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BACKGROUNDS: Acute transplant rejection is a major component of poor prognoses for organ transplantation. Owing to the multiple complex mechanisms involved, new treatments are still under exploration. Endometrial regenerative cells (ERCs) have been widely used in various refractory immune-related diseases, but the role of ERC-derived exosomes (ERC-Exos) in alleviating transplant rejection has not been extensively studied. Signaling lymphocyte activation molecule family 6 (SLAMF6) plays an important role in regulating immune responses. In this study, we explored the main mechanism by which ERC-Exos loaded with siSLAMF6 can alleviate allogeneic transplant rejection. METHODS: C57BL/6 mouse recipients of BALB/c mouse kidney transplants were randomly divided into four groups and treated with exosomes. The graft pathology was evaluated by H&E staining. Splenic and transplanted heart immune cell populations were analyzed by flow cytometry. Recipient serum cytokine profiles were determined by enzyme-linked immunosorbent assay (ELISA). The proliferation and differentiation capacity of CD4+ T cell populations were evaluated in vitro. The α-2,6-sialylation levels in the CD4+ T cells were determined by SNA blotting. RESULTS: In vivo, mice treated with ERC-siSLAMF6 Exo achieved significantly prolonged allograft survival. The serum cytokine profiles of the recipients were significantly altered in the ERC-siSLAMF6 Exo-treated recipients. In vitro, we found that ERC-siSLAMF6-Exo considerably downregulated α-2,6-sialyltransferase (ST6GAL1) expression in CD4+ T cells, and significantly reduced α-2,6-sialylation levels. Through desialylation, ERC-siSLAMF6 Exo therapy significantly decreased CD4+ T cell proliferation and inhibited CD4+ T cell differentiation into Th1 and Th17 cells while promoting regulatory T cell (Treg) differentiation. CONCLUSIONS: Our study indicated that ERC-Exos loaded with siSLAMF6 reduce the amount of sialic acid connected to α-2,6 at the end of the N-glycan chain on the CD4+ T cell surface, increase the number of therapeutic exosomes endocytosed into CD4+ T cells, and inhibit the activation of T cell receptor signaling pathways, which prolongs allograft survival. This study confirms the feasibility of using ERC-Exos as natural carriers combined with gene therapy, which could be used as a potential therapeutic strategy to alleviate allograft rejection.
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Endométrio , Exossomos , Rejeição de Enxerto , Transplante de Coração , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Animais , Exossomos/metabolismo , Rejeição de Enxerto/imunologia , Feminino , Camundongos , Endométrio/metabolismo , Aloenxertos , Citocinas/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Proliferação de Células , Sobrevivência de EnxertoRESUMO
BACKGROUND: The fall armyworm (FAW, Spodoptera frugiperda) is a polyphagous pest known for causing significant crop damage. The gut microbiota plays a pivotal role in influencing the biology, physiology and adaptation of the host. However, understanding of the taxonomic composition and functional characteristics of the gut microbiota in FAW larvae fed on different host plants remains limited. METHODS: This study utilized metagenomic sequencing to explore the structure, function and antibiotic resistance genes (ARGs) of the gut microbiota in FAW larvae transferred from an artificial diet to four distinct host plants: maize, sorghum, tomato and pepper. RESULTS: The results demonstrated significant variations in gut microbiota structure among FAW larvae fed on different host plants. Firmicutes emerged as the dominant phylum, with Enterococcaceae as the dominant family and Enterococcus as the prominent genus. Notably, Enterococcus casseliflavus was frequently observed in the gut microbiota of FAW larvae across host plants. Metabolism pathways, particularly those related to carbohydrate and amino acid metabolism, played a crucial role in the adaptation of the FAW gut microbiota to different host plants. KEGG orthologs associated with the regulation of the peptide/nickel transport system permease protein in sorghum-fed larvae and the 6-phospho-ß-glucosidase gene linked to glycolysis/gluconeogenesis as well as starch and sucrose metabolism in pepper-fed larvae were identified. Moreover, the study identified the top 20 ARGs in the gut microbiota of FAW larvae fed on different host plants, with the maize-fed group exhibiting the highest abundance of vanRC. CONCLUSIONS: Our metagenomic sequencing study reveals significant variations in the gut microbiota composition and function of FAW larvae across diverse host plants. These findings underscore the intricate co-evolutionary relationship between hosts and their gut microbiota, suggesting that host transfer profoundly influences the gut microbiota and, consequently, the adaptability and pest management strategies for FAW.
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Bactérias , Microbioma Gastrointestinal , Larva , Metagenômica , Sorghum , Spodoptera , Zea mays , Animais , Spodoptera/microbiologia , Spodoptera/genética , Larva/microbiologia , Microbioma Gastrointestinal/genética , Zea mays/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Sorghum/microbiologia , Solanum lycopersicum/microbiologia , Capsicum/microbiologia , MetagenomaRESUMO
BACKGROUND: With the backdrop of global climate change, the impact of climate change on respiratory diseases like asthma is receiving increasing attention. However, the effects of temperature and diurnal temperature range (DTR) on asthma are complex, and understanding these effects across different seasons, age groups, and sex is of utmost importance. METHODS: This study utilized asthma hospitalization data from Lanzhou, China, and implemented a distributed lag nonlinear model (DLNM) to investigate the relationship between temperature and DTR and asthma hospitalizations. It considered differences in the effects across various seasons and population subgroups. RESULTS: The study revealed that low temperatures immediately increase the risk of asthma hospitalization (RR = 1.2010, 95% CI: 1.1464, 1.2580), and this risk persists for a period of time. Meanwhile, both high and low DTR were associated with an increased risk of asthma hospitalization. Lower temperatures (RR = 2.9798, 95% CI: 1.1154, 7.9606) were associated with higher asthma risk in the warm season, while in the cold season, the risk significantly rose for the general population (RR = 3.6867, 95% CI: 1.7494, 7.7696), females (RR = 7.2417, 95% CI: 2.7171, 19.3003), and older individuals (RR = 18.5425, 95% CI: 5.1436, 66.8458). In the warm season, low DTR conditions exhibited a significant association with asthma hospitalization risk in males (RR = 7.2547, 95% CI: 1.2612, 41.7295) and adults aged 15-64 (RR = 9.9494, 95% CI: 2.2723, 43.5643). Children also exhibited noticeable risk within specific DTR ranges. In the cold season, lower DTR increases the risk of asthma hospitalization for the general population (RR = 3.1257, 95% CI: 1.4004, 6.9767). High DTR significantly increases the risk of asthma hospitalization in adults (RR = 5.2563, 95% CI: 2.4131, 11.4498). CONCLUSION: This study provides crucial insights into the complex relationship between temperature, DTR, and asthma hospitalization, highlighting the variations in asthma risk across different seasons and population subgroups.
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Asma , Hospitalização , Estações do Ano , Temperatura , Humanos , Asma/epidemiologia , Masculino , Feminino , China/epidemiologia , Adulto , Pessoa de Meia-Idade , Adolescente , Hospitalização/estatística & dados numéricos , Criança , Adulto Jovem , Pré-Escolar , Idoso , Lactente , Mudança Climática , Fatores de Risco , Recém-NascidoRESUMO
Detection and anti-detection with multispectral camouflage are of pivotal importance, while suffer from significant challenges due to the inherent contradiction between detection and anti-detection and conflict microwave and infrared (IR) stealth mechanisms. Here, a strategy is proposed to asymmetrically control transmitted microwave wavefront under radar-IR bi-stealth scheme using composite metasurface. It is engineered composed of infrared stealth layer (IRSL), microwave absorbing layer (MAL), and asymmetric microwave transmissive structure (AMTS) with polarization conversion from top to bottom. Therein, IR emissivity, microwave reflectivity, and transmissivity are simultaneously modulated by elaborately designing the filling ratio of ITO square patches on IRSL, which ensures both efficient microwave transmission and IR camouflage. Furthermore, full-polarized backward microwave stealth is achieved on MAL by transmitting and absorbing microwaves under x- and y- polarization, respectively, while forward wavefront is controlled by precise curvature phase compensation on AMTS according to ray-tracing technology. For verification, a proof-of-concept metadevice is numerically and experimentally characterized. Both results coincide well, demonstrating spiral detective wavefront manipulation under y-polarized forward wave excitation while effective reduction of radar cross section within 8-18 GHz and low IR emissivity (<0.3) for backward detection. This strategy provides a new paradigm for integration of detection and anti-detection with multispectral camouflage.
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Within One Health framework, the dissemination of antibiotic resistance genes (ARGs) and pathogenic bacteria by wild birds has attracted increasing attention. In this study, gut samples of wild birds opportunistically collected in Tianjin, China, situated along the East Asian-Australasian Flyway, were used to ascertain the realistic distribution of bacteria and ARGs in their intestinal tracts. These birds have different dietary habits (herbivore, carnivore, and omnivore) and residency statuses (resident and migratory birds). Using 16S rRNA gene sequencing and qPCR, we analyzed microbial communities and the abundance of high-risk ARGs and mobile genetic elements (MGEs). Birds with distinct ecological traits exhibited significant variations in gut bacterial composition, yet similar microbial diversity. Shigella sp. emerged as the core intestinal pathogen, with a mean relative abundance 2.57 to 1466 times higher than that of other pathogenic bacteria, and its concentration correlated with the host's trophic level as indicated by the δ15N values. The distribution of ARGs and MGEs also varied with bird ecological traits. All 10 targeted high-risk ARGs were detected in carnivores or passage migrants, while migratory birds carried significantly greater abundance of intI1 than residents (p < 0.05). The potential of migratory birds to harbor and disseminate pathogenic bacteria and ARGs cannot be ignored. Network analysis revealed blaTEM-1 presence in multiple core microorganisms, positively associated with Clostridioides difficile, emphasizing its risk potential. Positive dfrA12-intI1 correlation across trophic levels suggests potential for intI1-mediated transmission. Our study underscores the high potential risk posed by wild birds in carrying ARGs and pathogenic microorganisms, emphasizing the importance of further research and surveillance in this field.
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Systemic Lupus Erythematosus (SLE) is a chronic autoimmune inflammatory disorder characterized by alterations in the balance between inflammatory and regulatory cytokines. Mesenchymal stem cells (MSCs), which are non-hematopoietic stem cells with multipotent differentiation potential, due to their immunomodulatory, tissue repair, low immunogenicity, and chemotactic properties, have garnered increasing interest in SLE treatment. Studies increasingly reveal the heterogeneous nature of MSC populations. With sources including dental pulp, adipose tissue, bone marrow, and umbilical cord, the therapeutic effects of MSCs on SLE vary depending on their origin. This review consolidates clinical research on MSCs from different sources in treating SLE and analyzes the possible causes underlying these variable outcomes. Additionally, it elucidates five potential factors impacting the outcomes of MSC therapy in SLE: the influence of the microenvironment on MSCs, the complexity and paradoxical aspects of MSC mechanisms in SLE treatment, the heterogeneity of MSCs, the in vivo differentiation potential and post-transplant survival rates of MSCs, and disparities in MSC preparation conditions.
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This article proposes a new digital watermarking mechanism based on the Ethereum blockchain, Smart Contract, and Interplanetary File System (IPFS), with an enhanced Fast Walsh Hadamard Transform (FWHT) algorithm for watermark embedding and extraction. The proposed scheme aims to address the limitations of existing digital watermarking techniques, such as dependence on third-party platforms, by leveraging the decentralization feature of blockchain. The Smart Contract is used to manage the transaction between the parties involved in the watermarking process, while IPFS is used to store the watermark data. The enhanced FWHT algorithm is used to embed the watermark into the host image without affecting its visual quality. The results show that the proposed scheme outperforms the state-of-the-art algorithms in terms of both imperceptibility and robustness. Additionally, it demonstrates that our scheme can effectively resist various attacks. Therefore, our scheme can be a promising solution for image copyright protection, authentication applications, and image trading.
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Basal forebrain cholinergic neurons (BFCNs) extend long projections to multiple regions in the brain to regulate cognitive functions. Degeneration of BFCNs is seen with aging, after brain injury, and in neurodegenerative disorders. An increase in the amount of the immature proform of nerve growth factor (proNGF) in the cerebral cortex results in retrograde degeneration of BFCNs through activation of proNGF receptor p75NTR. Here, we investigated the signaling cascades initiated at the axon terminal that mediate proNGF-induced retrograde degeneration. We found that local axonal protein synthesis and retrograde transport mediated proNGF-induced degeneration initiated from the axon terminal. Analysis of the nascent axonal proteome revealed that proNGF stimulation of axonal terminals triggered the synthesis of numerous proteins within the axon, and pathway analysis showed that amyloid precursor protein (APP) was a key upstream regulator in cultured BFCNs and in mice. Our findings reveal a functional role for APP in mediating BFCN axonal degeneration and cell death induced by proNGF.
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Precursor de Proteína beta-Amiloide , Axônios , Prosencéfalo Basal , Fator de Crescimento Neural , Animais , Precursor de Proteína beta-Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/genética , Axônios/metabolismo , Axônios/patologia , Fator de Crescimento Neural/metabolismo , Fator de Crescimento Neural/genética , Prosencéfalo Basal/metabolismo , Prosencéfalo Basal/patologia , Camundongos , Receptores de Fator de Crescimento Neural/metabolismo , Receptores de Fator de Crescimento Neural/genética , Precursores de Proteínas/metabolismo , Precursores de Proteínas/genética , Neurônios Colinérgicos/metabolismo , Neurônios Colinérgicos/patologia , Degeneração Neural/metabolismo , Degeneração Neural/patologia , Camundongos Endogâmicos C57BL , Células Cultivadas , Transdução de SinaisRESUMO
BACKGROUND: The burden of common urologic diseases, including benign prostatic hyperplasia (BPH), urinary tract infections (UTI), urolithiasis, bladder cancer, kidney cancer, and prostate cancer, varies both geographically and within specific regions. It is essential to conduct a comprehensive and precise assessment of the global burden of urologic diseases. METHODS: We obtained data on incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) for the aforementioned urologic diseases by age, sex, location, and year from the Global Burden of Disease (GBD) 2021. We analyzed the burden associated with urologic diseases based on socio-demographic index (SDI) and attributable risk factors. The trends in burden over time were assessed using estimated annual percentage changes (EAPC) along with a 95% confidence interval (CI). RESULTS: In 2021, BPH and UTI were the leading causes of age-standardized incidence rate (ASIR) and age-standardized prevalence rate (ASPR), with rates of 5531.88 and 2782.59 per 100,000 persons, respectively. Prostate cancer was the leading cause of both age-standardized mortality rate (ASMR) and age-standardized DALYs rate (ASDR), with rates of 12.63 and 217.83 per 100,000 persons, respectively. From 1990 to 2021, there was an upward trend in ASIR, ASPR, ASMR, and ASDR for UTI, while urolithiasis showed a downward trend. The middle and low-middle SDI quintile levels exhibited higher incidence, prevalence, mortality, and DALYs related to UTI, urolithiasis, and BPH, while the high and high-middle SDI quintile levels showed higher rates for the three cancers. The burden of these six urologic diseases displayed diverse age and sex distribution patterns. In 2021, a high body mass index (BMI) contributed to 20.07% of kidney cancer deaths worldwide, while smoking accounted for 26.48% of bladder cancer deaths and 3.00% of prostate cancer deaths. CONCLUSIONS: The global burden of 6 urologic diseases presents a significant public health challenge. Urgent international collaboration is essential to advance the improvement of urologic disease management, encompassing the development of effective diagnostic screening tools and the implementation of high-quality prevention and treatment strategies.
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Carga Global da Doença , Neoplasias Renais , Hiperplasia Prostática , Neoplasias da Próstata , Neoplasias da Bexiga Urinária , Infecções Urinárias , Humanos , Masculino , Neoplasias da Próstata/epidemiologia , Hiperplasia Prostática/epidemiologia , Hiperplasia Prostática/complicações , Idoso , Pessoa de Meia-Idade , Infecções Urinárias/epidemiologia , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/mortalidade , Prevalência , Neoplasias Renais/epidemiologia , Neoplasias Renais/mortalidade , Feminino , Incidência , Urolitíase/epidemiologia , Urolitíase/complicações , Adulto , Anos de Vida Ajustados por Deficiência/tendências , Idoso de 80 Anos ou mais , Fatores de RiscoRESUMO
Zero-dimensional (0D) hybrid organic-inorganic bismuth halides have attracted immense scientific interest as promising candidates for lead-free materials. Here, by using a typical solvothermal method, two mixed-cation-phase 0D hybrid bismuth chlorides of [HPDA][H2PDA]BiCl6 (1) and [Hbzim][H2PA]BiCl6 (2) (PDA = bis(4-pyridyl)amine, bzim = benzimidazole, PA = 2-picolylamine) have been assembled based on a series of organic amine guests. Both compounds exhibit interesting photoluminescence phenomena, in which compound 1 exhibits a double emission property of blue fluorescence and yellow-green phosphorescence simultaneously, while compound 2 exhibits wide-band yellow-green emission under visible light excitation. The luminescence mechanism is explained by experiments and theoretical calculations. In view of the fact that halometallate units and the conjugated nitrogen heterocyclic systems can act as electron donors and electron acceptors, respectively, both compounds exhibit free radical-driven photochromism induced by electron transfer under xenon lamp irradiation at room temperature. In addition, benefiting from abundant hydrogen bond networks in structures, the two compounds show significant temperature-dependent proton conduction behavior in the range of 298-343 K, and the proton conductivity of both compounds is significantly improved after light irradiation. Our study demonstrates two novel hybrid mixed-cation-phase 0D hybrid bismuth halides with photoluminescence, photochromism, and photomodulated proton conduction properties, which enriches the dual-template-directed metal halide system and provides a feasible scheme for the synthesis of photoresponsive smart materials.
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Objective: To evaluate the efficacy, toxicity, and long-term outcomes of PD1 inhibitors plus chemotherapy versus re-irradiation/chemoradiotherapy in patients with unresectable locally recurrent T3-4 nasopharyngeal carcinoma (NPC). Methods: A retrospective analysis was conducted on 42 patients with recurrent nasopharyngeal cancer (NPC) after receiving immunochemotherapy or re-irradiation between February 2018 and May 2022 in Zhejiang Cancer Hospital. Overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were determined using the Kaplan-Meier method, log-rank test, and Cox proportional hazard regression. Results: With a median follow-up duration of 28.7 months (ranging from 7.2 to 63.9 months), the 3-year OS rate was 23.3% in the re-irradiotherapy (RI) group (N = 24) and 59.6% in the immunochemotherapy (IC) group (N = 18) (p = 0.042). The 3-year PFS, LRFS, and DMFS rates were not significantly different between the two groups (PFS: 45.3% vs. 62.6%, P = 0.482; LRFS: 54.4% vs. 62.6%, P =0.891; DMFS: 89.8% vs. 100.0%, P = 0.489). The univariate analysis revealed that regimen (HR: 0.354, 95% CI: 0.130-0.962, P = 0.042) was significantly correlated with OS. Multivariate analysis also showed that treatment regimen (HR: 0.329, 95% CI: 0.12-0.970, P =0.044) was the only significant prognostic factor associated with OS. The most common late toxicities in the RI group were xerostomia, deafness, and nasopharyngeal necrosis. Of these, nasopharyngeal necrosis was present in 16 patients (66.7%) and in 10 patients (41.7%) at a grade 3 or above. Nasopharyngeal necrosis is the main cause of death in the RI group. In contrast, in the IC group, grade 3 or higher immune-related adverse events or late adverse events were not observed. Conclusions: For unresectable locally recurrent NPC, re-irradiation is an effective treatment; nevertheless, the survival obtains are usually surpassed by serious late complications. For these individuals, chemotherapy in addition to an anti-PD-1 checkpoint inhibitor may be a helpful course of treatment.
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BACKGROUND: Immune dysfunction contributes to a high rate of infection in patients with acute decompensation of cirrhosis. CD52 is a glycoprotein prominently expressed in lymphocytes. Immune regulation by CD52 may be involved in adaptive immune dysfunction in cirrhosis. This study aimed to investigate the function of CD52 on CD4+ T cells on the blood of patients with acute decompensation of cirrhosis. METHODS: The expression of CD52 in the peripheral blood lymphocytes of 49 patients with cirrhosis was investigated using flow cytometry and transcriptomics. Potential cis-membrane ligands of CD52 were discovered via proximity labelling followed by proteomics. The function of CD52 on antigen-specific activation of CD4+ T cells was examined using flow cytometry in CD52 CRISPR-Cas9 knockout primary T cells. FINDINGS: CD52 expression was elevated in CD4+ T cells in acute decompensation of cirrhosis, and this elevation was correlated with increased disease severity and mortality. Components of the T cell receptor complex including TCRß, CD3γ and CD3ε were identified and validated as cis-membrane ligands of CD52. Knockout of CD52 promoted antigen-specific activation, proliferation, and pro-inflammatory cytokine secretion. INTERPRETATION: Membrane bound CD52 demonstrated cis-interaction with the T cell receptor and served as a dynamic regulator of antigen-specific activation of CD4+ T cells. The upregulation of CD52 in the periphery of acute decompensation of cirrhosis hinders the recognition of the T cell receptor by MHC, contributing to impaired T cell function. The development of an alternative anti-CD52 antibody is required to restore T cell function and prevent infections in cirrhosis. FUNDING: This study was supported by the NIHR Imperial Biomedical Research Centre, Institute for Translational Medicine and Therapeutics (P74713), Wellcome Trust (218304/Z/19/Z), and Medical Research Council (MR/X009904/1 and MR/R014019/1).
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Single B cells-based antibody platforms offer an effective approach for the discovery of useful antibodies for therapeutic or research purposes. Here we present a method for screening equine immunoglobins F(ab)2, which offers the potential advantage of reacting with multiple epitopes on the virus. Using equine influenza virus (EIV) as model, a hemagglutinin (HA) trimer was constructed to bait B cells in vaccinated horses. We screened 370 HA-specific B cells from 1 × 106 PBMCs and identified a diverse set of equine variable region gene sequences of heavy and light chains and then recombined with humanized Ig Fc. Recombinant equine Ig was then self-assembled in co-transfected 293 T cells, and subsequently optimized to obtain HA binding B-cell receptor (s). The recombinant antibodies exhibited a high binding affinity to the HA protein. Antibody H81 exhibited the highest cross neutralizing activities against EIV strains in vitro. Furthermore, it effectively protected EIV-challenged mice, resulting in significantly improved survival, reduced pulmonary inflammation and decreased viral titers. In silico predication identified a functional region of H81 comprising 27 key amino acids cross the main circulating EIV strains. The 12 amino acid residues in this region with the highest binding affinities were screened. Notably, the predicted epitopes of H81 encompassed the documented equine HA receptor binding site, validating its cross-neutralization. In summary, a rapid platform was successfully established to investigate the profiling of equine antigen-recognizing receptors (BCRs) following infection. This platform has the potential to optimize the screening of virus-neutralizing antibodies and aid in vaccine design.
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Anticorpos Neutralizantes , Anticorpos Antivirais , Linfócitos B , Infecções por Orthomyxoviridae , Animais , Cavalos , Infecções por Orthomyxoviridae/veterinária , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Camundongos , Anticorpos Antivirais/imunologia , Linfócitos B/imunologia , Anticorpos Neutralizantes/imunologia , Humanos , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Vírus da Influenza A Subtipo H3N8/imunologia , Vírus da Influenza A Subtipo H3N8/genética , Fragmentos Fab das Imunoglobulinas/imunologia , Fragmentos Fab das Imunoglobulinas/genética , Reações Cruzadas , Células HEK293 , Vacinas contra Influenza/imunologia , Memória Imunológica , Feminino , Epitopos/imunologiaRESUMO
The effect of casein phosphopeptides (CPP) and ferrous bisglycinate (FebisGly) at different ratios (1:20, 1:10, and 1:5 w/w) on iron supplementation was investigated. The in vitro bioaccessibility, structural changes, antioxidant activity, and the effect of absorption inhibitors were also explored. The results demonstrated that CPP enhanced the bioaccessibility of FebisGly by 68.72 % ± 0.18 % and increased the ß-sheet content from 21.60 % ± 0.23 % to 67.92 % ± 0.12 %, forming a stable secondary structure. The particle size distribution (PSD) and rheological analyses indicated that CPP significantly contributed to the formation of chelated irons, resulting in a uniform PSD and enhanced viscoelasticity. Moreover, it prolonged the gastric emptying time, reducing gastric irritation further. The carboxyl and amino groups in the CPP molecules participated in chelation reaction, improved the antioxidant activity, and competed with phytic acid, tannic acid, and cellulose for iron. Overall, these results laid a foundation for developing novel iron supplementation strategies.
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High-sensitivity C-reactive protein (hsCRP) to high-density lipoprotein cholesterol (HDL-C) ratio (CHR) is associated with coronary artery disease (CAD), but its predictive value for long-term adverse outcomes in patients with CAD following percutaneous coronary intervention (PCI) remains unexplored and is the subject of this study. Patients with CAD who underwent PCI at the Korea University Guro Hospital-Percutaneous Coronary Intervention (KUGH-PCI) Registry since 2004 were included. Patients were categorized into tertiles according to their CHR. The end points were all-cause mortality (ACM), cardiac mortality (CM) and major adverse cardiac events (MACEs). Kaplan-Meier analysis, multivariate Cox regression, restricted cubic spline (RCS) and sensitivity analyses were performed. A total of 3260 patients were included and divided into Group 1 (CHR <0.830, N = 1089), Group 2 (CHR = 0.830-3.782, N = 1085) and Group 3 (CHR >3.782, N = 1086). Higher CHR tertiles were associated with progressively greater risks of ACM, CM and MACEs (log-rank, p < 0.001). Multivariate Cox regression showed that patients in the highest tertile had greater risks of ACM (HR: 2.127 [1.452-3.117]), CM (HR: 3.575 [1.938-6.593]) and MACEs (HR: 1.337 [1.089-1.641]) than those in the lowest tertile. RCS analyses did not reveal a significant non-linear relationship between CHR and ACM, CM or MACEs. The significant associations remained significant in the sensitivity analyses, RCS analyses with or without extreme values, subgroup analyses and multiple imputations for missing data. Elevated CHR is a novel, independent risk factor for long-term ACM, CM and MACEs in CAD patients following PCI.
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Proteína C-Reativa , HDL-Colesterol , Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Masculino , Feminino , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Estudos Prospectivos , Pessoa de Meia-Idade , HDL-Colesterol/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/mortalidade , Idoso , Resultado do Tratamento , Valor Preditivo dos Testes , Fatores de RiscoRESUMO
Background: Previous research has demonstrated an association between gut microbiota and immune status with the development of several diseases. However, whether these factors contribute to polyps remains unclear. This study aims to use Mendelian randomization (MR) to investigate the causal relationship between gut microbiota and 4 types of polyps (nasal, gallbladder, colon, and gastric polyps), as well as to analyze the mediating role of immune traits. Methods: This study utilized large-scale GWAS meta-analyses of gut microbiota (MiBioGen Consortium), 731 immune traits, and 4 types of polyps (one from the FinnGen Consortium and three from the NBDC Human Database). Univariate MR with the inverse variance weighted (IVW) estimation method was employed as the primary analytical approach. A two-step MR analysis was performed to identify potential mediating immune traits. Additionally, multivariable MR approach based on Bayesian model averaging (MR-BMA) was employed to further prioritize gut microbiota and immune traits associated with polyp development. Results: Based on IVW method in univariate MR analysis, we identified 39 gut microbial taxa and 135 immune traits significantly causally associated with at least one type of polyp. For nasal polyps, 13 microbial taxa and 61 immune traits were causally associated. After false discovery rate (FDR) correction, CD3 on Central Memory CD8+ T cells and CD3 on CD4 regulatory T cells remained significant. MR-BMA identified 4 gut microbial taxa and 4 immune traits as high priority. For gallbladder polyps, 9 microbial taxa and 30 immune traits were causally associated. MR-BMA identified 8 microbial taxa and 6 immune traits as higher importance. For colon polyps, 6 microbial taxa and 21 immune traits were causally associated. MR-BMA identified 4 microbial taxa and 3 immune traits as higher importance. For gastric polyps, 12 microbial taxa and 33 immune traits were causally associated. Actinobacteria remained significant after FDR correction, and MR-BMA identified 7 gut microbial taxa and 6 immune traits as high priority. We identified 16 causal pathways with mediator directions consistent with the direction of gut microbiome-polyp association. Of these, 6 pathways were associated with the mechanism of nasal polyps, 1 with gallbladder polyps, 2 with colon polyps, and 7 with gastric polyps. Conclusions: Our findings shed light on the causal relationships between gut microbiota, immune traits, and polyp development, underscoring the crucial roles of gut microbiota and immune status in polypogenesis. Furthermore, these findings suggest potential applications in polyp prevention, early screening, and the development of effective strategies to reduce polyp risk.
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Microbioma Gastrointestinal , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Humanos , Microbioma Gastrointestinal/imunologia , Pólipos/imunologia , Pólipos/microbiologia , Predisposição Genética para DoençaRESUMO
The concept of clean and pollution-free energy development has promoted the rise of environmentally friendly silver-based chalcogenide nanocrystal (NC) solar cells, but currently reported silver-based NCs need complex synthesis processes at high temperatures that may bring zerovalent noble metal impurities for their high redox potentials. In this study, we report a facile synthesis of novel Ag3AuS2 NCs by injecting highly active oleylamine sulfur complexes as sulfur sources into metal precursor solutions at low temperatures of 60 °C. The obtained Ag3AuS2 NCs exhibit broad absorption spectra and high molar extinction coefficients (106 M-1 cm-1). Then, the Ag3AuS2 NCs are applied as the light-absorbing active layer in environmentally friendly thin-film solar cells. By introducing a hybrid mixture of charge acceptors and donors (NCs/P3HT hybrid film) at the interface, the device gains an absorption increment and enhanced charge extraction, achieving a final power conversion efficiency of 3.38%. This work demonstrates the enormous potential of Ag3AuS2 NCs from low-temperature preparation for photovoltaic applications.
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Trifluoroborate boronophenylalanine (BBPA) is a boron amino acid analog of 4boronophenylalanine (BPA) but with a trifluoroborate group (-BF3-) instead of a carboxyl group (-COOH). Clinical studies have shown that 18F-labeled BBPA ([18F]BBPA) can produce high-contrast tumor images in positron emission tomography (PET). Beyond PET imaging, BBPA is a theranostic agent for boron neutron capture therapy (BNCT). Because BBPA possesses an identical chemical structure to BNCT and PET, it can potentially predict the boron concentration for BNCT using [18F]BBPA-PET. The synthesis of BBPA was achieved by selectively fluorinating the α-aminoborate compound, taking advantage of the varying rates of solvolysis of the B-F bond. The study showcased the high-contrast [18F]BBPA-PET imaging in various tumor models, highlighting its broad applicability for both [18F]BBPA-PET and BBPA-BNCT. [18F]BBPA-PET tumor uptake remains consistent across various doses, including those used in BNCT. This enables accurate estimation of the boron concentration in tumors using [18F]BBPA-PET. With its dual boron structure, BBPA increases boron concentration in tumor cells and tumor tissues compared to BPA. Thus, less boron carrier is needed. This study introduces a new theranostic boron carrier that enhances boron accumulation in tumors, predicts boron concentration, and enhances the accuracy and effectiveness of BNCT.
RESUMO
BACKGROUND: This study aimed to evaluate six novel lymphocyte-based inflammatory markers (neutrophil-lymphocyte ratio, monocyte-lymphocyte ratio, platelet-lymphocyte ratio [PLR], systemic immune inflammation index [SII], systemic inflammatory response index, and systemic immune inflammation response index [SIIRI]) in patients with newly diagnosed coronary artery disease [CAD]. METHODS: A total of 959 patients newly diagnosed with CAD and underwent diagnostic coronary angiography were enrolled in this study and followed for major adverse cardiovascular events (MACEs), including cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. The best cutoff value was used to compare the six indicators. Cox risk regression analysis evaluated the relationship between novel lymphocyte-based inflammatory markers and MACEs in newly diagnosed CAD patients. RESULTS: During a mean follow-up period of 33.3 ± 9.9 months, 229 (23.9%) MACEs were identified. Multivariate Cox regression analysis showed that only SIIRI (hazard ratio [HR]: 5.853; 95% confidence interval [CI]: 4.092-8.371; p < .001) and PLR (HR: 1.725; 95% CI: 1.214-2.452; p = .002) were independent predictors of MACEs. Nevertheless, following the adjustment for covariates, only the SIIRI was found to be a significant predictor MACEs and its corresponding specific endpoint occurrences. The predictive ability of the model was improved when six different inflammatory markers were added to the basic model established by traditional risk factors, namely, the C-index increased, and the SIIRI increased most significantly (AUC: 0.778; 95% CI: 0.743-0.812; p < .001). However, among the six novel inflammatory markers, only SIIRI had improved net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (NRI: 0.187; 95% CI: 0.115-0.259, p < .001. IDI: 0.135; 95% CI: 0.111-0.159, p < .001), which was superior to the basic model established by traditional risk factors. CONCLUSIONS: SIIRI is independent predictor of MACEs in newly diagnosed CAD patients. SIIRI was superior to other measures in predicting MACEs. The combination of SIIRI and traditional risk factors can more accurately predict MACEs.
Assuntos
Biomarcadores , Doença da Artéria Coronariana , Inflamação , Linfócitos , Humanos , Doença da Artéria Coronariana/imunologia , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Linfócitos/imunologia , Prognóstico , Inflamação/diagnóstico , Inflamação/imunologia , Inflamação/sangue , Biomarcadores/sangue , Idoso , Angiografia Coronária , Neutrófilos/imunologia , Plaquetas/imunologia , Plaquetas/patologia , Fatores de Risco , SeguimentosRESUMO
BACKGROUND: Inflammation and malnutrition are related to adverse clinical outcomes in patients with coronary artery disease (CAD). However, it is unclear whether there is a relationship between the PNI (prognostic nutritional index) and RDW (red blood cell distribution width) regarding the impact on the prognosis in patients with CAD undergoing percutaneous coronary intervention (PCI). METHODS: A total of 5605 consecutive CAD patients undergoing PCI were selected retrospectively. The patients were stratified into four groups according to the PNI [high PNI (H-PNI) and low PNI (L-PNI)] and RDW [high RDW (H-RDW) and low RDW (L-RDW)]. The cutoff values of RDW and PNI were calculated using receiver-operating characteristic curve analysis. The primary endpoint was 1-year all-cause mortality (ACM). The secondary endpoint was major adverse cardiac cerebrovascular events (MACCEs), the composite of cardiac death (CD), the recurrence of MI, target lesion revascularization (TLR), and stroke. A Cox proportional hazards model was used to evaluate the association between the PNI, RDW, and clinical endpoints. RESULTS: During 1-year follow-up, 235 (4.19%) patients died. In multivariate regression analysis, the L-PNI/H-RDW group was found to have the highest risk of 1-year ACM [hazard ratio (HR) = 8.85, 95% confidence interval (CI): 5.96-13.15, p = 0.020] with the H-PNI/L-RDW group as a reference, followed by the L-PNI/L-RDW (HR = 3.96, 95% CI: 2.60-6.00, p < 0.001) and H-RDW/H-PNI groups (HR = 3.00, 95% CI: 1.99-4.50, p < 0.001). Nomograms were developed to predict the probability of 1-year ACM and MACCEs. CONCLUSIONS: CAD patients with L-PNI and H-RDW experienced the worst prognosis. The combination of PNI and RDW was a strong predictor of 1-year ACM. The coexistence of PNI and RDW appears to have a synergistic effect, providing further information for the risk stratification of CAD patients.