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Circulating tumor cells (CTC) are considered metastatic precursors that are shed from the primary or metastatic deposits and navigate the bloodstream before undergoing extravasation to establish distant metastases. Metabolic reprogramming appears to be a hallmark of metastatic progression, yet current methods for evaluating metabolic heterogeneity within organ-specific metastases in vivo are limited. To overcome this challenge, we present Biofluorescence Imaging-Guided Spatial Metabolic Tracing (BIGSMT), a novel approach integrating in vivo biofluorescence imaging, stable isotope tracing, stain-free laser capture microdissection, and liquid chromatography-mass spectrometry. This innovative technology obviates the need for staining or intricate sample preparation, mitigating metabolite loss, and substantially enhances detection sensitivity and accuracy through chemical derivatization of polar metabolites in central carbon pathways. Application of BIGSMT to a preclinical CTC-mediated metastasis mouse model revealed significant heterogeneity in the in vivo carbon flux from glucose into glycolysis and the tricarboxylic acid (TCA) cycle across distinct metastatic sites. Our analysis indicates that carbon predominantly enters the TCA cycle through the enzymatic reaction catalyzed by pyruvate dehydrogenase. Thus, our spatially resolved BIGSMT technology provides fresh insights into the metabolic heterogeneity and evolution during melanoma CTC-mediated metastatic progression and points to novel therapeutic opportunities.
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BACKGROUND: The detection and management of intracranial aneurysms (IAs) are vital to prevent life-threatening complications like subarachnoid hemorrhage (SAH). Artificial Intelligence (AI) can analyze medical images, like CTA or MRA, spotting nuances possibly overlooked by humans. Early detection facilitates timely interventions and improved outcomes. Moreover, AI algorithms offer quantitative data on aneurysm attributes, aiding in long-term monitoring and assessing rupture risks. METHODS: We screened four databases (PubMed, Web of Science, IEEE and Scopus) for studies using artificial intelligence algorithms to identify IA. Based on algorithmic methodologies, we categorized them into classification, segmentation, detection and combined, and then their merits and shortcomings are compared. Subsequently, we elucidate potential challenges that contemporary algorithms might encounter within real-world clinical diagnostic contexts. Then we outline prospective research trajectories and underscore key concerns in this evolving field. RESULTS: Forty-seven studies of IA recognition based on AI were included based on search and screening criteria. The retrospective results represent that current studies can identify IA in different modal images and predict their risk of rupture and blockage. In clinical diagnosis, AI can effectively improve the diagnostic accuracy of IA and reduce missed detection and false positives. CONCLUSIONS: The AI algorithm can detect unobtrusive IA more accurately in communicating arteries and cavernous sinus arteries to avoid further expansion. In addition, analyzing aneurysm rupture and blockage before and after surgery can help doctors plan treatment and reduce the uncertainties in the treatment process.
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Algoritmos , Inteligencia Artificial , Aneurisma Intracraneal , Aneurisma Intracraneal/diagnóstico por imagen , Humanos , Angiografía por Resonancia Magnética/métodosRESUMEN
Pancreatic cancer is the deadliest malignancy with a poor response to chemotherapy but is potentially indicated for ferroptosis therapy. Here we identified that cytoplasmic polyadenylation element binding protein 1 (CPEB1) regulates NRF2 proteostasis and susceptibility to ferroptosis in pancreatic ductal adenocarcinoma (PDAC). We found that CPEB1 deficiency in cancer cells promotes the translation of p62/SQSTM1 by facilitating mRNA polyadenylation. Consequently, upregulated p62 enhances NRF2 stability by sequestering KEAP1, an E3 ligase for proteasomal degradation of NRF2, leading to the transcriptional activation of anti-ferroptosis genes. In support of the critical role of this signaling cascade in cancer therapy, CPEB1-deficient pancreatic cancer cells display higher resistance to ferroptosis-inducing agents than their CPEB1-normal counterparts in vitro and in vivo. Furthermore, based on the pathological evaluation of tissue specimens from 90 PDAC patients, we established that CPEB1 is an independent prognosticator whose expression level is closely associated with clinical therapeutic outcomes in PDAC. These findings identify the role of CPEB1 as a key ferroptosis regulator and a potential prognosticator in pancreatic cancer.
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Ferroptosis , Factor 2 Relacionado con NF-E2 , Neoplasias Pancreáticas , Humanos , Ferroptosis/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Línea Celular Tumoral , Animales , Factores de Escisión y Poliadenilación de ARNm/metabolismo , Factores de Escisión y Poliadenilación de ARNm/genética , Ratones , Proteostasis , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/genética , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/genética , Ratones DesnudosRESUMEN
In order to enhance ecosystem stability and promote sustainable regional ecological, social, and economic development, it is crucial to explore the coupling relationship between ecosystem service supply and demand and the resilience of ecosystem, so as to propose scientific ecological management zones and strategies. Taking the vulnerable alpine ecosystem in Gannan Tibetan Autonomous Prefecture (Gannan Prefecture) as the study area, this paper comprehensively utilized multi-source data, grid analysis, ecosystem service supply and demand estimation model, and coupled coordination model to analyze the spatio-temporal differentiation and coordination pattern of ecosystem service supply and demand in the study area from 2000 to 2020. With the assistance of the Analytic Hierarchy Process (AHP), the ecosystem resilience index system was constructed to evaluate the regional ecological resilience. The results reveal the following: (1) In the past 20 years, the ecosystem service supply and resilience in Gannan Prefecture showed a fluctuating upward trend, and the demand continued to grow steadily. Their spatial differentiation were obvious, but the pattern remained stable. (2) There was a moderate incoordination indicated by the average coordination degree of the supply and demand coupling of ecosystem services, which rangeed between 0.3 and 0.4. (3) Gannan Prefecture was split into three ecological management zones, considering the spatial distribution of ecosystem service supply and demand, as well as resilience. Through system function monitoring and other measures, the ecological conservation zone will rely on its high resilience to support the restoration and self-sufficiency of the system, ensuring the stability and well-being of the ecosystem. The primary objectives of general protected zone includes environmental preservation, strict regulations, and the prevention of human intervention. To enhance their ecological background, key restoration zone must intensify the implementation of ecological restoration initiatives. To address the needs of the locals, strategies such as ecological compensation, optimizing the land use structure, and fostering the growth of environmentally friendly companies can be implemented simultaneously.
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Conservación de los Recursos Naturales , Ecosistema , EcologíaRESUMEN
Patients who suffer from sepsis typically experience acute lung injury (ALI). Extracellular vesicles (EVs) contain miRNAs, which are potentially involved in ALI. However, strategies to screen more effective EV-miRNAs as therapeutic targets are yet to be elucidated. In this study, functional EV-miRNAs were identified based on multiomics analysis of single-cell RNA sequencing of targeted organs and serum EV (sEV) miRNA profiles in patients with sepsis. The proportions of neutrophils and macrophages were increased significantly in the lungs of mice receiving sEVs from patients with sepsis compared with healthy controls. Macrophages released more EVs than neutrophils. MiR-125a-5p delivery by sEVs to lung macrophages inhibited Tnfaip3, while miR-221-3p delivery to lung neutrophils inhibited Fos. Macrophage membrane nanoparticles (MM NPs) loaded with an miR-125a-5p inhibitor or miR-221-3p mimic attenuated the response to lipopolysaccharide (LPS)-induced ALI. Transcriptome profiling revealed that EVs derived from LPS-stimulated bone marrow-derived macrophages (BMDMs) induced oxidative stress in neutrophils. Blocking toll-like receptor, CXCR2, or TNFα signaling in neutrophils attenuated the oxidative stress induced by LPS-stimulated BMDM-EVs. This study presents a novel method to screen functional EV-miRNAs and highlights the pivotal role of macrophage-derived EVs in ALI. MM NPs, as delivery systems of key sEV-miRNA mimics or inhibitors, alleviated cellular responses observed in sepsis-induced ALI. This strategy can be used to reduce septic organ damage, particularly lung damage, by targeting EVs.
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Lesión Pulmonar Aguda , Vesículas Extracelulares , Macrófagos , Ratones Endogámicos C57BL , MicroARNs , Nanopartículas , Sepsis , Animales , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/tratamiento farmacológico , Sepsis/metabolismo , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/química , MicroARNs/metabolismo , Ratones , Nanopartículas/química , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Humanos , Masculino , Lipopolisacáridos , Neutrófilos/metabolismo , Estrés Oxidativo/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , MultiómicaRESUMEN
PURPOSE: To investigate the role of coexisting RET/PTC rearrangement and TERT promoter mutation in the prognosis and therapeutic targeting in papillary thyroid cancer (PTC). METHODS: A total of 669 PTC patients with complete clinical follow-up and genetic data were pooled from thyroid cancer datasets TCGA, MSK MetTropism, and MSK-IMPACT, from whom 163 patients (112 women and 47 men, 4 unknown) with wild-type BRAF/RAS were identified, with median age (IQR) of 46.00 (33.00, 61.00) years and median follow-up time (IQR) of 16.13 (8.09, 27.91) months for comparative genotype cohort analysis of mortality. RESULTS: There was a significant concurrence index between RET/PTC and TERT promoter mutations, being 2.040 (95% CI 1.110-3.747, P = 0.023). Mortality occurred in 5/100 (5%) patients harboring neither mutation, 2/18 (11.1%) patients harboring TERT promoter mutation alone, 0/31 (0%) patients harboring RET/PTC alone, and 7/14 (50%) patients harboring both genetic alterations, corresponding to HRs (95% CI) of 1 (Reference), 2.469 (0.405-14.02), 3.296e-09 (0-inf), and 9.019 (2.635-30.87), respectively, which remained essentially unchanged after adjustment for patient race, sex, and age. Similar results were observed with BRAF/RAS and TERT promoter mutations. Mechanistically, RET/PTC used the MAP kinase pathway to upregulate the mutated TERT, but not the wild-type TERT, and, correspondingly, targeting RET and MEK could suppress mutated TERT but not the wild-type TERT. CONCLUSION: Coexisting RET/PTC and TERT promoter mutation identify PTC as a unique clinical entity with high mortality, providing new implications for genetic-based prognostication and potential therapeutic targeting of RET and MEK guided by RET/PTC and TERT status.
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Circular RNA (circRNA) plays a key part in the pathological process of gastric cancer (GC). The study is organized to analyze the function of circPRDM5 in GC cell tumor properties. Expression levels of circPRDM5, miR-485-3p, glucosaminyl (N-acetyl) transferase 4 (GCNT4), ki67, E-cadherin, N-cadherin, and hexokinase 2 (HK2) were analyzed by quantitative real-time polymerase chain reaction (PCR), Western blotting or immunohistochemistry assay. Cell proliferation was assessed by cell colony formation assay and 5-ethynyl-2'-deoxyuridine assay. Cell migration and invasion were investigated by transwell assay. Glycolysis was evaluated by the Seahorse XF Glycolysis Stress Test Kit. Dual-luciferase reporter assay and RNA pull-down assay were performed to identify the associations among circPRDM5, miR-485-3p, and GCNT4. Xenograft mouse model assay was conducted to determine the effects of circPRDM5 on tumor formation in vivo. CircPRDM5 and GCNT4 expression were downregulated, while miR-485-3p expression was upregulated in GC tissues and cells when compared with paracancerous tissues or human gastric epithelial cells. CircPRDM5 overexpression inhibited proliferation, migration, invasion, and glucose metabolism of GC cells; however, circPRDM5 depletion had the opposite effects. CircPRDM5 repressed tumor properties of GC cells in vivo. MiR-485-3p restoration relieved circPRDM5-induced effects in GC cells. GCNT4 overexpression remitted the promoting effects of miR-485-3p mimics on GC cell malignancy. CircPRDM5 acted as a sponge for miR-485-3p, and GCNT4 was identified as a target gene of miR-485-3p. Moreover, circPRDM5 regulated GCNT4 expression by interacting with miR-485-3p.CircPRDM5 acted as a miR-485-3p sponge to inhibit GC progression by increasing GCNT4 expression, proving a potential target for GC therapy.
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MicroARNs , Neoplasias Gástricas , Humanos , Animales , Ratones , Neoplasias Gástricas/genética , Glucólisis/genética , Proliferación Celular/genética , Glucosa , MicroARNs/genética , Línea Celular TumoralRESUMEN
When handling real-world data modeled by a complex network dynamical system, the number of the parameters is often much more than the size of the data. Therefore, in many cases, it is impossible to estimate these parameters and the exact value of each parameter is frequently less interesting than the distribution of the parameters. In this paper, we aim to estimate the distribution of the parameters in the mesoscopic neuronal network model from the macroscopic experimental data, for example, the BOLD (blood oxygen level dependent) signal. Herein, we assume that the parameters of the neurons and synapses are inhomogeneous but independently and identically distributed from certain distributions with unknown hyperparameters. Thus, we estimate these hyperparameters of the distributions of the parameters, instead of estimating the parameters themselves. We formulate this problem under the framework of data assimilation and hierarchical Bayesian method and present an efficient method named Hierarchical Data Assimilation (HDA) to conduct the statistical inference on the neuronal network model with the BOLD signal data simulated by the hemodynamic model. We consider the Leaky Integral-Fire (LIF) neuronal networks with four synapses and show that the proposed algorithm can estimate the BOLD signals and the hyperparameters with high preciseness. In addition, we discuss the influence on the performance of the algorithm configuration and the LIF network model setup.
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Algoritmos , Neuronas , Teorema de Bayes , Neuronas/fisiologíaRESUMEN
BACKGROUND: The rapid adoption of next-generation sequencing in clinical oncology has enabled detection of molecular biomarkers which are shared between multiple tumour types. Intra-tumour heterogeneity is a mechanism of therapeutic resistance and therefore an important clinical challenge. However, the tumour-related copy number variants (CNVs), as key regulators of cancer origination, development, and progression, across various types of cancers are poorly understood. METHODS: We performed pan-cancer CNV analysis of cancer-related genes in 15 types of cancers including 1438 cancerous patients by next-generation sequencing using a commercially available pan-cancer panel (Onco PanScan™). Downstream bioinformatics analysis was performed in order to detect CNVs, cluster analysis of the found CNVs, and comparison of the frequency of gained CNVs between different types of cancers. LASSO analysis was used for identification of the most important CNVs. RESULTS: We also identified 523 CNVs among which 16 CNVs were common while 22 CNVs were caner-specific CNVs. Meanwhile, FAM58A was most commonly found in all studied cancers in this study and significant differences were found in FAM58A between female and male patients (p = .001). Common CNVs, such as FOXA1, NFKBIA, HEY1, MECOM, CHD7, AGO2, were mutated in 6.79%, 8.45%, 7.51%, 6.43%, 7.59%, 8.16% of tumours, while most of these mutations have proven roles in positive regulation of transcription from RNA polymerase II promoter. 11 features including sex, DIS3, EPHB1, ERBB2, FLT1, HCK, KEAP1, MYD88, PARP3, TBX3, and TOP2A were found as the key features for classification of cancers using CNVs. CONCLUSION: The 16 common CNVs between cancers can be used to identify the target of pan-cancer drug design and targeted therapies. Additionally, 22 caner-specific CNVs can be used as unique diagnostic markers for each cancer type.
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Variaciones en el Número de Copia de ADN , Neoplasias , Humanos , Masculino , Femenino , Proteína 1 Asociada A ECH Tipo Kelch/genética , Factor 2 Relacionado con NF-E2/genética , Neoplasias/genética , Biología ComputacionalRESUMEN
Nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) are intracellular proteins with a central role in innate and adaptive immunity. As a member of pattern recognition receptors (PRRs), NLRs sense specific pathogen-associated molecular patterns, trigger numerous signaling pathways and lead to the secretion of various cytokines. In recent years, cumulative studies have revealed the significant impacts of NLRs in gastrointestinal (GI) inflammatory diseases and cancers. Deciphering the role and molecular mechanism of the NLR signaling pathways may provide new opportunities for the development of therapeutic strategies related to GI inflammatory diseases and GI cancers. This review presents the structures and signaling pathways of NLRs, summarizes the recent advances regarding NLR signaling in GI inflammatory diseases and GI cancers and describes comprehensive therapeutic strategies based on this signaling pathway.
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Enfermedades Gastrointestinales , Neoplasias , Humanos , Inmunidad Innata , Transducción de Señal , Receptores de Reconocimiento de Patrones , Proteínas NLR/metabolismoRESUMEN
OBJECTIVE: To investigate the efficacy and safety of pomalidomide based regimen in the treatment of high-risk multiple myeloma (MM). METHODS: Clinical data of 27 high-risk MM patients treated in Shanxi Bethune Hospital from January 2021 to December 2022 were retrospectively analyzed. All patients were treated with pomadomide based regimen for at least 2 consecutive cycles, and the early therapeutic effect and safety were observed. RESULTS: Overall remission rate (ORR) was 63.0%(17/27 cases) and deep remission rate was 22.2%(6/27 cases) after 2 cycles of treatment; ORR was 90.5%(19/21 cases) and deep remission rate was 66.7%(14/21 cases) after 4 cycles of treatment. Both ORR and deep remission rate were significantly higher after 4 cycles of treatment than 2 cycles (P=0.044, P=0.003). Beyond that, in the newly diagnosed and relapsed refractory MM groups, ORR after 2 cycles of treatment were 75%(9/12 cases) and 60%(9/15 cases), and deep remission rates were 25%(3/12 cases) and 20%(3/15 cases), respectively; ORR after 4 cycles of treatment were 100%(9/9 cases) and 83.3%(10/12 cases), and deep remission rates were 77.8%(7/9 cases) and 58.3%(7/12 cases), respectively, while there was no significant difference in remission rates between the two groups (P>0.05). In the group of creatinine ≥177 µmol/L, the serum creatinine level was significantly decreased after 2 cycles of treatment compared with that pre-treatment (P=0.001). The 1q21 amplified subgroup accounted for the largest proportion (21/27 cases), ORR was 66.7%(14/21 cases) and deep remission rate was 23.8%(5/21 cases) after 2 cycles of treatment, ORR was 88.9%(16/18 cases) and deep remission rate was 66.7%(12/18 cases) after 4 cycles of treatment. In all the symptoms, the most common adverse reactions were pulmonary infection in 9 cases and hematological adverse reactions of grade 1-2 in 8 cases. CONCLUSION: The pomalidomide-based treatment regimen has good early curative effect on the newly diagnosed and relapsed refractory high-risk MM, and also benefits to the high-risk cytogenetic MM, or MM with renal impairment. Therefore, this treatment regimen showed a good safety, and the long-term curative effect needs to be further assessed by more clinical data.
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The gut microbiome plays a significant role in methamphetamine addiction. Previous studies using short-read amplicon sequencing have described alterations in microbiota at the genus level and predicted function, in which taxonomic resolution is insufficient for accurate functional measurements. To address this limitation, we employed metagenome sequencing to intuitively associate species to functions of gut microbiota in methamphetamine-induced conditioned place preference. We observed differential perturbations of species-level functional profiling of the gut microbiota across phases of METH-induced CPP, with alterations in SCFA metabolism and bacterial motility at the acquisition phase and substance dependence-alcoholism pathway and amino acid metabolism at the extinction phase. Our findings suggest that reduced beneficial bacteria, i.e., Lactobacillus reuteri, contributed to the alteration of SCFA metabolism, while the increased abundance of Akkermansia muciniphila during the extinction phase may be associated with altered phenylalanine, tyrosine, and tryptophan metabolism and substance dependence pathway. Our study further supports the association between specific microbial taxa and METH-induced rewarding.
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Estimulantes del Sistema Nervioso Central , Microbioma Gastrointestinal , Metanfetamina , Metanfetamina/farmacología , Estimulantes del Sistema Nervioso Central/farmacología , Condicionamiento Clásico , RecompensaRESUMEN
Endometrial cancer (EC) is a major gynecological malignancy with rising morbidity and mortality worldwide. The aim of this study was to explore a safe and readily available sample and a sensitive and effective detection method and its biomarkers for early diagnosis of EC, which is critical for patient prognosis. This study designed a panel targeting variants for EC-related genes, assessed its technical performance by comparing it with whole-exon sequencing, and explored the diagnostic potential of endometrial biopsies using the Pipelle aspirator, cervical samples using the Pap brush, and vaginal specimens using the swab from 38 EC patients and 208 women with risk factors for EC by applying targeted panel sequencing (TPS). TPS produced high-quality data (Q30 > 85% and mapping ratios > 99.35%) and was found to have strong consistency with whole-exome sequencing (WES) in detecting pathogenic mutations (92.11%), calculating homologous recombination deficiency (HRD) scores (r = 0.65), and assessing the microsatellite instability (MSI) status of EC (100%). The sensitivity of TPS in detection of EC is slightly better than that of WES (86.84% vs. 84.21%). Of the three types of samples detected using TPS, endometrial biopsy using the Pipelle aspirator had the highest sensitivity in detection of pathogenic mutations (81.87%) and the best consistency with surgical tumor specimens in MSI (85.16%). About 84% of EC patients contained pathogenic mutations in PIK3CA, PTEN, TP53, ARID1A, CTNNB1, KRAS, and MTOR, suggesting that this small gene set can achieve an excellent pathogenic mutation detection rate in Chinese EC patients. The custom panel combined with ultra-deep sequencing serves as a sensitive method for detecting genetic lesions from endometrial biopsy using the Pipelle aspirator.
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Ceramides are important intermediates in the metabolism of sphingolipids. High-throughput liquid chromatography-mass spectrometry has been used extensively for monitoring the levels of serological ceramides, but is still limited by inadequate coverage or lack of sensitivity. Herein, a rapid, sensitive, and high-throughput isotope dilution liquid chromatography-negative ion electrospray tandem mass spectrometry (IDLC-nESI-MS/MS) method was developed and verified for accurate quantification of 41 ceramides, involving ceramides with C16-20 sphingosine, dihydro-ceramide, and dehydro-ceramide. This method was validated with excellent linearity (R2 > 0.99) and good recovery in the range of 90-110%. Intra- and inter-day imprecision were below 5.57% and 7.83% respectively. The improved high-throughput quantitative method developed in this study may aid in the accurate characterization of ceramides for understanding ceramide biology and application in disease diagnosis.
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Ceramidas , Espectrometría de Masas en Tándem , Espectrometría de Masas en Tándem/métodos , Cromatografía Liquida/métodos , Ceramidas/análisis , Esfingolípidos , Isótopos , Cromatografía Líquida de Alta Presión/métodos , Espectrometría de Masa por Ionización de Electrospray/métodosRESUMEN
Objective: The aim of our study was to assess the prevalence and geographic variation of obesity-related hypertension in China among adults aged 45 years or older. Methods: Data were derived from the China Health and Retirement Longitudinal Study (CHARLS) conducted in 2015. Stratified sample households covered 150 counties/districts and 450 villages/urban communities from 28 provinces by using household questionnaires, clinical measurements, and blood-based bioassays. A multivariable non-conditional logistic regression model was used to analyze the risk factors correlated with obesity-related hypertension. Results: The prevalence of obesity-related hypertension was 22.7%, ~120 million people, among adults aged 45 years or older in China. For people in the age ranges of 45-54, 55-64, 65-74, and ≥75 years, the prevalence of obesity-related hypertension was 16.7, 24.3, 27, and 26.7%, respectively, and the prevalence of obesity-related hypertension among hypertensive participants was 66.0, 60.9, 54.2, and 47.3%, respectively. Compared with non-obesity-related hypertension, the obesity-related hypertensive patients had a higher prevalence of diabetes mellitus, dyslipidemia, and hyperuricemia (all P < 0.0001). The prevalence of obesity-related hypertension showed a decreasing gradient from north to south and from east to west. Multivariate logistic regression analysis showed that female gender, living in urban areas, diabetes mellitus, dyslipidemia, and hyperuricemia were positively correlated with obesity-related hypertension. Conclusion: The prevalence of obesity-related hypertension among adults aged 45 years or older was high in China. Among hypertensive participants, older age was negatively correlated with obesity-related hypertension. Obesity-related hypertensive participants are more prone to aggregation of risk factors of atherosclerotic cardiovascular disease.
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Hipertensión , Persona de Mediana Edad , Humanos , Femenino , Anciano , Estudios Longitudinales , Hipertensión/epidemiología , Prevalencia , Obesidad/complicaciones , Obesidad/epidemiología , Factores de RiesgoRESUMEN
Understanding the extent of contamination, sources and various carcinogenic and non-carcinogenic risks associated with different heavy metals in soil-crop systems is crucial for the prevention of heavy metal pollution. A survey was undertaken to determine heavy metal concentrations and degree of pollution in soil-crop systems (rice, wheat, and corn) using various indices such as pollution factor (CF), geo-accumulation index (Igeo), enrichment coefficients and transfer coefficient, and to determine the source of heavy metals pollution in the Wanjiang Economic Zone, Anhui Province, China. A total of 308 pairs of soil-crop samples were collected in this study, comprising 245 pairs of soil-rice samples, 53 pairs of soil-wheat samples, and 10 pairs of soil-corn samples. The concentrations of cadmium (Cd) and nickel (Ni) in the soil of the study area exceeded the national limitation of heavy metals in the soil of China (GB 15618-2018, Soil Environmental Quality: Risk Control Standard for Soil Contamination of Agricultural Land. Ministry of Environmental Protection of China. Beijing. China). The concentrations of copper (Cu), zinc (Zn) and lead (Pb) were also above the national limits to a lesser extent. All eight heavy metals (Cd, Cu, Ni, Pb Zn, arsenic (As), chromium (Cr), and mercury (Hg)) exceeded the background values in the study area. The enrichment coefficients of rice, wheat and maize to Cd, Cu and Zn were higher than those to other elements. On the basis of Igeo, it can be indicated that the rhizosphere soil of rice was slightly polluted by Cd and Hg, while the concentrations of the other heavy metals were below the safety limits. The CF and pollution load index (PLI) indicated that the soil in the study area was heavily contaminated with heavy metals. A principal component analysis identified different sources of soil heavy metal pollution, that is, Cu, Pb, Zn and Cd from industrial sources, Cr and Ni from natural sources, and As and Hg from agricultural sources. The carcinogenic risk of heavy metals was related to the intake of crops. Residents in the study area ingest rice, wheat, and corn on a daily basis. On the basis this study, it is suggested that local governments should pay attention to the carcinogenic risk of heavy metals in rice.
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Mercurio , Metales Pesados , Oryza , Contaminantes del Suelo , Cadmio/análisis , China , Productos Agrícolas , Monitoreo del Ambiente , Plomo/análisis , Mercurio/análisis , Metales Pesados/análisis , Medición de Riesgo , Suelo , Contaminantes del Suelo/análisis , Zinc/análisisRESUMEN
The study aimed to explore the relationship between eosinophils and the prognosis of varicella in adults. We retrospectively reviewed the medical records of patients who were hospitalised in The Fifth People's Hospital of Suzhou with a diagnosis of adult varicella during the period between 1 January 2012 and 31 December 2020. Of the 359 patients, 228 (63.51%) had eosinopenia. The proportion of patients with mild type disease was significantly lower in the eosinopenia group than that in the non-eosinopenia group (50.44% vs. 65.65%, P = 0.006). The proportion of the patients with common type disease was significantly higher in the eosinopenia group than that in the non-eosinopenia group (39.47% vs. 28.24%, P = 0.039). The proportion of the patients with severe type disease was higher in the eosinopenia group, although the difference did not reach statistical significance (10.09% vs. 6.11%, P = 0.243). The rates of high fever (47.81% vs. 32.82%, P = 0.008; relative risk (RR) 1.296, 95% confidence interval (CI) 1.091-1.540), headache (43.42% vs. 22.14%, P < 0.001; RR 1.415, 95% CI 1.233-1.623), anorexia (53.51% vs. 35.88%, P = 0.001; RR 1.367, 95% CI 1.129-1.655) and complications (82.89% vs. 64.12%, P < 0.001; RR 2.106, 95% CI 1.460-3.038) were also significantly higher in the eosinopenia group. Among the complications, the liver injury and skin infection were more serious in the eosinopenia group. The disease course was significantly longer in the eosinopenia group than that in the non-eosinopenia group (9.43 ± 1.89 days vs. 8.73 ± 1.25 days, P < 0.001). The improvement rate of liver injury in the recovery period was lower in the eosinopenia group than that in the non-eosinopenia group (35.38% vs. 50%, P = 0.012). The study found that adult varicella patients with eosinopenia had a more serious condition, a higher morbidity of complications and a slower recovery. Blood eosinophils can be used as a new predictor of the severity of adult varicella.
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Agranulocitosis , Varicela , Adulto , Varicela/complicaciones , Varicela/epidemiología , Eosinófilos , Humanos , Recuento de Leucocitos , Estudios RetrospectivosRESUMEN
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus driving the ongoing coronavirus disease 2019 (COVID-19) pandemic, continues to rapidly evolve. Because of the limited efficacy of vaccination in prevention of SARS-CoV-2 transmission and continuous emergence of variants of concern (VOCs), orally bioavailable and broadly efficacious antiviral drugs are urgently needed. Previously, we showed that the parent nucleoside of remdesivir, GS-441524, has potent anti-SARS-CoV-2 activity. Here, we report that esterification of the 5'-hydroxyl moieties of GS-441524 markedly improved antiviral potency. This 5'-hydroxyl-isobutyryl prodrug, ATV006, demonstrated excellent oral bioavailability in rats and cynomolgus monkeys and exhibited potent antiviral efficacy against different SARS-CoV-2 VOCs in vitro and in three mouse models. Oral administration of ATV006 reduced viral loads and alleviated lung damage when administered prophylactically and therapeutically to K18-hACE2 mice challenged with the Delta variant of SARS-CoV-2. These data indicate that ATV006 represents a promising oral antiviral drug candidate for SARS-CoV-2.
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Tratamiento Farmacológico de COVID-19 , Profármacos , Adenosina/uso terapéutico , Adenosina Monofosfato/análogos & derivados , Animales , Antivirales/farmacología , Antivirales/uso terapéutico , Ratones , Profármacos/farmacología , Profármacos/uso terapéutico , Ratas , SARS-CoV-2RESUMEN
Background: Colorectal cancer (CRC) is the 3rd most common cancer and the 2nd leading cause of cancer-related death. Numerous studies have found that aberrations in cellular molecules play an important role in the development of tumors. Studying and determining the interactions between these molecules can contribute to the diagnosis, treatment, and prognosis of tumors. Methods: The GSE151021, GSE156720, and GSE156719 data sets were analyzed to screen the differentially expressed messenger RNAs (DEmRNAs), long non-coding RNAs (DElncRNAs), and microRNAs (DEmiRNAs) in CRC. Database for Annotation, Visualization and Integrated Discovery (DAVID) and the Search Tool for the Retrieval of Interacting Genes/Proteins software were used to examine gene enrichment and the hub genes. Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and UALCAN was used to verify the expression of the hub genes. To analyze the overall survival (OS) of the hub genes, Kaplan-Meier plotter (KM plotter) was performed. Finally, the miRCancer database, TargetScan, and GSE156719 were used to identify the targets of the identified miRNAs. To predict the lncRNA-miRNA interactions, we used DIANA-LncBase v2 and GSE156720. Finally, the visualization proteinprotein interaction (PPI), competitive endogenous RNA (ceRNA) network was constructed using Cytoscape v3.1. Results: By analyzing GSE151021 and GSE156720, 23 upregulated mRNAs and 10 downregulated mRNAs were identified as sharing the differentially expressed genes (DEGs) between CRC and adjacent tissues. Furthermore, nucleolar protein 14 (NOP14), the sonic hedgehog (SHH) signaling molecule, phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1), the BCL2 apoptosis regulator (BCL2), and zinc finger E-box binding homeobox 2 (ZEB2) were considered hub genes. The constructed lncRNA-miRNA-mRNA network revealed 7 intersecting miRNAs (4 upregulated and 3 downregulated), 79 lncRNAs (40 upregulated and 39 downregulated), and 5 mRNAs (3 upregulated and 2 downregulated). Finally, we determined that the dysregulation of lncRNAs, such as HCG16, CASC9, SNHG16, HAND2-AS1, and NR2F1-AS1, secluded altered the expression of several miRNAs, such as hsa-miR-193a-5p, hsa-miR-485-5p, hsa-miR-17-5p, and hsa-miR-92a-3p, and affected the occurrence and development of CRC. Conclusions: We identified a series of DElncRNAs, DEmRNAs, and DEmiRNAs in CRC that might be considered potential biomarkers in understanding the complex molecular pathways leading to CRC development.
RESUMEN
BACKGROUND: Diagnosing seronegative rheumatoid arthritis (RA) can be challenging due to complex diagnostic criteria. We sought to discover diagnostic biomarkers for seronegative RA cases by studying metabolomic and lipidomic changes in RA patient serum. METHODS: We performed comprehensive metabolomic and lipidomic profiling in serum of 225 RA patients and 100 normal controls. These samples were divided into a discovery set (n = 243) and a validation set (n = 82). A machine-learning-based multivariate classification model was constructed using distinctive metabolites and lipids signals. RESULTS: Twenty-six metabolites and lipids were identified from the discovery cohort to construct a RA diagnosis model. The model was subsequently tested on a validation set and achieved accuracy of 90.2%, with sensitivity of 89.7% and specificity of 90.6%. Both seropositive and seronegative patients were identified using this model. A co-occurrence network using serum omics profiles was built and parsed into six modules, showing significant association between the inflammation and immune activity markers and aberrant metabolism of energy metabolism, lipids metabolism and amino acid metabolism. Acyl carnitines (20:3), aspartyl-phenylalanine, pipecolic acid, phosphatidylethanolamine PE (18:1) and lysophosphatidylethanolamine LPE (20:3) were positively correlated with the RA disease activity, while histidine and phosphatidic acid PA (28:0) were negatively correlated with the RA disease activity. CONCLUSIONS: A panel of 26 serum markers were selected from omics profiles to build a machine-learning-based prediction model that could aid in diagnosing seronegative RA patients. Potential markers were also identified in stratifying RA cases based on disease activity.