RESUMO
Fungal infections have emerged as a major concern among immunocompromised patients, causing approximately 2 million deaths each year worldwide. However, the regulatory mechanisms underlying antifungal immunity remain elusive and require further investigation. The E3 ligase Trim26 belongs to the tripartite motif (Trim) protein family, which is involved in various biological processes, including cell proliferation, antiviral innate immunity, and inflammatory responses. Herein, we report that Trim26 exerts protective antifungal immune functions after fungal infection. Trim26-deficient mice are more susceptible to fungemia than their wild-type counterparts. Mechanistically, Trim26 restricts inflammatory neutrophils infiltration and limits proinflammatory cytokine production, which can attenuate kidney fungal load and renal damage during Candida infection. Trim26-deficient neutrophils showed higher proinflammatory cytokine expression and impaired fungicidal activity. We further demonstrated that excessive neutrophils infiltration in the kidney was because of the increased production of chemokines CXCL1 and CXCL2, which are mainly synthesized in the macrophages or dendritic cells of Trim26-deficient mice after Candida albicans infections. Together, our study findings unraveled the vital role of Trim26 in regulating antifungal immunity through the regulation of inflammatory neutrophils infiltration and proinflammatory cytokine and chemokine expression during candidiasis.
Assuntos
Candidíase , Neutrófilos , Animais , Camundongos , Antifúngicos , Candida albicans , Candidíase/metabolismo , Candidíase/microbiologia , Citocinas/metabolismo , Infiltração de Neutrófilos , Proteínas com Motivo Tripartido , Ubiquitina-Proteína LigasesRESUMO
BACKGROUND: Myelodysplastic syndrome (MDS) is known to arise through the pathogenic bone marrow mesenchymal stem cells (MSC) by interacting with hematopoietic stem cells (HSC). However, due to the strong heterogeneity of MDS patients, it is difficult to find common targets in studies with limited sample sizes. This study aimed to describe sequential molecular changes and identify biomarkers in MSC of MDS transformation. METHODS: Multidimensional data from three publicly available microarray and TCGA datasets were analyzed. MDS-MSC was further isolated and cultured in vitro to determine the potential diagnostic and prognostic value of the identified biomarkers. RESULTS: We demonstrated that normal MSCs presented greater molecular homogeneity than MDS-MSC. Biological process (embryonic skeletal system morphogenesis and angiogenesis) and pathways (p53 and MAPK) were enriched according to the differential gene expression. Furthermore, we identified HOXB3 and HOXB7 as potential causative genes gradually upregulated during the normal-MDS-AML transition. Blocking the HOXB3 and HOXB7 in MSCs could enhance the cell proliferation and differentiation, inhibit cell apoptosis and restore the function that supports hematopoietic differentiation in HSCs. CONCLUSION: Our comprehensive study of gene expression profiling has identified dysregulated genes and biological processes in MSCs during MDS. HOXB3 and HOXB7 are proposed as novel surrogate targets for therapeutic and diagnostic applications in MDS.
Assuntos
Genes Homeobox , Proteínas de Homeodomínio , Células-Tronco Mesenquimais , Síndromes Mielodisplásicas , Humanos , Biomarcadores , Perfilação da Expressão Gênica , Proteínas de Homeodomínio/genética , Síndromes Mielodisplásicas/genéticaRESUMO
In the present study, a novel silane coupling agent, designated INSi, was synthesized via a facile synthetic route, incorporating indole-functional moieties. This agent was further employed for the surface modification of homemade silica nanomicrospheres (SMPs). The ensuing nanomicrosphere composite, denoted as SiO2@IN, exemplified pronounced interfacial π-π interactions. Optimization of the reaction conditions was conducted using the response surface optimization technique. Subsequent validation of interfacial π-π interactions was accomplished through a synergistic approach, integrating theoretical calculations and comprehensive analyses of spectral and morphological attributes exhibited by the SiO2@IN.
RESUMO
The development of a low-cost and efficient oxygen evolution reaction (OER) electrode is of critical importance for water electrolysis technologies. The general approach to achieving a high-efficiency OER electrode is to regulate catalytic material structures by synthetic control. Here we reported an orthogonal approach to obtaining the OER electrode without intentional design and synthesis, namely, recycling MnO2 cathodes from failed rechargeable aqueous batteries and investigating them as ready-made catalytic electrodes. The recycled MnO2 cathode showed very little Zn2+ storage capacity but surprisingly high OER activity with a low overpotential of 307 mV at 10 mA cm-2 and a small Tafel slope of 77.9 mV dec-1, comparable to the state-of-the-art RuO2 catalyst (310 mV, 86.9 mV dec-1). In situ electrochemical and theoretical studies jointly revealed that the accelerated OER kinetics of the recycled MnO2 electrode was attributed to the enlarged active surface area of MnO2 and optimized electronic structure of Mn sites. This work suggests failed battery cathodes as successful catalysis electrodes for sustainable energy development.
RESUMO
Seawater electrolysis presents a promising avenue for green hydrogen production toward a carbon-free society. However, the electrode materials face significant challenges including severe chlorine-induced corrosion and high reaction overpotential, resulting in low energy conversion efficiency and low current density operation. Herein, we put forward a nanoporous nickel (npNi) cathode with high chlorine corrosion resistance for energy-efficient seawater electrolysis at industrial current densities (0.4-1 A cm-2). With the merits of an electrostatic chlorine-resistant surface, modulated Ni active sites, and a robust three-dimensional open structure, the npNi electrode showed a low hydrogen evolution reaction overpotential of 310 mV and a high electricity-hydrogen conversion efficiency of 59.7% at 400 mA cm-2 in real seawater and outperformed most Ni-based seawater electrolysis cathodes in recent publications and the commercial Ni foam electrode (459 mV, 46.4%) under the same test condition. In situ electrochemical impedance spectroscopy, high-frame-rate optical microscopy, and first-principles calculation revealed that the improved corrosion resistance, enhanced intrinsic activity, and mass transfer were responsible for the lowered electrocatalytic overpotential and enhanced energy efficiency.
RESUMO
OBJECTIVES: In this study, we describe the patterns of antibiotic prescription for neonates based on World Health Organization's (WHO) Essential Medicines List Access, Watch, and Reserve (AWaRe), and the Management of Antibiotic Classification (MAC) Guidelines in China. METHODS: One-day point-prevalence surveys (PPS) on antimicrobial prescriptions were conducted on behalf of hospitalized neonates in China from September 1 and November 30, annually from 2017 to 2019. RESULTS: Data was collected for a total of 2674 neonatal patients from 15 hospitals in 9 provinces across China of which 1520 were newborns who received at least one antibiotic agent. A total of 1943 antibiotic prescriptions were included in the analysis. The most commonly prescribed antibiotic was meropenem (11.8%). The most common reason for prescribing antibiotic to neonates was pneumonia (44.2%). There were 419 (21.6%), 1343 (69.1%) and 6 (0.3%) antibiotic prescriptions in the Access, Watch and Reserve groups, respectively. According to MAC Guidelines in China, there were 1090 (56.1%) antibiotic agents in the Restricted and 414 (21.3%) in the Special group. CONCLUSION: Broad-spectrum antibiotics included in the Watch and Special groups were likely to be overused in Chinese neonates.
Assuntos
Antibacterianos , Prescrições de Medicamentos , Humanos , Recém-Nascido , Prevalência , Pesquisas sobre Atenção à Saúde , Antibacterianos/uso terapêutico , China/epidemiologiaRESUMO
The heavy metal cadmium (Cd) is a toxic and bioaccumulative metal that can be enriched in the tissues and organs of living organisms through the digestive tract. However, more research is needed to determine whether food-sourced Cd affects the homeostasis of host gut microflora. In this study, the snail Bradybaena ravida (Benson) was used as a model organism fed with mulberry leaves spiked with different concentrations of Cd (0, 0.052, 0.71, and 1.94 mg kg-1). By combining 16S rRNA high-throughput sequencing with biochemical characterization, it was found that there were increases in the overall microbial diversity and abundances of pathogenic bacteria such as Corynebacterium, Enterococcus, Aeromonas, and Rickettsia in the gut of B. ravida after exposure to Cd. However, the abundances of potential Cd-resistant microbes in the host's gut, including Sphingobacterium, Lactococcus, and Chryseobacterium, decreased with increasing Cd concentrations in the mulberry leaves. In addition, there was a significant reduction in activities of energy, nutrient metabolism, and antioxidant enzymes for gut microbiota of snails treated with high concentrations of Cd compared to those with low ones. These findings highlight the interaction of snail gut microbiota with Cd exposure, indicating the potential role of terrestrial animal gut microbiota in environmental monitoring through rapid recognition and response to environmental pollution.
RESUMO
OBJECTIVE: To investigate plastic surgery repair's effects and adverse reactions in the clinical therapy of asymmetric double eyelids. METHODS: All 126 sufferers who came to the hospital for asymmetric double eyelid plastic repair from January 2022 to October 2022 were selected as the research objects, and they were divided into a control group and an observation group using the random number method, with 63 cases in each group, in which sufferers in the control group underwent full incision blepharoplasty and sufferers in the observation group underwent small incision liposuction with submerged sutures. The general data, treatment results, treatment satisfaction, related surgical indicators, and frequency of adverse reactions of the 2 groups of sufferers with asymmetric double eyelid plastic repair were compared. RESULTS: It had no statistically obvious distinction between the control group and the observation group of sufferers in terms of general data such as sex, age, weight, and height (P>0.05); the total therapy efficiency of the sufferers in the observation group (95.24%) was greater than the control group (74.60%), with P value <0.05; the total treatment satisfaction of the patients in the observation group (96.83%) was significantly higher than that in the control group (76.19%), with P value <0.05; compared with the control group, patients in the observation group had shorter operative time and healing time and less intraoperative bleeding, with P value <0.05; the total frequency of adverse reactions of sufferers in the observation group (4.76%) was less than the control group (17.46%), with P value <0.05. CONCLUSION: Small incision liposuction with submerged sutures for plastic repair has significant efficacy, relatively high patient satisfaction, and low incidence of adverse reactions, in line with patient esthetic review, which has a broad clinical application prospect.
RESUMO
Mesoporous metalâorganic frameworks (MOFs) are promising supports for the immobilization of enzymes, yet their applications are often limited by small pore apertures that constrain the size of encapsulated enzymes to below 5 nm. In this study, we introduced labile linkers (4,4',4''-(2,4,6-boroxintriyl)-tribenzoate, TBTB) with dynamic boroxine bonds into mesoporous PCN-333, resulting in PCN-333-TBTB with enhanced enzyme loading and protection capabilities. The selective breaking of B-O bonds creates defects in PCN-333, which effectively expands both window and cavity sizes, thereby unlocking hidden mesopores for enzyme encapsulation. Consequently, this strategy not only increases the adsorption kinetics of small enzymes (<5 nm) such as cytochrome c (Cyt C) and horseradish peroxidase (HRP), but also enables the immobilization of various large-sized enzymes (>5 nm), such as glycoenzymes. The glycoenzymes@PCN-333-TBTB platform was successfully applied to synthesize thirteen complex oligosaccharides and polysaccharides, demonstrating high activity and enhanced enzyme stability. The dynamic linker-mediated enzyme encapsulation strategy enables the immobilization of enzymes exceeding the inherent pore size of MOFs, thus broadening the scope of enzymatic catalytic reactions achievable with MOF materials.
RESUMO
BACKGROUND: Brain metastases (BMs) are the most frequent intracranial tumours associated with poor clinical outcomes. Radiotherapy is essential in the treatment of these tumours, although the optimal radiation strategy remains controversial. The present study aimed to assess whether whole brain radiation therapy with a simultaneous integrated boost (WBRT + SIB) provides any therapeutic benefit over WBRT alone. METHODS: We included and retrospectively analysed 82 patients who received WBRT + SIB and 83 who received WBRT alone between January 2012 and June 2021. Intracranial progression-free survival (PFS), local tumour control (LTC), overall survival (OS), and toxicity were compared between the groups. RESULTS: Compared to WBRT alone, WBRT + SIB improved intracranial LTC and PFS, especially in the lung cancer subgroup. Patients with high graded prognostic assessment score or well-controlled extracranial disease receiving WBRT + SIB had improved intracranial PFS and LTC. Moreover, WBRT + SIB also improved the long-term intracranial tumour control of small cell lung cancer patients. When evaluating toxicity, we found that WBRT + SIB might slightly increase the risk of radiation-induced brain injury, and that the risk increased with increasing dosage. However, low-dose WBRT + SIB had a tolerable radiation-induced brain injury risk, which was lower than that in the high-dose group, while it was comparable to that in the WBRT group. CONCLUSIONS: WBRT + SIB can be an efficient therapeutic option for patients with BMs, and is associated with improved intracranial LTC and PFS. Furthermore, low-dose WBRT + SIB (biologically effective dose [BED] ≤ 56 Gy) was recommended, based on the acceptable risk of radiation-induced brain injury and satisfactory tumour control. TRIAL REGISTRATION: Retrospectively registered.
Assuntos
Lesões Encefálicas , Neoplasias Encefálicas , Neoplasias Pulmonares , Lesões por Radiação , Humanos , Fracionamento da Dose de Radiação , Irradiação Craniana/efeitos adversos , Encéfalo/patologia , Neoplasias Encefálicas/secundário , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patologia , Lesões por Radiação/etiologiaRESUMO
To improve the retention and slow-release abilities of nitrogen (N) and phosphorus (P), an 82 %-purity struvite fertilizer (MAP-BC) was synthesized using magnesium-modified biochar and a solution with a 2:1 concentration ratio of NH4+ to PO43- at a pH of 8. Batch microscopic characterizations and soil column leaching experiments were conducted to study the retention and slow-release mechanisms and desorption kinetics of MAP-BC. The slow-release mechanism revealed that the dissolution rate of high-purity struvite was the dominant factor of NP slow release. The re-adsorption of NH4+ and PO43- by biochar and unconsumed MgO prolonged slow release. Mg2+ ionized by MgO could react with PO43- released from struvite to form Mg3(PO4)2. The internal biochar exhibited electrostatic attraction and pore restriction towards NH4+, while magnesium modification and nutrient loading formed a physical antioxidant barrier that ensured long-term release. The water diffusion experiment showed a higher cumulative release rate for PO43- compared to NH4+, whereas in soil column leaching, the trend was reversed, suggesting that soil's competitive adsorption facilitated the desorption of NH4+ from MAP-BC. During soil leaching, cumulative release rates of NH4+ and PO43- from chemical fertilizers were 3.55-3.62 times faster than those from MAP-BC. The dynamic test data for NH4+ and PO43- in MAP-BC fitted the Ritger-Peppas model best, predicting release periods of 163 days and 166 days, respectively. The leaching performances showed that MAP-BC reduced leaching solution volume by 5.58 % and significantly increased soil large aggregates content larger than 0.25 mm by 24.25 %. The soil nutrients retention and pH regulation by MAP-BC reduced leaching concentrations of NP. Furthermore, MAP-BC significantly enhanced plant growth, and it is more suitable as a NP source for long-term crops. Therefore, MAP-BC is expected to function as a long-term and slow-release fertilizer with the potential to minimize NP nutrient loss and replace part of quick-acting fertilizer.
Assuntos
Fertilizantes , Magnésio , Estruvita/química , Magnésio/química , Fertilizantes/análise , Óxido de Magnésio , Fósforo/química , Carvão Vegetal/química , Solo/química , Nitrogênio/análiseRESUMO
BACKGROUND: The conversion from a temporary to a permanent stoma (PS) following rectal cancer surgery significantly impacts the quality of life of patients. However, there is currently a lack of practical preoperative tools to predict PS formation. The purpose of this study is to establish a preoperative predictive model for PS using machine learning algorithms to guide clinical practice. METHODS: In this retrospective study, we analyzed clinical data from a total of 655 patients who underwent anterior resection for rectal cancer, with 552 patients from one medical center and 103 from another. Through machine learning algorithms, five predictive models were developed, and each was thoroughly evaluated for predictive performance. The model with superior predictive accuracy underwent additional validation using both an independent testing cohort and the external validation cohort. The Shapley Additive exPlanations (SHAP) approach was employed to elucidate the predictive factors influencing the model, providing an in-depth visual analysis of its decision-making process. RESULTS: Eight variables were selected for the construction of the model. The support vector machine (SVM) model exhibited superior predictive performance in the training set, evidenced by an AUC of 0.854 (95 % CI:0.803-0.904). This performance was corroborated in both the testing set and external validation set, where the model demonstrated an AUC of 0.851 (95%CI:0.748-0.954) and 0.815 (95%CI:0.710-0.919), respectively, indicating its efficacy in identifying the PS. CONCLUSIONS: The model(https://yangsu2023.shinyapps.io/psrisk/) indicated robust predictive performance in identifying PS after anterior resection for rectal cancer, potentially guiding surgeons in the preoperative stratification of patients, thus informing individualized treatment plans and improving patient outcomes.
Assuntos
Aprendizado de Máquina , Neoplasias Retais , Estomas Cirúrgicos , Humanos , Neoplasias Retais/cirurgia , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Máquina de Vetores de Suporte , Qualidade de Vida , Protectomia/métodos , AlgoritmosRESUMO
Chemotherapy is a crucial treatment for colorectal tumors. However, its efficacy is restricted by chemoresistance. Recently, Golgi dispersal has been suggested to be a potential response to chemotherapy, particularly to drugs that induce DNA damage. However, the underlying mechanisms by which Golgi dispersal enhances the capacity to resist DNA-damaging agents remain unclear. Here, we demonstrated that DNA-damaging agents triggered Golgi dispersal in colorectal cancer (CRC), and cancer stem cells (CSCs) possessed a greater degree of Golgi dispersal compared with differentiated cancer cells (non-CSCs). We further revealed that Golgi dispersal conferred resistance against the lethal effects of DNA-damaging agents. Momentously, Golgi dispersal activated the Golgi stress response via the PKCα/GSK3α/TFE3 axis, resulting in enhanced protein and vesicle trafficking, which facilitated drug efflux through ABCG2. Identification of Golgi dispersal indicated an unexpected pathway regulating chemoresistance in CRC.
Assuntos
Neoplasias Colorretais , Resistencia a Medicamentos Antineoplásicos , Complexo de Golgi , Células-Tronco Neoplásicas , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Humanos , Complexo de Golgi/metabolismo , Complexo de Golgi/efeitos dos fármacos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Dano ao DNA , Camundongos , Camundongos Nus , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/genética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêuticoRESUMO
OBJECTIVE: To assess the association between early initiation of parenteral nutrition (PN) and body growth in preterm infants with very low birth weight (VLBW). DESIGN: Causal inference analysis with confounders preselected by causal diagram based on the NeoNutriNet cohort containing data of infants born between 2011 and 2014 from 13 hospitals from 5 continents. PATIENTS: Neonates with birth weight ≤1500 g. INTERVENTIONS: PN initiated within the first day of life (early PN) versus within day 2-5 (delayed PN). MAIN OUTCOME MEASURES: The primary outcome was body weight z-scores at postmenstrual age (PMA) 36 weeks or early discharge or death, whichever comes first (WT z-score END). Secondary outcomes included WT z-scores at week 1 and 4 of life (WT z-scores CA1 and CA4), corresponding growth velocities (GVs), mortality and incidence of necrotising enterocolitis (NEC), and duration and episodes of antibiotic treatment. RESULTS: In total, 2151 infants were included in this study and 2008 infants were in the primary outcome analysis. Significant associations of early PN were found with WT z-score END (adjusted mean difference, 0.14 (95% CI 0.05 to 0.23)), CA4 (ß, 0.09 (0.04 to 0.14)) and CA1 (0.04 (0.01 to 0.08)), and GV PMA 36 weeks (1.02 (0.46 to 1.58)) and CA4 (1.03 (0.56 to 1.49), all p<0.001), but not with GV CA1 (p>0.05). No significant associations with mortality, incidence of NEC or antibiotic use was found (all p>0.05). CONCLUSIONS: For VLBW infants, PN initiated within the first day of life is associated with improved in-hospital growth.
Assuntos
Enterocolite Necrosante , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Nutrição Parenteral , Humanos , Recém-Nascido de muito Baixo Peso/crescimento & desenvolvimento , Recém-Nascido , Nutrição Parenteral/métodos , Estudos Retrospectivos , Feminino , Masculino , Recém-Nascido Prematuro/crescimento & desenvolvimento , Enterocolite Necrosante/epidemiologia , Enterocolite Necrosante/prevenção & controle , Idade GestacionalRESUMO
BACKGROUND: Assessing diet quality has been challenging, and the associations of diet quality and daily free sugar intake with depressive and/or anxiety symptoms have shown inconsistency. METHODS: A total of 1749 students aged 12-16 years were recruited using stratified random cluster sampling across three cities in China. The overall Global Dietary Recommendations (GDR) score, a novel indicator of diet quality, was constructed using the low-burden Diet Quality Questionnaire. Free sugar intake, including from beverages and foods, was measured using the Food Frequency Questionnaire. Daily free sugar intake was divided into low, medium, and high categories based on the latest version of the dietary guidelines for Chinese residents. Binomial and multinominal logistic regression analyses were used to examine the associations of the overall GDR score and daily free sugar intake categories or different sources of free sugar intake with depressive and/or anxiety symptoms. RESULTS: The overall GDR score was negatively associated with depressive symptoms (adjusted odds ratio[aOR] = 0.92, 95%CI: 0.87-0.98) and anxiety symptoms (0.95, 0.90-0.99), particularly with comorbid depression and anxiety (0.90, 0.84-0.97). Conversely, daily free sugar intake was positively associated with symptoms of depression and/or anxiety, the multiple aOR for symptoms depression or anxiety were significantly increased with higher daily free sugar intake (all Ptrend < 0.05). Both free sugar from beverages and from foods were positively associated with depressive and/or anxiety symptoms. These associations were consistent between males and females. LIMITATIONS: Cross-sectional design and self-reported symptoms. CONCLUSIONS: Diet quality was negatively associated with symptoms of depression or anxiety, especially with comorbid symptoms among adolescents. Daily free sugar intake, regardless of its sources, was positively associated with symptoms of depression and/or anxiety.
Assuntos
Dieta , Alimentos , Masculino , Feminino , Humanos , Adolescente , Estudos Transversais , Ansiedade/epidemiologia , Açúcares , Depressão/epidemiologiaRESUMO
The biological activities of heparan sulfate (HS) are intimately related to their molecular weights, degree and pattern of sulfation and homogeneity. The existing methods for synthesizing homogeneous sugar chains of low dispersity involve multiple steps and require stepwise isolation and purification processes. Here, we designed a mesoporous metal-organic capsule for the encapsulation of glycosyltransferase and obtained a microreactor capable of enzymatically catalyzing polymerization reactions to prepare homogeneous heparosan of low dispersity, the precursor of HS and heparin. Since the sugar chain extension occurs in the pores of the microreactor, low molecular weight heparosan can be synthesized through space-restricted catalysis. Moreover, the glycosylation co-product, uridine diphosphate (UDP), can be chelated with the exposed metal sites of the metal-organic capsule, which inhibits trans-cleavage to reduce the molecular weight dispersity. This microreactor offers the advantages of efficiency, reusability, and obviates the need for stepwise isolation and purification processes. Using the synthesized heparosan, we further successfully prepared homogeneous 6-O-sulfated HS of low dispersity with a molecular weight of approximately 6 kDa and a polydispersity index (PDI) of 1.032. Notably, the HS generated exhibited minimal anticoagulant activity, and its binding affinity to fibroblast growth factor 1 was comparable to that of low molecular weight heparins.
Assuntos
Heparitina Sulfato , Polimerização , Heparitina Sulfato/química , Anticoagulantes/química , Anticoagulantes/farmacologia , Anticoagulantes/síntese química , Peso Molecular , Porosidade , Humanos , Dissacarídeos/química , Glicosiltransferases/metabolismo , Glicosiltransferases/químicaRESUMO
OBJECTIVE: The genomic and molecular ecology involved in the stepwise continuum progression of lung adenocarcinoma (LUAD) from adenocarcinoma in situ (AIS) to minimally invasive adenocarcinoma (MIA) and subsequent invasive adenocarcinoma (IAC) remains unclear and requires further elucidation. We aimed to characterize gene mutations and expression landscapes, and explore the association between differentially expressed genes (DEGs) and significantly mutated genes (SMGs) during the dynamic evolution from AIS to IAC. METHODS: Thirty-five patients with ground-glass nodules (GGNs) lung adenocarcinomas were enrolled. Whole-exome sequencing (WES) and transcriptome sequencing (RNA-Seq) were conducted on all patients, encompassing both tumor samples and corresponding noncancerous tissues. Data obtained from WES and RNA-Seq were subsequently analyzed. RESULTS: The findings from WES delineated that the predominant mutations were observed in EGFR (49%) and ANKRD36C (17%). SMGs, including EGFR and RBM10, were associated with the dynamic evolution from AIS to IAC. Meanwhile, DEGs, including GPR143, CCR9, ADAMTS16, and others were associated with the entire process of invasive LUAD. We found that the signaling pathways related to cell migration and invasion were upregulated, and the signaling pathways of angiogenesis were downregulated across the pathological stages. Furthermore, we found that the messenger RNA (mRNA) levels of FAM83A, MAL2, DEPTOR, and others were significantly correlated with CNVs. Gene set enrichment analysis (GSEA) showed that heme metabolism and cholesterol homeostasis pathways were significantly upregulated in patients with EGFR/RBM10 co-mutations, and these patients may have poorer overall survival than those with EGFR mutations. Based on the six calculation methods for the immune infiltration score, NK/CD8+ T cells decreased, and Treg/B cells increased with the progression of early LUAD. CONCLUSIONS: Our findings offer valuable insights into the unique genomic and molecular features of LUAD, facilitating the identification and advancement of precision medicine strategies targeting the invasive progression of LUAD from AIS to IAC.
Assuntos
Adenocarcinoma de Pulmão , Sequenciamento do Exoma , Neoplasias Pulmonares , Mutação , Invasividade Neoplásica , Humanos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Transcriptoma , Perfilação da Expressão Gênica , Adenocarcinoma in Situ/genética , Adenocarcinoma in Situ/patologia , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Biomarcadores Tumorais/genéticaRESUMO
Importance: In China, parental labor migration often leaves children behind and is potentially adversely associated with children's health. However, the association between parental migration and aggression among their offspring remains largely underexplored. Objective: To investigate the associations of parental labor migration with total and subtypes of aggression among their offspring as well as potential sex differences therein. Design, Setting, and Participants: This cross-sectional study was conducted from February to October 2015 among students aged 11 to 20 years from 45 public middle and high schools across 5 provinces of China. Data analysis was performed from December 1, 2022, to August 1, 2023. Exposures: Parental migration, including migration status (yes or no), pattern (father, mother, or both), and the child's age at the initial parent-child separation. Main Outcomes and Measures: Total and subtypes of aggression (including physical aggression [PA], verbal aggression [VA], indirect aggression [IA], anger, and hostility) were measured using the Chinese version of the Buss-Warren Aggression Questionnaire. Binomial logistic regression analyses were used separately to estimate adjusted odds ratios (aORs) and 95% CIs of parental migration by total and subtypes of aggression. Results: A total of 15â¯301 participants (7900 [51.6%] male and 7401 [48.4%] female) aged 11 to 20 years (mean [SD] age, 15.1 [1.8] years) were included. Of these participants, 5961 (39.0%) experienced parental migration; 2451 (16.0%) met the criteria for total aggression, 2407 (15.7%) for PA, 2283 (14.9%) for VA, 2899 (18.9%) for IA, 2307 (15.1%) for anger, and 2564 (16.8%) for hostility. Parental migration was associated with total aggression (aOR, 1.11; 95% CI, 1.01-1.22); no significant association between parental migration and subtypes of aggression was found except for PA (aOR, 1.14; 95% CI, 1.03-1.25). Compared with children whose parents did not migrate, the aORs for total aggression and PA for participants whose father migrated were 1.12 (95% CI, 1.01-1.28) and 1.15 (95% CI, 1.03-1.29), respectively; for participants with both parents having migrated, the aORs were 1.16 (95% CI, 1.02-1.31) and 1.12 (95% CI, 1.04-1.24), respectively. Compared with children whose parents did not migrate, children who experienced initial separation from 1 or both parents at adolescence had an aOR for total aggression of 1.20 (95% CI, 1.04-1.36), children who experienced initial separation from 1 or both parents at school age or adolescence had an aOR for PA of 1.15 (95% CI, 1.01-1.32) and 1.26 (95% CI, 1.04-1.51), respectively. No sex differences were found in these associations. Conclusions and Relevance: In this cross-sectional study of Chinese children and adolescents, we found that parental migration, mainly of the father or both parents or an initial separation at adolescence or school age from 1 or both parents, was associated with higher odds of total aggression and PA among offspring. These associations were similar between male and female participants.
Assuntos
Agressão , Pais , Feminino , Masculino , Humanos , Adolescente , Estudos Transversais , Ira , ChinaRESUMO
MXenes, as a typical graphene-like material, excels in the realm of humidity sensing owing to its two-dimensional layer structure, high electrical conductivity, tunable chemical properties, hydrophilicity, and large specific surface area. This study proposed a quartz crystal microbalance (QCM) humidity sensor using a nanochitin/Ti3C2Tx MXene composite as a humidity-sensing material. The morphology, nanostructure, and elemental composition of nanochitin, Ti3C2Tx MXene, and nanochitin/Ti3C2Tx MXene composite materials were characterized using transmission electron microscopy, Fourier transform infrared spectroscopy, and X-ray diffraction. Compared to the pure Ti3C2Tx MXene-coated QCM humidity sensor, the nanochitin/Ti3C2Tx MXene-coated QCM humidity sensor exhibited a higher sensitivity (20.54 Hz/%RH) in the humidity range of 11.3% to 97.3%. The nanochitin/Ti3C2Tx Mxene-coated QCM humidity sensor also demonstrated low humidity hysteresis (2.12%RH), very fast response/recovery times (4.4/4.1 s), a high quality factor (37 k), and excellent repeatability and sustained stability over time. Eventually, a bimodal exponential kinetics adsorption model was utilized for the analysis of the response mechanism of the nanochitin/Ti3C2Tx MXene composite material-based QCM humidity sensor. This study provides new ideas for optimizing the moisture-sensitive performance of MXene-based QCM humidity sensors.
RESUMO
Cancer remains a significant global health issue, despite advances in screening and treatment. While existing tumor treatment protocols such as surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy have proven effective in enhancing the prognosis for some patients, these treatments do not benefit all patients. Consequently, certain types of cancer continue to exhibit a relatively low 5-year survival rate. Therefore, the pursuit of novel tumor intervention strategies may help improve the current effectiveness of tumor treatment. Over the past few decades, numerous species of protozoa and their components have exhibited anti-tumor potential via immune and non-immune mechanisms. This discovery introduces a new research direction for the development of new and effective cancer treatments. Through in vitro experiments and studies involving tumor-bearing mice, the anti-tumor ability of Toxoplasma gondii, Plasmodium, Trypanosoma cruzi, and other protozoa have unveiled diverse mechanisms by which protozoa combat cancer, demonstrating encouraging prospects for their application. In this review, we summarize the anti-tumor ability and anti-tumor mechanisms of various protozoa and explore the potential for their clinical development and application.