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INTRODUCTION: The relationship between preserved-ratio impaired spirometry (PRISm) and depression remains unclear. This study aimed to assess the bidirectional relationship between PRISm and depression using data from a national cohort. METHODS: Data from Wave 2 (2004-2005) to Wave 4 (2008-2009) of the English Longitudinal Study of Ageing (ELSA) were analyzed. Lung function and depressive symptoms were measured at baseline and follow-up. Cox proportional hazard models were used to calculate the hazard ratio (HR) of PRISm with depression (Study 1) and depression with PRISm (Study 2). RESULTS: Studies 1 and 2 included 2,934 and 2,277 participants, respectively. The follow-up period extended from Wave 2 to Wave 4. In univariate analyses, a bidirectional association between PRISm and depression was observed, with unadjusted HRs of 1.49 (95% confidence interval [CI], 1.12-1.99; P=0.007) in Study 1 and 1.69 (95% CI, 1.13-2.52; P=0.010) in Study 2. However, in multivariable Cox models, baseline PRISm was not associated with subsequent depression development (adjusted HR 1.26; 95% CI, 0.94-1.69; P=0.128). Conversely, participants with depression had a significantly higher risk of developing PRISm compared to those without depression (adjusted HR 1.54; 95% CI, 1.03-2.32; P=0.038). These findings were consistent with z-score-based interpretive strategies, with an adjusted HR of 1.30 (95% CI, 0.95-1.77; P=0.105) in Study 1 and 1.59 (95% CI, 1.03-2.47; P=0.038) in Study 2. CONCLUSIONS: Depression was associated with an increased risk of developing PRISm, whereas PRISm did not increase the risk of developing depression. Physicians should be vigilant for potential PRISm development in patients with depression.
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Background: Patients with non-small cell lung cancer (NSCLC) carrying SMARCA4 mutations (SMARCA4-Mut) tend to have more advanced disease and a poor prognosis. However, due to the rarity of this mutation and the lack of related studies, the characteristics of SMARCA4-Mut NSCLC patients remains poorly determined. To clarify the clinical characteristics and prognostic factors of SMARCA4-Mut NSCLC, we initiated the present study to provide a clinical reference. Methods: We used data from two cohorts of NSCLC-SMARCA4-mutated samples: The Cancer Genome Atlas (TCGA) database and our center's clinical data. The TCGA database was used to obtain 481 NSCLC-SMARCA4-Mut samples for clinical characterization. The center collected data on 224 consecutive NSCLC patients treated between December 2020 to July 2022. Among them, 26 harbored SMARCA4 mutations, and 20 were eligible for inclusion in the study. Clinical, pathological, and molecular features, as well as prognostic role of SMARCA4 mutations were analyzed. Additionally, we analyzed the prognostic impact of Napsin A expression in SMARCA4-Mut patients. Results: The TCGA database included 480 patients with SMARCA4-Mut NSCLC, 311 males (64.8%) and 169 females (35.2%), with a median age of 67 years. Among the 20 SMARCA4-Mut patients in our center series, 12 (60%) were males and 8 (40%) females, with a median age of 63. The intergroup prognostic correlation analysis showed that SMARCA4-Mut patients had significantly worse prognosis than those the wild-type SMARCA4 (SMARCA4-WT) (P=0.04). Within the SMARCA4-Mut group, patients with Napsin A expression had longer overall survival (OS) (P=0.03) than those without expression. Median survival in the Napsin A-positive and negative groups was 32 and 15 months, respectively. According to time-dependent receiver operating curve analysis, patients with Napsin A expression had significantly longer first-line treatment progression-free survival (PFS1) [area under the curve (AUC) =0.748] and OS (AUC =0.586). No prognostic value of Napsin A was found in patients SMARCA4-WT patients. Conclusions: SMARCA4-Mut is an adverse prognostic feature in NSCLC patients. Napsin A expression in SMARCA4-Mut patients is associated with prolonged OS.
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The management of diabetic wounds presents a formidable challenge in clinical settings due to elevated glucose levels, drug-resistant bacterial infections, and a deficiency of bioactive molecules in the microenvironment. To address this challenge, a glucose-responsive Hyaluronic acid Methacryloyl (HAMA)-Chitosan Methacryloyl (CSMA)-3-Methacrylamidophenylboronic acid (MPBA) loading Exosome (H-C-M@Exo) multifunctional hydrogel has been developed to enhance diabetic wound healing in this study. The H-C-M@Exo hydrogel exhibits remarkable features, including high hydrophilicity, excellent pressure resistance, antibacterial properties, and good biocompatibility. It uniquely possesses the ability to sustain the release of exosomes in response to glucose fluctuations. The H-C-M@Exo hydrogel can effectively reduce inflammation, significantly promote rapid re-epithelization, facilitate favorable collagen deposition, and stimulate abundant angiogenesis at the wound sites. Furthermore, the hydrogel induces localized regulation of M2 macrophage polarization, synergistically promoting diabetic angiogenesis and wound healing. These findings suggest H-C-M@Exo hydrogel is a promising biomaterial for the treatment of chronic diabetic wounds.
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The presence of vacancy defects significantly impacts thermal properties of materials. In this research, we delve into the effects of vacancy defects on the thermal conductivity of ternary alloy BaAgBi, employing molecular dynamics simulations coupled with a deep neural network potential (NNP). Initially, we validate the precision of our NNP by comparing their predictions for energy, atomic forces, phonon dispersion curves, phonon density of states, and vacancy formation energy with density functional theory calculations, ensuring a high degree of accuracy. Our findings reveal that the reduction in thermal conductivity due to vacancies aligns with the Debye-Callaway model, with variations depending on the type of vacancy. Specifically, Ba vacancies result in the most notable decrement in thermal conductivity, attributable to their low phonon participation ratio and high lattice distortion, both factors that enhance phonon scattering. Besides, we find that the high energy barrier (â¼1.66 eV) indicates that Ba vacancies hardly migrate at 300 K. This study helps us understand how vacancies affect thermal conductivity in BaAgBi and how different vacancy types affect it.
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Phage display is a vital tool for the discovery and development of affinity reagents such as antibodies and peptides, which have great potential in imaging, molecular recognition, biosensors, targeted delivery and other clinical applications. However, affinity reagents obtained by phage display are often subjected to a process called biopanning, which is considered time-consuming, labor-intensive and lacks accurate control, limiting the acquisition of high-quality affinity reagents. Over the last two decades, several microfluidic approaches have been designed to simplify the conventional biopanning process and to realize precise control. To better understand the advantages of microfluidics over traditional biopanning and the potential of microfluidics for other molecular screening strategies, we provided an overview of recent applications of microfluidics in phage display. Additionally, the next challenges and outlooks are discussed.
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Técnicas de Visualización de Superficie Celular , Técnicas de Visualización de Superficie Celular/métodos , Técnicas Analíticas Microfluídicas/instrumentación , Biblioteca de Péptidos , Microfluídica/métodos , Humanos , Péptidos/química , Péptidos/análisisRESUMEN
A new species Serangiumxinpingensis Huang & Wang, sp. nov. is described from Yunnan Province, China, as a newly discovered predator on Bemisiatabaci Gennadius (Hemiptera, Sternorrhyncha, Aleyrodidae). The new species is a valuable addition to the 14 species of this genus in China known before. A diagnosis, detailed description, including the structure of its immature stages, illustrations, and the distribution of the new species are provided.
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Ciliary neurotrophic factor (CNTF) acts as a potent neuroprotective agent in neuronal survival and regeneration, and can also induce the differentiation of several stem cells into neurons, which highlights the broad application of CNTF in biomedicine. However, large-scale production of bioactive recombinant human CNTF protein remains to be explored. Herein, this study aims to express a bioactive human CNTF protein on a large scale by genetically engineering a silk gland bioreactor of silkworm. Our results showed that CNTF protein was successfully expressed in the middle silk gland (MSG) of silkworm, which can be secreted into the silks with the amount of 3.2 mg/g cocoons. The fabrication of human CNTF-functionalized silk material was able to promote proliferation and migration of neural cells when compared to the natural silk protein. Importantly, this functional silk material could also facilitate neurite outgrowth of mouse retinal ganglion cell (RGC-5) cells. All these data demonstrated a high bioactivity of the recombinant human CNTF protein expressed in the MSG of silkworm. The further fabrication of different silk materials with CNTF bioactivity will give biomedical applications in tissue engineering and neuroregeneration.
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Camellia oleifera, an important tree species and source of edible oil in China, has received significant attention owing to the oil's high unsaturated fatty acid content, which has benefits for human health. However, the mechanisms underlying C. oleifera yield and oil quality are largely unknown. In this study, 180 F1 progenies were obtained from two parents with obvious differences in fruit- and oil-related traits. We constructed a high-density genetic map using a double digest restriction site-associated DNA sequencing (ddRAD-Seq) strategy in C. oleifera. This map spanned 3327 cM and anchored 2780 markers in 15 linkage groups (LGs), with an average marker interval of 1.20 cM. A total of 221 quantitative trait loci (QTLs) associated with fruit- and oil-related traits were identified across three years' worth of phenotypic data. Nine QTLs were detected simultaneously in at least two different years, located on LG02, LG04, LG05, LG06, and LG11, and explained 8.5-16.6% of the phenotypic variation in the corresponding traits, respectively. Seventeen major QTLs were obtained that explained 13.0-16.6% of the phenotypic variance. Eleven and five flanking SNPs of major QTLs for fruit- and oil-related traits were detected which could be used for marker-assisted selection in C. oleifera breeding programs. Furthermore, 202 potential candidate genes in QTL regions were identified based on the collinearity of the genetic map and the C. oleifera "CON" genome. A potential regulatory network controlling fruit development and oil biosynthesis was constructed to dissect the complex mechanism of oil accumulation. The dissection of these QTLs will facilitate the gene cloning underlying lipid synthesis and increase our understanding in order to enhance C. oleifera oil yield and quality.
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Camellia , Mapeo Cromosómico , Frutas , Aceites de Plantas , Sitios de Carácter Cuantitativo , Camellia/genética , Frutas/genética , Frutas/metabolismo , Frutas/crecimiento & desarrollo , Aceites de Plantas/metabolismo , Fenotipo , Análisis de Secuencia de ADN/métodos , Ligamiento GenéticoRESUMEN
The ability to regulate emotions is vital to successful social interactions. This study explores whether visual attention bias is associated with emotion dysregulation (ED) in early childhood. Parental reports of child ED (Child Behaviour Checklist (CBCL) and Temper Tantrum Scale) were examined in relation to child visual attention bias whilst viewing emotional faces. Results indicated that the level of eye gaze fixation towards emotional images and faces was associated with ED when social function (measured with the Social Responsiveness Scale), gender, age, and attention problems (measured from the CBCL subscale), were adjusted. The modifying effect on visual attention bias was evaluated using interaction analysis in the generalized linear model. The level of visual attention bias, indicated by the proportion of eye gaze fixation time on areas of interest (AOIs) in images displaying unpleasant emotions (such as anger), was inversely associated with the level of externalising problem behaviours (p = .014). Additionally, the association of eye gaze fixation time for AOIs displaying negative emotional cues with the level of externalising problem behaviours varied by age (p = .04), with younger children (aged < 70 months) demonstrating a stronger association than older children (aged ≥ 70 months). Findings suggest that young children with greater ED symptoms look less at unpleasant emotional cues. However, this relationship is attenuated as children become older. Further research to identify objective biomarkers that incorporate eye-tracking tasks may support prediction of ED-related mental health issues in the early years.
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Background: Sarcopenia is a disease characterized by decreased skeletal muscle mass and function in elderly individuals. Decreased hemoglobin levels is a marker of anemia. According to reports, there may be an association between anemia and sarcopenia, but research is inconsistent. Therefore, this meta-analysis aims to explore the association between sarcopenia and low hemoglobin levels. Methods: We searched PubMed, Embase, the Cochrane Library, Web of Science, Ovid, China National Knowledge Infrastructure (CNKI), and Wan Fang databases until September 2022. The present study included cross-sectional and case-control studies regarding low hemoglobin levels and sarcopenia. The studies were selected using inclusion and exclusion criteria. Studies were meta-analyzed by Review Manager 5.4 and Stata 16.0. We performed the heterogeneity test using the I 2 test. Subgroup analysis was carried out to explore the cause of heterogeneity. Egger test was used to evaluate publication bias. Results: Out of 1,550 initial studies, 16 studies were meta-analyzed. Sarcopenia participants had significantly lower levels of hemoglobin than controls (MD = -0.53, 95% CI: -0.68 to -0.37, p < 0.001). Subgroup analysis, performed in China population reported lower hemoglobin levels in the sarcopenia population (MD = -0.49, 95% CI: -0.65 to -0.33, p < 0.001). And sarcopenia based on AWGS criteria reported lower hemoglobin levels (MD = -0.49, 95% CI: -0.65 to -0.33, p < 0.001). Among the population from hospitals and communities, patients with sarcopenia have lower hemoglobin levels. Conclusion: Our meta-analysis found evidence that sarcopenia is associated with low hemoglobin levels. However, further large-scale prospective studies should be conducted in the future to further confirm our conclusions. Systematic review registration: PROSPERO, CDR42024532252.
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BACKGROUND: Research on the associations of type-specific bullying victimization and poly-bullying victimization with suicidal ideation is limited and contradictory. This study aimed to examine these associations among school-aged adolescents. METHODS: A total of 13,258 students from 3 middle schools and 4 high schools in a southern city in China completed a cross-sectional questionnaire in 2019. Multinomial logistic regressions were used to examine associations between type-specific bullying victimization and poly-victimization with suicidal ideation. RESULTS: The latent class analysis identified three subgroups of suicidal ideation: low (70.0 %), moderate (24.0 %), and high (6.0 %). Compared with non-bullying victimization in the past year, the corresponding adjusted odds ratios [aOR] (95 % CI) of moderate and high suicidal ideation for only physical victimization were 1.74 (1.15, 2.63) and 2.51 (1.18, 5.38), respectively, for only relational victimization were 1.26 (0.97, 1.62) and 2.48 (1.65, 3.71), respectively, for only verbal victimization were 1.45 (1.17, 1.78) and 1.42 (0.90, 2.22), respectively, for only property victimization were 1.30 (1.03, 1.65) and 1.31 (0.80, 2.16), respectively, and for sexual victimization were 1.38 (1.03, 1.83) and 2.45 (1.50, 3.99), respectively. Poly-bullying victimization was associated with moderate (aORtwo = 1.45 (1.24, 1.70); aORthree = 1.70 (1.41, 2.05), aORfour = 2.03 (1.61, 2.58), aORfive = 2.48 (1.74, 3.53)) and high suicidal ideation (aORtwo = 2.01 (1.49, 2.70), aORthree = 3.87 (2.86, 5.25), aORfour = 4.55 (3.20,6.46), aORfive = 7.90 (5.06, 12.33)). LIMITATIONS: The research design is cross-sectional, and relevant data was based on self-reports. CONCLUSIONS: Different types of bullying victimization were associated with suicidal ideation and poly-bullying victimization and suicidal ideation association shows a dose-response-relationship.
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Acoso Escolar , Víctimas de Crimen , Instituciones Académicas , Estudiantes , Ideación Suicida , Humanos , Adolescente , Acoso Escolar/estadística & datos numéricos , Acoso Escolar/psicología , Masculino , Femenino , China/epidemiología , Víctimas de Crimen/estadística & datos numéricos , Víctimas de Crimen/psicología , Estudios Transversales , Estudiantes/estadística & datos numéricos , Estudiantes/psicología , Encuestas y CuestionariosRESUMEN
BACKGROUND: Children and families from priority populations experienced significant psychosocial and mental health issues to the COVID-19 pandemic. Yet they also faced significant barriers to service access, particularly families from culturally and linguistically diverse (CALD) backgrounds. With most child and family health nurse clinics ceasing in-person consultations due to the pandemic, many children missed out on health and developmental checks. The aim of this study was to investigate the perspectives and experiences of family members and service providers from an urban, CALD community regarding the implementation of a digital, developmental surveillance, Watch Me Grow-Electronic (WMG-E) program. METHODS: Semi-structured interviews were conducted with 17 family members, service navigators, and service providers in a multicultural community in South Western Sydney, Australia. This qualitative study is an implementation evaluation which formed as part of a larger, two-site, randomised controlled trial of the WMG-E program. A reflexive thematic analysis approach, using inductive coding, was adopted to analyse the data. RESULTS: Participants highlighted the comprehensive and personalised support offered by existing child and family health services. The WMG-E was deemed beneficial because the weblink was easy and quick to use and it enabled access to a service navigator who support family access to relevant services. However, the WMG-E was problematic because of technology or language barriers, and it did not facilitate immediate clinician involvement when families completed the weblink. CONCLUSIONS: Families and service providers in this qualitative study found that using WMG-E empowered parents and caregivers to access developmental screening and learn more about their child's development and engage with relevant services. This beds down a new and innovative solution to the current service delivery gap and create mechanisms that can engage families currently not accessing services, and increases knowledge around navigating the health and social care services. Notwithstanding the issues that were raised by families and service providers, which include accessibility challenges for CALD communities, absence of clinical oversight during screening, and narrow scope of engagement with available services being offered, it is worth noting that improvements regarding these implementation factors must be considered and addressed in order to have longevity and sustainability of the program. TRIAL REGISTRATION: The study is part of a large randomised controlled trial (Protocol No. 1.0, Version 3.1) was registered with ANZCTR (registration number: ACTRN12621000766819) on July 21st, 2021 and reporting of the trial results will be according to recommendations in the CONSORT Statement.
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COVID-19 , Diversidad Cultural , Investigación Cualitativa , Humanos , Femenino , Masculino , Niño , Familia/psicología , Accesibilidad a los Servicios de Salud , Adulto , SARS-CoV-2 , Australia , Servicios de Salud del Niño/organización & administración , Navegación de Pacientes/organización & administración , Entrevistas como Asunto , Persona de Mediana EdadRESUMEN
OBJECTIVE: The association between thyroid function, coagulation and venous thromboembolism (VTE) has been reported in observational studies with conflicting findings. This study aimed to elucidate the causal effects of thyroid function on coagulation and VTE from a genetic perspective. METHODS: Two sample Mendelian randomization analysis was conducted using summary statistics from genome-wide association studies in a European population. Coagulation status was associated with nine coagulation-related factors (F VIII, F IX, F XI, Fibrinogen, Antithrombin-III, Thrombomodulin, Plasminogen activator inhibitor-1, Protein C and Protein S). Inverse variance weighting with random effect method was used as the main analytic approach with MR-Egger, weighted median, simple mode and weighted mode methods serving as complements. Sensitivity analyses including heterogeneity test, horizontal pleiotropy test and leave-one-out analysis were conducted to further assess the reliability of results. RESULTS: No genetic causal effects of thyroid function on VTE (including pulmonary embolism and deep venous thrombosis) were found. Genetically, hyperthyroidism was suggestively related to decreased Antithrombin-III (ß: -0.04 [95% CI: -0.06 to - 0.01], p = 0.010) and Protein C (ß: -0.03 [95% CI: -0.06 to 0.00], p = 0.045). No notable associations were observed between other thyroid function parameters and coagulation-related factors. CONCLUSION: We provide suggestive genetic evidence supporting the causal effect of hyperthyroidism on decreased level of anticoagulant factors including Antithrombin-III and Protein C. However, whether this genetic causality could lead to clinically significant hypercoagulable state and increased risk of VTE in hyperthyroid population needs to be further addressed.
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PURPOSE: To evaluate the efficacy of retinal massage combined with autologous blood covering in the treatment of persistent macular holes following vitrectomy in eyes with high myopia. SETTINGS AND DESIGN: Retrospective, consecutive case series in a tertiary eye center. METHODS: A total of 12 highly myopic eyes with persistent macular holes after vitrectomy and internal limiting membrane peeling received combined retinal massage, air/fluid exchange, autologous blood covering, and gas/silicone oil tamponade. Best-corrected visual acuity, axial length, and optical coherence tomographic images before and after the treatment were compared. RESULTS: The mean hole diameter before this intervention was 931.58 ± 244.58 Symbolm (range, 508-1270), and the axial length was 30.39 ± 2.13 mm (range, 27.08-34.64). During the 6-month follow-up period, hole closure was achieved in eight eyes (66.67%). The mean best-corrected visual acuity improved significantly from 1.40 ± 0.50 logarithm of the minimum angle of resolution (logMAR) at baseline to 1.10 ± 0.30 logMAR (P < 0.05). No complications were observed. CONCLUSIONS: Combined retinal massage and autologous blood covering, which is easy to manipulate, can promote the closure of persistent macular holes after vitrectomy and improve vision in high myopia with an axial length less than 29 mm.
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BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often require hospital readmission because of exacerbation of their condition. These frequent exacerbations reduce quality of life, work performance, and emotional health. However, few studies have investigated the risk factors for readmission and readmission rates in Asian patients with COPD. We conducted a systematic review to identify and understand the major risk factors for readmission in patients with COPD in Asia and the readmission rate. METHOD: We searched PubMed, MEDLINE, Embase, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and China Biomedical Literature Database from database inception to September 2023 to identify studies on the readmission rate and risk factors for COPD in Asian patients. Chinese search terms included "COPD," "chronic obstructive pulmonary disease," "risk factors," "recurrence," "readmission," and "acute exacerbation." English search terms included "chronic obstructive pulmonary disease," "COPD," "lung emphysema," "hospital admission," "patient readmission," and "readmission." We extracted first author, publication year, research area, sample size, sex, risk factors, and readmission rates. The included studies' quality was evaluated using the Agency of Healthcare Research and Quality. Meta-synthesis was conducted on readmission rates and risk factors for readmission. Subgroups were formed by age, research area, sample size, and research type, and meta-regression analysis was conducted on the 30-day, 90-day, and 365-day readmission rates of patients to determine the source of heterogeneity. Finally, the results' robustness was evaluated using sensitivity analysis. Begg and Egger tests were used to evaluate publication bias. RESULTS: Meta-analysis of 44 studies, with 169,255 participants, indicated that risk factors for COPD readmission in Asia included: history of multiple hospital admissions, ≥ 3 comorbidities, male sex, ratio of eosinophils percentage ≥ 2%, body mass index < 18.5, smoking history, pulmonary heart disease comorbidity, COPD assessment test score > 20, nutritional disorder, Neutrophil-to-Lymphocyte ratio > 7, and FEV1 < 50. The 30-, 90-, and 365-day readmission rates of patients were 19%, 31%, and 42%, respectively. CONCLUSIONS: Patients with COPD in Asia generally have high readmission rates and different risk factors. To reduce healthcare, economic, and social burdens, interventions should address major risk factors, early prevention, and screening.
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Readmisión del Paciente , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/terapia , Readmisión del Paciente/estadística & datos numéricos , Factores de Riesgo , Asia/epidemiologíaRESUMEN
BACKGROUND: Hepatitis B virus (HBV)-specific T cell response is a major host immune response to control the virus. However, it is still unclear how it affects long-term outcomes of chronic hepatitis B patients, especially those who stop nucleos(t)ide analogue (NA) therapy. We aimed to explore whether the HBV-specific T cell response at the end of treatment (EOT) was associated with clinical outcomes. METHODS: In a prospective cohort study, 51 HBeAg-negative patients who discontinued NA therapy were enrolled. RESULTS: In a mean follow-up of 25.3 months, 25 patients developed clinical relapse. We found that a stronger hepatitis B core (HBc)-specific T cell response at EOT was associated with a lower risk of clinical relapse. Compared to the low-response group, the high-response group had a lower risk of clinical relapse with hazard ratio of 0.21 (95% CI: 0.05-0.88). The high HBc-specific T cell response was associated with reduced surge of HBV DNA and HBcrAg during the first year of follow-up. The T cell response at EOT was comparable between different NA treatments. Notably, the overall HBV-specific T cell response could be partially restored along with clinical relapse; however, such reinvigorated T cell response was not associated with HBsAg seroclearance. CONCLUSIONS: A higher HBc-specific T cell response at EOT was associated with lower risk of clinical relapse and reduced surge of HBV DNA and HBcrAg levels off NA therapy.
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BACKGROUND: Cancer-associated fibroblasts (CAFs) are the prominent cell type in the tumor microenvironment (TME), and CAF subsets have been identified in various tumors. However, how CAFs spatially coordinate other cell populations within the liver TME to promote cancer progression remains unclear. METHODS: We combined multi-region proteomics (6 patients, 24 samples), 10X Genomics Visium spatial transcriptomics (11 patients, 25 samples), and multiplexed imaging (92 patients, 264 samples) technologies to decipher the expression heterogeneity, functional diversity, spatial distribution, colocalization, and interaction of fibroblasts. The newly identified CAF subpopulation was validated by cells isolated from 5 liver cancer patients and in vitro functional assays. RESULTS: We identified a liver CAF subpopulation, marked by the expression of COL1A2, COL4A1, COL4A2, CTGF, and FSTL1, and named F5-CAF. F5-CAF is preferentially located within and around tumor nests and colocalizes with cancer cells with higher stemness in hepatocellular carcinoma (HCC). Multiplexed staining of 92 patients and the bulk transcriptome of 371 patients demonstrated that the abundance of F5-CAFs in HCC was associated with a worse prognosis. Further in vitro experiments showed that F5-CAFs isolated from liver cancer patients can promote the proliferation and stemness of HCC cells. CONCLUSIONS: We identified a CAF subpopulation F5-CAF in liver cancer, which is associated with cancer stemness and unfavorable prognosis. Our results provide potential mechanisms by which the CAF subset in the TME promotes the development of liver cancer by supporting the survival of cancer stem cells.
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Fibroblastos Asociados al Cáncer , Carcinoma Hepatocelular , Neoplasias Hepáticas , Células Madre Neoplásicas , Microambiente Tumoral , Humanos , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Microambiente Tumoral/genética , Proteómica/métodos , Transcriptoma , Regulación Neoplásica de la Expresión Génica , Genómica/métodos , Proliferación Celular , Perfilación de la Expresión Génica , Línea Celular Tumoral , Pronóstico , MultiómicaRESUMEN
Nanofibers have emerged as a highly effective method for drug delivery, attributed to their remarkable porosity and ability to regulate drug release rates while minimizing toxicity and side effects. In this study, we successfully loaded the natural anticancer drugs curcumin (CUR) and hypocrellin A (HA) into pure poly(l-lactic acid) (PLLA) and PLLA-silk protein (PS) composite nanofibers through electrospinning technology. This result was confirmed through comprehensive analysis involving SEM, FTIR, XRD, DSC, TG, zeta potential, and pH stability analysis. The encapsulation efficiency of all samples exceeded 85%, demonstrating the effectiveness of the loading process. Additionally, the drug release doses were significantly higher in the composites compared to pure PLLA, owing to the enhanced crystallinity and stability of the silk proteins. Importantly, the composite nanofibers exhibited excellent pH stability in physiological and acidic environments. Furthermore, the drug-loaded composite nanofibers displayed strong inhibitory effects on cancer cells, with approximately 28% (HA) and 37% (CUR) inhibition of cell growth and differentiation within 72 h, while showing minimal impact on normal cells. This research highlights the potential for controlling drug release through the manipulation of fiber diameter and crystallinity, paving the way for wider applications of electrospun green nanomaterials in the field of medicine.
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Antineoplásicos , Proliferación Celular , Curcumina , Liberación de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Fibroínas , Nanofibras , Tamaño de la Partícula , Perileno , Fenol , Poliésteres , Quinonas , Curcumina/química , Curcumina/farmacología , Nanofibras/química , Fibroínas/química , Humanos , Antineoplásicos/química , Antineoplásicos/farmacología , Poliésteres/química , Quinonas/química , Quinonas/farmacología , Proliferación Celular/efectos de los fármacos , Fenol/química , Perileno/química , Perileno/análogos & derivados , Perileno/farmacología , Ensayo de Materiales , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Preparaciones de Acción Retardada/química , Supervivencia Celular/efectos de los fármacos , Línea Celular TumoralRESUMEN
BACKGROUND: Lung cancer still ranks first in the mortality rate of cancer. Uric acid is a product of purine metabolism in humans. Its presence in the serum is controversial; some say that its high levels have a protective effect against tumors, others say the opposite, that is, high levels increase the risk of cancer. Therefore, the aim of this study was to investigate the potential causal association between serum uric acid levels and lung cancer. METHODS: Mendelian randomization was used to achieve our aim. Sensitivity analyses was performed to validate the reliability of the results, followed by reverse Mendelian analyses to determine a potential reverse causal association. RESULTS: A significant causal association was found between serum uric acid levels and lung cancer in East Asian and European populations. Further sublayer analysis revealed a significant causal association between uric acid and small cell lung cancer, while no potential association was observed between uric acid and non-small cell lung cancer, squamous lung cancer, and lung adenocarcinoma. The sensitivity analyses confirmed the reliability of the results. Reverse Mendelian analysis showed no reverse causal association between uric acid and lung cancer. CONCLUSIONS: The results of this study suggested that serum uric acid levels were negatively associated with lung cancer, with uric acid being a potential protective factor for lung cancer. In addition, uric acid level monitoring was simple and inexpensive. Therefore, it might be used as a biomarker for lung cancer, promoting its wide use clinical practice.