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1.
Biochim Biophys Acta Mol Basis Dis ; 1870(3): 167023, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38218381

RESUMO

Cigarette smoke (CS) is the major risk factor for chronic obstructive pulmonary disease (COPD), and sarcopenia is one of the significant comorbidities of COPD. However, the pathogenesis of CS-related deficient skeletal muscle regeneration has yet to be clarified. The impact of CS on myoblast differentiation was examined, and then we determined which HDAC influenced the myogenic process and muscle atrophy in vitro and in vivo. Finally, we further investigated the potential mechanisms via RNA sequencing. Long-term CS exposure activated skeletal muscle primary satellite cells (SCs) while inhibiting differentiation, and defective myogenesis was also observed in C2C12 cells treated with CS extract (CSE). The level of HDAC9 changed in vitro and in vivo in CS exposure models as well as COPD patients, as detected by bioinformatics analysis. Our data showed that CSE impaired myogenic capacity and myotube formation in C2C12 cells via HDAC9. Moreover, inhibition of HDAC9 in mice exposed to CS prevented skeletal muscle dysfunction and promoted SC differentiation. The results of RNA-Seq analysis and verification indicated that HDAC9 knockout improved muscle differentiation in CS-exposed mice, probably by acting on the AKT/mTOR pathway and inhibiting the P53/P21 pathway. More importantly, the serum of HDAC9 KO mice exposed to CS alleviated the differentiation impairment of C2C12 cells caused by serum intervention in CS-exposed mice, and this effect was inhibited by LY294002 (an AKT/mTOR pathway inhibitor). These results suggest that HDAC9 plays an essential role in the defective regeneration induced by chronic exposure to CS.


Assuntos
Fumar Cigarros , Doença Pulmonar Obstrutiva Crônica , Humanos , Animais , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Doença Pulmonar Obstrutiva Crônica/genética , Atrofia Muscular/patologia , Músculo Esquelético/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Proteínas Repressoras/metabolismo
2.
Phys Chem Chem Phys ; 26(6): 5558-5568, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38284214

RESUMO

Rare base-pairs consists of guanine (G) paired with rare bases, such as 5-methylcytosine (5-meCyt), 5-hydroxymethylcytosine (5-hmCyt), 5-carboxylcytosine (5-caCyt), and 5-formylcytosine (5-fCyt), have become the focus of epigenetic research because they can be used as markers to detect some chronic diseases and cancers. However, the correlation detection of these rare base-pairs is limited, which in turn limits the development of diagnostic tests and devices. Herein, the interaction of rare base-pairs adsorbed on pure and B/N-doped γ-graphyne (γ-GY) nanosheets was explored using the density functional theory. The calculated adsorption energy showed that the system of rare base-pairs on B-doped γ-GY is more stable than that on pure γ-GY or N-doped γ-GY. Translocation time values indicate that rare base-pairs can be successfully distinguished as the difference in their translocation times is very large for pure and B/N-doped γ-GY nanosheets. Meanwhile, sensing response values illustrated that pure and B-doped γ-GY are the best for G-5-hmCyt adsorption, while the N-doped γ-GY is the best for G-Cyt adsorption. The findings indicate that translocation times and sensing response can be used as detection indexes for pure and B/N doped γ-GY, which will provide a new way for experimental scientists to develop the biosensor components.


Assuntos
Adsorção , Pareamento de Bases
3.
Sci Rep ; 14(1): 1772, 2024 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-38245594

RESUMO

This study aims to observe the clinical efficacy of the dual plasma molecular adsorption exchange system (DPMAES) in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF), with a focus on its regulatory effect on cytokine storm. A total of 60 HBV-ACLF patients were enrolled in this study. The observation group, comprising 30 patients, received DPMAES treatment, while the control group underwent PE treatment. We compared the efficacy changes between the two groups post-treatment. A total of 55 HBV-ACLF patients who completed the study were analyzed, Patients treated with DPMAES showed significant improvements in clinical outcomes. After DPMAES treatment, HBV-ACLF patients exhibited notably 90 day survival rate increased by 18% compared to those in the PE group. Moreover, total bilirubin levels decreased markedly, albumin and platelet levels increased compared to the PE group. After DPMAES treatment, the patient showed a significant decrease in inflammatory cytokine IL-6 (t = 5.046, P < 0.001) and a significant decrease in procalcitonin (t = 4.66, P < 0.001). DPMAES was more effective than PE in rapidly reducing TBiL, improving coagulation function and mitigating cytokine storm. It maintained platelet stability more effectively while minimizing albumin consumption to a greater extent, significantly improved 90-day survival.Trial registration: Chinese Clinical Trial Registry, ChiCTR2300076117.


Assuntos
Insuficiência Hepática Crônica Agudizada , Hepatite B Crônica , Hepatite B , Humanos , Adsorção , Síndrome da Liberação de Citocina , Hepatite B/complicações , Hepatite B/terapia , Vírus da Hepatite B , Albuminas/uso terapêutico , Prognóstico , Hepatite B Crônica/complicações , Hepatite B Crônica/terapia , Estudos Retrospectivos
4.
Sci Rep ; 14(1): 1128, 2024 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-38212524

RESUMO

To assess the clinical efficacy of Double Filtration Plasmapheresis (DFAPP), a novel blood purification method, in treating hyperlipidemic moderate/severe pancreatitis (HL-M/SAP). A total of 68 HL-M/SAP patients were enrolled in this study. The observation group, comprising 34 patients, received DFAPP treatment, while the control group underwent CVVH + PA treatment. We compared the efficacy changes between the two groups post-treatment. Patients treated with DFAPP showed significant improvements in clinical outcomes. After 72 h of DFAPP treatment, HL-M/SAP patients exhibited notably lower multiple organ failure scores and a reduced mortality rate compared to those in the CVVH + PA group. Triglyceride levels in HL-M/SAP patients treated with DFAPP for 48 h averaged 3.75 ± 1.95, significantly lower than the 9.57 ± 3.84 levels in the CVVH + PA group (P < 0.05). Moreover, CRP levels decreased markedly, IL-17 levels diminished, IL-10 levels increased, and the decline in IL-35 levels was significantly less pronounced compared to the CVVH + PA group. The recurrence rate of pancreatitis was also significantly lower after 6 months. The early implementation of DFAPP in HL-M/SAP patients effectively reduces triglyceride levels, suppresses pro-inflammatory factors, enhances anti-inflammatory factors, and mitigates cytokine storm-induced sepsis damage. Consequently, this leads to a decrease in the incidence of multiple organ failure, improved patient survival rates, and a reduce the recurrence rate of lipogenic pancreatitis.Trial registration: Chinese Clinical Trial Registry, ChiCTR2300076066.


Assuntos
Hemofiltração , Hiperlipidemias , Pancreatite , Humanos , Insuficiência de Múltiplos Órgãos/etiologia , Doença Aguda , Índice de Gravidade de Doença , Hemofiltração/efeitos adversos , Hemofiltração/métodos , Hiperlipidemias/terapia , Hiperlipidemias/etiologia , Plasmaferese , Triglicerídeos , China
5.
Virol J ; 21(1): 4, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38178220

RESUMO

BACKGROUND: Cross-species transmission of zoonotic IAVs to humans is potentially widespread and lethal, posing a great threat to human health, and their cross-species transmission mechanism has attracted much attention. miRNAs have been shown to be involved in the regulation of IAVs infection and immunity, however, few studies have focused on the molecular mechanisms underlying miRNAs and mRNAs expression after IAVs cross-species infection. METHODS: We used tree shrews, a close relative of primates, as a model and used RNA-Seq and bioinformatics tools to analyze the expression profiles of DEMs and DEGs in the nasal turbinate tissue at different time points after the newly emerged swine influenza A virus SW2783 cross-species infection with tree shrews, and miRNA-mRNA interaction maps were constructed and verified by RT-qPCR, miRNA transfection and luciferase reporter assay. RESULTS: 14 DEMs were screened based on functional analysis and interaction map, miR-760-3p, miR-449b-2, miR-30e-3p, and miR-429 were involved in the signal transduction process of replication and proliferation after infection, miR-324-3p, miR-1301-1, miR-103-1, miR-134-5p, miR-29a, miR-31, miR-16b, miR-34a, and miR-125b participate in negative feedback regulation of genes related to the immune function of the body to activate the antiviral immune response, and miR-106b-3p may be related to the cross-species infection potential of SW2783, and the expression level of these miRNAs varies in different days after infection. CONCLUSIONS: The miRNA regulatory networks were constructed and 14 DEMs were identified, some of them can affect the replication and proliferation of viruses by regulating signal transduction, while others can play an antiviral role by regulating the immune response. It indicates that abnormal expression of miRNAs plays a crucial role in the regulation of cross-species IAVs infection, which lays a solid foundation for further exploration of the molecular regulatory mechanism of miRNAs in IAVs cross-species infection and anti-influenza virus targets.


Assuntos
MicroRNAs , Animais , Humanos , Suínos , MicroRNAs/genética , MicroRNAs/metabolismo , Vírus da Influenza A Subtipo H3N2/genética , Tupaia , Perfilação da Expressão Gênica , Tupaiidae/genética , Musaranhos , RNA Mensageiro
6.
BMC Public Health ; 24(1): 85, 2024 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172728

RESUMO

BACKGROUND: The prevalence of hyperuricemia (HUA) is gradually increasing worldwide. HUA is closely related to diabetes, but the relationship between HUA and pancreatic ß-cells function in the population is unclear. The purpose of this article is to investigate the association between pancreatic ß-cells and HUA. METHODS: This cross-sectional study examined the association between pancreatic ß-cells and HUA in 1999-2004 using data from the National Health and Nutrition Examination Survey (NHANES). Subjects were divided into two groups: HUA and non-HUA. Pancreatic ß-cells function levels were assessed using homeostasis model assessment version 2-%S (HOMA2-%S), homeostasis model assessment version 2-%B (HOMA2-%B) and disposition index (DI). Multivariate logistic regression models and restricted cubic spline models were fitted to assess the association of pancreatic ß-cells function with HUA. RESULTS: The final analysis included 5496 subjects with a mean age of 46.3 years (standard error (SE), 0.4). The weighted means of HOMA2-%B, HOMA2-%S and DI were 118.1 (SE, 1.0), 69.9(SE, 1.1) and 73.9 (SE, 0.7), respectively. After adjustment for major confounders, participants in the highest quartile of HOMA2-%B had a higher risk of HUA (OR = 2.55, 95% CI: 1.89-3.43) compared to participants in the lowest quartile. In contrast, participants in the lowest quartile of HOMA2-%S were significantly more likely to have HUA than that in the highest quartile (OR = 3.87, 95% CI: 2.74-5.45), and similar results were observed in DI (OR = 1.98, 95% CI: 1.32-2.97). Multivariate adjusted restricted cubic spline analysis found evidence of non-linear associations between HOMA2-%B, HOAM2-%S, DI and the prevalence of HUA. CONCLUSION: Our finding illustrated the indicators of inadequate ß-cells compensation might be a new predictor for the presence of HUA in U.S. adults, highlighting a critical role of pancreatic ß-cells function on HUA.


Assuntos
Hiperuricemia , Adulto , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos Nutricionais , Hiperuricemia/epidemiologia , Estudos Transversais
7.
Int J Psychiatry Med ; 59(2): 182-198, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37222570

RESUMO

BACKGROUND: Resilience measures are typically based on subjective self-assessment, which is prone to bias. Objective biological/physiological measures of resilience are therefore needed. Hair cortisol concentration is a particularly promising candidate as a biomarker for resilience. METHODS: We conducted a meta-analytic review from inception to April 2023 in PubMed, EMBASE, Cochrane Library, and Psych Info databases. All data were analyzed using a random-effects model. RESULTS: Eight studies were identified that included a total of 1,064 adults. The random effects model demonstrated that resilience and hair cortisol concentration were inversely correlated (r = -0.18, 95% confidence interval [CI] = -0.27 to -0.09) with substantial heterogeneity (I2 = 54.2%, p = 0.03). The inverse association was stronger in those who were age 40 years or younger compared to those who were over 40 years. The correlation coefficients between psychological resilience and hair cortisol concentration among adults assessed by different resilience measures were r = -0.29 (95% CI = -0.49 to -0.08) for the CD-RISC-10; r = -0.21 (95% CI = -0.31 to -0.11) for the CDRISC- 25, and r = -0.08 (95% CI = -0.22 to 0.06) for the BRS. Six of eight studies examined the connection between resilience and perceived stress, where the weighted mean correlation coefficient was r = -0.45 (95% CI = -0.56 to -0.33), with considerable heterogeneity (I2 = 76.2%, p = 0.001). CONCLUSIONS: There is a negative association between psychological resilience and hair cortisol concentration based on these eight studies. Additional research, particularly prospective studies, is needed to determine whether hair cortisol concentration can be used as a biomarker for psychological resilience.


Assuntos
Testes Psicológicos , Resiliência Psicológica , Adulto , Humanos , Hidrocortisona/análise , Estudos Prospectivos , Cabelo/química , Estresse Psicológico/psicologia , Biomarcadores/análise
8.
ACS Omega ; 8(47): 45109-45114, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38046303

RESUMO

The mechanism underlying the rhodium(III)-catalyzed reaction of the C-H alkenylation/annulation reaction of salicylaldehydes with enynes has been thoroughly investigated using DFT calculations. Based on mechanistic studies, our focus primarily lies on the regioselectivity of asymmetric alkynes inserting into the Rh-C bond and the involvement of the auxiliary group OAc- in these reactions. Our theoretical study uncovers that, with acetate assistance, a stepwise SN2' cyclization, 1,3-Rh migration, ß-H elimination, and reductive elimination process occur. Furthermore, we also explore the role of substitution at Cα (CH3 vs H) in the reaction. As demonstrated in this work, these findings are applicable to other related reactions.

9.
Hum Vaccin Immunother ; 19(3): 2293299, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38100550

RESUMO

Cancer-testis antigen CT23 is a class of tumor-associated antigens (TAA) characterized by restricted expression in male germ cells and a variety of tumor tissues. Numerous studies have shown that CT23 is closely related to tumor cell viability, proliferation, metastasis and invasion. CT23 is immunogenic and can cause specific immune response in tumor patients. Therefore, it is considered to be one of the best target antigens for designing therapeutic tumor vaccines and T-cell-mediated tumor immunotherapy. In this study, we initially obtained seven HLA-A*0201-restricted CT23 epitope candidate peptides through the T cell epitope prediction program. Subsequently, a T2 cell binding assay revealed the potential binding of all candidate peptides with HLA-A2 molecules. Notably, peptide P7 (ALLVLCYSI) exhibited the highest affinity, as evidenced by a fluorescence index (FI) of 2.19. Dendritic cells (DCs) loaded with CT23 candidate peptide can stimulate CD8+T cell activation and proliferation, and compared with other candidate peptides, candidate peptide P7 is superior. The cytotoxic T lymphocytes (CTLs) stimulated by the peptide P7 had killing effect on tumor cells (HLA-A*0201+, CT23+), but no killing effect on tumor cells (HLA-A*0201-, CT23+). The CTLs induced by the peptide P7 also had a specific killing effect on T2 cells bearing the peptide P7. In summary, our findings suggest that the CT23 peptide P7 (ALLVLCYSI) can induce immune responses and holds potential for tumor-specific CTL therapy.


Assuntos
Neoplasias , Testículo , Humanos , Masculino , Linhagem Celular Tumoral , Antígeno HLA-A2 , Peptídeos , Linfócitos T Citotóxicos , Antígenos de Neoplasias , Epitopos de Linfócito T , Neoplasias/terapia , Neoplasias/metabolismo
10.
Environ Monit Assess ; 195(12): 1512, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37989793

RESUMO

Phenol, known for its bioaccumulative nature and severe toxicity to riverine organisms, poses complex challenges for ecological risk assessment. To tackle this issue, we developed a three-stage incremental assessment method, providing an integrated perspective on phenol toxicity risk for aquatic organisms. The findings indicated that phenol concentrations were generally higher in the aquatic environments of northern rivers, such as the Hun River, Taizi River, and Liao River, compared to those in southern China. The evaluation results at individual points showed that the ecological risk of phenol to aquatic organisms ranked from high to low during rainy, dry, and normal seasons, showing seasonal variation characteristics. Regarding spatial variation along the river, the ecological risk of phenol gradually increased from upper reaches, peaked in the middle reaches, and then decreased in the lower reaches. Considering the different species types, fish face a higher risk of toxic effects of phenol than invertebrates when exposed to phenol over a long period of time, probably due to the bioaccumulative nature of phenol. To address ecological risk control at the watershed scale, there is an urgent need to revise China's current river water quality standards. It is essential to increase the emphasis on ecological risk control for aquatic organisms. Developing more targeted and refined ecological risk control strategies for river phenols is crucial to maintain a healthier and more vibrant river ecosystem.


Assuntos
Ecossistema , Fenol , Poluentes Químicos da Água , Animais , Organismos Aquáticos , Biota , China , Monitoramento Ambiental/métodos , Fenol/efeitos adversos , Medição de Risco/métodos , Rios , Poluentes Químicos da Água/efeitos adversos
11.
Sci Rep ; 13(1): 17254, 2023 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-37828147

RESUMO

Developmental disabilities prevalence seem to be high in countries around the world. It's worth understanding the most recent prevalence and trends of developmental disabilities. The objective of this study is to examine the prevalence and trends of developmental disabilities of US children and adolescents. A total of 26,422 individuals aged 3-17 years were included. Annual data were examined from the National Health Interview Survey (2018-2021). Weighted prevalence for each of the selected developmental disabilities were calculated. The prevalence of any developmental disabilities in individuals was 16.65% (95% CI 16.03-17.26%), prevalence of attention deficit/hyperactivity disorder (ADHD), learning disability (LD), autism spectrum disorder (ASD), intellectual disability (ID), and other developmental delay were 9.57% (95% CI 9.09-10.06%), 7.45% (95% CI 7.00-7.89%), 2.94% (95% CI 2.67-3.21%), 1.72% (95% CI 1.51-1.93%), and 5.24% (95% CI 4.89-5.59%), respectively. Significant increases were observed for other developmental delay (4.02-6.05%) and co-occurring LD & ID (1.03-1.82%). Findings form this study highlight a high prevalence of any developmental disabilities, although no significant increase was observed. The prevalence of other developmental delay and co-occurring LD & ID were significantly increased. Further investigation is warranted to assess potentially modifiable risk factors and causes of developmental disabilities.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Deficiência Intelectual , Deficiências da Aprendizagem , Humanos , Criança , Adolescente , Deficiências do Desenvolvimento/epidemiologia , Transtorno do Espectro Autista/epidemiologia , Prevalência , Deficiências da Aprendizagem/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Deficiência Intelectual/epidemiologia
12.
Med Acupunct ; 35(5): 220-229, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37900872

RESUMO

Background: Pain management is a great burden on society; therefore, cost-effective and nonaddictive treatments for pain are urgently required. Needling of painful spots has been applied in acupuncture along with dry needling

14.
PLoS One ; 18(8): e0285116, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37535614

RESUMO

The Tibetan Plateau (TP), once considered a pristine environment, is now facing increased heavy metal pollution due to human activities, causing unprecedented ecological risks to soil organisms. However, little is known about the sensitivity and tolerance of different soil organisms to heavy metal toxicity in the high-altitude areas of the TP under the background of human activity intensity and future risk control priorities. In this study, we conducted an ecological risk assessment and threshold calculation for 10 heavy metals in soil for typical soil organisms, including Cd, Co, Cr, Cu, Ni, Pb, Zn, Mn, Sb, and Sn, using the species sensitivity distribution (SSD) method in the zone between Ranwu town and Renlongba glacier on the TP. The results revealed that most sampling sites had average levels of Cd, Sb and Ni exceeding their regional soil environmental background values and were the major contaminants. Impressively, the hitherto undeveloped Renlungba Glacier showed relatively high contamination levels of Sb and Ni. From the view of sensitivity differences, the toxicity risks of Cd, Cr, Cu, Ni and Pb were higher for terrestrial plants than for soil invertebrates based on the fitted heavy metal SSD curve trends. In terms of the ecological risk level, the average potentially affected fraction values of Zn and Ni reached 18.5% and 17.0%, respectively, with significant ecological risk at a few sampling sites. In terms of ecological risk thresholds, the Cd concentration at the 5% hazard concentration (HC5) control level was 0.05 mg/kg, which was the heavy metal with the highest risk in this study. Comparing the HC5 values of each heavy metal with the limit values in the current Chinese soil environmental quality standards, the existing administrative policies as a whole lack a powerful prevention of the potential ecological risk posed by heavy metals to soil organisms.


Assuntos
Metais Pesados , Poluentes do Solo , Humanos , Tibet , Monitoramento Ambiental , Solo , Cádmio/análise , Chumbo/análise , Poluentes do Solo/toxicidade , Poluentes do Solo/análise , China , Metais Pesados/toxicidade , Metais Pesados/análise , Medição de Risco
15.
Nat Commun ; 14(1): 4651, 2023 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-37532727

RESUMO

Understanding the genetic basis of rubber tree (Hevea brasiliensis) domestication is crucial for further improving natural rubber production to meet its increasing demand worldwide. Here we provide a high-quality H. brasiliensis genome assembly (1.58 Gb, contig N50 of 11.21 megabases), present a map of genome variations by resequencing 335 accessions and reveal domestication-related molecular signals and a major domestication trait, the higher number of laticifer rings. We further show that HbPSK5, encoding the small-peptide hormone phytosulfokine (PSK), is a key domestication gene and closely correlated with the major domestication trait. The transcriptional activation of HbPSK5 by myelocytomatosis (MYC) members links PSK signaling to jasmonates in regulating the laticifer differentiation in rubber tree. Heterologous overexpression of HbPSK5 in Russian dandelion (Taraxacum kok-saghyz) can increase rubber content by promoting laticifer formation. Our results provide an insight into target genes for improving rubber tree and accelerating the domestication of other rubber-producing plants.


Assuntos
Hevea , Hevea/genética , Borracha , Domesticação , Análise de Sequência de DNA , Genômica , Regulação da Expressão Gênica de Plantas
16.
JAMA Pediatr ; 177(9): 969-972, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37428487

RESUMO

This cross-sectional study uses data from the National Health Interview Survey to examine the prevalence of and trends in diagnosed learning disability among US children and adolescents from 1997 to 2021.


Assuntos
Deficiências da Aprendizagem , Criança , Humanos , Adolescente , Estados Unidos/epidemiologia , Prevalência , Deficiências da Aprendizagem/diagnóstico , Deficiências da Aprendizagem/epidemiologia , Inquéritos Epidemiológicos
17.
Front Neurosci ; 17: 1185078, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37304029

RESUMO

Objective: Brain neuroplasticity in which sleep affects the speed of information processing in the elderly population has not been reported. Therefore, this study was conducted to explore the effects of sleep on information processing speed and its central plasticity mechanism in the elderly. Methods: A total of 50 individuals aged 60 and older were enrolled in this case control study. All subjects were divided into two groups according to the sleep time: short sleep duration (< 360 min) (6 men and 19 women; mean age: 66.96 ± 4.28 years old), and non-short sleep duration (> 360 min) (13 men and 12 women). Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected, and the amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality (DC) were calculated for each participant. Two-sample t-tests were performed to compare the ALFF, ReHo, and DC maps between the two groups. Then, the relationships among clinical features, fMRI and cognitive function were analyzed using general linear model. Results: Short sleep duration group showed significantly increased ALFF value in the bilateral middle frontal gyrus and right insula; significantly increased ReHo value in the left superior parietal gyrus, and decreased ReHo value in the right crebellum; significantly decreased DC value in the left inferior occipital gyrus, left superior parietal gyrus and right cerebellum (p < 0.05, AlphaSim correction). The ALFF value of right insula is significantly associated with symbol digit modalities test (SDMT) score (ß = -0.363, p = 0.033). Conclusion: Short sleep duration and processing speed are significantly associated with remodeling spatial patterns of intrinsic brain activity in the elderly.

18.
J Environ Manage ; 342: 118253, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37295144

RESUMO

Heavy metal contamination in the surface sediments of large shallow lakes in China is becoming increasingly serious. However, more attention has been paid to the human health risk of heavy metals in the past, while little consideration has been given to aquatic organisms. Taking Taihu Lake as an example, we explored the spatial and temporal heterogeneity of the potential ecological risks of seven heavy metals (Cd, As, Cu, Pb, Cr, Ni, and Zn) to species at different taxonomic scales using an improved species sensitivity distribution (SSD) method. The results showed that all six heavy metals, except Cr, were exceeded to some extent compared to background levels, with Cd being the most severe exceedance. Based on the hazardous concentration for 5% of the species (HC5), Cd had the lowest HC5 value, implying the highest ecological risk of toxicity. Ni and Pb had the highest HC5 values and the lowest risk. Cu, Cr, As and Zn were at a relatively moderate levels. For the different groups of aquatic organisms, the ecological risk of most heavy metals was generally lower for vertebrates than for the whole species. The risk for invertebrates and algae was higher than that for all species. Zn and Cu had the highest potentially affected fractions (PAFs) for all classification cases, with mean PAFs of 30.25% and 47.2%, respectively. Spatially, the high ecological risk of sediment heavy metals was significantly related to the spatial characteristics of the type and intensity of human activities in the catchment. Administratively, the environmental quality standards for freshwater sediments proposed by America and Canada are insufficient to protected against the ecological risks of heavy metals in Taihu Lake. In the absence of such standards, China urgently needs to establish an approptiate system of environmental quality standards for heavy metals in lake sediments.


Assuntos
Metais Pesados , Poluentes Químicos da Água , Humanos , Lagos , Cádmio , Organismos Aquáticos , Chumbo , Medição de Risco , Poluentes Químicos da Água/análise , Sedimentos Geológicos , Monitoramento Ambiental , Metais Pesados/análise , China
19.
J Org Chem ; 88(11): 7320-7327, 2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37167409

RESUMO

The rhodium(III)-catalyzed reaction of aniline derivatives that contain a pyrimidine-directing group with vinylsilanes results in the formation of C3-substituted indoline derivatives. The reaction path and formation of the indoline product with density functional theory calculations were analyzed. This study reveals that the whole catalysis can be characterized in the following stages: (I) C-H activation via concerted metalation deprotonation, (II) 2,1-vinylsilane insertion, (III) deprotonation of the NH amide proton, (IV) the oxidation of Ag+, and (V) reductive elimination. These steps are kinetically and thermodynamically feasible for experimental realization under mild conditions, and the insertion step with a barrier of 22.0 kcal/mol should not only be the critical step of regioselectivity but also the rate-determining step during the whole catalysis. Computations reveal that the Ag+ oxidation can accelerate the reductive elimination step after the formation of natural intermediate, thus highlighting the role of Ag+ as a catalytic promoter for the oxidatively induced reactivity of the Rh catalyst in C3-substituted indoline synthesis.

20.
Acta Pharmacol Sin ; 44(10): 2103-2112, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37193754

RESUMO

Checkpoint inhibitors such as PD-1/PD-L1 antibody therapeutics are a promising option for the treatment of multiple cancers. Due to the inherent limitations of antibodies, great efforts have been devoted to developing small-molecule PD-1/PD-L1 signaling pathway inhibitors. In this study we established a high-throughput AlphaLISA assay to discover small molecules with new skeletons that could block PD-1/PD-L1 interaction. We screened a small-molecule library of 4169 compounds including natural products, FDA approved drugs and other synthetic compounds. Among the 8 potential hits, we found that cisplatin, a first-line chemotherapeutic drug, reduced AlphaLISA signal with an EC50 of 8.3 ± 2.2 µM. Furthermore, we showed that cisplatin-DMSO adduct, but not semplice cisplatin, inhibited PD-1/PD-L1 interaction. Thus, we assessed several commercial platinum (II) compounds, and found that bis(benzonitrile) dichloroplatinum (II) disturbed PD-1/PD-L1 interaction (EC50 = 13.2 ± 3.5 µM). Its inhibitory activity on PD-1/PD-L1 interaction was confirmed in co-immunoprecipitation and PD-1/PD-L1 signaling pathway blockade bioassays. Surface plasmon resonance assay revealed that bis(benzonitrile) dichloroplatinum (II) bound to PD-1 (KD = 2.08 µM) but not PD-L1. In immune-competent wild-type mice but not in immunodeficient nude mice, bis(benzonitrile) dichloroplatinum (II) (7.5 mg/kg, i.p., every 3 days) significantly suppressed the growth of MC38 colorectal cancer xenografts with increasing tumor-infiltrating T cells. These data highlight that platinum compounds are potential immune checkpoint inhibitors for the treatment of cancers.


Assuntos
Cisplatino , Inibidores de Checkpoint Imunológico , Neoplasias , Animais , Humanos , Camundongos , Anticorpos , Antígeno B7-H1/metabolismo , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Camundongos Nus , Neoplasias/tratamento farmacológico , Receptor de Morte Celular Programada 1 , Inibidores de Checkpoint Imunológico/farmacologia
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