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1.
Carcinogenesis ; 45(6): 409-423, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38366384

RESUMO

In recent decades, considerable evidence has emerged indicating the involvement of tRNA-derived fragments (tRFs) in cancer progression through various mechanisms. However, the biological effects and mechanisms of tRFs in lung adenocarcinoma (LUAD) remain unclear. In this study, we screen out tRF-29-79, a 5'-tRF derived from tRNAGlyGCC, through profiling the tRF expressions in three pairs of LUAD tissues. We show that tRF-29-79 is downregulated in LUAD and downregulation of tRF-29-79 is associated with poorer prognosis. In vivo and in vitro assay reveal that tRF-29-79 inhibits proliferation, migration and invasion of LUAD cells. Mechanistically, we discovered that tRF-29-79 interacts with the RNA-binding protein PTBP1 and facilitates the transportation of PTBP1 from nucleus to cytoplasm, which regulates alternative splicing in the 3' untranslated region (UTR) of SLC1A5 pre-mRNA. Given that SLC1A5 is a core transporter of glutamine, we proved that tRF-29-79 mediate glutamine metabolism of LUAD through affecting the stability of SLC1A5 mRNA, thus exerts its anticancer function. In summary, our findings uncover the novel mechanism that tRF-29-79 participates in glutamine metabolism through interacting with PTBP1 and regulating alternative splicing in the 3' UTR of SLC1A5 pre-mRNA.


Assuntos
Adenocarcinoma de Pulmão , Sistema ASC de Transporte de Aminoácidos , Proliferação de Células , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Ribonucleoproteínas Nucleares Heterogêneas , Neoplasias Pulmonares , Proteína de Ligação a Regiões Ricas em Polipirimidinas , Humanos , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Proteína de Ligação a Regiões Ricas em Polipirimidinas/metabolismo , Proteína de Ligação a Regiões Ricas em Polipirimidinas/genética , Sistema ASC de Transporte de Aminoácidos/metabolismo , Sistema ASC de Transporte de Aminoácidos/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Camundongos , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas/genética , Animais , Antígenos de Histocompatibilidade Menor/genética , Antígenos de Histocompatibilidade Menor/metabolismo , Movimento Celular , Prognóstico , Linhagem Celular Tumoral , Processamento Alternativo , Feminino , Glutamina/metabolismo , Masculino
2.
Toxicol Appl Pharmacol ; 486: 116946, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38679241

RESUMO

The pathogenesis of attention-deficit/hyperactivity disorder (ADHD) has not been fully elucidated. Gestational hypertension could double the probability of ADHD in the offspring, while the initial bacterial communication between the mother and offspring has been associated with psychiatric disorders. Thus, we hypothesize that antihypertensive treatment during pregnancy may abate the impairments in neurodevelopment of the offspring. To test this hypothesis, we chose Captopril and Labetalol, to apply to pregnant spontaneously hypertensive rat (SHR) dams and examined the outcomes in the male offspring. Our data demonstrated that maternal treatment with Captopril and Labetalol had long-lasting changes in gut microbiota and behavioral alterations, including decreased hyperactivity and increased curiosity, spatial learning and memory in the male offspring. Increased diversity and composition were identified, and some ADHD related bacteria were found to have the same change in the gut microbiota of both the dam and offspring after the treatments. LC-MS/MS and immunohistochemistry assays suggested elevated expression of brain derived neurotrophic factor (BDNF) and dopamine in the prefrontal cortex and striatum of offspring exposed to Captopril/ Labetalol, which may account for the improvement of the offspring's psychiatric functions. Therefore, our results support the beneficial long-term effects of the intervention of gestational hypertension in the prevention of ADHD.


Assuntos
Anti-Hipertensivos , Transtorno do Deficit de Atenção com Hiperatividade , Comportamento Animal , Captopril , Microbioma Gastrointestinal , Efeitos Tardios da Exposição Pré-Natal , Ratos Endogâmicos SHR , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Gravidez , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/induzido quimicamente , Feminino , Anti-Hipertensivos/farmacologia , Captopril/farmacologia , Masculino , Ratos , Comportamento Animal/efeitos dos fármacos , Labetalol/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipertensão Induzida pela Gravidez/induzido quimicamente , Dopamina/metabolismo
3.
Circ Res ; 131(9): e120-e134, 2022 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-36164984

RESUMO

BACKGROUND: Despite available clinical management strategies, chronic kidney disease (CKD) is associated with severe morbidity and mortality worldwide, which beckons new solutions. Host-microbial interactions with a depletion of Faecalibacterium prausnitzii in CKD are reported. However, the mechanisms about if and how F prausnitzii can be used as a probiotic to treat CKD remains unknown. METHODS: We evaluated the microbial compositions in 2 independent CKD populations for any potential probiotic. Next, we investigated if supplementation of such probiotic in a mouse CKD model can restore gut-renal homeostasis as monitored by its effects on suppression on renal inflammation, improvement in gut permeability and renal function. Last, we investigated the molecular mechanisms underlying the probiotic-induced beneficial outcomes. RESULTS: We observed significant depletion of Faecalibacterium in the patients with CKD in both Western (n=283) and Eastern populations (n=75). Supplementation of F prausnitzii to CKD mice reduced renal dysfunction, renal inflammation, and lowered the serum levels of various uremic toxins. These are coupled with improved gut microbial ecology and intestinal integrity. Moreover, we demonstrated that the beneficial effects in kidney induced by F prausnitzii-derived butyrate were through the GPR (G protein-coupled receptor)-43. CONCLUSIONS: Using a mouse CKD model, we uncovered a novel beneficial role of F prausnitzii in the restoration of renal function in CKD, which is, at least in part, attributed to the butyrate-mediated GPR-43 signaling in the kidney. Our study provides the necessary foundation to harness the therapeutic potential of F prausnitzii for ameliorating CKD.


Assuntos
Faecalibacterium prausnitzii , Insuficiência Renal Crônica , Animais , Butiratos/farmacologia , Butiratos/uso terapêutico , Modelos Animais de Doenças , Inflamação , Rim/fisiologia , Receptores Acoplados a Proteínas G/genética
4.
Phys Chem Chem Phys ; 26(5): 4541-4554, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38241021

RESUMO

The bottom-up prediction of thermodynamic and mechanical behaviors of polymeric materials based on molecular dynamics (MD) simulation is of critical importance in polymer physics. Although the atomistically informed coarse-grained (CG) model can access greater spatiotemporal scales and retain essential chemical specificity, the temperature-transferable CG model is still a big challenge and hinders widespread application of this technique. Herein, we use a silicone polymer, i.e., polydimethylsiloxane (PDMS), having an incredibly low chain rigidity as a model system, combined with an energy-renormalization (ER) approach, to systematically develop a temperature-transferable CG model. Specifically, by introducing temperature-dependent ER factors to renormalize the effective distance and cohesive energy parameters, the developed CG model faithfully preserved the dynamics, mechanical and conformational behaviors compared with the target all-atomistic (AA) model from glassy to melt regimes, which was further validated by experimental data. With the developed CG model featuring tremendously improved computational efficiency, we systematically explored the influences of cohesive interaction strength and temperature on the dynamical heterogeneity and mechanical response of polymers, where we observed consistent trends with other linear polymers with varying chain rigidity and monomeric structures. This study serves as an extension of our proposed ER approach of developing temperature transferable CG models with diverse segmental structures, highlighting the critical role of cohesive interaction strength on CG modeling of polymer dynamics and thermomechanical behaviors.

5.
Nano Lett ; 23(8): 3637-3644, 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-36898061

RESUMO

Upon crumpling, graphene sheets yield intriguing hierarchical structures with high resistance to compression and aggregation, garnering a great deal of attention in recent years for their remarkable potential in a variety of applications. Here, we aim to understand the effect of Stone-Wales (SW) defects, i.e., a typical topological defect of graphene, on the crumpling behavior of graphene sheets at a fundamental level. By employing atomistically informed coarse-grained molecular dynamics (CG-MD) simulations, we find that SW defects strongly influence the sheet conformation as manifested by the change in size scaling laws and weaken the self-adhesion of the sheet during the crumpling process. Remarkably, the analyses of the internal structures (i.e., local curvatures, stresses, and cross-section patterns) of crumpled graphene emphasize the enhanced mechanical heterogeneity and "glass-like" amorphous state elicited by SW defects. Our findings pave the way for understanding and exploring the tailored design of crumpled structure via defect engineering.

6.
Breast Cancer Res ; 25(1): 85, 2023 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-37461019

RESUMO

BACKGROUND: Chemoresistance involves metastasis and aggressiveness of breast cancer (BC). Chemotherapy-elicited exosomes have been reported to be associated with drug resistance and pro-metastatic capacity of BC cells. Non-coding RNAs (ncRNAs) are enriched in exosomes, which participated in generation, progression, and resistance of BC. However, the mechanism underlying the chemoresistance and metastasis in BC cells mediated by the BC-derived exosomal ncRNAs remained to be elucidated. METHODS: The effects of PTX-induced exosomal circBACH1 on BC cell function were assessed using RNA Binding Protein Immunoprecipitation (RIP), dual luciferase reporter gene, tube formation, CCK-8, and Western Blot assays. The circBACH1 and miR-217 expression levels were detected using quantitative real-time PCR (RT-qPCR) and Immunohistochemistry (IHC) assays in BC tissues and precancerous tissues of BC patients. RESULTS: CircBACH1 expression was increased in paclitaxel-treated BC-derived exosomes (PTX-EXO) and BC tissue. PTX-EXO was shown to promote PTX-resistance and angiogenesis through upregulation circBACH1. Downregulation of circBACH1 improved PTX-sensitiveness by suppressing the cell viability, stemness, migration, and angiogenesis of BC cells. Moreover, we found that miR-217 interacted with circBACH1 and targeted GTPase-activating SH3 domain-binding protein 2 (G3BP2) in BC cells. CircBACH1 combined miR-217 cotransfection suppressed the expression of G3BP2 proteins compared with circBACH1 treatment in MCF-7 cells. In addition, downregulation of G3BP2 suppressed BC cell migration. CONCLUSIONS: These results demonstrated that PTX-induced exosomal circBACH1 promoted stemness and migration of BC cells by sponging miR-217 to upregulate the expression of G3BP2, which provided a new therapeutic target for PTX-resistance and progression of BC via circBACH1/miR-217/G3BP2 axis.


Assuntos
Antineoplásicos , Neoplasias da Mama , MicroRNAs , RNA Circular , Feminino , Humanos , Proteínas Adaptadoras de Transdução de Sinal , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas de Ligação a RNA , Transdução de Sinais , RNA Circular/genética , RNA Circular/metabolismo , Exossomos/genética , Exossomos/metabolismo
7.
Cancer Sci ; 114(12): 4607-4621, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37770420

RESUMO

Evaluating the accuracy of pulmonary nodule diagnosis avoids repeated low-dose computed tomography (LDCT)/CT scans or invasive examination, yet remains a main clinical challenge. Screening for new diagnostic tools is urgent. Herein, we established a nomogram based on the diagnostic signature of five circulating tsRNAs and CT information to predict malignant pulmonary nodules. In total, 249 blood samples of patients with pulmonary nodules were selected from three different lung cancer centers. Five tsRNAs were identified in the discovery and training cohorts and the diagnostic signature was established by the randomForest algorithm (tRF-Ser-TGA-003, tRF-Val-CAC-005, tRF-Ala-AGC-060, tRF-Val-CAC-024, and tiRNA-Gln-TTG-001). A nomogram was developed by combining tsRNA signature and CT information. The high level of accuracy was identified in an internal validation cohort (n = 83, area under the receiver operating characteristic curve [AUC] = 0.930, sensitivity 100.0%, specificity 73.8%) and external validation cohort (n = 66, AUC = 0.943, sensitivity 100.0%, specificity 86.8%). Furthermore, the diagnostic ability of our model discriminating invasive malignant ones from noninvasive lesions was assessed. A robust performance was achieved in the diagnosis of invasive malignant lesions in both training and validation cohorts (discovery cohort: AUC = 0.850, sensitivity 86.0%, specificity 81.4%; internal validation cohort: AUC = 0.784, sensitivity 78.8%, specificity 78.1%; and external validation cohort: AUC = 0.837, sensitivity 85.7%, specificity 84.0%). This novel circulating tsRNA-based diagnostic model has potential significance in predicting malignant pulmonary nodules. Application of the model could improve the accuracy of pulmonary nodule diagnosis and optimize surgical plans.


Assuntos
Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Humanos , Nomogramas , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Tomografia Computadorizada por Raios X/métodos , Pulmão/patologia , Estudos Retrospectivos
8.
Blood ; 138(18): 1757-1767, 2021 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-34041523

RESUMO

Recent studies have shown that maternal anti-CD36 antibodies represent a frequent cause of fetal/neonatal alloimmune thrombocytopenia (FNAIT) in Asian and African populations. However, little is known about the pathomechanism and antenatal treatment of anti-CD36-mediated FNAIT. Here, we established a novel animal model to examine the clinical features of pups from immunized Cd36-/- female mice after breeding with wild-type male mice. Mild thrombocytopenia was observed, but high pup mortality was also documented (40.26%). Administration of intravenous immunoglobulin (IVIG) (1 g/kg) on days 7, 12, and 17 to immunized Cd36-/- mothers after breeding reduced fetal death (12.70%). However, delaying the IVIG administration series on days 10, 15, and 20 did not reduce fetal death (40.00%). In contrast, injection of deglycosylated anti-CD36 (deg-anti-CD36) polyclonal antibodies (5 mg/kg) on days 10, 15, and 20 significantly reduced fetal death (5.26%). Subsequently, monoclonal antibodies (mAbs) against mouse CD36 were developed, and one clone producing high-affinity anti-CD36 (termed 32-106) effectively inhibited maternal antibody binding and was therefore selected. Using the same approach of deg-anti-CD36, the administration of deg-32-106 significantly reduced fetal death (2.17%). Furthermore, immunized Cd36-/- mothers exhibited placental deficiency. Accordingly, maternal anti-CD36 antibodies inhibited angiogenesis of placenta endothelial cells, which could be restored by deg-32-106. In summary, maternal anti-CD36 antibodies caused a high frequency of fetal death in our animal model, associated with placental dysfunction. This deleterious effect could be diminished by the antenatal administration of IVIG and deg-mAb 32-106. Interestingly, treatment with deg-32-106 seems more beneficial considering the lower dose, later start of treatment, and therapy success.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antígenos CD36/imunologia , Trombocitopenia Neonatal Aloimune/terapia , Animais , Animais Recém-Nascidos , Anticorpos Monoclonais/imunologia , Modelos Animais de Doenças , Feminino , Humanos , Camundongos Endogâmicos C57BL , Gravidez , Cuidado Pré-Natal , Trombocitopenia Neonatal Aloimune/imunologia
9.
Histopathology ; 83(2): 211-228, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37071058

RESUMO

AIMS: Classification of histological patterns in lung adenocarcinoma (LUAD) is critical for clinical decision-making, especially in the early stage. However, the inter- and intraobserver subjectivity of pathologists make the quantification of histological patterns varied and inconsistent. Moreover, the spatial information of histological patterns is not evident to the naked eye of pathologists. METHODS AND RESULTS: We establish the LUAD-subtype deep learning model (LSDLM) with optimal ResNet34 followed by a four-layer Neural Network classifier, based on 40 000 well-annotated path-level tiles. The LSDLM shows robust performance for the identification of histopathological subtypes on the whole-slide level, with an area under the curve (AUC) value of 0.93, 0.96 and 0.85 across one internal and two external validation data sets. The LSDLM is capable of accurately distinguishing different LUAD subtypes through confusion matrices, albeit with a bias for high-risk subtypes. It possesses mixed histology pattern recognition on a par with senior pathologists. Combining the LSDLM-based risk score with the spatial K score (K-RS) shows great capacity for stratifying patients. Furthermore, we found the corresponding gene-level signature (AI-SRSS) to be an independent risk factor correlated with prognosis. CONCLUSIONS: Leveraging state-of-the-art deep learning models, the LSDLM shows capacity to assist pathologists in classifying histological patterns and prognosis stratification of LUAD patients.


Assuntos
Adenocarcinoma de Pulmão , Aprendizado Profundo , Neoplasias Pulmonares , Humanos , Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Prognóstico , Fatores de Risco
10.
Immunity ; 40(5): 785-800, 2014 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-24816404

RESUMO

Development of cancer has been linked to chronic inflammation, particularly via interleukin-23 (IL-23) and IL-17 signaling pathways. However, the cellular source of IL-17 and underlying mechanisms by which IL-17-producing cells promote human colorectal cancer (CRC) remain poorly defined. Here, we demonstrate that innate γδT (γδT17) cells are the major cellular source of IL-17 in human CRC. Microbial products elicited by tumorous epithelial barrier disruption correlated with inflammatory dendritic cell (inf-DC) accumulation and γδT17 polarization in human tumors. Activated inf-DCs induced γδT17 cells to secrete IL-8, tumor necrosis factor alpha, and GM-CSF with a concomitant accumulation of immunosuppressive PMN-MDSCs in the tumor. Importantly, γδT17 cell infiltration positively correlated with tumor stages and other clinicopathological features. Our study uncovers an inf-DC-γδT17-PMN-MDSC regulatory axis in human CRC that correlates MDSC-meditated immunosuppression with tumor-elicited inflammation. These findings suggest that γδT17 cells might be key players in human CRC progression and have the potential for treatment or prognosis prediction.


Assuntos
Neoplasias Colorretais/imunologia , Interleucina-17/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Células Th17/imunologia , Proliferação de Células , Células Dendríticas/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Humanos , Inflamação/imunologia , Interleucina-8/metabolismo , Ativação Linfocitária/imunologia , Células Mieloides/imunologia , Fator de Necrose Tumoral alfa/metabolismo
11.
Soft Matter ; 19(6): 1081-1091, 2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36722907

RESUMO

When a thin sheet is confined to a volume much smaller than its length (or width), it forms a complex state of sharp bends, point-like developable cones (d-cones) and extended ridges known as crumpled matter. One interesting feature of this state, is its high resistance to compression given its light weight. While the origins of this strength still remain a matter of debate, much has been learned through simple experiments and models. Very little work has explored how crumpling is affected by the sheet's topology, which is curious given the close relation between geometry and mechanics. In this work, we couple confocal microscopy with simple force experiments and coarse-grained molecular dynamics (CG-MD) simulations to explore how adding cuts to a sheet alters its behavior in the crumpled state. We find that cutting does not significantly alter the overall compressive behaviour: force scales as a power law irrespective of cuts and magnitudes are only slightly reduced by cutting. Remarkably, when examining regions of high curvature in the crumpled sheets we see evidence of significant changes in the distribution of curvature in cut sheets.

12.
Environ Res ; 224: 115541, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36828250

RESUMO

Heterocyclic hydrocarbons pollution generated by oil spills and oilfield wastewater discharges threatens the ecological environment and human health. Here we described a strategy that combines the greenhouse gas CO2 reduction with microbial remediation. In the presence of nitrate, CO2 can improve the biodegradation efficiency of the resins and asphaltenes in heavy oil, particularly the biodegradation selectivity of the polar heterocyclic compounds by the newly isolated Klebsiella michiganensis. This strain encoded 80 genes for the xenobiotic biodegradation and metabolism, and can efficiently utilize CO2 when degrading heavy oil. The total abundance of resins and asphaltenes decreased significantly with CO2, from 40.816% to 26.909%, to 28.873% with O2, and to 36.985% with N2. The transcripts per million (TPM) value of accA gene was 57.81 under CO2 condition, while respectively 8.86 and 21.23 under O2 and N2 conditions. Under CO2 condition, the total relative percentage of N1-type heterocyclic compounds was selectively decreased from 32.25% to 22.78%, resulting in the heavy oil viscosity decreased by 46.29%. These results demonstrated a novel anaerobic degradation mechanism that CO2 can promote the anaerobic biodegradation of heterocyclic hydrocarbons in heavy oil, which provides a promising biotreatment technology for the oil-contaminated water.


Assuntos
Poluição por Petróleo , Petróleo , Humanos , Petróleo/metabolismo , Dióxido de Carbono , Anaerobiose , Hidrocarbonetos , Campos de Petróleo e Gás , Biodegradação Ambiental
13.
BMC Musculoskelet Disord ; 24(1): 853, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37907913

RESUMO

INTRODUCTION: Pathological fractures of the femoral neck caused by necrosis of the femoral head are extremely rare. Here, we report a rare case of bilateral femoral head osteonecrosis extending to the femoral neck, with bilateral pathological fractures of the femoral neck occurring within a short period of time. CASE REPORT: A 65-year-old male with a 25-year history of daily consumption of 750 ml of liquor, presented with right hip pain after labor for 1 month. He subsequently sustained a right femoral neck fracture without trauma and underwent a right total hip arthroplasty. Two months later, he suffered a non-traumatic left femoral neck fracture and underwent a left total hip arthroplasty. Histopathological examination revealed osteonecrosis of the femoral head and neck, along with the presence of osteoclasts and granulomatous inflammation. Bone mineral density testing also showed osteoporosis. The bilateral femoral neck fractures were ruled out to be caused by any other pathological factors. DISCUSSION: This is the first report of pathological fractures of the bilateral femoral neck caused by femoral head necrosis. During the literature review process, we found that this case conforms to the histological characteristics of rapidly destructive hip disease and analyzed the etiology of femoral head necrosis and the pathogenesis of femoral neck fractures.


Assuntos
Fraturas do Colo Femoral , Necrose da Cabeça do Fêmur , Fraturas Espontâneas , Idoso , Humanos , Masculino , Fraturas do Colo Femoral/diagnóstico por imagem , Fraturas do Colo Femoral/etiologia , Fraturas do Colo Femoral/cirurgia , Cabeça do Fêmur , Necrose da Cabeça do Fêmur/diagnóstico por imagem , Necrose da Cabeça do Fêmur/etiologia , Necrose da Cabeça do Fêmur/cirurgia , Colo do Fêmur/diagnóstico por imagem , Colo do Fêmur/cirurgia , Fixação Interna de Fraturas , Fraturas Espontâneas/etiologia
14.
J Cell Mol Med ; 26(2): 436-448, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34877770

RESUMO

TP53 mutation is the most widespread mutation in lung adenocarcinoma (LUAD). Meanwhile, p53 (encoded by TP53) has recently been implicated in immune responses. However, it is still unknown whether TP53 mutation remodels the tumour microenvironment to influence tumour progression and prognosis in LUAD. In this study, we developed a 6-gene immune-related risk model (IRM) to predict the survival of patients with LUAD in The Cancer Genome Atlas (TCGA) cohort based on TP53 status, and the predictive ability was confirmed in 2 independent cohorts. TP53 mutation led to a decreased immune response in LUAD. Further analysis revealed that patients in the high-index group had observably lower relative infiltration of memory B cells and regulatory T cells and significantly higher relative infiltration of neutrophils and resting memory CD4+ T cells. Additionally, the IRM index positively correlated with the expression of critical immune checkpoint genes, including PDCD1 (encoding PD-1) and CD274 (encoding PD-L1), which was validated in the Nanjing cohort. Furthermore, as an independent prognostic factor, the IRM index was used to establish a nomogram for clinical application. In conclusion, this IRM may serve as a powerful prognostic tool to further optimize LUAD immunotherapy.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/patologia , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Prognóstico , Microambiente Tumoral/genética , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
15.
Langmuir ; 38(16): 4859-4869, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35420828

RESUMO

Sodium montmorillonite (Na-MMT) is one of the most commonly found swelling clay minerals with diverse engineering and technological applications. The nanomechanical properties of this mineral have been extensively investigated computationally utilizing molecular dynamics (MD) simulations to portray the molecular-level changes at different environmental conditions. As the environmentally found Na-MMT clays are generally sized within hundreds of nanometers, all-atomistic (AA) MD simulations of clays within such size range are particularly challenging due to computational inefficiency. Informed from atomistic modeling, a coarse-grained (CG) modeling technique can be employed to overcome the spatiotemporal limitation. The current study presents a modeling strategy to develop a computationally efficient model of Na-MMT clay with a typical size over ≃100 nm by shrinking the atomistic platelet thickness and reducing the number of center-layer atoms. Using the "strain-energy conservation" approach, the force field parameters for the CG model are obtained and the developed CG model can well preserve in-plane tension, shear, and bending behaviors of atomistic counterparts. Remarkably, the CG tactoid model of Na-MMT, a hierarchical multilayer structure, can reproduce the interlayer shear and adhesion as well as d-spacing among the clay sheets as of atomistic one to a good approximation while gaining significantly improved computational speed. Our study demonstrates the efficacy of the CG modeling framework, paving the way for the bottom-up multiscale prediction of mechanical behaviors of clay and related minerals.

16.
Microb Ecol ; 84(4): 1011-1028, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34845558

RESUMO

Water flooding is widely employed for oil production worldwide. However, there has never been a systematic investigation of the microbial communities occurring in oilfield water re-injection facilities. Here, we investigated the distribution of bacterial and archaeal communities in water re-injection facilities of an oilfield, and illustrated the combined influences of environmental variation and the microorganisms in injected water on the microbial communities. Bacterial communities from the surface injection facilities were dominated by aerobic or facultative anaerobic Betaproteobacteria, Alphaproteobacteria, and Flavobacteria, whereas Clostridia, Deltaproteobacteria, Anaerolineae, and Synergistia predominated in downhole of the injection wells, and Gammaproteobacteria, Betaproteobacteria, and Epsilonproteobacteria predominated in the production wells. Methanosaeta, Methanobacterium, and Methanolinea were dominant archaea in the injection facilities, while Methanosaeta, Methanomethylovorans, and Methanoculleus predominated in the production wells. This study also demonstrated that the microorganisms in injected water could be easily transferred from injection station to wellheads and downhole of injection wells, and environmental variation and diffusion-limited microbial transfer resulted from formation filtration were the main factors determining microbial community assembly in oil-bearing strata. The results provide novel information on the bacterial and archaeal communities and the underlying mechanisms occurring in oilfield water re-injection facilities, and benefit the development of effective microbiologically enhanced oil recovery and microbiologically prevented reservoir souring programs.


Assuntos
Archaea , Petróleo , Archaea/genética , Campos de Petróleo e Gás , Água , RNA Ribossômico 16S , Petróleo/microbiologia , Filogenia , Bactérias/genética
17.
Macromol Rapid Commun ; 43(24): e2200533, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35943220

RESUMO

The morphological stability of an organic photovoltaic (OPV) device is greatly affected by the dynamics of donors and acceptors occurring near the device's operational temperature. These dynamics can be quantified by the glass transition temperature (Tg ) of conjugated polymers (CPs). Because flexible side chains possess much faster dynamics, the cleavage of the alkyl side chains will reduce chain dynamics, leading to a higher Tg . In this work, the Tg s for CPs are systematically studied with controlled side chain cleavage. Isothermal annealing of polythiophenes featuring thermally cleavable side chains at 140 °C, is found to remove more than 95% of alkyl side chains in 24 h, and raise the backbone Tg from 23 to 75 °C. Coarse grain molecular dynamics simulations are used to understand the Tg dependence on side chain cleavage. X-ray scattering indicates that the relative degree of crystallization remains constantduring isothermal annealing process. The effective conjugation length is not influenced by thermal cleavage; however, the density of chromophore is doubled after the complete removal of alkyl side chains. The combined effect of enhancing Tg and conserving crystalline structures during the thermal cleavage process can provide a pathway to improving the stability of optoelectronic properties in future OPV devices.


Assuntos
Simulação de Dinâmica Molecular , Polímeros , Polímeros/química , Temperatura de Transição , Temperatura , Cristalização
18.
J Chem Phys ; 157(6): 064901, 2022 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-35963735

RESUMO

Cross-linking is known to play a pivotal role in the relaxation dynamics and mechanical properties of thermoset polymers, which are commonly used in structural applications because of their light weight and inherently strong nature. Here, we employ a coarse-grained (CG) polymer model to systematically explore the effect of cross-link density on basic thermodynamic properties as well as corresponding changes in the segmental dynamics and elastic properties of these network materials upon approaching their glass transition temperatures (Tg). Increasing the cross-link density unsurprisingly leads to a significant slowing down of the segmental dynamics, and the fragility K of glass formation shifts in lockstep with Tg, as often found in linear polymer melts when the polymer mass is varied. As a consequence, the segmental relaxation time τα becomes almost a universal function of reduced temperature, (T - Tg)/Tg, a phenomenon that underlies the applicability of the "universal" Williams-Landel-Ferry (WLF) relation to many polymer materials. We also test a mathematical model of the temperature dependence of the linear elastic moduli based on a simple rigidity percolation theory and quantify the fluctuations in the local stiffness of the network material. The moduli and distribution of the local stiffness likewise exhibit a universal scaling behavior for materials having different cross-link densities but fixed (T - Tg)/Tg. Evidently, Tg dominates both τα and the mechanical properties of our model cross-linked polymer materials. Our work provides physical insights into how the cross-link density affects glass formation, aiding in the design of cross-linked thermosets and other structurally complex glass-forming materials.

19.
Ecotoxicol Environ Saf ; 234: 113411, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35298971

RESUMO

Formaldehyde (CHOH), a common volatile organic compound, causes many adverse effects on human health. The highly exposed TiO2(001) facet possesses a high photodegradation efficiency of CHOH due to its excellent ability to trap photogenerated holes and high density of surface unsaturated Ti atoms (Ti5c) to bind CHOH. However, the rapid recombination of photoinduced electron-hole pairs of TiO2(001) limits the photodegradation efficiency. We adopted a strategy of decorating TiO2(001) with g-C3N4 quantum dots (QDs), exploiting the quantum effect of g-C3N4QDs and their combined staggered band structure. This decoration improves the photocatalytic activity of TiO2(001). Moreover, the chemical configuration of g-C3N4QDs/TiO2(001) and the combination mode between the g-C3N4QDs and TiO2(001) support were explored in detail using high-resolution transmission electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS), and density functional theory (DFT) calculations. Following the physiochemical characteristic results, the transport mechanism of photoinduced carriers was further analyzed by ultraviolet photoelectron spectroscopy (UPS), electron paramagnetic resonance (EPR), and Heyd-Scuseria-Ernzerh (HSE) exchange-correlation functional calculations. Finally, the performance and reaction mechanism of the photodegradation of CHOH by TiO2(001) and g-C3N4QDs/TiO2(001) were thoroughly investigated. The results show that the g-C3N4QDs were composed of an N-defect tri-s-triazine supported by TiO2(001) via a strong C-O-Ti chemical bond, which accelerated the separation of photoinduced carriers through a Z-scheme route. The photodegradation and mineralization efficiencies of CHOH were significantly promoted by 30% and 60% for g-C3N4QDs/TiO2(001) compared with those of TiO2(001). The photodegradation mechanism proceeded as CHOH - dioxymethylene - formate - carbonate - CO2. This study provides a surface engineering means to design highly active modified TiO2 for CHOH photodegradation.

20.
J Obstet Gynaecol Res ; 48(7): 1668-1674, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35388576

RESUMO

OBJECTIVE: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a bleeding disease that can cause fetal hydrops, a rare but life-threatening condition in which abnormal amounts of fluid accumulate in one or two areas of the fetus's body. A case of FNAIT with fetal hydrops caused by anti-HPA-15b antibodies was involved in this study, as we investigated whether or not anti-HPA-15b antibodies can induce endothelial angiogenesis and apoptosis. METHODS: The monoclonal antibody immobilization of platelet antigens assay (MAIPA) was used to identify anti-HPA-15b antibodies. The three groups in Tube formation and apoptosis assays were the PBS group, the AB serum IgG group, and the anti-HPA-15b serum IgG group, all reacted with HPA-15bb HUVEC. RESULTS: The presence of anti-HPA-15b antibodies was found in this case by MAIPA assay. The OD values are 0.33 and 0.21, reacted with HPA-15bb and HPA-15ab platelets, respectively (cutoff OD value = 0.2). Quantitative analysis revealed that the length of capillary-like tube induced by anti-HPA-15b antibodies was significantly decreased over that of AB serum IgG (*p = 0.0005), but weaker than when incubated with thrombin (**p = 0.0009). The apoptosis results show a significantly increased number of apoptotic endothelial cells in the anti-HPA-15b antibody IgG group when compared with the PBS and AB serum IgG groups (*p < 0.0001, **p < 0.0001). In addition, there is no statistical difference between the PBS and AB serum groups. CONCLUSION: Anti-HPA-15b antibodies can inhibit angiogenesis and induce apoptosis. This may associate with hydrops fetalis (HF), or fetal hydrops of FNAIT.


Assuntos
Antígenos de Plaquetas Humanas , Trombocitopenia Neonatal Aloimune , Anticorpos Monoclonais , Células Endoteliais , Feminino , Feto , Humanos , Hidropisia Fetal , Imunoglobulina G , Recém-Nascido
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