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1.
Nat Commun ; 15(1): 4850, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844782

RESUMO

Bacterial RNAP needs to form holoenzyme with σ factors to initiate transcription. While Staphylococcus aureus σA controls housekeeping functions, S. aureus σB regulates virulence, biofilm formation, persistence, cell internalization, membrane transport, and antimicrobial resistance. Besides the sequence difference, the spacers between the -35 element and -10 element of σB regulated promoters are shorter than those of σA regulated promoters. Therefore, how σB recognizes and initiates transcription from target promoters can not be inferred from that of the well studied σ. Here, we report the cryo-EM structures of S. aureus RNAP-promoter open complexes comprising σA and σB, respectively. Structural analyses, in combination with biochemical experiments, reveal the structural basis for the promoter specificity of S. aureus transcription. Although the -10 element of σA regulated promoters is recognized by domain σA2 as single-stranded DNA, the -10 element of σB regulated promoters is co-recognized by domains σB2 and σB3 as double-stranded DNA, accounting for the short spacers of σB regulated promoters. S. aureus RNAP is a validated target of antibiotics, and our structures pave the way for rational drug design targeting S. aureus RNAP.


Assuntos
Proteínas de Bactérias , Microscopia Crioeletrônica , RNA Polimerases Dirigidas por DNA , Regiões Promotoras Genéticas , Fator sigma , Staphylococcus aureus , Staphylococcus aureus/genética , Staphylococcus aureus/enzimologia , RNA Polimerases Dirigidas por DNA/metabolismo , RNA Polimerases Dirigidas por DNA/genética , RNA Polimerases Dirigidas por DNA/química , Fator sigma/metabolismo , Fator sigma/genética , Fator sigma/química , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/química , Regulação Bacteriana da Expressão Gênica , Modelos Moleculares , Transcrição Gênica , Ligação Proteica
2.
Cell Rep ; 43(5): 114200, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38717905

RESUMO

Innate lymphoid cells (ILCs), strategically positioned throughout the body, undergo population declines over time. A solution to counteract this problem is timely mobilization of multipotential progenitors from the bone marrow. It remains unknown what triggers the mobilization of bone marrow ILC progenitors (ILCPs). We report that ILCPs are regulated by the circadian clock to emigrate and generate mature ILCs in the periphery. We found that circadian-clock-defective ILCPs fail to normally emigrate and generate ILCs. We identified circadian-clock-controlled endocrine and cytokine cues that, respectively, regulate the retention and emigration of ILCPs at distinct times of each day. Activation of the stress-hormone-sensing glucocorticoid receptor upregulates CXCR4 on ILCPs for their retention in the bone marrow, while the interleukin-18 (IL-18) and RORα signals upregulate S1PR1 on ILCPs for their mobilization to the periphery. Our findings establish important roles of circadian signals for the homeostatic efflux of bone marrow ILCPs.


Assuntos
Relógios Circadianos , Animais , Camundongos , Citocinas/metabolismo , Camundongos Endogâmicos C57BL , Medula Óssea/metabolismo , Transdução de Sinais , Receptores CXCR4/metabolismo , Células da Medula Óssea/metabolismo , Células da Medula Óssea/citologia , Células Progenitoras Linfoides/metabolismo , Células Progenitoras Linfoides/citologia , Imunidade Inata , Movimento Celular , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Receptores de Glucocorticoides/metabolismo , Linfócitos/metabolismo , Linfócitos/imunologia
3.
Wounds ; 36(3): 73-79, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38684121

RESUMO

BACKGROUND: Anemia is prevalent among patients with T2DM with DFU. However, there is limited research on the relationship between Hb level and DFU. OBJECTIVE: To investigate the characteristics and relationship between Hb level and prognosis in patients with DFU. MATERIALS AND METHODS: A total of 212 patients with T2DM were included and grouped according to the presence (n = 105) or absence (n = 107) of DFU. The independent t test and multiple logistic regression analysis were used to analyze the effect of different factors on the occurrence of anemia in patients with DFU and whether Hb level could be used to predict prognosis. RESULTS: There were significant differences in clinical indicators that directly or indirectly contributed to anemia in patients with DFU (P < .05). Hb level was independently associated with DFU (OR, 0.899; P < .05). Hb levels were significantly decreased in patients aged 65 years or older (P < .05). Mild anemia was prevalent among most patients with DFU (59.62%). Hb level decreased with the severity of foot ulcer (P < .05) and was correlated with the duration of diabetes (R2 = 0.653; P < .05). The AUC value was 0.82, with a cutoff value of 122.5 g/L to identify patients with DFU at high risk of adverse outcomes. CONCLUSION: Anemia is common in patients with DFU. Anemia is a marker of DFU severity, and Hb level can predict poor prognosis in patients with DFU.


Assuntos
Anemia , Diabetes Mellitus Tipo 2 , Pé Diabético , Hemoglobinas , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/sangue , Pé Diabético/sangue , Masculino , Feminino , Estudos Transversais , Anemia/sangue , Pessoa de Meia-Idade , Hemoglobinas/metabolismo , Hemoglobinas/análise , Idoso , Prognóstico , Prevalência , Fatores de Risco , Índice de Gravidade de Doença
4.
Free Radic Biol Med ; 217: 157-172, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38552928

RESUMO

Obesity has significant repercussions for female reproductive health, including adverse effects on oocyte quality, fertility, embryo development and offspring health. Here, we showed that intermittent fasting (IF) has several notable effects on follicular development, oocyte development and maturation and offspring health in obese mice. IF treatment prevents obesity-associated germline-soma communication defects, mitochondrial dysfunction, oxidative damage, apoptosis, and spindle/chromosomal disruption. RNA-sequencing analysis of oocytes from normal diet (ND), high-fat diet (HFD), and HFD + IF mice indicated that IF treatment improved mitochondrial oxidative phosphorylation function and mRNA storage and translation, which was potentially mediated by the Smith-like family member 14 B (LSM14B). Knockdown of LSM14B by siRNA injection in oocytes from ND mice recapitulates all the translation, mitochondrial dysfunction and meiotic defect phenotypes of oocytes from HFD mice. Remarkably, the injection of Lsm14b mRNA into oocytes from HFD mice rescued the translation, mitochondrial dysfunction and meiotic defect phenotypes. These results demonstrated that dysfunction in the oocyte translation program is associated with obesity-induced meiotic defects, while IF treatment increased LSM14B expression and maternal mRNA translation and restored oocyte quality. This research has important implications for understanding the effects of obesity on female reproductive health and offers a potential nonpharmacological intervention to improve oocyte quality and fertility in obese individuals.


Assuntos
Jejum Intermitente , RNA Mensageiro Estocado , Animais , Feminino , Camundongos , Meiose , Camundongos Obesos , Doenças Mitocondriais/metabolismo , Obesidade/metabolismo , Oócitos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Mensageiro Estocado/metabolismo
5.
Discov Oncol ; 15(1): 51, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413457

RESUMO

PURPOSE: Lung cancer has a high morbidity and mortality rate of all cancers worldwide. Therefore, there is an urgent need for reliable cancer markers for diagnosis and prognosis of patients with lung cancer. METHODS: In this study, we used the bioinformatics database to compare the expression of the TBX2 subfamily at the transcriptional and protein levels in non-small cell lung cancer. Then, to confirm our bioinformatics analysis above, we used western bloting to determine the expression of TBX2, TBX3, TBX4 and TBX5 in human lung squamous carcinoma cell lines. Besides, low expression of TBX2 subfamily predicted a poor prognosis of patients with lung cancer. Finally, The methylation database was used to explore the relationship between the low expression of TBX2 subfamily and methylation of gene promoter region. RESULTS: Our data showed a significant decrease of TBX2 subfamily expression in lung cancer tissues of several histological subtypes. Finally, the methylation of TBX2 subfamily members in the promoter region of NSCLC was significantly higher than that in normal tissues. CONCLUSION: Our research provided sufficient evidence that TBX2 subfamily might play an inhibitory role in malignancy progression of lung cancer, which is promising to shed light on discovering a novel reliable cancer marker for prognosis of lung cancer patients.

6.
Environ Int ; 184: 108439, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38309194

RESUMO

Microwaves have the advantage of penetrating vegetation and exhibit sensitivity to properties such as vegetation water content (VWC); yet, their potential utility in the fire domain is infrequently investigated. This study elucidates the different impacts of the microwave VWC index EDVI on fire radiative energy (FRE) across various biome types and the significant predictive power for high-severity fires (defined based on FRE) in mainland Southeast Asia. While EDVI exhibits lower predictive power for high severe fires compared to the commonly used fire weather indices (e.g., FWI), an enhancement is observed when these predictors are used in combination. Either by employing EDVI or fire weather indices, the predictability of fires is found to be highest over forests and lowest over croplands. Factors such as increasing human influence and fuel limitation in croplands are likely reducing the roles of VWC and weather on fires, contributing to the lower prediction skill of EDVI and fire weather. These results indicate the usefulness of microwave VWC index in fire studies. Although fire weather presents more considerable impacts on fires, the microwave VWC index seem to still provide some complementary information in fire danger assessment.


Assuntos
Micro-Ondas , Tempo (Meteorologia) , Humanos , Ecossistema , Florestas , Água , Sudeste Asiático
7.
Child Abuse Negl ; 149: 106703, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38395020

RESUMO

BACKGROUND: Adverse childhood experiences (ACEs) profoundly disrupt preschoolers' attentional regulation development. Different patterns of ACEs may be associated with different attentional regulation outcomes. OBJECTIVE: Drawing from developmental systems theory and attachment theory, this study aimed to identify distinct patterns of early ACEs at age three and examined the associations of these patterns with preschoolers' attentional regulation at age five. PARTICIPANTS AND SETTING: This study used the two waves of longitudinal data from the Future of Families and Child Wellbeing Study (N = 4457). METHODS: First, this study applied latent class analysis (LCA) across nine indicators of ACEs at age three. Second, class membership was examined for associations with preschoolers' attentional regulation at age five. RESULTS: LCA identified four latent classes of ACEs: separation (41.2 %), parental incarceration (33 %), family dysfunction (20.8 %), and child abuse (5 %). Children in the child abuse class exhibited lower levels of attentional regulation than those in the family dysfunction class (0.33 standard deviation difference, p < .01) or separation class (0.48 standard deviation difference, p < .001). Children in the parental incarceration class demonstrated lower levels of attentional regulation than those in the separation class (0.63 standard deviation difference, p < .001). CONCLUSIONS: Findings provide implications for the need to prevent early child abuse and incorporate trauma-informed intervention programs to support preschoolers' attentional regulation during school-entry age.


Assuntos
Experiências Adversas da Infância , Maus-Tratos Infantis , Criança , Humanos , Análise de Classes Latentes , Saúde da Criança , Pais
8.
Biom J ; 66(1): e2200348, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38240577

RESUMO

An inference procedure is proposed to provide consistent estimators of parameters in a modal regression model with a covariate prone to measurement error. A score-based diagnostic tool exploiting parametric bootstrap is developed to assess adequacy of parametric assumptions imposed on the regression model. The proposed estimation method and diagnostic tool are applied to synthetic data generated from simulation experiments and data from real-world applications to demonstrate their implementation and performance. These empirical examples illustrate the importance of adequately accounting for measurement error in the error-prone covariate when inferring the association between a response and covariates based on a modal regression model that is especially suitable for skewed and heavy-tailed response data.


Assuntos
Simulação por Computador
9.
Intellect Dev Disabil ; 62(1): 14-26, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38281514

RESUMO

The New York State Office for People With Developmental Disabilities seeks to better understand the direct support professional (DSP) workforce and offer data-informed strategies for DSP retention. We used the 2018 NCI-IDD Staff Stability Survey (now called State of the Workforce Survey) to investigate agency-level factors influencing DSP tenure. A total 303 provider agencies completed the survey in New York State, representing 72,252 DSPs. Multiple linear regression analysis revealed that selected agency-level variables explained 12.6% of the variance in DSP tenure, R2 = .16, Radj2 = .126, F (11, 260) = 4.54, p < .05. This study yielded strong empirical evidence consistent with existing national reports and research on the role that wages, benefits, and supervisory support play on DSP tenure.


Assuntos
Pessoal de Saúde , Deficiência Intelectual , Humanos , Criança , New York , Deficiências do Desenvolvimento , Recursos Humanos
10.
Environ Pollut ; 344: 123240, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38154780

RESUMO

Recently, biomass has been regarded as a promising option for solid energy in China, which is promoted in the residential sector and firing power plants. We collected 200 PM2.5 samples (particulate matter with a aerodynamic diameter smaller than 2.5 µm) at multi-sites across Beijing from three individual sampling cases from 2015 to 2017. The levels of OC, OC fractions, EC, EC fractions, as well as K+ were measured. Then, we adopted the Positive Matrix Factorization 5.0 to apportion the sources of carbonaceous aerosols. The source apportionment results were compared with the estimates of source contribution using the bottom-up technical method with the latest emission inventories after the Action Plan was put into effect in 2013. Our results demonstrate that high pollution of carbonaceous aerosols originated from wood smoking based on the receptor modeling and bottom-up technical method in Beijing from 2015 to 2017. Future energy transition policy should focus on the technologies and regulations for reducing emissions from renewable biomass fuel combustion. This study highlights the importance of regulations that address emissions controls on fuels replacing coal combustion to meet the needs to mitigate air pollution from primary energy use.


Assuntos
Poluentes Atmosféricos , Pequim , Poluentes Atmosféricos/análise , Fumaça , Madeira/química , Estações do Ano , Monitoramento Ambiental/métodos , Material Particulado/análise , China , Atmosfera , Aerossóis/análise , Políticas , Carbono/análise
11.
Front Endocrinol (Lausanne) ; 14: 1236549, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37859983

RESUMO

Objective: To promote the development and therapeutic application of new medications, it is crucial to conduct a thorough investigation into the mechanism by which the traditional Chinese herb pair of Haizao-Kunbu (HK) treats Graves' disease (GD). Materials and methods: Chemical ingredients of HK, putative target genes, and GD-associated genes were retrieved from online public databases. Using Cytoscape 3.9.1, a compound-gene target network was established to explore the association between prosperous ingredients and targets. STRING, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway analyses visualized core targets and disease pathways. Additionally, we conducted a refined analysis of the binding interactions between active ingredients and their respective targets. To visualize these findings, we employed precise molecular docking techniques. Furthermore, we carried out molecular dynamics simulations to gain insights into the formation of more tightly bound complexes. Results: We found that there were nine key active ingredients in HK, which mainly acted on 21 targets. These targets primarily regulated several biological processes such as cell population proliferation, protein phosphorylation, and regulation of kinase activity, and acted on PI3K-AKT and MAPK pathways to treat GD. Analysis of the molecular interaction simulation under computer technology revealed that the key targets exhibited strong binding activity to active ingredients, and Fucosterol-AKT1 and Isofucosterol-AKT1 complexes were highly stable in humans. Conclusion: This study demonstrates that HK exerts therapeutic effects on GD in a multi-component, multi-target, and multi-pathway manner by regulating cell proliferation, differentiation, inflammation, and immunomodulatory-related targets. This study provides a theoretical foundation for further investigation into GD.


Assuntos
Doença de Graves , Simulação de Dinâmica Molecular , Humanos , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Doença de Graves/tratamento farmacológico , Doença de Graves/genética
12.
Elife ; 122023 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-37860954

RESUMO

The overall oocyte quality declines with aging, and this effect is strongly associated with a higher reactive oxygen species (ROS) level and the resultant oxidative damage. C-type natriuretic peptide (CNP) is a well-characterized physiological meiotic inhibitor that has been successfully used to improve immature oocyte quality during in vitro maturation. However, the underlying roles of CNP in maternally aged oocytes have not been reported. Here, we found that the age-related reduction in the serum CNP concentration was highly correlated with decreased oocyte quality. Treatment with exogenous CNP promoted follicle growth and ovulation in aged mice and enhanced meiotic competency and fertilization ability. Interestingly, the cytoplasmic maturation of aged oocytes was thoroughly improved by CNP treatment, as assessed by spindle/chromosome morphology and redistribution of organelles (mitochondria, the endoplasmic reticulum, cortical granules, and the Golgi apparatus). CNP treatment also ameliorated DNA damage and apoptosis caused by ROS accumulation in aged oocytes. Importantly, oocyte RNA-seq revealed that the beneficial effect of CNP on aged oocytes was mediated by restoration of mitochondrial oxidative phosphorylation, eliminating excessive mitophagy. CNP reversed the defective phenotypes in aged oocytes by alleviating oxidative damage and suppressing excessive PINK1/Parkin-mediated mitophagy. Mechanistically, CNP functioned as a cAMP/PKA pathway modulator to decrease PINK1 stability and inhibit Parkin recruitment. In summary, our results demonstrated that CNP supplementation constitutes an alternative therapeutic approach for advanced maternal age-related oocyte deterioration and may improve the overall success rates of clinically assisted reproduction in older women.


Assuntos
Técnicas de Maturação in Vitro de Oócitos , Peptídeo Natriurético Tipo C , Animais , Feminino , Camundongos , Células do Cúmulo/metabolismo , Técnicas de Maturação in Vitro de Oócitos/métodos , Meiose , Mitofagia , Peptídeo Natriurético Tipo C/farmacologia , Peptídeo Natriurético Tipo C/genética , Peptídeo Natriurético Tipo C/metabolismo , Oócitos/metabolismo , Proteínas Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo
13.
Child Abuse Negl ; 146: 106507, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37879255

RESUMO

BACKGROUND: Intimate partner violence (IPV) often co-occurs with childhood maltreatment and negatively impacts children's development. While previous research has shown a direct link between these experiences and children's self-regulation, less is known about the potential unique effect and bidirectional associations between them. OBJECTIVE: The present study aims to investigate the bidirectional effects among maternal IPV experiences, child maltreatment, and children's behavioral self-regulation. PARTICIPANTS AND SETTING: 4,402 participants from three waves of the longitudinal study of the Future of Families and Child Wellbeing Study (FFCWS) were included in the study. METHODS: Cross-lagged path analyses were conducted to examine the longitudinal reciprocal relationships among IPV, child maltreatment, and children's behavioral regulation when children were 3, 5, and 9 years old. RESULTS: IPV exposure at ages 3 and 5 was negatively associated with levels of behavioral self-regulation at ages 5 and 9, even after accounting for physical maltreatment, psychological maltreatment, or neglect. Neglect at ages 3 and 5 was found to be associated with lower levels of behavioral self-regulation at later ages, when IPV exposure was considered in the models. Lower levels of behavioral self-regulation at age 3 were found to be linked with higher levels of psychological maltreatment, physical maltreatment, neglect, and IPV exposure at age 5. CONCLUSION: This study revealed bidirectional effects between maternal IPV experiences, child maltreatment, and children's behavioral self-regulation. Furthermore, the study demonstrated that exposure to IPV during early childhood significantly predicts long-term behavioral self-regulation difficulties, even after controlling for the effects of child maltreatment.


Assuntos
Maus-Tratos Infantis , Exposição à Violência , Violência por Parceiro Íntimo , Autocontrole , Criança , Humanos , Pré-Escolar , Estudos Longitudinais , Maus-Tratos Infantis/psicologia , Violência por Parceiro Íntimo/psicologia , Abuso Físico/psicologia , Exposição à Violência/psicologia
14.
Am J Chin Med ; 51(8): 2157-2173, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37865871

RESUMO

Hemorrhagic shock (HS) is the leading cause of death in trauma patients. Inflammation following HS can lead to cardiac damage. Pachymic acid (PA), a triterpenoid extracted from Poria cocos, has been found to possess various biological activities, including anti-inflammatory and anti-apoptotic properties. Our research aims to investigate the protective effects of PA against HS-induced heart damage and the underlying mechanisms involved. Male Sprague-Dawley rats were intraperitoneally injected with PA (7.5 or 15[Formula: see text]mg/kg) daily for three days. Subsequently, we created a rat model of HS by drawing blood through a catheter inserted into the femoral artery followed by resuscitation. The results revealed that HS led to abnormalities in hemodynamics, serum cardiac enzyme levels, and cardiac structure, as well as induced cardiac apoptosis. However, pretreatment with PA effectively alleviated these effects. PA-pretreatment also suppressed mRNA and protein levels of interleukin (IL)-1[Formula: see text], IL-6, and tumor necrosis factor [Formula: see text] (TNF-[Formula: see text]) in the heart tissues of HS rats. Additionally, PA-pretreatment reduced inflammatory cell infiltration and M1 macrophage polarization while exaggerating M2 polarization in HS rat hearts. The study observed a decreased proportion of the expression of of M1 macrophages (CD86[Formula: see text]) and their marker (iNOS), along with an increased proportion of the expression of M2 macrophages (CD206[Formula: see text]) and their marker (Arg-1). Notably, PA-pretreatment suppressed NF-[Formula: see text]B pathway activation via inhibiting NF-[Formula: see text]B p65 phosphorylation and its nuclear translocation. In conclusion, PA-pretreatment ameliorates HS-induced cardiac injury, potentially through its inhibition of the NF-[Formula: see text]B pathway. Therefore, PA treatment holds promise as a strategy for mitigating cardiac damage in HS.


Assuntos
Traumatismos Cardíacos , Choque Hemorrágico , Triterpenos , Humanos , Masculino , Ratos , Animais , NF-kappa B/metabolismo , Choque Hemorrágico/complicações , Choque Hemorrágico/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais , Macrófagos/metabolismo , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Interleucina-1/metabolismo , Traumatismos Cardíacos/metabolismo
15.
J Adolesc Health ; 73(6): 1110-1116, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37676194

RESUMO

PURPOSE: Early adverse childhood experiences (ACEs) predict early onset of sexual intercourse. However, patterns of ACEs identified using latent class analysis (LCA) and their links to early sexual intercourse have been less examined. In this study, we apply LCA to identify ACEs profiles at age five and to examine whether these profiles differentially predict adolescents' sexual initiation. METHODS: We analyzed data obtained from the Future of Families and Child Wellbeing Study for 3,185 participants (male = 1,638; female = 1,547). This included parental/caregivers' reports of 10 types of ACEs when participants were on average at age five and youth self-report data on sexual intercourse before or at age 15. We used LCA to classify the participants into subgroups and multinomial logistic regressions to examine differences in early sexual initiation among the ACEs subgroups. RESULTS: LCA showed evidence of four classes for both genders: low adversity (51.8%), socioeconomic adversity (32.0%), family dysfunction (12.0%), and abuse (4.2%). We found class membership differences in early sexual intercourse in all three adversity classes compared to the low adversity group. Pairwise comparison tests further revealed that adolescents in the family dysfunction class had lesser odds of engaging in early sexual intercourse than their counterparts in the socioeconomic adversity and abuse classes. DISCUSSION: Our findings suggest that LCA could help identify meaningful and distinctive child adversity patterns while accounting for the co-occurrence of ACEs. This is particularly helpful in evaluating who might be at greatest health risk which can further inform more effective and targeted interventions.


Assuntos
Experiências Adversas da Infância , Maus-Tratos Infantis , Humanos , Masculino , Criança , Feminino , Adolescente , Coorte de Nascimento , Coito , Comportamento Sexual
16.
Adv Healthc Mater ; 12(30): e2301111, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37689976

RESUMO

This study investigates the effect of porosity and pore shape on the biological and mechanical behavior of additively manufactured scaffolds for bone tissue engineering (BTE). Polylactic acid scaffolds with varying porosity levels (15-78%) and pore shapes, including regular (rectangular pores), gyroid, and diamond (triply periodic minimal surfaces) structures, are fabricated by fused filament fabrication. Murine-derived macrophages and human bone marrow-derived mesenchymal stromal cells (hBMSCs) are seeded onto the scaffolds. The compressive behavior and surface morphology of the scaffolds are characterized. The results show that scaffolds with 15%, 30%, and 45% porosity display the highest rate of macrophage and hBMSC growth. Gyroid and diamond scaffolds exhibit a higher rate of macrophage proliferation, while diamond scaffolds exhibit a higher rate of hBMSC proliferation. Additionally, gyroid and diamond scaffolds exhibit better compressive behavior compared to regular scaffolds. Of particular note, diamond scaffolds have the highest compressive modulus and strength. Surface morphology characterization indicates that the surface roughness of diamond and gyroid scaffolds is greater than that of regular scaffolds at the same porosity level, which is beneficial for cell attachment and proliferation. This study provides valuable insights into porosity and pore shape selection for additively manufactured scaffolds in BTE.


Assuntos
Engenharia Tecidual , Alicerces Teciduais , Humanos , Animais , Camundongos , Alicerces Teciduais/química , Porosidade , Teste de Materiais , Força Compressiva , Engenharia Tecidual/métodos , Diamante
17.
Int Immunopharmacol ; 124(Pt A): 110860, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37716163

RESUMO

OBJECTIVE: Low molecular mass polypeptide 7 (LMP7) is an immunoproteasome subunit that regulates T cell amplification, differentiation, and inflammation and is involved in rheumatoid arthritis (RA) progression. This study intended to apply PR-957 (an anti-LMP7 agent) for RA treatment in vitro and in vivo and evaluate its interaction with LMP7-mediated CD4+ T cell imbalance. METHODS: Peripheral blood mononuclear cells (PBMCs) were obtained from 30 RA patients and 30 healthy controls. RA fibroblast-like synoviocytes (RA-FLSs) and CD4+ T cells were isolated from RA patients and then cocultured with PR-957 and/or LMP7 overexpression adenovirus (Ad-LMP7). Collagen-induced arthritis (CIA) mice were constructed and then treated with PR-957 and/or Ad-LMP7. RESULTS: LMP7 was higher in RA patients (versus healthy controls) and positively correlated with T helper (Th)1 cells, the Th1/Th2 ratio, Th17 cells, and the Th17/Treg ratio but not with Th2 or T regulatory (Treg) cells. PR-957 reduced Th1 and Th17 cells but increased Th2 and Treg cells in RA-CD4+ T cells, and this effect was partially reversed by Ad-LMP7 transfection. Interestingly, when cocultured with RA-CD4+ T cells, PR-957 increased RA-FLS apoptosis and decreased its invasive ability, viability, and inflammation, as suggested by IL-6, CCL2, MMP1, and MMP3; however, these phenomena were weakened in RA-FLSs without RA-CD4+ T cell coculture. In addition, Ad-LMP7 transfection attenuated the above effects of PR-957. In CIA mice, PR-957 decreased the arthritis score, synovial hyperproliferation and articular injury, inflammation in the synovium and serum, and the imbalance of Th1/Th2 and Th17/Treg in the spleen, and these effects were attenuated by Ad-LMP7. CONCLUSION: PR-957 ameliorates RA progression and inflammation by repressing LMP7-mediated CD4+ T cell imbalance.


Assuntos
Artrite Experimental , Artrite Reumatoide , Animais , Humanos , Camundongos , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Inflamação , Leucócitos Mononucleares , Peptídeos/farmacologia , Linfócitos T Reguladores , Células Th1 , Células Th17 , Linfócitos T CD4-Positivos
18.
J Appl Stat ; 50(11-12): 2373-2387, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37529565

RESUMO

In this paper, we propose a Susceptible-Infected-Removal (SIR) model with time fused coefficients. In particular, our proposed model discovers the underlying time homogeneity pattern for the SIR model's transmission rate and removal rate via Bayesian shrinkage priors. MCMC sampling for the proposed method is facilitated by the nimble package in R. Extensive simulation studies are carried out to examine the empirical performance of the proposed methods. We further apply the proposed methodology to analyze different levels of COVID-19 data in the United States.

19.
Rev Sci Instrum ; 94(7)2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37409911

RESUMO

The strategies that allow one single device to possess multiple controlled micro-/nano-manipulation functions are demanded by various fields. In this work, we have developed a probe-type ultrasonic sweeper with rich micro-/nano-manipulation functions, including concentration, decorating, transmedium extraction, and removal of micro-/nanoscale materials at the interface between a suspension film and a non-vibration substrate. The functions are implemented with a micro-manipulation probe (MMP) in contact with the substrate, which vibrates approximately linearly and perpendicularly to the substrate. Silver nanowires on the substrate can be sucked onto the vibrating MMP's tip and accumulate to form a microsheet. By moving the MMP horizontally, nanowires on its motional path can be sucked onto the MMP's tip, and controlled cleaning can be realized. If nanoparticles are mixed into the AgNW suspension uniformly, AgNWs in the accumulated microsheet can be decorated with the nanoparticles. More importantly, the accumulated nanomaterials on the MMP's tip can be transported freely in the suspension film and even extracted into air from the liquid film. To the best of our knowledge, the ultrasonic sweeper in this work possesses the richest micro-/nano-manipulation functions than any other existing acoustic manipulators. The finite element analyses indicate that the multiple manipulation functions achieved are caused by the acoustic radiation force generated by the ultrasonic field in the suspension film.


Assuntos
Nanopartículas , Nanofios , Ultrassom , Prata , Análise de Elementos Finitos
20.
Toxics ; 11(7)2023 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-37505575

RESUMO

The leaves of plants can be recommended as a cheap and sustainable environmental protection tool to mitigate PAHs with high toxicity in the ambient environment because they can serve as a reactor to remove ambient PAHs. Although previous studies have demonstrated that PAHs exhibit toxicological features, our knowledge about how ambient PAHs influence the leaves of plants is limited regarding the leaves of plants reducing ambient PAHs as a reactor. In this study, 1-year-old Rosa chinensis Jacq. with good growth potential was selected as a model plant. The leaves of Rosa chinensis Jacq. were exposed to 16 types of PAHs in the environmental concentration exposure group (0.1 µg L-1) and high-concentration exposure group (5 µg L-1) for seven days. In comparison, the leaves of Rosa chinensis Jacq. were exposed to de-ionized water and were chosen as the control group. During the exposure periods, the physiological parameters of leaves including, chlorophyll value, water content, temperature and nitrogen, were monitored using a chlorophyll meter. After 7 days of exposure, the leaves in the control and exposure groups were collected and used for whole-transcriptome analysis. Our results demonstrate that significant differentially expressed genes were observed in the leaves of Rosa chinensis Jacq. exposed to individual PAHs at 5 µg L-1 compared to the control group. These differentially expressed genes were involved in seven main pathways using bioinformatic analyses. In contrast, the levels of PAHs at environmentally relevant concentrations had negligible impacts on the physiological parameters and the gene transcription levels of the leaves of Rosa chinensis Jacq. Our results may provide direct evidence to remove ambient PAHs using terrestrial trees without considering the risk of PAHs at environmentally relevant concentrations on the leaves of terrestrial plants.

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