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RNA splicing is involved in cancer initiation and progression, but how it influences host antitumor immunity in the metabolically abnormal tumor microenvironment (TME) remains unclear. Here, we demonstrate that lactate modulates Foxp3-dependent RNA splicing to maintain the phenotypic and functional status of tumor-infiltrating regulatory T (Treg) cells via CTLA-4. RNA splicing in Treg cells was correlated with the Treg cell signatures in the TME. Ubiquitin-specific peptidase 39 (USP39), a component of the RNA splicing machinery, maintained RNA-splicing-mediated CTLA-4 expression to control Treg cell function. Mechanistically, lactate promoted USP39-mediated RNA splicing to facilitate CTLA-4 expression in a Foxp3-dependent manner. Moreover, the efficiency of CTLA-4 RNA splicing was increased in tumor-infiltrating Treg cells from patients with colorectal cancer. These findings highlight the immunological relevance of RNA splicing in Treg cells and provide important insights into the environmental mechanism governing CTLA-4 expression in Treg cells.
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Neoplasias , Linfócitos T Reguladores , Humanos , Antígeno CTLA-4 , Fatores de Transcrição Forkhead/genética , Ácido Láctico/metabolismo , Linfócitos do Interstício Tumoral , Neoplasias/genética , Neoplasias/metabolismo , Microambiente Tumoral , Proteases Específicas de Ubiquitina/metabolismoRESUMO
Biological fluids, the most complex blends, have compositions that constantly vary and cannot be molecularly defined1. Despite these uncertainties, proteins fluctuate, fold, function and evolve as programmed2-4. We propose that in addition to the known monomeric sequence requirements, protein sequences encode multi-pair interactions at the segmental level to navigate random encounters5,6; synthetic heteropolymers capable of emulating such interactions can replicate how proteins behave in biological fluids individually and collectively. Here, we extracted the chemical characteristics and sequential arrangement along a protein chain at the segmental level from natural protein libraries and used the information to design heteropolymer ensembles as mixtures of disordered, partially folded and folded proteins. For each heteropolymer ensemble, the level of segmental similarity to that of natural proteins determines its ability to replicate many functions of biological fluids including assisting protein folding during translation, preserving the viability of fetal bovine serum without refrigeration, enhancing the thermal stability of proteins and behaving like synthetic cytosol under biologically relevant conditions. Molecular studies further translated protein sequence information at the segmental level into intermolecular interactions with a defined range, degree of diversity and temporal and spatial availability. This framework provides valuable guiding principles to synthetically realize protein properties, engineer bio/abiotic hybrid materials and, ultimately, realize matter-to-life transformations.
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Materiais Biomiméticos , Biomimética , Polímeros , Conformação Proteica , Dobramento de Proteína , Proteínas , Sequência de Aminoácidos , Polímeros/síntese química , Polímeros/química , Proteínas/química , Materiais Biomiméticos/síntese química , Materiais Biomiméticos/química , Líquidos Corporais/química , Citosol/química , Soroalbumina Bovina/química , Biologia SintéticaRESUMO
Precise protein sequencing and folding are believed to generate the structure and chemical diversity of natural channels1,2, both of which are essential to synthetically achieve proton transport performance comparable to that seen in natural systems. Geometrically defined channels have been fabricated using peptides, DNAs, carbon nanotubes, sequence-defined polymers and organic frameworks3-13. However, none of these channels rivals the performance observed in their natural counterparts. Here we show that without forming an atomically structured channel, four-monomer-based random heteropolymers (RHPs)14 can mimic membrane proteins and exhibit selective proton transport across lipid bilayers at a rate similar to those of natural proton channels. Statistical control over the monomer distribution in an RHP leads to segmental heterogeneity in hydrophobicity, which facilitates the insertion of single RHPs into the lipid bilayers. It also results in bilayer-spanning segments containing polar monomers that promote the formation of hydrogen-bonded chains15,16 for proton transport. Our study demonstrates the importance of the adaptability that is enabled by statistical similarity among RHP chains and of the modularity provided by the chemical diversity of monomers, to achieve uniform behaviour in heterogeneous systems. Our results also validate statistical randomness as an unexplored approach to realize protein-like behaviour at the single-polymer-chain level in a predictable manner.
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Lipídeos/química , Prótons , Bicamadas Lipídicas , Modelos Moleculares , Conformação Molecular , PolímerosRESUMO
Topologically associating domain (TAD) boundaries are the flanking edges of TADs, also known as insulated neighborhoods, within the 3D structure of genomes. A prominent feature of TAD boundaries in mammalian genomes is the enrichment of clustered CTCF sites often with mixed orientations, which can either block or facilitate enhancer-promoter (E-P) interactions within or across distinct TADs, respectively. We will discuss recent progress in the understanding of fundamental organizing principles of the clustered CTCF insulator codes at TAD boundaries. Specifically, both inward- and outward-oriented CTCF sites function as topological chromatin insulators by asymmetrically blocking improper TAD-boundary-crossing cohesin loop extrusion. In addition, boundary stacking and enhancer clustering facilitate long-distance E-P interactions across multiple TADs. Finally, we provide a unified mechanism for RNA-mediated TAD boundary function via R-loop formation for both insulation and facilitation. This mechanism of TAD boundary formation and insulation has interesting implications not only on how the 3D genome folds in the Euclidean nuclear space but also on how the specificity of E-P interactions is developmentally regulated.
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G-quadruplexes (G4s) are noncanonical nucleic acid structures pivotal to cellular processes and disease pathways. Deciphering G4-interacting proteins is imperative for unraveling G4's biological significance. In this study, we developed a G4-targeting biotin ligase named G4PID, meticulously assessing its binding affinity and specificity both in vitro and in vivo. Capitalizing on G4PID, we devised a tailored approach termed G-quadruplex-interacting proteins specific biotin-ligation procedure (PLGPB) to precisely profile G4-interacting proteins. Implementing this innovative strategy in live cells, we unveiled a cohort of 149 potential G4-interacting proteins, which exhibiting multifaceted functionalities. We then substantiate the directly binding affinity of 7 candidate G4-interacting-proteins (SF3B4, FBL, PP1G, BCL7C, NDUV1, ILF3, GAR1) in vitro. Remarkably, we verified that splicing factor 3B subunit 4 (SF3B4) binds preferentially to the G4-rich 3' splice site and the corresponding splicing sites are modulated by the G4 stabilizer PDS, indicating the regulating role of G4s in mRNA splicing procedure. The PLGPB strategy could biotinylate multiple proteins simultaneously, which providing an opportunity to map G4-interacting proteins network in living cells.
Assuntos
Biotina , Quadruplex G , Humanos , Biotina/metabolismo , Ligação Proteica , Fatores de Processamento de RNA/metabolismo , Carbono-Nitrogênio Ligases/metabolismo , Carbono-Nitrogênio Ligases/genética , Splicing de RNA , Células HEK293 , Proteínas de Ligação a RNA/metabolismo , Células HeLaRESUMO
Hepatitis B virus (HBV) is a hepatotropic DNA virus that has a very compact genome. Due to this genomic density, several distinct mechanisms are used to facilitate the viral life cycle. Recently, accumulating evidence show that G-quadruplex (G4) in different viruses play essential regulatory roles in key steps of the viral life cycle. Although G4 structures in the HBV genome have been reported, their function in HBV replication remains elusive. In this study, we treated an HBV replication-competent cell line and HBV-infected cells with the G4 structure stabilizer pyridostatin (PDS) and evaluated different HBV replication markers to better understand the role played by the G4. In both models, we found PDS had no effect on viral precore RNA (pcRNA) or pre-genomic RNA (pgRNA), but treatment did increase HBeAg/HBc ELISA reads and intracellular levels of viral core/capsid protein (HBc) in a dose-dependent manner, suggesting post-transcriptional regulation. To further dissect the mechanism of G4 involvement, we used in vitro-synthesized HBV pcRNA and pgRNA. Interestingly, we found PDS treatment only enhanced HBc expression from pgRNA but not HBeAg expression from pcRNA. Our bioinformatic analysis and CD spectroscopy revealed that pgRNA harbors a conserved G4 structure. Finally, we introduced point mutations in pgRNA to disrupt its G4 structure and observed the resulting mutant failed to respond to PDS treatment and decreased HBc level in in vitro translation assay. Taken together, our data demonstrate that HBV pgRNA contains a G4 structure that plays a vital role in the regulation of viral mRNA translation.
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Quadruplex G , Vírus da Hepatite B , Hepatite B , Humanos , Proteínas do Capsídeo/química , Proteínas do Capsídeo/metabolismo , Hepatite B/virologia , Antígenos E da Hepatite B/metabolismo , Vírus da Hepatite B/genética , Vírus da Hepatite B/metabolismo , RNA Viral/genética , RNA Viral/metabolismo , Proteínas do Core Viral/química , Proteínas do Core Viral/metabolismo , Replicação Viral/genética , Linhagem Celular , Quadruplex G/efeitos dos fármacos , Biossíntese de Proteínas/efeitos dos fármacos , Biossíntese de Proteínas/genética , Mutação , Aminoquinolinas/farmacologiaRESUMO
BACKGROUND & AIMS: Lack of thorough knowledge about the complicated immune microenvironment (IM) within a variety of liver metastases (LMs) leads to inappropriate treatment and unsatisfactory prognosis. We aimed to characterize IM subtypes and investigate potential mechanisms in LMs. METHODS: Mass cytometry was applied to characterize immune landscape of a primary liver cancers and liver metastases cohort. Transcriptomic and whole-exome sequencing were used to explore potential mechanisms across distinct IM subtypes. Single-cell transcriptomic sequencing, multiplex fluorescent immunohistochemistry, cell culture, mouse model, Western blot, quantitative polymerase chain reaction, and immunohistochemistry were used for validation. RESULTS: Five IM subtypes were revealed in 100 LMs and 50 primary liver cancers. Patients featured terminally exhausted (IM1) or rare T-cell-inflamed (IM2 and IM3) immune characteristics showed worse outcome. Increased intratumor heterogeneity, enriched somatic TP53, KRAS, APC, and PIK3CA mutations and hyperactivated hypoxia signaling accounted for the formation of vicious subtypes. SLC2A1 promoted immune suppression and desert via increasing proportion of Spp1+ macrophages and their inhibitory interactions with T cells in liver metastatic lesions. Furthermore, SLC2A1 promoted immune escape and LM through inducing regulatory T cells, including regulatory T cells and LAG3+CD4+ T cells in primary colorectal cancer. CONCLUSIONS: The study provided integrated multi-omics landscape of LM, uncovering potential mechanisms for vicious IM subtypes and confirming the roles of SLC2A1 in regulating tumor microenvironment remodeling in both primary tumor and LM lesions.
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Neoplasias Hepáticas , Multiômica , Animais , Camundongos , Mutação , Neoplasias Hepáticas/patologia , Sequenciamento do Exoma , Microambiente TumoralRESUMO
Nanomaterials doped with high atom number elements can improve the efficacy of cancer radiotherapy, but their clinical application faces obstacles, such as being difficult to degrade in vivo, or still requiring relatively high radiation dose. In this work, a bismuth oxycarbonate-based ultrathin nanosheet with the thickness of 2.8 nm for safe and efficient tumor radiotherapy under low dose of X-ray irradiation is proposed. The high oxygen content (62.5% at%) and selective exposure of the facets of ultrathin 2D nanostrusctures facilitate the escape of large amounts of oxygen atoms on bismuth nanosheets from surface, forming massive oxygen vacancies and generating reactive oxygen species that explode under the action of X-rays. Moreover, the exposure of almost all atoms to environmental factors and the nature of oxycarbonates makes the nanosheets easily degrade into biocompatible species. In vivo studies demonstrate that nanosheets could induce apoptosis in cancer cells after low dose of X-ray irradiation without causing any damage to the liver or kidney. The tumor growth inhibition effect of radiotherapy increases from 49.88% to 90.76% with the help of bismuth oxycarbonate nanosheets. This work offers a promising future for nanosheet-based clinical radiotherapies of malignant cancers.
Assuntos
Bismuto , Nanoestruturas , Oxigênio , Bismuto/química , Oxigênio/química , Animais , Nanoestruturas/química , Humanos , Neoplasias/terapia , Camundongos , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacosRESUMO
Dyslipidemia is a prevalent metabolic disorder in older adults and has negative effects on cardiovascular health. However, the combined effect of paraben, bisphenol A (BPA), and triclosan (TCS) exposure on dyslipidemia and the underlying mechanisms remain unclear. This cross-sectional study recruited 486 individuals ≥60 years in Shenzhen, China. Morning spot urine samples were collected and analyzed for four parabens, BPA, TCS, and 8-hydroxy-2'-deoxyguanosine (8-OHdG), a typical biomarker for oxidative stress, using mass spectrometry. Blood samples were tested for lipid levels using an automated biochemical analyzer. Quantile-based g-computation (QGC) was used to assess the combined effects of exposures on dyslipidemia. Mediation analysis was applied to investigate the mediating role of 8-OHdG between exposure and dyslipidemia. QGC showed that co-exposure to parabens, BPA, and TCS was positively linked with hypercholesterolemia (OR: 1.17, 95%CI: 1.10-1.24, P<0.001) and hyper-LDL-cholesterolemia (OR: 1.35, 95%CI: 1.05-1.75, P=0.019). Methylparaben (MeP), n-propyl paraben (PrP), and butylparaben (BtP) were the major contributors. 8-OHdG mediated 6.5% and 13.0% of the overall effect of the examined chemicals on hypercholesterolemia and hyper-LDL-cholesterolemia, respectively (all P<0.05). Our study indicated that co-exposure to parabens, BPA, and TCS is associated with dyslipidemia and oxidative stress partially mediate the association. Future research is needed to explore additional mechanisms underlying these relationships.
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BACKGROUND: Modifying diet is crucial for diabetes and complication management. Numerous studies have shown that adjusting eating habits to align with the circadian rhythm may positively affect metabolic health. However, eating midpoint, eating duration, and their associations with diabetic kidney disease (DKD) are poorly understood. METHODS: The National Health and Nutrition Examination Survey (2013-2020) was examined for information on diabetes and dietary habits. From the beginning and ending times of each meal, we calculated the eating midpoint and eating duration. Urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g and/or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 were the specific diagnostic criteria for DKD. RESULTS: In total, details of 2194 subjects with diabetes were collected for analysis. The overall population were divided into four subgroups based on the eating midpoint quartiles. The prevalence of DKD varied noticeably (P = 0.037) across the four categories. When comparing subjects in the second and fourth quartiles of eating midpoint to those in the first one, the odds ratios (ORs) of DKD were 1.31 (95% CI, 1.03 to 1.67) and 1.33 (95% CI, 1.05 to 1.70), respectively. And after controlling for potential confounders, the corresponding ORs of DKD in the second and fourth quartiles were 1.42 (95% CI, 1.07 to 1.90) and 1.39 (95% CI, 1.04 to 1.85), respectively. CONCLUSIONS: A strong correlation was found between an earlier eating midpoint and a reduced incidence of DKD. Eating early in the day may potentially improve renal outcomes in patients with diabetes.
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Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Humanos , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Inquéritos Nutricionais , Estudos Transversais , Rim , Taxa de Filtração Glomerular , Diabetes Mellitus Tipo 2/complicaçõesRESUMO
BACKGROUND: In recent years, the incidence of depression during pregnancy has gradually increased, and the disorder of lipid metabolism in patients with depression is an important research direction. Therefore, this study aimed to explore the correlation between depression during pregnancy and metabolic syndrome (MS). METHODS: A total of 113 pregnant women diagnosed as depression during pregnancy from November 2019 to January 2022 were selected as the observation group. After excluding 3 cases, 110 cases were finally included. And 102 pregnant women who were not diagnosed as depression during pregnancy in the same period were selected as the control group. After excluding 2 cases, 100 cases were finally included for comparative study. The levels of various parameters, including serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), C-reactive protein (CRP), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were compared between the two groups. Furthermore, the Edinburgh Postnatal Depression Scale (EPDS) was used to evaluate the depression scores of postpartum women. Additionally, the correlation between EPDS scores and clinical indexes was assessed in patients with depression during pregnancy. RESULTS: We observed that the body weight, EPDS score, the proportion of hyperglycemia, hypertension, and dyslipidemia were significantly higher in the observation group compared to the control group (p < 0.001). Furthermore, the observation group exhibited significantly higher levels of TG, TC, HDL-C, LDL-C, FPG, CRP, SBP, and DBP than the control group (p < 0.001). Pearson linear correlation analysis revealed that TG, TC, HDL-C, LDL-C, FPG, CRP, SBP, and DBP levels were positively correlated with EPDS scores (p < 0.001). CONCLUSION: This study indicates a specific correlation between MS and depression during pregnancy, and MS-related indicators are positively correlated with EPDS scores among these individuals.
Assuntos
Depressão , Síndrome Metabólica , Complicações na Gravidez , Humanos , Feminino , Gravidez , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/sangue , Adulto , Complicações na Gravidez/sangue , Depressão/sangue , Depressão/epidemiologia , Estudos de Casos e ControlesRESUMO
Vascular endothelial cell barrier disruption is a hallmark of sepsis-induced acute lung injury (ALI). Mesenchymal stem cells (MSCs)-based therapy has been regarded as a promising treatment for repairing injured lungs, and mitochondrial transfer was shown to be important for the therapeutic effects of MSCs. Here we investigated the ability of MSCs to modulate endothelial barrier integrity through mitochondrial transfer in sepsis-induced ALI. We found that mitochondrial transfer from MSCs to LPS-induced PMVECs through forming tunneling nanotubes (TNTs). Due to the inhibition of TNTs (using LAT-A), MSCs-mediated reparation on PMVECs functions, including cell apoptosis, MMP, ATP generation, TEER level and monolayer permeability of FITC-dextran were greatly inhibited. In addition, silencing of mitochondrial transcription factor A (TFAM) in MSCs could also partly inhibit the TNTs formation and aggravate the LPS-induced mitochondrial dysfunction and permeability barrier in PMVECs. Furthermore, the LPS-induced pulmonary edema and higher pulmonary vascular permeability were alleviated by MSCs while that of lung tissue bounced back after MSCs were pre-incubated by LAT-A and or down-regulation of TFAM. Therefore, we firstly revealed that regulation of TFAM expression in MSCs played a critical role to improve the permeability barrier of PMVECs by TNTs mediating mitochondrial transfer in sepsis-associated ALI. This study provided a new therapeutic strategy for the treatment of sepsis-induced ALI.
Assuntos
Lesão Pulmonar Aguda , Células-Tronco Mesenquimais , Sepse , Humanos , Lipopolissacarídeos , Apoptose , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/metabolismo , Pulmão/metabolismo , Mitocôndrias , Células-Tronco Mesenquimais/metabolismo , Sepse/complicações , Sepse/genética , Sepse/metabolismo , Permeabilidade , Proteínas de Ligação a DNA/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Mitocondriais/metabolismoRESUMO
Objective: To evaluate the value of the cardiac magnetic resonance intravoxel incoherent motion (IVIM) technique in microcirculatory dysfunction in patients with hypertrophic cardiomyopathy (HCM). Methods: The medical records of 19 patients with HCM in our hospital from January 2020 to May 2021 were collected retrospectively, and 23 healthy people with a similar age and gender distribution to the patients with HCM were included as controls. All the included subjects underwent clinical assessment and cardiac magnetic resonance imaging. The original IVIM images were analysed, and the imaging parameters of each segment were measured. The HCM group was divided into non-hypertrophic myocardium and hypertrophic myocardium groups. The differences in imaging parameters between the normal and HCM groups were compared. A Spearman correlation analysis was used to explore the correlation between end-diastolic thickness (EDTH) and each IVIM parameter. Results: The D∗ and f values in the HCM group were lower than those in the normal group (p < 0.0001 and p = 0.004, respectively). The f, D, D∗, and EDTH values of the hypertrophic segment, non-hypertrophic segment, and normal groups were statistically significant (p < 0.05). The difference in D∗ values among the mild, moderate, severe, and very severe HCM groups was statistically significant (p < 0.05). There was a statistically significant difference in EDTH among the mild, moderate, severe, and very severe groups (p < 0.001). There were significant differences in the values of D, D∗, and f between the non-delayed enhancement group and the delayed enhancement group (p < 0.05). The EDTH values of 304 segments in the HCM group were negatively correlated with f (r = -0.219, p = 0.028) and D∗ values (r = -0.310, p < 0.001). Conclusion: The use of IVIM technology can achieve a non-invasive early quantitative assessment of microvascular disease in HCM without the injection of a contrast agent and provide a reference for the early diagnosis of and intervention in myocardial ischemia in patients with HCM.
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Cardiomiopatia Hipertrófica , Humanos , Estudos Retrospectivos , Microcirculação , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Meios de Contraste , Espectroscopia de Ressonância MagnéticaRESUMO
The platelet/high-density lipoprotein cholesterol ratio (PHR) is a novel inflammatory and hypercoagulability marker that represents the severity of metabolic syndrome. Liver metabolic syndrome is manifested by nonalcoholic fatty liver disease (NAFLD), which is associated with inflammation and hypercoagulability. This cross-sectional investigation aimed to identify the relationship between PHR and NAFLD. Participants in the National Health and Nutrition Examination Survey (NHANES) 2017-2020 were evaluated for hepatic steatosis and fibrosis using vibration-controlled transient elastography. The PHR was calculated as the ratio of platelets to high-density lipoprotein cholesterol. Increased PHR was associated with an increased incidence of NAFLD and hepatic fibrosis. Compared with patients in the first PHR quartile, after adjustment for clinical variables, the corresponding odds ratio (OR) for NAFLD in the fourth quartile was 2.36 (95% CI, 1.76 to 3.18) (p < 0.05); however, the OR for hepatic fibrosis was not statistically significant (p > 0.05). Furthermore, restricted cubic spline analyses showed an S-shaped association between PHR and NAFLD and an L-shaped relationship between PHR and hepatic fibrosis. The results support the effectiveness of PHR as a marker for NAFLD and hepatic fibrosis. Therefore, interventions to improve the PHR may be of benefit in reducing the incidence of both hepatic steatosis and fibrosis.
Assuntos
Síndrome Metabólica , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/patologia , Síndrome Metabólica/epidemiologia , Inquéritos Nutricionais , HDL-Colesterol , Plaquetas , Estudos Transversais , Fígado/patologia , Cirrose Hepática/etiologiaRESUMO
While most studies assessed the acute toxicity of saxitoxin (STX), fewer studies focus on the long-term degenerative effects of STX on the central nervous system. We investigated the cognitive impairment and hippocampal damages of 6 months' exposure of low-dose STX to C57BL/6NJ mice with behavioral tests, H&E staining, and Western blots, and the possible mechanism (Ppp1C, YAP1, tau-phosphorylation) underlies the pathological changes. Furthermore, we discussed the specific localization of YAP1 in N2a cells induced by STX and the effect of inactivated Ppp1C on its downstream protein YAP1 in the Hippo signal pathway. We found STX intoxicated mice showed declined cognitive performance in both NOR test and MWM test, degenerations in the CA1 area of hippocampi. STX induced up-regulation expression of Ppp1C and YAP1 in hippocampus and N2a cells. Meanwhile, STX treatment induced cell apoptosis and Tau protein hyperphosphorylation. In addition, STX treatment promoted YAP1 cytoplasmic retention that indicates the activation of Hippo pathway, while depletion of Ppp1C inactivate YAP1 during the treatment of STX. Our results highlight the role of Ppp1C and YAP1 cytoplasmic retention in chronic low-dose STX intoxication.
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Disfunção Cognitiva , Saxitoxina , Animais , Camundongos , Cognição , Disfunção Cognitiva/induzido quimicamente , Camundongos Endogâmicos C57BL , Saxitoxina/toxicidade , Transdução de SinaisRESUMO
In view of the serious side effects of chlortetracycline (CTC) on the human body, it is particularly important to develop rapid, sensitive, and selective technologies for the detection of CTC in food. In this work, a molecularly imprinted electrochemical sensor with [Fe(CN)6]3-/4- as signal probe was proposed for the highly sensitive and selective detection of CTC. For this purpose, TiO2, which acts as an interlayer scaffold, was uniformly grown on the surface of Ti3C2Tx sheets through a simple two-step calcination process using Ti3C2Tx as the precursor to effectively avoid the stacking of Ti3C2Tx layers due to hydrogen bonding and van der Waals forces. This endowed TiO2@Ti3C2Tx with large specific surface, abundant functional sites, and rapid mass transfer. Then, polypyrrole molecularly imprinted polymers (MIPs) with outstanding electrical conductivity were modified on the surface of TiO2@Ti3C2Tx via simple electro-polymerization, where the pyrrole was employed as a polymeric monomer and the CTC provided a source of template molecules. This will not only provide specific recognition sites for CTC, but also facilitate electron transport on the electrode surface. The synergistic effects between TiO2@Ti3C2Tx and polypyrrole MIPs afforded the TiO2@Ti3C2Tx/MIP-based electrochemical sensor excellent detection properties toward CTC, including ultra-low limits of detection (LOD) (0.027 nM), a wide linear range (0.06-1000 nM), and outstanding stability, reproducibility, selectivity, and feasibility in real samples. The results indicate that this strategy is feasible and will broaden the horizon for highly sensitive and selective detection of CTC.
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Clortetraciclina , Grafite , Impressão Molecular , Humanos , Polímeros/química , Titânio , Impressão Molecular/métodos , Grafite/química , Técnicas Eletroquímicas/métodos , Reprodutibilidade dos Testes , Pirróis/química , Limite de Detecção , Polímeros Molecularmente Impressos , EletrodosRESUMO
Mercuric ion (Hg2+) in aqueous media is extremely toxic to the environment and organisms. Therefore, the ultra-trace electrochemical determination of Hg2+ in the environment is of critical importance. In this work, a new electrochemical Hg2+ sensing platform based on porous activated carbon (BC/Cu2O) modified with cuprous oxide was developed using a simple impregnation pyrolysis method. Differential pulse anodic stripping voltammetry (DPASV) was used to investigate the sensing capability of the BC/Cu2O electrode towards Hg2+. Due to the excellent conductivity and large specific surface area of BC, and the excellent catalytic activity of Cu2O nanoparticles, the prepared BC/Cu2O electrode exhibited excellent electrochemical activity. The high sensitivity of the proposed system resulted in a low detection limit of 0.3 ng·L-1 and a wide linear response in the ranges from 1.0 ng·L-1 to 1.0 mg·L-1. In addition, this sensor was found to have good accuracy, acceptable precision, and reproducibility. All of these results show that the BC/Cu2O composite is a promising material for Hg2+ electrochemical detection.
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A meta-analysis study was conducted to assess the influence of the wound adjuncts therapy of closed incision negative pressure wound therapy (ciNPWT) on stopping groin site wound infection (SWSI) in arterial surgery. A comprehensive literature examination till January 2023 was implemented and 2186 linked studies were appraised. The picked studies contained 2133 subjects with groin surgical wounds of arterial surgery in the picked studies' baseline, 1043 of them were using ciNPWT, and 1090 were using standard care. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were used to calculate the consequence of the wound adjuncts therapy of ciNPWT on stopping groin SWSI in arterial surgery by the dichotomous and continuous styles and a fixed or random model. The ciNPWT had a significantly lower SWSI (OR, 0.42; 95% CI, 0.33-0.55, P < .001), superficial SWSI (OR, 0.46; 95% CI, 0.33-0.66, P < .001), and deep SWSI (OR, 0.39; 95% CI, 0.25-0.63, P < .001) compared with the standard care in groin surgical wound of arterial surgery. The ciNPWT had a significantly, lower SWSI, superficial SWSI, and deep SWSI compared with the standard care in groin surgical wounds of arterial surgery. Although precautions should be taken when commerce with the consequences because some of the picked studies for this meta-analysis was with low sample sizes.
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Tratamento de Ferimentos com Pressão Negativa , Ferida Cirúrgica , Humanos , Ferida Cirúrgica/terapia , Ferida Cirúrgica/complicações , Virilha/cirurgia , Tratamento de Ferimentos com Pressão Negativa/efeitos adversos , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/diagnóstico , Procedimentos Cirúrgicos Vasculares/efeitos adversosRESUMO
BACKGROUND: This study was designed to unravel the genomic landscape and evolution of early-stage subsolid lung adenocarcinomas (SSN-LUADs) manifesting as pure ground-glass nodules (pGGNs), heterogeneous ground-glass nodules (HGGNs) and part-solid nodules (PSNs). METHODS: Samples subjected to either broad-panel next-generation sequencing (NGS) or whole-exome sequencing (WES) were included. Clinicopathologic and genomic features were compared among pGGN, HGGN and PSN, while tumour evolutionary trajectories and mutational signatures were evaluated in the entire cohort. RESULTS: In total, 247 SSN-LUAD samples subjected to broad-panel NGS and 125 to WES were identified. Compared with PSNs, HGGNs had significantly lower tumour mutation count (P < 0.001), genomic alteration count (P < 0.001), and intra-tumour heterogeneity (P = 0.005). Statistically significant upward trends were observed in alterations involving driver mutations and oncogenic pathways from pGGNs to HGGNs to PSNs. EGFR mutation was proved to be a key early event in the progression of SSN-LUADs, with subsequently two evolutionary trajectories involving either RBM10 or TP53 mutation in the cancer-evolution models. CONCLUSIONS: This study provided evidence for unravelling the previously unknown genomic underpinnings associated with SSN-LUAD evolution from pGGN to HGGN to PSN, proving that HGGN was an intermediate SSN form between pGGN and PSN genetically.