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1.
Water Res ; 255: 121530, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38564897

RESUMO

A huge chemical potential difference exists between the acid mine drainage (AMD) and the alkaline neutralization solution, which is wasted in the traditional AMD neutralization process. This study reports, for the first time, the harvest of this chemical potential energy through a controlled neutralization of AMD using H+-conductive films. Polyamide films with controllable thickness achieved much higher H+ conductance than a commercially available cation exchange membrane (CEM). Meanwhile, the optimal polyamide film had an excellent H+/Ca2+ selectivity of 63.7, over two orders of magnitude higher than that of the CEM (0.3). The combined advantages of fast proton transport and high proton/ion selectivity greatly enhanced the power generation of the AMD battery. The power density was 3.1 W m-2, which is over one order of magnitude higher than that of the commercial CEM (0.2 W m-2). Our study provides a new sustainable solution to address the environmental issues of AMD while simultaneously enabling clean energy production.

2.
Nat Commun ; 15(1): 2825, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561362

RESUMO

Ten-eleven translocation (TET) 2 is an enzyme that catalyzes DNA demethylation to regulate gene expression by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine, functioning as an essential epigenetic regulator in various biological processes. However, the regulation and function of TET2 in adipocytes during obesity are poorly understood. In this study, we demonstrate that leptin, a key adipokine in mammalian energy homeostasis regulation, suppresses adipocyte TET2 levels via JAK2-STAT3 signaling. Adipocyte Tet2 deficiency protects against high-fat diet-induced weight gain by reducing leptin levels and further improving leptin sensitivity in obese male mice. By interacting with C/EBPα, adipocyte TET2 increases the hydroxymethylcytosine levels of the leptin gene promoter, thereby promoting leptin gene expression. A decrease in adipose TET2 is associated with obesity-related hyperleptinemia in humans. Inhibition of TET2 suppresses the production of leptin in mature human adipocytes. Our findings support the existence of a negative feedback loop between TET2 and leptin in adipocytes and reveal a compensatory mechanism for the body to counteract the metabolic dysfunction caused by obesity.


Assuntos
Dioxigenases , Leptina , Animais , Humanos , Masculino , Camundongos , Adipócitos/metabolismo , Peso Corporal , Dioxigenases/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Retroalimentação , Leptina/metabolismo , Mamíferos/metabolismo , Obesidade/genética , Obesidade/metabolismo
3.
Anal Sci ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649628

RESUMO

Analyzing new psychoactive substances (NPSs) in forensic laboratories present a formidable challenge globally. Within illicit drug analysis, gas chromatography-mass spectrometry (GC-MS) emerges as a robust analytical tool. This study endeavors to assess and compare peak resolution in the analysis of illicit drugs, specifically focusing on 21 synthetic cathinones, encompassing 9 cathinone isomers. Varied GC-MS operating conditions, including distinct GC-MS columns and thermal gradients, were systematically employed for the simultaneous analysis of these synthetic cathinones. The study utilized HP-1 nonpolar and HP-5MS low-bleed columns to achieve optimal analyte resolution through modulation of GC-MS oven conditions. Mass spectra were meticulously recorded within a mass-to-charge (m/z) range spanning from 40 to 500 in full scan mode. The data showed that the cathinone isomers slightly differed in retention times and mass spectra. The GC oven conditions affected the peak resolution for chromatographic separation even with the same column. The peak resolution improved using a slower thermal gradient heat speed with a prolonged analysis time. Conclusively, the interplay of GC columns and thermal gradients emerged as pivotal factors impacting peak resolution in the analysis of illicit drugs. These empirical insights contribute to a nuanced understanding of peak resolution dynamics and facilitate the identification of synthetic cathinones, including their isomers, in seized materials through the judicious application of GC-MS methodologies.

4.
Int J Surg ; 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38446845

RESUMO

BACKGROUND: Omentoplasty is commonly used in various surgeries. However, its effectiveness is unsure due to lack of convincing data and research. To clarify the impact of omentoplasty on postoperative complications of various procedures, this systematic review and meta-analysis was performed. METHODS: A systematic review of published literatures from four databases: PubMed, Web of Science, Cochrane Library, and Embase before July 14, 2022. We primarily included publications on five major surgical operations performed in conjunction with omentoplasty: thoracic surgery, esophageal surgery, gastrointestinal surgery, pelvi-perineal surgery, and liver surgery. The protocol was registered in PROSPERO. RESULTS: This review included 25 273 patients from 91 studies (n=9 670 underwent omentoplasty). Omentoplasty was associated with a lower risk of overall complications particularly in gastrointestinal (RR 0.53; 95%CI 0.39-0.72) and liver surgery (RR 0.54; 95%CI 0.39-0.74). Omentoplasty reduced the risk of postoperative infection in thoracic (RR 0.38; 95%CI 0.18-0.78) and liver surgery (RR 0.39; 95%CI 0.29-0.52). In patients undergoing esophageal (RR 0.89; 95%CI 0.80-0.99) and gastrointestinal (RR 0.28; 95%CI 0.23-0.34) surgery with a BMI greater than 25, omentoplasty is significantly associated with a reduced risk of overall complications compared to patients with normal BMI. No significant differences were found in pelvi-perineal surgery, except infection in patients whose BMI ranged from 25 kg/m2 to 29.9 kg/m2 (RR 1.25; 95%CI 1.04-1.50) and anastomotic leakage in patients aged over 60 (RR 0.59; 95%CI-0.39-0.91). CONCLUSION: Omentoplasty can effectively prevent postoperative infection. It is associated with a lower incidence of multiple postoperative complications in gastrointestinal and liver surgery.

5.
Postgrad Med J ; 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38439557

RESUMO

PURPOSE: To explore the relationship between liver fat content (LFC) and nonalcoholic fatty liver disease (NAFLD) and determine the new threshold of LFC to diagnose NAFLD. METHODS: The data from questionnaire survey, general physical examination, laboratory examination, and image examination were collected. Multivariate regression analysis, receiver operating characteristic curve analysis, smooth curve fitting, and threshold effect analysis were performed using the R software to investigate the relationship between LFC and NAFLD and to identify the new threshold of LFC to diagnose NAFLD. RESULTS: The prevalence of NAFLD was 30.42%, with a significantly higher prevalence in men than in women. Regression analyses demonstrated that LFC odds ratio [95% confidence interval (CI)] was 1.28 (95% CI: 1.24-1.31) in fully-adjust model. Analysis of the LFC quartile, with Q1 as a reference, revealed that the odds ratios of NAFLD were 1.47 (95% CI: 1.08-1.99), 2.29 (95% CI: 1.72-3.06), and 10.02 (95% CI: 7.45-13.47) for Q2, Q3, and Q4 groups, respectively. Smooth curve fitting and threshold effect analysis displayed a nonlinear relationship between LFC and NAFLD, and the threshold was 4.5%. The receiver operating characteristic curve indicated that when LFC was 4.5%, the area under curve (95% CI) was 0.80 (0.79-0.82), and the sensitivity and specificity of LFC in diagnosing NAFLD were 0.64% and 0.82%, respectively. CONCLUSION: The relationship between LFC and NAFLD was sigmoidal, with an inflection point of 4.5%.

7.
J Environ Manage ; 356: 120558, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38522270

RESUMO

Green innovation is important and beneficial for the green development of enterprises. The development of digital technology could improve the asymmetry of information and affect the enterprise's financing modes. Currently, a definitive conclusion about the relationship between the digital transformation and green technology innovation has not reached. Additionally, studies have not yet fully explored the impact pathways of corporate digital transformation on green innovation through corporate financing modes. To fill this void, this study collected data of Chinese A-share listed companies from 2010 to 2020. The empirical analysis results showed that digital transformation significantly enhanced enterprises' green innovation abilities. Furthermore, mediating models were utilized to explore how enterprise financing modes mediate the impact of digital transformation on the enterprise green innovation. Results indicated that through internal financing and bank loans as "bridges", digital transformation promoted enterprise green innovation. However, digital transformation did not have a significant impact on enterprise green innovation through venture capital. Moreover, heterogeneity analyses revealed significant differences among different groups of enterprises. This study expands the research field related to digital transformation and enterprise green innovation by providing empirical evidence to uncover the impact of digital transformation on enterprise green innovation. Findings of this study contribute not only to enterprise managerial decision-makers to better leverage digital transformation through corporate financing to accelerate green innovation, but also to government policymakers to design policies to stimulate enterprise green innovation.


Assuntos
Governo , Políticas , China
8.
Chem Commun (Camb) ; 60(31): 4194-4197, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38516918

RESUMO

A zincophilic PAN@Zn(OTF)2 (PZO) separator with an extremely thin thickness of 65.6 µm is introduced. This separator with a low cost of 6.1 $ m-2, exhibiting excellent mechanical and wettability properties. The cell with the PZO separator exhibits impressive electrochemical performances both in symmetrical Zn||Zn cell and Zn||NVO full cell.

9.
Neuroepidemiology ; 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38484721

RESUMO

OBJECTIVE: This study aims to examine the potential factors associated with marital status and determine the association between marital status and cognitive impairment in a multi-ethnic Asian population. METHOD: This study included 2321 participants from Singapore Multi-Ethnic Cohort revisit study (aged 40-89). Participants were classified into married and unmarried group at baseline and follow-up according to self-reported marital status. Mini-Mental Status Examination (MMSE) was administered, and cognitive impairment was defined as a MMSE <26. We conducted both cross-sectional and longitudinal analyses to examine the association of marital status at one time point as well as marital transition with cognitive impairment. RESULTS: Of the 2321 participants, a total of 1914 (82.5%) were married. The factors associated with marital status included younger age, male sex, higher household income, higher education, and higher physical activity levels. Additionally, married participants also had higher alternative healthy eating index (AHEI-2010) scores, and a lower burden of hypertension and diabetes. Among those who were married, the median (Q1, Q3) MMSE score was 29 (28,30) while those who were unmarried was 29 (27, 30) (p <0.01). Participants who had never been married had the highest odds of cognitive impairment compared to their married counterparts (Model III: OR=1.48, 95% CI: 1.03, 2.14). Older age (p-interaction value=0.003) and Indian ethnicity (p-interaction value=0.028) further strengthened these associations. CONCLUSION: Marriage was associated with lower odds of cognitive impairment. Marriage provides social support, companionship, and engagement in mentally stimulating activities contributing to better cognitive health. By identifying risk factors such as marital status, interventions and support systems can be developed to promote healthy cognitive aging.

10.
Dev Comp Immunol ; 155: 105158, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38467323

RESUMO

This study investigated the effects of two distinct probiotics, Leuconostoc mesenteroides B4 (B4) and Bacillus pumilus D5 (D5), along with their combination, on the diet of white shrimp (Litopenaeus vannamei) during an eight-week feeding trial. The diets tested included B4 + dextran at 107 CFU/g feed (the B4 group), D5 alone at 107 CFU/g feed (the D5 group), and a combination of B4 + dextran and D5 at 5 × 106 CFU/g feed each (the B4+dextran + D5 group). Relative to the control group, those administered probiotics exhibited moderate enhancements in growth. By the eighth week, the weight gain for the B4, D5, and B4+D5 groups was 696.50 ± 78.15%, 718.53 ± 130.73%, and 693.05 ± 93.79%, respectively, outperforming the control group's 691.66 ± 31.10% gain. The feed conversion ratio was most efficient in the B4 group (2.16 ± 0.06), closely followed by B4+D5 (2.21 ± 0.03) and D5 (2.22 ± 0.06), with the control group having the highest ratio (2.27 ± 0.03). While phenoloxidase activity was somewhat elevated in the B4 and D5 groups, no significant differences were noted in respiratory burst activity or total hemocyte count across all groups. Challenge tests at weeks 4 and 8 showed that the B4 + D5 combination offered superior protection against AHPND-causing Vibrio parahaemolyticus. The 4-week cumulative survival rate was highest in shrimp treated with B4 + dextran + D5 (56.25%), followed by B4 + dextran (31.25%), control (18.75%), and lowest in D5 (12.5%). By week 8, the B4 + dextran + D5 (43.75%) and B4 + dextran (37.5%) groups significantly outperformed the control group (6.25%, p < 0.05), with no significant difference observed between the D5 group (37.5%) and the control group at day 56. Analysis of the shrimp's foregut microbiota revealed an increase in unique OTUs in the B4 and B4 + D5 groups. Compared to the control, Proteobacteria abundance was reduced in all probiotic groups. Potential pathogens like Vibrio, Bacteroides, Neisseria, Botrytis, Clostridioides, and Deltaentomopoxvirus were detected in the control but were reduced or absent in probiotic groups. Beneficial microbes such as Methanobrevibacter and Dictyostelium in the B4+D5 group, and Sugiyamaella in the B4 group, showed significant increases. Probiotics also led to higher transcript levels of nitric oxide synthase in the hemocytes, and lysozyme and transglutaminase in the midgut, along with lysozyme and α2-macroglobulin in the foregut. Notably, the combined B4 + D5 probiotics synergistically enhanced the expression of superoxide dismutase and prophenoloxidase in the foregut, indicating an improved immune response. In summary, this study demonstrates that the probiotics evaluated, especially when used in combination, significantly boost the expression of specific immune-related genes, enhance the bacterial diversity and richness of the intestine, and thus prevent the colonization and proliferation of Vibrio spp. in L. vannamei.


Assuntos
Bacillus , Dictyostelium , Leuconostoc mesenteroides , Penaeidae , Probióticos , Vibrio parahaemolyticus , Animais , Resistência à Doença , Muramidase/metabolismo , Leuconostoc , Dextranos/metabolismo , Vibrio parahaemolyticus/fisiologia , Dieta , Imunidade Inata
11.
RSC Adv ; 14(12): 8240-8250, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38482069

RESUMO

Prostate-specific antigen (PSA) serves as a critical biomarker for the early detection and continuous monitoring of prostate cancer. However, commercial PSA detection methods primarily rely on antigen-antibody interactions, leading to issues such as high costs, stringent storage requirements, and potential cross-reactivity due to PSA variant sequence homology. This study is dedicated to the precise design and synthesis of molecular entities tailored for binding with PSA. By employing a million-level virtual screening to obtain potential PSA compounds and effectively guiding the synthesis using machine learning methods, the resulting lead compounds exhibit significantly improved binding affinity compared to those developed before by researchers using high-throughput screening for PSA, substantially reducing screening and development costs. Unlike antibody detection, the design of these small molecules offers promising avenues for advancing prostate cancer diagnostics. Furthermore, this study establishes a systematic framework for the rapid development of customized ligands that precisely target specific protein entities.

12.
Sci Rep ; 14(1): 4932, 2024 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-38418847

RESUMO

One potential approach for treating obesity is to increase energy expenditure in brown and white adipose tissue. Here we aimed to achieve this outcome by targeting mitochondrial uncoupler compounds selectively to adipose tissue, thus avoiding side effects from uncoupling in other tissues. Selective drug accumulation in adipose tissue has been observed with many lipophilic compounds and dyes. Hence, we explored the feasibility of conjugating uncoupler compounds with a lipophilic C8-hydrocarbon chain via an ether bond. We found that substituting the trifluoromethoxy group in the uncoupler FCCP with a C8-hydrocarbon chain resulted in potent uncoupling activity. Nonetheless, the compound did not elicit therapeutic effects in mice, likely as a consequence of metabolic instability resulting from rapid ether bond cleavage. A lipophilic analog of the uncoupler compound 2,6-dinitrophenol, in which a C8-hydrocarbon chain was conjugated via an ether bond in the para-position (2,6-dinitro-4-(octyloxy)phenol), exhibited increased uncoupling activity compared to the parent compound. However, in vivo pharmacokinetics studies suggested that 2,6-dinitro-4-(octyloxy)phenol was also metabolically unstable. In conclusion, conjugation of a hydrophobic hydrocarbon chain to uncoupler compounds resulted in sustained or improved uncoupling activity. However, an ether bond linkage led to metabolic instability, indicating the need to conjugate lipophilic groups via other chemical bonds.


Assuntos
Tecido Adiposo Marrom , Tecido Adiposo , Camundongos , Animais , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo/metabolismo , Obesidade/metabolismo , Metabolismo Energético , Tecido Adiposo Branco/metabolismo , Éteres , Fenóis/farmacologia , Proteína Desacopladora 1/metabolismo
13.
Int J Mol Sci ; 25(3)2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38338646

RESUMO

Chinese cabbage is the most widely consumed vegetable crop due to its high nutritional value and rock-bottom price. Notably, the presence of the physiological disease petiole spot significantly impacts the appearance quality and marketability of Chinese cabbage. It is well known that excessive nitrogen fertilizer is a crucial factor in the occurrence of petiole spots; however, the mechanism by which excessive nitrogen triggers the formation of petiole spots is not yet clear. In this study, we found that petiole spots initially gather in the intercellular or extracellular regions, then gradually extend into intracellular regions, and finally affect adjacent cells, accompanied by cell death. Transcriptomic and proteomic as well as physiology analyses revealed that the genes/proteins involved in nitrogen metabolism exhibited different expression patterns in resistant and susceptible Chinese cabbage lines. The resistant Chinese cabbage line has high assimilation ability of NH4+, whereas the susceptible one accumulates excessive NH4+, thus inducing a burst of reactive oxygen species (ROS). These results introduce a novel perspective to the investigation of petiole spot induced by the nitrogen metabolism pathway, offering a theoretical foundation for the development of resistant strains in the control of petiole spot.


Assuntos
Brassica , Proteômica , Perfilação da Expressão Gênica , Transcriptoma , Brassica/metabolismo , Nitrogênio/metabolismo
14.
Behav Res Ther ; 175: 104502, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38402674

RESUMO

Disgust imagery represents a potential pathological mechanism for disgust-related disorders. However, it remains controversial as to whether disgust can be conditioned with disgust-evoking mental imagery serving as the unconditioned stimulus (US). Therefore, we examined this using a conditioned learning paradigm in combination with event-related potential (ERP) analysis in 35 healthy college students. The results indicated that the initial neutral face (conditioned stimulus, CS+) became more disgust-evoking, unpleasant, and arousing after pairing with disgust-evoking imagery (disgust CS+), compared to pairing with neutral (neutral CS+) and no (CS-) imagery. Moreover, we observed that mental imagery-based disgust conditioning was resistant to extinction. While the disgust CS + evoked larger P3 and late positive potential amplitudes than CS- during acquisition, no significant differences were found between disgust CS+ and neutral CS+, indicating a dissociation between self-reported and neurophysiological responses. Future studies may additionally acquire facial EMG as an implicit index of conditioned disgust. This study provides the first neurobiological evidence that associative disgust learning can occur without aversive physical stimuli, with implications for understanding how disgust-related disorders may manifest or deteriorate without external perceptual aversive experiences, such as in obsessive-compulsive disorder (OCD).


Assuntos
Asco , Transtorno Obsessivo-Compulsivo , Humanos , Emoções/fisiologia , Medo/psicologia , Aprendizagem , Transtorno Obsessivo-Compulsivo/psicologia , Extinção Psicológica/fisiologia
15.
Environ Sci Pollut Res Int ; 31(11): 17481-17493, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38342832

RESUMO

Excessive phosphorus will lead to eutrophication in aquatic environment; the efficient removal of phosphorus is crucial for wastewater engineering and surface water management. This study aimed to fabricate a nanorod-like sepiolite-supported MgO (S-MgO) nanocomposite with high specific surface area for efficient phosphate removal using a facile microwave-assisted method and calcining processes. The impact of solution pH, adsorbent dosage, contact time, initial phosphate concentrations, Ca2+ addition, and N/P ratio on the phosphate removal was extensively examined by the batch experiments. The findings demonstrated that the S-MgO nanocomposite exhibited effective removal performance for low-level phosphate (0 ~ 2.0 mM) within the pH range of 3.0 ~ 10.0. Additionally, the nanocomposite can synchronously remove phosphate and ammonium in high-level nutrient conditions (> 2.0 mM), with the maximum removal capacities of 188.49 mg P/g and 89.78 mg N/g. Quantitative and qualitative analyses confirmed the successful harvesting of struvite in effluent with high-phosphate concentrations, with the mechanisms involved attributed to a synergistic combination of sorption and struvite crystallization. Due to its proficient phosphate removal efficiency, cost-effectiveness, and substantial removal capacity, the developed S-MgO nanocomposite exhibits promising potential for application in phosphorus removal from aquatic environments.


Assuntos
Silicatos de Magnésio , Nanocompostos , Poluentes Químicos da Água , Fósforo/química , Estruvita/química , Óxido de Magnésio , Nitrogênio , Fosfatos/química
16.
Clin Exp Optom ; : 1-9, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38175925

RESUMO

CLINICAL RELEVANCE: The possibility that changes in blue-yellow visual thresholds and some retinal thickness measures in children with diabetes mellitus may be observed before any visible fundus changes points to the possibility of these measures being a useful predictor that the risks of diabetic retinopathy are higher in some children than in others. INTRODUCTION: Previous studies showed mixed results on chromatic and achromatic contrast sensitivity early in the course of diabetes mellitus, and the findings of these studies may have been influenced by a lack of experimental sensitivity to visual deficits, a bias towards tritan-like errors or the cognitive demands of the tests and variations in sample composition. The purpose of this study was to evaluate colour and contrast thresholds and retinal thickness in children with type 1 diabetes mellitus compared with age-matched controls. METHODS: A prospective case-control study was carried out on 9-14-year-old children with type 1 diabetes mellitus (49 cases) and age matched controls (49) in which isoluminant red-green and blue-yellow and achromatic luminance contrast thresholds were measured. Fundus photography was used to grade diabetic retinopathy. Retinal thickness parameters were measured using optical coherence tomography. Data on the duration of diabetes mellitus, glycaemic control (HbA1c), blood glucose level, body mass index, blood pressure and blood oxygenation at the time of testing were obtained. RESULTS: The cases mostly had poorly controlled diabetes, HbA1c 8.6% (6.4-12.8%), for an average (range) duration of 5 (0.4-12) years. The cases had significantly higher blue-yellow thresholds (p = 0.02) and greater total retinal and inner retinal thickness (p < 0.05) than controls. No cases had diabetic retinopathy. Within the cases, poorer visual function and systemic health measures were associated with thinner retinal structures and greater global loss volume percentage in the ganglion cell complex. CONCLUSION: Blue-yellow thresholds of cases were raised compared to normal. Within the cases, higher luminance contrast thresholds were also associated with, mostly, ganglion cell complex reductions.

17.
Zootaxa ; 5399(1): 65-78, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38221175

RESUMO

The genera Echinovelleda Breuning, 1936 and Propedicellus Huang, Huang & Liu, 2020 are revised. The latterisconsideredto be ajunior synonym of theformer based on a comprehensive morphological investigation, especially on the characteristics of male endophallus. Two new species are described from China, viz. Echinovelleda mumuae Bi & Mu sp. nov. from Yunnan and Guangxi, and E. protochinensis Bi & Lin sp. nov. from Yunnan and Sichuan. New records are reported for previously described taxa including one new country record of a morphologically similar genus, Hechinoschema Thomson, 1857 from China. Illustrations of habitus, endophallic structure, major diagnostic features for all studied taxa, as well as a distributional map are provided.


Assuntos
Besouros , Masculino , Animais , Estruturas Animais , Tamanho Corporal , China , Tamanho do Órgão
18.
Bioact Mater ; 31: 463-474, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37701451

RESUMO

Human induced pluripotent stem cell derived cardiac fibroblasts (hiPSC-CFs) play a critical role in modeling human cardiovascular diseases in vitro. However, current culture substrates used for hiPSC-CF differentiation and expansion, such as Matrigel and tissue culture plastic (TCPs), are tissue mismatched and may provide pathogenic cues. Here, we report that hiPSC-CFs differentiated on Matrigel and expanded on tissue culture plastic (M-TCP-iCFs) exhibit transcriptomic hallmarks of activated fibroblasts limiting their translational potential. To alleviate pathogenic activation of hiPSC-CFs, we utilized decellularized extracellular matrix derived from porcine heart extracellular matrix (HEM) to provide a biomimetic substrate for improving hiPSC-CF phenotypes. We show that hiPSC-CFs differentiated and expanded on HEM (HEM-iCFs) exhibited reduced expression of hallmark activated fibroblast markers versus M-TCP-iCFs while retaining their cardiac fibroblast phenotype. HEM-iCFs also maintained a reduction in expression of hallmark genes associated with pathogenic fibroblasts when seeded onto TCPs. Further, HEM-iCFs more homogenously integrated into an hiPSC-derived cardiac organoid model, resulting in improved cardiomyocyte sarcomere development. In conclusion, HEM provides an improved substrate for the differentiation and propagation of hiPSC-CFs for disease modeling.

19.
Front Immunol ; 14: 1282612, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38143749

RESUMO

Background: The immune background of the overall population before and after the outbreak of SARS-CoV-2 in China remains unexplored. And the level of neutralizing antibodies is a reliable indicator of individual immunity. Objectives: This study aimed to assess the immune levels of different population groups during a viral outbreak and identify the factors influencing these levels. Methods: We measured the levels of neutralizing antibodies in 12,137 participants using the COVID19 Neutralizing Antibody Detection kit. The dynamics of neutralizing antibodies were analyzed using a generalized additive model, while a generalized linear model and multi-factor analysis of variance were employed to investigate the influencing factors. Additionally, statistical methods were used to compare neutralizing antibody levels among subgroups of the real-world population. Results: Participants who received booster doses exhibited significantly higher levels of neutralizing antibodies compared to those who received only one or two doses (p<0.001). Both elderly [22.55 (5.12, 62.03) IU/mL, 55%] and minors [21.41 (8.15, 45.06) IU/mL, 56%] showed lower positivity rates and neutralizing antibody levels compared to young adults [29.30 (9.82, 188.08) IU/mL, 62%] (p<0.001). Furthermore, the HIV-positive group demonstrated a slightly lower seropositivity rate compared to the healthy group across the three vaccination time points. Notably, three months after the large-scale infection, both the neutralizing antibody level and positivity rate in real-world populations were higher than the previous record [300 (300, 300) IU/mL, 89%; 27.10 (8.77, 139.28) IU/mL, 60%], and this difference was statistically significant. Conclusions: Increasing vaccine dosage enhances neutralizing antibody levels, resulting in greater and longer-lasting immunity. Monitoring immune levels in older individuals and those with AIDS is crucial. Additionally, the neutralizing antibodies generated from vaccination have not yet reached the threshold for achieving herd immunity, while individuals exhibit higher immune levels following a large-scale infection. These findings provide valuable insights for guiding new strategies in vaccine administration.


Assuntos
COVID-19 , Vacinas , Idoso , Adulto Jovem , Humanos , SARS-CoV-2 , Anticorpos Neutralizantes , China/epidemiologia , Anticorpos Antivirais
20.
J Comput Assist Tomogr ; 47(6): 959-966, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37948372

RESUMO

OBJECTIVE: This study aimed to perform an assessment of brain microstructure in children with autism aged 2 to 5 years using relaxation times acquired by synthetic magnetic resonance imaging. MATERIALS AND METHODS: Thirty-four children with autism spectrum disorder (ASD) (ASD group) and 17 children with global developmental delay (GDD) (GDD group) were enrolled, and synthetic magnetic resonance imaging was performed to obtain T1 and T2 relaxation times. The differences in brain relaxation times between the 2 groups of children were compared, and the correlation between significantly changed T1/T2 and clinical neuropsychological scores in the ASD group was analyzed. RESULTS: Compared with the GDD group, shortened T1 relaxation times in the ASD group were distributed in the genu of corpus callosum (GCC) ( P = 0.003), splenium of corpus callosum ( P = 0.002), and right thalamus (TH) ( P = 0.014), whereas shortened T2 relaxation times in the ASD group were distributed in GCC ( P = 0.011), left parietal white matter ( P = 0.035), and bilateral TH (right, P = 0.014; left, P = 0.016). In the ASD group, the T2 of the left parietal white matter is positively correlated with gross motor (developmental quotient [DQ] 2) and personal-social behavior (DQ5), respectively ( r = 0.377, P = 0.028; r = 0.392, P = 0.022); the T2 of the GCC was positively correlated with DQ5 ( r = 0.404, P = 0.018); and the T2 of the left TH is positively correlated with DQ2 and DQ5, respectively ( r = 0.433, P = 0.009; r = 0.377, P = 0.028). All significantly changed relaxation values were not significantly correlated with Childhood Autism Rating Scale scores. CONCLUSIONS: The shortened relaxometry times in the brain of children with ASD may be associated with the increased myelin content and decreased water content in the brain of children with ASD in comparison with GDD, contributing the understanding of the pathophysiology of ASD. Therefore, the T1 and T2 relaxometry may be used as promising imaging markers for ASD diagnosis.


Assuntos
Transtorno do Espectro Autista , Encefalopatias , Substância Branca , Humanos , Pré-Escolar , Criança , Transtorno do Espectro Autista/diagnóstico por imagem , Transtorno do Espectro Autista/patologia , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia
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