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The blood-brain barrier (BBB) protects the central nervous system from infections or harmful substances1; its impairment can lead to or exacerbate various diseases of the central nervous system2-4. However, the mechanisms of BBB disruption during infection and inflammatory conditions5,6 remain poorly defined. Here we find that activation of the pore-forming protein GSDMD by the cytosolic lipopolysaccharide (LPS) sensor caspase-11 (refs. 7-9), but not by TLR4-induced cytokines, mediates BBB breakdown in response to circulating LPS or during LPS-induced sepsis. Mice deficient in the LBP-CD14 LPS transfer and internalization pathway10-12 resist BBB disruption. Single-cell RNA-sequencing analysis reveals that brain endothelial cells (bECs), which express high levels of GSDMD, have a prominent response to circulating LPS. LPS acting on bECs primes Casp11 and Cd14 expression and induces GSDMD-mediated plasma membrane permeabilization and pyroptosis in vitro and in mice. Electron microscopy shows that this features ultrastructural changes in the disrupted BBB, including pyroptotic endothelia, abnormal appearance of tight junctions and vasculature detachment from the basement membrane. Comprehensive mouse genetic analyses, combined with a bEC-targeting adeno-associated virus system, establish that GSDMD activation in bECs underlies BBB disruption by LPS. Delivery of active GSDMD into bECs bypasses LPS stimulation and opens the BBB. In CASP4-humanized mice, Gram-negative Klebsiella pneumoniae infection disrupts the BBB; this is blocked by expression of a GSDMD-neutralizing nanobody in bECs. Our findings outline a mechanism for inflammatory BBB breakdown, and suggest potential therapies for diseases of the central nervous system associated with BBB impairment.
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Barrera Hematoencefálica , Encéfalo , Células Endoteliales , Gasderminas , Inflamación , Animales , Femenino , Humanos , Masculino , Ratones , Membrana Basal/metabolismo , Membrana Basal/ultraestructura , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/patología , Barrera Hematoencefálica/ultraestructura , Barrera Hematoencefálica/virología , Encéfalo/metabolismo , Encéfalo/patología , Encéfalo/ultraestructura , Caspasas Iniciadoras/metabolismo , Dependovirus , Células Endoteliales/metabolismo , Células Endoteliales/ultraestructura , Gasderminas/antagonistas & inhibidores , Gasderminas/metabolismo , Inflamación/patología , Inflamación/metabolismo , Klebsiella pneumoniae/fisiología , Receptores de Lipopolisacáridos/metabolismo , Lipopolisacáridos/sangre , Lipopolisacáridos/farmacología , Ratones Endogámicos C57BL , Piroptosis , Sepsis/metabolismo , Sepsis/patología , Sepsis/microbiología , Análisis de la Célula Individual , Uniones Estrechas/metabolismo , Uniones Estrechas/ultraestructuraRESUMEN
The pituitary represents an essential hub in the hypothalamus-pituitary-adrenal (HPA) axis. Pituitary hormone-producing cells (HPCs) release several hormones to regulate fundamental bodily functions under normal and stressful conditions. It is well established that the pituitary endocrine gland modulates the immune system by releasing adrenocorticotropic hormone (ACTH) in response to neuronal activation in the hypothalamus. However, it remains unclear how systemic inflammation regulates the transcriptomic profiles of pituitary HPCs. Here, we performed single-cell RNA-sequencing (scRNA-seq) of the mouse pituitary and revealed that upon inflammation, all major pituitary HPCs respond robustly in a cell type-specific manner, with corticotropes displaying the strongest reaction. Systemic inflammation also led to the production and release of noncanonical bioactive molecules, including Nptx2 by corticotropes, to modulate immune homeostasis. Meanwhile, HPCs up-regulated the gene expression of chemokines that facilitated the communication between the HPCs and immune cells. Together, our study reveals extensive interactions between the pituitary and immune system, suggesting multifaceted roles of the pituitary in mediating the effects of inflammation on many aspects of body physiology.
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Hormona Liberadora de Corticotropina , Hipófisis , Ratones , Animales , Hormona Liberadora de Corticotropina/genética , Hipófisis/metabolismo , Hormona Adrenocorticotrópica/genética , Hormona Adrenocorticotrópica/metabolismo , Hormona Adrenocorticotrópica/farmacología , Inflamación/genética , Perfilación de la Expresión GénicaRESUMEN
Endometrial cancer (EC) is the most prevalent gynecological epithelial malignancy. DNA methylation is a promising cancer biomarker, but limited use for detecting EC. We previously found that the level of cysteine dioxygenase 1 (CDO1) promoter methylation was elevated in EC patients through methylomics, but the role and mechanism of CDO1 in EC remained unclear. Here, the methylation level of CDO1 promoter was detected by Bisulfite-sequencing PCR (BSP) and methylation-specific PCR (MSP) (bisulfite-conversion-based PCR methods, which remain the most commonly used techniques for methylation detection). Cells were incubated with erastin (the ferroptosis activator). Cell vitality was measured using the cell counting kit-8 (CCK-8) assay. FAM83H-AS1 cellular distribution was analyzed by the fluorescence in situ hybridization (FISH) assay. Lipid ROS level was examined by BODIPY-C11 staining. The interactions between FAM83H-AS1, CDO1, and DNA methyltransferase1 (DNMT1) were analyzed by RNA binding protein immunoprecipitation (RIP) or chromatin immunoprecipitation (ChIP) assay. The xenograft mouse model was utilized to test CDO1 and FAM83H-AS1's influence on tumor development in vivo. Results showed that CDO1 was hypermethylated and downregulated in EC. CDO1 knockdown reduced erastin-induced ferroptosis in EC cells. Mechanistically, DNMT1 is a DNA methyltransferase, which can transfer methyl groups to cytosine nucleotides in genomic DNA. Long non-coding RNA (lncRNA) FAM83H-AS1 increased CDO1 promoter methylation level and inhibited its expression in EC cells by recruiting DNMT1. CDO1 knockdown or FAM83H-AS1 overexpression promoted EC tumor growth in vivo. LncRNA FAM83H-AS1 inhibited ferroptosis in EC by recruiting DNMT1 to increase CDO1 promoter methylation level and inhibit its expression.
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As the resident immune cells in the central nervous system (CNS), microglia orchestrate immune responses and dynamically sculpt neural circuits in the CNS. Microglial dysfunction and mutations of microglia-specific genes have been implicated in many diseases of the CNS. Developing effective and safe vehicles for transgene delivery into microglia will facilitate the studies of microglia biology and microglia-associated disease mechanisms. Here, we report the discovery of adeno-associated virus (AAV) variants that mediate efficient in vitro and in vivo microglial transduction via directed evolution of the AAV capsid protein. These AAV-cMG and AAV-MG variants are capable of delivering various genetic payloads into microglia with high efficiency, and enable sufficient transgene expression to support fluorescent labeling, Ca2+ and neurotransmitter imaging and genome editing in microglia in vivo. Furthermore, single-cell RNA sequencing shows that the AAV-MG variants mediate in vivo transgene delivery without inducing microglia immune activation. These AAV variants should facilitate the use of various genetically encoded sensors and effectors in the study of microglia-related biology.
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Dependovirus , Microglía , Dependovirus/genética , Técnicas de Transferencia de Gen , Terapia Genética/métodos , Vectores Genéticos/genética , Transducción GenéticaRESUMEN
The molecular details of an electrocatalytic interface play an essential role in the production of sustainable fuels and value-added chemicals. Many electrochemical reactions exhibit strong cation-dependent activities, but how cations affect reaction kinetics is still elusive. We report the effect of cations (K+, Li+, and Ba2+) on the interfacial water structure using second-harmonic generation (SHG) and classical molecular dynamics (MD) simulation. The second- (χH2O(2)) and third-order (χH2O(3)) optical susceptibilities of water on Pt are smaller in the presence of Ba2+ compared to those of K+, suggesting that cations can affect the interfacial water orientation. MD simulation reproduces experimental SHG observations and further shows that the competition between cation hydration and interfacial water alignment governs the net water orientation. The impact of cations on interfacial water supports a cation hydration-mediated mechanism for hydrogen electrocatalysis; i.e., the reaction occurs via water dissociation followed by cation-assisted hydroxide/water exchange on Pt. Our study highlights the role of interfacial water in electrocatalysis and how innocent additives (such as cations) can affect the local electrochemical environment.
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ABSTRACT: Sepsis-induced myocardial dysfunction commonly occurs in individuals with sepsis and is a severe complication with high morbidity and mortality rates. This study aimed to investigate the effects and potential mechanisms of the natural steroidal sapogenin ruscogenin (RUS) against lipopolysaccharide (LPS)-induced myocardial injury in septic mice. We found that RUS effectively alleviated myocardial pathological damage, normalized cardiac function, and increased survival in septic mice. RNA sequencing demonstrated that RUS administration significantly inhibited the activation of the NOD-like receptor signaling pathway in the myocardial tissues of septic mice. Subsequent experiments further confirmed that RUS suppressed myocardial inflammation and pyroptosis during sepsis. In addition, cultured HL-1 cardiomyocytes were challenged with LPS, and we observed that RUS could protect these cells against LPS-induced cytotoxicity by suppressing inflammation and pyroptosis. Notably, both the in vivo and in vitro findings indicated that RUS inhibited NOD-like receptor protein-3 (NLRP3) upregulation in cardiomyocytes stimulated with LPS. As expected, knockdown of NLRP3 blocked the LPS-induced activation of inflammation and pyroptosis in HL-1 cells. Furthermore, the cardioprotective effects of RUS on HL-1 cells under LPS stimulation were abolished by the novel NLRP3 agonist BMS-986299. Taken together, our results suggest that RUS can alleviate myocardial injury during sepsis, at least in part by suppressing NLRP3-mediated inflammation and pyroptosis, highlighting the potential of this molecule as a promising candidate for sepsis-induced myocardial dysfunction therapy.
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Antiinflamatorios , Modelos Animales de Enfermedad , Lipopolisacáridos , Ratones Endogámicos C57BL , Miocitos Cardíacos , Proteína con Dominio Pirina 3 de la Familia NLR , Piroptosis , Sepsis , Transducción de Señal , Espirostanos , Animales , Lipopolisacáridos/toxicidad , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Miocitos Cardíacos/metabolismo , Espirostanos/farmacología , Sepsis/tratamiento farmacológico , Sepsis/complicaciones , Sepsis/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Piroptosis/efectos de los fármacos , Masculino , Transducción de Señal/efectos de los fármacos , Línea Celular , Antiinflamatorios/farmacología , Ratones , Cardiomiopatías/prevención & control , Cardiomiopatías/patología , Cardiomiopatías/metabolismo , Cardiomiopatías/tratamiento farmacológico , Cardiomiopatías/inducido químicamente , Mediadores de Inflamación/metabolismoRESUMEN
Overactivation of cardiac fibroblasts (CFs) is one of the main causes of myocardial fibrosis (MF), and inhibition of CF activation is a crucial strategy for MF therapy. A previous study by our group demonstrated that leonurine (LE) effectively inhibits collagen synthesis and myofibroblast generation originated from CFs, and eventually mitigates the progression of MF (where miR-29a-3p is likely to be a vital mediator). However, the underlying mechanisms involved in this process remain unknown. Thus, the present study aimed to investigate the precise role of miR-29a-3p in LE-treated CFs, and to elucidate the pharmacological effects of LE on MF. Neonatal rat CFs were isolated and stimulated by angiotensin II (Ang II) to mimic the pathological process of MF in vitro. The results show that LE distinctly inhibits collagen synthesis, as well as the proliferation, differentiation and migration of CFs, all of which could be induced by Ang II. In addition, LE promotes apoptosis in CFs under Ang II stimulation. During this process, the down-regulated expressions of miR-29a-3p and p53 are partly restored by LE. Either knockdown of miR-29a-3p or inhibition of p53 by PFT-α (a p53 inhibitor) blocks the antifibrotic effect of LE. Notably, PFT-α suppresses miR-29a-3p levels in CFs under both normal and Ang II-treated conditions. Furthermore, ChIP analysis confirmed that p53 is bound to the promoter region of miR-29a-3p, and directly regulates its expression. Overall, our study demonstrates that LE upregulates p53 and miR-29a-3p expression, and subsequently inhibits CF overactivation, suggesting that the p53/miR-29a-3p axis may play a crucial role in mediating the antifibrotic effect of LE against MF.
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MicroARNs , Ratas , Animales , Angiotensina II/farmacología , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Fibrosis , Colágeno Tipo I/metabolismo , Fibroblastos/metabolismoRESUMEN
This study investigated the removal performance of ofloxacin (OFL) by a novel electro-Fenton enhanced microfiltration membrane. The membranes used in this study consisted of metal-organic framework derived porous carbon, carbon nanotubes and Fe2+, which were able to produce hydroxyl radicals (â¢OH) in-situ via reducing O2 to hydrogen peroxide. Herein, membrane filtration with bias not only concentrated the pollutants to the level that could be efficiently treated by electro-Fenton but also confined/retained the toxic intermediates within the membrane to ensure a prolonged contact time with the oxidants. After validated by experiments, the applied bias of -1.0 V, pH of 3 and electrolyte concentration of 0.1 M were the relatively optimum conditions for OFL degradation. Under these conditions, the average OFL removal rate could be reach 75% with merely 5% membrane flux loss after 4 cycles operation by filtrating 1 mg/L OFL. Via decarboxylation reaction, piperazinyl ring opening, dealkylation and ipso substitution reaction, etc., OFL could be gradually and efficiently degraded to intermediate products and even to CO2 by â¢OH. Moreover, the oxidation reaction was preferred to following first-order reaction kinetics. This research verified a possibility for antibiotic removal by electro-enhanced microfiltration membrane.
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Nanotubos de Carbono , Contaminantes Químicos del Agua , Ofloxacino , Porosidad , Antibacterianos , Oxidantes , Peróxido de Hidrógeno , Oxidación-ReducciónRESUMEN
BACKGROUND: Recently, numerous publications on Helicobacter pylori (H. pylori) have been published, but bibliometric analyses on this research field are scarce. To address this gap, we conducted a bibliometric analysis to provide a comprehensive overview and to explore the current research states and hotspots in this field. MATERIALS AND METHODS: Publications on H. pylori from 2002 to 2021 were retrieved from the Web of Science Core Collection database (WoSCC). Trends in publications and citations were analyzed using Excel 2021. VOSviewer and Citespace were used to perform bibliometrics analysis. RESULTS: 36,266 publications on H. pylori were retrieved from the WoSCC database. In general, we observed an increasing trend in the number of publications over the past 20 years. The United States was the most productive and influential country, with the largest proportion of both publications and total citations. Helicobacter, US Department of Veterans Affairs, and Graham, David were the most productive journals, institutions and authors, respectively. Further analysis the co-occurrence and burst detection of keywords revealed that the most common keywords were "Helicobacter pylori," "gastric cancer," and "gastritis," all keywords were divided into eight main clusters, and the most important current research hotspot was the relationship between H. pylori infection and the changes of gut microbiota. CONCLUSIONS: The United States has been the most productive and influential country on H. pylori research, and H. pylori-related research remains an active research field. The relationship between H. pylori infection and the changes of gut microbiota is a research hotspot attracting significant attention.
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Infecciones por Helicobacter , Helicobacter pylori , Helicobacter , Humanos , Bibliometría , Bases de Datos Factuales , Infecciones por Helicobacter/epidemiologíaRESUMEN
Intimate interface design at the molecular level in heterojunctions deserves significant attention since the charge transfer efficiency at the interfaces can greatly affect the catalytic performance. Herein, an efficient interface engineering strategy was reported to design a titanium porphyrin metal-organic framework-ZnIn2S4 (TMF-ZIS) core-shell heterojunction which is tightly connected via coordination bonds (-N-Zn-). Such interfacial chemical bonds as the directional carrier transfer channels afforded improved charge separation efficiency compared to the physical composite of TMF and ZIS without chemical bonding. As a result, the optimized TMF-ZIS composite showed a 13.37 mmol·g-1·h-1 H2 production which is 47.7, 3.3, and 2.4 times that of TMF, ZIS, and mechanical mixing samples, respectively. Moreover, the composite also exhibited high photocatalytic tetracycline hydrochloride (TCH) degradation efficiency. Profiting from the core-shell structures, the ZIS shell efficiently prevented the aggregation and photocorrosion of TMF core particles which afforded enhanced chemical stability. Such an interface engineering strategy will be a versatile method to obtain highly effective organic-inorganic heterojunctions and offer new ideas for modulating the interfaces in the heterojunctions at the molecular level.
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To achieve rapid detection of carbapenem-resistant Escherichia coli strains, a pattern recognition method based on electrospray ionization Orbitrap mass spectrometry (ESI-Orbitrap MS) was used for the analysis of drug-resistant, and sensitive strains of metabolites were analyzed. Results of five clustering methods applied to analytical data of metabolites were evaluated using iso-phenotypic coefficients. The effectiveness of three methods, principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA), was compared. Univariate statistics such as t-test and fold change were also used to examine the screened differential information. Both PLS-DA and OPLS-DA could achieve rapid identification of strain classes, and OPLS-DA was more powerful in screening 96 significantly different ions. This work is expected to be useful for rapid and accurate identification of strains.
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Escherichia coli , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masa por Ionización de Electrospray/métodos , Análisis Discriminante , Análisis por Conglomerados , Análisis de Componente Principal , Metabolómica/métodos , Cromatografía Líquida de Alta Presión/métodosRESUMEN
OBJETIVES: To investigate the positional changes in the temporomandibular joint (TMJ) disc-condyle-fossa complex of patients with anterior disc displacement without reduction (ADDWoR) and to evaluate the effect of disc repositioning (DR) surgery. MATERIAL AND METHODS: Fifteen patients with unilateral ADDWoR (30 joints) were included. MRI of the TMJ was performed at T0 (1 week before surgery), T1 (1 month after surgery), and T2 (9-12 months after surgery). The glenoid fossa, disc, and condyle were reconstructed and analyzed using Mimics software. RESULTS: In the patients with unilateral ADDWoR, the disc on the ADD side showed a tendency to downward shift in the coronal direction and forward shift in the sagittal direction; the condyle of ADD side showed a tendency to backward shift in the sagittal direction and upward shift in the coronal direction. When comparing the same ADDwoR TMJ at T0, T1, and T2, the disc was found to move upward and backward after DR surgery at T1 and T2, and the condyle was found to move upward and backward after DR surgery at T1 but returned to the original position at T2. CONCLUSIONS: ADDWoR leads to forward and downward displacement of the disc relative to the condyle and upward displacement of the condyle relative to the tuberosity. DR surgery improved upon the structural abnormalities of the TMJ complex, for which stability was maintained as determined in the 9 to 12 month postoperative follow-up. CLINIC RELEVANCE: DR surgery effectively and constantly improves the positional abnormalities of the TMJ complex.
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Luxaciones Articulares , Trastornos de la Articulación Temporomandibular , Humanos , Cóndilo Mandibular/cirugía , Trastornos de la Articulación Temporomandibular/cirugía , Luxaciones Articulares/cirugía , Disco de la Articulación Temporomandibular/cirugía , Imagen por Resonancia Magnética , Articulación Temporomandibular/cirugíaRESUMEN
It is controversial that high-fluoride and high-iodine combined exposure affects the prevalence of dental fluorosis and goiter. The aim of this study was to explore the potential association between high-fluoride and high-iodine combined exposure with dental fluorosis and goiter. We retrieved relevant articles from PubMed, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database and China Science and Technology Journal Database (VIP). The query format was 1 # "Fluorosis" OR "Fluoride," 2 # "Iodine" OR "Iodide," and 3 # 1 AND 2. A total of 20 papers were included in this study after independent review by two investigators. Our analysis showed that high-fluoride and high-iodine biphasic exposure was significantly associated with the prevalence of goiter (OR = 4.69, 95% CI 2.82-7.80, P < 0.001). The prevalence of dental fluorosis was also significantly raised (OR = 11.71, 95% CI 7.57-18.14, P < 0.001). Sensitivity analysis suggested that combined statistics of multiple studies were reliable. For goiter, subgroup analysis revealed study province, sample size and published year as sources of heterogeneity (P < 0.001). For dental fluorosis, only sample size was the impact factor of heterogeneity. As well, funnel plot, Begg's test and Egger's test suggested there was no publication bias (P > 0.05). Overall, our study demonstrates that high-fluoride and high-iodine combined exposure is a risk factor for occurrence of dental fluorosis and goiter. The chronic of high-fluoride and high-iodine combined exposure is a significant higher risk of disease than normal.
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Fluorosis Dental , Bocio , Yodo , Humanos , Fluoruros/toxicidad , Fluoruros/análisis , Fluorosis Dental/epidemiología , Fluorosis Dental/etiología , Factores de Riesgo , PrevalenciaRESUMEN
AIMS: Inflammation is a key feature of endothelial dysfunction induced by angiotensin (Ang) II. The purpose of this study was to explore the role of Nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome in endothelial dysfunction in Ang II-induced hypertension. MATERIALS AND METHODS: We analyzed blood pressure and vascular function of wild-type (WT) and Nlrp3 knockout (Nlrp3-/-) mice, treated with Ang II. In vitro, we mainly tested the endothelial nitric oxide synthase (eNOS) phosphorylation expression of human umbilical vein endothelial cells (HUVECs). KEY FINDINGS: Here we showed that 14-day Ang II infusion into mice resulted in the elevation of blood pressure, NLRP3 expression, serum interleukin (IL)-1ß level, and the decline of endothelium-dependent relaxation function, p-eNOS-Ser1177 expression in aortas. Nlrp3 deficiency reduced Ang II-induced blood pressure elevation and endothelial dysfunction. In vitro, NLRP3 was involved in the effect of Ang II on reducing p-eNOS-Ser1177 expression. Moreover, the direct effect of IL-1ß on vascular endothelial injury could be observed in both vivo and vitro. SIGNIFICANCE: Our result demonstrates that the NLRP3 inflammasome is critically involved in the detrimental effects of Ang II on vascular endothelium in hypertension via the activation of IL-1ß, placing NLRP3 as a potential target for therapeutic interventions in conditions with endothelial dysfunction in hypertension.
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Hipertensión , Inflamasomas , Angiotensina II/farmacología , Animales , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Hipertensión/inducido químicamente , Hipertensión/metabolismo , Inflamasomas/metabolismo , Inflamasomas/farmacología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismoRESUMEN
BACKGROUND: To identify the association between albuminuria and dementia or cognitive impairment. METHODS: The literature search was performed to identify relevant scientific studies through August 2019, including PubMed/Medline and EMBASE. For inclusion, the studies had to fulfil the following criteria: population-based cohort, case-control or cross-sectional studies; quantifying an association of albuminuria with cognitive impairment or dementia; and reported odds ratio (OR), and the corresponding 95% confidential interval (95% CI). Random effects model was used to yield pooled estimates. RESULTS: A total of 16 studies (11 cohort studies and five cross-sectional studies) were included in the meta-analyses. Based on the fully adjusted estimates, albuminuria was associated with a significant higher risk of cognitive impairment or dementia. Furthermore, the same trend existed for cognitive impairment and dementia, respectively. In addition, both of Alzheimer's diseases (AD) and vascular dementia (VaD) were significantly associated with albuminuria. CONCLUSION: Albuminuria was significantly associated with cognitive impairment and dementia. Corresponding to an earlier subclinical time-point in kidney disease progress, albuminuria may be a potential factor predicting the future occurrence of dementia.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Demencia , Albuminuria/complicaciones , Enfermedad de Alzheimer/complicaciones , Disfunción Cognitiva/complicaciones , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/epidemiología , Estudios Transversales , Demencia/complicaciones , Demencia/diagnóstico , Demencia/epidemiología , HumanosRESUMEN
A rapid and accurate analytical method was established to identify CREC and CSEC. Orbitrap-MS was used to detect the polypeptide of CREC and CSEC strains, and MS data were analyzed by pattern recognition analyses such as hierarchical cluster analysis (HCA), principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA). HCA based on the farthest distance method could well distinguish the two types of E.â coli, and the cophenetic correlation coefficient of the farthest distance method was 0.901. Comparing the results of PCA, PLS-DA, and OPLS-DA, OPLS-DA exhibited the highest accuracy in predicting the CREC and CSEC strains. A total of 26â compounds were identified, and six of the compounds were the highly significant difference between the two types of strains. MS combined with pattern recognition can achieve a more comprehensive and efficient statistical analysis of complex biological samples.
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Carbapenémicos , Escherichia coli , Cromatografía Líquida de Alta Presión , Análisis Discriminante , Análisis de los Mínimos Cuadrados , Péptidos , Análisis de Componente PrincipalRESUMEN
OBJECTIVES: Patients with high mandibular plane facial morphology are the most dominant facial type who experience TMJ abnormalities with resultant condylar resorption, affecting the orthodontic and orthognathic treatment outcomes. The study aimed to quantitatively assess the three-dimensional condylar remodeling during the presurgical orthodontics and after orthognathic surgery of the retrognathic mandible with a high mandibular plane angle. The study also investigated the correlation between the resultant remodeling based on the hypothesis that condylar resorption following orthognathic surgery is a part of a progressive presurgical resorption process. MATERIALS AND METHODS: The study included adults with mandibular retrognathism and high mandibular plane angle who have computed tomography scans (CT) obtained before any treatment (T0), after completion of presurgical treatment before surgery (T1), and at long-term follow-up after surgery (T2). DICOM of CT scan was gathered and processed using ITK-SNAP and 3D Slicer software. The interval between T0 and T1 was represented as a presurgical phase, while between T1 and T2 was defined as a postsurgical phase (T1-T2). RESULTS: Twenty-five patients (50 condyles) were included with a mean age of 23 ± 3.2 years. The mean of the follow-up during the presurgical phase was 19.8 ± 7.1 months and 15.5 ± 5.5 months during the postsurgical phase. The condylar volume during the presurgical phase (T0-T1) was relatively stable (- 3.3 ± 37.2mm3). However, during the postsurgical phase (T1-T2), the volume was significantly reduced - 113.8 ± 98.3mm3 (P < 0.001). Localized condylar surface resorption during the postsurgical phase was significantly higher than during the presurgical phase (P < 0.05). No correlation was found between the localized condylar surface remodeling during the presurgical and postsurgical phases. However, a negative statistically significant correlation existed between the overall condylar volume changes during the presurgical and postsurgical phases (r = 0.502, P < 0.001). CONCLUSION: Significant condylar resorption following orthognathic surgery of the retrognathic mandible with a high mandibular plane angle might occur regardless of the presurgical status of the condyle. CLINICAL RELEVANCE: The study provided an evidence to be discussed with the patients and considered throughout the treatment of mandibular retrognathia with high mandibular plane angle.
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Cirugía Ortognática , Procedimientos Quirúrgicos Ortognáticos , Retrognatismo , Adulto , Humanos , Adulto Joven , Cóndilo Mandibular/diagnóstico por imagen , Cóndilo Mandibular/cirugía , Retrognatismo/cirugía , Mandíbula , Cefalometría , Estudios RetrospectivosRESUMEN
BACKGROUND: This study aimed to quantify the morphological changes of temporomandibular joint (TMJ) discs after disc repositioning surgery using the three-dimensional (3D) modeling. METHODS: Thirty patients who diagnosed with unilateral ADDwoR were included to compare the morphological differences between ADDWoR discs and normal discs, and fifteen patients who experienced unilateral or bilateral disc repositioning surgery were included to analyze the morphological changes before and after disc repositioning surgery. Disc 3D reconstruction and analyses were performed using magnetic resonance imaging (MRI) data. RESULTS: In the unilateral ADDwoR patients, volume, superficial area, length, and maximum longitudinal-sectional area of the ADDwoR disc were significantly smaller compared with the non-affected discs. However, there was no significant difference in width and cross-sectional areas between ADDwoR discs and non-affected discs. In patients who subjected to disc repositioning surgery, disc volume, superficial area, length, width and maximum longitudinal-sectional area of TMJ discs were markedly increased 6 months after surgery. CONCLUSIONS: This study demonstrated that the TMJ discs tended to be morphologically smaller in volume and shorter in length under ADDwoR status. Importantly, the ADDwoR discs tended to morphologically recover toward non-affected discs after 6 months follow-up following TMJ disc repositioning surgery.
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Luxaciones Articulares , Trastornos de la Articulación Temporomandibular , Humanos , Luxaciones Articulares/diagnóstico por imagen , Luxaciones Articulares/cirugía , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos , Articulación Temporomandibular , Disco de la Articulación Temporomandibular/diagnóstico por imagen , Disco de la Articulación Temporomandibular/patología , Disco de la Articulación Temporomandibular/cirugía , Trastornos de la Articulación Temporomandibular/diagnóstico por imagen , Trastornos de la Articulación Temporomandibular/patología , Trastornos de la Articulación Temporomandibular/cirugíaRESUMEN
Immunosignal hybridization chain reaction (isHCR) combines antibody-antigen interactions with hybridization chain reaction (HCR) technology, which results in amplification of immunofluorescence signals by up to two to three orders of magnitude with low background. isHCR's highly modular and easily adaptable design enables the technique to be applied broadly, and we further optimized its use in multiplexed imaging and in state-of-the-art tissue expansion and clearing techniques.
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Técnicas de Amplificación de Ácido Nucleico/métodos , Hibridación de Ácido Nucleico/métodos , Animales , Anticuerpos , Antígenos , Conducta Animal , Encéfalo/metabolismo , Regulación de la Expresión Génica , Células HEK293 , Humanos , Inmunohistoquímica , Ratones , Unión ProteicaRESUMEN
We developed a dual-adeno-associated-virus expression system that enables strong and sparse labeling of individual neurons with cell-type and projection specificity. We demonstrated its utility for whole-brain reconstruction of midbrain dopamine neurons and striatum-projecting cortical neurons. We further extended the labeling method for rapid reconstruction in cleared thick brain sections and simultaneous dual-color labeling. This labeling system may facilitate the process of generating mesoscale single-neuron projectomes of mammalian brains.