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Background: Emerging studies reveal a shared pathophysiological underpinning for metabolic problems and mental illnesses. The present study aimed to determine the association between atherogenic index of plasma (AIP) and the incidence of major depressive disorder (MDD). Methods: 7,951 subjects of US adults were collected from the National Health and Nutrition Examination Survey (NHANES) 2005-2018. MDD was evaluated through the Patient Health Questionnaire (PHQ-9). Multivariate logistic regression, sensitivity analysis, and spline smoothing plot method were used to identify the relationship between AIP and MDD. The cut-off point was calculated using recursive partitioning analysis when segmenting effects emerged. The area under the receiver operating characteristic (ROC) curve (AUC) and Hosmer-Lemeshow test were conducted to evaluate the performance of AIP in identifying MDD. Subgroup analyses and interaction tests were used to explore whether the association was stable in different populations. Results: A positive correlation between AIP and PHQ-9 score and MDD was both observed in 7,951 subjects included in the study, with a significant threshold of -0.42 determined using recursive partitioning analysis. In the fully adjusted model, a positive association between AIP and PHQ-9 score and MDD was observed (ß=0.46, 95% CI 0.14~0.78; OR=1.42, 95% CI 1.04~1.93). Individuals in the highest AIP quartile had a 0.39-unit higher PHQ-9 score (ß=0.39, 95% CI 0.12~0.66) and a significantly 33% greater risk of MDD than those in the lowest AIP quartile (OR=1.33, 95% CI 1.02~1.73). Spline smoothing plot analysis further confirmed the positive and non-linear association between AIP and PHQ-9 and MDD. ROC analysis (AUC=0.771) and the Hosmer-Lemeshow test (χ2 = 14.239, P=0.076) suggested an excellent performance and goodness-of-fit of the relatively optimal model. DCA and CIC analysis also revealed a favorable overall net benefit and clinical impact of the model. Subgroup analyses and interaction tests revealed that the association between AIP and PHQ-9 score and MDD remained consistent across different subgroups and was not modified by other covariates, and this positive correlation was more pronounced in those with diabetes or hypertension. Conclusion: An elevated AIP is linked to a higher chance of MDD, especially in those with diabetes or hypertension. Resolving dyslipidemia and managing comorbidities may help reduce the likelihood of developing MDD.
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Hypertension is the most prevalent cardiovascular disease, affecting one-third of adults. All antihypertensive drugs have potential side effects. Gut metabolites influence hypertension. The objective of this study was to identify antihypertensive gut metabolites through network pharmacology and molecular docking techniques and to validate their antihypertensive mechanisms via in vitro experiments. A total of 10 core antihypertensive targets and 18 gut metabolites that act on hypertension were identified. Four groups of protein metabolites, namely, CXCL8-baicalein, CXCL8-baicalin, CYP1A1-urolithin A, and PTGS2-equol, which have binding energies of - 7.7, - 8.5, - 7.2, and - 8.8 kcal-mol-1, respectively, were found to have relatively high affinities. Based on its drug-likeness properties in silico and toxicological properties, equol was identified as a potential antihypertensive metabolite. On the basis of the results of network pharmacology and molecular docking, equol may exert antihypertensive effects by regulating the IL-17 signaling pathway and PTGS2. A phenylephrine-induced H9c2 cell model was subsequently utilized to verify that equol inhibits cell hypertrophy (P < 0.05) by inhibiting the IL-17 signaling pathway and PTGS2 (P < 0.05). This study demonstrated that equol has the potential to be developed as a novel therapeutic agent for the treatment of hypertension.
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BACKGROUND: Triglyceride (TG) and its related metabolic indices are recognized as important biomarker gauging cardiovascular diseases. This study aimed to explore the association between multiple TG-derived metabolic indices including the atherogenic index of plasma (AIP), triglyceride-glucose (TyG) index, triglyceride glucose-body mass index (TyG-BMI) and cardiovascular outcomes to identify valuable predictors for cardiovascular prognosis in patients with type 2 diabetes (T2DM) and coronary heart disease (CHD). METHODS: Data of 1034 patients with T2DM and CHD from China-Japan Friendship Hospital between January 2019 and March 2022 were collected and analyzed. Multivariate Cox proportional hazards models and restricted cubic spline (RCS) analysis were conducted to examine the associations between AIP, TyG index, TyG-BMI and major adverse cardiac and cerebrovascular events (MACCEs). The area under the receiver operating characteristic (ROC) curve (AUC) was used to screen the most valuable predictor. Kaplan-Meier curve analysis was employed to examine the relationship between the predictor and prognosis. The goodness-of-fit of models was evaluated using the calibration curve and χ2 likelihood ratio test. Subgroup analysis and interaction test were performed to control for confounding factors. RESULTS: The overall incidence of MACCEs was 31.04% during a median of 13.3 months of follow-up. The results showed that AIP, TyG index and TyG-BMI were all positively correlated with the risk of MACCEs in patients with T2DM and CHD (P < 0.05). Furthermore, ROC (AUC = 0.899) suggested that AIP had the strongest ability to predict the risk of MACCEs, and the highest AIP values enhanced the risk by 83.5% in the population. RCS model demonstrated that AIP was nonlinearly associated with the incident cardiovascular outcomes (P for nonlinear = 0.0118). The Kaplan-Meier analysis for MACCEs grouped by the AIP tertiles indicated that the probability of cumulative incidences of MACCEs was significantly higher in patients with a higher AIP (all Log rank P < 0.001). Meanwhile, the calibration curve demonstrated an excellent goodness-of-fit of the multivariate model (χ2 = 13.210, P = 0.105). Subgroup analysis revealed that the trend of positive association of AIP with cardiovascular risk was similar across subgroups except in non-hypertensive individuals. CONCLUSION: Our study, for the first time, may provide valuable information that multiple TG-derived metabolic indices play a crucial role in the risk of MACCEs and it is recommended to monitor the AIP for lipid management in patients with established T2DM and CHD.
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Biomarcadores , Glicemia , Doença das Coronárias , Diabetes Mellitus Tipo 2 , Triglicerídeos , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Triglicerídeos/sangue , Incidência , Medição de Risco , Idoso , Biomarcadores/sangue , Doença das Coronárias/diagnóstico , Doença das Coronárias/epidemiologia , Doença das Coronárias/sangue , Prognóstico , Glicemia/metabolismo , Fatores de Tempo , China/epidemiologia , Estudos Retrospectivos , Índice de Massa Corporal , Fatores de Risco , Valor Preditivo dos TestesRESUMO
Acute liver failure (ALF) is a highly fatal disease, necessitating the advancement and optimization of alternative therapeutic strategies to benefit patients awaiting liver transplantation. In this study, we innovatively established the antioxidant nanozyme-hepatocyte-like cells (HLCs) microtissue sheets (HS/N-Au@composite) for ALF therapy. We first prepared a 3D-printed hyaluronic acid/gelatin/sodium alginate scaffold with N-acetylcysteine (NAC)-capped gold nanoclusters (NAC-Au NCs), forming the N-Au@hydrogel. For the encapsulation of HLC spheroids, we used a biocompatible hybrid hydrogel composed of decellularized extracellular matrix (dECM), thrombin, and fibrinogen, resulting in the HS@dECM hydrogel. Utilizing 3D printing technology, we integrated the N-Au@hydrogel with the HS@dECM hydrogel to create the HS/N-Au@composite for in situ transplantation to treat ALF. Our results demonstrated that NAC-Au NCs effectively mitigated reactive oxygen species (ROS)-induced liver necrosis in ALF. Additionally, the N-Au@hydrogel provided mechanical support, ensuring the proper landing and effective functioning of the transplanted HLC spheroids. The HS/N-Au@composite synergistically decreased serum transaminase levels, reduced the accumulation of pro-inflammatory cytokines, accelerated liver function recovery, and promoted liver regeneration in ALF treatment. This combination of HLC spheroids and NAC-Au NCs nanozymes via 3D-printed composite scaffolds represents a promising strategy for enhancing hepatocyte transplantation and advancing stem cell regenerative medicine in ALF therapy.
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The specific induction of hepatic differentiation presents a significant challenge in developing alternative liver cell sources and viable strategies for clinical therapy of acute liver failure (ALF). The past decade has witnessed the blossom of microRNAs in regenerative medicine. Herein, microRNA 122-functionalized tetrahedral framework nucleic acid (FNA-miR-122) has emerged as an unprecedented and potential platform for directing the hepatic differentiation of adipose-derived mesenchymal stem cells (ADMSCs), which offers a straightforward and cost-effective method for generating functional hepatocyte-like cells (FNA-miR-122-iHep). Additionally, we have successfully established a liver organoid synthesis strategy by optimizing the co-culture of FNA-miR-122-iHep with endothelial cells (HUVECs), resulting in functional Hep:HUE-liver spheroids. Transcriptome analysis not only uncovered the potential molecular mechanisms through which miR-122 influences hepatic differentiation in ADMSCs, but also clarified that Hep:HUE-liver spheroids could further facilitate hepatocyte maturation and improved tissue-specific functions, which may provide new hints to be used to develop a hepatic organoid platform. Notably, compared to transplanted ADMSCs and Hep-liver spheroid, respectively, both FNA-miR-122-iHep-based single cell therapy and Hep:HUE-liver spheroid-based therapy showed high efficacy in treating ALF in vivo. Collectively, this research establishes a robust system using microRNA to induce ADMSCs into functional hepatocyte-like cells and to generate hepatic organoids in vitro, promising a highly efficient therapeutic approach for ALF.
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OBJECTIVE: To investigate the relationship between uric acid to high-density lipoprotein cholesterol ratio (UHR) and circulating α-klotho levels in U.S. adults. METHODS: A cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016. Circulating α-klotho was defined as the dependent variable and UHR was defined as the independent variable. Multivariable linear regression was performed to assess the relationship between the independent and dependent variables. The nonlinear relationship and effect size between UHR and α-klotho were evaluated using smooth curve fitting and threshold effect analysis. Subgroup analysis and sensitivity analysis were conducted to determine the stability of the results. The diagnostic performance of UHR and α-klotho in common elderly diseases was compared using ROC (Receiver Operating Characteristic) analysis. RESULTS: Among 12,849 participants, there was a negative relationship between the UHR and circulating α-klotho. In the fully adjusted overall model, each unit increase in UHR was associated with a decrease of 4.1 pg/mL in α-klotho. The threshold effect analysis showed that before the inflection point of 8.2, each unit increase in UHR was associated with a decrease of 15.0 pg/mL in α-klotho; beyond the inflection point of 8.2, each unit increase in UHR was associated with a decrease of 2.8 pg/mL in α-klotho. Subgroup analyses and sensitivity analysis indicated that the relationship between UHR and α-klotho remained stable across most populations. The ROC diagnostic test indicated that the evaluative efficacy of UHR in diagnosing age-related diseases was comparable to that of α-klotho. CONCLUSION: This study revealed that the UHR was associated with the circulating α-klotho concentration, with a negative association observed in most cases. This finding suggested that the UHR might be a promising indicator for evaluating circulating α-klotho levels.
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HDL-Colesterol , Glucuronidase , Proteínas Klotho , Inquéritos Nutricionais , Ácido Úrico , Humanos , Ácido Úrico/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Glucuronidase/sangue , HDL-Colesterol/sangue , Estudos Transversais , Adulto , Idoso , Curva ROCRESUMO
OBJECTIVE: Exploring the relationship between the cardiometabolic index (CMI) and serum testosterone levels as well as testosterone deficiency in American adult males. Additionally, comparing the diagnostic value of the CMI with several common obesity and metabolism indices for identifying testosterone deficiency. METHODS: This cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016. Serum testosterone levels and testosterone deficiency were used as dependent variables, with the cardiometabolic index as the independent variable. Multivariable regression was used to assess the relationship between the independent and dependent variables, while subgroup analyses were performed to ensure the stability of the results. Smooth curve fitting was utilized to evaluate the nonlinear relationship between the CMI and testosterone levels. Receiver operating characteristic curves (ROC) were plotted for several obesity and metabolism prediction indices and the area under the curve was calculated to compare the specificity and sensitivity of each diagnostic index in the diagnosis of testosterone deficiency. RESULTS: Among 3541 adult male participants, CMI is negatively associated with serum testosterone levels and positively associated with testosterone deficiency. In the fully adjusted model, for every unit increase in CMI, serum testosterone decreased by 14.89 ng/dl. Comparing the highest quartile to the lowest quartile of CMI, each unit increase in CMI, serum testosterone decreased by 98.58 ng/dl. Furthermore, each unit increase in CMI was associated with a 16% increase in incidence of testosterone deficiency. By plotting the ROC curves, we found that the AUCs for Lipid Accumulation Product (LAP), Body Mass Index (BMI), Weight Adjusted Waist Index (WWI), CMI, Visceral Adiposity Index (VAI) and Triglyceride glucose index (TyG) were 0.73, 0.72, 0.71, 0.69, 0.66, and 0.66 respectively. CONCLUSION: Elevated levels of CMI are associated with lower testosterone levels and an increased risk of testosterone deficiency. The predictive value of the LAP was superior to that of CMI, while the predictive value of CMI was higher than VAI and TyG.
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Inquéritos Nutricionais , Testosterona , Humanos , Masculino , Testosterona/sangue , Adulto , Estudos Transversais , Pessoa de Meia-Idade , Curva ROC , Obesidade/sangue , Obesidade/epidemiologia , Índice de Massa Corporal , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/diagnósticoRESUMO
Ammonia (NH3) is a versatile and important compound with a wide range of uses, which is currently produced through the demanding Haber-Bosch process. Electrocatalytic nitrate reduction into ammonia (NRA) has recently emerged as a sustainable approach for NH3synthesis under ambient conditions. However, the NRA catalysis is a complex multistep electrochemical process with competitive hydrogen evolution reaction that usually results in poor selectivity and low yield rate for NH3synthesis. With maximum atom utilization and well-defined catalytic sites, single atom catalysts (SACs) display high activity, selectivity and stability toward various catalytic reactions. Very recently, a number of SACs have been developed as promising NRA electrocatalysts, but systematical discussion about the key factors that affect their NRA performance is not yet to be summarized to date. This review focuses on the latest breakthroughs of SACs toward NRA catalysis, including catalyst preparation, catalyst characterization and theoretical insights. Moreover, the challenges and opportunities for improving the NRA performance of SACs are discussed, with an aim to achieve further advancement in developing high-performance SACs for efficient NH3synthesis.
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BACKGROUND: Chinese patent medicines (CPMs) are widely used in China as an adjuvant treatment in dilated cardiomyopathy with heart failure (DCM-HF). However, comprehensive and systematic evidence supporting the beneficial effects of CPMs combined with current complementary and alternative medicine (CAM) treatments against DCM-HF was limited. This network meta-analysis (NMA) aimed to assess and rank the relative efficacy of eight different CPMs for DCM-HF. METHODS: To retrieve randomized controlled trials (RCTs) focusing on the use of CPMs combined with CAM for DCM-HF, the databases of PubMed, Embase, Web of Science Core Collection, Cochrane Library, ProQuest, China National Knowledge Infrastructure (CNKI), China Science Periodical Database (CSPD), Chinese Citation Database (CCD), Chinese Biomedical Literature Database (CBM), and ClinicalTrials.gov were comprehensively searched from their inception to 29 February 2024. The quality of the included RCTs was examined using the Cochrane Risk of Bias assessment tool, version 2.0 (RoB 2). Surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the relative efficacy. Bayesian network meta-analysis was designed to assess the efficacy of different CPMs. RESULTS: After applying the inclusion and exclusion criteria, a total of 77 eligible RCTs involving 6980 patients were enrolled. The outcomes assessed included clinical effectiveness rate (CER), left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), 6-min walk test (6MWT), brain natriuretic peptide (BNP), and cardiac output (CO). The results of the NMA indicated that Qili Qiangxin capsule (QLQX), Wenxin granule (WX), Tongxinluo capsule (TXL), Qishen Yiqi dropping pill (QSYQ), Shexiang Baoxin pill (SXBX), Yangxinshi tablet (YXST), Yixinshu capsule (YXSC), and Getong Tongluo capsule (GTTL) combined with CAM significantly improved performance compared with CAM alone in treating DCM-HF. YXST + CAM (MD = - 9.93, 95% CI - 12.83 to - 7.03) had the highest probability of being the best treatment on account of the enhancement of LVEF. WX + CAM had the highest likelihood of being the best treatment considering the improvement in LVEDD (MD = - 11.7, 95% CI - 15.70 to - 7.79) and 6MWT (MD = - 51.58, 95% CI - 73.40 to - 29.76). QLQX + CAM (MD = - 158.59, 95% CI - 267.70 to - 49.49) had the highest likelihood of being the best intervention for the reduction in BNP. TXL + CAM (MD = - 0.93, 95% CI - 1.46 to - 0.40) might be the optimal choice for increasing CO levels in DCM-HF patients. No serious treatment-emergent adverse events were observed. CONCLUSION: This NMA suggested that adding CPMs to the current CAM treatment exerted a more positive effect on DCM-HF. Thereinto, QLQX + CAM, TXL + CAM, WX + CAM, and YXST + CAM showed a preferable improvement in patients with DCM-HF when unified considering the clinical effectiveness rate and other outcomes. Furthermore, due to the lack of information on CPMs against DCM-HF and the uneven distribution of included studies among interventions, more high-quality studies are needed to provide more robust evidence to support our findings. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (CRD42023482669).
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Teorema de Bayes , Cardiomiopatia Dilatada , Medicamentos de Ervas Chinesas , Insuficiência Cardíaca , Metanálise em Rede , Humanos , Cardiomiopatia Dilatada/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Medicina Tradicional Chinesa/métodos , Medicamentos sem Prescrição/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Volume Sistólico , Resultado do TratamentoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Indigenous communities have long relied on medicinal plants (MPs) for primary healthcare. The ethnomedicinal knowledge are different among ethnic groups since the local flora and people's health beliefs generally vary among biocultural backgrounds. China with its diverse biocultural environment is rich in culturally important plant species including MPs. They are also essential in the context of conservation of plant resources and the related traditional medical knowledge, requiring an integrated perspective on these MPs. AIM OF THE STUDY: Focusing on the MPs used by the minority ethnic groups, this study assesses the diversity of MPs in China used in local indigenous traditions, as well as their conservation needs. MATERIALS AND METHODS: The MPs used by the 18 selected minority ethnic groups were extracted from an ethnic MP dictionary. After standardizing, the names then were compiled as an inventory. Next, following statistics were computed: the number of species in each order and family, species used by each ethnic group, species documented in the national herbal resource dataset, species adopted in drug standards, and species at different levels of conservation lists. The overall similarity of the MPs used by the ethnic groups included was achieved using a cluster and principal component analysis. RESULTS: In total 5886 vascular plant species are reported as medicines in the 18 ethnic groups, which belong to 1657 genera and 243 families. It is found that 3195 species are used exclusively by one ethnic group, indicating their cultural salience and potential restrictedness in ecological terms. Moreover, 1159 species are included in national/regional drug standards, indicating their importance in the national medical flora. However, only 3541 species of them are documented in the national herbal resource dataset, and 761 species are at different levels of threatened status, highlighting the conservation needs of Chinese MPs and the related traditional medical knowledge. CONCLUSIONS: Using a quantitative approach, for the first time the present study reveals the high level of taxonomic diversity of MPs used by minority ethnic groups of China. However, of these species, 40% are still not inventoried in the national herbal resource dataset, and more than half are used exclusively by one ethnic group, and around 13% are included in the conservation lists of different levels. These together urge the conservation of MP resources and related traditional medical knowledge. Additionally, we recommend fostering the cross-cultural communication the regional ethnomedicinal knowledge, for the purpose of maximizing the benefits of regional plants to human.
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Conservação dos Recursos Naturais , Etnicidade , Grupos Minoritários , Plantas Medicinais , Plantas Medicinais/classificação , China/etnologia , Humanos , Grupos Minoritários/estatística & dados numéricos , Medicina Tradicional Chinesa , Etnobotânica , FitoterapiaRESUMO
Liver fibrosis is a chronic pathological condition lacking specific clinical treatments. Stem cells, with notable potential in regenerative medicine, offer promise in treating liver fibrosis. However, stem cell therapy is hindered by potential immunological rejection, carcinogenesis risk, efficacy variation, and high cost. Stem cell secretome-based cell-free therapy offers potential solutions to address these challenges, but it is limited by low delivery efficiency and rapid clearance. Herein, an innovative approach for in situ implantation of smart microneedle (MN) arrays enabling precisely controlled delivery of multiple therapeutic agents directly into fibrotic liver tissues is developed. By integrating cell-free and platinum-based nanocatalytic combination therapy, the MN arrays can deactivate hepatic stellate cells. Moreover, they promote excessive extracellular matrix degradation by more than 75%, approaching normal levels. Additionally, the smart MN arrays can provide hepatocyte protection while reducing inflammation levels by ≈70-90%. They can also exhibit remarkable capability in scavenging almost 100% of reactive oxygen species and alleviating hypoxia. Ultimately, this treatment strategy can effectively restrain fibrosis progression. The comprehensive in vitro and in vivo experiments, supplemented by proteome and transcriptome analyses, substantiate the effectiveness of the approach in treating liver fibrosis, holding immense promise for clinical applications.
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Cirrose Hepática , Agulhas , Animais , Cirrose Hepática/terapia , Camundongos , Modelos Animais de Doenças , Humanos , Masculino , Sistema Livre de CélulasRESUMO
BACKGROUND: The latitudinal diversity gradient (LDG), characterized by an increase in species richness from the poles to the equator, is one of the most pervasive biological patterns. However, inverse LDGs, in which species richness peaks in extratropical regions, are also found in some lineages and their causes remain unclear. Here, we test the roles of evolutionary time, diversification rates, and niche conservatism in explaining the inverse LDG of Potentilla (ca. 500 species). We compiled the global distributions of ~ 90% of Potentilla species, and reconstructed a robust phylogenetic framework based on whole-plastome sequences. Next, we analyzed the divergence time, ancestral area, diversification rate, and ancestral niche to investigate the macroevolutionary history of Potentilla. RESULTS: The genus originated in the Qinghai-Tibet Plateau during the late Eocene and gradually spread to other regions of the Northern Hemisphere posterior to the late Miocene. Rapid cooling after the late Pliocene promoted the radiating diversification of Potentilla. The polyploidization, as well as some cold-adaptive morphological innovations, enhanced the adaptation of Potentilla species to the cold environment. Ancestral niche reconstruction suggests that Potentilla likely originated in a relatively cool environment. The species richness peaks at approximately 45 °N, a region characterized by high diversification rates, and the environmental conditions are similar to the ancestral climate niche. Evolutionary time was not significantly correlated with species richness in the latitudinal gradient. CONCLUSIONS: Our results suggest that the elevated diversification rates in middle latitude regions and the conservatism in thermal niches jointly determined the inverse LDG in Potentilla. This study highlights the importance of integrating evolutionary and ecological approaches to explain the diversity pattern of biological groups on a global scale.
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Biodiversidade , Filogenia , Potentilla , Potentilla/genética , Potentilla/fisiologia , Ecossistema , Evolução BiológicaRESUMO
The emerging stem cell-derived hepatocyte-like cells (HLCs) are the alternative cell sources of hepatocytes for treatment of highly lethal acute liver failure (ALF). However, the hostile local environment and the immature cell differentiation may compromise their therapeutic efficacy. To this end, human adipose-derived mesenchymal stromal/stem cells (hASCs) are engineered into different-sized multicellular spheroids and co-cultured with 3D coaxially and hexagonally patterned human umbilical vein endothelial cells (HUVECs) in a liver lobule-like manner to enhance their hepatic differentiation efficiency. It is found that small-sized hASC spheroids, with a diameter of ≈50 µm, show superior pro-angiogenic effects and hepatic differentiation compared to the other counterparts. The size-dependent functional enhancements are mediated by the Wnt signaling pathway. Meanwhile, co-culture of hASCs with HUVECs, at a HUVECs/hASCs seeding density ratio of 2:1, distinctly promotes hepatic differentiation and vascularization both in vitro and in vivo, especially when endothelial cells are patterned into hollow hexagons. After subcutaneous implantation, the mini-liver, consisting of HLC spheroids and 3D-printed interconnected vasculatures, can effectively improve liver regeneration in two ALF animal models through amelioration of local oxidative stress and inflammation, reduction of liver necrosis, as well as increase of cell proliferation, thereby showing great promise for clinical translation.
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Células Endoteliais da Veia Umbilical Humana , Células-Tronco Mesenquimais , Impressão Tridimensional , Esferoides Celulares , Esferoides Celulares/citologia , Humanos , Animais , Células-Tronco Mesenquimais/citologia , Camundongos , Diferenciação Celular/fisiologia , Engenharia Tecidual/métodos , Fígado , Hepatócitos/citologia , Modelos Animais de Doenças , Falência Hepática/terapia , Técnicas de Cocultura/métodosRESUMO
The ever-growing demands for efficient energy storage accelerate the development of high-rate lithium-metal battery (LMB) with desirable energy density, power density, and cycling stability. Nevertheless, the practical application of LMB is critically impeded by internal temperature rise and lithium dendrite growth, especially at high charge/discharge rates. It is highly desired but remains challenging to develop high-performance thermotolerant separators that can provide favorable channels to enable fast Li+ transport for high-rate operation and simultaneously homogenize the lithium deposition for dendrite inhibition. Polyimide-based separators with superior thermal properties are promising candidate alternatives to the commercial polyolefin-based separators, but previous strategies of designing either nanoporous or microporous channels in polyimide-based separators often meet a dilemma. Here, a facile and scalable approach is reported to develop a polyimide fiber/aerogel (denoted as PIFA) separator with the microporous polyimide fiber membrane sandwiched between two nanoporous polyimide aerogel layers, which can enable LMBs with remarkable capacity retention of 97.2% after 1500 cycles at 10 C. The experimental and theoretical studies unravel that the sandwiched structure of PIFA can appreciably enhance the electrolyte adsorption and ionic conductivity; while, the aerogel coating can effectively inhibit dendrite growth to realize durable high-rate LMBs.
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Phylogenomic conflicts are widespread among genomic data, with most previous studies primarily focusing on nuclear datasets instead of organellar genomes. In this study, we investigate phylogenetic conflict analyses within and between plastid and mitochondrial genomes using Potentilla as a case study. We generated three plastid datasets (coding, noncoding, and all-region) and one mitochondrial dataset (coding regions) to infer phylogenies based on concatenated and multispecies coalescent (MSC) methods. Conflict analyses were then performed using PhyParts and Quartet Sampling (QS). Both plastid and mitochondrial genomes divided the Potentilla into eight highly supported clades, two of which were newly identified in this study. While most organellar loci were uninformative for the majority of nodes (bootstrap value < 70%), PhyParts and QS detected conflicting signals within the two organellar genomes. Regression analyses revealed that conflict signals mainly occurred among shorter loci, whereas longer loci tended to be more concordant with the species tree. In addition, two significant disagreements between the two organellar genomes were detected, likely attributed to hybridization and/or incomplete lineage sorting. Our results demonstrate that mitochondrial genes can fully resolve the phylogenetic relationships among eight major clades of Potentilla and are not always linked with plastome in evolutionary history. Stochastic inferences appear to be the primary source of observed conflicts among the gene trees. We recommend that the loci with short sequence length or containing limited informative sites should be used cautiously in MSC analysis, and suggest the joint application of concatenated and MSC methods for phylogenetic inference using organellar genomes.
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Genoma Mitocondrial , Genomas de Plastídeos , Potentilla , Rosaceae , Filogenia , Potentilla/genética , Rosaceae/genética , Plastídeos/genéticaRESUMO
Acute liver failure (ALF) is a critical life-threatening disease that occurs due to a rapid loss in hepatocyte functions. Hepatocyte transplantation holds great potential for ALF treatment, as it rapidly supports liver biofunctions and enhances liver regeneration. However, hepatocyte transplantation is still limited by renewable and ongoing cell sources. In addition, intravenously injected hepatocytes are primarily trapped in the lungs and have limited efficacy because of the rapid clearance in vivo. Here, we designed a Y-shaped DNA nanostructure to deliver microRNA-122 (Y-miR122), which could induce the hepatic differentiation and maturation of human mesenchymal stem cells. mRNA sequencing analysis revealed that the Y-miR122 promoted important hepatic biofunctions of the induced hepatocyte-like cells including fat and lipid metabolism, drug metabolism, and liver development. To further improve hepatocyte transplantation efficiency and therapeutic effects in ALF treatment, we fabricated protective microgels for the delivery of Y-miR122-induced hepatocyte-like cells based on droplet microfluidic technology. When cocultured with human umbilical vein endothelial cells in microgels, the hepatocyte-like cells exhibited an increase in hepatocyte-associated functions, including albumin secretion and cytochrome P450 activity. Notably, upon transplantation into the ALF mouse model, the multiple cell-laden microgels effectively induced the restoration of liver function and enhanced liver regeneration. Overall, this study presents an efficient approach from the generation of hepatocyte-like cells to hepatocyte transplantation in ALF therapy.
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Falência Hepática Aguda , Transplante de Células-Tronco Mesenquimais , MicroRNAs , Microgéis , Camundongos , Animais , Humanos , MicroRNAs/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Microfluídica , Falência Hepática Aguda/terapia , Falência Hepática Aguda/induzido quimicamente , Hepatócitos/metabolismo , Fígado/metabolismo , Diferenciação CelularRESUMO
Polyimide aerogel fibers hold promise for intelligent thermal management fabrics, but their scalable production faces challenges due to the sluggish gelation kinetics and the weak backbone strength. Herein, a strategy is developed for fast and scalable fabrication of crosslinked polyimide (CPI) aerogel fibers by wet-spinning and ambient pressure drying via UV-enhanced dynamic gelation strategy. This strategy enables fast sol-gel transition of photosensitive polyimide, resulting in a strongly-crosslinked gel skeleton that effectively maintains the fiber shape and porous nanostructure. Continuous production of CPI aerogel fibers (length of hundreds of meters) with high specific modulus (390.9 kN m kg-1) can be achieved within 7 h, more efficiently than previous methods (>48 h). Moreover, the CPI aerogel fabric demonstrates almost the same thermal insulating performance as down, but is about 1/8 the thickness of down. The strategy opens a promisingly wide-space for fast and scalable fabrication of ultrathin fabrics for personal thermal management.
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BACKGROUND: Impatiens sect. Impatiens is distributed across the Northern Hemisphere and has diversified considerably, particularly within the Hengduan Mountains (HDM) in southwest China. Yet, the infra-sectional phylogenetic relationships are not well resolved, largely due to limited taxon sampling and an insufficient number of molecular markers. The evolutionary history of its diversification is also poorly understood. In this study, plastome data and the most complete sampling to date were used to reconstruct a robust phylogenetic framework for this section. The phylogeny was then used to investigate its biogeographical history and diversification patterns, specifically with the aim of understanding the role played by the HDM and past climatic changes in its diversification. RESULTS: A stable phylogeny was reconstructed that strongly supported both the monophyly of the section and its division into seven major clades (Clades I-VII). Molecular dating and ancestral area reconstruction suggest that sect. Impatiens originated in the HDM and Southeast China around 11.76 Ma, after which different lineages dispersed to Northwest China, temperate Eurasia, and North America, mainly during the Pliocene and Pleistocene. An intercontinental dispersal event from East Asia to western North America may have occurred via the Bering Land Bridge or Aleutian Islands. The diversification rate was high during its early history, especially with the HDM, but gradually decreased over time both within and outside the HDM. Multiple linear regression analysis showed that the distribution pattern of species richness was strongly associated with elevation range, elevation, and mean annual temperature. Finally, ancestral niche analysis indicated that sect. Impatiens originated in a relatively cool, middle-elevation area. CONCLUSIONS: We inferred the evolutionary history of sect. Impatiens based on a solid phylogenetic framework. The HDM was the primary source or pump of its diversity in the Northern Hemisphere. Orogeny and climate change may have also shaped its diversification rates, as a steady decrease in the diversification rate coincided with the uplift of the HDM and climate cooling. These findings provide insights into the distribution pattern of sect. Impatiens and other plants in the Northern Hemisphere.
Assuntos
Balsaminaceae , Impatiens , Filogenia , Evolução Biológica , China , FilogeografiaRESUMO
BACKGROUND: The triglyceride-glucose (TyG) index has been proposed as a reliable surrogate marker of insulin resistance and an independent predictor of major adverse cardiovascular events (MACEs). Several recent studies have shown the relationship between the TyG index and cardiovascular outcomes; however, the role of the TyG index in chronic coronary syndrome (CCS) progression has not been extensively assessed especially in population after revascularization. This study aimed to investigate the prognostic value of the TyG index in predicting MACEs in CCS patients undergoing percutaneous coronary intervention (PCI). METHODS: The data for the study were taken from the Hospital Information System database in China-Japan Friendship Hospital over the period 2019-2021. Eligible participants were divided into groups according to the TyG index tertiles. The Boruta algorithm was performed for feature selection. Multivariate Cox proportional hazards models and restricted cubic spline (RCS) analysis were applied to examine the dose-response relationship between the TyG index and endpoint, and the results were expressed with hazard ratio (HR) and 95% confidence interval (CI) values. The area under the receiver operating characteristic (ROC) curve (AUC), decision curve analysis (DCA), and clinical impact curve (CIC) were plotted to comprehensively evaluate the predictive accuracy and clinical value of the model. The goodness-of-fit of models was evaluated using the calibration curve and χ2 likelihood ratio test. RESULTS: After applying inclusion and exclusion criteria, 1353 patients with CCS undergoing PCI were enrolled in the study. After adjusting for all confounders, we found that those with the highest TyG index had a 59.5% increased risk of MACEs over the 1-year follow-up (HR 1.595, 95% CI 1.370 ~ 1.855). Using the lowest TyG index tertile as the reference (T1), the fully adjusted HRs (95% CIs) for endpoints was 1.343 (1.054 ~ 1.711) in the middle (T2) and 2.297 (1.842 ~ 2.864) in highest tertile (T3) (P for trend < 0.001). The TyG index had an excellent predictive performance according to the results of AUC 0.810 (0.786, 0.834) and χ2 likelihood ratio test (χ2 = 7.474, P = 0.486). DCA and CIC analysis also suggested a good overall net benefit and clinical impact of the multivariate model. The results in the subgroup analysis were consistent with the main analyses. RCS model demonstrated that the TyG index was nonlinearly associated with the risk of MACEs within one year (P for nonlinear < 0.001). CONCLUSION: The elevated TyG index is associated with an increased risk of cardiovascular events and predicts future MACEs in patients with CCS undergoing PCI independently of known cardiovascular risk factors, indicating that the TyG index may be a potential marker for risk stratification and prognosis in CCS patients undergoing PCI.