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1.
Lipids Health Dis ; 23(1): 177, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38851716

RESUMO

BACKGROUND: Exposure to different concentration levels of fatty acids (FAs) may have an impact on depression. However, previous studies using individual FAs may not reflect the performance of mixtures of various FAs, and the associations of FA patterns with depression remain unclear. METHODS: We conducted the cross-sectional analysis in 792 adults aged 18 and older with available serum FAs and depression screening data in the National Health and Nutrition Examination Survey (NHANES) 2011-2012. The serum concentrations of thirty FAs were measured using gas chromatography-mass spectrometry and their percentage compositions were subsequently calculated. Depression was defined as the Patient Health Questionnaire-9 score ≥ 10. We employed principal component analysis to derive serum FA patterns. We examined the association between these patterns and depression in the overall population and various subgroups through survey-weighted logistic regression. RESULTS: Four distinct patterns of serum FAs were identified: 'high eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA); low docosatetraenoic acid (DTA) and docosapentaenoic acid (DPA) n-6', 'high long-chain saturated FA and long chain FA', 'low median-chain saturated FA and myristoleic acid' and 'low capric acid and lauric acid; high gamma-linolenic acid (GLA) and stearidonic acid (SDA)' pattern. Individuals in the high tertile of 'high EPA and DHA; low DTA and DPA n-6' pattern score had 0.46 (95% CI: 0.22, 0.93) lower odds of developing depression compared to individuals in the lowest tertile after adjusting for confounders such as age, sex, physical activity and total energy intake, etc. The odds ratio (OR) of depression was increased in the population with the highest tertile of 'low capric acid and lauric acid; high GLA and SDA' pattern (OR: 2.45, 95% CI: 1.24, 4.83). In subgroup analyses, we observed that the association between 'high EPA and DHA; low DTA and DPA n-6' and depression persisted among specific demographic and lifestyle subgroups, including females, non-Mexican Americans, non-obese, those aged over 60 years, smokers and drinkers. Similarly, 'low capric acid and lauric acid; high GLA and SDA' showed stable associations in female, non-Mexican Americans and smokers. CONCLUSIONS: Serum FA patterns are associated with depression, and their relationships vary across sex, race, BMI, age, smoking and drinking subgroups, highlighting the importance of considering specific FA patterns within these demographic and lifestyle categories. Utilization of combined FA administration may serve as a mitigation measure against depression in these specific populations.


Assuntos
Depressão , Ácidos Graxos , Inquéritos Nutricionais , Humanos , Feminino , Masculino , Depressão/sangue , Depressão/epidemiologia , Adulto , Pessoa de Meia-Idade , Ácidos Graxos/sangue , Estudos Transversais , Estados Unidos/epidemiologia , Ácidos Decanoicos/sangue , Ácido Eicosapentaenoico/sangue , Idoso , Ácidos Graxos Insaturados/sangue , Adulto Jovem , Adolescente , Análise de Componente Principal
2.
Phytomedicine ; 129: 155688, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38728920

RESUMO

BACKGROUND: Malignant breast cancer cells trigger the over-activation of osteoclast precursor cells, leading to bone loss and severe pain. Targeted inhibition of osteoclast differentiation has emerged as an important strategy for treating bone syndromes induced by breast cancer. PURPOSE: The objective is to discover natural osteoclast inhibitor to treat osteoclastogenesis and bone destruction induced by breast cancer, and clarify the specific mechanisms. METHODS: Recepteur d'origine Nantais (RON) protein was employed to search the natural osteoclast inhibitor for breast cancer-induced osteoclastogenesis by molecular docking, molecular dynamics simulation and cellular thermal shift assay (CETSA). In the in vitro experiment, breast cancer MDA-MB-231 cell-conditioned medium (MDA-MB-231 CM) was used to induce osteoclastogenesis in murine bone marrow-derived macrophages (BMMs), aiming to elucidate the effects and mechanisms of the natural osteoclast inhibitor. In the in vivo model, MDA-MB-231 cells was injected into the mouse tibia to evaluate the therapeutic effect of drug on breast cancer-induced bone destruction. RESULTS: We discovered a significant increase in the expression of RON during MDA-MB-231 CM-induced osteoclast differentiation in vitro. Molecular docking analysis found that oroxylin A (OA), a flavonoid derived from the Chinese medicine Scutellaria baicalensis Georgi, showed binding ability with RON, while its impact and mechanism on breast cancer-induced osteoclastogenesis and osteolysis remains unclear. Molecular dynamics simulation and CETSA further revealed that OA bound directly to the RON protein, and it also decreased RON expression in breast cancer CM-induced osteoclastogenesis. Correspondingly, OA suppressed the MDA-MB-231 CM-induced osteoclastogenesis and bone resorption in vitro. The downstream signals of RON including Src and NFATc1, as well as the osteoclast-specific genes, were downregulated by OA. Of interesting, the suppressive effect of OA on osteoclastogenesis induced by MDA-MB-231 CM was abolished after RON was knocked down by the specific RON-siRNA, this further confirmed that OA showed inhibitory effects on osteoclasts through targeting RON. In addition, we found that OA attenuated MDA-MB-231 cell-induced osteolysis and reduced the number of osteoclasts in vivo. CONCLUSION: Our results indicate that OA acts as a natural RON inhibitor to suppress breast cancer-induced osteoclastogenesis and osteolysis. This provides new strategy for treating breast cancer-induced bone destruction and related syndromes.


Assuntos
Neoplasias da Mama , Flavonoides , Simulação de Acoplamento Molecular , Osteoclastos , Osteogênese , Osteólise , Animais , Feminino , Humanos , Camundongos , Neoplasias da Mama/tratamento farmacológico , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Flavonoides/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteólise/tratamento farmacológico , Receptores Proteína Tirosina Quinases , Camundongos Nus
3.
Ecotoxicol Environ Saf ; 278: 116452, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38744066

RESUMO

The aim of this research was to examine the correlation between the exposure to bisphenol analogues (BPs), such as bisphenol A (BPA), bisphenol F (BPF), and bisphenol S (BPS), and the risk of developing systemic lupus erythematosus (SLE). Ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was utilized to measure the levels of BPA, BPF, and BPS in the urine of 168 female participants diagnosed with SLE and 175 female participants who were deemed healthy controls. Logistic regression models were utilized to assess the connections between levels of bisphenol and the risk of SLE. The findings indicated that levels of BPA and BPF in the urine of individuals with SLE were markedly elevated compared to those in the control group. Higher exposure to BPA and BPF exhibited positive dose-response relationships with increased SLE risk. No significant associations were identified between BPS and the risk of SLE. These findings suggest exposure to BPA and BPF may be implicated as novel environmental triggers in the development of autoimmunity such as SLE. The significantly increased levels of these bisphenol analogues detected in SLE patients versus healthy controls, along with the associations between higher exposures and elevated SLE risk, which offers crucial hints for comprehending how endocrine-disrupting substances contribute to the genesis of autoimmune illnesses. Further research using robust longitudinal assessments of bisphenol analogue exposures is warranted to corroborate these epidemiological findings. Overall, this study highlights potential environmental risk factors for SLE while calling for additional investigation into the impact of bisphenol exposures on autoimmunity development.


Assuntos
Compostos Benzidrílicos , Lúpus Eritematoso Sistêmico , Fenóis , Sulfonas , Lúpus Eritematoso Sistêmico/induzido quimicamente , Fenóis/urina , Humanos , Compostos Benzidrílicos/urina , Feminino , Adulto , Exposição Ambiental/estatística & dados numéricos , Espectrometria de Massas em Tandem , Poluentes Ambientais , Pessoa de Meia-Idade , Disruptores Endócrinos , Autoimunidade/efeitos dos fármacos , Estudos de Casos e Controles , Adulto Jovem
4.
Front Public Health ; 12: 1373044, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601492

RESUMO

Objectives: To investigate the causal relationships between pneumoconiosis and rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and gout. Methods: The random-effects inverse variance weighted (IVW) approach was utilized to explore the causal effects of the instrumental variables (IVs). Sensitivity analyses using the MR-Egger and weighted median (WM) methods were did to investigate horizontal pleiotropy. A leave-one-out analysis was used to avoid the bias resulting from single-nucleotide polymorphisms (SNPs). Results: There was no causal association between pneumoconiosis and SLE, RA or gout in the European population [OR = 1.01, 95% CI: 0.94-1.10, p = 0.74; OR = 1.00, 95% CI: 0.999-1.000, p = 0.50; OR = 1.00, 95% CI: 1.000-1.001, p = 0.55]. Causal relationships were also not found in pneumoconiosis due to asbestos and other mineral fibers and SLE, RA and gout [OR = 1.01, 95% CI: 0.96-1.07, p = 0.66; OR = 1.00, 95% CI: 1.00-1.00, p = 0.68; OR = 1.00, 95% CI: 1.00-1.00, p = 0.20]. Conclusion: Our study suggests that pneumoconiosis may have no causal relationship with the three inflammatory immune diseases.


Assuntos
Gota , Doenças do Sistema Imunitário , Lúpus Eritematoso Sistêmico , Pneumoconiose , Humanos , Análise da Randomização Mendeliana , Pneumoconiose/epidemiologia
5.
Nat Commun ; 15(1): 2440, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38499579

RESUMO

As a milestone in the exploration of topological physics, Fermi arcs bridging Weyl points have been extensively studied. Weyl points, as are Fermi arcs, are believed to be only stable when preserving translation symmetry. However, no experimental observation of aperiodic Fermi arcs has been reported so far. Here, we continuously twist a bi-block Weyl meta-crystal and experimentally observe the twisted Fermi arc reconstruction. Although both the Weyl meta-crystals individually preserve translational symmetry, continuous twisting operation leads to the aperiodic hybridization and scattering of Fermi arcs on the interface, which is found to be determined by the singular total reflection around Weyl points. Our work unveils the aperiodic scattering of Fermi arcs and opens the door to continuously manipulating Fermi arcs.

6.
Front Pharmacol ; 15: 1342121, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38529184

RESUMO

Objective: Our previous studies substantiated that the biological activity of Schisandra chinensis lignans during the treatment of Alzheimer's disease (AD) was mediated by neurotransmitter levels, and 15 of its active components were identified. However, the pharmacokinetic and pharmacodynamic relationship of Schisandra chinensis lignans has been less studied. The objective of this study was to investigate the relationship between the pharmacokinetics and pharmacodynamics of Schisandra chinensis lignans in the treatment of AD, and to establish a pharmacokinetic-pharmacodynamic (PK-PD) model. Methods and Results: Herein, we established a microdialysis-ultra performance liquid chromatography-triple quadruple mass spectrometry (MD-LC-TQ-MS) technique that could simultaneously and continuously collect and quantitatively analyze the active compounds and neurotransmitters related to the therapeutic effects of Schisandra chinensis in awake AD rats. Eight lignans were detected in the hippocampus, and a PK-PD model was established. The fitted curves highlighted a temporal lag between the maximum drug concentration and the peak drug effect. Following treatment, the levels of four neurotransmitters tended to converge with those observed in the sham operation group. Conclusion: By establishing a comprehensive concentration-time-effect relationship for Schisandra chinensis lignans in AD treatment, our study provides novel insights into the in vivo effects of these lignans in AD rats.

7.
Acta Pharmacol Sin ; 45(4): 790-802, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38191913

RESUMO

Osteoporosis results from overactivation of osteoclasts. There are currently few drug options for treatment of this disease. Since the successful development of allosteric inhibitors, phosphatases have become attractive therapeutic targets. Protein phosphatase 1, regulatory subunit 15 A (PPP1R15A), is a stress-responsive protein, which promotes the UPR (unfolded protein response) and restores protein homeostasis. In this study we investigated the role of PPP1R15A in osteoporosis and osteoclastogenesis. Ovariectomy (OVX)-induced osteoporosis mouse model was established, osteoporosis was evaluated in the left femurs using micro-CT. RANKL-stimulated osteoclastogenesis was used as in vitro models. We showed that PPP1R15A expression was markedly increased in BMMs derived from OVX mice and during RANKL-induced osteoclastogenesis in vitro. Knockdown of PPP1R15A or application of Sephin1 (a PPP1R15A allosteric inhibitor in a phase II clinical trial) significantly inhibited osteoclastogenesis in vitro. Sephin1 (0.78, 3.125 and 12.5 µM) dose-dependently mitigated the changes in NF-κB, MAPK, and c-FOS and the subsequent nuclear factor of activated T cells 1 (NFATc1) translocation in RANKL-stimulated BMMs. Both Sephin1 and PPP1R15A knockdown increased the phosphorylated form of eukaryotic initiation factor 2α (eIF2α); knockdown of eIF2α reduced the inhibitory effects of Sephin1 on NFATc1-luc transcription and osteoclast formation. Furthermore, Sephin1 or PPP1R15A knockdown suppressed osteoclastogenesis in CD14+ monocytes from osteoporosis patients. In OVX mice, injection of Sephin1 (4, 8 mg/kg, i.p.) every two days for 6 weeks significantly inhibited bone loss, and restored bone destruction and decreased TRAP-positive cells. This study has identified PPP1R15A as a novel target for osteoclast differentiation, and genetic inhibition or allosteric inhibitors of PPP1R15A, such as Sephin1, can be used to treat osteoporosis. This study revealed that PPP1R15A expression was increased in osteoporosis in both human and mice. Inhibition of PPP1R15A by specific knockdown or an allosteric inhibitor Sephin1 mitigated murine osteoclast formation in vitro and attenuated ovariectomy-induced osteoporosis in vivo. PPP1R15A inhibition also suppressed pathogenic osteoclastogenesis in CD14+ monocytes from osteoporosis patients. These results identify PPP1R15A as a novel regulator of osteoclastogenesis and a valuable therapeutic target for osteoporosis.


Assuntos
Guanabenzo , Osteoporose , Animais , Feminino , Humanos , Camundongos , Diferenciação Celular , Guanabenzo/análogos & derivados , Guanabenzo/uso terapêutico , NF-kappa B/metabolismo , Fatores de Transcrição NFATC/metabolismo , Osteoclastos , Osteogênese , Osteoporose/tratamento farmacológico , Ovariectomia , Proteína Fosfatase 1/metabolismo , Proteína Fosfatase 1/farmacologia , Ligante RANK/metabolismo
8.
Viruses ; 15(11)2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-38005826

RESUMO

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. The interplay between innate and adaptive immune responses plays a crucial role in managing COVID-19. Cell therapy has recently emerged as a promising strategy to modulate the immune system, offering immense potential for the treatment of COVID-19 due to its customizability and regenerative capabilities. This review provides an overview of the various subsets of immune cell subsets implicated in the pathogenesis of COVID-19 and a comprehensive summary of the current status of immune cell therapy in COVID-19 treatment.


Assuntos
COVID-19 , Humanos , COVID-19/terapia , SARS-CoV-2 , Tratamento Farmacológico da COVID-19 , Imunoterapia , Terapia Baseada em Transplante de Células e Tecidos , Imunidade Inata
9.
Opt Express ; 31(20): 32865-32874, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37859079

RESUMO

Metamaterials, thoughtfully designed, have demonstrated remarkable success in the manipulation of electromagnetic waves. More recently, deep learning can advance the performance in the field of metamaterial inverse design. However, existing inverse design methods based on deep learning often overlook potential trade-offs of optimal design and outcome diversity. To address this issue, in this work we introduce contrastive learning to implement a simple but effective global ranking inverse design framework. Viewing inverse design as spectrum-guided ranking of the candidate structures, our method creates a resemblance relationship of the optical response and metamaterials, enabling the prediction of diverse structures of metamaterials based on the global ranking. Furthermore, we have combined transfer learning to enrich our framework, not limited in prediction of single metamaterial representation. Our work can offer inverse design evaluation and diverse outcomes. The proposed method may shrink the gap between flexibility and accuracy of on-demand design.

10.
Entropy (Basel) ; 25(10)2023 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-37895498

RESUMO

The Minimum Vertex Weighted Coloring (MinVWC) problem is an important generalization of the classic Minimum Vertex Coloring (MinVC) problem which is NP-hard. Given a simple undirected graph G=(V,E), the MinVC problem is to find a coloring s.t. any pair of adjacent vertices are assigned different colors and the number of colors used is minimized. The MinVWC problem associates each vertex with a positive weight and defines the weight of a color to be the weight of its heaviest vertices, then the goal is the find a coloring that minimizes the sum of weights over all colors. Among various approaches, reduction is an effective one. It tries to obtain a subgraph whose optimal solutions can conveniently be extended into optimal ones for the whole graph, without costly branching. In this paper, we propose a reduction algorithm based on maximal clique enumeration. More specifically our algorithm utilizes a certain proportion of maximal cliques and obtains lower bounds in order to perform reductions. It alternates between clique sampling and graph reductions and consists of three successive procedures: promising clique reductions, better bound reductions and post reductions. Experimental results show that our algorithm returns considerably smaller subgraphs for numerous large benchmark graphs, compared to the most recent method named RedLS. Also, we evaluate individual impacts and some practical properties of our algorithm. Furthermore, we have a theorem which indicates that the reduction effects of our algorithm are equivalent to that of a counterpart which enumerates all maximal cliques in the whole graph if the run time is sufficiently long.

11.
Immunology ; 170(4): 567-578, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37688314

RESUMO

Sepsis is a life-threatening disease characterized by multiple organ dysfunction. B cells play a pivotal role in sepsis. Here, we first observed the significantly reduced Flot2 gene expression in B cells from patients with bacterial sepsis and endotoxin-induced septic mice. However, the effects of Flot2 on sepsis and B-cell immunity remain unknown. Thus, we sorted B cells from Flot2 knockout (Flot2-/- ) mice, RNA-seq revealed significantly upregulated effector B cell (Beff) cytokines such as Il6, Il1b and Cxcl10 after Flot2 deficiency, while it showed no effect on the expression of regulatory B cell (Breg) cytokines such as Il10, Tgfb. Consistently, elevated Beff cytokine IL-6 and unchanged Breg cytokine IL-10 were shown in B cells from Flot2-/- mice. Similar results were subsequently observed in B cell-specific Flot2 knockout chimeric mice. Notably, Flot2 deficiency aggravated sepsis with increased lung injury and shortened survival time in vivo by facilitating Beffs but not Bregs. Taken together, our data identify Flot2 as a novel controller of B cells, Flot2 deficiency amplifies inflammation by affecting Beffs to participate in the pathogenesis and progression of sepsis.


Assuntos
Linfócitos B Reguladores , Sepse , Animais , Camundongos , Citocinas/metabolismo , Inflamação/genética
12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(4): 1164-1170, 2023.
Artigo em Chinês | MEDLINE | ID: mdl-37551493

RESUMO

OBJECTIVE: To investigate a case of delayed hemolytic transfusion reaction (DHTR), and find the reason and coping strategies to prevent similar incidents in the future. METHODS: Relative antibody identification was carried out, suitable erythrocytes was screened, and relevant indicators after transfusion were evaluated. Medical record and laboratory report of the patient were reviewed, the cause was analyzed, and corresponding treatment was carried out. RESULTS: The patient suffered from DHTR caused by IgM anti-M antibody and low body temperature cardiopulmonary bypass. After anti-hemolytic treatment, the patient was gradually improved, the bilirubin gradually decreased, and finally cured and discharged. CONCLUSION: When the transfusion department finds any antibodies which have activity at room temperature but no respond at 37 ℃, they should communicate with clinical medical staff in time. Warm transfusion should be used during blood transfusion to prevent transfusion-related hemolytic reaction.

13.
Materials (Basel) ; 16(12)2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37374539

RESUMO

The present study investigates the flexural behavior of reinforced concrete (RC) beams; the longitudinal reinforcing rebars of the beams were corroded and then strengthened with carbon fiber-reinforced polymer (CFRP). The corrosion of the longitudinal tension reinforcing rebars in eleven beam specimens was accelerated in order to obtain different corrosion levels. Afterwards, the beam specimens were strengthened by bonding one layer of CFRP sheets to the tension side to restore the strength loss due to the corrosion. The failure modes, flexural capacity, and midspan deflection of the specimens with different corrosion levels of the longitudinal tension reinforcing rebars were obtained by the four-point bending test. It was found that the flexural capacity of the beam specimens decreased with the increase in the corrosion level of the longitudinal tension reinforcing rebars and that the relative flexural strength was only 52.5% when the corrosion level was 25.6%. The stiffness of the beam specimens decreased significantly when the corrosion level was higher than 20%. Through a regression analysis of the test results, a model for the flexural bearing capacity of the corroded RC beams strengthened with CFRP was proposed in the study.

14.
Int Immunopharmacol ; 120: 110316, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37253315

RESUMO

Bone is a preferred metastatic site of advanced breast cancer and the 5-year overall survival rate of breast cancer patients with bone metastasis is only 22.8%. Targeted inhibition of osteoclasts can treat skeletal-related events (SREs) in breast cancer patients. Polyphyllin VII (PP7), a pennogenyl saponin isolated from traditional Chinese herb Paris polyphylla, exhibits strong anti-inflammatory and anti-cancer activities. In this study, we evaluated the effect of PP7 on metastatic breast cancer-induced bone destruction in vivo and the underlying mechanisms. We found that intraperitoneal injection of 1 mg/kg PP7 significantly ameliorated the breast cancer MDA-MB-231 cell-induced osteolysis in mice. Mechanistically, PP7 (0.125-0.5 µM) inhibited the conditioned medium of MDA-MB-231 cells (MDA-MB-231 CM)-induced osteoclast formation in bone marrow-derived macrophages (BMMs). Furthermore, PP7 markedly reduced MDA-MB-231 CM-induced osteoclastic bone resorption and F-actin rings formation in vitro. During MDA-MB-231 CM-induced osteoclastogenesis, the activation of c-Fos and NFATc1 signaling was significantly downregulated by PP7, and finally osteoclast-related genes such as Oscar, Atp6v0d2, Mmp9 and ß3 integrin were decreased. In addition, the formation of osteoblast was promoted by PP7 treatment. Our current findings revealed PP7 as a potential safe agent for preventing and treating bone destruction in breast cancer patients with bone metastases.


Assuntos
Reabsorção Óssea , Neoplasias , Osteólise , Saponinas , Animais , Camundongos , Osteogênese , Osteólise/tratamento farmacológico , Osteoclastos , Saponinas/farmacologia , Proteínas Proto-Oncogênicas c-fos , Ligante RANK/farmacologia , Diferenciação Celular
15.
Transportation (Amst) ; : 1-19, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36530965

RESUMO

On-demand app-based shared mobility services have created new opportunities for complementing traditional fixed-route transit through transit agencies' efforts to incorporate them into their service provision. This paper presents one of the first studies that rigorously examine riders' responses to a pilot aimed at providing such a transit-supplementing service. The study conducts latent class analysis on riders of the Via to Transit program, a mobility pilot in the Seattle region where on-demand service was offered to connect transit riders to light rail stations. The analysis identifies three distinct rider groups with heterogenous responses to the on-demand service: (1) riders who previously used private cars or ride-hailing; (2) riders who were pedestrians and bikers but switched likely because of safety concern; (3) mostly socio-economically disadvantaged riders who previously relied on the bus, but switched to the new service for the convenience and speed. These results point to rich transportation policy implications, which can inform decision-making by public transit agencies as they are exploring alternative ways to deliver the mobility services. Supplementary Information: The online version contains supplementary material available at 10.1007/s11116-022-10351-3.

16.
Transp Res Part A Policy Pract ; 159: 84-95, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-36246189

RESUMO

Paratransit services developed under the Americans with Disabilities Act are a critical transportation means for persons with disabilities to meet their basic needs, but the COVID-19 pandemic posed an unprecedented challenge to service providers. To safeguard transportation equity, this study used complete records of service trips and riders obtained from the Access Transportation Program in the Seattle region for an empirical analysis aimed at answering two research questions. First, how did the ridership and trip purposes of paratransit change after the outbreak of COVID-19? Second, what factors explained the users' changing levels of service usage in response to the pandemic? Statistical methods, including a Hurdle model, were employed as the analytical tools. The results show that paratransit ridership dramatically decreased during 2020 with the most substantial reductions of working and non-essential personal trips, and that most of the remaining trips were for medical purposes. The results also indicate that riders' service usage during the pandemic was associated with their sociodemographic characteristics, disability conditions, and pre-pandemic travel demand. When controlling for other factors, riders who lived in neighborhoods with lower income and lower access to personal vehicles were more dependent on the service. Based on the empirical findings, we recommend that when developing plans for future disruptive events, public transit agencies should promptly implement safety measures, identify and prioritize neighborhoods that are most in need of mobility services, and actively pursue collaboration with other organizations for innovative service delivery options.

17.
Pharmacol Res ; 185: 106517, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36265554

RESUMO

Regulatory B cells (Bregs) potently suppress immune disorders, including allergic contact hypersensitivity (CHS). IKKß overactivation is prominent in various inflammatory diseases. However, its effect on Bregs has not been defined. This study is to investigate the new regulator and inhibitory mechanism of Bregs. IkkßC46A transgenic mice with a Cys46 mutation, resulting in increased IKKß activation, were employed for analysis. IL-10-competent CD9+ Bregs were expanded in IkkßC46A mice and B cell specific-IkkßC46A mutation mice. IkkßC46A mutant CD9+ Bregs had stronger suppressive effects on CD4+ and CD8+ T cells in vitro and CHS responses in vivo. The inhibitory CD9+ Bregs from IkkßC46A mice were characterized by upregulated Neuropilin 2 (Nrp2) and IL-10 in comparison with that of Ikkßwt mice. Interestingly, increased expression of Nrp2 was observed in CD9+ Bregs compared with that of CD9- B cells in wild-type mice. The suppressive activity of wild-type CD9+ Bregs in vitro was attenuated by inhibition of Nrp2 on Bregs or silencing its ligand Sema3f on CD4+ T cells. Our findings delineate a distinct role of IKKß activation in enhancing Bregs to disturb the immune balance. It identifies Nrp2 as a novel regulatory molecule of Bregs that partly contributes to B cell-mediated immune tolerance.


Assuntos
Linfócitos B Reguladores , Doenças do Sistema Imunitário , Animais , Camundongos , Linfócitos T CD8-Positivos/metabolismo , Quinase I-kappa B/metabolismo , Doenças do Sistema Imunitário/metabolismo , Interleucina-10 , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neuropilina-2/genética , Neuropilina-2/metabolismo
18.
J Inflamm Res ; 15: 5293-5308, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36124208

RESUMO

Purpose: Sepsis is a condition that derives from a dysregulated host response to infection. Although B lymphocytes play a pivotal role in immune response, little is known about status of their terminally differentiated cells, antibody-secreting cells (ASCs) during immunosuppressive phase of sepsis, especially in elderly patients. Our aim was to extensively characterize the immune functions of ASCs in elderly septic patients. Patients and Methods: Clinical and laboratory data were collected on days 1, 3, and 7 of hospitalization. Circulating ASCs were evaluated by flow cytometry from fresh whole blood in elderly septic patients at the onset of disease. RNA sequencing analyzed ASCs gene expression profile. Receiver operating characteristic (ROC) curve analysis and logistic regression predicted the survival rate of 28-day mortality. Results: A total of 103 septic patients were enrolled. The number and proportion of ASCs among total lymphocytes dramatically increased in septic patients, and RNA sequencing analysis showed that ASCs from septic patients exhibited a different gene expression profile. Furthermore, we found these ASCs could promote the function of T cells. Logistic regression analysis showed ASCs population was an independent outcome predictor in septic shock patients. Conclusion: Our study revealed the complex nature of immune disorders in sepsis and identified circulating ASCs population as a useful biomarker for predicting mortality in elderly septic patients, which provided a novel clue to combat this severe disease.

19.
Materials (Basel) ; 15(15)2022 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-35955364

RESUMO

The stress-strain relation of recycled aggregate concrete (RAC) after carbonation is very important to the assessment of the durability of RAC. The objective of this study is to investigate the uniaxial compressive stress-strain curves of RAC after carbonation. In this study, the specimens were prepared with 70-mm diameter and 140-mm height cylinders, and the carbonation of the specimens was accelerated after curing 28 days. Then a uniaxial compressive loading test on the specimens was performed by using a mechanical testing machine. The results show that the peak stress (σ0) and elastic modulus (Ec) of all specimens increase with the increase of carbonation depth. The ratio of ultimate strain to peak strain (εu/ε0) and relative toughness of the specimens decrease with the increase of carbonation depth. Furthermore, carbonation has a stronger effect on natural coarse aggregate concrete (NAC) than the 50% replacement rate of RAC with similar compressive strength. Stress-strain models of recycled aggregate concrete with different carbonation depths were established according to experimental results.

20.
Transp Res Rec ; 2676(3): 621-633, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35694240

RESUMO

This study investigates the impacts of ride-hailing, which we define as mobility services consisting of both conventional taxis and app-based services offered by transportation network companies, on individual mode choice. We examine whether ride-hailing substitutes for or complements travel by driving, public transit, or walking and biking. The study overcomes some of the limitations of convenience samples or cross-sectional surveys used in past research by employing a longitudinal dataset of individual travel behavior and socio-demographic information. The data include three waves of travel log data collected between 2012 to 2018 in transit-rich areas of the Seattle region. We conducted individual-level panel data modeling, estimating independently pooled models and fixed-effect models of average daily trip count and duration for each mode, while controlling for various factors that affect travel behavior. The results provide evidence of substitution effects of ride-hailing on driving. We found that cross-sectionally, participants who used more ride-hailing tended to drive less, and that longitudinally, an increase in ride-hailing usage was associated with fewer driving trips. No significant associations were found between ride-hailing and public transit usage or walking and biking. Based on detailed travel data of a large population in a major US metropolitan area, the study highlights the value of collecting and analyzing longitudinal data to understand the impacts of new mobility services.

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