RESUMO
PURPOSE: To investigate the value of 2-deoxy-18f-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) and circulating tumor cells (CTCs) for the differential diagnosis of patients with benign lung diseases and those with NSCLC. To explore the phenotypic heterogeneity of CTCs and their correlation with FDG uptake in patients with Stage I-IV NSCLC. METHODS: Blood specimens from patients with benign lung diseases and patients with primary NSCLC were collected for the detection of CTCs and their subtypes (epithelial, mixed, and mesenchymal) and analyzed for 18F-FDG PET/CT tumor metabolic parameters, including the maximum standardized uptake value (SUVmax), standard uptake value (SUL), metabolic tumor volume of primary lesion (MTV), total lesion glycolysis of primary lesion (TLG). Clinical data including age, gender, smoking history, tumor size, TNM stage and pathology type were also collected. The value of the two method alone and in combination for the differential diagnosis of benign and malignant was comparatively analyzed. Finally, the differences in CTC and its subtypes in different stages of NSCLC were compared, and FDG metabolic parameters were correlated with CTC subtypes. RESULTS: There were a total of 65 patients with pulmonary diseases, including 12 patients with benign pulmonary diseases and 53 patients with NSCLC. The mean age was 67 ± 10 (38-89 years), 27 were females and 38 were males. 31 (22 males and 9 females) had a long history of smoking. The mean size of the largest diameter of all single lesions was 36 ± 22 mm with a range of 10-108 mm. Seven out of 12 benign diseases were inflammatory granulomatous lesions and 5 were inflammatory pseudotumours. Twenty-four out of 53 NSCLC were adenocarcinomas and 29 were squamous carcinomas. Twelve out of 53 patients with NSCLC were in Stage I, 10 were in Stage II, 17 were in Stage III and 14 were in Stage IV. SUVmax, SUL, MTV, TLG, total CTCs, epithelial CTCs, and mixed CTCs were all valuable in the differential diagnosis of benign and malignant. TLG combined with mixed CTCs was statistically different from all other diagnostic methods (p < 0.05) and higher than any other diagnostic criteria. In the differential diagnosis of benign and Stage I NSCLC, only total CTC (Z = -2.188 p = 0.039) and mixed CTCs (Z = -3.020 p = 0.014) had certain diagnostic efficacy, and there was no statistical difference between them (p = 0.480). Only mesenchymal CTCs differed in Stage I-IV NSCLC, with a higher number of those who developed distant metastases than those who had non-distant metastases. Epithelial CTCs correlated with SUVmax (r = 0.333, p = 0.015) and SUL (r = 0.374, p = 0.006). Mmesenchymal CTCs correlated with MTV (r = 0.342, p = 0.018) and TLG (r = 0.319, p = 0.02). Further subgroup analyses revealed epithelial CTCs were correlated with SUVmax (r = 0.543, p = 0.009) and SUL (r = 0.552, p = 0.008), and the total CTCs was correlated with SUVmax (r = 0.622, p = 0.003), SUL (r = 0.652, p = 0.003), MTV (r = 0.460, p = 0.031), and TLG (r = 0.472, p = 0.027) in the early group (Stage I-II). Only mesenchymal CTCs was associated with MTV (r = 0.369, p = 0.041), and TLG (r = 0.415, p = 0.02) in the intermediate-late group (Stage III-IV). CONCLUSION: Both FDG PET metabolic parameters and CTCs demonstrated diagnostic value for NSCLC, and combining TLG with mixed CTCs could enhance their diagnostic efficacy. The total CTCs and mixed CTCs showed greater diagnostic value than FDG PET in distinguishing benign lesions from Stage I NSCLC. In NSCLC patients, the epithelial CTCs exhibited a positive correlation with SUVmax and SUL, while mesenchymal CTCs correlated with MTV, and TLG. Besides, epithelial CTCs showed stronger correlations with SUVmax and SUL, and total CTCs showed stronger correlations with SUVmax, SUL, MTV, and TLG in Stage I-II NSCLC. Only mesenchymal CTCs in Stage III-IV NSCLC showed correlations with MTV and TLG. Stage IV NSCLC cases displayed a higher number of mesenchymal CTCs.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Fluordesoxiglucose F18 , Neoplasias Pulmonares , Células Neoplásicas Circulantes , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Masculino , Feminino , Células Neoplásicas Circulantes/patologia , Células Neoplásicas Circulantes/metabolismo , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Pessoa de Meia-Idade , Idoso , Diagnóstico Diferencial , Estadiamento de Neoplasias , Adulto , Idoso de 80 Anos ou mais , Compostos RadiofarmacêuticosRESUMO
BACKGROUND: In China's expanding dairy industry, a lack of oversight regarding antimicrobial use and increasing antimicrobial resistance are evident. Selective treatments of dairy cows for clinical mastitis or dry cow therapy are proposed to promote judicious antimicrobial use without adversely impacting cattle health. These approaches have been successfully implemented on farms in other countries. METHODS: On 28 October 2023, a 2-day in-person seminar was held in Beijing, China, on selective antimicrobial treatments of dairy cows for clinical mastitis or dry cow therapy on large Chinese dairy farms. Concurrently, a qualitative study involving 15 technical managers from the 13 largest Chinese dairy groups used focus group discussions and questionnaires to explore perspectives on selective treatments of dairy cows for clinical mastitis or dry cow therapy. The main outcomes assessed were opinions and concerns regarding implementing selective antimicrobial treatments. RESULTS: Although there was diversity of cognition on AMR and selective treatments, the technical managers were generally positive regarding adoption of selective treatments. However, they expressed a need for more evidence and tools, including anticipated economic impacts, effects of delaying treatment until diagnosis, accurate interpretation of milk recording data, safe use of internal teat sealants, and spread of pathogens. Participants stressed the need for awareness, staff training, farm management, and China-specific standards, suggesting large-scale trials to assess efficacy of selective treatments. CONCLUSION: The findings revealed key challenges and barriers currently impeding selective AMU practices. These insights could inform efforts to promote judicious AMU on farms through targeted treatment regimens, reducing mounting selective pressure driving resistance.
RESUMO
Current research on the stellate ganglion (SG) has shifted from merely understanding its role as a collection of neurons to recognizing its importance in immune regulation. As part of the autonomic nervous system (ANS), the SG plays a crucial role in regulating cardiovascular function, particularly cardiac sympathetic nerve activity. Abnormal SG function can lead to disordered cardiac electrical activity, which in turn affects heart rhythm stability. Studies have shown that excessive activity of the SG is closely related to the occurrence of arrhythmias, especially in the context of inflammation. Abnormal activity of the SG may trigger excessive excitation of the sympathetic nervous system (SNS) through neuroimmune mechanisms, thereby increasing the risk of arrhythmias. Simultaneously, the inflammatory response of the SG further aggravates this process, forming a vicious cycle. However, the causal relationship between SG, inflammation, and arrhythmias has not yet been fully clarified. Therefore, this article deeply explores the key role of the SG in arrhythmias and its complex relationship with inflammation, providing relevant clinical evidence. It indicates that interventions targeting SG function and inflammatory responses have potential in preventing and treating inflammation-related arrhythmias, offering a new perspective for cardiovascular disease treatment strategies.
RESUMO
Although previous research has shown that inflammation is associated with development of colorectal cancer (CRC), questions remain about whether inflammatory factor-secreting bacteria play a crucial role in CRC development. The potential role of gut microbiota in secreting inflammatory factors involved in the carcinogenesis of CRC among Chinese patients was explored in this study. 16S rRNA sequencing was utilized to evaluate the distinct microbial characteristics between patients with CRC and colorectal adenoma. The serum levels of TNF-α, IL-6 and IL-10 were measured using Enzyme-linked immunosorbent assay (ELISA), while the expression of LRG1 and TGF-ß1 in tissues was evaluated by immunohistochemistry. The correlation between gut microbiota and inflammatory factor signaling was analyzed. Compared with the adenoma group, CRC patients exhibit distinct pathologies. Moreover, elevated levels of CEA, erythrocytes and haemoglobin in the blood of CRC patients were found. In addition, CRC patients have significantly higher levels of TNF-α, IL-6, IL-10, LRG1 and TGF-ß1. Spearman correlation analysis revealed that LRG1 was positively related to IL-6 and TNF-α, respectively. The correlation analysis results of TGF-ß1 were consistent with the above. The abundance of Blautia and Streptococcus was lower in CRC patients, while the relative abundance of Alistipes, Peptostreptococcus and Porphyromonas was significantly elevated. Moreover, positive correlations between Alistipes and inflammatory factor signaling were also found. Our results suggest that gut commensal Alistipes is a key bacterium with pro-inflammatory properties in the CRC carcinogenesis. TNF-α and IL-6 associated with Alistipes might activate LRG1/TGF-ß1 signaling which contributed to the carcinogenesis of CRC.
RESUMO
BACKGROUND: Respiratory syncytial virus (RSV) is a prominent etiological agent of lower respiratory tract infections in children, responsible for approximately 80% of cases of pediatric bronchiolitis and 50% of cases of infant pneumonia. Despite notable progress in the diagnosis and management of pediatric RSV infection, the current biomarkers for early-stage detection remain insufficient to meet clinical needs. Therefore, the development of more effective biomarkers for early-stage pediatric respiratory syncytial virus infection (EPR) is imperative. METHODS: The datasets used in this study were derived from the Gene Expression Omnibus (GEO) database. We used GSE188427 dataset as the training set to screen for biomarkers. Biomarkers of EPR were screened by Weighted Gene Co-expression Network Analysis (WGCNA), three machine-learning algorithms (LASSO regression, Random Forest, XGBoost), and other comprehensive bioinformatics analysis techniques. To evaluate the diagnostic value of these biomarkers, multiple external and internal datasets were employed as validation sets. Next, an examination was performed to investigate the relationship between the screened biomarkers and the infiltration of immune cells. Furthermore, an investigation was carried out to identify potential small molecule compounds that interact with selected diagnostic markers. Finally, we confirmed that the expression levels of the selected biomarkers exhibited a significant increase following RSV infection, and they were further identified as having antiviral properties. RESULTS: The study found that lymphocyte antigen 6E (LY6E) and Transcobalamin-2 (TCN2) are two biomarkers with diagnostic significance in EPR. Analysis of immune cell infiltration showed that they were associated with activation of multiple immune cells. Furthermore, our analysis demonstrated that small molecules, 3'-azido-3'-deoxythymine, methotrexate, and theophylline, have the potential to bind to TCN2 and exhibit antiviral properties. These compounds may serve as promising therapeutic agents for the management of pediatric RSV infections. Additionally, our data revealed an upregulation of LY6E and TCN2 expression in PBMCs from patients with RSV infection. ROC analysis indicated that LY6E and TCN2 possessed diagnostic value for RSV infection. Finally, we confirmed that LY6E and TCN2 expression increased after RSV infection and further inhibited RSV infection in A549 and BEAS-2B cell lines. Importantly, based on TCN2, our findings revealed the antiviral properties of a potentially efficacious compound, vitamin B12. CONCLUSION: LY6E and TCN2 are potential peripheral blood diagnostic biomarkers for pediatric RSV infection. LY6E and TCN2 inhibit RSV infection, indicating that LY6E and TCN2 are potential therapeutic target for RSV infection.
Assuntos
Biomarcadores , Infecções por Vírus Respiratório Sincicial , Humanos , Biomarcadores/metabolismo , Bases de Dados Genéticas , Redes Reguladoras de Genes , Aprendizado de Máquina , Reprodutibilidade dos Testes , Infecções por Vírus Respiratório Sincicial/virologia , Infecções por Vírus Respiratório Sincicial/diagnóstico , Curva ROCRESUMO
Continuous directed evolution of base editors (BEs) has been successful in bacteria cells, but not yet in mammalian cells. Here, we report the development of a Continuous Directed Evolution system in Mammalian cells (CDEM). CDEM enables the BE evolution in a full-length manner with Cas9 nickase. We harness CDEM to evolve the deaminases of cytosine base editor BE3 and adenine base editors, ABEmax and ABE8e. The evolved cytidine deaminase variants on BE4 architecture show not only narrowed editing windows, but also higher editing purity and low off-target activity without a trade-off in on-targeting activity. The evolved ABEmax and ABE8e variants exhibit narrowed or shifted editing windows to different extents, and lower off-target effects. The results illustrate that CDEM is a simple but powerful approach to continuously evolve BEs without size restriction in the mammalian environment, which is advantageous over continuous directed evolution system in bacteria cells.
Assuntos
Adenina , Sistemas CRISPR-Cas , Citidina Desaminase , Citidina , Evolução Molecular Direcionada , Edição de Genes , Edição de Genes/métodos , Humanos , Adenina/metabolismo , Evolução Molecular Direcionada/métodos , Citidina/metabolismo , Citidina/genética , Citidina Desaminase/metabolismo , Citidina Desaminase/genética , Células HEK293 , Proteína 9 Associada à CRISPR/metabolismo , Proteína 9 Associada à CRISPR/genética , AnimaisRESUMO
Cholangiocarcinoma (CCA) is a rare but highly invasive cancer, with its incidence rising in recent years. Currently, surgery remains the most definitive therapeutic option for CCA. However, similar to other malignancies, most CCA patients are not eligible for surgical intervention at the time of diagnosis. The chemotherapeutic regimen of gemcitabine combined with cisplatin is the standard treatment for advanced CCA, but its effectiveness is often hampered by therapeutic resistance. Recent research highlights the remarkable plasticity of tumor-associated macrophages (TAMs) within the tumor microenvironment (TME). TAMs play a crucial dual role in either promoting or suppressing tumor development, depending on the factors that polarize them toward pro-tumorigenic or anti-tumorigenic phenotypes, as well as their interactions with cancer cells and other stromal components. In this review, we critically examine recent studies on TAMs in CCA, detailing the expression patterns and prognostic significance of different TAM subtypes in CCA, the mechanisms by which TAMs influence CCA progression and immune evasion, and the potential for reprogramming TAMs to enhance anticancer therapies. This review aims to provide a framework for deeper future research.
Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Progressão da Doença , Microambiente Tumoral , Macrófagos Associados a Tumor , Humanos , Colangiocarcinoma/imunologia , Colangiocarcinoma/patologia , Colangiocarcinoma/etiologia , Colangiocarcinoma/terapia , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo , Neoplasias dos Ductos Biliares/imunologia , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/terapia , Neoplasias dos Ductos Biliares/etiologia , Microambiente Tumoral/imunologia , Animais , Evasão TumoralRESUMO
PLCD3 belongs to the phospholipase C delta group and is involved in numerous biological functions, including cell growth, programmed cell death, and specialization. However, the role of PLCD3 in lung cancer still needs further investigation. This research aimed to investigate if PLCD3 influences glycolytic reprogramming and lung cancer development through the PKC-dependent Rap1 signaling pathway. This study found that PLCD3 was increased in lung cancer tissues. PLCD3 promotes the proliferation and invasion of lung cancer cells by activating the PKC-dependent Rap1 pathway. The detailed process involves PLCD3 triggering PKC, which subsequently stimulates the Rap1 pathway, leading to glycolytic reprogramming that supplies adequate energy and metabolic substrates necessary for the growth and spread of lung cancer cells. Moreover, PLCD3 can also promote the metastasis and invasion of lung cancer cells by activating the Rap1 pathway. This study reveals the mechanism of PLCD3 in lung cancer and provides new ideas for the treatment of lung cancer. Inhibiting PLCD3, PKC, and the Rap1 pathway may be an effective strategy for treating lung cancer.
RESUMO
OBJECTIVE: The purpose of this study is to construct an organ system-centered undergraduate nursing professional training model and explore its application effect. METHODS: This study is divided into two steps. In the early stage, literature review and expert consultation were used to establish the training mode (curriculum and assessment standard) of nursing undergraduate specialty based on organ system reform. Secondly, a cross-sectional survey method was used to investigate the training quality of nursing students who graduated from Jinzhou Medical University from 2007 to 2017 under this model. RESULTS: A five-module curriculum system was established, including general courses, public basic courses, professional education courses, expanding elective courses and concentrated practical teaching. Under the teaching reform of organ system, the nursing graduates of Jinzhou Medical University, who are mainly employed in public hospitals, are generally not satisfied with their jobs, salaries, contents and prospects. Their overall satisfaction with their alma mater is very high; Graduates have certain independent core competence; Employers are basically satisfied with graduates. CONCLUSION: The training mode of undergraduate nursing specialty based on organ system reform basically meets the training requirements and objectives.
RESUMO
BACKGROUND: To investigate the cross-sectional and longitudinal associations between depressive symptoms and the prevalence of frailty and its components in a nationally representative sample of middle-aged and older Chinese adults. METHOD: The China Health and Retirement Longitudinal Study (CHARLS) provided data on 2581 (after inclusion and exclusion criteria) adults aged ≥ 45 years. Every two years, face-to-face, computer-aided personal interviews (CAPI), and structured questionnaires were used to follow up with the respondents. The Chinese version of the Center for Epidemiologic Studies-Depression Scale (CES-D) was used to evaluate depressive symptoms, and the Fried criteria were used to measure frailty. The odds ratio (OR) and 95% confidence interval (CI) for the association of exposure (depressive symptoms at baseline) with the onset of the outcome (frailty and its components) in the individuals at baseline were analyzed by binary logistic regression. RESULTS: At baseline, 11.62% of participants had frailty, and 57.92% had depressive symptoms. In the cross-sectional analysis, depressive symptoms (OR = 5.222, 95%CI 3.665-7.442) were associated with frailty. In the longitudinal analysis, after adjusting for the full set of covariates among participants free of baseline frailty, depressive symptoms were significantly associated with incident frailty during the short term (OR = 2.193, 95%CI 1.324-3.631) and the long term (OR = 1.926, 95%CI 1.021-3.632). Meanwhile, depressive symptoms were associated with an increased risk of weakness (OR = 1.990, 95%CI 1.250-3.166), slowness (OR = 1.395, 95%CI 1.044-1.865), and exhaustion (OR = 2.827, 95%CI 2.150-3.719) onset during the short-term. Depressive symptoms were associated with an increased risk of exhaustion (OR = 2.869, 95%CI 2.004-4.109) onset during the long-term. CONCLUSION: Among middle-aged and older adults, depressive symptoms could predict frailty during 2 years of follow-up and 4 years of follow-up. When considering potential confounding factors, depressive symptoms were considered a predictor of weakness, slowness, and exhaustion. Interventions aimed at preventing depressive symptoms may be beneficial in reducing frailty and its components.
Assuntos
Depressão , Fragilidade , Humanos , Estudos Longitudinais , Masculino , Feminino , Depressão/epidemiologia , Pessoa de Meia-Idade , Idoso , China/epidemiologia , Fragilidade/epidemiologia , Fragilidade/psicologia , Estudos Transversais , Prevalência , Idoso Fragilizado/estatística & dados numéricos , Idoso Fragilizado/psicologia , Idoso de 80 Anos ou mais , Inquéritos e QuestionáriosRESUMO
Klebsiella pneumoniae is a primary cause of clinical mastitis in dairy cows, with prevention being crucial, as treatments often fail due to antimicrobial resistance. Recent studies identified type I fimbrial antigens of K. pneumoniae as promising vaccine candidates, but there are limited research data. In this study, 3 fimbriae genes (fimA, fimC and fimG) were cloned and recombinantly expressed in Escherichia coli and their protective efficacy against K. pneumoniae evaluated in a mouse model. All 3 recombinant fimbriae proteins elicited strong humoral immune responses in mice, significantly increasing IgG, IgG1 and IgG2a. Notably, using a model of mice challenged with an intraperitoneal injection of bacteria, FimG significantly reduced bacterial loads in the spleen and lung, whereas FimA and FimC had limited protection for these organs. Either active or passive immunization with FimG produced substantial protective effects in mice challenged with K. pneumoniae LD100; in contrast, the mortality rate in the FimA-immunized group was similar to that of the control group, whereas FimC had weak protection. We concluded that the FimG recombinant protein vaccine had a favorable protective effect, with potential for immunization against K. pneumoniae mastitis.
Assuntos
Anticorpos Antibacterianos , Vacinas Bacterianas , Modelos Animais de Doenças , Proteínas de Fímbrias , Infecções por Klebsiella , Klebsiella pneumoniae , Camundongos Endogâmicos BALB C , Animais , Klebsiella pneumoniae/imunologia , Camundongos , Infecções por Klebsiella/prevenção & controle , Infecções por Klebsiella/imunologia , Infecções por Klebsiella/microbiologia , Proteínas de Fímbrias/imunologia , Proteínas de Fímbrias/genética , Feminino , Vacinas Bacterianas/imunologia , Vacinas Bacterianas/administração & dosagem , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Proteínas Recombinantes/imunologia , Fímbrias Bacterianas/imunologia , Imunoglobulina G/sangue , Imunidade HumoralRESUMO
We present a novel approach to induce charge density waves (CDWs) in metallic MA2Z4 materials, resembling the behavior observed in transition metal dichalcogenides (TMDCs). This method leverages the intercalating architecture to maintain the same crystal field and Fermi surface topologies. Our investigation reveals that CDW instability in these materials arises from electron-phonon coupling (EPC) between the d band and longitudinal acoustic (LA) phonons, mirroring TMDC's behavior. By combining α-MA2Z4 with 1H-MX2 materials in a predictive CDW phase diagram using critical EPC constants, we demonstrate the feasibility of extending CDW across material families with comparable crystal fields and reveal the crucial role in CDW instability of the competition between ionic charge transfer and electron correlation. We further uncover a strain-induced Mott transition in ß2-NbGe2N4 monolayer featuring star-of-David patterns. This work highlights the potential of intercalating architecture to engineer CDW materials, expanding our understanding of CDW instability and correlation physics.
RESUMO
Cell division cycle 5-like (CDC5L) protein is implicated in the development of various cancers. However, its role in the progression of lung adenocarcinoma (LUAD) remains uncertain. Our findings revealed frequent upregulation of CDC5L in LUAD, which correlated with poorer overall survival rates and advanced clinical stages. In vitro experiments demonstrated that CDC5L overexpression stimulated the proliferation, migration, and invasion of LUAD cells, whereas CDC5L knockdown exerted suppressive effects on these cellular processes. Furthermore, silencing CDC5L significantly inhibited tumor growth and metastasis in a xenograft mouse model. Mechanistically, CDC5L activates the Wnt/ß-catenin signaling pathway by transcriptionally regulating WNT7B, thereby promoting LUAD progression. Besides, METTL14-mediated m6A modification contributed to CDC5L upregulation in an IGF2BP2-dependent manner. Collectively, our study uncovers a novel molecular mechanism by which the m6A-induced CDC5L functions as an oncogene in LUAD by activating the Wnt/ß-catenin pathway through transcriptional regulation of WNT7B, suggesting that CDC5L may serve as a promising prognostic marker and therapeutic target for LUAD.
RESUMO
Regarding the rheological properties of fluids, certain nanoparticles can markedly modify the rheological behavior of low surface tension solutions by interacting with surfactant molecules. In this work, a low surface tension fluid with cetyltrimethylammonium chloride was prepared, and the silica nanoparticles were uniformly dispersed into it by ultrasonic dispersion. By adjusting the size, shape, and concentration of nanoparticles, the fluid behavior can be changed from Newtonian to non-Newtonian with finely tuned viscosity and characterized by a shear-thinning rheological behavior. In addition, this work explored how variations in environmental temperature and solution pH affect the rheological responses of the low surface tension suspension system. The experimental findings revealed that increasing the temperature substantially decreases the system's viscosity and induces a shear-thickening behavior. It is particularly significant that, under extreme pH conditions (either strongly acidic or alkaline), the viscosity of the nanoparticle suspensions was markedly enhanced at a particle concentration of 10 000 ppm. This interesting result coincided with a notable reduction in the zeta potential and an increase in the average particle size, suggesting an intensified aggregation of particles within the suspension system. A mechanism detailing the interaction between silica nanoparticles and surfactant micelles was proposed. This work indicates that the incorporation of nanoparticles into surfactant solutions offers a powerful approach to modulating fluid rheology across various conditions.
RESUMO
Malnutrition early in life may have adverse effects on health later in life. The relationship between malnutrition and obesity parameters (body mass index [BMI] and waist circumference [WC]) and type 2 diabetes is inconsistent. This study aimed to identify the effects of famine exposure and obesity parameters on type 2 diabetes individually or in combination among middle-aged and older adults in China. Data were extracted from the China Health and Retirement Longitudinal Study Wave1 in 2011. The sample involved 13,065 adults aged 45 to 90. The t- or F test was employed to compare age among groups. The chi-square test was utilized to compare baseline characteristics according to the categorical WC levels/BMI levels/famine exposure and examine between-group differences in type 2 diabetes (diabetes and non-diabetes). Odds ratio (OR) and 95% confidence interval (CI) were estimated by logistic regression models to estimate the individual and combined associations of BMI/WC levels and famine exposure with the prevalence of type 2 diabetes. In this study, 1559 (11.93%) individuals were exposed to Chinese famine during their fetal stage, 5132 (39.28%) and 4428 (33.89%) in childhood and adolescence/adulthood, respectively. Among BMI measurements, 3780 (28.93%) were overweight, and 1487 (11.38%) were obese, whereas WC measurements showed that 5408 (41.39%) were obesity. In addition, 831 (45.48%) males and 996 (54.52%) females reported type 2 diabetes. In multivariable-adjusted regression models, obesity parameters and famine exposure were independently associated with type 2 diabetes prevalence among all participants (Pâ <â .001). In the interaction analysis, there existed a trend of higher odds for prevalence of type 2 diabetes across all groups compared to the combination of no-exposed and normal BMI/WC level group (the most increase in odds, adolescence/adulthood-exposed group with central obesity in WC levels: OR 4.51 (95% CI = 3.42-5.95); adolescence/adulthood-exposed group with obesity in BMI levels: OR 5.84 (95% CI = 4.11-8.30; P for interaction <.001). The findings for females exhibited similar to the overall participants, when by gender stratification. Our results suggest famine exposure and obesity parameters have positive combined effects on type 2 diabetes in middle-aged and older adults in China.
Assuntos
Índice de Massa Corporal , Diabetes Mellitus Tipo 2 , Fome Epidêmica , Obesidade , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Transversais , Idoso , China/epidemiologia , Obesidade/epidemiologia , Fome Epidêmica/estatística & dados numéricos , Circunferência da Cintura , Idoso de 80 Anos ou mais , Prevalência , Estudos LongitudinaisRESUMO
Piglet birth weight is associated with preweaning survival, and its related traits have been included in the breeding program. Thus, understanding its genetic basis is essential. This study identified four birth weight-associated genomic regions on chromosomes 2, 4, 5, and 7 through genome-wide association study analysis in 7286 pigs from three different pure breeds using the FarmCPU model. The genetic and phenotypic variance explained by the four candidate regions is 8.42% and 1.85%, respectively. Twenty-eight candidate genes were detected, of which APPL2, TGFBI, MACROH2A1, and SEC22B have been reported to affect body growth or development. In addition, 21 H3K4me3-enriched peaks overlapped with the birth weight-associated genomic regions were identified by integrating the genome-wide association study results with our previous ChIP-seq and RNA-seq data generated in the pig placenta, a fetal organ relevant to birth weight, and three of the regulatory regions influence TGFBI, MACROH2A1, and SEC22B expression. This study provides new insights into understanding the mechanisms for birth weight. Further investigating the variants in the regulatory regions would help identify the functional variants for birth weight in pigs.
RESUMO
Relapse remains the main cause of treatment failure in patients with myeloid malignancies even after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We observed a particularly low incidence of relapse in patients prepared with fludarabine, busulfan and melphalan in our previous study and this multicenter retrospective analysis aimed to confirm the feasibility of the regimen and to identify the potential prognostic factors. This study was performed using registry data from adults patients with myeloid malignancies who underwent their first allo-HSCT following fludarabine(≥100 mg/m2), busulfan (≥3.2 mg/kg) and melphalan (≥100 mg/m2) based conditioning at nine transplantation centers in China between Jan. 2020 and Mar. 2022. A total of 221 consecutive patients (AML n = 171, MDS-IB-1 or 2 n = 44, CMML n = 6) with median age of 46 were enrolled in this study. The median follow-up was 507 days for survivors. The 2-year NRM, CIR, OS and DFS were 10.6% ± 2.2%, 14.8% ± 3.3%, 79.4% ± 3.7% and 74.6% ± 3.7%, respectively. In multivariate analyses, high HCT-CI (≥3) was the only independent factor for higher NRM [hazard ratio (HR), 2.96; 95% confidence interval (CI), 1.11 to 7.90; p = 0.030] and ECOG score ≥2 was the only independent factor for inferior OS (HR, 2.43; 95%CI, 1.15 to 5.16; p = 0.020) and DFS (HR, 2.12; 95%CI, 1.13 to 4.02; p = 0.020). AML diagnosis and positive measurable residual disease (MRD) at transplantation were predictors for higher CIR (HR = 7.92, 95%CI 1.05-60.03, p = 0.045; HR = 3.64, 95%CI 1.40-9.44, p = 0.008; respectively), while post-transplantation cyclophosphamide based graft-versus-host disease prophylaxis was associated with lower CIR (HR = 0.24 95%CI 0.11-0.54, p = 0.001). The intensity of conditioning regimen did not impact CIR, NRM, DFS and OS. These results supported that double alkylating agents of busulfan and melphalan based conditioning regimens were associated with low relapse rate and acceptable NRM in adult patients with myeloid malignancies. The optimal dose remained to be confirmed by further prospective studies.
RESUMO
Wheat starch fermentation slurry is the main substrate for producing Ganmianpi, a traditional Chinese fermented wheat starch-based noodle. In the present work, the microbial population dynamics and metabolite changes in wheat starch fermentation slurry at different fermentation times (0, 1, 2, 3, and 4 days) were measured by using high-throughput sequencing analysis and headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME/GC-MS) methods. The texture and sensory properties of Ganmianpi made from fermented starch slurry are also evaluated. The results showed that Latilactobacillus curvatus and Leuconostoc citreum were the dominant bacteria in wheat starch fermentation slurry, while Saccharomyces cerevisiae and Kazachstania wufongensis were identified as the main species of fungi. With the extension of fermentation time, the reducing sugar content first increased and then decreased, when the titratable acidity content showed an increasing trend, and the nonvolatile acid was significantly higher than the volatile acid. A total of 62 volatile flavor compounds were identified, and the highest content is alcohols, followed by acids. Fermentation significantly reduced the hardness and chewiness of Ganmianpi, and increased its resilience and cohesiveness. Ganmianpi made from fermented starch slurry for two and three days showed a higher sensory score than other samples. The present study is expected to provide a theoretical basis for exploiting the strains with potential for commercial application as starter cultures and quality improvement of Ganmianpi.
RESUMO
BACKGROUND: The purpose of this study was to investigate the role of legumain in metabolic dysfunction, diagnosis, and prognosis in patients with atherosclerosis. METHODS: Plasma levels of legumain from patients with atherosclerosis (nâ =â 320) and healthy controls (nâ =â 320), expression of legumain in atheromatous plaque and secreted from monocyte-derived macrophages were measured using enzyme-linked-immunosorbent assay, reverse transcription-polymerase chain reaction, Western blot, immunohistochemistry, and fluorescence. RESULTS: Data demonstrated that atherosclerotic patients had higher plasma level of legumain than healthy controls, which was a diagnostic and prognostic marker and corrected with the degree of atherosclerosis. It found that atheromatous plaque and endothelial cell had higher legumain expression than non-atherosclerotic arteries (controls). Legumain showed significantly increased secretion from pro-inflammatory M1 compared to pro-resolving M2 macrophages during monocyte-derived macrophages, which was localized to structures resembling foam cells. CONCLUSION: In conclusion, our data indicate that legumain expression is upregulated in both plasma and plaques of patients with atherosclerosis, which is associated with metabolic dysfunction of endothelial cell and might be a diagnostic and prognostic marker of atherosclerosis.
Assuntos
Aterosclerose , Biomarcadores , Cisteína Endopeptidases , Macrófagos , Humanos , Cisteína Endopeptidases/metabolismo , Cisteína Endopeptidases/sangue , Masculino , Feminino , Aterosclerose/diagnóstico , Aterosclerose/metabolismo , Prognóstico , Pessoa de Meia-Idade , Macrófagos/metabolismo , Biomarcadores/sangue , Biomarcadores/metabolismo , Placa Aterosclerótica/metabolismo , Idoso , Estudos de Casos e Controles , Regulação para Cima , AdultoRESUMO
Clear cell renal cell carcinoma (ccRCC) is a common kidney cancer with subtle early symptoms, high recurrence rates, and low sensitivity to traditional treatments like radiotherapy and chemotherapy. Identifying novel therapeutic targets is critical. The expression level of adenylate kinases 7 (AK7) in ccRCC was examined by the TCGAportal and UALCAN databases. The effect of AK7 on proliferation, invasion and migration of ccRCC cell lines was evaluated by cell assay. The correlation between AK7 expression and prognosis, as well as its direct relationship with immunotherapy efficacy, was analyzed using CANCERTOOL and Kaplan-Meier plotter data. Moreover, the TISIDB database was used to study the relationship between AK7 and immune markers. The effect of overexpressed AK7 combined with PD1 monoclonal antibody on ccRCC was evaluated in animal experiments. The results showed that low level of AK7 expression was observed in ccRCC tissues. The expression of AK7 can regulate the proliferation, invasion, and migration of human ccRCC cell lines. The level of AK7 expression was associated with OS of ccRCC patients. This was potentially due to the negative connection between AK7 expression and CD8+ T cell depletion, indicating that immunotherapy might be less effective in individuals with low AK7 expression. Conversely, augmenting AK7 demonstrated an enhanced effectiveness of anti-PD1 therapy. The findings of our research strongly indicated that AK7 could serve as both a prognostic indicator and therapeutic target for patients with ccRCC. Moreover, the overexpression of AK7 combined with anti-PD1 held promising potential as a therapeutic approach for treating ccRCC.