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In recent years, single-cell analyses have revealed the heterogeneity of the tumour microenvironment (TME) at the genomic, transcriptomic, and proteomic levels, further improving our understanding of the mechanisms of tumour development. Single-cell RNA sequencing (scRNA-seq) technology allow analysis of the transcriptome at the single-cell level and have unprecedented potential for exploration of the characteristics involved in tumour development and progression. These techniques allow analysis of transcript sequences at higher resolution, thereby increasing our understanding of the diversity of cells found in the tumour microenvironment and how these cells interact in complex tumour tissue. Although scRNA-seq has emerged as an important tool for studying the tumour microenvironment in recent years, it cannot be used to analyse spatial information for cells. In this regard, spatial transcriptomics (ST) approaches allow researchers to understand the functions of individual cells in complex multicellular organisms by understanding their physical location in tissue sections. In particular, in related research on tumour heterogeneity, ST is an excellent complementary approach to scRNA-seq, constituting a new method for further exploration of tumour heterogeneity, and this approach can also provide unprecedented insight into the development of treatments for pancreatic cancer (PC). In this review, based on the methods of scRNA-seq and ST analyses, research progress on the tumour microenvironment and treatment of pancreatic cancer is further explained.
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Neoplasias Pancreáticas , Análise de Sequência de RNA , Análise de Célula Única , Transcriptoma , Microambiente Tumoral , Microambiente Tumoral/genética , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Transcriptoma/genética , Perfilação da Expressão Gênica , AnimaisRESUMO
BACKGROUND: To introduce a three-dimensional convolutional neural network (3D CNN) leveraging transfer learning for fusing PET/CT images and clinical data to predict EGFR mutation status in lung adenocarcinoma (LADC). METHODS: Retrospective data from 516 LADC patients, encompassing preoperative PET/CT images, clinical information, and EGFR mutation status, were divided into training (n = 404) and test sets (n = 112). Several deep learning models were developed utilizing transfer learning, involving CT-only and PET-only models. A dual-stream model fusing PET and CT and a three-stream transfer learning model (TS_TL) integrating clinical data were also developed. Image preprocessing includes semi-automatic segmentation, resampling, and image cropping. Considering the impact of class imbalance, the performance of the model was evaluated using ROC curves and AUC values. RESULTS: TS_TL model demonstrated promising performance in predicting the EGFR mutation status, with an AUC of 0.883 (95%CI = 0.849-0.917) in the training set and 0.730 (95%CI = 0.629-0.830) in the independent test set. Particularly in advanced LADC, the model achieved an AUC of 0.871 (95%CI = 0.823-0.919) in the training set and 0.760 (95%CI = 0.638-0.881) in the test set. The model identified distinct activation areas in solid or subsolid lesions associated with wild and mutant types. Additionally, the patterns captured by the model were significantly altered by effective tyrosine kinase inhibitors treatment, leading to notable changes in predicted mutation probabilities. CONCLUSION: PET/CT deep learning model can act as a tool for predicting EGFR mutation in LADC. Additionally, it offers clinicians insights for treatment decisions through evaluations both before and after treatment.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Retrospectivos , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/genética , Mutação , Redes Neurais de Computação , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Aprendizado de Máquina , Receptores ErbB/genéticaRESUMO
NEW FINDINGS: What is the central question of this study? What are the morphological features and microRNA (miRNA) expression features of extracellular vesicles (EVs) from haemorrhoids (Hae-EVs) and normal tissues? What are the potential functions of the differentially expressed (DE) miRNAs in Hae-EVs? What is the main finding and its importance? We present, for the first time, the morphological features and miRNA profile of human Hae-EVs. Four hundred and forty-seven significant DE-miRNAs were identified. Gene ontology and pathway analysis of the DE-miRNAs indicated diverse roles of the Hae-EVs through different pathways. Our findings provide EV-based pathological features and the underlying mechanism of haemorrhoids. ABSTRACT: Extracellular vesicles (EVs) play important roles in many pathophysiologies as cell-to-cell communication vehicles. However, the features and potential functions of the EVs in haemorrhoids remain unclear. Therefore, we performed microRNA (miRNA) microarray analysis in EVs derived from haemorrhoid tissue to identify the profile of miRNAs in these EVs and predict their potential functions. We obtained typical EVs from both haemorrhoid and control tissues. Microarray analysis identified 447 miRNAs with significant differential expresssion (DE): 245 upregulated and 202 downregulated. The top three upregulated miRNAs in haemorrhoid EVs (Hae-EVs), namely miR-6741-3p, miR-6834-3p and miR-4254, were detected by RT-qPCR in both Hae-EVs and haemorrhoid tissues. Interestingly, we found a different expression pattern in the haemorrhoid tissues from that in Hae-EVs. The potential target genes of these DE-miRNAs were predicted by the miRWalk and miRDB databases. Gene ontology (GO) analysis of the target genes showed that the DE-miRNAs contributed mainly to protein kinase activity, transcriptional activity and ubiquitin-protein function. KEGG search found that the DE-miRNAs might regulate the MAPK and Ras signalling pathways. These findings revealed, for the first time, the miRNA profiles in Hae-EVs and provided potential targets and pathways involved in the pathological process.
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Vesículas Extracelulares , Hemorroidas , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Hemorroidas/genética , Hemorroidas/metabolismo , Vesículas Extracelulares/metabolismoRESUMO
Water reclamation is the most effective way to continuously provide clean water to combat catastrophic global water scarcity. However, current technology for water purification is not conducive to sustainability due to the high energy consumption and negative environmental impact. Here, we introduce an innovative method by utilizing the hierarchical microstructure of bamboo for water purification. Natural bamboo was delignified followed by freeze-drying to obtain a bamboo aerogel with a porosity of 72.0%; then, the bamboo aerogel was coated with silver nanoparticles to form a hierarchical bamboo/silver nanoparticle composite. The scanning electron microscopy images and energy-dispersive X-ray spectroscopy results indicated that the silver nanoparticles were uniformly attached to the parenchyma cell surface. By physical adsorption and catalytic reduction, the bamboo/silver nanoparticle composite was able to degrade methylene blue by more than 96.7%, which is mainly attributed to the large specific surface area of the bamboo providing more space for the purification reaction. This composite can be potentially used for board applications with its high porosity, mechanical reliability, and sustainability.
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SHR0302, a selective JAK1 inhibitor developed by Jiangsu Hengrui Pharmaceutical Co., was intended for the treatment of rheumatoid arthritis. In this study, we evaluated the pharmacokinetics, mass balance, and metabolism of SHR0302 in six healthy Chinese male subjects after a single 8 mg (80 µCi) oral dose of [14C]SHR0302.SHR0302 was absorbed rapidly (Tmax = 0.505 h), and the average t1/2 of the SHR0302-related components in plasma was approximately 9.18 h. After an oral dose was administered, the average cumulative excretion of the radioactive components was 100.56% ± 1.51%, including 60.95% ± 11.62% in urine and 39.61% ± 10.52% in faeces.A total of 16 metabolites were identified. In plasma, the parent drug SHR0302 accounted for 90.42% of the total plasma radioactivity. In urine, SHR161279 was the main metabolite, accounting for 33.61% of the dose, whereas the parent drug SHR0302 only accounted for 5.1% of the dose. In faeces, the parent drug SHR0302 accounted for 23.73% of the dose, and SHR161279 was the significant metabolite, accounting for 5.67% of the dose. In conclusion, SHR0302-related radioactivity was mainly excreted through urine (60.95%) and secondarily through faeces (39.61%).The metabolic reaction of SHR0302 in the human body is mainly through mono-oxidation and glucuronidation. The main metabolic location of SHR0302 in the human body is the pyrrolopyrimidine ring.
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Líquidos Corporais , Ácidos Sulfúricos , Humanos , Masculino , Fezes , Administração Oral , Radioisótopos de Carbono , Janus Quinase 1RESUMO
BACKGROUND: Pemphigus vulgaris (PV) is a potentially fatal autoimmune bullous disease primarily caused by acantholysis of keratinocytes attributed to pathogenic desmoglein-3 (Dsg3) autoantibodies. Interleukin-37 (IL-37) reportedly plays important roles in a variety of autoimmune diseases, but its role in PV is not clear. OBJECTIVES: To investigate whether IL-37 plays a role in the occurrence and progression of PV. METHODS: HaCaT keratinocytes were stimulated with anti-Dsg3 antibody to establish an in vitro PV model, which was defined as anti-Dsg3 group. Cells incubated with medium without anti-Dsg3 treatment were used as control. IL-37 was cultured with these cells infected with or without lentiviral vector shRNA-Caveolin-1 (sh-Cav-1-LV). Cell dissociation assay and immunocytofluorescence were performed to assess keratinocyte dissociation, keratin retraction and Dsg3 endocytosis. Real-time PCR was used to detect the mRNA level of Cav-1, and western blot was used to determine the protein expression of Cav-1, Dsg3, STAT3 and phosphorylated-STAT3 (p-STAT3). RESULTS: The anti-Dsg3 group showed more cell debris, increased keratin retraction, increased Dsg3 endocytosis, reduced Cav-1 expression and co-localization than the control group, while IL-37 treatment neutralized all of these changes. Interestingly, Cav-1 knockdown supressed the inhibitory effect of IL-37 on keratinocyte dissociation and Dsg3 internalization. The protein expression of p-STAT3 was increased in keratinocytes of the PV model but decreased by IL-37. Re-activation of the STAT3 pathway by colivelin supressed the inhibitory effect of IL-37 on keratinocyte dissociation and Dsg3 internalization, along with upregulation of Cav-1 and Dsg3. CONCLUSIONS: IL-37 inhibited keratinocyte dissociation and Dsg3 endocytosis in an in vitro PV model through the upregulating Cav-1 and inhibiting STAT3 pathway.
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Caveolina 1 , Interleucinas , Humanos , Autoanticorpos , Caveolina 1/metabolismo , Caveolina 1/farmacologia , Desmogleína 3 , Endocitose , Interleucinas/metabolismo , Queratinócitos/metabolismo , Queratinas/metabolismo , Pênfigo/patologia , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/farmacologia , Regulação para CimaRESUMO
Circular RNAs (circRNAs) are linked to the regulation of sepsis-induced acute kidney injury (AKI). However, the function of circITCH in the development of sepsis-induced AKI is still unclear. The levels of circITCH, miR-579-3p and ZEB2 were examined by real-time PCR and immunoblotting. Then, the roles of circITCH in cell viability, apoptosis, and inflammation in lipopolysaccharide (LPS)-treated HK-2 cells were evaluated. The further mechanism was investigated using rescue assays. CircITCH was downregulated in septic AKI patients and LPS-triggered HK-2 cells. CircITCH overexpression restored cell viability in LPS-treated HK-2 cells and restrained apoptosis and inflammatory cytokine production. CircITCH negatively regulated miR-579-3p, thereby upregulating ZEB2 expression. Taken together, circITCH alleviates LPS-induced HK-2 cell injury by regulating miR-579-3p/ZEB2 signal axis, which provides a theoretical basis for AKI therapy.
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Injúria Renal Aguda , MicroRNAs , Sepse , Humanos , Lipopolissacarídeos/farmacologia , Injúria Renal Aguda/genética , Sepse/complicações , Sepse/genética , Apoptose/genética , MicroRNAs/genética , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genéticaRESUMO
Extracellular vesicles (EVs) play important roles in cardiovascular diseases by delivering their RNA cargos. However, the features and possible role of the lncRNAs and mRNAs in cardiac EVs during ischemia-reperfusion (IR) remain unclear. Therefore, we performed RNA sequencing analysis to profile the features of lncRNAs and mRNAs and predicted their potential functions. Here, we demonstrated that the severity of IR injury was significantly correlated with cardiac EV production. RNA sequencing identified 73 significantly differentially expressed (DE) lncRNAs (39 upregulated and 34 downregulated) and 720 DE-mRNAs (317 upregulated and 403 downregulated). Gene Ontology (GO) and pathway analysis were performed to predict the potential functions of the DE-lncRNAs and mRNAs. The lncRNA-miRNA-mRNA ceRNA network showed the possible functions of DE-lncRNAs with DE-mRNAs which are enriched in the pathways of T cell receptor signalling pathway and cell adhesion molecules. Moreover, the expressions of ENSMUST00000146010 and ENSMUST00000180630 were negatively correlated with the severity of IR injury. A significant positive correlation was revealed between TCONS_00010866 expression and the severity of the cardiac injury. These findings revealed the lncRNA and mRNA profiles in the heart derived EVs and provided potential targets and pathways involved in cardiac IR injury.
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Vesículas Extracelulares , MicroRNAs , RNA Longo não Codificante , Traumatismo por Reperfusão , Camundongos , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Redes Reguladoras de Genes , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , MicroRNAs/genética , Traumatismo por Reperfusão/genética , Perfilação da Expressão GênicaRESUMO
Accumulating evidence suggests that supplementation of n-3 PUFA was associated with reduction in risk of major cardiovascular events. This meta-analysis was to systematically evaluate whether daily supplementation and accumulated intake of n-3 PUFA are associated with improved left ventricular (LV) remodelling in patients with chronic heart failure (CHF). Articles were obtained from Pubmed, Clinical key and Web of Science from inception to January 1 in 2021, and a total of twelve trials involving 2162 participants were eligible for inclusion. The sources of study heterogeneity were explained by I2 statistic and subgroup analysis. Compared with placebo groups, n-3 PUFA supplementation improved LV ejection fraction (LVEF) (eleven trials, 2112 participants, weighted mean difference (WMD) = 2·52, 95 % CI 1·25, 3·80, I2 = 87·8 %) and decreased LV end systolic volume (five studies, 905 participants, WMD = -3·22, 95 % CI 3·67, -2·77, I2 = 0·0 %) using the continuous variables analysis. Notably, the high accumulated n-3 PUFA dosage groups (≥ 600 g) presented a prominent improvement in LVEF, while the low and middle accumulated dosage (≤ 300 and 300-600 g) showed no effects on LVEF. In addition, n-3 PUFA supplementation decreased the levels of pro-inflammatory mediators including TNF-α, IL-6 (IL-6) and hypersensitive c-reactive protein. Therefore, the present meta-analysis demonstrated that n-3 PUFA consumption was associated with a substantial improvement of LV function and remodelling in patients subjected to CHF. The accumulated dosage of n-3 PUFA intake is vital for its cardiac protective role.
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Furmonertinib (Alflutinib, AST2818), as a third-generation epidermal growth factor receptor inhibitor with an advanced efficacy and a relatively wide safety window, has been commercially launched in China recently. However, previous clinical studies demonstrated its time- and dose-dependent clearance in a multiple-dose regimen. In vitro drug metabolism and pharmacokinetic studies have suggested that furmonertinib is mainly metabolized by cytochrome P450 3A4 (CYP3A4) and can induce these enzymes via an increased mRNA expression. This study investigated two important evaluation criteria of CYP3A4 induction by furmonertinib through quantitative proteomics and probe metabolite formation: simultaneous (1) protein expression and (2) enzyme activity with sandwich-cultured primary human hepatocytes in the same well of cell culture plates. Results confirmed that furmonertinib was a potent CYP3A4 inducer comparable with rifampin and could be used as a positive model drug in in vitro studies to evaluate the induction potential of other drug candidates in preclinical studies. In addition, inconsistencies were observed between the protein expression and enzyme activities of CYP3A4 in cells induced by rifampin but not in groups treated with furmonertinib. As such, furmonertinib could be an ideal positive control in the evaluation of CYP3A4 induction. The cells treated with 10 µM rifampin expressed 20.16 ± 5.78 pmol/mg total protein, whereas the cells induced with 0.5 µM furmonertinib expressed 4.8 ± 0.66 pmol/mg protein compared with the vehicle (0.1% dimethyl sulfoxide), which contained 0.65 ± 0.45 pmol/mg protein. The fold change in the CYP3A4 enzyme activity in the cells treated with rifampin was 5.22 ± 1.13, which was similar to that of 0.5 µM furmonertinib (3.79 ± 0.52).
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Indutores do Citocromo P-450 CYP3A/farmacologia , Hepatócitos/efeitos dos fármacos , Indóis/farmacologia , Piridinas/farmacologia , Pirimidinas/farmacologia , Rifampina/farmacologia , Animais , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Proteômica , Ratos , Ratos Sprague-DawleyRESUMO
This study was intended to delineate the profile of double-negative T cells (DNTs) in NOD.Cg-Prkdcscid Il2rgtm1wj /SzJ mice and cytokines released from DNTs in vivo and in vitro. Total 4 × 107 cells of RC1012 injection per mice were intravenously infused. IFN-γ, TNF-α, IL-1ß, IL-2, IL-4, IL-6, IL-10 were measured in vivo and in vitro. A quantitative polymerase chain reaction (PCR) was employed to determine the gene copies of Notch2-NLA per DNT cell from collected organs. Cytokines were significantly increased in vitro (4 h) and in vivo (3 h). DNT cells were distributed into the lung, liver, heart, and kidney earlier, and redistributed to lymphocyte homing spleen and bone marrow, which seemed to frame a two-compartment pharmacokinetics (PK) model but more data are needed to confirm this, and the clearance of DNT cells fell into first-order kinetics.
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Citocinas/imunologia , Linfócitos T/transplante , Administração Intravenosa , Animais , Medula Óssea/imunologia , Feminino , Humanos , Imunoterapia Adotiva , Rim/imunologia , Fígado/imunologia , Pulmão/imunologia , Masculino , Camundongos Mutantes , Miocárdio/imunologia , Receptor Notch2/genética , Baço/imunologia , Linfócitos T/imunologia , Distribuição TecidualRESUMO
Objective: To investigate the risk factors affecting the survival of patients with gastrointestinal stromal tumors (GISTs) in different age groups. Methods: Information on 6089 GIST patients was screened from the Surveillance, Epidemiology, and End Results (SEER) database. Risk factor analysis was performed using a chi-square test (univariate analysis). Survival analysis was performed using the Kaplan-Meier method (log-rank test) and the COX proportional hazard model. p Value < .05 was considered statistically significant. Results: Analyzed statistically to reveal that in addition to tumor size, mitotic index, and primary location, age, gender, race, and surgical treatment also were independent risk factors for GISTs. Gender, race, and location of disease influenced the survival rate of patients, which was higher in the young group (≤60 years old) than the elderly group (>60 years). Risk factors such as primary location, tumor diameter, and mitotic index varied significantly between the different age groups. Conclusions: Age, gender, race, and surgical treatment are independent risk factors that influence the prognosis in patients with GISTs. Some risk factors affecting prognosis are age dependent.
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Fatores Etários , Neoplasias Gastrointestinais/mortalidade , Tumores do Estroma Gastrointestinal/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Índice Mitótico , Análise Multivariada , Prognóstico , Fatores de Risco , Programa de SEER , Análise de SobrevidaRESUMO
CD4+ T-cells play crucial roles in the injured heart. However, the way in which different CD4+ T subtypes function in the myocardial infarction/reperfusion (MI/R) heart is still poorly understood. We aimed to detect the dynamic profile of distinct CD4+ subpopulation-associated cytokines/chemokines by relying on a closed-chest acute murine MI/R model. The protein levels of 26 CD4+ T-cell-associated cytokines/chemokines were detected in the heart tissues and serum of mice at day 7 and day 14 post-MI/R or sham surgery. The mRNA levels of IL-4, IL-6, IL-13, IL-27, MIP-1ß, MCP-3, and GRO-α were measured in blood mononuclear cells. The protein levels of IL-4, IL-6, IL-13, IL-27, MIP-1ß, MCP-3, and GRO-α increased in both injured heart tissues and serum, while IFN-γ, IL-12P70, IL-2, IL-1ß, IL-18, TNF-α, IL-5, IL-9, IL-17A, IL-23, IL-10, eotaxin, MIP-1α, RANTES, MCP-1, and MIP-2 increased only in MI/R heart tissues in the day 7 and day 14 groups compared to the sham group. In serum, the IFN-γ, IL-23, and IL-10 levels were downregulated in the MI/R model at both day 7 and day 14 compared to the sham. Compared with the protein expressions in injured heart tissues at day 7, IFN-γ, IL-12P70, IL-2, IL-18, TNF-α, IL-6, IL-4, IL-5, IL-9, IL-17A, IL-23, IL-27, IL-10, eotaxin, IP-10, RANTES, MCP-1, MCP-3, and GRO-α were reduced, while IL-1ß and MIP-2 were elevated at day 14. IL-13 and MIP-1ß showed higher levels in the MI/R serum at day 14 than at day 7. mRNA levels of IL-4, IL-6, IL-13, and IL-27 were increased in the day 7 group compared to the sham, while MIP-1ß, MCP-3, and GRO-α mRNA levels showed no significant difference between the MI/R and sham groups in blood mononuclear cells. Multiple CD4+ T-cell-associated cytokines/chemokines were upregulated in the MI/R hearts at the chronic stage. These results provided important evidence necessary for developing future immunomodulatory therapies after MI/R.
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Linfócitos T CD4-Positivos/metabolismo , Quimiocinas/metabolismo , Citocinas/metabolismo , Infarto do Miocárdio/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Animais , Quimiocina CCL3/sangue , Quimiocina CCL3/metabolismo , Interleucina-10/sangue , Interleucina-10/metabolismo , Interleucina-13/sangue , Interleucina-13/metabolismo , Interleucina-4/sangue , Interleucina-4/metabolismo , Interleucina-6/sangue , Interleucina-6/metabolismo , Leucócitos Mononucleares/metabolismo , Masculino , Camundongos , Infarto do Miocárdio/sangue , Traumatismo por Reperfusão Miocárdica/sangueRESUMO
In this study, we analyzed the tea polyphenol composition, volatile flavor composition and storage stability of steamed beef with black tea. The molecular docking and dynamics were used to elucidate the interaction mechanism between the active components of black tea and myofibrillar proteins. The highest content of caffeine (CAF) was found in black tea steamed beef products, followed by catechin (C), epicatechin gallate (ECG), epicatechin gallate (EGCG) and theaflavins (TF). Steamed beef with black tea showed low ΔE* value, low TBARS value, low carbonyl content as well as high sulfhydryl content during storage. The addition of C, CAF, ECG, EGCG and TF enhanced the oxidative stability of myofibrillar protein. In this study, the effects of active components of black tea on the oxidative stability of myofibrillar protein and their interactions were determined, which could provide a reference for the application of black tea and its active components in meat products. At the same time, it can provide new ideas for the development of new meat products.
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Camellia sinensis , Catequina , Animais , Bovinos , Chá , Simulação de Acoplamento Molecular , Catequina/análise , Cafeína , Polifenóis , AntioxidantesRESUMO
Background: Tibetan Plateau is one of the most typical areas of biodiversity in the world because of its unique environmental and regional units, which breed unique biological communities and concentrate on many unique and rare wild animals and plants. Research on Chironomidae in the Tibetan Plateau is relatively weak. At present, the identification of Chironomidae species mainly depends on male adults, while identification of larvae and pupae is relatively difficult and there is less research on them. New information: During the investigations of insect diversity in the Tibetan Plateau, larval and pupal stages of Orthocladiusnitidoscutellatus Lundström, 1915 and Psectrocladiusnevalis Akhrorov, 1977 were described and illustrated. Matching and identification of larval and pupal stages were based on DNA barcodes. Neighbour-joining trees were reconstructed, based on known Orthocladius and Psectrocladius COI DNA barcodes, respectively.
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Trichoptera is one of the most evolutionarily successful aquatic insect lineages and is highly valued value in adaptive evolution research. This study presents the chromosome-level genome assemblies of Himalopsyche anomala and Eubasilissa splendida achieved using PacBio, Illumina, and Hi-C sequencing. For H. anomala and E. splendida, assembly sizes were 663.43 and 859.28 Mb, with scaffold N50 lengths of 28.44 and 31.17 Mb, respectively. In H. anomala and E. splendida, we anchored 24 and 29 pseudochromosomes, and identified 11,469 and 10,554 protein-coding genes, respectively. The high-quality genomes of H. anomala and E. splendida provide critical genomic resources for understanding the evolution and ecology of Trichoptera and performing comparative genomics analyses.
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Bases de Dados Genéticas , Genoma de Inseto , Insetos , Animais , Hibridização Genômica Comparativa , Ecologia , Insetos/genéticaRESUMO
Hepatocellular carcinoma (HCC) is a major global cause of death, with epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC)-like properties contributing to its metastasis. DEAD box helicase 56 (DDX56) is involved in carcinogenesis, but its role in EMT induction and stem phenotype maintenance is unclear. This study assessed the impact of DDX56 absence on HCC cell stemness and EMT. DDX56 was found to be overexpressed in HCC tissues, correlating with disease stage and prognosis. In vitro, DDX56 stimulated tumor cell proliferation, migration, invasion, EMT, and stemness. It also enhanced maternal embryonic leucine-zipper kinase (MELK)-mediated forkhead box protein M1 (FOXM1) expression, regulating cancer stemness and malignant traits. In vivo, DDX56 knockdown in tumor-bearing mice reduced tumorigenicity and lung metastasis by modulating the MELK-FOXM1 signaling pathway. Collectively, DDX56 initiates stem cell-like traits in HCC and promotes EMT via MELK-FOXM1 activation, shedding light on HCC pathogenesis and suggesting a potential anti-cancer therapeutic target.
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Background: Immune cells play a crucial role in the development and progression of pancreatic cancer, yet the causal relationship remains uncertain due to complex immune microenvironments and conflicting research findings. Mendelian randomization (MR), this study aims to delineate the causal relationships between immune cells and pancreatic cancer while identifying intermediary factors. Methods: The genome-wide association study (GWAS) data on immune cells, pancreatic cancer, and plasma metabolites are derived from public databases. In this investigation, inverse variance weighting (IVW) as the primary analytical approach to investigate the causal relationship between exposure and outcome. Furthermore, this study incorporates MR-Egger, simple mode, weighted median, and weighted mode as supplementary analytical approaches. To ensure the reliability of our findings, we further assessed horizontal pleiotropy and heterogeneity and evaluated the stability of MR results using the Leave-one-out method. In conclusion, this study employed mediation analysis to elucidate the potential mediating effects of plasma metabolites. Results: Our investigation revealed a causal relationship between immune cells and pancreatic cancer, highlighting the pivotal roles of CD11c+ monocytes (odds ratio, ORIVW=1.105; 95% confidence interval, 95%CI: 1.002-1.218; P=0.045), HLA DR+ CD4+ antigen-presenting cells (ORIVW=0.920; 95%CI: 0.873-0.968; P=0.001), and HLA DR+ CD8br T cells (ORIVW=1.058; 95%CI: 1.002-1.117; P=0.041) in pancreatic cancer progression. Further mediation analysis indicated that oxalate (proportion of mediation effect in total effect: -11.6%, 95% CI: -89.7%, 66.6%) and the mannose to trans-4-hydroxyproline ratio (-19.4, 95% CI: -136%, 96.8%) partially mediate the relationship between HLA DR+ CD8br T cells and pancreatic cancer in nature. In addition, our analysis indicates that adrenate (-8.39%, 95% CI: -18.3%, 1.54%) plays a partial mediating role in the association between CD11c+ monocyte and pancreatic cancer, while cortisone (-26.6%, 95% CI: 138%, -84.8%) acts as a partial mediator between HLA DR+ CD4+ AC and pancreatic cancer. Conclusion: This MR investigation provides evidence supporting the causal relationship between immune cell and pancreatic cancer, with plasma metabolites serving as mediators. Identifying immune cell phenotypes with potential causal effects on pancreatic cancer sheds light on its underlying mechanisms and suggests novel therapeutic targets.
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Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/genética , Monócitos/imunologia , Monócitos/metabolismo , Fatores de Risco , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Microfibers, a prevalent form of microplastics, undergo diverse environmental interactions resulting in varied morphological changes. These changes can offer insights into their environmental trajectories. Despite its importance, comprehensive studies on microfiber morphology are scarce. This study collected 233 microfibers from the East China Sea and South China Sea. Based on morphological features observed in microscopic images of microfibers, such as curvature, cross-sectional shapes, diameter variations, and crack shapes, we identified a general morphological pattern, classifying the environmental microfibers into three distinct morphological types. Our findings highlight noticeable differences in morphological metrics (e.g., length, diameter, and surface roughness) across three types, especially the diameter. Microfibers of Type I had an average diameter of 19.45 ± 4.93 µm, significantly smaller than Type II (263.00 ± 75.15 µm) and Type III (299.68 ± 85.62 µm). Within the three-dimensional (3D) space fully defined by these quantitative parameters, the clustering results of microfibers are also consistent with the proposed morphology pattern, with each category showing a potential correlation with specific chemical compositions. Type I microfibers correspond to synthetic cellulose, while 94.79 % of Types II and III are composed of polymers. Notably, we also validated the great applicability of the morphology categories to microfibers in diverse environmental compartments, including water and sediments in nearshore and offshore areas. This classification aids in the efficient determination of microfiber sources and the assessment of their ecological risks, marking a significant advancement in microfiber environmental studies.
Assuntos
Monitoramento Ambiental , Microplásticos , China , Poluentes Químicos da Água , Oceanos e MaresRESUMO
The study aimed to assay the allergenicity of shrimp tropomyosin (TM) following covalent conjugation with quercetin (QR) and chlorogenic acid (CA). The structure of the TM-polyphenol covalent conjugates was examined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), circular dichroism (CD), fluorescence, differential scanning calorimetry (DSC), and Fourier Transform infrared spectroscopy (FTIR). Potential allergenicity was evaluated using in vitro and in vivo methods. The results showed that QR and CA induced structural changes in TM through aggregation. RBL-2H3 cell results showed that TM-QR and TM-CA covalent conjugates reduced the release of ß-hexosaminidase and histamine, respectively. In the mice model, TM-QR and TM-CA covalent conjugates reduced the level of IgE, IgG, IgG1, histamine, and mMCP-1 in sera. Furthermore, the allergenicity was reduced by suppressing Th2-related cytokines (IL-4, IL-5, IL-13) and promoting Th1-related cytokines (IFN-γ). These research findings demonstrate that the covalent binding of TM with QR and CA, modifies the allergenic epitopes of shrimp TM, thereby reducing its potential allergenicity. This approach holds practical applications in the production of low-allergenicity food within the food industry.