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Disturbance of neurovascular coupling (NVC) is suggested to be one potential mechanism in type 2 diabetes mellitus (T2DM) associated mild cognitive impairment (MCI). However, NVC evidence derived from functional magnetic resonance imaging ignores the relationship of neuronal activity with vascular injury. Twenty-seven T2DM patients without MCI and thirty healthy controls were prospectively enrolled. Brain regions with changed susceptibility detected by quantitative susceptibility mapping (QSM) were used as seeds for functional connectivity (FC) analysis. NVC coefficients were estimated using combined degree centrality (DC) with susceptibility or cerebral blood flow (CBF). Partial correlations between neuroimaging indicators and cognitive decline were investigated. In T2DM group, higher susceptibility values in right hippocampal gyrus (R.PHG) were found and were negatively correlated with Naming Ability of Montreal Cognitive Assessment. FC increased remarkably between R.PHG and right middle temporal gyrus (R.MTG), right calcarine gyrus (R.CAL). Both NVC coefficients (DC-QSM and DC-CBF) reduced in R.PHG and increased in R.MTG and R.CAL. Both NVC coefficients in R.PHG and R.MTG increased with the improvement of cognitive ability, especially for executive function. These demonstrated that QSM and DC-QSM coefficients can be promising biomarkers for early evaluation of cognitive decline in T2DM patients and help to better understand the mechanism of NVC.
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Disfunção Cognitiva , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Encéfalo , Disfunção Cognitiva/patologia , Cognição/fisiologia , Lobo Temporal , Imageamento por Ressonância Magnética/métodosRESUMO
The photon-counting light laser detection and ranging (LiDAR), especially the Geiger mode avalanche photon diode (Gm-APD) LiDAR, can obtain three-dimensional images of the scene, with the characteristics of single-photon sensitivity, but the background noise limits the imaging quality of the laser radar. In order to solve this problem, a depth image estimation method based on a two-dimensional (2D) Kaniadakis entropy thresholding method is proposed which transforms a weak signal extraction problem into a denoising problem for point cloud data. The characteristics of signal peak aggregation in the data and the spatio-temporal correlation features between target image elements in the point cloud-intensity data are exploited. Through adequate simulations and outdoor target-imaging experiments under different signal-to-background ratios (SBRs), the effectiveness of the method under low signal-to-background ratio conditions is demonstrated. When the SBR is 0.025, the proposed method reaches a target recovery rate of 91.7%, which is better than the existing typical methods, such as the Peak-picking method, Cross-Correlation method, and the sparse Poisson intensity reconstruction algorithm (SPIRAL), which achieve a target recovery rate of 15.7%, 7.0%, and 18.4%, respectively. Additionally, comparing with the SPIRAL, the reconstruction recovery ratio is improved by 73.3%. The proposed method greatly improves the integrity of the target under high-background-noise environments and finally provides a basis for feature extraction and target recognition.
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Bacterial infection is the most common complication in wound healing, highlighting an urgent need for the development of innovative antibacterial technologies and treatments to address the growing threats posed by bacterial infections. Black phosphorus nanosheets (BPNSs), as a promising two-dimensional nanomaterial, have been utilized in treating infected wounds. However, BP's limited stability restricts its application. In this study, we enhance BP's stability and its antibacterial properties by anchoring gallium ions (Ga3+) onto BP's surface, creating a novel antibacterial platform. This modification reduces BP's electron density and enhances its antibacterial capabilities through a synergistic effect. Under near-infrared (NIR) irradiation, the BP/Ga3+ combination exerts antibacterial effects via photothermal therapy (PTT) and photodynamic therapy (PDT), while also releasing Ga3+. The Ga3+ employ a 'Trojan horse strategy' to disrupt iron metabolism, significantly boosting the antibacterial efficacy of the complex. This innovative material offers a viable alternative to antibiotics and holds significant promise for treating infected wounds and aiding skin reconstruction.
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Antibacterianos , Gálio , Fósforo , Cicatrização , Gálio/farmacologia , Gálio/uso terapêutico , Cicatrização/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Humanos , Animais , Nanoestruturas/uso terapêutico , Infecção dos Ferimentos/tratamento farmacológico , Fotoquimioterapia/métodos , Infecções Bacterianas/tratamento farmacológico , Camundongos , Terapia Fototérmica/métodosRESUMO
The Panxi area in Sichuan Province is the main area for the production of truffles in China, and several species of truffle are known to exist in this region. Nevertheless, it is unclear what the differences in chemical composition between the truffles are. Using an ultra-high-performance liquid chromatography quadrupole/orbitrap high-resolution mass spectrometry coupled with Compound Discoverer 3.0, we identified chemical components in three mainly known truffles from the Panxi region. Further analysis of chemical composition differences was conducted using principal component analysis, and orthogonal partial least squares discriminant analysis. Note that, 78.9% of the variance was uncovered by the principal component analysis model. As a result of the orthogonal partial least squares discriminant analysis model, the three species of truffles (Tuber pesudohimalayense, Tuber indicum, and Tuber sinense) from Panxi were better discriminated, with R2 X, R2 Y, and Q2 being 0.821, 0.993, and 0.947, respectively. In this study, 87 components were identified. T. pesudohimalayense contained significantly higher levels of nine different compounds than the other two species. Hence, it was possible to identify similarities and differences between three species of truffles from Panxi in terms of chemical composition. This can be used as a basis for quality control.
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Espectrometria de Massas , China , Análise DiscriminanteRESUMO
OBJECTIVE: White spot lesions (WSLs), the earliest evidence of enamel demineralization, are considered amenable to intervention to achieve a remineralized or arrested state of caries. The management of WSLs is quite challenging, and there is no definitive cure as yet. We performed a network meta-analysis to assess the efficacy of seven therapies for WSLs and gave a hierarchy of them. MATERIALS AND METHODS: We systematically searched the PubMed, EMBASE, Cochrane, and Web of Science databases (last search: July 2022) to identify all relevant studies. We limited our search to studies published in English. Randomized controlled designed in vitro/clinical trials related to the efficacy of the seven therapies for WSLs were included. Data extraction was performed independently by two reviewers. The risk of bias (ROB) 2.0 tool from Cochrane and a previous in vitro methodological tool will be used for the quality assessment. Variations in quantitative light-induced fluorescence (QLF), laser fluorescence (LF), and lesions area were the primary outcome measures. Standard mean difference (SMD) was used as the effect size for the Network meta-analysis (NMA). Consistency and inconsistency tests were conducted. The hierarchy of 7 treatment effects was evaluated using surface probabilities under cumulative ranking (SUCRA). Publication bias was evaluated using a bias plot. RESULTS: Forty-two articles were included in the systematic review. Thirty-one of them, with a total of 1906 participants, were included in the network meta-analysis. The studies owned a low and moderate risk of bias. This analysis does not suffer from significant inconsistency. The difference between 4 groups 'self-assembled peptide (SAP) P11-4', 'P11-4 + Fluoride Varnish (FV)', 'Resin Infiltration (RI)', 'casein phosphor peptides-amorphous calcium fluoride phosphate (CPP-ACFP)' and the 'Control' group was found to be statistically significant. Compared to the 'FV' and 'casein phosphor peptides-amorphous calcium phosphate (CPP-ACP)' groups, the 'P11-4 + FV" group and 'RI" group made a significant difference. The hierarchy was evident in the SUCRA values of 7 therapies. P11-4 + FV and RI were considered effective therapies compared to the control group or the FV group (gold standard group). CONCLUSIONS: The available evidence suggests that resin infiltration and P11-4 in combination with fluoride varnish had advantages over gold standard (FV). The effect of tricalcium phosphate-based drugs and fluoride is not very noticeable. Overall, drugs based on P11-4 and resin infiltration will be better therapies. Using more than two drugs in combination also would increase efficacy.
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Cariostáticos , Cárie Dentária , Humanos , Cariostáticos/uso terapêutico , Fluoretos Tópicos/uso terapêutico , Caseínas/uso terapêutico , Metanálise em Rede , Cárie Dentária/tratamento farmacológico , Fluoretos/uso terapêutico , Remineralização DentáriaRESUMO
Due to the strong scattering of fog and the strong background noise, the signal-to-background ratio (SBR) is extremely low, which severely limits the 3D imaging capability of single-photon detector array through fog. Here, we propose an outdoor three-dimensional imaging algorithm through fog, which can separate signal photons from non-signal photons (scattering and noise photons) with SBR as low as 0.003. This is achieved by using the observation model based on multinomial distribution to compensate for the pile-up, and using dual-Gamma estimation to eliminate non-signal photons. We show that the proposed algorithm enables accurate 3D imaging of 1.4 km in the visibility of 1.7 km. Compared with the traditional algorithms, the target recovery (TR) of the reconstructed image is improved by 20.5%, and the relative average ranging error (RARE) is reduced by 28.2%. It has been successfully demonstrated for targets at different distances and imaging times. This research successfully expands the fog scattering estimation model from indoor to outdoor environment, and improves the weather adaptability of the single-photon detector array.
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According to the major differences of agricultural characters among various Aconitum carmichaelii cultivars, the lateral roots of Ai-leaf and Dahua-leaf A.carmichaelii plants were selected as the research objects. And the Illumina Hiseq high-throughput platform was used for transcriptome sequencing, assembly and annotation. We mostly focused the activity differential transcripts, metabolism pathways and enrichment functions. The results showed that a total of 52.23 Gb nucleotide bases were obtained from 6 A.carmichaelii transcriptome databases, with 52 471 unigenes and 28 765 matched annotation. There were 1 052 transcripts of the two kinds of A.carmichaelii with a difference of more than 2 times, 808 of which were annotated. Through GO and COG analysis, they were found to mainly concentrate in metabolic processes, cell processes, catalytic processes and transport processes, connections and other functions. KEGG analysis showed that 262 DEGs were enriched in 78 metabolic pathways, such as starch and sucrose metabolism, plant hormone signaling, carbon compounded transport etc. It was implied that many genes in Dahua-leaf A.carmichaelii regulated the conversion of starch to small molecules such as sucrose, glucose and maltose, while some other genes regulated the accumulation of amino acids, which may be the important biological principles for the formation of the differences between the quality and disease resistance of two leaf types of A.carmichaelii. This study will provide reference datas for A.carmichaelii breeding research.
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Aconitum , Transcriptoma , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Sequenciamento de Nucleotídeos em Larga Escala , Anotação de Sequência MolecularRESUMO
Proteolysis in fermented milk, a complex and dynamic process, depends on the starter cultures used. This study aimed to evaluate the influence of Lactobacillus plantarum or Bifidobacterium animalis subsp. lactis, or both, co-fermented with Streptococcus thermophilus, on the changes in the proteolysis profile of fermented milk during 21-day storage at 4 °C, including the pH value, proteolytic degree, protease activity, aminopeptidase activity, free amino acid content, and electrophoresis performance. The results showed that the treatments with co-cultures exhibited a higher amount of free amino groups and neutral protease activity at an extracellular level, whereas lower pH values and aminopeptidase activities towards the six substrates at an intracellular level than the ones with a single-strain of S. thermophilus over the refrigerated storage were observed. In co-fermentation with S. thermophilus, B. animalis subsp. lactis did not significantly affect the concentrations of most free amino acids, while contributions of L. plantarum were found. Electrophoresis indicated that the mixed starters, especially the co-cultures containing L. plantarum, showed a stronger degradation for caseins than the pure S. thermophilus culture. These findings suggest that culture combinations may influence the proteolysis characteristics of the fermented products, and probiotic cultures must be carefully chosen for fermented production.
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Bifidobacterium animalis , Produtos Fermentados do Leite/análise , Armazenamento de Alimentos , Lactobacillus plantarum , Streptococcus thermophilus , Aminoácidos , Bifidobacterium animalis/metabolismo , Fermentação , Microbiologia de Alimentos , Lactobacillus plantarum/metabolismo , Peptídeo Hidrolases , Proteólise , Streptococcus thermophilus/metabolismoRESUMO
Bioorthogonal ligations have been designed and optimized to provide new experimental avenues for understanding biological systems. Generally, these optimizations have focused on improving reaction rates and orthogonality to both biology and other members of the bioorthogonal reaction repertoire. Less well explored are reactions that permit control of bioorthogonal reactivity in space and time. Here we describe a strategy that enables modular control of the cyclopropene-tetrazine ligation. We developed 3-N-substituted spirocyclopropenes that are designed to be unreactive towards 1,2,4,5-tetrazines when bulky N-protecting groups sterically prohibit the tetrazine's approach, and reactive once the groups are removed. We describe the synthesis of 3-N spirocyclopropenes with an appended electron withdrawing group to promote stability. Modification of the cyclopropene 3-N with a bulky, light-cleavable caging group was effective at stifling its reaction with tetrazine, and the caged cyclopropene was resistant to reaction with biological nucleophiles. As expected, upon removal of the light-labile group, the 3-N cyclopropene reacted with tetrazine to form the expected ligation product both in solution and on a tetrazine-modified protein. This reactivity caging strategy leverages the popular carbamate protecting group linkage, enabling the use of diverse caging groups to tailor the reaction's activation modality for specific applications.
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Carbamatos/química , Ciclopropanos/química , Compostos de Espiro/química , Carbamatos/síntese química , Carbamatos/efeitos da radiação , Ciclopropanos/síntese química , Ciclopropanos/efeitos da radiação , Compostos Heterocíclicos com 1 Anel/química , Cinética , Compostos de Espiro/síntese química , Compostos de Espiro/efeitos da radiaçãoRESUMO
Lipidated cyclopropenes serve as useful bioorthogonal reagents for imaging cell membranes due to the cyclopropene's small size and ability to ligate with pro-fluorescent tetrazines. Previously, the lipidation of cyclopropenes required modification at the C3 position because methods to append lipids at C1/C2 were not available. Herein, we describe C1/C2 lipidation with the biologically active lipid ceramide and a common phospholipid using a cyclopropene scaffold whose reactivity with 1,2,4,5-tetrazines has been caged.
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The NDST3 gene at 4q26 was a functional candidate gene for mental disorders. Recently, a novel genome-wide significant risk locus at chromosome 4q26 was identified and the top single nucleotide polymorphism rs11098403 in the vicinity of NDST3 gene was reported to confer risk of schizophrenia in Caucasian. Nevertheless, association between NDST3 gene polymorphisms and schizophrenia, bipolar disorder, or major depressive disorders has not been well studied in the Han Chinese population. To further investigate whether NDST3 is a risk gene for these mental disorders, we genotyped and analyzed eight tag SNPs (rs11098403, rs10857057, rs2389521, rs4833564, rs6837896, rs7689157, rs3817274, rs609512) covering NDST3 gene in 1,248 schizophrenia cases, 1,056 major depression cases, 1,344 bipolar disorder cases, and 1,248 controls of Chinese origin. However, there was no significant difference in allelic or genotypic frequency observed between each case group and healthy controls. Accordingly, our study does not support that the NDST3 gene plays a major role in schizophrenia, bipolar disorder, and major depressive disorder in the Han Chinese population.
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Transtornos Mentais/genética , Sulfotransferases/genética , Alelos , Povo Asiático/genética , Transtorno Bipolar/enzimologia , Transtorno Bipolar/genética , Estudos de Casos e Controles , Transtorno Depressivo Maior/enzimologia , Transtorno Depressivo Maior/genética , Etnicidade/genética , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Haplótipos , Humanos , Masculino , Transtornos Mentais/enzimologia , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Esquizofrenia/enzimologia , Esquizofrenia/genética , Sulfotransferases/metabolismoRESUMO
A series of curcumin derivatives as potent dual inhibitors of xanthine oxidase (XOD) and urate transporter 1 (URAT1) was discovered as anti-hyperuricemic agents. These compounds proved efficient effects on anti-hyperuricemic activity and uricosuric activity in vivo. More importantly, some of them exhibited proved efficient effects on inhibiting XOD activity and suppressing uptake of uric acid via URAT1 in vitro. Especially, the treatment of 4d was demonstrated to improve uric acid over-production and under-excretion in oxonate-induced hyperuricemic mice through regulating XOD activity and URAT1 expression. Docking study was performed to elucidate the potent XOD inhibition of 4d. Compound 4d may serve as a tool compound for further design of anti-hyperuricemic drugs targeting both XOD and URAT1.
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Curcumina/análogos & derivados , Curcumina/uso terapêutico , Inibidores Enzimáticos/química , Inibidores Enzimáticos/uso terapêutico , Hiperuricemia/tratamento farmacológico , Transportadores de Ânions Orgânicos/antagonistas & inibidores , Proteínas de Transporte de Cátions Orgânicos/antagonistas & inibidores , Xantina Oxidase/antagonistas & inibidores , Animais , Curcumina/farmacologia , Inibidores Enzimáticos/farmacologia , Células HEK293 , Humanos , Hiperuricemia/metabolismo , Masculino , Camundongos , Modelos Moleculares , Transportadores de Ânions Orgânicos/metabolismo , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Ácido Úrico/metabolismo , Xantina Oxidase/metabolismoRESUMO
A type of novel rhodanine-based 4-anilinoquinazoline, which designed the combination between quinazoline as the backbone and various substituted biological rhodanine groups as the side chain, have been synthesized, and their antiproliferative activities were also evaluated firstly. These compounds displayed good antiproliferative activity and EGFR-TK inhibitory activity. Among them, compound 8d showed good inhibitory activity (IC50=2.7µM for Hep G2, IC50=3.1µM for A549) and molecular docking of 8d into EGFR TK active site was also performed, this inhibitor well fitting the active site might well explain its excellent inhibitory activity.
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Compostos de Anilina/síntese química , Antineoplásicos/síntese química , Receptores ErbB/antagonistas & inibidores , Inibidores de Proteínas Quinases/síntese química , Quinazolinas/síntese química , Rodanina/química , Compostos de Anilina/farmacologia , Antineoplásicos/farmacologia , Domínio Catalítico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Receptores ErbB/química , Receptores ErbB/metabolismo , Humanos , Simulação de Acoplamento Molecular , Ligação Proteica , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/farmacologia , Relação Estrutura-AtividadeRESUMO
The influence of Eleutherine bulbosa (EB) extract at various levels (1, 4, 7, 10 or 13 g/kg) on the myofibrillar protein oxidation and moisture migration of yak meat in Fenton oxidation system was investigated. The results showed that inclusion of EB extract in yak meat efficiently inhibited carbonyl formation triggered by hydroxyl radicals. Supplementation of EB extract at 1-10 g/kg manifested more contents of the active sulfhydryl, ε-NH2 groups and α-helix structure, and higher solubility of myofibrillar proteins (MPs), but alleviated the turbidity of MPs. However, adding high level of EB extract (13 g/kg) induced the loss of free amine and α-helix content and resulted in more aggregation of MPs. The SDS-PAGE demonstrated that adding 1-7 g/kg EB extract had an obvious protective effect for myosin heavy chain and actin, whereas 10 or 13 g/kg EB extract led to weakened intensities of protein bands. DSC and LF-NMR analysis revealed that 7 g/kg EB extract had appreciable effects on thermal stabilities of MPs, and improved the hydration of yak meat induced by oxidation, while 13 g/kg EB extract accelerated MP structure destabilization and lowered water retention. Our results suggested that incorporation of low levels of EB extract (1-7 g/kg) effectively retarded the oxidative damage to MPs and EB extract could be a promising natural antioxidant in meat processing.
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Proteínas Musculares , Oxirredução , Extratos Vegetais , Animais , Bovinos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Proteínas Musculares/química , Estresse Oxidativo/efeitos dos fármacos , Miofibrilas/química , Carne Vermelha/análise , Água , Antioxidantes/farmacologiaRESUMO
OBJECTIVES: To investigate the clinical outcomes of anterior cervical decompression and fusion (ACDF) surgery for the treatment of Hirayama disease (HD). METHODS: In this study, 15 patients with HD who underwent ACDF operation between March 2022 and March 2023 with complete data were retrospectively analyzed. Following the diagnosis, conservative treatment was ineffective, and thus, disease progression severely affected the quality of life (QOL) of patients. ACDF was performed in the China-Japan Friendship Hospital, and patients were regularly followed up postoperatively. The cervical range of motion (ROM), the anteroposterior and transverse diameter of the spinal cord, and their ratio was measured before and after the operation. The neurologic function of patients before and after the last follow-up was evaluated using the selected brief-Michigan Hand Questionnaire (sb-MHQ), whilst the overall therapeutic effect after the operation was evaluated using Odom's criteria. RESULTS: All patients were followed up for an average of 12 ± 4.5 (6-18) months. Dynamic X-ray displayed that the ROM of cervical vertebrae decreased from 72.73 ± 12.72° (53-97°) to 33.53° ± 10.34° (15-54°) (P < 0.001). Moreover, flexion cervical magnetic resonance imaging (MRI) performed after the operation revealed that spinal cord compression was markedly relieved, and the ratio of the anteroposterior diameter of the spinal cord to the transverse diameter increased from 0.27 ± 0.09 to 0.43 ± 0.03 (P < 0.001). At the last follow-up visit, finger extension tremor symptoms were alleviated, although they did not completely disappear. Contrastingly, muscle atrophy showed no significant improvement. Finally, the sb-MHQ score significantly increased from 17.33±1.76 preoperatively to 24.80±1.78 at the last follow-up (P<0.001). CONCLUSIONS: Our results collectively highlighted the efficacy of ACDF for the treatment of HD. This procedure can limit excessive cervical flexion and repeated compression of the spinal cord during cervical movement and considerably improve upper limb functions.
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Vértebras Cervicais , Descompressão Cirúrgica , Fusão Vertebral , Atrofias Musculares Espinais da Infância , Humanos , Atrofias Musculares Espinais da Infância/cirurgia , Masculino , Fusão Vertebral/métodos , Descompressão Cirúrgica/métodos , Vértebras Cervicais/cirurgia , Resultado do Tratamento , Estudos Retrospectivos , Adulto , Adulto Jovem , Feminino , Adolescente , Amplitude de Movimento Articular , Qualidade de Vida , SeguimentosRESUMO
The conjugation of chitopentaose (CHP) on ß-lactoglobulin (ßLg) via Maillard reaction was used to desensitize ßLg. The stable ßLg-CHP conjugate (ßC-4) was formed at 4 h incubation, which contains 5 CHP attached molecules and a conjugated degree of 42 %. The conjugation promoted the thermal stability and emulsifying properties of ßLg, and inhibited the immunoglobulin E (IgE) combining capacity by decreasing the content of ß-sheet in ßLg. Moreover, ßLg-CHP conjugates were imparted with anti-oxidant properties and anti-inflammatory activities. Further, the combined action of inhibited IgE combining capacity and anti-inflammatory activities improved the allergy desensitization in ßLg sensitized mice. The results showed that overexpressed IgE and inflammatory factors, unbalanced Th1-/Th2- immune cytokines were significantly attenuated after ßLg was conjugated with CHP, avoiding the inflammatory lesions in spleen and colon. Additionally, the adverse changes in gut microbiota were alleviated in ßC-4 group with a decrease of Bacteroidetes and increase of Firmicutes at phylum level and the probiotic bacteria of Lactobacillaceae was significantly improved at the family level. Thus, the conjugation of CHP can desensitize allergic reaction caused by ßLg.
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Hipersensibilidade , Lactoglobulinas , Animais , Camundongos , Reação de Maillard , Imunoglobulina E , Anti-InflamatóriosRESUMO
A brain-computer interface (BCI) serves as a direct communication channel between brain activity and external devices, typically a computer or robotic limb. Advances in technology have led to the increasing use of intracranial electrical recording or stimulation in the treatment of conditions such as epilepsy, depression, and movement disorders. This indicates that BCIs can offer clinical neurological rehabilitation for patients with disabilities and functional impairments. They also provide a means to restore consciousness and functionality for patients with sequelae from major brain diseases. Whether invasive or non-invasive, the collected cortical or deep signals can be decoded and translated for communication. This review aims to provide an overview of the advantages of endovascular BCIs compared with conventional BCIs, along with insights into the specific anatomical regions under study. Given the rapid progress, we also provide updates on ongoing clinical trials and the prospects for current research involving endovascular electrodes.
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OBJECTIVES: This study aims to investigate and predict the therapeutic agents associated with disulfidptosis in periodontitis. DESIGN: The dataset GSE10334 was downloaded from the Gene Expression Omnibus (GEO) database and used to train a least absolute shrinkage and selection operator (LASSO) regression and support vector machine recursive feature elimination (SVM-RFE) algorithm to identify genes associated with disulfidptosis in periodontitis. GSE16134 validation sets, polymerase chain reaction (PCR), and gingival immunofluorescence were used to verify the results.Single-gene Gene Set Enrichment Analysis (GSEA) was performed to explore the potential mechanisms and functions of the characterized genes. Immune infiltration and correlation analyses were performed, and competing endogenous RNA (ceRNA) networks were constructed. Effective therapeutic drugs were then predicted using the DGIdb database, and molecular docking was used to validate binding affinity. RESULTS: Six genes (SLC7A11, SLC3A2, RPN1, NCKAP1, LRPPRC, and NDUFS1) associated with disulfidptosis in periodontitis were obtained. Validation results from external datasets and experiments were consistent with the screening results. Single-gene GSEA analysis was mainly enriched for antigen presentation and immune-related pathways and functions.Immune infiltration and correlation analyses revealed significant regulatory relationships between these genes and plasma cells, resting dendritic cell, and activated NK cells. The ceRNA network was visualized. And ME-344, NV-128, and RILUZOLE, which have good affinity to target genes, were identified as promising agents for the treatment of periodontitis. CONCLUSIONS: SLC7A11, SLC3A2, RPN1, NCKAP1, LRPPRC, and NDUFS1 are targets associated with disulfidptosis in periodontitis, and ME-344, NV-128, and RILUZOLE are promising agents for the treatment of periodontitis.
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Periodontite , Humanos , Periodontite/genética , Simulação de Acoplamento Molecular , Máquina de Vetores de Suporte , Bases de Dados Genéticas , Algoritmos , Relevância ClínicaRESUMO
OBJECTIVES: Demineralized bone matrix (DBM) is a well-established bone graft material widely accepted by dentists and the public for its favorable osteoconductivity and osteoinductive potential. This article aimed to provide a narrative review of the current therapeutic applications and limitations of DBM in maxillofacial bone defects. STUDY SELECTION, DATA, AND SOURCES: Randomized controlled trials, prospective or retrospective clinical studies, case series and reports, and systematic reviews. MEDLINE, PubMed, and Google Scholar were searched using keywords. CONCLUSIONS: Some evidence supported the therapeutic application of DBM in periodontal intrabony defects, maxillary sinus lifts, ridge preservation, ridge augmentation, alveolar cleft repair, orthognathic surgery, and other regional maxillofacial bone defects. However, the limitations of DBM should be considered when using it, including potential low immunogenicity, instability of osteoinductive potential, handling of the graft material, and patient acceptance. CLINICAL SIGNIFICANCE: With the increasing demand for the treatment of maxillofacial bone defects, DBM is likely to play a greater role as a promising bone graft material. Safe and effective combination treatment strategies and how to maintain a stable osteoinductive potential will be the future challenges of DBM research.
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Matriz Óssea , Regeneração Óssea , Humanos , Matriz Óssea/transplante , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento , Transplante ÓsseoRESUMO
Three previously undescribed compounds including a polyketide (1) and two lactams (2 and 3) were obtained from Tuber indicum. The structures of new findings were elucidated by HRESIMS, NMR as well as NMR and ECD calculations. Transcriptome analysis through RNA-seq revealed that compound 2 exhibits immunosuppressive activity. Lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages were employed as a model to explore the effect of these compounds in immunosuppressive activity. The results showed that 2 could reduce the generation of inflammatory mediators including nitric oxide (NO), reactive oxygen species (ROS), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS). Western blotting analysis demonstrated that 2 could suppressed the PI3K pathway by decreasing the levels of p-PI3K and p-Akt, while increasing the levels of p-PTEN. The anti-inflammatory activity of 2 was further confirmed using a zebrafish in vivo model.