RESUMO
The design and syntheses of new birefringent crystals will be of great importance in commercial applications and materials science. A series of ultraviolet (UV) birefringent crystals, AX·(H2SeO3)n (A = K, Cs; X = Cl, Br; n = 1, 2), with large sizes up to 23 × 6 × 3 mm3, was successfully synthesized by simple aqueous solution method. These four compounds belong to three different space groups. Isomorphic KCl·(H2SeO3)2 and CsCl·(H2SeO3)2 crystallize in the P1¯ space group, while CsBr·(H2SeO3)2 and CsCl·H2SeO3 crystallize in the P21/m and P21/c space groups, respectively. They exhibit cocrystal structures composed of [2(H2SeO3)]∞ and [AX]∞ frameworks, ingeniously inheriting the large optical anisotropy of selenite and the wide band gap of alkali metal halide. And it proves that these compounds indeed possess large birefringence (0.1-0.17 at 532 nm) and short UV cutoff edges (227-239 nm), achieving a balance of optical properties. This research affords a simple and viable strategy for the design and syntheses of new UV birefringent crystals. Besides, it is also found that the n value and ionic size (A and X ions) have important influences on the crystal structures and optical properties of AX·(H2SeO3)n. And this will promote further understanding of the alkali metal halide selenite family.
RESUMO
White matter hyperintensities (WMHs) refer to a group of diseases with numerous etiologies while oligodendrocytes remain the centerpiece in the pathogenesis of WMHs. Ring Finger Protein 216 (RNF216) encodes a ubiquitin ligase, and its mutation begets WMHs, ataxia, and cognitive decline in patients. Yet no study has revealed the function of RNF216 in oligodendroglia and WHIs before. In this study, we summarized the phenotypes of RNF216-mutation cases and explored the normal distribution of RNF216 in distinct brain regions and neuronal cells by bioinformatic analysis. Furthermore, MO3.13, a human oligodendrocyte cell line, was applied to study the function alteration after RNF216 knockdown. As a result, WMHs were the most common symptom in RNF216-mutated diseases, and RNF216 was indeed relatively enriched in corpus callosum and oligodendroglia in humans. The downregulation of RNF216 in oligodendroglia remarkably hampered cell proliferation by inhibiting the Akt pathway while having no significant effect on cell injury and oligodendrocyte maturation. Combining clinical, bioinformatical, and experimental evidence, our study implied the pivotal role of RNF216 in WMHs which might serve as a potent target in the therapy of WMHs.
Assuntos
Proliferação de Células , Oligodendroglia , Ubiquitina-Proteína Ligases , Substância Branca , Humanos , Mutação com Perda de Função , Oligodendroglia/metabolismo , Oligodendroglia/citologia , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Substância Branca/metabolismo , Substância Branca/patologia , Substância Branca/citologiaRESUMO
Chiral mesoporous silica (mSiO2) nanomaterials have gained significant attention during the past two decades. Most of them show a topologically characteristic helix; however, little attention has been paid to the molecular-scale chirality of mSiO2 frameworks. Herein, we report a chiral amide-gel-directed synthesis strategy for the fabrication of chiral mSiO2 nanospheres with molecular-scale-like chirality in the silicate skeletons. The functionalization of micelles with the chiral amide gels via electrostatic interactions realizes the growth of molecular configuration chiral silica sols. Subsequent modular self-assembly results in the formation of dendritic large mesoporous silica nanospheres with molecular chirality of the silica frameworks. As a result, the resultant chiral mSiO2 nanospheres show abundant large mesopores (â¼10.1 nm), high pore volumes (â¼1.8 cm3·g-1), high surface areas (â¼525 m2·g-1), and evident CD activity. The successful transfer of the chirality from the chiral amide gels to composited micelles and further to asymmetric silica polymeric frameworks based on modular self-assembly leads to the presence of molecular chirality in the final products. The chiral mSiO2 frameworks display a good chiral stability after a high-temperature calcination (even up to 1000 °C). The chiral mSiO2 can impart a notable decline in ß-amyloid protein (Aß42) aggregation formation up to 79%, leading to significant mitigation of Aß42-induced cytotoxicity on the human neuroblastoma line SH-ST5Y cells in vitro. This finding opens a new avenue to construct the molecular chirality configuration in nanomaterials for optical and biomedical applications.
Assuntos
Doença de Alzheimer , Nanosferas , Humanos , Nanosferas/química , Peptídeos beta-Amiloides , Dióxido de Silício/química , Micelas , Géis , AmidasRESUMO
A MOF-on-MOF heterostructure is attractive in material science because of its potential combined effects in catalysis. However, precisely controlling the growth pattern at the metal-organic framework (MOF) nucleation stage to manipulate the metallic composition and structure dimensionality remain a challenge. Herein, we introduce a polyvinylpyrrolidone-assist kinetic-control strategy to achieve the "anti-epitaxial growth" pattern of a foreign MOF nucleus on the (111) facets of UiO-66-NH2 octahedron seeds, and construct diverse two-dimensional-on-three-dimensional (2D-on-3D) MOF heterostructures (2D-on-3D Cu, Zn, Cd, Co, and Ni). Notably, the 2D-on-3D Cu exhibits a unique "dimensionality-hybrid" effect in photocatalysis which led to a significant photoactivity enhancement over those of the traditional "dimensionality-identical" 2D, 3D and 3D-on-3D MOF structures.
RESUMO
Background: The Scoliosis Research Society (SRS)-22 outcomes have been shown to be correlated with radiographic parameter of adolescent idiopathic scoliosis (AIS). A recent study suggested that curve patterns might play a role in assessing the influence of deformity on patient's reported outcomes. The aim of this study was to examine the relationship between radiographic parameters and SRS-22 questionnaire outcomes in female patients with adolescent AIS among the Chinese population based on five curve patterns.Patients and Methods: The radiographic data and SRS-22 questionnaires of 259 female AIS patients were reviewed. Radiographic measurements included: Cobb angle of the major curve, T1 tilt angle, apical vertebral rotation, apical vertebral translation (AVT), thoracic kyphosis, and lumbar lordosis. Curve patterns included single thoracic (T), single thoracolumbar/lumbar (TL), double thoracic (DT), double major (DM), and triple major (TM). The correlation between radiographic measurements and each domain in SRS-22 was determined by Pearson's correlation coefficient.Results: The curve magnitude and AVT of the major curve were found to be significantly correlated with the self-image domain in all cases (Cobb angle: r = -0.426, p = 0.002; AVT: r = -0.281, p=0.006) and in all curve patterns except for TM. Compared to other groups, the TM group had a significantly larger major curve than the DT group and TL group (p ≤ 0.004). In TM group, the self-image scores were lower than TL group (p =0.018), and the function scores were lower than that in T, TL (p < 0.001) and DM groups (p =0.013). In the DT group, the T1 tilt was significantly correlated with the self-image domain (r = -0.376, p =0.004). In the T group, coronal curve magnitude was significantly correlated with function domain (r = -0.397, p < 0.001).Conclusion: Our findings suggested curve patterns should be considered in evaluating the correlations between radiographic parameters and SRS-22 outcomes in patients with AIS.
RESUMO
BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder featuring the behavioral and psychological symptoms of dementia. Patients with early-onset AD that exhibits first as psychotic symptoms usually lack obvious cognitive impairment, so they may be misdiagnosed with late-onset schizophrenia. CASE PRESENTATION: We report a patient who had prominent psychotic symptoms at the age of 60 and was initially diagnosed with very-late-onset-schizophrenia-like psychosis. Psychotic symptoms disappeared rapidly after treatment with olanzapine, and the patient later showed extrapyramidal symptoms and decline in cognitive function. Brain magnetic resonance imaging (MRI) showed frontotemporal atrophy, and positron emission tomography (PET) showed extensive areas of hypometabolism in the frontal cortex and head of the caudate nucleus. The patient's SORL1 gene was found to carry a heterozygrous mutation (c.296A > G). The patient was eventually diagnosed with early-onset AD. CONCLUSIONS: Our case suggests that clinicians should consider the possibility of early-onset AD in middle-aged or elderly patients whose first symptoms are the behavioral and psychological symptoms of dementia. To distinguish early-onset AD from late-onset schizophrenia, clinicians should evaluate cognitive function, perform MRI and PET, and search for SORL1 mutations.
Assuntos
Doença de Alzheimer , Transtornos Psicóticos , Esquizofrenia , Idoso , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Humanos , Proteínas Relacionadas a Receptor de LDL/genética , Imageamento por Ressonância Magnética , Proteínas de Membrana Transportadoras/genética , Pessoa de Meia-Idade , Mutação , Tomografia por Emissão de Pósitrons , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/etiologia , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/tratamento farmacológicoRESUMO
BACKGROUND: The purpose of this study was to investigate the psychological status of the general population in mainland China during the outbreak of coronavirus disease 2019 (COVID-19), and to explore the factors influencing psychological distress, in order to provide the basis for further psychological intervention programs. METHODS: We administered three questionnaires on-line to a convenience sample of the general population from different regions of mainland China from February 1 to February 4, 2020. We used the Mandarin versions of the six-item Kessler psychological distress scale (K6), the Simplified Coping Style Questionnaire (SCSQ), and the Social Support Rating Scale (SSRS). We also collected demographic data and other information related to the COVID-19 outbreak. Multivariate binary logistic regression analysis was used to identify factors influencing psychological distress. RESULTS: Of 1607 respondents, 1588 returned valid questionnaires and were included in the analysis. Nearly one quarter (22.8%) had high levels of psychological distress (K6 score ≥ 13). Individuals with higher psychological distress were more likely to be unmarried, spend more than 6 h per day searching for information about COVID-19, more frequently adopt a passive coping style, and report less social support than those with lower psychological distress. CONCLUSIONS: The COVID-19 outbreak in China has a great impact on the mental health status of the general population. Active coping strategies and increased social support are significantly correlated with decreased psychological distress, and may serve as the basis for psychological interventions.
Assuntos
Adaptação Psicológica , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Angústia Psicológica , Apoio Social , Adulto , Betacoronavirus , COVID-19 , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/psicologia , Feminino , Humanos , Masculino , Pneumonia Viral/epidemiologia , Pneumonia Viral/psicologia , Saúde Pública/métodos , SARS-CoV-2 , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: This study aimed to investigate the mental state of medical staff and medical students in the early stages of the SARS-CoV-2 outbreak, as well as analyze the risk factors of serious mental illness (SMI), so as to provide a scientific basis for further psychological intervention and management. METHOD: A cross-sectional survey was conducted from February 2-7, 2020. The Kessler 6 Psychological Distress Scale and a general information questionnaire were administered on-line to a convenience sample of 548 medical staff and medical students in China. Multivariate binary logistic regression analysis was used to screen the risk factors of SMI in medical staff and medical students. RESULTS: Of the 505 respondents in the final analysis, 188 (37.23%) were at high risk of SMI. Respondents were at significantly higher risk of SMI if they had been suspected of being infected with the SARS-CoV-2 (OR = 7.00, 95% CI: 1.19-41.14), had relatives suspected of being infected with the SARS-CoV-2 (OR = 23.60, 95% CI: 1.11-501.30), felt concerned towards media coverage of outbreak-related information (OR = 11.95, 95% CI: 3.07-46.57), recently dreamed related to SARS-CoV-2 (OR = 4.21, 95% CI: 2.22-8.01), experienced difficulty in controlling emotions during SARS-CoV-2 epidemic (OR = 3.25, 95% CI: 1.66-6.37), or spent hours watching outbreaks per day (OR = 1.29, 95% CI: 1.13-1.46). CONCLUSION: Our findings highlight that medical staff and medical students were vulnerable to SMI during the early stages of the SARS-CoV-2 outbreak and identify the factors associated with SMI which can be used to formulate psychological interventions to improve the mental health. The independent risk factors for SMI among them are suspicion that they or relatives were infected with the SARS-CoV-2, greater interest in media reports about the epidemic, frequency of recent dreams related to SARS-CoV-2, difficulty in controlling emotions during the epidemic, and hours spent watching outbreaks per day.
Assuntos
Infecções por Coronavirus/psicologia , Pessoal de Saúde/psicologia , Pneumonia Viral/psicologia , Estudantes de Medicina/psicologia , Adulto , Betacoronavirus , COVID-19 , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Estudos Transversais , Surtos de Doenças , Feminino , Humanos , Masculino , Saúde Mental , Pandemias , Pneumonia Viral/epidemiologia , Fatores de Risco , SARS-CoV-2 , Inquéritos e QuestionáriosRESUMO
Head and neck cancer (HNC) remains one of the most malignant tumors with a significantly high mortality. DNA methylation exerts a vital role in the prognosis of HNC. In this study, we try to screen abnormal differential methylation genes (DMGs) and pathways in Head-Neck Squamous Cell Carcinoma via integral bioinformatics analysis. Data of gene expression microarrays and gene methylation microarrays were obtained from the Cancer Genome Atlas database. Aberrant DMGs were identified by the R Limma package. We conducted the Cox regression analysis to select the prognostic aberrant DMGs and site-speciï¬c methylation. Five aberrant DMGs were recognized that significantly correlated with overall survival. The prognostic model was constructed based on five DMGs (PAX9, STK33, GPR150, INSM1, and EPHX3). The five DMG models acted as prognostic biomarkers for HNC. The area under the curve based on the five DMGs predicting 5-year survival is 0.665. Moreover, the correlation between the DMGs/site-speciï¬c methylation and gene expression was also explored. The findings demonstrated that the five DMGs can be used as independent prognostic biomarkers for predicting the prognosis of patients with HNC. Our study might lay the groundwork for further mechanism exploration in HNC and may help identify diagnostic biomarkers for early stage HNC.
Assuntos
Biomarcadores Tumorais/genética , Metilação de DNA , Epigênese Genética , Epigenoma , Neoplasias de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Idoso , Epóxido Hidrolases/genética , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Fator de Transcrição PAX9/genética , Prognóstico , Proteínas Serina-Treonina Quinases/genética , Receptores Acoplados a Proteínas G/genética , Proteínas Repressoras/genética , Fatores de Risco , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Fatores de TempoRESUMO
BACKGROUND The aim of this study was to determine whether higher density screw constructs resulted in better surgical outcomes in patients with scoliosis secondary to Marfan syndrome (MF-S) with large thoracic curves (≥70°). MATERIAL AND METHODS There were 34 MF-S patients who met the inclusion criteria and were evaluated radiographically before surgery, 2 weeks after operation, and at the final follow-up. The mean screw density was taken as the boundary, and patients were categorized as either in the high density (HD) group or the low density (LD) group. Parameters measured included coronal Cobb angle, T5-T12 kyphosis (TK), and T12-S1 lordosis (LL). Additionally, the operation duration, estimated blood loss, screw accuracy, complication rate, and clinical outcomes were compared between the 2 groups. RESULTS The mean screw density of all patients was 1.40±0.15 (range 1.13 to 1.67). Correction rate of the thoracic curve was closely related to the screw density at the concave side (r=0.783, P=0.007). Intergroup comparison showed a significantly higher correction rate of the thoracic coronal curve in HD group (56.59±4.80% versus 44.54±9.61%, P=0.036). At last follow-up, coronal correction loss of >5° occurred in 8 cases (47.1%) in the LD group and 3 cases (17.6%) in the HD group. Both groups demonstrated improvement in each domain of the SRS-22 questionnaire after surgery and no significant intergroup difference was found. CONCLUSIONS The high-density pedicle screw construct contributed to the significantly improved correction rate of thoracic curves in MF-S patients with large thoracic curves (≥70°). Additionally, increasing of pedicle screw number could help to enhance the structural stability and reduce the correction loss during the follow-up period.
Assuntos
Síndrome de Marfan/cirurgia , Parafusos Pediculares , Escoliose/cirurgia , Vértebras Torácicas/cirurgia , Adolescente , Feminino , Humanos , Masculino , Resultado do Tratamento , Adulto JovemRESUMO
This paper aims to discuss the nursing and safety of silver needle diathermy in the treatment for ankylosing spondylitis. We nursed 46 patients with ankylosing spondylitis treated with silver needle diathermy. Specific nursing was focused on physical condition evaluation and mental nursing before treatment, observation during and after treatment, diet nursing, needle eye nursing, functional training and propaganda and education when discharged. The result suggested that all the patients received mental nursing, diet guide, skin care, health education, functional training and follow-up visit from the nurse and all of them could endure silver needle diathermy as discomfort or drug allergy was barely found, so were slight scald and skin infection nearby the needle eye caused by fainting during acupuncture, accidental puncture or overheat. Follow-up visit showed that no patient suffered obvious untoward effect and the pain, joint range of motion and living condition were distinctly improved a week after discharging. In conclusion, during the treatment for ankylosing spondylitis applying silver needle diathermy, the nursing before, during and after the treatment can obviously reduce the complication, accelerate the recovery, which is highly safe.
Assuntos
Terapia por Acupuntura , Diatermia , Agulhas , Prata , Espondilite Anquilosante/enfermagem , Espondilite Anquilosante/terapia , Terapia por Acupuntura/efeitos adversos , Terapia por Acupuntura/instrumentação , Terapia por Acupuntura/enfermagem , Adolescente , Adulto , Diatermia/efeitos adversos , Diatermia/instrumentação , Diatermia/enfermagem , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Agulhas/efeitos adversos , Espondilite Anquilosante/diagnóstico , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: To establish a CT-based radiomics nomogram for preoperative prediction of KRAS mutation and prognostic stratification in colorectal cancer (CRC) patients. METHODS: In a retrospective analysis, 408 patients with confirmed CRC were included, comprising 168 cases in the training set, 111 cases in the internal validation set, and 129 cases in the external validation set. Radiomics features extracted from the primary tumors were meticulously screened to identify those closely associated with KRAS mutation. Subsequently, a radiomics nomogram was constructed by integrating these radiomics features with clinically significant parameters. The diagnostic performance was assessed through the area under the receiver operating characteristic curve (AUC). Lastly, the prognostic significance of the nomogram was explored, and Kaplan-Meier analysis was employed to depict survival curves for the high-risk and low-risk groups. RESULTS: A radiomics model was constructed using 19 radiomics features significantly associated with KRAS mutation. Furthermore, a nomogram was developed by integrating these radiomics features with two clinically significant parameters (age, tumor location). The nomogram achieved AUCs of 0.834, 0.813, and 0.811 in the training set, internal validation set, and external validation set, respectively. Additionally, the nomogram effectively stratified patients into high-risk (KRAS mutation) and low-risk (KRAS wild-type) groups, demonstrating a significant difference in overall survival (P < 0.001). Patients categorized in the high-risk group exhibited inferior overall survival in contrast to those classified in the low-risk group. CONCLUSIONS: The CT-based radiomics nomogram demonstrates the capability to effectively predict KRAS mutation in CRC patients and stratify their prognosis preoperatively.
Assuntos
Neoplasias Colorretais , Mutação , Nomogramas , Proteínas Proto-Oncogênicas p21(ras) , Tomografia Computadorizada por Raios X , Humanos , Feminino , Masculino , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Pessoa de Meia-Idade , Prognóstico , Idoso , Adulto , Valor Preditivo dos Testes , Idoso de 80 Anos ou mais , RadiômicaRESUMO
AIMS: Traumatic brain injury (TBI) stands as a significant concern in public health, frequently leading to enduring neurological deficits. Long non-coding RNA H19 (lncRNA H19) exerts a potential regulator role in the pathology of brain injury. This study investigates the effects of lncRNA H19 knockdown (H19-KD) on the pathophysiology of TBI and its potential neuroprotective mechanisms. METHODS: Controlled cortical impact was employed to establish a stable TBI mouse model. The expression levels of various genes in perilesional cortex and striatum tissue after TBI was detected by RT-qPCR. AAV9-shRNA-H19 was injected into the lateral ventricle of mice to knockdown the expression of lncRNA H19. Various behavioral tests were performed to evaluate sensorimotor and cognitive functions after TBI. Immunofluorescence and Nissl staining were performed to assess brain tissue damage and neuroinflammation. The Nrf2 and HO-1 expression was performed by Western blot. RESULTS: After TBI, the expression of lncRNA H19 was elevated in perilesional tissue and gradually reverted to baseline. Behavioral tests demonstrated that H19-KD significantly promoted the recovery of sensorimotor and cognitive functions after TBI. Besides, H19-KD reduced brain tissue loss, preserved neuronal integrity, and ameliorated white matter damage at the histological level. In addition, H19-KD restrained the pro-inflammatory and facilitated anti-inflammatory phenotypes of microglia/macrophages, attenuating the neuroinflammatory response after TBI. Furthermore, H19-KD promoted activation of the Nrf2/HO-1 axis after TBI, while suppression of Nrf2 partially abolished the neuroprotective effect. CONCLUSION: H19-KD exerts neuroprotective effects after TBI in mice, partially mediated by the activation of the Nrf2/HO-1 axis.
Assuntos
Lesões Encefálicas Traumáticas , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2 , RNA Longo não Codificante , Recuperação de Função Fisiológica , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Lesões Encefálicas Traumáticas/patologia , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/genética , Camundongos , Recuperação de Função Fisiológica/fisiologia , Masculino , Técnicas de Silenciamento de Genes/métodos , Heme Oxigenase-1/metabolismo , Proteínas de MembranaRESUMO
Inflammasomes are closely associated with the progression of multiple cancers. We established an inflammasome-related gene (IRG)-based model to predict the survival of patients with hepatocellular carcinoma (HCC). The RNA-sequencing data and clinical information of HCC patients were downloaded from the cancer genome atlas-liver hepatocellular carcinoma database, and the differentially expressed inflammasome-related gene were screened. Seven prognostic differentially expressed inflammasome-related genes were identified by univariate Cox analysis and incorporated into the risk model using least absolute shrinkage and selection operator-Cox algorithm. The predictive accuracy of the risk model was evaluated through the Kaplan-Meier, receiver operating characteristic and Cox regression analyses. The performance of the model was verified in the International Cancer Genome Consortium-Liver Cancer - RIKEN, JP cohort. A nomogram was constructed to predict the 1-, 2-, 3- ,and 5-year survival of HCC patients, and its performance was evaluated using calibration curves. The significantly enriched gene ontology terms, Kyoto encyclopedia of genes and genomes pathways and infiltrating immune cell populations associated with the IRG model were also analyzed to explore of the potential molecular mechanisms and immunotherapeutic targets. An independent and highly accurate prognostic model consisting of 7 IRGs was established and verified in 2 independent HCC cohorts. The IRG model was significantly associated with cell division and cell cycle. In addition, the high-risk group was more likely to have greater infiltration of immune cells and higher expression of immune checkpoint-related genes compared to the low-risk group. An IRG-based model was established to predict 1-, 2-, 3-, and 5-year survival rate in individual HCC patients, which provides new insights into the role of inflammasomes in HCC.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Inflamassomos , NomogramasRESUMO
As blood-brain barrier (BBB) disruption emerges as a common problem in the early stages of neurodegenerative diseases, the crucial roles of barrier-type brain endothelial cells (BECs), the primary part of the BBB, have been reported in the pathophysiology of neurodegenerative diseases. The mechanisms of how early vascular dysfunction contributes to the progress of neurodegeneration are still unclear, and understanding BEC functions is a promising start. Our understanding of the BBB has gone through different stages, from a passive diffusion barrier to a mediator of central-peripheral interactions. BECs serve two seemingly paradoxical roles: as a barrier to protect the delicate brain from toxins and as an interface to constantly receive and release signals, thus maintaining and regulating the homeostasis of the brain. Most previous studies about neurodegenerative diseases focus on the loss of barrier functions, and far too little attention has been paid to the active regulations of BECs. In this review, we present the current evidence of BEC dysfunction in neurodegenerative diseases and explore how BEC signals participate in the pathogenesis of neurodegenerative diseases.
RESUMO
Maintaining a diverse and well-balanced nasal and oral microbiota is vital for human health. However, the impact of indoor microbiome and metabolites on nasal and oral microbiota remains largely unknown. Fifty-six children in Shanghai were surveyed to complete a questionnaire about their personal and environmental characteristics. The indoor microbiome and metabolites from vacuumed indoor dust were profiled via shotgun metagenomics and untargeted liquid chromatography-mass spectrometry (LC-MS). The nasal and oral microbiota in children was characterized using full-length 16S rRNA sequencing from PacBio. Associations between personal/environmental characteristics and the nasal/oral microbiota were calculated using PERMANOVA and regression analyses. We identified 6247, 431, and 342 microbial species in the indoor dust, nasal, and oral cavities, respectively. The overall nasal and oral microbial composition showed significant associations with environmental tobacco smoke (ETS) exposure during pregnancy and early childhood (p = 0.005 and 0.03, respectively), and the abundance of total indoor flavonoids and two mycotoxins (deoxynivalenol and nivalenol) (p = 0.01, 0.02, and 0.03, respectively). Notably, the abundance of several flavonoids, such as baicalein, eupatilin, isoliquiritigenin, tangeritin, and hesperidin, showed positive correlations with alpha diversity and the abundance of protective microbial taxa in nasal and oral cavities (p < 0.02), suggesting their potential beneficial roles in promoting nasal/oral health. Conversely, high carbohydrate/fat food intake and ETS exposure diminished protective microorganisms while augmenting risky microorganisms in the nasal/oral cavities. Further, potential microbial transfer was observed from the indoor environment to the childhood oral cavity (Moraxella catarrhalis, Streptococcus mitis, and Streptococcus salivarius), which could potentially increase virulence factors related to adherence and immune modulation and vancomycin resistance genes in children. This is the first study to reveal the association between the indoor microbiome/metabolites and nasal/oral microbiota using multi-omic approaches. These findings reveal potential protective and risk factors related to the indoor microbial environment.
RESUMO
The Class-I histone deacetylases (HDACs) mediate microglial inflammation and neurological dysfunction after traumatic brain injury (TBI). However, whether the individual Class-I HDACs play an indispensable role in TBI pathogenesis remains elusive. HDAC2 has been shown to upregulate pro-inflammatory genes in myeloid cells under brain injuries such as intracerebral hemorrhage, thereby worsening outcomes. Thus, we hypothesized that HDAC2 drives microglia toward a pro-inflammatory neurotoxic phenotype in a murine model of controlled cortical impact (CCI). Our results revealed that HDAC2 expression was highly induced in CD16/CD32+ pro-inflammatory microglia 3 and 7d after TBI. Surprisingly, microglia-targeted HDAC2 knockout (HDAC2 miKO) mice failed to demonstrate a beneficial phenotype after CCI/TBI compared to their wild-type (WT) littermates. HDAC2 miKO mice exhibited comparable levels of grey and white matter injury, efferocytosis, and sensorimotor and cognitive deficits after CCI/TBI as WT mice. RNA sequencing of isolated microglia 3d after CCI/TBI indicated the elevation of a panel of pro-inflammatory cytokines/chemokines in HDAC2 miKO mice over WT mice, and flow cytometry showed further elevated brain infiltration of neutrophils and B cells in HDAC2 miKO mice. Together, this study does not support a detrimental role for HDAC2 in microglial responses after TBI and calls for investigation into alternative mechanisms.
RESUMO
Passengers are at a higher risk of respiratory infections and chronic diseases due to microbial exposure in airline cabins. However, the presence of virulence factors (VFs), antimicrobial resistance genes (ARGs), metabolites, and chemicals are yet to be studied. To address this gap, we collected dust samples from the cabins of two airlines, one with textile seats (TSC) and one with leather seats (LSC), and analyzed the exposure using shotgun metagenomics and LC/MS. Results showed that the abundances of 17 VFs and 11 risk chemicals were significantly higher in TSC than LSC (p < 0.01). The predominant VFs in TSC were related to adherence, biofilm formation, and immune modulation, mainly derived from facultative pathogens such as Haemophilus parainfluenzae and Streptococcus pneumoniae. The predominant risk chemicals in TSC included pesticides/herbicides (carbofuran, bromacil, and propazine) and detergents (triethanolamine, diethanolamine, and diethyl phthalate). The abundances of these VFs and detergents followed the trend of TSC > LSC > school classrooms (p < 0.01), potentially explaining the higher incidence of infectious and chronic inflammatory diseases in aircraft. The level of ARGs in aircraft was similar to that in school environments. This is the first multi-omic survey in commercial aircraft, highlighting that surface material choice is a potential intervention strategy for improving passenger health.
RESUMO
Single crystals of the title compound, [K(C18H36N2O6)][Mn(C44H24Cl4N4)(C7H7S)]·2C4H8O, were obtained by the solvent evaporation method. The MnII cation is coordinated by four pyrrole N atoms (Np) of the porphyrin ring and one S atom of the apical 4-methyl-benzene-thiol-ate ligand with the average Mn-Np and the apical Mn-S bond lengths being 2.160â (9) and 2.4642â (8)â Å, respectively. Two tetra-hydro-furan solvent mol-ecules and a potassium cation chelated inside a [2.2.2]cryptand (4,7,13,16,21,24-hexa-oxa-1,10-di-aza-bicyclo[8.8.8]hexa-cosa-ne) are also present.