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The submarine-confined bubble swarm is considered an important constraining environment for the early evolution of living matter due to the abundant gas/water interfaces it provides. Similarly, the spatiotemporal characteristics of the confinement effect in this particular scenario may also impact the origin, transfer, and amplification of chirality in organisms. Here, we explore the confinement effect on the chiral hierarchical assembly of the amphiphiles in the confined bubble array stabilized by the micropillar templates. Compared with the other confinement conditions, the assembly in the bubble scenario yields a fractal morphology and exhibits a unique level of the chiral degree, ordering, and orientation consistency, which can be attributed to the characteristic interfacial effects of the rapidly formed gas/water interfaces. Thus, molecules with a balanced amphiphilicity can be more favorable for the promotion. Not limited to the pure enantiomers, chiral amplification of the enantiomer-mixed assembly is observed only in the bubble scenario. Beyond the interfacial mechanism, the fast formation kinetics of the confined liquid bridges in the bubble scenario endows the assembly with the tunable hierarchical morphology when regulating the amphiphilicity, aggregates, and confined spaces. Furthermore, the chiral-induced spin selectivity (CISS) effect of the fractal hierarchical assembly was systematically investigated, and a strategy based on photoisomerization was developed to efficiently modulate the CISS effect. This work provides insights into the robustness of confined bubble swarms in promoting a chiral hierarchical assembly and the potential applications of the resulting chiral hierarchical patterns in solid-state spintronic and optical devices.
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Osteoporosis is one of the chronic complications of type 1 diabetes with high risk of fracture. The prevention of diabetic osteoporosis is of particular importance. Static magnetic fields (SMFs) exhibit advantages on improvement of diabetic complications. The biological effects and mechanism of SMFs on bone health of type 1 diabetic mice and functions of bone cells under high glucose have not been clearly clarified. In animal experiment, six-week-old male C57BL/6J mice were induced to type 1 diabetes and exposed to SMF of 0.4-0.7 T for 4 h/day lasting for 6 weeks. Bone mass, biomechanical strength, microarchitecture and metabolism were determined by DXA, three-point bending assay, micro-CT, histochemical and biochemical methods. Exposure to SMF increased BMD and BMC of femur, improved biomechanical strength with higher ultimate stress, stiffness and elastic modulus, and ameliorated the impaired bone microarchitecture in type 1 diabetic mice by decreasing Tb.Pf, Ct.Po and increasing Ct.Th. SMF enhanced bone turnover by increasing the level of markers for bone formation (OCN and Collagen I) as well as bone resorption (CTSK and NFAT2). In cellular experiment, MC3T3-E1 cells or primary osteoblasts and RAW264.7 cells were cultured in 25 mM high glucose-stimulated diabetic marrow microenvironment under differentiation induction and exposed to SMF. SMF promoted osteogenesis with higher ALP level and mineralization deposition in osteoblasts, and it also enhanced osteoclastogenesis with higher TRAP activity and bone resorption in osteoclasts under high glucose condition. Further, SMF increased iron content with higher FTH1 expression and regulated the redox level through activating HO-1/Nrf2 in tibial tissues, and lowered hepatic iron accumulation by BMP6-mediated regulation of hepcidin and lipid peroxidation in mice with type 1 diabetes. Thus, SMF may act as a potential therapy for improving bone health in type 1 diabetes with regulation on iron homeostasis metabolism and redox status.
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Reabsorção Óssea , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Osteoporose , Camundongos , Masculino , Animais , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Experimental/terapia , Camundongos Endogâmicos C57BL , Osteoblastos/metabolismo , Osteogênese , Ferro/metabolismo , Oxirredução , Campos Magnéticos , GlucoseRESUMO
CRISPR/Cas12a is a single effector nuclease that, like CRISPR/Cas9, has been harnessed for genome editing based on its ability to generate targeted DNA double strand breaks (DSBs). Unlike the blunt-ended DSB generated by Cas9, Cas12a generates sticky-ended DSB that could potentially aid precise genome editing, but this unique feature has thus far been underutilized. In the current study, we found that a short double-stranded DNA (dsDNA) repair template containing a sticky end that matched one of the Cas12a-generated DSB ends and a homologous arm sharing homology with the genomic region adjacent to the other end of the DSB enabled precise repair of the DSB and introduced a desired nucleotide substitution. We termed this strategy 'Ligation-Assisted Homologous Recombination' (LAHR). Compared to the single-stranded oligo deoxyribonucleotide (ssODN)-mediated homology directed repair (HDR), LAHR yields relatively high editing efficiency as demonstrated for both a reporter gene and endogenous genes. We found that both HDR and microhomology-mediated end joining (MMEJ) mechanisms are involved in the LAHR process. Our LAHR genome editing strategy, extends the repertoire of genome editing technologies and provides a broader understanding of the type and role of DNA repair mechanisms involved in genome editing.
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Sistemas CRISPR-Cas , Edição de Genes , Sistemas CRISPR-Cas/genética , Quebras de DNA de Cadeia Dupla , Reparo do DNA por Junção de Extremidades/genética , Recombinação Homóloga/genética , Reparo de DNA por RecombinaçãoRESUMO
OBJECTIVE: Lactobacillus salivarius is a probiotic bacteria strain in human and animal diets. The administration of probiotics to weaned piglets may improve their growth by optimizing the gastrointestinal bacterial composition. To further investigate the effect of bacterial communication between the gastrointestinal tract and lungs on bodily immunity, we reared weaned piglets in a low-ammonia gas environment. L. salivarius was supplemented to explore its effects on pulmonary immunity and its potential for bacterial translocation. RESULTS: One hundred sixty weaned piglets were allocated to four groups: L. salivarius-supplemented, L. reuteri-supplemented, control, and antibiotic drug (aureomycin)-supplemented. The feeding duration was 28 d. The body weights of piglets administered a strain of Lactobacillus were better than those of the control (P < 0.01). The transcription level of immune factors interleukin 2 (IL-2), IL-4, interferon α (IFN-α), and tumor necrosis factor α (TNF-α) in cells of the ileum and lung was significantly higher (P < 0.01). Lung and ileal mucus tissues were isolated to sequence the bacterial composition, which suggested a higher richness in the lungs at the phylum level, which was not significant in the ileum. Functional bacteria were more abundant in the ileum and lungs. The proportion of the genera of Lactobacillus, Prevotella, Actinobacillus, and Prevotellaceae_ NK3B31_group increased in two tissues, and a lower ratio of Streptococcus, Escherichia-Shigella, and mycoplasma was detected. The correlation between the microbial genus composition and the levels of immune factors suggests that the abundance of Lactobacillus plays the same positive role in the lungs and ileum. Mycoplasmas play a negative role in ileal and pulmonary immunity. More Lactobacillus reuteri and anaerobic probiotic bacteria were detected in the lungs. CONCLUSION: The colonization of Lactobacillus salivarius and Lactobacillus reuteri in the membrane of the ileum optimized the ileal microbial composition, enrolled other probiotic bacteria translating to the lung, improved the abundance of pulmonary microbiota, and enhanced immunity after exposure to low concentrations of ammonia.
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BACKGROUND: As substitutes for antibiotics, probiotic bacteria protect against digestive infections caused by pathogenic bacteria. Ligilactobacillus salivarius is a species of native lactobacillus found in both humans and animals. Herein, a swine-derived Ligilactobacillus salivarius was isolated and shown to colonize the ileal mucous membrane, thereby promoting nutritional digestion, absorption, and immunity. To evaluate its probiotic role, the entire genome was sequenced, the genetic information was annotated, and the metabolic information was analyzed. RESULTS: The phylogenetic relationship indicated that the bacteria was closer to L. salivarius MT573555.1 and MT585431.1. Functional genes included transporters, membrane proteins, enzymes, heavy metal resistance proteins, and putative proteins; metabolism-related genes were the most abundant. The six types of metabolic pathways secreted by L. salivarius were mainly composed of secretory transmembrane proteins and peptides. The secretory proteins of L. salivarius were digestive enzymes, functional proteins that regulate apoptosis, antibodies, and hormones. Non-targeted metabolomic analysis of L. salivarius metabolites suggested that ceramide, pyrrolidone- 5- carboxylic acid, N2-acetyl-L-ornithine, 2-ethyl-2-hydroxybutyric acid, N-lactoyl-phenylalanine, and 12 others were involved in antioxidation, repair of the cellular membrane, anticonvulsant, hypnosis, and appetite inhibition. Metabolites of clavaminic acid, antibiotic X14889C, and five other types of bacteriocins were identified, namely phenyllactic acid, janthitrem G, 13-demethyl tacrolimus, medinoside E, and tertonasin. The adherence and antioxidation of L. salivarius were also predicted. No virulence genes were found. CONCLUSION: The main probiotic properties of L. salivarius were identified using genomic, metabonomic, and biochemical assays, which are beneficial for porcine feeding. Our results provided deeper insights into the probiotic effects of L. salivarius.
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Ligilactobacillus salivarius , Humanos , Animais , Suínos , Filogenia , Genômica , Metabolômica , Antibacterianos , AntioxidantesRESUMO
In this study, we collected feces of Tibetan piglets from Nyingchi area for isolation, culture, identification, virulence gene analysis and drug resistance analysis of Escherichia Coli. The results demonstrated a 41.3% isolation rate of Diarrheagenic Escherichia Coli from Tibetan pigs with the main phylogenetic groups: group A (68.6%) and group B2 (15.7%). Typical E.coli accounted for 76.5%. The highest detection rates of porcine virulence genes were E.coli heat-resistant enterotoxin STb (58.82%) and F107 fimbrial subunit (23.53%). The highest detection rates of virulence genes from Tibetan pigs were fimC (80.39%) and ompA (76.47%). A drug sensitivity test showed that Diarrheagenic Escherichia Coli from Tibetan pigs had high drug resistance rates to mezlocillin, doxycycline and gentamicin. This study comprehensively analyzed the species composition, virulence and drug resistance of Diarrheagenic Escherichia Coli from Tibetan pigs, which provided a clearer and more targeted idea for the prevention and treatment of yellow and white dysentery in Tibetan pigs in the future.
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Infecções por Escherichia coli , Animais , Suínos , Infecções por Escherichia coli/veterinária , Infecções por Escherichia coli/tratamento farmacológico , Virulência , Tibet , Filogenia , Diarreia/veterinária , Escherichia coli , Resistência a MedicamentosRESUMO
Visualization of individual electronic states ascribed to specific unoccupied orbitals at the atomic scale can reveal fundamental information about chemical bonding, but it is challenging since bonding often results in only subtle variations in the whole density of states. Here, we utilize atomic-resolution energy-loss near-edge fine structure (ELNES) spectroscopy to map out the electronic states attributed to specific unoccupied p_{z} orbital around a fourfold coordinated silicon point defect in graphene, which is further supported by theoretical calculations. Our results illustrate the power of atomic-resolution ELNES towards the probing of defect-site-specific electronic orbitals in monolayer crystals, providing insights into understanding the effect of chemical bonding on the local properties of defects in solids.
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BACKGROUND: Fractures are the most common orthopedic diseases. It is known that static magnetic fields (SMFs) can contribute to the maintenance of bone health. However, the effect and mechanism of SMFs on fracture is still unclear. This study is aim to investigate the effect of moderate static magnetic fields (MMFs) on bone structure and metabolism during fracture healing. METHODS: Eight-week-old male C57BL/6J mice were subjected to a unilateral open transverse tibial fracture, and following treatment under geomagnetic field (GMF) or MMF. The micro-computed tomography (Micro-CT) and three-point bending were employed to evaluate the microarchitecture and mechanical properties. Endochondral ossification and bone remodeling were evaluated by bone histomorphometric and serum biochemical assay. In addition, the atomic absorption spectroscopy and ELISA were utilized to examine the influence of MMF exposure on iron metabolism in mice. RESULTS: MMF exposure increased bone mineral density (BMD), bone volume per tissue volume (BV/TV), mechanical properties, and proportion of mineralized bone matrix of the callus during fracture healing. MMF exposure reduced the proportion of cartilage in the callus area during fracture healing. Meanwhile, MMF exposure increased the number of osteoblasts in callus on the 14th day, and reduced the number of osteoclasts on the 28th day of fracture healing. Furthermore, MMF exposure increased PINP and OCN levels, and reduced the TRAP-5b and ß-CTX levels in serum. It was also observed that MMF exposure reduced the iron content in the liver and callus, as well as serum ferritin levels while elevating the serum hepcidin concentration. CONCLUSIONS: MMF exposure could accelerate fracture healing via promote the endochondral ossification and bone formation while regulating systemic iron metabolism during fracture healing. This study suggests that MMF may have the potential to become a form of physical therapy for fractures.
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Consolidação da Fratura , Fraturas Ósseas , Masculino , Animais , Camundongos , Consolidação da Fratura/fisiologia , Microtomografia por Raio-X , Camundongos Endogâmicos C57BL , Calo Ósseo/diagnóstico por imagem , Calo Ósseo/fisiologia , Campos Magnéticos , FerroRESUMO
Many studies indicated that static magnetic fields (SMFs) have anti-cancer effects. However, effect of SMFs on cancer cells with strength exceeding 12 T are rarely reported. The intracellular iron could participate in the reactive oxygen species (ROS) production and affect cell proliferation. This study aimed to investigate the effect of 12 T high static magnetic field (HiSMF) on osteosarcoma cells and the relationship with intracellular iron. The 12 T HiSMF was generated by a superconducting magnet. The proliferation was evaluated by CCK-8 assays and cell counting. The apoptosis, cell cycle distribution, and ROS were evaluated by flow cytometry. Intracellular iron status was evaluated by atomic absorption spectroscopy and Calcein-AM/2,2'-bipyridyl. The expression of cell cycle and iron metabolism-related genes were analyzed by Western Blot. The result showed that 12 T HiSMF exposure suppressed the proliferation of osteosarcoma cell lines MNNG/HOS, U-2 OS, and MG63 via cell cycle arrest in S and G2/M. Meanwhile, 12 T HiSMF increasing intracellular ROS, and its antitumor effect was reduced by antioxidant. Furthermore, the intracellular total and free iron levels, the expression of FTH1 and DMT1 were increased by 12 HiSMF. The iron chelator (DFO) could reduce the cytotoxicity of 12 T HiSMF on osteosarcoma cells. Moreover, 12 T HiSMF could enhance the cytotoxicity of cisplatin and sorafenib in osteosarcoma cells. In Conclusion, 12 T HiSMF could suppress osteosarcoma cells proliferation via intracellular iron and ROS related cell cycle arrest, and have application potential in osteosarcoma therapy combined with sorafenib and cisplatin.
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Neoplasias Ósseas , Osteossarcoma , Apoptose , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Cisplatino/farmacologia , Humanos , Ferro , Campos Magnéticos , Osteossarcoma/genética , Espécies Reativas de Oxigênio/metabolismo , Sorafenibe/farmacologiaRESUMO
An arbitrary unknown quantum state cannot be measured precisely or replicated perfectly. However, quantum teleportation enables unknown quantum states to be transferred reliably from one object to another over long distances, without physical travelling of the object itself. Long-distance teleportation is a fundamental element of protocols such as large-scale quantum networks and distributed quantum computation. But the distances over which transmission was achieved in previous teleportation experiments, which used optical fibres and terrestrial free-space channels, were limited to about 100 kilometres, owing to the photon loss of these channels. To realize a global-scale 'quantum internet' the range of quantum teleportation needs to be greatly extended. A promising way of doing so involves using satellite platforms and space-based links, which can connect two remote points on Earth with greatly reduced channel loss because most of the propagation path of the photons is in empty space. Here we report quantum teleportation of independent single-photon qubits from a ground observatory to a low-Earth-orbit satellite, through an uplink channel, over distances of up to 1,400 kilometres. To optimize the efficiency of the link and to counter the atmospheric turbulence in the uplink, we use a compact ultra-bright source of entangled photons, a narrow beam divergence and high-bandwidth and high-accuracy acquiring, pointing and tracking. We demonstrate successful quantum teleportation of six input states in mutually unbiased bases with an average fidelity of 0.80 ± 0.01, well above the optimal state-estimation fidelity on a single copy of a qubit (the classical limit). Our demonstration of a ground-to-satellite uplink for reliable and ultra-long-distance quantum teleportation is an essential step towards a global-scale quantum internet.
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LIGHT is a member of the TNF superfamily and a proinflammatory cytokine involved in liver pathogenesis. Many liver diseases involve activation of Toll-like receptor 3 (TLR3), which is activated by double-stranded RNA (dsRNA). However, the involvement of LIGHT in TLR3 implicated liver diseases is not clear. In this study, we investigated the role of LIGHT in TLR3 involved liver pathogenesis by using a mouse model of TLR3 agonist poly(I:C)-induced hepatitis. We found LIGHT expression at both protein and mRNA level in liver tissues is dramatically increased during the course of poly(I:C)-induced liver injury. This induction depends on NF-κB activation as pretreating the mice with a NF-κB inhibitor abrogates LIGHT upregulation. Importantly, blockade of the LIGHT signaling pathway with the recombinant LIGHT receptor HVEM protein ameliorates liver injury in poly(I:C)-induced hepatitis. Conclusions. These results indicate that LIGHT amplification by NF-κB plays a significant role in TLR3 involved hepatitis and points LIGHT to be a potential drug target for liver disease therapy.
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Hepatite , NF-kappa B , Receptor 3 Toll-Like , Citocinas , Hepatite/genética , Hepatite/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Poli I-C/farmacologia , Transdução de Sinais , Receptor 3 Toll-Like/genética , Receptor 3 Toll-Like/metabolismo , Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética , Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo , Animais , Camundongos , Modelos Animais de Doenças , Doença AgudaRESUMO
We present an illustrative case series in which high spatial resolution black blood (BB) MRI sequences were used as an adjunct in the acute management of intracranial aneurysms with diagnostic uncertainty regarding rupture status. Several acute management dilemmas are discussed including the surveillance of previously treated ruptured intracranial aneurysms, identifying culprit lesion(s) amongst multiple ruptured intracranial aneurysms, and risk stratifying incidental unruptured intracranial aneurysms. We present our experience which supports the evaluation of this vessel wall imaging technique in larger multi-centre observational studies. MR imaging was performed on a 3.0 Tesla Siemens Somatom Vida system and sequences used included: Susceptibility Weighted Imaging, Diffusion Weighted Imaging & 3D T1 pre- and post-contrast-enhanced BB sequences.
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As a basic task and key link of space situational awareness, space target recognition has become crucial in threat analysis, communication reconnaissance and electronic countermeasures. Using the fingerprint features carried by the electromagnetic signal to recognize is an effective method. Because traditional radiation source recognition technologies are difficult to obtain satisfactory expert features, automatic feature extraction methods based on deep learning have become popular. Although many deep learning schemes have been proposed, most of them are only used to solve the inter-class separable problem and ignore the intra-class compactness. In addition, the openness of the real space may invalidate the existing closed-set recognition methods. In order to solve the above problems, inspired by the application of prototype learning in image recognition, we propose a novel method for recognizing space radiation sources based on a multi-scale residual prototype learning network (MSRPLNet). The method can be used for both the closed- and open-set recognition of space radiation sources. Furthermore, we also design a joint decision algorithm for an open-set recognition task to identify unknown radiation sources. To verify the effectiveness and reliability of the proposed method, we built a set of satellite signal observation and receiving systems in a real external environment and collected eight Iridium signals. The experimental results show that the accuracy of our proposed method can reach 98.34% and 91.04% for the closed- and open-set recognition of eight Iridium targets, respectively. Compared to similar research works, our method has obvious advantages.
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Age-related macular degeneration (AMD) is the leading cause of blindness in elderly people, with limited treatment options available for most patients. AMD involves the death of retinal pigment epithelium (RPE) and photoreceptor cells, with mitochondria dysfunction being a critical early event. In the current study, we utilized our unique resource of human donor RPE graded for AMD presence and severity to investigate proteome-wide dysregulation involved in early AMD. Organelle-enriched fractions of RPE were isolated from donors with early AMD (n = 45) and healthy age-matched controls (n = 32) and were analyzed by UHR-IonStar, an integrated proteomics platform enabling reliable and in-depth proteomic quantification in large cohorts. A total of 5941 proteins were quantified with excellent analytical reproducibility, and with further informatics analysis, many biological functions and pathways were found to be significantly dysregulated in donor RPE samples with early AMD. Several of these directly pinpointed changes in mitochondrial functions, e.g., translation, ATP metabolic process, lipid homeostasis, and oxidative stress. These novel findings highlighted the value of our proteomics investigation by allowing a better understanding of the molecular mechanisms underlying early AMD onset and facilitating both treatment development and biomarker discovery.
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Degeneração Macular , Epitélio Pigmentado da Retina , Humanos , Idoso , Epitélio Pigmentado da Retina/metabolismo , Proteômica , Reprodutibilidade dos Testes , Degeneração Macular/metabolismo , Estresse OxidativoRESUMO
It is generally believed that few-layer films of wurtzite materials remove the destabilizing dipole by converting to a flat hexagonal structure. However, using first-principles calculations, we demonstrate that contrary to the existing consensus these few-layer hexagonal films exhibit a small symmetric rumpling and are not perfectly flat. We then perform a systematic study of the rumpling behavior of a range of few-layer III-V and II-VI films. The symmetric rumpled configuration enables such films to cancel out the dipole and thereby to avoid the polar instability. This stabilization mechanism is quite distinct from those known for bulk and few-layer polar materials. Compared to the perfectly flat films, the rumpled films exhibit lower electrostatic potential energy, lower total energy, higher bonding strength, and thus greater stability and larger band gaps. We also discuss the relationship between rumpling behavior, interlayer interactions, and ionicity through electrostatic analysis.
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Paeonol is the bioactive component in Paeonia lactiflora Pall., Cynanchum paniculatum and Paeonia × suffruticosa Andr. Paeonol has been previously demonstrated to inhibit the release of tumor necrosis factor α (TNF-α) and interluekin 6 (IL-6) in chondrocytes. Sirtuin 1 (SIRT1) is downregulated in degraded cartilage and paeonol could induce nuclear accumulation of SIRT1. Therefore, the present study aims to investigate the possible role of paeonol in chondrocyte inflammation and cartilage protection in osteoarthritis (OA) as well as its regulation of SIRT1. Primary chondrocytes from rat knee joints were transfected with short hairpin (sh) - SIRT1 and (or) paeonol prior to IL-1ß exposure, and then inflammatory response, apoptosis, and extracellular matrix (ECM) degradation in the cells were evaluated concurrent with the activation of the nuclear factor κß (NF-κß) signaling pathway. Increased levels of TNF-α, IL-17, IL-6, matrix metalloproteinase 1 (MMP-1), MMP-3, and MMP-13 along with decreased tissue inhibitor of metalloproteinases 1 and type II collagen levels were found in IL-1ß-stimulated chondrocytes. Chondrocyte apoptosis was elevated and the NF-κß signaling pathway was activated in response to IL-1ß treatment. Paeonol enhanced SIRT1 expression to inactivate the NF-κß signaling pathway, thereby ameliorating inflammatory cytokine secretion, ECM degradation, and chondrocyte apoptosis. In conclusion, the results of the present study confirm the potential of paeonol as a candidate OA drug.
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Condrócitos , Osteoartrite , Acetofenonas/metabolismo , Acetofenonas/farmacologia , Acetofenonas/uso terapêutico , Animais , Células Cultivadas , Condrócitos/metabolismo , Interleucina-1beta/metabolismo , NF-kappa B/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/patologia , Ratos , Sirtuína 1/metabolismoRESUMO
Foodborne mycotoxins are toxic metabolites that are produced by fungi. The widespread contamination of food and its by-products by mycotoxins is a global food safety problem that potentially threatens public health and other exposed animals. Most foodborne mycotoxins induce hepatotoxicity. However, only few studies have investigated the regulatory mechanisms of mitochondrial calcium transport monomers in mycotoxin-induced hepatotoxicity. Therefore, according to relevant studies and reports, this review suggests that intracellular Ca(2 +) homeostasis and mitochondrial Ca(2 +) uniporter are involved in the regulation of mycotoxin-induced hepatotoxicity. This review provides some ideas for future research involving mitochondrial Ca(2 +) uniporter in the molecular targets of mycotoxin-induced hepatotoxicity, as well as a reference for the research and development of related drugs and the treatment of related diseases.
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Doença Hepática Induzida por Substâncias e Drogas , Micotoxinas , Animais , Cálcio , Canais de Cálcio , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Contaminação de Alimentos/análise , Micotoxinas/toxicidadeRESUMO
OBJECTIVES: This study evaluated the associated biological effects of radio-frequency (RF) exposure at 16 T magnetic resonance imaging (MRI) on mice health. MATERIAL AND METHODS: A total of 48 healthy 8-week-old male C57BL/6 mice were investigated. A 16 T high static magnetic field (HiSMF) was generated by a superconducting magnet, and a radiofrequency (RF) electromagnetic field for hydrogen resonance at 16 T (700 MHz) was transmitted via a homemade RF system. The mice were exposed inside the 16 T HiSMF with the 700 MHz RF field for 60 min, and the body weight, organ coefficients, histomorphology of major organs, and blood indices were analyzed for the basal state of the mice on day 0 and day 14. The Heat Shock Protein 70 (HSP70), cyclooxygenase 2 (COX2), and interleukin- 6 (IL-6) were used to evaluate the thermal effects on the brain. Locomotor activity, the open field test, tail suspension test, forced swimming test, and grip strength test were used to assess the behavioral characteristics of the mice. RESULTS: The 16 T HiSMF with 700 MHz RF electromagnetic field exposure had no significant effects on body weight, organ coefficients, or histomorphology of major organs in the mice. On day 0, the expressions of HSP70 and COX2 in the brain were increased by 16 T HiSMF with 700 MHz RF electromagnetic field exposure. However, the expression of HSP70, COX2, and IL-6 had no significant difference compared with the sham group on day 14. Compared with the sham groups, the meancorpuscularvolume (MCV) on day 0 and the total protein (TP) on day 14 were increased significantly, whereas the other blood indices did not change significantly. The 16 T HiSMF with 700 MHz RF electromagnetic field exposure caused the mice to briefly circle tightly but had no effect on other behavioral indicators. CONCLUSIONS: In summary, 16 T HiSMF with 700 MHz RF electromagnetic field exposure for 60 min did not have severe effects on mice.
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Osteoporosis and sarcopenia (termed "Osteosarcopenia"), the twin-aging diseases, are major contributors to reduced bone mass and muscle weakness in the elderly population. Connexin 43 (Cx43) in osteocytes has been previously reported to play vital roles in bone homeostasis and muscle function in mature mice. The Cx43-formed gap junctions (GJs) and hemichannels (HCs) in osteocytes are important portals for the exchange of small molecules in cell-to-cell and cell-to-extracellular matrix, respectively. However, the roles of Cx43-based GJs and HCs in both bone and muscle aging are still unclear. Here, we used two transgenic mouse models with overexpression of the dominant negative Cx43 mutants primarily in osteocytes driven by the 10-kb Dmp1 promoter, R76W mice (inhibited gap junctions but enhanced hemichannels) and Δ130-136 mice (both gap junction and hemichannels are inhibited), to determine the actions of Cx43-based hemichannels (HCs) and gap junctions (GJs) in the regulation of bone and skeletal muscle from aged mice (18 months) as compared with those from adult mice (10 months). We demonstrated that enhancement of Cx43 HCs reduces bone mass due to increased osteoclast surfaces while the impairment of Cx43 HCs increases osteocyte apoptosis in aged mice caused by reduced PGE2 levels. Furthermore, altered mitochondrial homeostasis with reduced expression of Sirt-1, OPA-1, and Drp-1 resulted in excessive ROS level in muscle soleus (SL) of aged transgenic mice. In vitro, the impairment of Cx43 HCs in osteocytes from aged mice also promoted muscle collagen synthesis through activation of TGFß/smad2/3 signaling because of reduced PGE2 levels in the PO CM. These findings indicate that the enhancement of Cx43 HCs while GJs are inhibited reduces bone mass, and the impairment of Cx43 HCs inhibits PGE2 level in osteocytes and this reduction promotes muscle collagen synthesis in skeletal muscle through activation of TGFß/smad2/3 signaling, which together with increased ROS level contributes to reduced muscle force in aged mice.
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Conexina 43 , Osteócitos , Animais , Masculino , Camundongos , Colágeno/metabolismo , Conexina 43/genética , Conexina 43/metabolismo , Dinoprostona/metabolismo , Junções Comunicantes/metabolismo , Camundongos Transgênicos , Músculo Esquelético/metabolismo , Osteócitos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Crescimento Transformador beta/metabolismoRESUMO
KCTD15 is associated with body mass index and fat deposition in humans, mice and chickens. However, the function of KCTD15 in pig fat deposition remains unclear. In this study, we cloned and analysed the cDNA sequence of porcine KCTD15. The full length of the mRNA sequence of KCTD15 is 4,091 bp, encoding 283 amino acids. The protein is hydrophilic, it has a relative molecular mass of about 31.9 kDa and an isoelectric point of 7.09 with no signal peptide sequence or transmembrane structure. Expression analysis showed that KCTD15 expression level was significantly higher in the tissues of Large White pigs (LW) than in those of Tibetan pigs (TP) and Diannan Small-ear pigs (DN) at 6 months of age, whereas its expression level in embryonic tissues of LW at 60 days was lower than that in tissues of TP and Wujin pigs (WJ). In pig primary adipocytes, the expression level of KCTD15 is high in the early stage of differentiation and gradually decreases in later stages. Additionally, the single-nucleotide polymorphism (SNP) site T-2030C (T/C mutation, located 2,030 bp upstream of the start codon) showed a dominant allele T with high promoter activity in the LW population and a dominant allele C in the TP and WJ populations. Our results indicate that KCTD15 is involved in pig fat deposition and that T-2030C is an important regulatory site for transcriptional activity, affecting fat deposition.