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1.
BMC Ophthalmol ; 24(1): 254, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38872161

RESUMO

OBJECTIVE: The aim of this study is to elucidate the factors contributing to the occurrence of retinal detachment (RD) following prophylactic vitrectomy in cases of acute retinal necrosis (ARN) syndrome. METHODS: A retrospective examination was undertaken, encompassing the medical records of patients diagnosed with ARN who underwent prophylactic vitreous intervention at the Ophthalmology Department of Wuhan University Renmin Hospital East Campus between October 2019 and September 2023. Subsequently, patients who manifested RD in the postoperative period were identified, and a comprehensive analysis was conducted to ascertain the factors underlying the occurrence of RD post-surgery. RESULTS: This study comprised 14 cases (involving 14 eyes) of patients diagnosed with ARN who underwent prophylactic vitreous intervention. The findings revealed that 4 patients experienced postoperative RD, resulting in an incidence rate of 28.57%. Notably, among these cases, 3 cases of RD manifested in the presence of silicone oil, while 1 case occurred subsequent to the removal of silicone oil. All 4 cases of RD exhibited varied degrees of proliferative vitreoretinopathy. Following the occurrence of RD, all patients underwent a secondary vitreous intervention coupled with silicone oil tamponade, leading to successful reattachment of the retina. However, despite these interventions, there was no significant enhancement observed in postoperative visual outcomes when compared to preoperative levels. CONCLUSION: RD following prophylactic vitrectomy in cases of ARN is not an infrequent occurrence and is primarily linked to the postoperative onset of proliferative vitreoretinopathy.


Assuntos
Complicações Pós-Operatórias , Descolamento Retiniano , Síndrome de Necrose Retiniana Aguda , Acuidade Visual , Vitrectomia , Humanos , Vitrectomia/métodos , Descolamento Retiniano/cirurgia , Descolamento Retiniano/etiologia , Síndrome de Necrose Retiniana Aguda/diagnóstico , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Acuidade Visual/fisiologia , Complicações Pós-Operatórias/prevenção & controle , Tamponamento Interno , Idoso , Adulto Jovem , Óleos de Silicone/administração & dosagem , Incidência
3.
Sci Rep ; 14(1): 12413, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816563

RESUMO

With its high energy consumption and pollutant emissions, the iron and steel industry is a significant source of air pollution and carbon emissions in the Beijing-Tianjin-Hebei (BTH) region. To improve air quality and reduce greenhouse gas emissions, a series of policies involving ultra-low emission, synergistic reduction of pollution, and carbon application have been implemented in the region. This study has assessed air pollutant and CO2 emission patterns in the iron and steel industry of the region by employing co-control effects coordinate system, marginal abatement cost curve, and numerical modeling, along with the synergistic benefits of typical technologies. The results have demonstrated that: (1) the intensive production activities pertinent to iron and steel enterprises has contributed greatly to the emission in Tangshan and Handan, where the sintering process is the main source of SO2, NOx, PM2.5, and CO, accounting for 64.86%, 55.15%, 29.98%, and 46.43% of the total emissions, respectively. (2) Among the typical pollution control and reduction measures, industrial restructuring and adjustment of the energy-resource structure have led to the greatest effects on emission reduction. Technologies exhibiting great potential in emission reduction and high-cost efficiency such as Blast Furnace Top Gas Recovery Turbine Unit (TRT) need to be promoted. (3) In Tangshan city with the highest level of steel production, the iron and steel production activities contributed to the concentration of 30.51% of PM2.5, 50.67% of SO2, and 42.54% of NO2 during the non-heating period. During the heating period, pollutants pertinent to the combustion of fossil energy for heating have increased, while iron and steel induced emissions have decreased to 23.7%, 34.32%, and 29.13%, respectively. By 2030, it is speculated that the contribution of the iron and steel industry to air quality will be significantly decreased as result of successful implementation of ultra-low emission policies and typical synergistic reduction technologies.

4.
Anal Chem ; 96(15): 5922-5930, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38575388

RESUMO

Mitochondrial therapy is a promising new strategy that offers the potential to achieve precise disease diagnosis or maximum therapeutic response. However, versatile mitochondrial theranostic platforms that integrate biomarker detection and therapy have rarely been exploited. Here, we report a charge-reversal nanomedicine activated by an acidic microenvironment for mitochondrial microRNA (mitomiR) detection and ion-interference therapy. The transporter liposome (DD-DC) was constructed from a pH-responsive polymer and a positively charged phospholipid, encapsulating NaCl nanoparticles with coloading of the aggregation-induced emission (AIE) fluorogens AIEgen-DNA/G-quadruplexes precursor and brequinar (NAB@DD-DC). The negatively charged nanomedicine ensured good blood stability and high tumor accumulation, while the charge-reversal to positive in response to the acidic pH in the tumor microenvironment (TME) and lysosomes enhanced the uptake by tumor cells and lysosome escape, achieving accumulation in mitochondria. The subsequently released Na+ in mitochondria not only contributed to the formation of mitomiR-494 induced G-quadruplexes for AIE imaging diagnosis but also led to an osmolarity surge that was enhanced by brequinar to achieve effective ion-interference therapy.


Assuntos
Compostos de Bifenilo , Quadruplex G , MicroRNAs , Nanopartículas , Neoplasias , Quinaldinas , Humanos , Cloreto de Sódio , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Mitocôndrias , Concentração de Íons de Hidrogênio , Linhagem Celular Tumoral , Microambiente Tumoral
5.
Environ Sci Pollut Res Int ; 31(20): 29656-29668, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38587778

RESUMO

The substantial amount of mercury emissions from coal-fired flue gas causes severe environmental contamination. With the Minamata Convention now officially in force, it is critical to strengthen mercury pollution control. Existing activated carbon injection technologies suffer from poor desulfurization performance and risk secondary-release risks. Therefore, considering the potential industrial application of adsorbents, we selected cost-effective and readily available activated coke (AC) as the carrier in this study. Four metal selenides-copper, iron, manganese, and tin-were loaded onto the AC to overcome the application problems of existing technologies. After 120 min of adsorption, the CuSe/AC exhibited the highest efficiency in removing Hg0, surpassing 80% according to the experimental findings. In addition, the optimal adsorption temperature window was 30-120 °C, the maximum adsorption rate was 2.9 × 10-2 mg·g-1·h-1, and the effectiveness of CuSe/AC in capturing Hg0 only dropped by 5.2% in the sulfur-containing atmosphere. The physicochemical characterization results indicated that the AC surface had a uniform loading of CuSe with a nanosheet structure resembling polygon and that the Cu-to-Se atomic ratio was close to 1:1. Finally, two possible Hg0 reaction pathways on CuSe/AC were proposed. Moreover, it was elucidated that the highly selective binding of Hg0 with ligand-unsaturated Se- was the key factor in achieving high adsorption efficiency and sulfur resistance in the selenium-functionalized AC adsorbent. This finding offers substantial theoretical support for the industrial application of this adsorbent.


Assuntos
Carvão Mineral , Coque , Mercúrio , Selênio , Adsorção , Selênio/química , Mercúrio/química , Poluentes Atmosféricos/química
6.
Cerebrovasc Dis Extra ; 14(1): 46-57, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38648746

RESUMO

INTRODUCTION: Acute ischemic stroke (AIS) stands as a leading cause of death and disability globally. This study aimed to investigate the risk factors and relevance linked with AIS in patients undergoing maintenance hemodialysis (MHD) and to create and validate nomogram models. METHODS: We examined the medical records of 314 patients with stage 5 chronic kidney disease (CKD 5) undergoing MHD, who sought neurology outpatient department consultation for suspected AIS symptoms between January 2018 and December 2023. These 314 patients were randomly divided into the training cohort (n = 222) and validation cohort (n = 92). The least absolute shrinkage selection operator (LASSO) regression model was employed for optimal feature selection in the AIS risk model. Subsequently, multivariable logistic regression analysis was used to construct a predictive model incorporating the features selected through LASSO. This predictive model's performance was assessed using the C-index and the area under the receiver operating characteristic curve (AUC). Additionally, calibration and clinical utility were evaluated through calibration plots and decision curve analysis (DCA). The model's internal validation was conducted using the validation cohort. RESULTS: Predictors integrated into the prediction nomogram encompassed cardiovascular disease (CVD) (odds ratio [OR] 7.95, 95% confidence interval [CI] 2.400-29.979), smoking (OR 5.7, 95% CI: 1.661-21.955), dialysis time (OR: 5.91, 95% CI: 5.866-29.979), low-density lipoprotein (OR: 2.99, 95% CI: 0.751-13.007), and fibrin degradation products (OR: 5.47, 95% CI: 1.563-23.162). The model exhibited robust discrimination, with a C-index of 0.877 and 0.915 in the internal training and validation cohorts, respectively. The AUC for the training set was 0.857, and a similar AUC of 0.905 was achieved in the validation cohort. DCA demonstrated a positive net benefit within a threshold risk range of 2-96%. CONCLUSION: The proposed nomogram effectively identifies MHD patients at high risk of AIS at an early stage. This model holds the potential to aid clinicians in making preventive recommendations.


Assuntos
AVC Isquêmico , Nomogramas , Valor Preditivo dos Testes , Diálise Renal , Humanos , Masculino , Feminino , Diálise Renal/efeitos adversos , Medição de Risco , AVC Isquêmico/diagnóstico , AVC Isquêmico/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Pessoa de Meia-Idade , Idoso , Reprodutibilidade dos Testes , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Prognóstico , Técnicas de Apoio para a Decisão
7.
Neurosci Lett ; 826: 137712, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38447888

RESUMO

Glaucoma is a kind of neurodegenerative disorder characterized by irreversible loss of retinal ganglion cells (RGCs) and permanent visual impairment. It is reported that resveratrol (RES) is a promising drug for neurodegenerative diseases. However, the detailed molecular mechanisms underlying its protective potential have not yet been fully elucidated. The present study sought to investigate whether resveratrol could protect RGCs and retinal function triggered by acute ocular hypertension injury through the SIRT1/NF-κB pathway. An experimental glaucoma model was generated in C57BL/6J mice. Resveratrol was intraperitoneally injected for 5 days. Sirtinol was injected intravitreally on the day of retinal AOH injury. RGC survival was determined using immunostaining. TUNEL staining was conducted to evaluate retinal cell apoptosis. ERG was used to evaluate visual function. The proteins Brn3a, SIRT1, NF-κB, IL-6, Bax, Bcl2, and Cleaved Caspase3 were determined using western blot. The expression and localisation of SIRT1 and NF-κB in the retina were detected by immunofluorescence. Our data indicated that resveratrol treatment significantly increased Brn3a-labelled RGCs and reduced RGC apoptosis caused by AOH injury. Resveratrol administration also remarkably decreased NF-κB, IL-6, Bax, and Cleaved Caspase3 proteins and increased SIRT1 and Bcl2 proteins. Furthermore, resveratrol treatment obviously inhibited the reduction in ERG caused by AOH injury. Importantly, simultaneous administration of resveratrol and sirtinol abrogated the protective effect of resveratrol, decreased NF-κB protein expression, and increased SIRT1 protein levels. These results suggest that resveratrol administration significantly mitigates retinal AOH-induced RGCs loss and retinal dysfunction, and that this neuroprotective effect is partially regulated through the SIRT1/NF-κB pathway.


Assuntos
Benzamidas , Glaucoma , Naftóis , Hipertensão Ocular , Camundongos , Animais , Resveratrol/farmacologia , Resveratrol/uso terapêutico , NF-kappa B/metabolismo , Sirtuína 1/metabolismo , Proteína X Associada a bcl-2 , Interleucina-6 , Camundongos Endogâmicos C57BL , Hipertensão Ocular/tratamento farmacológico , Glaucoma/tratamento farmacológico
8.
ACS Omega ; 9(6): 7230-7238, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38371808

RESUMO

Diterpenoid tanshinones (DTs) are a bioactive fraction extracted from Salvia miltiorrhiza. High-performance liquid chromatography analysis revealed the presence of four compounds, namely, tanshinone IIA, tanshinone I, cryptotanshinone, and dihydrotanshinone. In this study, we aimed to propose a possible mechanism for the anti-lung cancer effect of DT. To do so, we utilized a lung cancer nude mice model and a lung cancer cell line (PC9) to investigate the effect of DT on lung cancer. We employed immunohistochemistry, enzyme-linked immunosorbent assay, hematoxylin and eosin staining, and immunofluorescence to analyze the pharmacological role of DT in the inhibition of lung cancer growth. The results showed that DT inhibited tumor growth, induced apoptosis in the nude mice model, and reduced inflammatory cell infiltration. Additionally, DT inhibited PC9 lung cancer cells, growth, proliferation, and migration. The mechanism of action of DT involves not only directly inhibiting cell proliferation and migration but also improving the tumor microenvironment. DT significantly increased the expression of important intestinal gap junction proteins, such as zonula occludens 1 (ZO-1) and occludin I. This upregulation contributes to the reinforcement of the intestinal mucosal barrier, thereby reducing the paracellular transport of lipopolysaccharides (LPS) through the intestine. Consequently, the decreased LPS levels lead to the inhibition of NF-κB expression and downregulation of macrophage polarization, as indicated by the decreased expression of CD68. In conclusion, this study has confirmed that DT has anti-lung cancer properties by improving the inflammatory tumor microenvironment via regulating macrophage polarization and inhibiting LPS-associated immune response. These results provide new insights into the mechanism of DT action against lung cancer.

9.
Laryngoscope ; 134(7): 3030-3037, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38380991

RESUMO

OBJECTIVE: To assess whether adenotonsillectomy improves levels of inflammatory and cardiometabolic markers in children with polysomnographically diagnosed obstructive sleep apnea (OSA). DATA SOURCES: Two authors independently searched PubMed, Embase, and Cochrane databases up to August 16, 2022, for studies relating to pre- and post-operative levels of serum markers in pediatric patients undergoing adenotonsillectomy. REVIEW METHODS: Data were extracted from included articles into a structured proforma. Meta-analyses of the standardized mean difference (SMD) were conducted in random-effects models. We calculated the probability of benefit (POB) and number needed to treat (NNT) for outcomes that demonstrated a statistically significant effect after adenotonsillectomy. The primary outcomes were changes in serum markers including C-reactive protein (CRP), high-sensitivity CRP (hs-CRP), Insulin-like growth factor 1 (IGF-1), interleukin-10 (IL-10), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), Brain natriuretic peptide (BNP), insulin, glucose, total cholesterol, triglyceride, low-density lipoprotein (LDL), high-density lipoprotein (HDL). RESULTS: We screened 1616 studies and included 26 studies with 1331 participants. Meta-analysis was performed on 20 of the included studies. Adenotonsillectomy was associated with a significant decrease in insulin levels (SMD = -0.322, 95% Confidence Interval (CI) = -0.583 to -0.061), CRP (SMD = -0.946, 95% CI = -1.578 to -0.314), and BNP (SMD = -1.416, 95% CI = -2.355 to -0.477) and significant increase in levels of IGF-1 (SMD = 0.691, 95% CI = 0.207 to 1.176). There were no significant changes in levels of triglyceride, total cholesterol, TNF-α, LDL, HDL, glucose, IL-10, and IL-6. CONCLUSION: In children with polysomnographically diagnosed OSA, adenotonsillectomy was associated with improvements in serum biomarkers, comprising lower CRP, insulin, and BNP, and higher IGF-1. Laryngoscope, 134:3030-3037, 2024.


Assuntos
Adenoidectomia , Biomarcadores , Proteína C-Reativa , Apneia Obstrutiva do Sono , Tonsilectomia , Humanos , Apneia Obstrutiva do Sono/cirurgia , Apneia Obstrutiva do Sono/sangue , Biomarcadores/sangue , Criança , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Interleucina-10/sangue , Interleucina-6/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/análise , Fator de Necrose Tumoral alfa/sangue , Peptídeo Natriurético Encefálico/sangue , Pré-Escolar
10.
bioRxiv ; 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38370833

RESUMO

Spatial transcriptomics has emerged as a powerful tool for dissecting spatial cellular heterogeneity but as of today is largely limited to gene expression analysis. Yet, the life of RNA molecules is multifaceted and dynamic, requiring spatial profiling of different RNA species throughout the life cycle to delve into the intricate RNA biology in complex tissues. Human disease-relevant tissues are commonly preserved as formalin-fixed and paraffin-embedded (FFPE) blocks, representing an important resource for human tissue specimens. The capability to spatially explore RNA biology in FFPE tissues holds transformative potential for human biology research and clinical histopathology. Here, we present Patho-DBiT combining in situ polyadenylation and deterministic barcoding for spatial full coverage transcriptome sequencing, tailored for probing the diverse landscape of RNA species even in clinically archived FFPE samples. It permits spatial co-profiling of gene expression and RNA processing, unveiling region-specific splicing isoforms, and high-sensitivity transcriptomic mapping of clinical tumor FFPE tissues stored for five years. Furthermore, genome-wide single nucleotide RNA variants can be captured to distinguish different malignant clones from non-malignant cells in human lymphomas. Patho-DBiT also maps microRNA-mRNA regulatory networks and RNA splicing dynamics, decoding their roles in spatial tumorigenesis trajectory. High resolution Patho-DBiT at the cellular level reveals a spatial neighborhood and traces the spatiotemporal kinetics driving tumor progression. Patho-DBiT stands poised as a valuable platform to unravel rich RNA biology in FFPE tissues to study human tissue biology and aid in clinical pathology evaluation.

11.
J Biomol Struct Dyn ; : 1-17, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38173145

RESUMO

Focal Adhesion Kinase (FAK) is an important target for tumor therapy and is closely related to tumor cell genesis and progression. In this paper, we selected 46 FAK inhibitors with anticancer activity in the pyrrolo pyrimidine backbone to establish 3D/2D-QSAR models to explore the relationship between inhibitory activity and molecular structure. We have established two ideal models, namely, the Topomer CoMFA model (q2= 0.715, r2= 0.984) and the Holographic Quantitative Structure-Activity Relationship (HQSAR) model (q2= 0.707, r2= 0.899). Both models demonstrate excellent external prediction capabilities.Based on the QSAR results, we designed 20 structurally modified novel compounds, which were subjected to molecular docking and molecular dynamics studies, and the results showed that the new compounds formed many robust interactions with residues within the active pocket and could maintain stable binding to the receptor proteins. This study not only provides a powerful screening tool for designing novel FAK inhibitors, but also presents a series of novel FAK inhibitors with high micromolar activity that can be used for further characterization. It provides a reference for addressing the shortcomings of drug metabolism and drug resistance of traditional FAK inhibitors, as well as the development of novel clinically applicable FAK inhibitors.Communicated by Ramaswamy H. Sarma.

12.
Histol Histopathol ; : 18707, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38293776

RESUMO

Tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) type IIb are the predominant causes of drug-refractory epilepsy in children. Dysmorphic neurons (DNs), giant cells (GCs), and balloon cells (BCs) are the most typical pathogenic profiles in cortical lesions of TSC and FCD IIb patients. However, mechanisms underlying the pathological processes of TSC and FCD IIb remain obscure. The Plexin-B2-Sema4C signalling pathway plays critical roles in neuronal morphogenesis and corticogenesis during the development of the central nervous system. However, the role of the Plexin-B2 system in the pathogenic process of TSC and FCD IIb has not been identified. In the present study, we investigated the expression and cell distribution characteristics of Plexin-B2 and Sema4C in TSC and FCD IIb lesions with molecular technologies. Our results showed that the mRNA and protein levels of Plexin-B2 expression were significantly increased both in TSC and FCD IIb lesions versus that in the control cortex. Notably, Plexin-B2 was also predominantly observed in GCs in TSC epileptic lesions and BCs in FCD IIb lesions. In contrast, the expression of Sema4C, the ligand of Plexin-B2, was significantly decreased in DNs, GCs, and BCs in TSC and FCD IIb epileptic lesions. Additionally, Plexin-B2 and Sema4C were expressed in astrocytes and microglia cells in TSC and FCD IIb lesions. Furthermore, the expression of Plexin-B2 was positively correlated with seizure frequency in TSC and FCD IIb patients. In conclusion, our results showed the Plexin-B2-Sema4C system was abnormally expressed in cortical lesions of TSC and FCD IIb patients, signifying that the Plexin-B2-Sema4C system may play a role in the pathogenic development of TSC and FCD IIb.

13.
Ann Surg Open ; 4(4): e339, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38144489

RESUMO

Objective: To examine the association between the performance of mapping biopsies and surgical outcomes postexcision of extramammary Paget's disease (EMPD). Background: Primary EMPD is a rare entity associated with poorly defined surgical margins and difficult-to-access sites of lesions. Surgical resection with clear margins remains the preferred management method. The use of mapping biopsies might be beneficial, particularly in lowering disease recurrence. Methods: Available literature was reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology before a fixed-effect meta-analysis was performed to identify the presence of a correlation between performing mapping biopsies and positive margins on permanent sections as well as disease-free survival. Additional study results not included in the quantitative assessment were qualitatively assessed and reported. Results: A total of 12 studies were shortlisted for final analysis. 294 patients who underwent mapping biopsies and 48 patients who did not undergo mapping biopsies were included in the assessment. Forest plot analysis revealed a pooled rate ratio of 0.50 (95% CI, 0.32-0.77) in the prevalence of positive margins in patients with mapping biopsies performed as compared to patients without. The pooled rate ratio of the prevalence of disease-free survival in patients with mapping biopsies performed as compared to patients without was 1.38 (95% CI, 1.03-1.84). Qualitative assessment of the remaining selected studies revealed equivocal results. Conclusions: Mapping biopsies are able to improve EMPD surgical excision outcomes but given the rarity of the disease and heterogeneity of mapping biopsy procedures, further confirmation with randomized controlled trials or a larger patient pool is necessary.

14.
Vet Sci ; 10(12)2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38133254

RESUMO

Lymphoma is the most common haematological malignancy affecting dogs and has a high incidence in the Bullmastiff breed. The aim of this study was to identify risk loci predisposing this breed to the disease. The average age of lymphoma diagnosis in 55 cases was less than 6 years, similar to the median age of 64 cases from our clinical and pathology databases. When fine-scale population structure was explored using NETVIEW, cases were distributed throughout an extended pedigree. When genotyped cases (n = 49) and dogs from the control group (n = 281) were compared in a genome-wide association analysis of lymphoma risk, the most prominent associated regions were detected on CFA13 and CFA33. The top SNPs in a 5.4 Mb region on CFA13 were significant at a chromosome-wide level, and the region was fine-mapped to ~1.2 Mb (CFA13: 25.2-26.4 Mb; CanFam3.1) with four potential functional candidates, including the MYC proto-oncogene bHLH transcription factor (MYC) and a region syntenic with the human and mouse lncRNA Pvt1 oncogene (PVT1). A 380 Kb associated region at CFA33: 7.7-8.1 Mb contained the coding sequence for SUMO specific peptidase7 (SENP7) and NFK inhibitor zeta (NFKBIZ) genes. These genes have annotations related to cancer, amongst others, and both have functional links to MYC regulation. Genomic signatures identified in lymphoma cases suggest that increased risk contributed by the regions identified by GWAS may complement a complex predisposing genetic background.

15.
Genet Test Mol Biomarkers ; 27(12): 384-392, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38156907

RESUMO

Background: RNA-binding motif proteins (RBMs) have been widely implicated in the tumorigenesis of multiple human cancers but rarely investigated in glioblastoma (GBM). Methods: The expression level of RBM47 and its correlation with prognosis of GBM were examined using bioinformatics, quantitative reverse transcription PCR, and Western blot analysis. The colony formation assay and Cell Counting Kit-8 assay were used to determine the biological role of RBM47 in GBM. To measure invasiveness we used the wound healing assay and transwell assay. The regulatory relationship between RBM47 and the epithelial-to-mesenchymal transition (EMT) was examined by Western blot analysis and bioinformatic analysis. Results: Through integrative analysis of clinical proteomic and genomic tumor datasets, we found that RBM47 is significantly upregulated in GBM mesenchymal subtype, and its high expression is correlated with poor prognosis. In in vitro biological experiments, we observed a significant inhibitory effect of RBM47 knockdown on colony formation and cell growth using GBM cell lines. Conversely, overexpression of RBM47 restored and accelerated these processes. Moreover, in vitro, wound healing assays demonstrated the role of RBM46 in promoting and cell migration and invasion. Mechanistically, RBM47 enhances invasive capacity through the activation of the EMT program. In RBM47-knockdown cells, the expression levels of Vimentin and CD44 were suppressed, and the level of E-cadherin was increased. Conclusions: Taken together our results demonstrate the tumor promoting characteristics of RBM46 and suggest that it could be used both as a therapeutic target and prognostically.


Assuntos
Glioblastoma , Humanos , Glioblastoma/genética , Glioblastoma/metabolismo , Linhagem Celular Tumoral , Proteômica , Movimento Celular/genética , Invasividade Neoplásica/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
16.
Vet Sci ; 10(9)2023 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-37756103

RESUMO

There has been considerable interest in studying cancer in dogs and its potential as a model system for humans. One area of research has been the search for genetic risk variants in canine lymphoma, which is amongst the most common canine cancers. Previous studies have focused on a limited number of breeds, but none have included Border Collies. The aims of this study were to identify relationships between Border Collie lymphoma cases through an extensive pedigree investigation and to utilise relationship information to conduct genome-wide association study (GWAS) analyses to identify risk regions associated with lymphoma. The expanded pedigree analysis included 83,000 Border Collies, with 71 identified lymphoma cases. The analysis identified affected close relatives, and a common ancestor was identified for 54 cases. For the genomic study, a GWAS was designed to incorporate lymphoma cases, putative "carriers", and controls. A case-control GWAS was also conducted as a comparison. Both analyses showed significant SNPs in regions on chromosomes 18 and 27. Putative top candidate genes from these regions included DLA-79, WNT10B, LMBR1L, KMT2D, and CCNT1.

17.
Chemosphere ; 340: 139866, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37633603

RESUMO

In this paper, the degradation of o-DCB under different gas-phase parameter conditions was investigated using the SDBD-NTP system. The results showed that the increase in initial and oxygen concentrations had opposite effects on the degradation of o-DCB. Among them, the increase of oxygen concentration promoted the degradation of o-DCB. Relative humidity promoted and then inhibited the degradation of o-DCB. The highest degradation efficiency of o-DCB was achieved at RH = 15%, reaching 91% at 29W. In the study of by-products, it was found that O3 and NOx were the main inorganic by-products, and that different oxygen levels and relative humidity conditions had a large effect on the production of O3 and NOx. In all of them, the concentration of O3 decreased with the increase of input power. NOx increased with increasing oxygen concentration, but the increase in relative humidity inhibited the production of NO and N2O and promoted the conversion of NO2. A study of organic by-products revealed this. In the absence of oxygen, a higher number of benzene products appeared. Whereas, with the addition of oxygen, only in the by-products under conditions where no relative humidity was introduced, benzene ring products were predominantly present in the by-products. However, when RH was added, n-hexane was found to be present in the by-products. This may be because the introduction of OH• favors the destruction of the benzene ring. Finally, the possible reaction pathways and reaction mechanisms of o-DCB under different gas-phase parameters are given. It provides a reference for future related scientific research as well as scientific problems in practical applications.


Assuntos
Benzeno , Clorobenzenos , Oxigênio , Tecnologia
18.
Nat Commun ; 14(1): 4760, 2023 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-37553321

RESUMO

Long-read RNA sequencing (RNA-seq) is a powerful technology for transcriptome analysis, but the relatively low throughput of current long-read sequencing platforms limits transcript coverage. One strategy for overcoming this bottleneck is targeted long-read RNA-seq for preselected gene panels. We present TEQUILA-seq, a versatile, easy-to-implement, and low-cost method for targeted long-read RNA-seq utilizing isothermally linear-amplified capture probes. When performed on the Oxford nanopore platform with multiple gene panels of varying sizes, TEQUILA-seq consistently and substantially enriches transcript coverage while preserving transcript quantification. We profile full-length transcript isoforms of 468 actionable cancer genes across 40 representative breast cancer cell lines. We identify transcript isoforms enriched in specific subtypes and discover novel transcript isoforms in extensively studied cancer genes such as TP53. Among cancer genes, tumor suppressor genes (TSGs) are significantly enriched for aberrant transcript isoforms targeted for degradation via mRNA nonsense-mediated decay, revealing a common RNA-associated mechanism for TSG inactivation. TEQUILA-seq reduces the per-reaction cost of targeted capture by 2-3 orders of magnitude, as compared to a standard commercial solution. TEQUILA-seq can be broadly used for targeted sequencing of full-length transcripts in diverse biomedical research settings.


Assuntos
Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Perfilação da Expressão Gênica/métodos , Análise de Sequência de RNA/métodos , RNA/genética , Isoformas de Proteínas/genética , Transcriptoma/genética
19.
Environ Sci Technol ; 57(31): 11510-11519, 2023 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-37489803

RESUMO

Accurately tracking carbon flows is the first step toward reducing the climate impacts of the iron and steel industry (ISI), which is still lacking in China. In this study, we track carbon flows from coal/mineral mines to end steel users by coupling the cross-process material and energy flow model, point-based emission inventory, and interprovincial trade matrices. In 2020, ISI emitted 2288 Tg of CO2 equivalent (CO2eq, including CH4 and CO2), 96% of which came from energy use and 4% from raw material decomposition. Often overlooked off-gas use and CH4 leakage in coal mines account for 25% of life-cycle emissions. Due to limited scrap resources and a high proportion of pig iron feed, the life-cycle emission intensity of the electric arc furnace (EAF) (1.15 t CO2eq/t steel) is slightly lower than the basic oxygen furnace (BOF) (1.58 t CO2eq/t steel) in China. In addition, over 49% of producer-based emissions are driven by interprovincial coal/coke/steel trade. In particular, nearly all user-based emissions in Zhejiang and Beijing are transferred to steelmaking bases. Therefore, we highlight the need for life-cycle and spatial shifts in user-side carbon management.


Assuntos
Poluentes Atmosféricos , Ferro , Animais , Suínos , Poluentes Atmosféricos/análise , Carbono , Aço , Dióxido de Carbono/análise , Carvão Mineral , China
20.
Adv Sci (Weinh) ; 10(25): e2206663, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37404090

RESUMO

Endocrine therapy is the frontline treatment for estrogen receptor (ER) positive breast cancer patients. However, the primary and acquired resistance to endocrine therapy drugs remain as a major challenge in the clinic. Here, this work identifies an estrogen-induced lncRNA, LINC02568, which is highly expressed in ER-positive breast cancer and functional important in cell growth in vitro and tumorigenesis in vivo as well as endocrine therapy drug resistance. Mechanically, this work demonstrates that LINC02568 regulates estrogen/ERα-induced gene transcriptional activation in trans by stabilizing ESR1 mRNA through sponging miR-1233-5p in the cytoplasm. Meanwhile, LINC02568 contributes to tumor-specific pH homeostasis by regulating carbonic anhydrase CA12 in cis in the nucleus. The dual functions of LINC02568 together contribute to breast cancer cell growth and tumorigenesis as well as endocrine therapy drug resistance. Antisense oligonucleotides (ASO) targeting LINC02568 significantly inhibits ER-positive breast cancer cell growth in vitro and tumorigenesis in vivo. Furthermore, combination treatment with ASO targeting LINC02568 and endocrine therapy drugs or CA12 inhibitor U-104 exhibits synergistic effects on tumor growth. Taken together, the findings reveal the dual mechanisms of LINC02568 in regulating ERα signaling and pH homeostasis in ER-positive breast cancer, and indicated that targeting LINC02568 might represent a potential therapeutic avenue in the clinic.


Assuntos
Neoplasias da Mama , RNA Longo não Codificante , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Receptor alfa de Estrogênio/genética , Receptores de Estrogênio/uso terapêutico , RNA Longo não Codificante/genética , Linhagem Celular Tumoral , Estrogênios/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Carcinogênese
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