippocampus and inhibited the expression of caspase-3 by suppressing ERS. Surprisingly, the induction of neuroinflammation and the increased expression of inflammatory cytokines in the hippocampus following an HFD were attenuated by Sr treatment. Sr significantly attenuated the activation of microglia and astrocytes induced by an HFD. The expression of phospho-p38, ERK, and NF-κB was consistently significantly increased in the HFD group, and treatment with Sr decreased their expression. Moreover, Sr prevented HFD-induced damage to the ultra-structural synaptic architecture. This study implies that Sr has beneficial effects on repairing the damage to the hippocampus induced by an HFD, revealing that Sr could be a potential candidate for protection from neural damage caused by NAFLD.
Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Ratones , Animales , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedades Neuroinflamatorias , Dieta Alta en Grasa/efectos adversos , Hipocampo/metabolismo , Plasticidad Neuronal , Ratones Endogámicos C57BL , Hígado/metabolismoRESUMEN
In recent years, electrochemical oxidation (EO) shows the characteristics of green and high efficiency in removing chemical oxygen demand (COD) and ammonia nitrogen (NH3-N) from wastewater, which has been favored by researchers. However, at present, most of current studies on EO remain in laboratory stage, reports about pilot-scale or even industrial tests with large treatment capacity are few, which slowing down the use of the advanced technology to practical application. In this study, bench-scale tests, pilot-scale tests (treatment capacity 200-500 L/h), and industrial tests (treatment capacity 100 m3/h) were carried out by EO technology in view of the characteristics of tungsten smelting wastewater (TSW) with high salinity (NaCl), COD, and NH3-N. Results showed that the removal of COD and NH3-N was a competitive reaction in the EO process, and COD could be removed more preferentially than NH3-N. When NH3-N content was low, the influent pH had a minimal effect on its removal, and when NH3-N content was high, increasing the influent pH was beneficial to its removal. Industrial tests showed that the one-step removal of COD and NH3-N in TSW met the standard, and the power consumption per cubic meter of wastewater was only 4.2 kW h, and the treatment cost was much lower than the two-step process of "breaking point chlorination to remove NH3-N and adding oxidant to remove COD". This study has successfully realized industrial application of EO technology in TSW treatment for the first time and provided a successful case, which is helpful to accelerate the popularization and application of this technology in the field of high salinity organic ammonia nitrogen wastewater treatment.
Asunto(s)
Amoníaco , Aguas Residuales , Amoníaco/análisis , Tungsteno , Análisis de la Demanda Biológica de Oxígeno , Salinidad , Nitrógeno/análisis , Eliminación de Residuos Líquidos/métodosRESUMEN
BACKGROUND: The development of deep learning (DL) algorithms for use in dentistry is an emerging trend. Periodontitis is one of the most prevalent oral diseases, which has a notable impact on the life quality of patients. Therefore, it is crucial to classify periodontitis accurately and efficiently. This systematic review aimed to identify the application of DL for the classification of periodontitis and assess the accuracy of this approach. METHODS: A literature search up to November 2023 was implemented through EMBASE, PubMed, Web of Science, Scopus, and Google Scholar databases. Inclusion and exclusion criteria were used to screen eligible studies, and the quality of the studies was evaluated by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology with the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) tool. Random-effects inverse-variance model was used to perform the meta-analysis of a diagnostic test, with which pooled sensitivity, specificity, positive likelihood ratio (LR), negative LR, and diagnostic odds ratio (DOR) were calculated, and a summary receiver operating characteristic (SROC) plot was constructed. RESULTS: Thirteen studies were included in the meta-analysis. After excluding an outlier, the pooled sensitivity, specificity, positive LR, negative LR and DOR were 0.88 (95%CI 0.82-0.92), 0.82 (95%CI 0.72-0.89), 4.9 (95%CI 3.2-7.5), 0.15 (95%CI 0.10-0.22) and 33 (95%CI 19-59), respectively. The area under the SROC was 0.92 (95%CI 0.89-0.94). CONCLUSIONS: The accuracy of DL-based classification of periodontitis is high, and this approach could be employed in the future to reduce the workload of dental professionals and enhance the consistency of classification.
Asunto(s)
Aprendizaje Profundo , Humanos , Sensibilidad y Especificidad , Curva ROC , Algoritmos , Oportunidad RelativaRESUMEN
Oral inflammatory diseases (OIDs) are a group of dental diseases with multiple clinical manifestations that impact the majority of the world's population. Many studies have investigated the associations between individual OID traits and genomic variants, but whether pleiotropic loci are shared by oral inflammatory traits remains poorly understood. Here, we conducted multitrait joint analyses based on the summary statistics of genome-wide association studies (GWASs) of five dental traits from the UK Biobank. Among these genome-wide significant loci, two were novel for both painful gums and toothache. We identified causal variants at each novel locus, and functional annotation based on multiomics data suggested IL10 and IL12A/TRIM59 as potential candidate genes at the novel pleiotropic loci. Subsequent analyses of pathway enrichment and protein-protein interaction networks suggested the involvement of the candidate genes in immune regulation. In conclusion, our results uncover novel pleiotropic loci for OID traits and highlight the importance of immune regulation in the pathogenesis of OIDs. These findings will enhance our understanding of the pathogenesis of OIDs and be beneficial for risk screening, prevention, and the development of novel drugs targeting the immune regulation of OIDs.
Asunto(s)
Pleiotropía Genética , Enfermedades de la Boca/genética , Estomatitis/genética , Estudios de Cohortes , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Inflamación/epidemiología , Inflamación/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Enfermedades de la Boca/epidemiología , Fenotipo , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , Carácter Cuantitativo Heredable , Estomatitis/epidemiología , Enfermedades Estomatognáticas/epidemiología , Enfermedades Estomatognáticas/genética , Proteínas de Motivos Tripartitos/genética , Reino Unido/epidemiologíaRESUMEN
Oxygen reduction reaction (ORR) is the key reaction on cathode of rechargeable zinc-air batteries (ZABs). However, the lack of protons in alkaline conditions limits the rate of ORR. Herein, an activating water strategy is proposed to promote oxygen electrocatalytic activity by enhancing the proton production from water dissociation. FeP nanoparticles (NPs) are coupled on N-doped wood-derived catalytically active carbon (FeP-NWCC) to associate bifunctional active sites. In alkaline, FeP-NWCC possesses outstanding catalytic activities toward ORR (E1/2 = 0.86 V) and Oxygen evolution reaction (OER) (overpotential is 310 mV at 10 mA cm-2 ). The liquid ZABs assembled by FeP-NWCC deliver superior peak power density (144 mW cm-2 ) and cycle stability (over 450 h). The quasi-solid-state ZABs based on FeP-NWCC also display excellent performances. Theoretical calculation illustrates that the superb bifunctional performance of FeP-NWCC results from the elevated dissociation efficiency of water via FeP NPs to assist the oxygen catalytic process. The strategy of activating water provides a new perspective for the design of ORR/OER bifunctional catalysts. This work is a model for the application of forest biomass.
Asunto(s)
Oxígeno , Agua , Catálisis , Suministros de Energía Eléctrica , Oxígeno/química , Protones , Madera , Zinc/químicaRESUMEN
Membrane proteins mediate a plethora of cellular functions and represent important targets for drug development. Unlike soluble proteins, membrane proteins require native-like environments to fold correctly and be active. Therefore, modern structural biology techniques have aimed to determine the structure and dynamics of these membrane proteins at physiological temperature and in liquid crystalline lipid bilayers. With the flourishing of new NMR methodologies and improvements in sample preparations, magic angle spinning (MAS) and oriented sample solid-state NMR (OS-ssNMR) spectroscopy of membrane proteins is experiencing a new renaissance. Born as antagonistic approaches, these techniques nowadays offer complementary information on the structural topology and dynamics of membrane proteins reconstituted in lipid membranes. By spinning biosolid samples at the magic angle (θ = 54.7°), MAS NMR experiments remove the intrinsic anisotropy of the NMR interactions, increasing spectral resolution. Internuclear spin interactions (spin exchange) are reintroduced by RF pulses, providing distances and torsion angles to determine secondary, tertiary, and quaternary structures of membrane proteins. OS-ssNMR, on the other hand, directly detects anisotropic NMR parameters such as dipolar couplings (DC) and anisotropic chemical shifts (CS), providing orientational constraints to determine the architecture (i.e., topology) of membrane proteins relative to the lipid membrane. Defining the orientation of membrane proteins and their interactions with lipid membranes is of paramount importance since lipid-protein interactions can shape membrane protein conformations and ultimately define their functional states.In this Account, we report selected studies from our group integrating MAS and OS-ssNMR techniques to give a comprehensive view of the biological processes occurring at cellular membranes. We focus on the main experiments for both techniques, with an emphasis on new implementation to increase both sensitivity and spectral resolution. We also describe how the structural constraints derived from both isotropic and anisotropic NMR parameters are integrated into dynamic structural modeling using replica-averaged orientational-restrained molecular dynamics simulations (RAOR-MD). We showcase small membrane proteins that are involved in Ca2+ transport and regulate cardiac and skeletal muscle contractility: phospholamban (PLN, 6 kDa), sarcolipin (SLN, 4 kDa), and DWORF (4 kDa). We summarize our results for the structures of these polypeptides free and in complex with the sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA, 110 kDa). Additionally, we illustrate the progress toward the determination of the structural topology of a six transmembrane protein associated with succinate and acetate transport (SatP, hexamer 120 kDa). From these examples, the integrated MAS and OS-ssNMR approach, in combination with modern computational methods, emerges as a way to overcome the challenges posed by studying large membrane protein systems.
Asunto(s)
Membrana Dobles de Lípidos/química , Proteínas de la Membrana/química , Resonancia Magnética Nuclear Biomolecular , Membrana Dobles de Lípidos/metabolismo , Proteínas de la Membrana/metabolismo , Simulación de Dinámica MolecularRESUMEN
In this work, the radiation responses of silicon photonic passive devices built in silicon-on-insulator (SOI) technology are investigated through high energy neutron and 60Co γ-ray irradiation. The wavelengths of both micro-ring resonators (MRRs) and Mach-Zehnder interferometers (MZIs) exhibit blue shifts after high-energy neutron irradiation to a fluence of 1×1012 n/cm2; the blue shift is smaller in MZI devices than in MRRs due to different waveguide widths. Devices with SiO2 upper cladding layer show strong tolerance to irradiation. Neutron irradiation leads to slight changes in the crystal symmetry in the Si cores of the optical devices and accelerated oxidization for devices without SiO2 cladding. A 2-µm top cladding of SiO2 layer significantly improves the radiation tolerance of these passive photonic devices.
RESUMEN
Bone regeneration and remodeling are complex physiological processes that are regulated by key transcription factors. Understanding the regulatory mechanism of key transcription factors on the osteogenic differentiation of mesenchymal stem cells (MSCs) is a key issue for successful bone regeneration and remodeling. In the present study, we investigated the regulatory mechanism of the histone deacetylase Sirtuin 7 (SIRT7) on the key transcription factor OSX and osteogenesis of MSCs. In this study, we found that SIRT7 knockdown increased ALP activity and in vitro mineralization and promoted the expression of the osteogenic differentiation markers DSPP, DMP1, BSP, OCN, and the key transcription factor OSX in MSCs. In addition, SIRT7 could associate with RNA binding motif protein 6 (RBM6) to form a protein complex. Moreover, RBM6 inhibited ALP activity, the expression of DSPP, DMP1, BSP, OCN, and OSX in MSCs, and the osteogenesis of MSCs in vivo. Then, the SIRT7/RBM6 protein complex was shown to downregulate the level of H3K18Ac in the OSX promoter by recruiting SIRT7 to the OSX promoter and inhibiting the expression of OSX isoforms 1 and 2. Furthermore, lncRNA PLXDC2-OT could associate with the SIRT7/RBM6 protein complex to diminish its binding and deacetylation function in the OSX promoter and its inhibitory function on OSX isoforms 1 and 2 and to promote the osteogenic potential of MSCs.
Asunto(s)
Células Madre Mesenquimatosas , ARN Largo no Codificante , Proteínas de Unión al ARN , Sirtuinas , Factor de Transcripción Sp7 , Diferenciación Celular/genética , Células Cultivadas , Humanos , Células Madre Mesenquimatosas/metabolismo , Osteogénesis/genética , Isoformas de Proteínas/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Proteínas de Unión al ARN/metabolismo , Sirtuinas/metabolismo , Factor de Transcripción Sp7/genética , Factor de Transcripción Sp7/metabolismoRESUMEN
OBJECTIVES: To explore whether the inorganic nitrate has a protective effect on biological damage induced by cone-beam computed tomography (CBCT) and compare it with Vitamin C. MATERIALS AND METHODS: Sixty Wistar rats were randomly separated into 6 groups: control group, irradiation (IR) group, NaNO3 group, IR + NaNO3 group, Vitamin C group, and IR + Vitamin C group. Rats were whole-body irradiated with CBCT four times. The absorbed dose of the skin surface was measured using thermoluminescent dosemeter chips and the mean whole-body absorbed dose was calculated. Peripheral blood was collected at 0.5 h and 24 h after irradiation. Bodyweight and organ index of rats before and after irradiation were analyzed. The bone marrow was taken for micronucleus test. Lymphocytes were isolated from peripheral blood for γ-H2AX immunofluorescence assay, apoptosis and reactive oxygen species (ROS) analysis. Total antioxidant capacity (TAC), malondialdehyde (MDA) and superoxide dismutase (SOD) in serum were detected. RESULTS: The mean absorbed dose of four whole-body CBCT scans for rats was 73.04 mGy. Bodyweight and organ index before and after irradiation with X-ray had no significant differences. The micronuclei frequency of IR + NaNO3 and IR + Vitamin C groups showed a significant decrease than that in the IR group, which was not significantly different from that of the control group. The γ-H2AX foci rates in the IR + NaNO3 group and the IR + Vitamin C group were significantly lower than that in the IR group. In addition, the foci rate of the IR + NaNO3 group returned to the baseline level of the control group 24 h after CBCT scanning. The apoptosis of lymphocytes in rats did not increase. The IR + NaNO3 group (P < 0.001) or IR + Vitamin C group (P < 0.001) showed a significant increase in ROS positive cells rate with the control group, while were significantly lower than those in the IR group (P < 0.01). In addition, the ROS-positive cell rate in the IR + NaNO3 group was significantly lower than that in the IR + Vitamin C group. The MDA in the serum of rats increased significantly, while SOD and TAC decreased significantly at 0.5 h after irradiation. CONCLUSIONS: Compared with Vitamin C, inorganic nitrate had better preventive effects on biological damage induced by CBCT scans in rats.
Asunto(s)
Antioxidantes , Nitratos , Administración Oral , Animales , Antioxidantes/farmacología , Ácido Ascórbico/farmacología , Tomografía Computarizada de Haz Cónico , Óxidos de Nitrógeno , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno , Superóxido DismutasaRESUMEN
The hydrogenation of CO2-derived carbonates to methanol is an alternative route for the indirect utilization of abundant C1 sources. Various Cu/SiO2catalysts with different copper loading content prepared by using an ammonia evaporation hydrothermal method are implemented to evaluate the catalytic performance of ethylene carbonate (EC) hydrogenation to methanol and ethylene glycol (EG). The Cu loading content was identified to significantly affect the Cu nanoparticles (NPs) size and metal-support interaction. Highly dispersed Cu NPs restricted and embedded in copper phyllosilicate presented a smaller average particle size than the impregnated Cu/SiO2-IM catalyst. ThexCu/SiO2catalyst with ultrafine Cu NPs showed abundant Cu-O-Si interfaces, acidic sites, and coherent Cu0and Cu+species. The 5Cu/SiO2catalyst achieved methanol yield of 76% and EG yield of 98% at EC conversion of 99%, and no obvious deactivation was observed after long-term operation. The superior catalytic performance of the 5Cu/SiO2catalyst is attributed to the synergetic effect between the appropriate Cu0surface area which provides sufficient active hydrogen, and the atomic ratio of Cu+for the polarization and activation of carbon-oxygen bonds.
RESUMEN
The fibroblast growth factor (FGF) pathway plays an important role in epithelial-mesenchymal interactions during tooth development. Nevertheless, how the ligands, receptors, and antagonists of the FGF pathway are involved in epithelial-mesenchymal interactions remains largely unknown. Miniature pigs exhibit tooth anatomy and replacement patterns like those in humans and hence can serve as large animal models. The present study investigated the spatiotemporal expression patterns of critical genes encoding FGF ligands (FGF3, FGF4, FGF7, and FGF9), antagonists (SPRY2 and SPRY4) and receptors (FGFR1, FGFR2, and FGFR3) in the third deciduous molars of miniature pigs at the cap (embryonic day 40, E40), early bell (E50), and late bell (E60) stages. The results of in situ hybridization (ISH) with tyramide signal amplification and of qRT-PCR analysis revealed increased expression of FGF7, FGFR1, FGFR2, and SPRY4 in dental epithelium and of FGF7 and FGFR1 in mesenchyme from E40 to E50. In contrast, the results revealed decreased expression of FGF3, FGF4, FGF9, and FGFR3 in dental epithelium and of FGF4, FGF9, FGFR2, and FGFR3 in the mesenchyme from E40 to E60. Mesenchyme signals of FGF3, FGF4, FGF7, SPRY2, FGFR2, and FGFR3 were concentrated in the odontoblast layer from E50 to E60. The distinct expression patterns of these molecules indicated elaborate regulation during dental morphogenesis. Our results provide a foundation for further investigation into fine-tuning dental morphogenesis and odontogenesis by controlling interactions between dental epithelium and mesenchyme, thus promoting tooth regeneration in large mammals.