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1.
Rapid Commun Mass Spectrom ; 38(14): e9763, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38745395

RESUMO

OBJECTIVE: Carotid atherosclerosis is a chronic progressive vascular disease that can be complicated by stroke in severe cases. Prompt diagnosis and treatment of high-risk patients are quite difficult due to the lack of reliable clinical biomarkers. This study aimed to explore potential plaque metabolic markers of stroke-prone risk and relevant targets for pharmacological intervention. METHOD: Carotid intima and plaque sample tissues were obtained from 20 patients with cerebrovascular symptoms of carotid origin. An untargeted metabolomics approach based on liquid chromatography-tandem mass spectrometry was utilized to characterize the metabolic profiles of the tissues. Multivariate and univariate analysis tools were used. RESULTS: A total of 154 metabolites were significantly altered in carotid plaque when compared with thickened intima. Of these, 62 metabolites were upregulated, whereas 92 metabolites were downregulated. Support vector machines identified the 15 most important metabolites, such as N-(cyclopropylmethyl)-N'-phenylurea, 9(S)-HOTrE, ACar 12:2, quinoxaline-2,3-dithiol, and l-thyroxine, as biomarkers for high-risk plaques. Metabolic pathway analysis showed that abnormal purine and nucleotide metabolism, amino acid metabolism, glutathione metabolism, and vitamin metabolism may contribute to the occurrence and progression of carotid atherosclerotic plaque. CONCLUSIONS: Our study identifies the biomarkers and related metabolic mechanisms of carotid plaque, which is stroke-prone, and provides insights and ideas for the precise prevention and targeted intervention of the disease.


Assuntos
Biomarcadores , Metabolômica , Placa Aterosclerótica , Espectrometria de Massas em Tandem , Humanos , Espectrometria de Massas em Tandem/métodos , Masculino , Feminino , Biomarcadores/análise , Biomarcadores/metabolismo , Pessoa de Meia-Idade , Idoso , Placa Aterosclerótica/química , Placa Aterosclerótica/metabolismo , Metabolômica/métodos , Cromatografia Líquida/métodos , Doenças das Artérias Carótidas/metabolismo , Metaboloma
2.
Front Pharmacol ; 15: 1364160, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38694921

RESUMO

Objective: Bioinformatics methods were applied to investigate the pivotal genes and regulatory networks associated with atherosclerotic carotid artery stenosis (ACAS) and provide new insights for the treatment of this disease. Methods: The study utilized five ACAS datasets (GSE100927, GSE11782, GESE28829, GSE41571, and GSE43292) downloaded from the NCBI GEO database. The first four datasets were combined as the training set (n = 99), while GSE43292 (n = 64) was used as the validation set. Difference analysis and functional enrichment analysis were then performed on the training set. The pathogenic targets of ACAS were screened by protein-protein interaction networks and MCODE analyses, combined with three machine learning algorithms. The results were next verified by analysis of inter-group differences and ROC curve analysis. Next, immune-related function and immune cell correlation analyses were performed, and plaques of human ACAS were applied to verify the results via immunohistochemistry (IH) and immunofluorescence (IF). Finally, the competing endogenous RNAs (ceRNA) and transcription factors (TFs) regulatory networks of the characterized genes were constructed. Results: A total of 177 differentially expressed genes were identified, including 67 genes downregulated and 110 genes upregulated. Gene set enrichment analysis revealed that five pathways were active in the experimental group, including xenograft rejection, autoimmune thyroid disease, graft-versus-host disease, leishmaniasis infection, and lysosomes. Four key genes were identified, with C3AR1 being upregulated and FBLN5, PPP1R12A, and TPM1 being downregulated. The analysis of inter-group differences demonstrated that the four characterized genes were differentially expressed in both the control and experimental groups. The ROC analysis showed that they had high AUC values in both the training and validation sets. Therefore, a predictive ACAS patient nomogram model based on the screened genes was established. Correlation analysis revealed a positive correlation between C3AR1 expression and neutrophils, which was further validated in IH and IF. One or multiple lncRNAs may compete with the characterized genes for binding miRNAs. Additionally, each characterized gene interacts with multiple TFs. Conclusion: Four pivotal genes were screened, and relevant ceRNA and TFs were predicted. These molecules may exert a crucial role in ACAS and serve as potential biomarkers and therapeutic targets.

3.
BMC Bioinformatics ; 25(1): 164, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664601

RESUMO

Multimodal integration combines information from different sources or modalities to gain a more comprehensive understanding of a phenomenon. The challenges in multi-omics data analysis lie in the complexity, high dimensionality, and heterogeneity of the data, which demands sophisticated computational tools and visualization methods for proper interpretation and visualization of multi-omics data. In this paper, we propose a novel method, termed Orthogonal Multimodality Integration and Clustering (OMIC), for analyzing CITE-seq. Our approach enables researchers to integrate multiple sources of information while accounting for the dependence among them. We demonstrate the effectiveness of our approach using CITE-seq data sets for cell clustering. Our results show that our approach outperforms existing methods in terms of accuracy, computational efficiency, and interpretability. We conclude that our proposed OMIC method provides a powerful tool for multimodal data analysis that greatly improves the feasibility and reliability of integrated data.


Assuntos
Análise de Célula Única , Análise por Conglomerados , Análise de Célula Única/métodos , Biologia Computacional/métodos , Humanos , Algoritmos
4.
Int J Biol Macromol ; 268(Pt 1): 131704, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38670198

RESUMO

Mosquitoes form a vital group of vector insects, which can transmit various diseases and filarial worms. The cuticle is a critical structure that protects mosquitoes from adverse environmental conditions and penetration resistance. Thus, cuticle proteins can be used as potential targets for controlling the mosquito population. In the present study, we found that AaCPR100A is a structural protein in the soft cuticle, which has flexibility and elasticity allowing insects to move or fly freely, of Aedes aegypti. RNA interference (RNAi) of AaCPR100A caused high mortality in Aedes aegypti larvae and adults and significantly decreased the egg hatching rate. Transmission electron microscopy (TEM) analysis revealed that the larval microstructure had no recognizable endocuticle in AaCPR100A-deficient mosquitoes. A yeast two-hybrid assay was performed to screen proteins interacting with AaCPR100A. We verified that the G12-like protein had the strongest interaction with AaCPR100A using yeast two-hybrid and GST pull-down assays. Knockdown of G12-like transcription resulted in high mortality in Ae. aegypti larvae, but not in adults. Interestingly, RNAi of G12-like rescued the high mortality of adults caused by decreased AaCPR100A expression. Additionally, adults treated with G12-like dsRNA were found to be sensitive to low temperature, and their eggshell formation and hatching were decreased. Overall, our results demonstrated that G12-like may interacts with AaCPR100A, and both G12-like and AaCPR100A are involved in Ae. aegypti cuticle development and eggshell formation. AaCPR100A and G12-like can thus be considered newly potential targets for controlling the Ae. aegypti mosquito.

5.
Clin Transl Allergy ; 14(1): e12334, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38282195

RESUMO

BACKGROUND: Chronic rhinosinusitis (CRS) is usually accompanied by mucin hypersecretion that can lead to mucus accumulation and impair nasal mucociliary clearance, thus exacerbating airway inflammation. Abnormal mucin hypersecretion is regulated by different T helper (Th) cytokines, which are associated with different endotype-driven inflammatory responses. Therefore, it is of great significance to understand how these factors regulate mucin hypersecretion to provide precise treatment strategies for different endotypes of CRS. BODY: Thus far, the most common endotypes of CRS are classified as type 1, type 2, or type 3 immune responses based on innate and adaptive cell-mediated effector immunity, and the representative Th cytokines in these immune responses, such as IFN-γ, TNF-α, IL-4, IL-5, IL-13, IL-10, IL-17, and IL-22, play an important regulatory role in mucin secretion. We reviewed all the related literature in the PubMed database to determine the expression of these Th cytokines in CRS and the role they play in the regulation of mucin secretion. CONCLUSION: We believe that the main Th cytokines involved in specific endotypes of CRS play a key role in regulating abnormal mucin secretion, which contributes to better understanding of the pathogenesis of CRS and provides therapeutic targets for airway inflammatory diseases associated with mucin hypersecretion.

6.
Immunity ; 57(1): 106-123.e7, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38159573

RESUMO

When the filtrate of the glomerulus flows through the renal tubular system, various microscopic sediment particles, including mineral crystals, are generated. Dislodging these particles is critical to ensuring the free flow of filtrate, whereas failure to remove them will result in kidney stone formation and obstruction. However, the underlying mechanism for the clearance is unclear. Here, using high-resolution microscopy, we found that the juxtatubular macrophages in the renal medulla constitutively formed transepithelial protrusions and "sampled" urine contents. They efficiently sequestered and phagocytosed intraluminal sediment particles and occasionally transmigrated to the tubule lumen to escort the excretion of urine particles. Mice with decreased renal macrophage numbers were prone to developing various intratubular sediments, including kidney stones. Mechanistically, the transepithelial behaviors of medulla macrophages required integrin ß1-mediated ligation to the tubular epithelium. These findings indicate that medulla macrophages sample urine content and remove intratubular particles to keep the tubular system unobstructed.


Assuntos
Cálculos Renais , Rim , Camundongos , Animais , Macrófagos
7.
J Am Chem Soc ; 146(1): 1167-1173, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38127733

RESUMO

Nonradiative multiphonon transitions play a crucial role in understanding charge carrier dynamics. To capture the non-Condon effect in nonadiabatic molecular dynamics (NA-MD), we develop a simple and accurate method to calculate noncrossing and crossing k-point NA coupling in momentum space on an equal footing and implement it with a trajectory surface hopping algorithm. Multiple k-point MD trajectories can provide sufficient nonzero momentum multiphonons coupled to electrons, and the momentum conservation is maintained during nonvertical electron transition. The simulations of indirect bandgap transition in silicon and intra- and intervalley transitions in graphene show that incorporation of the non-Condon effect is needed to correctly depict these types of charge dynamics. In particular, a hidden process is responsible for the delayed nonradiative electron-hole recombination in silicon: the thermal-assisted rapid trapping of an excited electron at the conduction band minimum by a long-lived higher energy state through a nonvertical transition extends charge carrier lifetime, approaching 1 ns, which is about 1.5 times slower than the direct bandgap recombination. For graphene, intervalley scattering takes place within about 225 fs, which can occur only when the intravalley relaxation proceeds to about 50 fs to gain enough phonon momentum. The intra- and intervalley scattering constitute energy relaxation, which completes within sub-500 fs. All the simulated time scales are in excellent agreement with experiments. The study establishes the underlying mechanisms for a long-lived charge carrier in silicon and valley scattering in graphene and underscores the robustness of the non-Condon approximation NA-MD method, which is suitable for rigid, soft, and large defective systems.

8.
J Am Chem Soc ; 145(47): 25887-25893, 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-37966512

RESUMO

Ultrafast charge and spin dynamics have immense effects on the applications of topological insulators (TIs). By performing spin-adiabatic nonadiabatic molecular dynamics simulations in the presence of electron-phonon (e-ph) and spin-phonon couplings, we investigate temperature-dependent intra- and interband charge and spin relaxation dynamics via the bulk and surface paths in the three-dimensional TI Bi2Te3. The e-ph coupling dominates charge relaxation in the bulk path, and the relaxation rate is positively correlated with temperature due to the large energy gaps and weak spin polarization. Conversely, the relaxation dynamics exhibits an opposite temperature dependence in the surface path because of electron re-excitation and spin mismatching induced by spin-phonon coupling, which arises from small energy gaps and strong spin polarization. The two mechanisms rationalize the charge carriers being long-lived in the bulk and surface phases at low and room temperature, respectively. Additionally, strong thermal fluctuations of the topological states' magnetic moments destroy the spin-momentum locking and trigger backscattering at room temperature.

9.
Microbiome ; 11(1): 163, 2023 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-37496083

RESUMO

BACKGROUND: Antibiotics are widely used for prophylactic therapy and for improving the growth performance of chicken. The problem of bacterial drug resistance caused by antibiotic abuse has previously attracted extensive attention; however, the influence of early-day use of prophylactic antibiotics on the gut microflora and on the disease resistance ability in chicks has not been explored. Here, we comprehensively evaluate the growth performance, gut microbial dynamics, level of antibiotic resistance genes (ARGs) in the gut microbial community, and resistance to H9N2 avian influenza virus (AIV) in chickens following long-term and short-term early-day prophylactic antibiotic treatment. RESULTS: Unexpectedly, long-term prophylactic enrofloxacin treatment slowed the growth rate of chickens, whereas short-term antibiotics treatments were found to increase the growth rate, but these changes were not statistically significant. Strikingly, expansions of Escherichia-Shigella populations were observed in early-life prophylactic antibiotics-treated groups of chickens, which is in contrast to the general perception that antibiotics should control their pathogenicity in chicks. The gut microbiota composition of chickens treated long term with antibiotics or received early-day antibiotics treatment tend to be more dramatically disturbed compared to the gut microbiome of chickens treated with antibiotics for a short term at a later date, especially after H9N2 AIV infection. CONCLUSIONS: Our data provide evidence that early-day and long-term antibiotic treatments have a more adverse effect on the intestinal microbiome of chickens, compared to short-term late age antibiotic treatment. Furthermore, our metagenomic data reveal that both long-term and short-term antibiotic treatment increase the relative abundance of ARGs. Our findings highlight the adverse effects of prophylactic antibiotic treatment and provide a theoretical basis for the cautious administration of antibiotics in food-producing animal management. Video Abstract.


Assuntos
Microbioma Gastrointestinal , Vírus da Influenza A Subtipo H9N2 , Microbiota , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Microbioma Gastrointestinal/genética , Vírus da Influenza A Subtipo H9N2/genética , Galinhas/microbiologia
10.
J Phys Chem Lett ; 14(23): 5403-5409, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37279169

RESUMO

Ultrafast demagnetization in magnetic metals is the key to spintronics devices. Taking iron as a prototypical system, we investigate the demagnetization mechanism by simulating the charge and spin dynamics using nonadiabatic molecular dynamics in the presence of explicit spin-orbit coupling (SOC). Strong SOC drives ultrafast spin-flip of electrons and holes, which trigger demagnetization and remagnetization, respectively. Their confrontation decreases the demagnetization ratio and finishes the demagnetization within 167 fs, agreeing with the experimental time scale. The joint spin-flip of electrons and holes correlated with the electron-phonon coupling-induced fast electron-hole recombination further decreases the maximum demagnetization ratio, below 5% of experimental value. Although the Elliott-Yafet electron-phonon scattering model can rationalize the ultrafast spin-flip process, it fails to reproduce the experimental maximum demagnetization ratio. The study suggests the key role of SOC on spin dynamics and emphasizes the interplay between SOC and electron-phonon interactions on the ultrafast demagnetization.

11.
Int J Gen Med ; 16: 1603-1619, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37152272

RESUMO

Background: Hepatocellular carcinoma (HCC) is one of the most common type of cancers, but there is still a lack of known biomarkers for the effective diagnosis or prognosis of HCC. Myristoylated alanine-rich C-kinase substrate (MARCKS) is a substrate of protein kinase C, which was located in the cell plasma membrane. The purpose of our study was to evaluate the role of MARCKS in HCC. Methods: The role of MARCKS in HCC was explored by bioinformatics and experiment. Results: We demonstrated that MARCKS expression was significantly elevated in HCC datasets of TCGA. MARCKS was up-regulated in tumor sample in HCC. Functional enrichment indicated that MARCKS-related differentially expressed genes (DEGs) were mainly enriched in cell junction tissue, response to growth factors and cell population proliferation. Tumor and ECM-receptor interactions related pathways were enriched by the KEGG. MARCKS expression in HCC patients was higher in females, younger individuals, and those at worse clinical stages. Cox regression analysis showed that MARCKS expression was a risk factor for overall survival and disease-specific survival of patients. Conclusion: MARCKS was up-regulated in HCC, may play a crucial role in HCCs, and has prognostic value for clinical outcomes.

12.
Nanomaterials (Basel) ; 13(9)2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37177052

RESUMO

A coupling mechanism between flicker noise and hot carrier degradation (HCD) is revealed in this work. Predicting the flicker noise properties of fresh and aged devices is becoming essential for circuit designs, requiring an understanding of the fundamental noise behaviors. While certain models for fresh devices have been proposed, those for aged devices have not been reported yet because of the lack of a clear mechanism. The flicker noise of aged FinFETs is characterized based on the measure-stress-measure (MSM) method and analyzed from the device physics. It is found that both the mean and deviations of the noise power spectral density increase compared with the fresh counterparts. A coupling mechanism is proposed to explain the trap time constants, leading to the trap characterizations in their energy profiles. The amplitude and number of contributing traps are also changing and are dependent on the mode of HCD and determined by the position of the induced traps. A microscopic picture is developed from the perspective of trap coupling, reproducing well the measured noise of advanced nanoscale FinFETs. The finding is important for accurate flicker noise calculations and aging-aware circuit designs.

13.
Front Aging Neurosci ; 15: 1142163, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37032832

RESUMO

Introduction: Ischemic stroke (IS) is a type of stroke that leads to high mortality and disability. Anoikis is a form of programmed cell death. When cells detach from the correct extracellular matrix, anoikis disrupts integrin junctions, thus preventing abnormal proliferating cells from growing or attaching to an inappropriate matrix. Although there is growing evidence that anoikis regulates the immune response, which makes a great contribution to the development of IS, the role of anoikis in the pathogenesis of IS is rarely explored. Methods: First, we downloaded GSE58294 set and GSE16561 set from the NCBI GEO database. And 35 anoikis-related genes (ARGs) were obtained from GSEA website. The CIBERSORT algorithm was used to estimate the relative proportions of 22 infiltrating immune cell types. Next, consensus clustering method was used to classify ischemic stroke samples. In addition, we used least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE) and random forest (RF) algorithms to screen the key ARGs in ischemic stroke. Next, we performed receiver operating characteristics (ROC) analysis to assess the accuracy of each diagnostic gene. At the same time, the nomogram was constructed to diagnose IS by integrating trait genes. Then, we analyzed the correlation between gene expression and immune cell infiltration of the diagnostic genes in the combined database. And gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis were performed on these genes to explore differential signaling pathways and potential functions, as well as the construction and visualization of regulatory networks using NetworkAnalyst and Cytoscape. Finally, we investigated the expression pattern of ARGs in IS patients across age or gender. Results: Our study comprehensively analyzed the role of ARGs in IS for the first time. We revealed the expression profile of ARGs in IS and the correlation with infiltrating immune cells. And The results of consensus clustering analysis suggested that we can classify IS patients into two clusters. The machine learning analysis screened five signature genes, including AKT1, BRMS1, PTRH2, TFDP1 and TLE1. We also constructed nomogram models based on the five risk genes and evaluated the immune infiltration correlation, gene-miRNA, gene-TF and drug-gene interaction regulatory networks of these signature genes. The expression of ARGs did not differ by sex or age. Discussion: This study may provide a beneficial reference for further elucidating the pathogenesis of IS, and render new ideas for drug screening, individualized therapy and immunotherapy of IS.

14.
Nat Commun ; 14(1): 2488, 2023 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-37120646

RESUMO

Wildlife is reservoir of emerging viruses. Here we identified 27 families of mammalian viruses from 1981 wild animals and 194 zoo animals collected from south China between 2015 and 2022, isolated and characterized the pathogenicity of eight viruses. Bats harbor high diversity of coronaviruses, picornaviruses and astroviruses, and a potentially novel genus of Bornaviridae. In addition to the reported SARSr-CoV-2 and HKU4-CoV-like viruses, picornavirus and respiroviruses also likely circulate between bats and pangolins. Pikas harbor a new clade of Embecovirus and a new genus of arenaviruses. Further, the potential cross-species transmission of RNA viruses (paramyxovirus and astrovirus) and DNA viruses (pseudorabies virus, porcine circovirus 2, porcine circovirus 3 and parvovirus) between wildlife and domestic animals was identified, complicating wildlife protection and the prevention and control of these diseases in domestic animals. This study provides a nuanced view of the frequency of host-jumping events, as well as assessments of zoonotic risk.


Assuntos
COVID-19 , Quirópteros , Vírus , Animais , Animais Domésticos/virologia , Animais Selvagens/virologia , Animais de Zoológico/virologia , Quirópteros/virologia , Mamíferos/virologia , Pangolins/virologia , Filogenia , Zoonoses/virologia
15.
J Phys Chem Lett ; 14(11): 2715-2721, 2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-36892969

RESUMO

The giant spin-orbit coupling (SOC) of a heavy lead element significantly extends charge carrier lifetimes of lead halide perovskites (LHPs). The physical mechanism remains unclear and requires a quantum dynamics perspective. Taking methylammonium lead iodide (MAPbI3) as a prototypical system and using non-adiabatic molecular dynamics combined with 1/2 electron correction, we show that SOC notably reduces the non-radiative electron-hole (e-h) recombination by decreasing the non-adiabatic coupling (NAC) primarily as a result of SOC decreasing the e-h wave function overlap by reshaping the electron and hole wave functions. Second, SOC causes spin mismatch subject to spin-mixed states, which further decreases NAC. The charge carrier lifetime is about 3-fold longer in the present of SOC relative to the absence of SOC. Our study generates the fundamental understanding of SOC minimizing non-radiative charge and energy losses in LHPs.

16.
J Environ Manage ; 330: 117214, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36623386

RESUMO

A park that had used reclaimed water as the sole water supply for fourteen years, was selected to analyze the distribution, sources and risks of 16 priority polycyclic aromatic hydrocarbons (PAHs) in waters and sediments. The effects of phytoremediation were investigated in waterbodies classified as phytoremediation, transitional and non-phytoremediation areas. Diagnostic ratio (DR) and principal component analysis (PCA) were used to analyze the sources of PAHs, while risk quotient (RQ) was used as risk assessment tool. Results showed that ∑PAH concentrations in sediments ranged from 29.4 to 1245.6 ng‧g-1, with average of 354.3 ng‧g-1, corresponding to a moderate pollution level. The concentration of PAHs in water ranged from 10.6 to 326.3 ng‧L-1, with average of 147.2 ng‧L-1, corresponding to a low pollution level. The ∑PAHs in sediments showed a downward trend from northwest to southeast along with the water flow direction, with average values of 459.5, 362.9 and 246.1 ng‧L-1 in the upstream, midstream and downstream, respectively. In contrast, PAH concentrations in water were consistent with recreational activities in the urban park area. There were 95% of water samples and 72% of sediment samples obtaining the Ant/(Ant + Phe) > 0.1 and Flu/(Flu + Pyr) > 0.5, indicating that coal combustion was the major source of PAHs in both the water and sediment. The RQ∑PAH(NCs) values in water and sediment were all between 1 and 800, while RQ∑PAH(MPCs) reached equal to 0, suggesting that ∑PAHs presented a low ecological risk. Acenaphthene accounted for 28.4% of RQ(NCs), and became the most risk PAH in water column. Aquatic plants effectively removed high-ring PAHs from water and middle-ring PAHs from sediments, reducing the overall risks posed by PAHs.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , Água/análise , Monitoramento Ambiental , Poluentes Químicos da Água/análise , Medição de Risco , China , Sedimentos Geológicos
18.
J Exp Clin Cancer Res ; 41(1): 322, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36372898

RESUMO

BACKGROUND: Cancer stem cells (CSCs) are regarded as the "seed cells" for tumorigenesis, metastasis, recurrence and drug resistance. However, specific surface markers of CSCs of different origins have not been documented. METHODS: Single-cell sequencing was used to analyze the highly expressed genes in cancer stem cells of gastric cancer patients, and it was verified that AQP5 was specifically highly expressed in gastric cancer stem cells (GC-CSCs) in vivo and in vitro. The effect of AQP5-promoting LGR5 on the malignant biological function of GC-CSCs was investigated. The mechanism by which AQP5 affects GC-CSCs was explored through transcriptome sequencing, proteomic detection, mass spectrometry, etc. RESULTS: We report the identification and validation of AQP5 as a potentially specific surface marker of GC-CSCs. AQP5 was significantly upregulated in CSCs isolated from gastric cancer patients and in spheroid cells, and AQP5 was coexpressed with the canonical stem marker LGR5. Biologically, AQP5 promoted the sphere formation, proliferation, migration and invasion of GC cells in vitro and enhanced tumorigenesis in vivo. Furthermore, AQP5 coordinated with LGR5 and synergistically promoted the tumorigenesis of GC-CSCs. At the mechanistic level, AQP5 activated autophagy by inducing the LC3I/LC3II transformation in GC-CSCs, which was crucial for the biological functions of AQP5. Finally, we demonstrated that AQP5 recruited the E3 ligase TRIM21 to the key autophagy protein ULK1 and induced the K63-mediated ubiquitination of ULK1. CONCLUSIONS: We elucidate a novel surface marker, AQP5, which is specifically expressed by GC-CSCs. Furthermore, our study creates a link between AQP5 and LGR5 and highlights the necessity of targeting both surface markers simultaneously as a promising approach for the treatment of gastric cancer patients.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Proteômica , Células-Tronco Neoplásicas/metabolismo , Transformação Celular Neoplásica/metabolismo , Carcinogênese/metabolismo , Ubiquitinação , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Aquaporina 5/genética , Aquaporina 5/metabolismo
19.
Acta Trop ; 236: 106693, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36116548

RESUMO

BACKGROUND: Trichomonas vaginalis (T. vaginalis) is an extracellular flagellated protozoan parasitizing the human genital and urinary tracts. T. vaginalis infection impacts human reproductive function, but whether it causes infertility is still a matter of debate. METHODS: In this work, we consulted 205 relevant articles, which were classified into three categories: epidemiological investigations (100), review articles (43), and research articles (62). RevMan 5.4 was used to conduct a meta-analysis of the articles reporting epidemiological investigations comparing the incidence of T. vaginalis infection between infertile and fertile groups. Review and research articles were used to summarize the pathogenesis of infertility caused by T. vaginalis. RESULTS: The results indicated that rate of T. vaginalis infection in the infertile group was significantly higher than that in the fertile group. Moreover, the epidemiological surveys showed that the infertility rates of population infected with T. vaginalis were significantly higher than that of population without T. vaginalis infection. Nine out of ten (90%) related review articles stated that T. vaginalis infection causes infertility, and the review and research articles indicated the main pathogenic mechanisms of infertility caused by T. vaginalis were as follows: T. vaginalis impairs sperm quality, resulting in infertility; the immune response triggered by T. vaginalis infection impacts human reproductive function. CONCLUSION: Our results confirm that there is a correlation between T. vaginalis infection and infertility, and T. vaginalis infection can lead to infertility. The study provides a foundation for further investigations into its pathogenesis.


Assuntos
Infertilidade , Tricomoníase , Trichomonas vaginalis , Fertilidade , Humanos , Infertilidade/complicações , Masculino , Reprodução , Sêmen , Tricomoníase/complicações , Tricomoníase/epidemiologia
20.
J Phys Chem Lett ; 13(32): 7532-7540, 2022 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-35947434

RESUMO

We conducted ab initio molecular dynamics (AIMD) and nonadiabatic MD to simulate polaron formation and recombination in all-inorganic Cs3Bi2Br9 perovskite. The meticulously designed AIMD simulations show that two types of small hole polaron, including localized and semidelocalized small hole polaron on either an intralayer or an interlayer Br dimer, are adiabatically formed within 1.71 ps. The localized small hole polaron reduces nonadiabatic coupling and decoherence time and, thus, delays charge recombination to 213 ns. In contrast, the dominant semidelocalized polaron increases nonadiabatic coupling by enhancing electron-hole overlap and restores the energy gap and decoherence time to the pristine system, accelerating recombination to 4.7 ns compared to a 10 ns charge carrier lifetime in the pristine system. All the obtained time scales agree well with experiments. The study offers a fundamental understanding of the excited-state dynamics of small hole polaron in Cs3Bi2Br9 and helps to design high-performance perovskite optoelectronics and photovoltaics.

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