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Three newly discovered Melanogaster species, namely M.cyaneus, M.diqingensis, and M.truncatisporus, are introduced and illustrated based on both morphological and molecular data from Sichuan and Yunnan provinces in China. A multigene phylogenetic analysis (nrITS, nrLSU, and rpb2) was performed mainly to verify the placement of the new species in Melanogaster. A second, nrITS-only phylogenetic analysis comprising more Melanogaster species for which only ITS sequences were available, was used to infer the relationship between the new species and as many known Melanogaster species as possible. Specimens of M.cyaneus, M.diqingensis, and M.truncatisporus formed three independent clades in a phylogenetic tree inferred from the ITS data set. The robust support from ITS for these clades and genetic similarity with other species being lower than 93.2% suggest that these three species are indeed distinct from the other Melanogaster species in the phylogeny. Morphologically, M.cyaneus is characterized by its blue or bluish gleba, light brown to yellowish brown peridium, and subglobose to globose basidiospores, 6.2-15 × 4.6-9.0 µm. Melanogasterdiqingensis is distinguished from other Melanogaster species by its pale yellow to brown-yellow peridium and obovate to subglobose basidiospores, 3.0-5.1 × 2.0-4.0 µm. Melanogastertruncatisporus is diagnosed by its subglobose to globose or irregularly elongate-pyriform basidiomata, pale yellow to deeply orange-yellow peridium, and subglobose to globose or pyriform, truncate basidiospores. Additionally, infrageneric classification based on the number of peridium layers, the average thickness of the peridium, and the average length and width of basidiospores was tested with M.cyaneus, M.diqingensis, and M.truncatisporus. Orthogonal partial least squares discriminant (OPLS-DA) analysis placed the three new species within the Melanogaster, Rivulares, and Variegati sections, respectively. However, the morphologically circumscribed sections were not monophyletic in the phylogenetic tree. Therefore, the current infrageneric classification should be abandoned.
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Brain disorders represent an ever-increasing health challenge worldwide. While conventional drug therapies are less effective due to the presence of the blood-brain barrier, infusion-based methods of drug delivery to the brain represent a promising option. Since these methods are mechanically controlled and involve multiple physical phases ranging from the neural and molecular scales to the brain scale, highly efficient and precise delivery procedures can significantly benefit from a comprehensive understanding of drug-brain and device-brain interactions. Behind these interactions are principles of biophysics and biomechanics that can be described and captured using mathematical models. Although biomechanics and biophysics have received considerable attention, a comprehensive mechanistic model for modeling infusion-based drug delivery in the brain has yet to be developed. Therefore, this article reviews the state-of-the-art mechanistic studies that can support the development of next-generation models for infusion-based brain drug delivery from the perspective of fluid mechanics, solid mechanics, and mathematical modeling. The supporting techniques and database are also summarized to provide further insights. Finally, the challenges are highlighted and perspectives on future research directions are provided. STATEMENT OF SIGNIFICANCE: Despite the immense potential of infusion-based drug delivery methods for bypassing the blood-brain barrier and efficiently delivering drugs to the brain, achieving optimal drug distribution remains a significant challenge. This is primarily due to our limited understanding of the complex interactions between drugs and the brain that are governed by principles of biophysics and biomechanics, and can be described using mathematical models. This article provides a comprehensive review of state-of-the-art mechanistic studies that can help to unravel the mechanism of drug transport in the brain across the scales, which underpins the development of next-generation models for infusion-based brain drug delivery. More broadly, this review will serve as a starting point for developing more effective treatments for brain diseases and mechanistic models that can be used to study other soft tissue and biomaterials.
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BACKGROUND: Cilia loss and impaired motile ciliary functions are among the typical pathological features of chronic rhinosinusitis with nasal polyps (CRSwNP). IL17A and IL22 are the canonical cytokines of type 3 inflammation, exhibiting similar functional effects on epithelial cells. In this study, we sought to examine the effects of IL17A and IL22 on ciliated cells and investigate the potential involvement of Hippo-YAP signaling in their influence on ciliogenesis. METHODS: We assessed both the mRNA and protein expression levels of IL17A and IL22 in nasal tissues obtained from patients with CRSwNP and compared them to those from healthy controls. To further explore the impact of IL17A and IL22, we established a primary human nasal epithelial cell model using different concentrations (2 ng/mL, 10 ng/mL, 50 ng/mL) for a duration of 28 days in an air-liquid interface culture. Additionally, we employed the inhibitor verteporfin to investigate whether IL17A and IL22 exert their effects on ciliated cells via the Hippo-YAP pathway. RESULTS: The mRNA and protein levels of IL17A and IL22 in CRSwNP were significantly higher than those in healthy controls, revealing a robust correlation between IL17A and IL22. YAP was highly expressed in the nucleus of ciliated cells in CRSwNP and displayed a positive correlation with clinical symptoms. Both IL17A and IL22 were found to reduce the number of ciliated cells. IL17A, but not IL22, suppressed ciliogenesis by disrupting the proper development and docking of the basal body of ciliated cells, resulting in motile ciliary dysfunctions. Furthermore, the expression of YAP within the nucleus of ciliated cells gradually declined as these cells reached the final stage of differentiation. However, this process was obstructed by IL17A only. YAP inhibitors, such as verteporfin, markedly reversed the effects of IL17A by increasing the proportion of ciliated cells, suppressing nuclear YAP expression in these cells, and enhancing ciliary beating frequency. CONCLUSIONS: Both IL17A and IL22 are overexpressed in nasal epithelium of CRSwNP, which is associated with the impairment of epithelial cell differentiation. Furthermore, IL17A has been shown to exert a disruptive effect on morphogenesis of motile cilia via activation of YAP.
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Objective:To investigate the criteria for selecting surgical approaches for frontal and ethmoid sinus osteomas of different locations and sizes on CT imaging. Methods:Using sagittal and coronal CT images, the following lines were delineated: the F-lineï¼a horizontal line passing nasofrontal beakï¼, the M-lineï¼a vertical line passing paries medialis orbitaeï¼, and the P-lineï¼a vertical line passing the center of the pupilï¼. Classification of frontal and ethmoid sinus osteomas was based on their relationship with these lines. Appropriate surgical approaches were selected, including pure endoscopic approaches, endoscopic combined with eyebrow incision approach, and endoscopic combined with coronal incision approach. This method was applied to a single center at the Third Affiliated Hospital of Sun Yat-sen University for endoscopic resection of frontal and ethmoid sinus osteoma. Case Data: Sixteen cases of ethmoid sinus osteomas were treated from January 2020 to September 2023. Among these cases, there were 9 males and 7 females, with ages ranging from 18 to 69 years, and a median age of 48 years. Results:Thirteen cases underwent pure endoscopic resection of the osteoma, while in three cases, a combined approach was utilized. Among the combined approach cases, two exceeded both the M-line and the F-line but did not cross the P-line; therefore, they underwent endoscopic combined with eyebrow incision approach. One case exceeded all three lines and thus underwent endoscopic combined with coronal incision. In all cases, complete resection of the osteoma was achieved as per preoperative planning, and none of the patients experienced significant postoperative complications. Conclusion:For frontal and ethmoid sinus osteomas, it is advisable to perform a thorough preoperative radiological assessment. Based on the size of the osteoma and its relationship to the three lines, an appropriate surgical approach should be chosen to optimize the diagnostic and treatment plan.
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Endoscopia , Seio Etmoidal , Seio Frontal , Osteoma , Neoplasias dos Seios Paranasais , Tomografia Computadorizada por Raios X , Humanos , Osteoma/cirurgia , Osteoma/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Seio Frontal/cirurgia , Seio Frontal/diagnóstico por imagem , Seio Etmoidal/cirurgia , Seio Etmoidal/diagnóstico por imagem , Adolescente , Tomografia Computadorizada por Raios X/métodos , Neoplasias dos Seios Paranasais/cirurgia , Neoplasias dos Seios Paranasais/diagnóstico por imagem , Endoscopia/métodos , Adulto JovemRESUMO
The vagus nerve, a pivotal link within the gut-brain axis, plays a critical role in maintaining homeostasis and mediating communication between the gastrointestinal tract and the brain. It has been reported that gastrointestinal infection by Salmonella typhimurium (S. typhimurium) triggers gut inflammation and manifests as anxiety-like behaviors, yet the mechanistic involvement of the vagus nerve remains to be elucidated. In this study, we demonstrated that unilateral cervical vagotomy markedly attenuated anxiety-like behaviors induced by S. typhimurium SL1344 infection in C57BL/6 mice, as evidenced by the open field test and marble burying experiment. Furthermore, vagotomy significantly diminished neuronal activation within the nucleus of the solitary tract and amygdala, alongside mitigating aberrant glial cell activation in the hippocampus and amygdala. Additionally, vagotomy notably decreases serum endotoxin levels, counters the increase in splenic Salmonella concentration, and modulates the expression of inflammatory cytokines-including IL-6, IL-1ß, and TNF-α-in both the gastrointestinal tract and brain, with a concurrent reduction in IL-22 and CXCL1 expression. This intervention also fostered the enrichment of beneficial gut microbiota, including Alistipes and Lactobacillus species, and augmented the production of gamma-aminobutyric acid (GABA) in the gut. Administration of GABA replicated the vagotomy's beneficial effects on reducing gut inflammation and anxiety-like behavior in infected mice. However, blockade of GABA receptors with picrotoxin abrogated the vagotomy's protective effects against gut inflammation, without influencing its impact on anxiety-like behaviors. Collectively, these findings suggest that vagotomy exerts a protective effect against infection by promoting GABA synthesis in the colon and alleviating anxiety-like behavior. This study underscores the critical role of the vagus nerve in relaying signals of gut infection to the brain and posits that targeting the gut-brain axis may offer a novel and efficacious approach to preventing gastrointestinal infections and associated behavioral abnormalities.
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Ansiedade , Microbioma Gastrointestinal , Camundongos Endogâmicos C57BL , Vagotomia , Nervo Vago , Ácido gama-Aminobutírico , Animais , Ansiedade/metabolismo , Camundongos , Nervo Vago/metabolismo , Masculino , Ácido gama-Aminobutírico/metabolismo , Salmonella typhimurium , Citocinas/metabolismo , Eixo Encéfalo-Intestino , Encéfalo/metabolismo , Infecções por Salmonella/metabolismo , Comportamento Animal , Hipocampo/metabolismo , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Inflamação/metabolismo , Tonsila do Cerebelo/metabolismoRESUMO
The ApoE4 allele is the strongest genetic determinant for Alzheimer's disease (AD), while obesity is a strong environmental risk for AD. The modulatory effect of the ApoE genotype on aging-related cognitive function in tandem with a high-fat diet (HFD) remains uncertain. This study aimed to elucidate the effects of ApoE3/ApoE4 genotypes in aged mice exposed to a HFD, and the benefits of n-3 polyunsaturated fatty acids (PUFAs) from fish oil. Remarkably, the HFD led to weight gain and lipid accumulation, more pronounced in ApoE3 mice, while ApoE4 mice experienced exacerbated cerebral insulin resistance, neuroinflammation, and oxidative stress. Critically, n-3 PUFAs modulated the cerebral insulin signaling via the IRS-1/AKT/GLUT4 pathway, mitigated microglial hyperactivity, and reduced IL-6 and MDA levels, thereby counteracting cognitive deficits. These findings highlight the contrasting impacts of ApoE genotypes on aging mice exposed to a HFD, supporting n-3 PUFAs as a strategic nutritional intervention for brain health, especially for ApoE4 carriers.
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Doença de Alzheimer , Ácidos Graxos Ômega-3 , Camundongos , Animais , Dieta Hiperlipídica/efeitos adversos , Apolipoproteína E4/genética , Apolipoproteína E4/metabolismo , Apolipoproteína E3/genética , Apolipoproteínas E/genética , Genótipo , Cognição , Doença de Alzheimer/genética , Doença de Alzheimer/prevenção & controle , Doença de Alzheimer/metabolismo , Envelhecimento , Camundongos TransgênicosRESUMO
Cordycepin has good antitumor activity, but its clinical application is limited due to the easy deamination of N6 in structure. In this study, a large lipolysis group was introduced at the cordycepin N6 to improve the problem, cordycepin derivatives (3a-4c) were synthesized, and biological evaluation of compounds was studied. In this study, the vitro antitumor activity of the compounds against MCF7 cells, HepG2 cells and SGC-7901 cells was evaluated by MTT assay. In the results, compound 4a showed the most obvious inhibitory effect on MCF7 cells with an IC50 value of 27.57 ± 0.52 µM, which was much lower than cordycepin. Compound 4a showed high selectivity between MCF7 and normal MCF-10A cells. Further biological evaluation showed that compound 4a promoted apoptosis and blocked the cell cycle in the G0/G1 phase. Then, Western Blot was used to detect related apoptotic proteins. It was found that Compound 4a could down-regulate the expression of Bcl-2 protein and up-regulate the expression of p53, Bax, Caspase-3 and Caspase-9 proteins. The mitochondrial membrane potential decreased continuously and the positive expression rate decreased. It was speculated that compound 4a induced the apoptosis of MCF7 cells through the mitochondrial pathway.
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Apoptose , Desoxiadenosinas , Desoxiadenosinas/farmacologia , Western Blotting , Ciclo CelularRESUMO
Keloid is a fibroproliferative disease of unknown aetiology, which has a significant impact the quality of life of patients. Ferroptosis plays an important role in the occurrence and development of fibrosis, but there is still a lack of research related to keloids. The objective of this work was to identify the hub genes related to ferroptosis in keloid to better understand the keloid process. The microarray data (GSE7890 GSE145725, and GSE44270) (23 keloid and 22 normal fibroblast) were analysed via the gene expression comprehensive database (GEO). Only GSE7890 met the FerrDB database. Cell cycle and pathway analysis were performed with gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed to differentially expressed genes (DEG). The differential genes were confirmed in other GEO datasets (GSE145725 and GSE44270), and multi-fibrosis-gene correlation analysed. To validate these hub genes, quantitative real-time PCR (qRT-PCR) was conducted. A total of 581 DEGs were screened, with 417 genes down-regulated and 164 genes up-regulated, with 11 ferroptosis genes significantly up-regulated in both keloid and normal tissue, and 6 genes are consistent with our findings and are associated with multiple fibrosis genes. The qRT-PCR results and tissues of normal skin and keloid agreed with our predictions. Our findings provide new evidence for the ferroptosis-related molecular pathways and biomarker of keloid.
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Ferroptose , Queloide , Humanos , Ferroptose/genética , Queloide/genética , Qualidade de Vida , Biomarcadores , Biologia ComputacionalRESUMO
Quinidine has been used as an anticonvulsant to treat patients with KCNT1-related epilepsy by targeting gain-of-function KCNT1 pathogenic mutant variants. However, the detailed mechanism underlying quinidine's blockade against KCNT1 (Slack) remains elusive. Here, we report a functional and physical coupling of the voltage-gated sodium channel NaV1.6 and Slack. NaV1.6 binds to and highly sensitizes Slack to quinidine blockade. Homozygous knockout of NaV1.6 reduces the sensitivity of native sodium-activated potassium currents to quinidine blockade. NaV1.6-mediated sensitization requires the involvement of NaV1.6's N- and C-termini binding to Slack's C-terminus and is enhanced by transient sodium influx through NaV1.6. Moreover, disrupting the Slack-NaV1.6 interaction by viral expression of Slack's C-terminus can protect against SlackG269S-induced seizures in mice. These insights about a Slack-NaV1.6 complex challenge the traditional view of 'Slack as an isolated target' for anti-epileptic drug discovery efforts and can guide the development of innovative therapeutic strategies for KCNT1-related epilepsy.
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Epilepsia , Canal de Sódio Disparado por Voltagem NAV1.6 , Quinidina , Animais , Humanos , Camundongos , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Homozigoto , Canal de Sódio Disparado por Voltagem NAV1.6/genética , Proteínas do Tecido Nervoso/genética , Quinidina/farmacologia , SódioRESUMO
Microcystin-degrading bacteria first degrade microcystins by microcystinase A (MlrA) to cleave the cyclic structure of microcystins at the Adda-Arg site of microcystin-LR, microcystin-RR, and microcystin-YR, but the cleavage of the other microcystins was not clear. In our study, the microcystin-degrading bacterium Sphingopyxis sp. C-1 as wild type and that of mlrA-disrupting mutant, Sphingopyxis sp. CMS01 were used for microcystins biodegradation. The results showed MlrA degraded microcystin-LA, microcystin-LW, microcystin-LY, microcystin-LF, and nodularin. MlrA could cleave the Adda-L-amino acid site.
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Microcistinas , Sphingomonadaceae , Sphingomonadaceae/genética , Sphingomonadaceae/metabolismo , Biodegradação AmbientalRESUMO
PURPOSE: Prostate cancer (PCa) is often considered as a "cold" tumor with low responsiveness to immunotherapy. Recent evidence suggests the activation of specific immune cells, such as tumor-associated macrophages (TAMs), could potentially influence the efficacy of immunotherapy in PCa. However, the relationship between TAMs and PD-L1, a significant regulator in immunotherapy, within PCa remains unexplored. METHODS: In this study, we assessed TAM infiltration and PD-L1 expression levels in a local cohort of 95 PCa tissue samples and two publicly available PCa datasets. We employed a combination of bioinformatics and experimental techniques, including gene set enrichment analysis, CIBERSORTx, tissue microarray, immunohistochemistry staining, and analysis of single-cell sequencing datasets, to provide a comprehensive understanding of the association between PD-L1 and TAMs in the PCa microenvironment. RESULTS: The study showed that CD68+ TAMs and CD163+ TAMs (M2-TAMs) were more abundant in the tumor microenvironment than in non-cancerous surrounding tissues. The infiltration of CD163+ TAMs was significantly associated with the Gleason score and risk stratification of PCa. Importantly, elevated PD-L1 expression correlated significantly with high infiltration of CD163+ TAMs. Furthermore, patients displaying high levels of CD163+ TAMs and PD-L1 expression exhibited shorter times to biochemical recurrence-free survival. CONCLUSION: Our study suggests that CD163+ TAMs are closely associated with PD-L1 expression and can act as a valuable prognostic indicator for PCa. The high infiltration of M2-TAMs, coupled with the overexpression of PD-L1, may contribute to immune escape mechanisms in PCa, thereby influencing disease prognosis.
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Neoplasias da Próstata , Macrófagos Associados a Tumor , Humanos , Masculino , Antígeno B7-H1/metabolismo , Imunoterapia , Macrófagos/metabolismo , Prognóstico , Neoplasias da Próstata/patologia , Microambiente Tumoral , Macrófagos Associados a Tumor/metabolismoRESUMO
OBJECTIVES: As a critical component of the epithelial barrier, tight junctions (TJs) are essential in nasal mucosa against pathogen invasion. However, the function of TJs has rarely been reported in nasal inverted papilloma (NIP). This study aims to investigate the potential factors of TJs' abnormality in NIP. METHODS: We assessed the expression of ZO-1, occludin, claudin-1, claudin-3, and claudin-7 in healthy controls and NIP by real-time quantitative polymerase chain reaction and immunofluorescent staining. The correlation between TJs expression and neutrophil count, TH 1/TH 2/TH 17 and regulatory T cell biomarkers, and the proportion of nasal epithelial cells was investigated. RESULTS: Upregulation of ZO-1, occludin, claudin-1, and claudin-7, along with downregulation of claudin-3, was found in NIP compared to control (all p < 0.05). An abnormal proportion with a lower number of ciliated cells (control vs. NIP: 37.60 vs. 8.67) and goblet cells (12.52 vs. 0.33) together with a higher number of basal cells (45.58 vs. 124.00) in NIP. Meanwhile, claudin-3 was positively correlated with ciliated and goblet cells (all p < 0.01). Additionally, neutrophils were excessively infiltrated in NIP, negatively correlated with ZO-1, but positively with claudin-3 (all p < 0.05). Furthermore, FOXP3, IL-10, TGF-ß1, IL-5, IL-13, and IL-22 levels were induced in NIP (all p < 0.01). Occludin level was negatively correlated with IL-10, IL-5, IL-13, and IL-22, whereas ZO-1 was positively with TGF-ß1 (all p < 0.05). CONCLUSION: Nasal epithelial barrier dysfunction with TJs anomalies is commonly associated with abnormal proliferation and differentiation of epithelial cells and imbalance of immune and inflammatory patterns in NIP. LEVEL OF EVIDENCE: NA Laryngoscope, 134:552-561, 2024.
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Papiloma Invertido , Junções Íntimas , Humanos , Interleucina-10/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Ocludina/metabolismo , Interleucina-13/metabolismo , Claudina-1/metabolismo , Claudina-3/genética , Claudina-3/metabolismo , Interleucina-5/metabolismo , Células Epiteliais/metabolismoRESUMO
The prevalence of Alzheimer's disease (AD) continues to rise due to the increasing aging population. Among the various genetic factors associated with AD, apolipoprotein E (ApoE), a lipid transporter, stands out as the primary genetic risk factor. Specifically, individuals carrying the ApoE4 allele exhibit a significantly higher risk. However, emerging research indicates that dietary factors play a prominent role in modifying the risk of AD. Docosahexaenoic acid (DHA), a prominent ω-3 fatty acid, has garnered considerable attention for its potential to ameliorate cognitive function. The intricate interplay between DHA and the ApoE genotype within the brain, which may influence DHA's utilization and functionality, warrants further investigation. This review meticulously examines experimental and clinical studies exploring the effects of DHA on cognitive decline. Special emphasis is placed on elucidating the role of ApoE gene polymorphism and the underlying mechanisms are discussed. These studies suggest that early DHA supplementation may confer benefits to cognitively normal older adults carrying the ApoE4 gene. However, once AD develops, ApoE4 non-carriers may experience greater benefits compared to ApoE4 carriers, although the overall effectiveness of DHA supplementation at this stage is limited. Potential mechanisms underlying these differential effects may include accelerated DHA catabolism in ApoE4 carriers, impaired transport across the blood-brain barrier (BBB), and compromised lipidation and circulatory function in ApoE4 carriers. Thus, the supplementation of DHA may represent a potential intervention strategy aimed at compensating for these deficiencies in ApoE4 carriers prior to the onset of AD.
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Doença de Alzheimer , Disfunção Cognitiva , Humanos , Idoso , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Apolipoproteína E4/genética , Apolipoproteína E4/metabolismo , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Docosa-Hexaenoicos/metabolismo , Envelhecimento , Disfunção Cognitiva/tratamento farmacológicoRESUMO
Dopaminergic neurons in the substantia nigra (SN) expressing SUR1/Kir6.2 type ATP-sensitive potassium channels (K-ATP) are more vulnerable to rotenone or metabolic stress, which may be an important reason for the selective degeneration of neurons in Parkinson's disease (PD). Baicalein has shown neuroprotective effects in PD animal models. In this study, we investigated the effect of baicalein on K-ATP channels and the underlying mechanisms in rotenone-induced apoptosis of SH-SY5Y cells. K-ATP currents were recorded from SH-SY5Y cells using whole-cell voltage-clamp recording. Drugs dissolved in the external solution at the final concentration were directly pipetted onto the cells. We showed that rotenone and baicalein opened K-ATP channels and increased the current amplitudes with EC50 values of 0.438 µM and 6.159 µM, respectively. K-ATP channel blockers glibenclamide (50 µM) or 5-hydroxydecanoate (5-HD, 250 µM) attenuated the protective effects of baicalein in reducing reactive oxygen species (ROS) content and increasing mitochondrial membrane potential and ATP levels in rotenone-injured SH-SY5Y cells, suggesting that baicalein protected against the apoptosis of SH-SY5Y cells by regulating the effect of rotenone on opening K-ATP channels. Administration of baicalein (150, 300 mg·kg-1·d-1, i.g.) significantly inhibited rotenone-induced overexpression of SUR1 in SN and striatum of rats. We conducted surface plasmon resonance assay and molecular docking, and found that baicalein had a higher affinity with SUR1 protein (KD = 10.39 µM) than glibenclamide (KD = 24.32 µM), thus reducing the sensitivity of K-ATP channels to rotenone. Knockdown of SUR1 subunit reduced rotenone-induced apoptosis and damage of SH-SY5Y cells, confirming that SUR1 was an important target for slowing dopaminergic neuronal degeneration in PD. Taken together, we demonstrate for the first time that baicalein attenuates rotenone-induced SH-SY5Y cell apoptosis through binding to SUR1 and activating K-ATP channels.
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Flavanonas , Neuroblastoma , Canais de Potássio Corretores do Fluxo de Internalização , Humanos , Ratos , Animais , Canais KATP , Rotenona/farmacologia , Receptores de Sulfonilureias , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Glibureto/farmacologia , Simulação de Acoplamento Molecular , Apoptose , Neurônios Dopaminérgicos/metabolismo , Trifosfato de Adenosina/farmacologiaRESUMO
The constitutive model for the porosity-permeability relationship is a powerful tool to estimate and design the transport properties of porous materials, which has attracted significant attention for the advancement of novel materials. However, in comparison with other materials, biomaterials, especially natural and artificial tissues, have more complex microstructures e.g. high anisotropy, high randomness of cell/fibre dimensions/position and very low porosity. Consequently, a reliable microstructure-permeability relationship of fibrous biomaterials has proven elusive. To fill this gap, we start a mathematical derivation from the fundamental brain white matter (WM) formed by nerve fibres. This is augmented by a numerical characterisation and experimental validations to obtain an anisotropic permeability tensor of the brain WM as a function of the tissue porosity. A versatile microstructure generation software (MicroFiM) for fibrous biomaterial with complex microstructure and low porosity was built accordingly and made freely accessible here. Moreover, we propose an anisotropic poro-hyperelastic model enhanced by the newly defined porosity-permeability tensor relationship which precisely captures the tissues macro-scale permeability changes due to the microstructural deformation in an infusion scenario. The constitutive model, theories and protocols established in this study will both provide improved design strategies to tailor the transport properties of fibrous biomaterials and enable the non-invasive characterisation of the transport properties of biological tissues. This will lead to the provision of better patient-specific medical treatments, such as drug delivery. STATEMENT OF SIGNIFICANCE: Due to the microstructural complexity, a reliable microstructure-permeability relationship of fibrous biomaterials has proven elusive, which hinders our way of tuning the fluid transport property of the biomaterials by directly programming their microstructure. The same problem hinders non-invasive characterisations of fluid transport properties in biological tissues, which can significantly improve the efficiency of treatments e.g. drug delivery, directly from the tissues accessible microstructural information, e.g. porosity. Here, we developed a validated mathematical formulation to link the random microstructure to a fibrous material's macroscale permeability tensor. This will advance our capability to design complex biomaterials and make it possible to non-invasively characterise the permeability of living tissues for precise treatment planning. The newly established theory and protocol can be easily adapted to various types of fibrous biomaterials.
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Materiais Biocompatíveis , Substância Branca , Humanos , Materiais Biocompatíveis/química , Porosidade , PermeabilidadeRESUMO
Perkinsosis has been recognized as one of the major threats to natural and farmed bivalve populations, many of which are of commercial as well as environmental significance. Three Perkinsus species have been identified in China, and the Manila clam (Ruditapes philippinarum) was the most frequently infected species in northern China. Although the occurrence and seasonal variation of Perkinsus spp. have previously been examined, the pathological characteristics of these infections in wild Manila clams and sympatric species in China have seldom been reported. In the present study, the prevalence and intensity of Perkinsus infection in wild populations of Manila clams and 10 sympatric species from three sites were investigated by Ray's fluid thioglycolate medium (RFTM) assay seasonally across a single year. Perkinsus infection was only identified in Manila clams, with a high prevalence (274/284 = 96.48 %) and low intensity (89.8 % with a Mackin value ≤ 2, suggesting generally low-intensity infections) throughout the year. Heavily infected clams were mainly identified in Tianheng in January, which displayed no macroscopic signs of disease. An overview of the whole visceral mass section showed that the trophozoites mostly aggregated in gills and connective tissue of the digestive tract, to a lesser extent in the mantle and foot, and even less frequently in adductor muscle and connective tissues of the gonad. PCR and ITS-5.8S rRNA sequencing of 93 representative RFTM-positive samples revealed a 99.69 to 100 % DNA sequence identity to Perkinsus olseni. Unexpectedly, significantly higher infection intensities were usually identified in January and April when the Condition Index (CI) was relatively high. We propose that factors associated with the anthropogenic harvesting pressure and irregular disturbances should be responsible for the uncommon seasonal infection dynamics of perkinsosis observed in the present study.
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Alveolados , Bivalves , Animais , Estações do Ano , Sequência de Bases , Reação em Cadeia da Polimerase , China , Alveolados/genéticaRESUMO
Autism Spectrum Disorder (ASD), a complex neurodevelopmental disorder marked by social communication deficits and repetitive behaviors, may see symptom amelioration through gut microbiota modulation. This study investigates the effects of a synbiotic - specifically a probiotic amplified by prebiotic supplementation - on ASD-like mouse model's social deficiencies. This model was established via valproic acid injection into pregnant females. Post-weaning, male progeny received daily synbiotic treatment, a combination of Lactobacillus reuteri (L. reuteri) and inulin, for four weeks. Results indicated that the synbiotic rectified social impairments and attenuated inflammatory cytokine expressions in the brain. Moreover, synbiotic intervention protected gut barrier integrity and altered the gut microbiota composition, enhancing the butyrate-producing Bifidobacterium abundance. The synbiotic elevated metabolites such as butyrate and 3-hydroxybutyric acid (3-HB), alongside upregulated genes associated with 3-HB synthesis in the colon and liver, and brain receptors. Conclusively, the synbiotic combination of L. reuteri and inulin mitigated ASD-related social impairments, partially via their regulatory effect on the gut-brain axis.
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Transtorno do Espectro Autista , Limosilactobacillus reuteri , Simbióticos , Feminino , Masculino , Camundongos , Animais , Inulina , Eixo Encéfalo-Intestino , Transtorno do Espectro Autista/terapia , ButiratosRESUMO
Central nervous system (CNS) disorders present a growing and costly global health challenge, accounting for over 11% of the diseases burden in high-income countries. Despite current treatments, patients often experience persistent symptoms that significantly affect their quality of life. Dietary polysaccharides have garnered attention for their potential as interventions for CNS disorders due to their diverse mechanisms of action, including antioxidant, anti-inflammatory, and neuroprotective effects. Through an analysis of research articles published between January 5, 2013 and August 30, 2023, encompassing the intervention effects of dietary polysaccharides on Alzheimer's disease, Parkinson's disease, depression, anxiety disorders, autism spectrum disorder, epilepsy, and stroke, we have conducted a comprehensive review with the aim of elucidating the role and mechanisms of dietary polysaccharides in various CNS diseases, spanning neurodegenerative, psychiatric, neurodevelopmental disorders, and neurological dysfunctions. At least four categories of mechanistic bases are included in the dietary polysaccharides' intervention against CNS disease, which involves oxidative stress reduction, neuronal production, metabolic regulation, and gut barrier integrity. Notably, the ability of dietary polysaccharides to resist oxidation and modulate gut microbiota not only helps to curb the development of these diseases at an early stage, but also holds promise for the development of novel therapeutic agents for CNS diseases. In conclusion, this comprehensive review strives to advance therapeutic strategies for CNS disorders by elucidating the potential of dietary polysaccharides and advocating interdisciplinary collaboration to propel further research in this realm.
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This work, using the first-principles theory, uses the Ni-decorated WSe2 (Ni-WSe2) monolayer as a novel gas sensing material upon CO and HCHO in the dry-type transformers in order to evaluate their operation status. Results indicate that the Ni atom can be stably adsorbed on the TW site of the pristine WSe2 monolayer with the binding force of -4.33 eV. Via the gas adsorption analysis, it is found that the Ni-WSe2 monolayer performs chemisorption upon CO and HCHO molecules, with adsorption energies of -2.27 and -1.37 eV, respectively. The analyses of the band structure and Frontier molecular orbital manifest the potential of the Ni-WSe2 monolayer as a resistance-type gas sensor upon CO and HCHO, with sensing responses of 55.9 and 30.9% based on the band gap change and of 55.0 and 38.5% based on the energy gap change. The analysis of the density of state clearly shows the modified electronic property of the Ni-WSe2 monolayer in gas adsorptions. On the other hand, the analysis of the work function (WF) reveals the limited possibility to explore the Ni-WSe2 monolayer as a WF-based gas sensor for CO and HCHO detections. This work systemically studies the sensing potential of the Ni-WSe2 monolayer upon two typical gas species in the dry-type transformers, which is meaningful to explore novel nanomaterial-based gas sensors to monitor the operation condition of electrical equipment.
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The oil of Torreya grandis (TGO), a common nut in China, is considered to be a bioactive edible oil and has a great value in functional food development. In this study, the neuroprotective effects of TGO were investigated on a scopolamine (SCOP)-induced C57BL/6J mouse model. The mice were pretreated with TGO for 30 days (1000 mg per kg per day and 3000 mg per kg per day, i.g.). Behavioral tests showed that the supplementation of TGO could prevent the cognitive deficits induced by SCOP. TGO rebalanced the disorder of the cholinergic system by upgrading the level of acetylcholine. TGO also alleviated the over-activation of microglia and inhibited neuroinflammation and oxidative stress. Additionally, TGO could regulate the composition of gut microbiota, increase the production of short-chain fatty acids, and decrease the content of lipopolysaccharides in the serum. In conclusion, TGO has the potential to prevent loss of memory and impairment of cognition, which may be related to its regulation of the gut microbiota-metabolite-brain axis.