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1.
Mol Plant Pathol ; 25(5): e13462, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38695630

RESUMO

MicroRNAs (miRNAs) are widely involved in various biological processes of plants and contribute to plant resistance against various pathogens. In this study, upon sugarcane mosaic virus (SCMV) infection, the accumulation of maize (Zea mays) miR398b (ZmmiR398b) was significantly reduced in resistant inbred line Chang7-2, while it was increased in susceptible inbred line Mo17. Degradome sequencing analysis coupled with transient co-expression assays revealed that ZmmiR398b can target Cu/Zn-superoxidase dismutase2 (ZmCSD2), ZmCSD4, and ZmCSD9 in vivo, of which the expression levels were all upregulated by SCMV infection in Chang7-2 and Mo17. Moreover, overexpressing ZmmiR398b (OE398b) exhibited increased susceptibility to SCMV infection, probably by increasing reactive oxygen species (ROS) accumulation, which were consistent with ZmCSD2/4/9-silenced maize plants. By contrast, silencing ZmmiR398b (STTM398b) through short tandem target mimic (STTM) technology enhanced maize resistance to SCMV infection and decreased ROS levels. Interestingly, copper (Cu)-gradient hydroponic experiments demonstrated that Cu deficiency promoted SCMV infection while Cu sufficiency inhibited SCMV infection by regulating accumulations of ZmmiR398b and ZmCSD2/4/9 in maize. These results revealed that manipulating the ZmmiR398b-ZmCSD2/4/9-ROS module provides a prospective strategy for developing SCMV-tolerant maize varieties.


Assuntos
Resistência à Doença , MicroRNAs , Doenças das Plantas , Potyvirus , Zea mays , Zea mays/virologia , Zea mays/genética , Potyvirus/fisiologia , Potyvirus/patogenicidade , Doenças das Plantas/virologia , Doenças das Plantas/genética , Resistência à Doença/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Regulação da Expressão Gênica de Plantas , Espécies Reativas de Oxigênio/metabolismo
2.
Front Oncol ; 14: 1324181, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38699643

RESUMO

Background: The current treatment strategy for metastatic Hormone-Sensitive Prostate Cancer (mHSPC) is the combination of Androgen Receptor Signaling Inhibitors (ARSIs) medicines with androgen deprivation therapy (ADT). However, there is a lack of real-world data comparing the efficacy of different ARSI pharmaceuticals. Therefore, the objective of this study was to compare the effectiveness and safety of bicalutamide, abiraterone, enzalutamide, and apalutamide in combination with ADT for patients with mHSPC. Methods: We retrospectively analyzed 82 patients diagnosed with mHSPC, including 18 patients treated with abiraterone acetate with prednisone, 21 patients with enzalutamide, 20 patients with apalutamide, and 23 patients with bicalutamide. We evaluated PSA progression-free survival (PSA-PFS), imaging progression-free survival (r PFS), castration resistance progression-free survival (CRPC-PFS), and overall survival (OS) using Kaplan-Meier survival analyses. Additionally, we explored relevant factors affecting prognosis through univariate and multivariate Cox risk-proportionality models. PSA response rates at 3, 6, and 12 months, nadir PSA levels (nPSA), and time to nadir (TTN) in different medication subgroups after treatment were documented, and we used one-way ANOVA to determine the effect of these measures on patient prognosis. Results: In comparison with bicalutamide, both enzalutamide and apalutamide have shown significant advantages in delaying disease progression among mHSPC patients. Specifically, enzalutamide has been found to significantly prolong PSA-PFS (HR 2.244; 95% CI 1.366-3.685, p=0.001), rPFS (HR 2.539; 95% CI 1.181-5.461; p= 0.007), CRPC-PFS (HR 2.131; 95% CI 1.295-3.506; p= 0.003), and OS (HR 2.06; 95% CI 1.183-3.585; P=0.005). Similarly, apalutamide has significantly extended PSA-PFS (HR 5.071; 95% CI 1.711-15.032; P= 0.003) and CRPC-PFS (HR 6.724; 95% CI 1.976-22.878; P=0.002) among patients. On the other hand, the use of abiraterone in combination with ADT did not demonstrate a significant advantage in delaying diseases progression when compared with the other three agents in mHSPC patients. There were no significant differences in overall adverse event rates among the four pharmaceuticals in terms of safety. Additionally, the observation of PSA kinetics revealed that enzalutamide, apalutamide, and abiraterone acetate had a significant advantage in achieving deep PSA response (PSA ≤ 0.2 ng/ml) compared with bicalutamide (p=0.007 at 12 months). Enzalutamide and apalutamide exhibited preeminence efficacy, with no substantial difference observed between the two medications. Conclusions: Abiraterone, enzalutamide, and apalutamide were found to significantly reduce and stabilize PSA levels in mHSPC patients more quickly and thoroughly than bicalutamide. Furthermore, enzalutamide and apalutamide were found to significantly prolong survival and delay disease progression in mHSPC patients compared with bicalutamide. It should be noted that abiraterone did not demonstrate a significant advantage in delaying disease compared with enzalutamide and apalutamide. After conducting drug toxicity analyses, it was determined that there were no significant differences among the four drugs.

3.
Sci Technol Adv Mater ; 25(1): 2336399, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628978

RESUMO

Photovoltaic-thermoelectric (PV-TE) tandem system has been considered as an effective way to fully utilize the solar spectrum, and has been demonstrated in a perovskite solar cell (PSC)-thermoelectric (TE) configuration. However, the conventional PSC-TE tandem architecture cannot convert infrared light transmitted through the upper PSC into heat effectively, impeding the heat-electricity conversion of TE devices. Herein, a semi-transparent PSC-photothermal-TE tandem system is designed for improved photothermal utilization. Through optimizing the buffer layer of the back transparent electrode, semi-transparent PSC with a power conversion efficiency (PCE) of 13% and an average transmittance of 53% in the range of 800-1500 nm was obtained. On this basis, a photothermal thin film was introduced between the semi-transparent PSC and the TE device, which increased the efficiency contribution ratio of the TE device from 14% to 19%, showing enhanced utilization of AM 1.5 G solar spectrum and improved photo-thermal-electric conversion efficiency.


We have constructed a semi-transparent perovskite solar cell-photothermal-thermoelectric tandem system through the optimization of transparent back electrode and the introduction of photothermal thin-film, realizing enhanced utilization of solar energy.

4.
Pestic Biochem Physiol ; 201: 105893, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38685255

RESUMO

Potato virus Y (PVY) is one of the most important pathogens in the genus Potyvirus that seriously harms agricultural production. Copper (Cu), as a micronutrient, is closely related to plant immune response. In this study, we found that foliar application of Cu could inhibit PVY infection to some extent, especially at 7 days post inoculation (dpi). To explore the effect of Cu on PVY infection, transcriptome sequencing analysis was performed on PVY-infected tobacco with or without Cu application. Several key pathways regulated by Cu were identified, including plant-pathogen interaction, inorganic ion transport and metabolism, and photosynthesis. Moreover, the results of virus-induced gene silencing (VIGS) assays revealed that NbMLP423, NbPIP2, NbFd and NbEXPA played positive roles in resistance to PVY infection in Nicotiana benthamiana. In addition, transgenic tobacco plants overexpressing NtEXPA11 showed increased resistance to PVY infection. These results contribute to clarify the role and regulatory mechanism of Cu against PVY infection, and provide candidate genes for disease resistance breeding.


Assuntos
Cobre , Resistência à Doença , Nicotiana , Doenças das Plantas , Potyvirus , Nicotiana/virologia , Nicotiana/genética , Potyvirus/fisiologia , Cobre/farmacologia , Doenças das Plantas/virologia , Resistência à Doença/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Perfilação da Expressão Gênica , Plantas Geneticamente Modificadas/virologia , Regulação da Expressão Gênica de Plantas , Transcriptoma
5.
Cell Death Dis ; 15(4): 278, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637559

RESUMO

Myelodysplastic syndromes (MDS) are a heterogeneous group of pre-leukemic hematopoietic disorders characterized by cytopenia in peripheral blood due to ineffective hematopoiesis and normo- or hypercellularity and morphologic dysplasia in bone marrow (BM). An inflammatory BM microenvironment and programmed cell death of hematopoietic stem/progenitor cells (HSPCs) are thought to be the major causes of ineffective hematopoiesis in MDS. Pyroptosis, apoptosis and necroptosis (collectively, PANoptosis) are observed in BM tissues of MDS patients, suggesting an important role of PANoptosis in MDS pathogenesis. Caspase 8 (Casp8) is a master regulator of PANoptosis, which is downregulated in HSPCs from most MDS patients and abnormally spliced in HSPCs from MDS patients with SRSF2 mutation. To study the role of PANoptosis in hematopoiesis, we generated inducible Casp8 knockout mice (Casp8-/-). Mx1-Cre-Casp8-/- mice died of BM failure within 10 days of polyI:C injections due to depletion of HSPCs. Rosa-ERT2Cre-Casp8-/- mice are healthy without significant changes in BM hematopoiesis within the first 1.5 months after Casp8 deletion. Such mice developed BM failure upon infection or low dose polyI:C/LPS injections due to the hypersensitivity of Casp8-/- HSPCs to infection or inflammation-induced necroptosis which can be prevented by Ripk3 deletion. However, impaired self-renewal capacity of Casp8-/- HSPCs cannot be rescued by Ripk3 deletion due to activation of Ripk1-Tbk1 signaling. Most importantly, mice transplanted with Casp8-/- BM cells developed MDS-like disease within 4 months of transplantation as demonstrated by anemia, thrombocytopenia and myelodysplasia. Our study suggests an essential role for a balance in Casp8, Ripk3-Mlkl and Ripk1-Tbk1 activities in the regulation of survival and self-renewal of HSPCs, the disruption of which induces inflammation and BM failure, resulting in MDS-like disease.


Assuntos
Síndromes Mielodisplásicas , Animais , Humanos , Camundongos , Transtornos da Insuficiência da Medula Óssea/complicações , Caspase 8/genética , Caspase 8/metabolismo , Inflamação/metabolismo , Camundongos Knockout , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/metabolismo
6.
Membranes (Basel) ; 14(4)2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38668101

RESUMO

The high concentration of chloride ions in desulphurization wastewater is the primary limiting factor for its reusability. Monovalent anion selective electrodialysis (S-ED) enables the selective removal of chloride ions, thereby facilitating the reuse of desulfurization wastewater. In this study, different concentrations of NaCl and Na2SO4 were used to simulate different softened desulfurization wastewater. The effects of current density and NaCl and Na2SO4 concentration on ion flux, permselectivity (PSO42-Cl-) and specific energy consumption were studied. The results show that Selemion ASA membrane exhibits excellent permselectivity for Cl- and SO42-, with a significantly lower flux observed for SO42- compared to Cl-. Current density exerts a significant influence on ion flux; as the current density increases, the flux of SO42- also increases but at a lower rate than that of Cl-, resulting in an increase in permselectivity. When the current density reaches 25 mA/cm2, the permselectivity reaches a maximum of 50.4. The increase in NaCl concentration leads to a decrease in the SO42- flux; however, the permselectivity is reduced due to the elevated Cl-/SO42- ratio. The SO42- flux increases with the increase in Na2SO4 concentration, while the permselectivity increases with the decrease in Cl-/SO42- ratio.

7.
J Med Internet Res ; 26: e46777, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38635981

RESUMO

BACKGROUND: As global populations age and become susceptible to neurodegenerative illnesses, new therapies for Alzheimer disease (AD) are urgently needed. Existing data resources for drug discovery and repurposing fail to capture relationships central to the disease's etiology and response to drugs. OBJECTIVE: We designed the Alzheimer's Knowledge Base (AlzKB) to alleviate this need by providing a comprehensive knowledge representation of AD etiology and candidate therapeutics. METHODS: We designed the AlzKB as a large, heterogeneous graph knowledge base assembled using 22 diverse external data sources describing biological and pharmaceutical entities at different levels of organization (eg, chemicals, genes, anatomy, and diseases). AlzKB uses a Web Ontology Language 2 ontology to enforce semantic consistency and allow for ontological inference. We provide a public version of AlzKB and allow users to run and modify local versions of the knowledge base. RESULTS: AlzKB is freely available on the web and currently contains 118,902 entities with 1,309,527 relationships between those entities. To demonstrate its value, we used graph data science and machine learning to (1) propose new therapeutic targets based on similarities of AD to Parkinson disease and (2) repurpose existing drugs that may treat AD. For each use case, AlzKB recovers known therapeutic associations while proposing biologically plausible new ones. CONCLUSIONS: AlzKB is a new, publicly available knowledge resource that enables researchers to discover complex translational associations for AD drug discovery. Through 2 use cases, we show that it is a valuable tool for proposing novel therapeutic hypotheses based on public biomedical knowledge.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Reconhecimento Automatizado de Padrão , Bases de Conhecimento , Aprendizado de Máquina , Conhecimento
8.
Int Immunopharmacol ; 132: 111940, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38593503

RESUMO

Glutathione metabolism (GM) is a crucial part of various metabolic and pathophysiological processes. However, its role in lung adenocarcinoma (LUAD) has not been comprehensively studied. This study aimed to explore the potential relationship between GM genes, the prognosis, and the immune microenvironment of patients with LUAD. We constructed a risk signature model containing seven GM genes using Lasso combined Cox regression and validated it using six GEO datasets. Our analysis showed that it is an independent prognostic factor. Functional enrichment analysis revealed that the GM genes were significantly enriched in cell proliferation, cell cycle regulation, and metabolic pathways. Clinical and gene expression data of patients with LUAD were obtained from the TCGA database and patients were divided into high- and low-risk groups. The high-risk patient group had a poor prognosis, reduced immune cell infiltration, poor response to immunotherapy, high sensitivity to chemotherapy, and low sensitivity to targeted therapy. Subsequently, single-cell transcriptome analysis using the GSE143423 and GSE127465 datasets revealed that the core SMS gene was highly enriched in M2 Macrophages. Finally, nine GEO datasets and multiple fluorescence staining revealed a correlation between the SMS expression and M2 macrophage polarization. Our prognostic model in which the core SMS gene is closely related to M2 macrophage polarization is expected to become a novel target and strategy for tumor therapy.


Assuntos
Adenocarcinoma de Pulmão , Regulação Neoplásica da Expressão Gênica , Glutationa , Neoplasias Pulmonares , Macrófagos , Microambiente Tumoral , Humanos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/mortalidade , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Prognóstico , Glutationa/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Bases de Dados Genéticas , Ativação de Macrófagos/genética , Perfilação da Expressão Gênica , Biomarcadores Tumorais/genética , Feminino
9.
Int J Biol Macromol ; 268(Pt 1): 131628, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38631577

RESUMO

MicroRNAs (miRNAs) play important roles in plant defense against various pathogens. ε-poly-l-lysine (ε-PL), a natural anti-microbial peptide produced by microorganisms, effectively suppresses tobacco mosaic virus (TMV) infection. To investigate the anti-viral mechanism of ε-PL, the expression profiles of miRNAs in TMV-infected Nicotiana tabacum after ε-PL treatment were analyzed. The results showed that the expression levels of 328 miRNAs were significantly altered by ε-PL. Degradome sequencing was used to identify their target genes. Integrative analysis of miRNAs target genes and gene-enriched GO/KEGG pathways indicated that ε-PL regulates the expression of miRNAs involved in critical pathways of plant hormone signal transduction, host defense response, and plant pathogen interaction. Subsequently, virus induced gene silencing combined with the short tandem targets mimic technology was used to analyze the function of these miRNAs and their target genes. The results indicated that silencing miR319 and miR164 reduced TMV accumulation in N. benthamiana, indicating the essential roles of these miRNAs and their target genes during ε-PL-mediated anti-viral responses. Collectively, this study reveals that microbial source metabolites can inhibit plant viruses by regulating crucial host miRNAs and further elucidate anti-viral mechanisms of ε-PL.

10.
Front Oncol ; 14: 1355454, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38482208

RESUMO

Background and aims: With the rapid growth of artificial intelligence (AI) applications in various fields, understanding its impact on liver cancer research is paramount. This scientometrics project aims to investigate publication trends and topics in AI-related publications in liver cancer. Materials and Methods: We employed a search strategy to identify AI-related publications in liver cancer using Scopus database. We analyzed the number of publications, author affiliations, and journals that publish AI-related publications in liver cancer. Finally, the publications were grouped based on intended application. Results: We identified 3950 eligible publications (2695 articles, 366 reviews, and 889 other document types) from 1968 to August 3, 2023. There was a 12.7-fold increase in AI-related publications from 2013 to 2022. By comparison, the number of total publications on liver cancer increased by 1.7-fold. Our analysis revealed a significant shift in trends of AI-related publications on liver cancer in 2019. We also found a statistically significant consistent increase in numbers of AI-related publications over time (tau = 0.756, p < 0.0001). Eight (53%) of the top 15 journals with the most publications were radiology journals. The largest number of publications were from China (n=1156), the US (n=719), and Germany (n=236). The three most common publication categories were "medical image analysis for diagnosis" (37%), "diagnostic or prognostic biomarkers modeling & bioinformatics" (19%), and "genomic or molecular analysis" (18%). Conclusion: Our study reveals increasing interest in AI for liver cancer research, evidenced by a 12.7-fold growth in related publications over the past decade. A common application of AI is in medical imaging analysis for various purposes. China, the US, and Germany are leading contributors.

11.
Virology ; 594: 110061, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38518441

RESUMO

The occurrence of geminiviruses causes significant economic losses in many economically important crops. In this study, a novel geminivirus isolated from tobacco in Sichuan province of China, named tomato leaf curl Chuxiong virus (TLCCxV), was characterized by small RNA-based deep sequencing. The full-length of TLCCxV genome was determined to be 2744 nucleotides (nt) encoding six open reading frames. Phylogenetic and genome-wide pairwise identity analysis revealed that TLCCxV shared less than 91% identities with reported geminiviruses. A TLCCxV infectious clone was constructed and successfully infected Nicotiana benthamiana, N. tabacum, N. glutinosa, Solanum lycopersicum and Petunia hybrida plants. Furthermore, expression of the V2, C1 and C4 proteins through a potato virus X vector caused severe chlorosis or necrosis symptom in N. benthamiana. Taken together, we identified a new geminivirus in tobacco plants, and found that V2, C1 and C4 contribute to symptom development.


Assuntos
Begomovirus , Geminiviridae , Geminiviridae/genética , Nicotiana , Filogenia , Virulência , Doenças das Plantas , Begomovirus/genética , China
12.
Urol Oncol ; 42(5): 144-154, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38485644

RESUMO

Prostatic acinar adenocarcinoma accounts for approximately 95% of prostate cancer (CaP) cases. The remaining 5% of histologic subtypes of CaP are known to be more aggressive and have recently garnered substantial attention. These histologic subtypes - namely, prostatic ductal adenocarcinoma (PDA), intraductal carcinoma of the prostate (IDC-P), and cribriform carcinoma of the prostate (CC-P) - typically exhibit distinct growth characteristics, genomic features, and unique oncologic outcomes. For example, PTEN mutations, which cause uncontrolled cell growth, are frequently present in IDC-P and CC-P. Germline mutations in homologous DNA recombination repair (HRR) genes (e.g., BRCA1, BRCA2, ATM, PALB2, and CHEK2) are discovered in 40% of patients with IDC-P, while only 9% of patients without ductal involvement had a germline mutation. CC-P is associated with deletions in common tumor suppressor genes, including PTEN, TP53, NKX3-1, MAP3K7, RB1, and CHD1. Evidence suggests abiraterone may be superior to docetaxel as a first-line treatment for patients with IDC-P. To address these and other critical pathological attributes, this review examines the molecular pathology, genetics, treatments, and oncologic outcomes associated with CC-P, PDA, and IDC-P with the objective of creating a comprehensive resource with a centralized repository of information on PDA, IDC-P, and CC-P.


Assuntos
Adenocarcinoma , Neoplasias da Próstata , Masculino , Humanos , Próstata/patologia , Adenocarcinoma/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia , Neoplasias da Próstata/patologia , Proliferação de Células
13.
Phytomedicine ; 127: 155476, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38430586

RESUMO

BACKGROUND: Herpes simplex virus type 1 (HSV-1)-induced herpes simplex encephalitis (HSE) has a high mortality rate in clinically immunocompromised patients, while recovered patients often experience neurological sequelae due to neuroinflammation. Nucleoside drugs and nucleoside analogues such as acyclovir and ganciclovir are mainly used in clinical treatment, and the emergence of resistant viral strains makes the development of new anti-herpesvirus encephalitis drugs urgent. Resveratrol is a multifunctional, plant-derived bioactive compound and its antiviral potential is attracting much attention. PURPOSE: This study aimed to investigate the anti-HSV-1 mechanism of resveratrol in microglial cells and in the HSE mouse model. METHODS: The antiviral effect of resveratrol on HSV-1 infection was investigated by plaque assay, virus titer, immunofluorescence, Western blot and time-of-addition assay. The influence of resveratrol on stimulator of interferon gene (STING)/Nuclear Factor kappa B (NF-κB) signaling pathway-mediated neuroinflammation was examined by Western blot, RT-qPCR and ELISA. The interaction between resveratrol and STING/heat shock protein 90 beta (HSP90ß) was evaluated by molecular modeling, co-immunoprecipitation, and drug affinity responsive target stability assay. The therapeutic effect of resveratrol on HSE was evaluated in the HSE mouse model by analyzing weight loss, neurodegenerative symptoms and histopathological scores. RESULTS: Resveratrol inhibited the early process of HSV-1 infection, and interfered with the STING/NF-κB signaling pathway to attenuate HSV-1-induced neuroinflammation and microglial M1 polarization, independent of its classical target Sirtuin1. Mechanistically, resveratrol completely bound to Glu515 and Lys491 of HSP90ß, thus disrupting the HSP90ß-STING interaction and promoting STING degradation. Resveratrol also significantly alleviated viral encephalitis and neuroinflammation caused by HSV-1 in the HSE mouse model. CONCLUSION: Resveratrol acted as a non-classical HSP90ß inhibitor, binding to the STING-HSP90ß interaction site to promote STING degradation and attenuate HSV-1-induced encephalitis and neuroinflammation. These findings suggest the alternative strategy of targeting HSP90ß and resveratrol-mediated inhibition of HSP90ß as a potential antiviral approach.


Assuntos
Encefalite por Herpes Simples , Herpes Simples , Herpesvirus Humano 1 , Animais , Camundongos , Humanos , Encefalite por Herpes Simples/tratamento farmacológico , Encefalite por Herpes Simples/diagnóstico , Antivirais/farmacologia , Antivirais/uso terapêutico , Resveratrol/farmacologia , Resveratrol/uso terapêutico , NF-kappa B/metabolismo , Doenças Neuroinflamatórias , Herpes Simples/tratamento farmacológico
14.
Biochem Pharmacol ; 222: 116111, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38458329

RESUMO

Bladder cancer (BC) is the most common cancer of the urinary tract, with poor survival, high recurrence rates, and lacking of targeted drugs. In this study, we constructed a library to screen compounds inhibiting bladder cancer cells growth. Among them, SRT1720 was identified to inhibit bladder cancer cell proliferation in vitro and in vivo. SRT1720 treatment also suppressed bladder cancer cells migration, invasion and induced apoptosis. Mechanism studies shown that SRT1720 promoted autophagosomes accumulation by inducing early-stage autophagy but disturbed the late-stage of autophagy by blocking fusion of autophagosomes and lysosomes. SRT1720 appears to induce autophagy related proteins expression and alter autophagy-related proteins acetylation to impede the autophagy flux. LAMP2, an important lysosomal associated membrane protein, may mediate SRT1720-inhibited autophagy flux as SRT1720 treatment significantly deacetylated LAMP2 which may influence its activity. Taken together, our results demonstrated that SRT1720 mediated apoptosis and autophagy flux inhibition may be a novel therapeutic strategy for bladder cancer treatment.


Assuntos
Autofagia , Neoplasias da Bexiga Urinária , Humanos , Autofagossomos/metabolismo , Compostos Heterocíclicos de 4 ou mais Anéis/metabolismo , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/metabolismo , Apoptose , Lisossomos/metabolismo
15.
J Vis Exp ; (205)2024 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-38513228

RESUMO

This corrects the article 10.3791/66075.

16.
World J Urol ; 42(1): 114, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38431764

RESUMO

BACKGROUND: The factors influencing fluid absorption in mini-percutaneous nephrolithotripsy (mini-PCNL) are still unknown. We aim to investigate the factors that influence irrigation fluid absorption during mini-PCNL. METHODS: A total of 94 patients who underwent mini-PCNL were included in this prospective study. The endoscopic surgical monitoring system (ESMS) was used to measure the volume of irrigation fluid absorbed during the procedure. Irrigating time, the total volume of irrigation fluid, stone size, S.T.O.N.E. score, hemoglobin, electrolyte levels, and postoperative complications were recorded. RESULTS: A significant correlation was observed between fluid absorption and the presence of postoperative fever, and based on this phenomenon, patients were divided into low and high fluid absorption groups. The serum creatinine level in the high fluid absorption group was significantly high (7 vs. 16.5, p = 0.02). Significant differences were observed between the low and high fluid absorption groups in terms of mean stone size (21.70 mm vs. 26.78 mm), presence of stone burden ≥ 800 mm2 (4% vs. 23%), S.T.O.N.E. score > 8 (4% vs. 38%), the fluid used > 18,596 ml (19% vs. 78%), irrigation time (55.61 min vs. 91.28 min), and perfusion rate (24% vs. 45%) (all p < 0.05). The rates of postoperative fever and SIRS in the high fluid absorption group were significantly high (p < 0.05). CONCLUSIONS: Mean stone size, presence of stone burden ≥ 800 mm2, S.T.O.N.E. score > 8, the fluid used > 18596 mL, irrigation time, and perfusion rate are risk factors of intraoperative fluid absorption in mini-PCNL.


Assuntos
Cálculos Renais , Litotripsia , Nefrostomia Percutânea , Humanos , Estudos Prospectivos , Nefrostomia Percutânea/métodos , Cálculos Renais/terapia , Fatores de Risco , Resultado do Tratamento
17.
Artigo em Inglês | MEDLINE | ID: mdl-38548696

RESUMO

INTRODUCTION: The optimal management of blunt thoracic aortic injury (BTAI) remains controversial, with experienced centers offering therapy ranging from medical management to TEVAR. We investigated the utility of a machine learning (ML) algorithm to develop a prognostic model of risk factors on mortality in patients with BTAI. METHODS: The Aortic Trauma Foundation registry was utilized to examine demographics, injury characteristics, management and outcomes of patients with BTAI. A STREAMLINE (A Simple, Transparent, End-To-End Automated Machine Learning Pipeline Facilitating Data Analysis and Algorithm Comparison) model as well as logistic regression (LR) analysis with imputation using chained equations was developed and compared. RESULTS: From a total of 1018 patients in the registry, 702 patients were included in the final analysis. Of the 258 (37%) patients who were medically managed, 44 (17%) died during admission, 14 (5.4%) of which were aortic related deaths. 444 (63%) patients underwent TEVAR and 343 of which underwent TEVAR within 24 hours of admission. Amongst TEVAR patients, 39 (8.8%) patients died and 7 (1.6%) had aortic related deaths. (Table 1) Comparison of the STREAMLINE and LR model showed no significant difference in ROC curves and high AUCs of 0.869 (95% CI, 0.813 - 0.925) and 0.840 (95% CI, 0.779 - 0.900) respectively in predicting in-hospital mortality. Unexpectedly, however, the variables prioritized in each model differed between models (Figure 1A-B). The top three variables identified from the LR model were similar to that from existing literature. The STREAMLINE model, however, prioritized location of the injury along the lesser curve, age and aortic injury grade (Figure 1A). CONCLUSIONS: Machine learning provides insight on prioritization of variables not typically identified in standard multivariable logistic regression. Further investigation and validation in other aortic injury cohorts are needed to delineate the utility of ML models. LEVEL OF EVIDENCE: Level IIIStudy TypeOriginal research (prognostic/epidemiological).

18.
BMC Psychiatry ; 24(1): 210, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38500067

RESUMO

BACKGROUND: Current research has been focusing on non-suicidal self-injury (NSSI) behaviors among adolescents with depression. Although family intimacy and adaptability are considered protective factors for NSSI, evidence supporting this relationship is lacking. OBJECTIVE: This study aims to examine the mechanisms operating in the relationship between family intimacy and adaptability and NSSI behaviors among adolescents. METHODS: A self-administered general demographic information questionnaire, the Behavioral Functional Assessment Scale for Non-Suicidal Self-Injury, the Family Intimacy and Adaptability Scale, the Connor-Davidson Resilience Scale, and the Self-Assessment of Depression Scale were distributed among adolescents with depression in three tertiary hospitals in Jiangsu Province. RESULTS: The relationship between family intimacy and adaptability and NSSI was assessed among 596 adolescents with depression. The results revealed the following: (1) Family intimacy and adaptability were negatively correlated with NSSI behavior. (2) Psychological resilience and depression levels acted as chain mediators in the relationship between family intimacy and adaptability and NSSI behavior. CONCLUSIONS: Enhancing psychological resilience, controlling depressive symptoms, and reducing depression severity among adolescents by improving their family intimacy and adaptability are conducive to preventing and mitigating their NSSI behaviors.


Assuntos
Resiliência Psicológica , Comportamento Autodestrutivo , Adolescente , Humanos , Análise de Mediação , Comportamento Autodestrutivo/psicologia , Testes Psicológicos
19.
Obes Surg ; 34(5): 1717-1725, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38507149

RESUMO

PURPOSE: To evaluate the influence of anisodamine injection at the Zusanli (ST36) on early postoperative recovery quality in patients who have undergone laparoscopic sleeve gastrectomy. MATERIALS AND METHODS: 141 patients undergoing laparoscopic sleeve gastrectomy were randomly divided into the control group (group C), the normal saline group (group S) and the anisodamine group (group A). Acupuncture point injections were administered after induction of general anesthesia. The quality of recovery-40 questionnaire (QoR-40) scores were documented preoperatively (D0) and on the 1st (D1), 3rd (D3) and 7th (D7) days postoperatively. Additional metrics included: the numerical rating scale (NRS) for pain, postoperative nausea and vomiting (PONV), assessment and analgesic consumption 24-h post-extubation and the initial postoperative times for ambulation and anal exhaust. Substance P (SP), ß-endorphin (ß-EP), motilin (MTL) and gastrin (GAS) were quantified at 24-h post-surgery. RESULTS: Compared with group C, group A demonstrated an elevation in QoR-40 scores and physical comfort dimensions during D1-3, and an increased pain scores during D1-7; group S exhibited an augmentation in QoR-40 scores and pain scores on D1 (p < 0.05). Compared with group S, group A improved QoR-40 scores on D1 and pain scores during D1-3 (p < 0.05). SP, ß-EP, MTL and GAS presented significant variances among the groups 24-h post-surgery (p < 0.05). There were significant differences between the groups in NRS pain scores and PONV scores at 24-h postoperatively, dosage of dizocin on the first postoperative day, and time to first anal defecation (p < 0.05). CONCLUSION: The administration of anisodamine via ST36 acupoint injections has been demonstrated to facilitate the recuperation of gastrointestinal functionality, to alleviate postoperative pain and nausea, and substantially to enhance the quality of early postoperative recovery.


Assuntos
Cirurgia Bariátrica , Laparoscopia , Obesidade Mórbida , Alcaloides de Solanáceas , Humanos , Náusea e Vômito Pós-Operatórios , Pontos de Acupuntura , Obesidade Mórbida/cirurgia , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle
20.
Small ; : e2310749, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308118

RESUMO

The unfavorable morphology and high crystallization temperature (Tc ) of inorganic perovskites pose a significant challenge to their widespread application in photovoltaics. In this study, an effective approach is proposed to enhance the morphology of cesium lead triiodide (CsPbI3 ) while lowering its Tc . By introducing dimethylammonium acetate into the perovskite precursor solution, a rapid nucleation stage is facilitated, and significantly enhances the crystal growth of the intermediate phase at low annealing temperatures, followed by a slow crystal growth stage at higher annealing temperatures. This results in a uniform and dense morphology in CsPbI3 perovskite films with enhanced crystallinity, simultaneously reducing the Tc from 200 to 150 °C. Applying this approach in positive-intrinsic-negative (p-i-n) inverted cells yields a high power conversion efficiency of 19.23%. Importantly, these cells exhibit significantly enhanced stability, even under stress at 85 °C.

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