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1.
Rev Sci Instrum ; 95(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38564326

RESUMO

Optical thin films with high-reflectivity (HR) are essential for applications in quantum precision measurements. In this work, we propose a coating technique based on reactive magnetron sputtering with RF-induced substrate bias to fabricate HR-optical thin films. First, atomically flat SiO2 and Ta2O5 layers have been demonstrated due to the assistance of radio-frequency plasma during the coating process. Second, a distributed Bragg reflector (DBR) mirror with an HR of ∼99.999 328% centered at 1397 nm has been realized. The DBR structure is air-H{LH}19-substrate, in which the L and H denote a single layer of SiO2 with a thickness of 237.8 nm and a single layer of Ta2O5 with a thickness of 171.6 nm, respectively. This novel coating method would facilitate the development of HR reflectors and promote their wide applications in precision measurements.

2.
Environ Pollut ; 345: 123467, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38311157

RESUMO

N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPDQ) has raised significant concerns due to its widespread distribution and high toxicity to aquatic organisms. However, the cardiac developmental toxicity of 6PPDQ and the underlying mechanisms remain unclear. In this study, we observed no notable alterations in heart morphology or embryo survival in zebrafish embryos exposed to 6PPDQ (0.2-2000 µg/L) up to 3 days post-fertilization (dpf). However, concentrations at 2 µg/L or higher induced cardiac dysfunctions, leading to lethal effects at later stages (6-8 dpf). We further found that the aryl hydrocarbon receptor (AHR) inhibitor CH22351 attenuated 6PPDQ-induced cardiac dysfunctions, implicating the involvement of AHR signal pathway. Moreover, 6PPDQ exposure led to an overproduction of reactive oxygen species (ROS) and an upregulation of genes associated with oxidative stress (sod1, sod2, and nrf2a). This was accompanied by an increase in oxidative DNA damage and the induction of p53-dependent extrinsic apoptosis. Co-exposure to the ROS scavenger N-acetylcysteine effectively counteracted the DNA damage and apoptosis induced by 6PPDQ. Importantly, inhibition of AHR or its downstream target cyp1b1 attenuated 6PPDQ-induced oxidative stress, DNA damage, and apoptosis. In conclusion, our results provide evidence that 6PPDQ induces oxidative stress through the AHR/cyp1b1 signaling pathway, leading to DNA damage and extrinsic apoptosis, ultimately resulting in cardiac dysfunction.


Assuntos
Receptores de Hidrocarboneto Arílico , Peixe-Zebra , Animais , Peixe-Zebra/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Estresse Oxidativo , Transdução de Sinais , Cardiotoxicidade/metabolismo , Apoptose , Embrião não Mamífero
3.
Environ Toxicol Pharmacol ; 106: 104393, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38367920

RESUMO

Recent evidence indicates that PM2.5 poses a risk for congenital heart diseases, but the mechanisms remain unclear. We hypothesized that AHR activated by PM2.5 might cause mitochondrial damage via PGC-1α dysregulation, leading to heart defects. We initially discovered that the PGC-1α activator ZLN005 counteracted cardiac defects in zebrafish larvae exposed to EOM (extractable organic matter) from PM2.5. Moreover, ZLN005 attenuated EOM-induced PGC-1α downregulation, mitochondrial dysfunction/biogenesis, and apoptosis. EOM exposure not only decreased PGC-1α expression levels, but suppressed its activity via deacetylation, and SIRT1 activity is required during both processes. We then found that SIRT1 expression levels and NAD+/NADH ratio were reduced in an AHR-dependent way. We also demonstrated that AHR directly suppressed the transcription of SIRT1 while promoted the transcription of TiPARP which consumed NAD+. In conclusion, our study suggests that PM2.5 induces mitochondrial damage and heart defects via AHR/SIRT1/PGC-1α signal pathway.


Assuntos
NAD , Sirtuína 1 , Animais , Sirtuína 1/genética , Peixe-Zebra , Apoptose , Material Particulado/toxicidade
4.
Pediatr Res ; 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347169

RESUMO

INTRODUCTION: Epidemiological evidence suggests an association between CS and offspring metabolic syndrome (MetS), but whether a causal relationship exists is unknown. METHODS: In this study, timed-mated Wistar rat dams were randomly assigned to cesarean section (CS), vaginal delivery (VD), and surrogate groups. The offspring from both CS and VD groups were reared by surrogate dams until weaning, and weaned male offspring from both groups were randomly assigned to receive normal diet (ND) or high-fat/high-fructose diet (HFF) ad libitum for 39 weeks. RESULTS: By the end of study, CS-ND offspring gained 17.8% more weight than VD-ND offspring, while CS-HFF offspring gained 36.4% more weight than VD-HFF offspring. Compared with VD-ND offspring, CS-ND offspring tended to have increased triglycerides (0.27 mmol/l, 95% CI, 0.05 to 0.50), total cholesterol (0.30 mmol/l, -0.08 to 0.68), and fasting plasma glucose (FPG) (0.30 mmol/l, -0.01 to 0.60); more pronounced differences were observed between CS-HFF and VD-HFF offspring in these indicators (triglyceride, 0.66 mmol/l, 0.35 to 0.97; total cholesterol, 0.46 mmol/l, 0.13 to 0.79; and FPG, 0.55 mmol/l, 0.13 to 0.98). CONCLUSIONS: CS offspring were more prone to adverse metabolic profile and HFF might exacerbate this condition, indicating the association between CS and MetS is likely to be causal. IMPACT: Whether the observed associations between CS and MetS in non-randomized human studies are causally relevant remains undetermined. Compared with vaginally born offspring rats, CS born offspring gained more body weight and tended to have compromised lipid profiles and abnormal insulin sensitivity, suggesting a causal relationship between CS and MetS that may be further amplified by a high-fat/high-fructose diet. Due to the high prevalence of CS births globally, greater clinical consideration must be given to the potential adverse effects of CS, and whether these risks should be made known to patients in clinical practice merits evaluation.

5.
Int J Biol Macromol ; 257(Pt 2): 128707, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38101663

RESUMO

The proper management of phosphorus (P) from wastewater is crucial for sustainable development consideration. Herein, we developed a strategy which combines adsorption via tailored adsorbents and electrochemically-driven struvite precipitation (ESP) for P recovery. Novel polydopamine-modified Ce-MOF/chitosan composite beads (PDA@Ce-MOF-CS) were prepared by a facile in situ growth of Ce-MOF crystals incorporated natural polymers and PDA coating. The physicochemical properties of PDA@Ce-MOF-CS were characterized. Both batch and fixed-bed column experiments were conducted to evaluate its adsorption performances. Representatively, PDA@Ce-MOF-CS performed good selectivity for P removal and exhibited a maximum adsorption capacity of 161.13 mg P/g at pH 3 and 318 K. Meanwhile, the developed adsorbent showed great reusability after ten regeneration cycles as well as good adsorption stability. The dominant mechanism for efficient P adsorption included electrostatic attraction, surface precipitation and ligand exchange. Interestingly, PDA@Ce-MOF-CS exhibited a remarkable adsorption capacity of 92.86 mg P/g by treating real P-rich electroplating wastewater, and the desorbed P in the eluate could be effectively recovered and converted into a solid fertilizer as struvite via ESP. Overall, this work provided a new research direction for P recovery from wastewater as struvite by combined technologies with the help of macroscopic MOF architectures.


Assuntos
Quitosana , Poluentes Químicos da Água , Estruvita , Fósforo , Quitosana/química , Águas Residuárias , Adsorção , Poluentes Químicos da Água/análise , Cinética , Fosfatos/química
6.
Artigo em Inglês | MEDLINE | ID: mdl-38083423

RESUMO

Retinal visual prosthetic devices aim to restore vision via electrical stimulation delivered on the retina. While a number of devices have been commercially available, the stimulation strategies applied have not met the expectations of end-users. These stimulation strategies involve the neurons being activated based on their spatial properties, regardless of their functions, which may lead to lower visual acuity. The ability to predict light-evoked neural activities thus becomes crucial for the development of a retinal prosthetic device with better visual acuity. In addition to temporal nonlinearity, the spatial relationship between the 2-dimensional light stimulus and the spiking activity of neuron populations is the main barrier to accurate predictions. Recent advances in deep learning offer a possible alternative for neural activity prediction tasks. With proven performance on nonlinear sequential data in fields such as natural language processing and computer vision, the emerging transformer model may be adapted to predict neural activities. In this study, we built and evaluated a deep learning model based on the transformer to explore its predictive capacity in light-evoked retinal spikes. Our preliminary results show that the model is possible to achieve good performance in this task. The high versatility of deep learning models may allow us to make retinal activity predictions in more complex physiological environments and potentially enhance the visual acuity of retinal prosthetic devices in the future by enabling us to anticipate the desired neural responses to electrical stimuli.


Assuntos
Células Ganglionares da Retina , Próteses Visuais , Células Ganglionares da Retina/fisiologia , Retina/fisiologia , Acuidade Visual , Estimulação Elétrica/métodos
7.
Sensors (Basel) ; 23(22)2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-38005675

RESUMO

Aiming at challenges such as the high complexity of the network model, the large number of parameters, and the slow speed of training and testing in cross-view gait recognition, this paper proposes a solution: Multi-teacher Joint Knowledge Distillation (MJKD). The algorithm employs multiple complex teacher models to train gait images from a single view, extracting inter-class relationships that are then weighted and integrated into the set of inter-class relationships. These relationships guide the training of a lightweight student model, improving its gait feature extraction capability and recognition accuracy. To validate the effectiveness of the proposed Multi-teacher Joint Knowledge Distillation (MJKD), the paper performs experiments on the CASIA_B dataset using the ResNet network as the benchmark. The experimental results show that the student model trained by Multi-teacher Joint Knowledge Distillation (MJKD) achieves 98.24% recognition accuracy while significantly reducing the number of parameters and computational cost.

8.
Inorg Chem ; 62(44): 18009-18013, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37870376

RESUMO

Ratiometric luminescent thermometers with excellent performance often require the luminescent materials to possess high thermal stability and relative sensitivity (Sr). However, such luminescent materials are very rare, especially in physiological (298-323 K) and high-temperature (>373 K) regions. Here we report the synthesis and luminescent property of [Tb0.995Eu0.005(pfbz)2(phen)Cl] (3), which not only exhibits high Sr in physiological temperature but also has a Sr up to 7.47% K-1 at 440 K, the largest Sr at 440 K in known lanthanide-based coordination compound luminescent materials.

9.
World J Gastrointest Surg ; 15(9): 2074-2082, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37901723

RESUMO

BACKGROUND: Lupus mesenteric vasculitis (LMV) is a serious condition that may occur as an acute manifestation of gastrointestinal (GI) involvement and is not easily diagnosed by physicians. Delayed diagnosis and treatment of LMV may lead to rapid disease progression and can be life threatening. CASE SUMMARY: A previously healthy 27-year-old woman presented with abdominal pain following a history of fatigue and consumption of cold water. Laboratory investigations, physical examinations, and enhanced abdominal computed tomography (CT) suggested systemic lupus erythematosus complicated by LMV. She received treatments, such as GI decompression, somatostatin, glucocorticoids, and immunosuppressants, and was evaluated using color ultrasonography. Twenty days later, the patient reported no stomach discomfort and was able to consume semi-liquid food. Laboratory investigations showed that inflammatory factors decreased to normal levels and complement levels increased slightly. One year after discharged, she recovered with methylprednisolone being tapered to 4 mg per day, mycophenolate mofetil to 0.75 g bid, and hydroxychloroquine to 0.2 g bid; however, only C3 complement level was slightly below the normal level. CONCLUSION: Early diagnosis of LMV is essential for successful treatment; this depends on a combination of clinical manifestations, laboratory investigations, and imaging findings. Enhanced CT is preferred, but ultrasonography can be used for prompt screening and follow-up.

10.
J Cancer Res Clin Oncol ; 149(19): 17371-17381, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37843556

RESUMO

BACKGROUND: Convincing studies demonstrated that cervicovaginal microbiota disorder and toll-like receptor 9 (TLR9) high expression were related to cervical carcinogenesis. However, the effects of cervicovaginal microbiota integration TLR9 in cervical cancerization are unclear. Based on the biological basis that unmethylated cytosine-phosphate-guanine (CpG) motifs of bacteria could activate TLR9, we explored the effects of cervicovaginal microbiota disorder and CpG motif-TLR9 axis change in cervical carcinogenesis. METHODS: A total of 341 participants, including 124 normal cervical (NC), 90 low-grade cervical intraepithelial neoplasia (CIN1), 78 high-grade cervical intraepithelial neoplasia (CIN2/3) and 49 squamous cervical cancer (SCC), diagnosed by pathology were enrolled in the study. Here, metagenomic shotgun sequencing was used to reveal cervicovaginal microbiota characteristics, and TLR9 protein was detected by western blotting. RESULTS: Our results showed that the diversity of cervicovaginal microbiota gradually increased along with the poor development of cervical lesions, showing the abundance of Lactobacillus crispatus and Lactobacillus iners decreased, while the abundance of pathogenic bacteria gradually increased. The level of TLR9 expression was gradually increased with cervicovaginal microbiota diversity increasing, the abundance of Lactobacillus decreasing, and we found a positive correlation dependency relationship (r = 0.384, P = 0.002) between TLR9 and GTCGTT motif content. Stratified analysis based on HPV16 infection, we found that the characteristics of cervicovaginal microbiota and increased TLR9 expression were also closely related to HPV16 infection. CONCLUSIONS: Cervicovaginal microbiota dysbiosis might lead to the CpG motif increased, which was closely associated with TLR9 high expression, and ultimately might promote the progression of cervical lesions.


Assuntos
Carcinogênese , Colo do Útero , Microbiota , Receptor Toll-Like 9 , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Vagina , Feminino , Humanos , Bactérias , Fosfatos , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/metabolismo , Displasia do Colo do Útero/genética , Displasia do Colo do Útero/microbiologia , Displasia do Colo do Útero/patologia , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/microbiologia , Neoplasias do Colo do Útero/patologia , Vagina/microbiologia , Colo do Útero/microbiologia
11.
J Immunother Cancer ; 11(9)2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37657842

RESUMO

Current methods for biomarker discovery and target identification in immuno-oncology rely on static snapshots of tumor immunity. To thoroughly characterize the temporal nature of antitumor immune responses, we developed a 34-parameter spectral flow cytometry panel and performed high-throughput analyses in critical contexts. We leveraged two distinct preclinical models that recapitulate cancer immunoediting (NPK-C1) and immune checkpoint blockade (ICB) response (MC38), respectively, and profiled multiple relevant tissues at and around key inflection points of immune surveillance and escape and/or ICB response. Machine learning-driven data analysis revealed a pattern of KLRG1 expression that uniquely identified intratumoral effector CD4 T cell populations that constitutively associate with tumor burden across tumor models, and are lost in tumors undergoing regression in response to ICB. Similarly, a Helios-KLRG1+ subset of tumor-infiltrating regulatory T cells was associated with tumor progression from immune equilibrium to escape and was also lost in tumors responding to ICB. Validation studies confirmed KLRG1 signatures in human tumor-infiltrating CD4 T cells associate with disease progression in renal cancer. These findings nominate KLRG1+ CD4 T cell populations as subsets for further investigation in cancer immunity and demonstrate the utility of longitudinal spectral flow profiling as an engine of dynamic biomarker discovery.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Linfócitos T CD4-Positivos , Subpopulações de Linfócitos T , Imunoterapia , Biomarcadores , Receptores Imunológicos , Lectinas Tipo C
12.
Medicina (Kaunas) ; 59(7)2023 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-37512096

RESUMO

Background and Objectives: Triple-negative breast cancer (TNBC), a highly aggressive and heterogeneous subtype of breast cancer, accounts for ap-proximately 10-15% of all breast cancer cases. Currently, there is no effective therapeutic target for TNBC. Tu-mor-associated macrophages (TAMs), which can be phenotypically classified into M1 and M2 subtypes, have been shown to influence the prognosis of various cancers, including ovarian cancer. This study aimed to investigate the role of M1/M2 macrophages in the TNBC tumor microenvironment (TME), with a focus on identifying prognostic genes and predicting immunotherapy response. Materials and Methods: The study employed the CIBERSORT algorithm to analyze immune cell expression in the TME. Genes associated with the M1/M2 macrophage ratio were identified using Pearson correlation analysis and used to classify patients into dis-tinct clusters. Dimensionality reduction techniques, including univariate Cox regression and Lasso, were applied to these genes. The expression of prognostic genes was validated through immunohistochemistry. Results: The study found a high prevalence of TAMs in the TME. Among the patient clusters, 109 differentially expressed genes (DEGs) were identified. Three significant DEGs (LAMP3, GZMB, and CXCL13) were used to construct the riskScores. The riskScore model effectively stratified patients based on mortality risk. Gene Set Enrichment Analysis (GSEA) associated the riskScore with several significant pathways, including mismatch repair, JAK/STAT3 signaling, VEGF signaling, antigen processing presentation, ERBB signaling, and P53 signaling. The study also predicted patient sensitivity to im-munotherapy using the riskScores. The expression of the three significant DEGs was validated through immunohisto-chemistry. Conclusions: The study concluded that the riskScore model, based on the M1/M2 macrophage ratio, is a valid prognostic tool for TNBC. The findings underscore the importance of the TME in TNBC progression and prognosis and highlight the po-tential of the riskScore model in predicting immunotherapy response in TNBC patients.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/terapia , Prognóstico , Imunoterapia , Contagem de Células Sanguíneas , Microambiente Tumoral/genética
13.
Angew Chem Int Ed Engl ; 62(35): e202305985, 2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37403425

RESUMO

Covalent organic frameworks (COFs) have wide-ranging applications, and their host-guest interactions play an essential role in the achievement of COF functions. To investigate these host-guest interactions, it is necessary to locate all atoms, especially hydrogen atoms. However, it is difficult to determine the hydrogen atomic positions in COFs because of the complexities in synthesizing high-quality large single crystals. Three-dimensional electron diffraction (3D ED) has unique advantages for the structural determination of nanocrystals and identification of light atoms. In this study, it was demonstrated for the first time that the hydrogen atoms of a COF, not only on the framework but also on the guest molecule, can be located by 3D ED using continuous precession electron diffraction tomography (cPEDT) under cryogenic conditions. The host-guest interactions were clarified with the location of the hydrogen atoms. These findings provide novel insights into the investigation of COFs.

14.
Nanomaterials (Basel) ; 13(12)2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-37368290

RESUMO

Clinoptilolite (CP) was successfully synthesized via a hydrothermal route in the presence of polyethylene glycol (PEG), and it was then delaminated by washing using Zn2+ containing acid. HKUST-1, as one kind of the Cu-based MOFs, showed a high CO2 adsorption capacity owing to its large pore volume and specific surface area. In the present work, we selected one of the most efficient ways for preparing the HKUST-1@CP compounds via coordination between exchanged Cu2+ and ligand (trimesic acid). Their structural and textural properties were characterized by XRD, SAXS, N2 sorption isotherms, SEM, and TG-DSC profiles. Particularly, the effect of the additive PEG (average molecular weight of 600) on the induction (nucleation) periods and growth behaviors were detailed and investigated in the hydrothermal crystallization procedures of synthetic CPs. The corresponding activation energies of induction (En) and growth (Eg) periods during crystallization intervals were calculated. Meanwhile, the pore size of the inter-particles of HKUST-1@CP was 14.16 nm, and the BET specific area and pore volume were 55.2 m2/g and 0.20 cm3/g, respectively. Their CO2 and CH4 adsorption capacities and selectivity were preliminarily explored, showing 0.93 mmol/g for HKUST-1@CP at 298 K with the highest selective factor of 5.87 for CO2/CH4, and the dynamic separation performance was evaluated in column breakthrough experiments. These results suggested an efficient way of preparing zeolites and MOFs composites that is conducive to being a promising adsorbent for applications in gas separation.

15.
Front Public Health ; 11: 1128552, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37213615

RESUMO

Background: Most studies have focused on overweight/obesity and its secular trend, with insufficient studies on the factors influencing thinness and trends recently. To examine the trends of prevalence and sociodemographic determinants of thinness, overweight, and obesity among Chinese children and adolescents aged 7 to 18 years from 2010 to 2018. Methods: This study was based on cross-sectional data of 11,234 children and adolescents aged 7 to 18 years from the Chinese Family Panel Studies (CFPS) in 2010, 2014, and 2018, including anthropometric and sociodemographic characteristics variables. The nutritional status of each individual was determined according to China and WHO criteria. The demographic characteristics of different subgroups were tested by chi-square, and log-binomial regression was used to analyze the trend of prevalence and the relationship between sociodemographic characteristics and different nutritional statuses. Results: After adjusting for age, from 2010 to 2018, the overall prevalence of thinness decreased, and the prevalence of overweight increased in Chinese children and adolescents. The overall prevalence of obesity declined in boys and increased in girls, but in adolescents aged 16-18 years, it increased significantly. Log-binomial regression analysis showed that among all subjects, time (years), 16-18 years were negatively associated with thinness, while 13-15 years, walking to school, large family size, and paternal age at childbirth older than 30 years old were positively associated with thinness; 10-12/13-15/16-18 years, boarding at school, medium and large family sizes, and mother's education at junior middle school/junior high school and above were negatively associated with overweight/obesity, while time (years), boys were positively associated with overweight/obesity in the multivariate model by adjusting for the statistically significant factors (all p < 0.05). Conclusion: Chinese children and adolescents are facing a double burden of malnutrition. Future public health policies and interventions should prioritize high-risk groups specifically young age groups, boys, larger family sizes and so on.


Assuntos
Sobrepeso , Magreza , Adolescente , Criança , Feminino , Humanos , Masculino , Estudos Transversais , População do Leste Asiático , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Magreza/epidemiologia
16.
Toxicology ; 487: 153466, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36841371

RESUMO

Accumulating evidence suggests an association between maternal PM2.5 exposure and congenital heart diseases, but the underlying mechanisms remain unclear. We previously reported that PM2.5 induces cardiac malformations in zebrafish embryos via the aryl hydrocarbon receptor (AHR) pathway, which mediates the generation of reactive oxygen species (ROS). Since mitochondria are not only the main source of ROS but also sensitive to oxidative damage, we hypothesize that mitochondria may play an important role in the cardiac developmental toxicity of PM2.5. In this study, we demonstrated that extractable organic matter (EOM) from PM2.5 caused mitochondrial dysfunction in the heart of zebrafish embryos, including increased mitochondrial ROS (mtROS) levels, mitochondrial permeability transition pore (mPTP) opening, mitochondrial membrane potential (MMP) collapse, reduced mitochondrial ATP levels, and decreased expression levels of the mRNAs encoding mitochondrial proteins, which were attenuated by either pharmacological or genetic inhibition of AHR. We further demonstrated that improving mitochondrial function by inhibiting mPTP opening with Cyclosporin A suppressed the EOM-induced intracellular ROS and mtROS generation, MMP collapse, intrinsic apoptosis, and heart defects. Moreover, the EOM-induced mPTP opening was counteracted by inhibiting mtROS with mitoquinone mesylate (MitoQ). Supplementation with MitoQ also attenuated the EOM-induced mitochondrial dysfunction, apoptosis and heart defects. Additionally, knockdown of cyp1a1 but not cyp1b1 attenuated the EOM-induced mtROS generation and heart defects. Taken together, this study indicates that PM2.5 triggers mtROS generation via AHR-mediated cyp1a1 overexpression, which then causes mPTP opening and mitochondrial dysfunction, leading to apoptosis and heart defects.


Assuntos
Cardiopatias Congênitas , Peixe-Zebra , Animais , Peixe-Zebra/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Material Particulado/toxicidade , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Mitocôndrias/metabolismo , Potencial da Membrana Mitocondrial
17.
bioRxiv ; 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36711647

RESUMO

Current methods for biomarker discovery and target identification in immuno-oncology rely on static snapshots of tumor immunity. To thoroughly characterize the temporal nature of antitumor immune responses, we developed a 34-parameter spectral flow cytometry panel and performed high-throughput analyses in critical contexts. We leveraged two distinct preclinical models that recapitulate cancer immunoediting (NPK-C1) and immune checkpoint blockade (ICB) response (MC38), respectively, and profiled multiple relevant tissues at and around key inflection points of immune surveillance and escape and/or ICB response. Machine learning-driven data analysis revealed a pattern of KLRG1 expression that uniquely identified intratumoral effector CD4 T cell populations that constitutively associate with tumor burden across tumor models, and are lost in tumors undergoing regression in response to ICB. Similarly, a Helios - KLRG1 + subset of tumor-infiltrating regulatory T cells (Tregs) was associated with tumor progression from immune equilibrium to escape, and were also lost in tumors responding to ICB. Validation studies confirmed KLRG1 signatures in human tumorinfiltrating CD4 T cells associate with disease progression in renal cancer. These findings nominate KLRG1 + CD4 T cell populations as subsets for further investigation in cancer immunity and demonstrate the utility of longitudinal spectral flow profiling as an engine of dynamic biomarker and/or target discovery.

18.
Cell Biol Toxicol ; 39(4): 1753-1772, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36520315

RESUMO

Triptolide (TP) exhibits therapeutic potential against multiple diseases. However, its application in clinics is limited by TP-induced hepatoxicity. TP can activate invariant natural killer T (iNKT) cells in the liver, shifting Th1 cytokine bias to Th2 cytokine bias. The damaging role of iNKT cells in TP-induced hepatoxicity has been established, and iNKT cell deficiency can mitigate hepatotoxicity. However, the activation of iNKT cells in vitro by TP requires the presence of antigen-presenting cells. Therefore, we hypothesized that TP could induce dendritic cells (DCs) to activate iNKT cells, thereby leading to hepatotoxicity. The hepatic conventional DCs (cDCs) exhibited immunogenic activities after TP administration, upregulating the expression of CD1d, co-stimulatory molecules, and IL-12. Neutralization with IL-12p40 antibody extenuated TP-induced hepatotoxicity and reduced iNKT cell activation, suggesting that IL-12 could cause liver injury by activating iNKT cells. TP triggered the activation and upregulation of STING signaling pathway and increased endoplasmic reticulum (ER) stress. Downregulation of STING reduced cDC immunogenicity, inhibiting the activation of iNKT cells and hepatic damage. These indicated the regulatory effects of STING pathway on cDCs and iNKT cells, and the important roles it plays in hepatoxicity. ER stress inhibitor, 4-phenylbutyrate (4-PBA), also suppressed iNKT cell activation and liver injury, which might be regulated by the STING signaling pathway. Our results demonstrated the possible mechanisms underlying TP-induced hepatoxicity, where the activation of cDCs and iNKT cells was stimulated by upregulated STING signaling and increased ER stress as a result of TP administration.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Células T Matadoras Naturais , Humanos , Células T Matadoras Naturais/metabolismo , Transdução de Sinais , Citocinas/metabolismo , Interleucina-12/metabolismo , Interleucina-12/farmacologia , Estresse do Retículo Endoplasmático , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo
19.
Front Pediatr ; 11: 1301137, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38322243

RESUMO

Objective: This study offers a bibliometric analysis of the current situation, hotspots, and cutting-edge domains of genetic factors of adolescent idiopathic scoliosis (AIS). Methods: All publications related to genetic factors of AIS from January 1, 1992, to February 28, 2023, were searched from the Web of Science. CiteSpace software was employed for bibliometric analysis, collecting information about countries, institutions, authors, journals, and keywords of each article. Results: A cumulative number of 308 articles have been ascertained. Since 2006, publications relating to genetic factors of AIS have significantly increased. China leads in both productivity and influence in this area, with the Chinese Academy of Medical Sciences being the most productive institution. The most prolific scholars in this field are Y. Qiu and Z. Z. Zhu. The publications that contributed the most were from Spine and European Spine Journal. The most prominent keywords in the genetic factors of AIS were "fibrillin gene", "menarche", "calmodulin", "estrogen receptor gene", "linkage analysis", "disc degeneration", "bone mineral density", "melatonin signaling dysfunction", "collagen gene", "mesenchymal stem cell", "LBX1", "promoter polymorphism", "Bone formation", "cerebrospinal fluid flow" and "extracellular matrix". Conclusion: This analysis provides the frontiers and trends of genetic factors in AIS, including relevant research, partners, institutions and countries.

20.
Angew Chem Int Ed Engl ; 61(49): e202213960, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36178633

RESUMO

We report a metal-organic framework (MOF) with a rare two-dimensional (2D) secondary building unit (SBU). The SBU comprises mixed-valent Fe2+ and Fe3+ metal ions bridged by oxygen atoms pertaining to the polytopic ligand 3,3',4,4',5,5'-hexahydroxybiphenyl, which also define the iron-oxide 2D layers. Overall, the anionic framework exhibits rare topology and evidences strong electronic communication between the mixed-valence iron sites. These results highlight the importance of dimensionality control of MOF SBUs for discovering new topologies in reticular chemistry, and especially for improving electronic communication within the MOF skeleton.

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