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BACKGROUND: The present study is to evaluate the clinical characteristics of patients with temporomandibular disorders (TMD). METHODS: A total of 3362 TMD patients were included. Each participant had complete medical records according to the diagnostic criteria for temporomandibular disorders (DC/TMD). The clinical characteristics including symptoms and signs in relation to age and gender were analyzed. RESULTS: The mean age of the patients seeking care was 29.89 ± 13.73Y, and 68.6% of patients were aged 16-35 years. The female-to-male ratio of patients was 2.2: 1, and the average age of males was significantly lower than that of females. The prevalence of clicking symptoms decreased with age, while the prevalence of pain symptoms and limitations in jaw movement increased with age. Females were more likely to have limitations in jaw movement than males. Among the patients with pain, the average visual analogue scale (VAS) was 2.96 ± 1.23. The average VAS score of acute TMD patients (≤ 3 months) was significantly higher than that of chronic TMD patients (> 3 months). CONCLUSIONS: The majority of TMD patients seeking care were young people. The number and average age of female patients was higher than the males. Female patients were more likely to have limitations in jaw movement than males.
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Transtornos da Articulação Temporomandibular , Humanos , Masculino , Feminino , Transtornos da Articulação Temporomandibular/epidemiologia , Adulto , Estudos Retrospectivos , Adolescente , Fatores Sexuais , Fatores Etários , Adulto Jovem , Dor Facial , Pessoa de Meia-Idade , Medição da Dor , PrevalênciaRESUMO
Dendrobine (DDB), an alkaloid isolated from the Chinese herb Dendrobium, has antioxidant and anti-inflammatory effects; however, whether DDB reduces oleic acid (OA)-induced lipid accumulation remains unclear. OA-induced lipid accumulation model of HepG2 cells were treated with DDB. Cellular lipid deposition was assessed by Oil Red O (ORO) staining and triglyceride and total cholesterol detection. RNA-Sequencing (RNA-seq), biological function analysis, and transcription factor (TFs) prediction were combined to identify key TF in the DDB-treated OA model. Finally, the roles of FOS and METTL14 were examined using a DDB-induced lipid accumulation model. DDB inhibited OA-induced lipid accumulation. We identified 895 differentially expressed genes (DEGs) that were mainly enriched in various biological processes of lipid synthesis and transport. Four transcription factors (SOX9, MLXIPL, FOS, and JUN) associated with lipid metabolism and FOS levels in the OA-induced lipid accumulation model after DDB treatment had the greatest changes in expression change. Overexpression of FOS alleviates the inhibitory effect of DDB on OA-induced lipid accumulation. METTL14 is a target gene of FOS, and simultaneous interference with METTL14 in cells with high FOS expression restored the alleviating effect of DDB on lipid accumulation. DDB alleviated OA-induced lipid accumulation by inhibiting the FOS/METTL14 pathway.
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INTRODUCTION: Oxidative stress and neuroapoptosis are significant pathological processes that occur in response to intracerebral hemorrhage (ICH), however, the optimal therapeutic strategy to treat these responses remains unknown. Pterostilbene (PTE) influences neural cell survival in in the pathology of a number of neurological diseases, but the mechanisms underlying this influence at present are not clear. The objective of the present study was to examine the potential impact of PTE on mitigating oxidative stress and neuronal apoptosis following ICH, while also elucidating the potential underlying pathways. MATERIAL & METHOD: For in vivo experimentation, male C57BL/6 mice were used to establish ICH models. Wet-to-dry weight ratios were utilized to assess the degree of cerebral edema in the context of PTE intervention. Behavioral experiments were conducted to evaluate neurological dysfunction and cognitive impairment, and hematoxylin and eosin staining was employed to observe histopathological changes in the brain. Furthermore, oxidative stress levels in hippocampal tissues were measured, and cell apoptosis was examined using TUNEL staining and western blotting techniques. In vitro experiments were conducted to evaluate the extent of oxidative stress and neural apoptosis after sirtuin 1 (SIRT1) siRNA treatment. Immunofluorescence cytochemistry was used to analyze the immunofluorescence colocalization of SIRT1 and NeuN. RESULT: Mice that experienced ICH exhibited worsening neurological deterioration, increased oxidative stress and neuronal cell apoptosis. However, the addition of PTE was found to lessen these effects. Furthermore, PTE was found to activate the SIRT1-mediated Nrf2 pathway in mice with ICH. When SIRT1 was inhibited, levels of oxidative stress and neuronal apoptosis increased, even in the presence of PTE. CONCLUSION: The present study provided evidence to indicate that PTE can suppress oxidative damage and neuronal apoptosis following ICH by activating the SIRT1/Nrf2 pathway.
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BACKGROUND: Syndecan 4 (SDC4), a type I transmembrane proteoglycan, serves as a critical link between chondrocytes and the extracellular matrix. OBJECTIVE: This study aimed to explore the role of SDC4 in cartilage degeneration of temporomandibular joint osteoathritis (TMJOA). METHODS: Condylar chondrocytes were stimulated with varying concentrations of recombinant rat interleukin-1ß (rrIL-1ß) and SDC4 small interfering RNA (si-SDC4). Anti-SDC4 ectodomain-specific antibodies or IgG were intra-articularly administrated in a TMJOA model rats. SDC4 conditional knockout (SDC4-cKO) and Sdc4flox/flox mice were induced TMJOA. Cartilage degeneration was assessed using haematoxylin & eosin (H&E) and safranin O (SO) staining. Protein levels of SDC4, matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase with a thrombospondin motifs 5 (ADAMTS5), tumour necrosis factor α (TNFα), type II collagen (Col-II), aggrecan (ACAN), cleaved caspase 3 (CASP3), Ki67 and related pathways in condylar cartilage were evaluated by immunohistochemical (IHC) staining or western blot assays. RESULTS: SDC4 expression was evidently increased in MIA-model animals compared to control groups. rrIL-1ß stimulation increased the expression of SDC4, MMP3 and ADAMTS5 expression in chondrocytes, while decreasing the expression of Col-II. These effects were reversed by si-SDC4 in vitro. In vivo, SDC4 blockade reduced the death of chondrocytes and the loss of cartilage matrix, which was evidenced by increased expression of Col-II and ACAN, and a decrease in SDC4, MMP13 and cleaved-CASP3-positive cells. Furthermore, the protein levels of ACAN and Ki67 were elevated, and the ERK1/2 and P38 signalling pathways were activated following SDC4 inhibition. CONCLUSIONS: SDC4 inhibition significantly ameliorates condylar cartilage degeneration, which was mediated, at least partly, through P38 and ERK1/2 signalling. Inhibition of SDC4 may be of great value for the treatment of TMJOA.
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Lactobacillus plantarum AR495 is a widely used probiotic for the treatment of various digestive diseases, including irritable bowel syndrome (IBS). However, the specific mechanisms of L. plantarum AR495 in alleviating IBS remain unclear. Abnormal intestinal tryptophan metabolism can cause disordered immune responses, gastrointestinal peristalsis, digestion and sensation, which is closely related to IBS pathogenesis. The aim of this study is to explore the effects and mechanisms of L. plantarum AR495 in regulating tryptophan metabolism. Primarily, tryptophan and its related metabolites in patients with IBS and healthy people were analyzed, and an IBS rat model of acetic acid enema plus restraint stress was established to explore the alleviation pathway of L. plantarum AR495 in tryptophan metabolism. It was found that the 5-HT pathway was significantly changed, and the 5-HTP and 5-HT metabolites were significantly increased in the feces of patients with IBS, which were consistent with the results obtained for the IBS rat model. Maladjusted 5-HT could increase intestinal peristalsis and lead to an increase in the fecal water content and shapeless stool in rats. On the contrary, these two metabolites could be restored to normal levels via intragastric administration of L. plantarum AR495. Further study of the metabolic pathway showed that L. plantarum AR495 could effectively reduce the abundance of 5-HT by inhibiting the expression of enterochromaffin cells rather than promoting its decomposition. In addition, the results showed that L. plantarum AR495 did not affect the expression of SERT. To sum up, L. plantarum AR495 could restore the normal levels of 5-HT by inhibiting the abnormal proliferation of enterochromaffin cells and the excessive activation of TPH1 to inhibit the intestinal peristalsis in IBS. These findings provide insights for the use of probiotics in the treatment of IBS and other diarrheal diseases.
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Colo , Síndrome do Intestino Irritável , Lactobacillus plantarum , Probióticos , Ratos Sprague-Dawley , Serotonina , Triptofano , Síndrome do Intestino Irritável/metabolismo , Síndrome do Intestino Irritável/terapia , Síndrome do Intestino Irritável/microbiologia , Lactobacillus plantarum/metabolismo , Animais , Triptofano/metabolismo , Ratos , Probióticos/farmacologia , Humanos , Masculino , Colo/metabolismo , Colo/microbiologia , Serotonina/metabolismo , Feminino , Adulto , Pessoa de Meia-Idade , Modelos Animais de Doenças , Fezes/microbiologia , Adulto JovemRESUMO
Rabies virus (RABV) causes a fatal neurological disease, consisting of unsegmented negative-strand RNA, which encodes five structural proteins (3'-N-P-M-G-L-5'). Apolipoprotein D (ApoD), a lipocalin, is upregulated in the nervous system after injury or pathological changes. Few studies have focused on the role of ApoD during virus infection so far. This study demonstrated that ApoD is upregulated in the mouse brain (in vivo) and C8-D1A cells (in vitro) after RABV infection. By upregulating ApoD expression in C8-D1A cells, we found that ApoD facilitated RABV replication. Additionally, Co-immunoprecipitation demonstrated that ApoD interacted with RABV glycoprotein (G protein). The interaction could promote RABV replication by upregulating the cholesterol level. These findings revealed a novel role of ApoD in promoting RABV replication and provided a potential therapeutic target for rabies.
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Apolipoproteínas D , Colesterol , Vírus da Raiva , Raiva , Replicação Viral , Animais , Feminino , Humanos , Masculino , Camundongos , Apolipoproteínas D/metabolismo , Apolipoproteínas D/genética , Encéfalo/virologia , Encéfalo/metabolismo , Linhagem Celular , Colesterol/metabolismo , Células HEK293 , Raiva/metabolismo , Raiva/virologia , Vírus da Raiva/fisiologia , Regulação para CimaRESUMO
Twisted bilayer graphene (tBLG) provides a fascinating platform for engineering flat bands and inducing correlated phenomena. By designing the stacking architecture of graphene layers, twisted multilayer graphene can exhibit different symmetries with rich tunability. For example, in twisted monolayer-bilayer graphene (tMBG) which breaks the C2z symmetry, transport measurements reveal an asymmetric phase diagram under an out-of-plane electric field, exhibiting correlated insulating state and ferromagnetic state respectively when reversing the field direction. Revealing how the electronic structure evolves with electric field is critical for providing a better understanding of such asymmetric field-tunable properties. Here we report the experimental observation of field-tunable dichotomic electronic structure of tMBG by nanospot angle-resolved photoemission spectroscopy (NanoARPES) with operando gating. Interestingly, selective enhancement of the relative spectral weight contributions from monolayer and bilayer graphene is observed when switching the polarity of the bias voltage. Combining experimental results with theoretical calculations, the origin of such field-tunable electronic structure, resembling either tBLG or twisted double-bilayer graphene (tDBG), is attributed to the selectively enhanced contribution from different stacking graphene layers with a strong electron-hole asymmetry. Our work provides electronic structure insights for understanding the rich field-tunable physics of tMBG.
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Topological Dirac nodal-line semimetals host topologically nontrivial electronic structure with nodal-line crossings around the Fermi level, which could affect the photocarrier dynamics and lead to novel relaxation mechanisms. Herein, by using time- and angle-resolved photoemission spectroscopy, we reveal the previously inaccessible linear dispersions of the bulk conduction bands above the Fermi level in a Dirac nodal-line semimetal PtSn4, as well as the momentum and temporal evolution of the gapless nodal lines. A surprisingly ultrafast relaxation dynamics within a few hundred femtoseconds is revealed for photoexcited carriers in the nodal line. Theoretical calculations suggest that such ultrafast carrier relaxation is attributed to the multichannel scatterings among the complex metallic bands of PtSn4 via electron-phonon coupling. In addition, a unique dynamic relaxation mechanism contributed by the highly anisotropic Dirac nodal-line electronic structure is also identified. Our work provides a comprehensive understanding of the ultrafast carrier dynamics in a Dirac nodal-line semimetal.
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BACKGROUND: Rectus abdominis separation (DRA) affects pelvic stability and body image. No studies have explored the effects of manual massage on early postpartum DRA and postpartum depression. AIM: To analyze the curative effect of massage on early postpartum DRA and its impact on postpartum depression and thus its ability promote the overall psychosomatic rehabilitation of postpartum women. METHODS: Data were retrospectively collected on 70 primiparous women with postpartum DRA who underwent rehabilitation at the Postpartum Rehabilitation Center of Huzhou Maternal and Child Health Hospital from October 2022 to September 2023. The patients were divided into the Group S (35 cases, biomimetic electrical stimulation treatment) and Group L (35 cases, biomimetic electrical stimulation combined with manual massage treatment). Baseline data, the edinburgh postpartum depression scale (EPDS) score, and the visual analog scale (VAS) scores for rectus abdominis distance, waist circumference, and lower back pain before and after treatment were compared. RESULTS: No significant differences were found in the baseline data, rectus abdominis distance, waist circumference, and VAS and EPDS scores between the two groups before treatment (P > 0.05). After treatment, the distance between rectus abdominis and waist circumference in Group L were significantly smaller than those in Group S (P < 0.05). Furthermore, lower back pain (VAS score) and the EPDS score in Group L were significantly lower than those in Group S (P < 0.05). CONCLUSION: Manual massage can significantly reduce early postpartum DRA, waist circumference, and back pain and improve the patient's mental state and postpartum depression.
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Person re-identification (ReID) typically encounters varying degrees of occlusion in real-world scenarios. While previous methods have addressed this using handcrafted partitions or external cues, they often compromise semantic information or increase network complexity. In this paper, we propose a new method from a novel perspective, termed as OAT. Specifically, we first use a Transformer backbone with multiple class tokens for diverse pedestrian feature learning. Given that the self-attention mechanism in the Transformer solely focuses on low-level feature correlations, neglecting higher-order relations among different body parts or regions. Thus, we propose the Second-Order Attention (SOA) module to capture more comprehensive features. To address computational efficiency, we further derive approximation formulations for implementing second-order attention. Observing that the importance of semantics associated with different class tokens varies due to the uncertainty of the location and size of occlusion, we propose the Entropy Guided Fusion (EGF) module for multiple class tokens. By conducting uncertainty analysis on each class token, higher weights are assigned to those with lower information entropy, while lower weights are assigned to class tokens with higher entropy. The dynamic weight adjustment can mitigate the impact of occlusion-induced uncertainty on feature learning, thereby facilitating the acquisition of discriminative class token representations. Extensive experiments have been conducted on occluded and holistic person re-identification datasets, which demonstrate the effectiveness of our proposed method.
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Magic-angle twisted bilayer graphene exhibits correlated phenomena such as superconductivity and Mott insulating states related to the weakly dispersing flat band near the Fermi energy. Such a flat band is expected to be sensitive to both the moiré period and lattice relaxations. Thus, clarifying the evolution of the electronic structure with the twist angle is critical for understanding the physics of magic-angle twisted bilayer graphene. Here we combine nano-spot angle-resolved photoemission spectroscopy and atomic force microscopy to resolve the fine electronic structure of the flat band and remote bands, as well as their evolution with twist angle from 1.07° to 2.60°. Near the magic angle, the dispersion is characterized by a flat band near the Fermi energy with a strongly reduced band width. Moreover, we observe a spectral weight transfer between remote bands at higher binding energy, which allows to extract the modulated interlayer spacing near the magic angle. Our work provides direct spectroscopic information on flat band physics and highlights the important role of lattice relaxations.
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Cyclic di-GMP (c-di-GMP) is a second messenger that promotes biofilm formation in several bacterial species, but the mechanisms are often unclear. Here, we report that c-di-GMP promotes biofilm formation in mycobacteria in a manner dependent on the nucleoid-associated protein Lsr2. We show that c-di-GMP specifically binds to Lsr2 at a ratio of 1:1. Lsr2 upregulates the expression of HadD, a (3R)-hydroxyacyl-ACP dehydratase, thus promoting the synthesis of keto-mycolic acid and biofilm formation. Thus, Lsr2 acts as a c-di-GMP receptor that links the second messenger's function to lipid synthesis and biofilm formation in mycobacteria.
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GMP Cíclico/análogos & derivados , Mycobacterium , Ácidos Micólicos , Adipogenia , Cetoácidos , BiofilmesRESUMO
Transition metal dichalcogenide (TMDC) films exhibit rich phases and superstructures, which can be controlled by the growth conditions as well as post-growth annealing treatment. Here, the selective growth of monolayer TaTe2 films with different phases as well as superstructures using molecular beam epitaxy (MBE) is reported. Monolayer 1H-TaTe2 and 1T-TaTe2 films can be selectively controlled by varying the growth temperature, and their different electronic structures are revealed through the combination of angle-resolved photoemission spectroscopy measurements (ARPES) and first-principles calculations. Moreover, post-growth annealing of the 1H-TaTe2 film further leads to a transition from a 19 × 19 $\sqrt {19}{\times }\sqrt {19}$ superstructure to a new 2 × 2 superstructure, where two gaps are observed in the electronic structure and persist up to room temperature. First-principles calculations reveal the role of the phonon instability in the formation of superstructures and the effect of local atomic distortions on the modified electronic structures. This work demonstrates the manipulation of the rich phases and superstructures of monolayer TaTe2 films by controlling the growth kinetics and post-growth annealing.
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BACKGROUND: Abnormal lipid metabolism is involved in the development of osteoarthritis (OA). ATP-binding cassette protein G1 (ABCG1) is crucial in mediating the outflow of cholesterol, phosphatidylcholine and sphingomyelin and reducing intracellular lipid accumulation. OBJECTIVE: This study aimed to evaluate whether ABCG1 participates in the abnormal adipogenesis of chondrocytes in osteoarthritic cartilage of temporomandibular joint. METHODS: Eight-week-old female rats were subjected to unilateral anterior crossbite (UAC) to induce OA in the temporomandibular joint (TMJ). Histochemical staining, immunohistochemical (IHC) staining, and qRT-PCR were performed. Primary condylar chondrocytes of rats were transfected with ABCG1 shRNA or overexpression lentivirus and then stimulated with fluid flow shear stress (FFSS). Cells were collected for oil red O staining, immunofluorescence staining, and qRT-PCR analysis. RESULTS: Abnormal adipogenesis, characterized by increased expression of Adiponectin, CCAAT/enhancer-binding protein α (Cebpα), fatty acid binding protein 4 (Fabp4) and Perilipin1, was enhanced in the degenerative cartilage of TMJ OA in rats with UAC, accompanied by decreased expression of ABCG1. After FFSS stimulation, we observed lipid droplets in the cytoplasm of cultured cells with increased expression of Adiponectin, Cebpα, Fabp4 and Perilipin1 and decreased expression of ABCG1. Knockdown of Abcg1 induced abnormal adipogenesis and differentiation of condylar chondrocytes. Overexpression of ABCG1 alleviated the abnormal adipogenesis and differentiation of condylar chondrocytes induced by FFSS. CONCLUSIONS: Abnormal adipogenesis of chondrocytes and decreased ABCG1 expression were observed in degenerative cartilage of TMJ OA. ABCG1 overexpression effectively inhibits the adipogenesis of chondrocytes and thus alleviates TMJ condylar cartilage degeneration.
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Cartilagem Articular , Má Oclusão , Osteoartrite , Animais , Feminino , Ratos , Trifosfato de Adenosina/metabolismo , Adipogenia , Adiponectina/metabolismo , Cartilagem Articular/metabolismo , Condrócitos/metabolismo , Má Oclusão/metabolismo , Articulação Temporomandibular/metabolismoRESUMO
Time-periodic light field can dress the electronic states and lead to light-induced emergent properties in quantum materials. While below-gap pumping is regarded favorable for Floquet engineering, so far direct experimental evidence of momentum-resolved band renormalization still remains missing. Here, we report experimental evidence of light-induced band renormalization in black phosphorus by pumping at photon energy of 160 meV, which is far below the band gap, and the distinction between below-gap pumping and near-resonance pumping is revealed. Our Letter demonstrates light-induced band engineering upon below-gap pumping, and provides insights for extending Floquet engineering to more quantum materials.
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The prenatal prevalence of isolated ventriculomegaly is 0.039%-0.087%. Most isolated mild ventriculomegaly (MV) fetuses (>90%) have a favorable prognosis. However, 5.6% to 7.9% of fetuses with isolated MV have adverse neurodevelopmental outcomes. In this study, we reported the first case of prenatal Snijders Blok-Fisher syndrome (OMIM: #618604) caused by a truncating variant of POU3F3 (OMIM: *602480) in a fetus with transient isolated bilateral MV. The results of karyotype analysis, chromosomal microarray analysis, and TORCH infection evaluation for the fetus were all negative. However, a de novo likely pathogenic nonsense variant of NM_006236.3 (POU3F3): c.640C > T [rs1254251078] p.(Q214*) was identified by whole-exome sequencing (WES). Despite sufficient genetic counseling, the mother refused to undertake further brain magnetic resonance imaging (MRI) and decided to keep the fetus. She gave birth to a male infant through a full-term vaginal delivery. With a long-term follow-up, the infant unfortunately gradually presented with delayed motor development. The postnatal brain MRI of the proband showed dysplasia of the corpus callosum and ventriculomegaly. Considering the high probability of misdiagnosis for such cases, we further summarized the prenatal phenotypes from 19 reported patients with variants in POU3F3. The results revealed that 14 patients displayed a normal prenatal ultrasonographic manifestation, while only approximately 26.32% of fetuses showed MV or cysts without structural deformity. Thus our findings expand the variant spectrum of POU3F3 and suggest the importance of undertaking WES and brain MRI when the fetus has isolated bilateral MV.
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The diabetes-cancer association remains underexplained. Here, we describe a glucose-signaling axis that reinforces glucose uptake and glycolysis to consolidate the Warburg effect and overcome tumor suppression. Specifically, glucose-dependent CK2 O-GlcNAcylation impedes its phosphorylation of CSN2, a modification required for the deneddylase CSN to sequester Cullin RING ligase 4 (CRL4). Glucose, therefore, elicits CSN-CRL4 dissociation to assemble the CRL4COP1 E3 ligase, which targets p53 to derepress glycolytic enzymes. A genetic or pharmacologic disruption of the O-GlcNAc-CK2-CSN2-CRL4COP1 axis abrogates glucose-induced p53 degradation and cancer cell proliferation. Diet-induced overnutrition upregulates the CRL4COP1-p53 axis to promote PyMT-induced mammary tumorigenesis in wild type but not in mammary-gland-specific p53 knockout mice. These effects of overnutrition are reversed by P28, an investigational peptide inhibitor of COP1-p53 interaction. Thus, glycometabolism self-amplifies via a glucose-induced post-translational modification cascade culminating in CRL4COP1-mediated p53 degradation. Such mutation-independent p53 checkpoint bypass may represent the carcinogenic origin and targetable vulnerability of hyperglycemia-driven cancer.
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Neoplasias , Proteína Supressora de Tumor p53 , Animais , Camundongos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Glucose , Ubiquitina-Proteína Ligases/metabolismo , Carcinogênese/genética , Transformação Celular Neoplásica/genéticaRESUMO
BACKGROUND: Neuronal apoptosis and inflammation are the key pathogenic features of secondary brain injury, which results in the neurological impairment that traumatic brain injury (TBI) patients experience. Ursolic Acid (UA) has been shown to have neuroprotective properties against brain damage, however, detailed mechanisms have not been fully disclosed. Research on brain-related microRNAs (miRNAs) has opened up new possibilities for the neuroprotective treatment of UA by manipulating miRNAs. The present study was designed to investigate the impact of UA on neuronal apoptosis and the inflammatory response in TBI mice. METHODS: The mice's neurologic condition was assessed using the modified neurological severity score (mNSS) and the learning and memory abilities were assessed using the Morris water maze (MWM). Cell apoptosis, oxidative stress, and inflammation were utilized to examine the impact of UA on neuronal pathological damage. miR-141-3p was selected to evaluate whether UA influences miRNAs in a way that has neuroprotective benefits. RESULTS: The results showed that UA markedly decreased brain edema and neuronal mortality through oxidative stress and neuroinflammation in TBI mice. Using data from the GEO database, we found that miR-141-3p was considerably downregulated in TBI mice and that this downregulation was reversed by UA treatment. Further studies have shown that UA regulates miR-141-3p expression to exhibit its neuroprotective effect in mouse models and cell injury models. Then, miR-141-3p was discovered to directly target PDCD4 in TBI mice and neurons, a well-known PI3K/AKT pathway regulator in the neurons. Most importantly, the upregulation of phosphorylated (p)-AKT and p-PI3K provided the most compelling evidence that UA reactivated the PI3K/AKT pathway in the TBI mouse model, which was through regulating miR-141-3p. CONCLUSION: Our findings support the notion that UA can improve TBI by modulating miR-141 mediated PDCD4/PI3K/AKT signaling pathway.
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Lesões Encefálicas Traumáticas , MicroRNAs , Camundongos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/genética , Lesões Encefálicas Traumáticas/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Apoptose/fisiologia , Inflamação/metabolismo , Ácido UrsólicoRESUMO
Direction of arrival (DOA) estimation for conformal arrays is challenging due to non-omnidirectional element patterns and shadow effects. Conical conformal array (CCA) can avoid the shadow effect at small elevation angles. So CCA is suitable for DOA estimation on both azimuth and elevation angles at small elevation angles. However, the element pattern in CCA cannot be obtained by conventional directional element coordinate transformation. Its local element pattern also has connection with the cone angle. The paper establishes the CCA radiation pattern in local coordinate system using 2-D coordinate transformation. In addition, in the case of large elevation angle, only half elements of the CCA can receive signal due to the shadow effect. The array degrees of freedom (DOF) are reduced by halves. We introduce the difference coarray method, which increases the DOF. Moreover, we propose a more accurate propagator method for 2-D cases. This method constructs a new propagation matrix and reduces the estimation error. In addition, this method reduces computational complexity by using linear computations instead of eigenvalue decomposition (EVD) and avoids spectral search. Simulation and experiment verify the estimation performance of the CCA. Both demonstrate the CCA model established in this paper is corresponding to the designed CCA antenna, and the proposed algorithms meet the needs of CCA angle detection. When the number of array elements is 12, the estimation accuracy is about 5 degrees.
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The deleterious effects of aflatoxins, especially aflatoxin B1 (AFB1) which are widespread at all stages of food production, on the reproductive system have been widely reported in males. However, it is still far from fully understood about the toxic effect and molecular mechanism after exposure to AFB1 in various testicular cells, especially Sertoli cells (SCs) which provide various energy materials and support to the developing germ cells as nurse cells. In this work, we examined the effects of AFB1 in dairy goat SCs on lactate production and autophagy, and the role of autophagy on AFB1-induced reduction in lactate production. Mechanistically, AFB1 destroyed the energy balance and reduced the secretion of lactate in dairy goat SCs (P < 0.01), resulting in a reduced level of ATP (P < 0.01) and phosphorylation of AMPK (P < 0.01). Subsequently, activated AMPK triggers autophagy by directly phosphorylating ULK1 (P < 0.05). The enhancement of autophagy partially reversed the AFB1-induced decrease in lactate secretion by promoting glucose utilization (P < 0.01) and increasing the expression of proteins related to lactate secretion in dairy goat SCs (P < 0.05) such as GLUT1, GLUT3, LDHA, and MCT4. Collectively, our study suggests that AFB1 inhibits the secretion of lactate which supply for germ cell development by damaging the "Warburg-like" metabolism of dairy goat SCs. Moreover, autophagy contributes to the resistance of glucose metabolism damage induced by AFB1. DATA AVAILABILITY: All data generated or analyzed in this study are available from the corresponding authors upon request.