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1.
Prostate ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38629249

RESUMO

BACKGROUND: KI67 is a well-known biomarker reflecting cell proliferation. We aim to elucidate the predictive role of KI67 in the efficacy of abiraterone for patients with advanced prostate cancer (PCa). METHODS: Clinicopathological data of 152 men with metastatic PCa, who received abiraterone therapy were retrospectively collected. The KI67 positivity was examined by immunohistochemistry using the prostate biopsy specimen. The predictive value of KI67 on the therapeutic efficacy of abiraterone was explored using Kaplan-Meier curve and Cox regression analysis. The endpoints included prostate-specific antigen (PSA) progression-free survival (PSA-PFS), radiographic PFS (rPFS), and overall survival (OS). RESULTS: In total, 85/152 (55.9%) and 67/152 (44.1%) cases, respectively, received abiraterone at metastatic hormone-sensitive (mHSPC) and castration-resistant PCa (mCRPC) stage. The median KI67 positivity was 20% (interquartile range: 10%-30%). Overall, KI67 rate was not correlated with PSA response. Notably, an elevated KI67-positive rate strongly correlated with unfavorable abiraterone efficacy, with KI67 ≥ 30% and KI67 ≥ 20% identified as the optimal cutoffs for prognosis differentiation in mHSPC (median PSA-PFS: 11.43 Mo vs. 26.43 Mo, p < 0.001; median rPFS: 16.63 Mo vs. 31.90 Mo, p = 0.003; median OS: 21.77 Mo vs. not reach, p = 0.005) and mCRPC (median PSA-PFS: 7.17 Mo vs. 12.20 Mo, p = 0.029; median rPFS: 11.67 Mo vs. 16.47 Mo, p = 0.012; median OS: 21.67 Mo vs. not reach, p = 0.073) patients, respectively. Multivariate analysis supported the independent predictive value of KI67 on abiraterone efficacy. In subgroup analysis, an elevated KI67 expression was consistently associated with unfavorable outcomes in the majority of subgroups. Furthermore, data from another cohort of 79 PCa patients with RNA information showed that those with KI67 RNA levels above the median had a significantly shorter OS than those below the median (17.71 vs. 30.72 Mo, p = 0.035). CONCLUSIONS: This study highlights KI67 positivity in prostate biopsy as a strong predictor of abiraterone efficacy in advanced PCa. These insights will assist clinicians in anticipating clinical outcomes and refining treatment decisions for PCa patients.

2.
Int J Surg ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38573063

RESUMO

BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a non-invasive technique that provides valuable insights into molecular profiles and tumor disease management. This study aimed to evaluate the prognostic significance of circulating tumor DNA (ctDNA) in urothelial carcinoma (UC) through a systematic review and meta-analysis. METHODS: A comprehensive search was conducted in MEDLINE, EMBASE, and the Cochrane Library from the inception to December 2023. Studies investigating the prognostic value of ctDNA in UC were included. Hazard ratios (HRs) of disease-free survival (DFS) and overall survival (OS) were extracted. Overall meta-analysis and subgroup exploration stratified by metastatic status, ctDNA sampling time, treatment type, and detection method was performed using the R software (version 4.2.2). RESULTS: A total of sixteen studies with 1725 patients were included. Fourteen studies assessed the association between baseline ctDNA status and patient outcomes. Patients with elevated ctDNA levels exhibited significantly worse DFS (HR=6.26; 95% CI, 3.71-10.58, P<0.001) and OS (HR=4.23; 95% CI, 2.72-6.57, P<0.001) regardless of metastatic status, ctDNA sampling time, treatment type and detection methods. Six studies evaluated the prognostic value of ctDNA dynamics in UC. Patients who showed a decrease or clearance in ctDNA levels during treatment or observation demonstrated more favorable DFS (HR=0.26, 95% CI, 0.17-0.41, P<0.001) and OS (HR=0.21, 95% CI, 0.11-0.38, P<0.001) compared to those who did not. The association remained consistent across the subgroup analysis based on metastatic status and detection methods. In the immune checkpoint inhibitor-treated setting, both lower baseline ctDNA level and ctDNA decrease during the treatment were significantly associated with more favorable oncologic outcomes. Furthermore, specific gene mutations such as FGFR3 identified in ctDNA also demonstrated predictive value in UC patients. CONCLUSION: This meta-analysis demonstrates a strong association of ctDNA status and its dynamic change with survival outcomes in UC, suggesting substantial clinical utility of ctDNA testing in prognosis prediction and decision making in this setting.

3.
Biochim Biophys Acta Mol Basis Dis ; 1870(5): 167157, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38582266

RESUMO

Statins are the first line of choice for the treatment for atherosclerosis, but their use can cause myotoxicity, a common side effect that may require dosage reduction or discontinuation. The exact mechanism of statin-induced myotoxicity is unknown. Previous research has demonstrated that the combination of idebenone and statin yielded superior anti-atherosclerotic outcomes. Here, we investigated the mechanism of statin-induced myotoxicity in atherosclerotic ApoE-/- mice and whether idebenone could counteract it. After administering simvastatin to ApoE-/- mice, we observed a reduction in plaque formation as well as a decrease in their exercise capacity. We observed elevated levels of lactic acid and creatine kinase, along with a reduction in the cross-sectional area of muscle fibers, an increased presence of ragged red fibers, heightened mitochondrial crista lysis, impaired mitochondrial complex activity, and decreased levels of CoQ9 and CoQ10. Two-photon fluorescence imaging revealed elevated H2O2 levels in the quadriceps, indicating increased oxidative stress. Proteomic analysis indicated that simvastatin inhibited the tricarboxylic acid cycle. Idebenone treatment not only further reduced plaque formation but also ameliorated the impaired exercise capacity caused by simvastatin. Our study represents the inaugural comprehensive investigation into the mechanisms underlying statin-induced myotoxicity. We have demonstrated that statins inhibit CoQ synthesis, impair mitochondrial complex functionality, and elevate oxidative stress, ultimately resulting in myotoxic effects. Furthermore, our research marks the pioneering identification of idebenone's capability to mitigate statin-induced myotoxicity by attenuating oxidative stress, thereby safeguarding mitochondrial complex functionality. The synergistic use of idebenone and statin not only enhances the effectiveness against atherosclerosis but also mitigates statin-induced myotoxicity.

4.
Anal Chem ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38656982

RESUMO

Electrochemiluminescence (ECL) imaging, a rapidly evolving technology, has attracted significant attention in the field of cellular imaging. However, its primary limitation lies in its inability to analyze the motion behaviors of individual particles in live cellular environments. In this study, we leveraged the exceptional ECL properties of quantum dots (QDs) and the excellent electrochemical properties of carbon dots (CDs) to develop a high-brightness ECL nanoprobe (CDs-QDs) for real-time ECL imaging between living cells. This nanoprobe has excellent signal-to-noise ratio imaging capabilities for the single-particle tracking (SPT) of biomolecules. Our finding elucidated the enhanced ECL mechanism of CDs-QDs in the presence of reactive oxygen species through photoluminescence, electrochemistry, and ECL techniques. We further tracked the movement of single particles on membrane nanotubes between live cells and confirmed that the ECL-based SPT technique using CD-QD nanoparticles is an effective approach for monitoring the transport behaviors of biomolecules on membrane nanotubes between live cells. This opens a promising avenue for the advancement of ECL-based single-particle detection and the dynamic quantitative imaging of biomolecules.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38432330

RESUMO

OBJECTIVE: This systematic review and meta-analysis aimed to quantitatively compare the effects of telerehabilitation and home-based exercise for shoulder disorders. DATA SOURCES: We conducted a search for eligible studies in PubMed, EMBASE, Web of Science, Cochrane Library, and MEDLINE databases following Preferred Reporting Items for Systematic Review and Meta-analyses guidelines. STUDY SELECTION: Independent reviewers selected randomized controlled trials that compared the effects of telerehabilitation and home-based exercise in individuals with shoulder disorders. DATA EXTRACTION: Two reviewers independently conducted data extraction and assessed the risk of bias using the Cochrane Risk of Bias tool. DATA SYNTHESIS: A total of 7 studies with 508 participants were included. Compared with home-based exercise, telerehabilitation showed superior improvements in range of motion (flexion: standardized mean difference [SMD] 0.35, 95% confidence interval [CI] 0.14 to 0.56; abduction: SMD 0.37, 95% CI 0.16 to 0.58; external rotation: SMD 0.43, 95% CI 0.22 to 0.64; internal rotation: SMD 0.33, 95% CI 0.08 to 0.58), functional outcomes (Shoulder Pain and Disability Index: SMD -0.37, 95% CI -0.61 to -0.12; shortened Disabilities of the Arm, Shoulder and Hand questionnaire: mean difference [MD] -4.51, 95% CI -8.70 to -0.32), and quality of life (EuroQol Five Dimensions Questionnaire: MD 0.04, 95% CI 0.01 to 0.07). Telerehabilitation was not different from home-based exercise in terms of pain relief (SMD -0.19, 95% CI -0.60 to 0.23). Subgroup analysis demonstrated that telerehabilitation provided significant pain relief when sustained for over 12 weeks (SMD -0.46, 95% CI -0.81 to -0.11). CONCLUSIONS: Telerehabilitation is more effective than home-based exercise in improving range of motion, functional outcomes, and quality of life for patients with shoulder disorders. Telerehabilitation significantly outperforms home-based exercise in relieving pain when continued for over 12 weeks.

6.
Clin Cancer Res ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38512114

RESUMO

PURPOSE: Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare and lethal subtype of kidney cancer. However, the optimal treatments and molecular correlates of benefits for FH-deficient RCC are currently lacking. EXPERIMENTAL DESIGN: A total of 91 patients with FH-deficient RCC from 15 medical centers between 2009 and 2022 were enrolled in this study. Genomic and bulk RNA sequencing (RNA-seq) were performed on 88 and 45 untreated FH-deficient RCCs, respectively. Single-cell RNA-seq was performed to identify biomarkers for treatment response. Main outcomes included disease-free survival (DFS) for localized patients, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) for metastatic patients. RESULTS: In the localized setting, we found that a cell cycle progression signature enabled to predict disease progression. In the metastatic setting, first-line immune checkpoint inhibitor plus tyrosine kinase inhibitor (ICI+TKI) combination therapy showed satisfactory safety and was associated with a higher ORR (43.2% vs. 5.6%), apparently superior PFS (median PFS: 17.3 vs. 9.6 months, P=0.016) and OS (median OS: not reached vs. 25.7 months, P=0.005) over TKI monotherapy. Bulk and single-cell RNA-seq data revealed an enrichment of memory and effect T cells in responders to ICI plus TKI combination therapy. Furthermore, we identified a signature of memory and effect T cells that was associated with the effectiveness of ICI plus TKI combination therapy. CONCLUSIONS: ICI plus TKI combination therapy may represent a promising treatment option for metastatic FH-deficient RCC. A memory/active T cell-derived signature is associated with the efficacy of ICI+TKI but necessitates further validation.

8.
iScience ; 27(4): 109394, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38510123

RESUMO

With the rapid development of quantum computing, a variety of quantum convolutional neural networks (QCNNs) are proposed. However, only 1/2n2 features of an n-qubits input are transferred to the next layer in a quantum pooling layer, which results in the accuracy reduction. To solve this problem, a QCNN with a degressive circuit is proposed. In order to enhance the ability of extracting global features, we remove the parameters sharing strategy in the quantum convolutional layer and design a quantum convolutional kernel with global eyesight. In addition, to prevent a sharp feature reduction, a degressive parameterized quantum circuit is adopted to construct the pooling layer. Then the Z-basis measurement is only performed on the first qubit to control the operations on other qubits. Compared with the state-of-the-art QCNN, i.e., hybrid quantum-classical convolutional neural network, the accuracy of our model increased by 0.9%, 1%, and 3%, respectively, in three tasks: quantum state classification, binary code recognition, and quaternary code recognition.

9.
Nano Lett ; 24(8): 2544-2552, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38349341

RESUMO

Labeling the genome and envelope of a virus with multicolor quantum dots (QDs) simultaneously enables real-time monitoring of viral uncoating and genome release, contributing to our understanding of virus infection mechanisms. However, current labeling techniques require genetic modification, which alters the virus's composition and infectivity. To address this, we utilized the CRISPR/Cas13 system and a bioorthogonal metabolic method to label the Japanese encephalitis virus (JEV) genome and envelopes with different-colored QDs in situ. This technique allows one-step two-color labeling of the viral envelope and intraviral genome with QDs harnessing virus infection. In combination with single-virus tracking, we visualized JEV uncoating and genome release in real time near the endoplasmic reticulum of live cells. This labeling strategy allows for real-time visualization of uncoating and genome release at the single-virus level, and it is expected to advance the study of other viral infection mechanisms.


Assuntos
Pontos Quânticos , Viroses , Vírus , Humanos , Envelope Viral/metabolismo , Proteínas do Envelope Viral
10.
Chemosphere ; 350: 141105, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38171394

RESUMO

The efficient biodegradation of volatile chlorinated hydrocarbons using microbial fuel cells (MFCs) offers a feasible approach for purifying waste gas and alleviating energy crises. However, power generation is limited by poor pollutant biodegradation and slow electron transfer. The bifunctional bacterium Acinetobacter sp. HY-99C was screened and used to improve the performance of a conventional MFC. The inoculation of strain HY-99C into the conventional MFC promoted the formation of a compact biofilm with high metabolic activity and an enriched bifunctional genus (Acinetobacter), which resulted in the accelerated decomposition of chlorinated aromatic compounds into biodegradable organic acids. This led to efficient chlorobenzene removal and power generation from the MFC, with a chlorobenzene elimination capacity of 70.8 g m-3 h-1 and power density of 89.6 mW m-2, which are improved over those of previously reported MFCs. This study provides novel insights into enhancing pollutant removal and power generation in MFCs.


Assuntos
Fontes de Energia Bioelétrica , Poluentes Ambientais , Fontes de Energia Bioelétrica/microbiologia , Gases , Bactérias , Clorobenzenos , Eletrodos , Eletricidade
11.
Comput Med Imaging Graph ; 112: 102336, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38244280

RESUMO

Rigid pre-registration involving local-global matching or other large deformation scenarios is crucial. Current popular methods rely on unsupervised learning based on grayscale similarity, but under circumstances where different poses lead to varying tissue structures, or where image quality is poor, these methods tend to exhibit instability and inaccuracies. In this study, we propose a novel method for medical image registration based on arbitrary voxel point of interest matching, called query point quizzer (QUIZ). QUIZ focuses on the correspondence between local-global matching points, specifically employing CNN for feature extraction and utilizing the Transformer architecture for global point matching queries, followed by applying average displacement for local image rigid transformation.We have validated this approach on a large deformation dataset of cervical cancer patients, with results indicating substantially smaller deviations compared to state-of-the-art methods. Remarkably, even for cross-modality subjects, it achieves results surpassing the current state-of-the-art.


Assuntos
Algoritmos , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos
12.
Sci Bull (Beijing) ; 69(4): 502-511, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-37993331

RESUMO

Viral envelope fusion with the host plasma membrane (PM) for genome release is a hallmark step in the life cycle of many enveloped viruses. This process is regulated by a complex network of biomolecules on the PM, but robust tools to precisely elucidate the dynamic mechanisms of virus-PM fusion events are still lacking. Here, we developed a quantitative single-virus tracking approach based on highly efficient dual-color labelling of viruses and batch trajectory analysis to achieve the spatiotemporal quantification of fusion events. This approach allows us to comprehensively analyze the membrane fusion mechanism utilized by pseudotyped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the single-virus level and precisely elucidate how the relevant biomolecules synergistically regulate the fusion process. Our results revealed that SARS-CoV-2 may promote the formation of supersaturated clusters of cholesterol to facilitate the initiation of the membrane fusion process and accelerate the viral genome release.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/metabolismo , Glicoproteína da Espícula de Coronavírus/genética , Membrana Celular/metabolismo , Fusão de Membrana
13.
Cancer Res ; 84(1): 154-167, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-37847513

RESUMO

Intraductal carcinoma of the prostate (IDC-P) is a lethal prostate cancer subtype that generally coexists with invasive high-grade prostate acinar adenocarcinoma (PAC) but exhibits distinct biological features compared with concomitant adenocarcinoma. In this study, we performed whole-exome, RNA, and DNA-methylation sequencing of IDC-P, concurrent invasive high-grade PAC lesions, and adjacent normal prostate tissues isolated from 22 radical prostatectomy specimens. Three evolutionary patterns of concurrent IDC-P and PAC were identified: early divergent, late divergent, and clonally distant. In contrast to those with a late divergent evolutionary pattern, tumors with clonally distant and early divergent evolutionary patterns showed higher genomic, epigenomic, transcriptional, and pathologic heterogeneity between IDC-P and PAC. Compared with coexisting PAC, IDC-P displayed increased expression of adverse prognosis-associated genes. Survival analysis based on an independent cohort of 505 patients with metastatic prostate cancer revealed that IDC-P carriers with lower risk International Society of Urological Pathology (ISUP) grade 1-4 adenocarcinoma displayed a castration-resistant free survival as poor as those with the highest risk ISUP grade 5 tumors that lacked concurrent IDC-P. Furthermore, IDC-P exhibited robust cell-cycle progression and androgen receptor activities, characterized by an enrichment of cellular proliferation-associated master regulators and genes involved in intratumoral androgen biosynthesis. Overall, this study provides a molecular groundwork for the aggressive behavior of IDC-P and could help identify potential strategies to improve treatment of IDC-P. SIGNIFICANCE: The genomic, transcriptomic, and epigenomic characterization of concurrent intraductal carcinoma and adenocarcinoma of the prostate deepens the biological understanding of this lethal disease and provides a genetic basis for developing targeted therapies.


Assuntos
Adenocarcinoma , Carcinoma Intraductal não Infiltrante , Neoplasias da Próstata , Masculino , Humanos , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Intraductal não Infiltrante/patologia , Próstata/patologia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Neoplasias da Próstata/patologia , Genômica , Gradação de Tumores
14.
Chem Soc Rev ; 53(2): 1058, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38116765

RESUMO

Correction for 'Virus-mimicking nanosystems: from design to biomedical applications' by Hao-Yang Liu et al., Chem. Soc. Rev., 2023, 52, 8481-8499, https://doi.org/10.1039/D3CS00138E.

15.
Cell Rep ; 42(12): 113563, 2023 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-38088929

RESUMO

The carcinogenesis and progression of hepatocellular carcinoma (HCC) are closely related to viral infection and intestinal bacteria. However, little is known about bacteria within the HCC tumor microenvironment. Here, we showed that intratumoral Mycoplasma hyorhinis (M. hyorhinis) promoted the initiation and progression of HCC by enhancing nuclear ploidy. We quantified M. hyorhinis in clinical tissue specimens of HCC and observed that patients with high M. hyorhinis load had poor prognosis. We found that gastrointestinal M. hyorhinis can retrogradely infect the liver through the oral-duodenal-hepatopancreatic ampulla route. We further found that the increases in mononuclear polyploidy and cancer stemness resulted from mitochondrial fission caused by intracellular M. hyorhinis. Mechanistically, M. hyorhinis infection promoted the decay of mitochondrial fusion protein (MFN) 1 mRNA in an m6A-dependent manner. Our findings indicated that M. hyorhinis infection promoted pathological polyploidization and suggested that Mycoplasma clearance with antibiotics or regulating mitochondrial dynamics might have the potential for HCC therapy.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Infecções por Mycoplasma , Mycoplasma hyorhinis , Mycoplasma , Humanos , Mycoplasma hyorhinis/genética , Mycoplasma hyorhinis/metabolismo , Infecções por Mycoplasma/metabolismo , Infecções por Mycoplasma/microbiologia , Infecções por Mycoplasma/patologia , Microambiente Tumoral
16.
ACS Biomater Sci Eng ; 9(12): 6567-6585, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-37956022

RESUMO

Photo-cross-linked hydrogels, which respond to light and induce structural or morphological transitions, form a microenvironment that mimics the extracellular matrix of native tissue. In the last decades, photo-cross-linked hydrogels have been widely used in cartilage and osteochondral tissue engineering due to their good biocompatibility, ease of fabrication, rapid in situ gel-forming ability, and tunable mechanical and degradable properties. In this review, we systemically summarize the different types and physicochemical properties of photo-cross-linked hydrogels (including the materials and photoinitiators) and explore the biological properties modulated through the incorporation of additives, including cells, biomolecules, genes, and nanomaterials, into photo-cross-linked hydrogels. Subsequently, we compile the applications of photo-cross-linked hydrogels with a specific focus on cartilage and osteochondral repair. Finally, current limitations and future perspectives of photo-cross-linked hydrogels are also discussed.


Assuntos
Cartilagem , Hidrogéis , Hidrogéis/química , Cartilagem/química , Cartilagem/metabolismo , Engenharia Tecidual , Matriz Extracelular
17.
Bioengineering (Basel) ; 10(11)2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-38002438

RESUMO

The detection of Coronavirus disease 2019 (COVID-19) is crucial for controlling the spread of the virus. Current research utilizes X-ray imaging and artificial intelligence for COVID-19 diagnosis. However, conventional X-ray scans expose patients to excessive radiation, rendering repeated examinations impractical. Ultra-low-dose X-ray imaging technology enables rapid and accurate COVID-19 detection with minimal additional radiation exposure. In this retrospective cohort study, ULTRA-X-COVID, a deep neural network specifically designed for automatic detection of COVID-19 infections using ultra-low-dose X-ray images, is presented. The study included a multinational and multicenter dataset consisting of 30,882 X-ray images obtained from approximately 16,600 patients across 51 countries. It is important to note that there was no overlap between the training and test sets. The data analysis was conducted from 1 April 2020 to 1 January 2022. To evaluate the effectiveness of the model, various metrics such as the area under the receiver operating characteristic curve, receiver operating characteristic, accuracy, specificity, and F1 score were utilized. In the test set, the model demonstrated an AUC of 0.968 (95% CI, 0.956-0.983), accuracy of 94.3%, specificity of 88.9%, and F1 score of 99.0%. Notably, the ULTRA-X-COVID model demonstrated a performance comparable to conventional X-ray doses, with a prediction time of only 0.1 s per image. These findings suggest that the ULTRA-X-COVID model can effectively identify COVID-19 cases using ultra-low-dose X-ray scans, providing a novel alternative for COVID-19 detection. Moreover, the model exhibits potential adaptability for diagnoses of various other diseases.

18.
Cancer Med ; 12(24): 22370-22380, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37986697

RESUMO

BACKGROUND: The mutational pattern of homologous recombination repair (HRR)-associated gene alterations in Chinese urothelial carcinoma (UC) necessitates comprehensive sequencing efforts, and the clinical implications of HRR gene mutations in UC remain to be elucidated. MATERIALS AND METHODS: We delineated the mutational landscape of 343 Chinese UC patients from West China Hospital and 822 patients from The Cancer Genome Atlas (TCGA) using next-generation sequencing (NGS). Data from 182 metastatic UC patients from MSK-IMPACT cohort were used to assess the association between HRR mutations and immunotherapy efficacy. Comprehensive transcriptomic analysis was performed to explore the impact of HRR mutations on tumor immune microenvironment. RESULTS: Among Chinese UC patients, 34% harbored HRR gene mutations, with BRCA2, ATM, BRCA1, CDK12, and RAD51C being the most prevalently mutated genes. Mutational signatures contributing to UC differed between patients with and without HRR mutations. Signature 22 for exposure to aristolochic acid was only observed in Chinese UC patients. The presence of HRR mutations was correlated with higher tumor mutational burden, neoantigen burden, and PD-L1 expression. Importantly, patients with HRR mutations exhibited significantly improved prognosis following immunotherapy compared to those without HRR mutations. CONCLUSIONS: Our findings provide valuable insights into the genomic landscape of Chinese UC patients and underscore the molecular rationale for utilizing immunotherapy in UC patients with HRR mutations.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/terapia , Reparo de DNA por Recombinação , Genes cdc , Mutação , Microambiente Tumoral/genética
19.
Front Microbiol ; 14: 1267404, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38029186

RESUMO

In the context of climate change and human factors, the drought problem is a particularly serious one, and environmental pollution caused by the abuse of chemical fertilizers and pesticides is increasingly serious. Endophytic fungi can be used as a protection option, which is ecologically friendly, to alleviate abiotic stresses on plants, promote plant growth, and promote the sustainable development of agriculture and forestry. Therefore, it is of great significance to screen and isolate endophytic fungi that are beneficial to crops from plants in special habitats. In this study, endophytic fungi were isolated from Cotoneaster multiflorus, and drought-tolerant endophytic fungi were screened by simulating drought stress with different concentrations of PEG-6000, and the growth-promoting effects of these drought-tolerant strains were evaluated. A total of 113 strains of endophytic fungi were isolated and purified from different tissues of C. multiflorus. After simulated drought stress, 25 endophytic fungi showed strong drought tolerance. After ITS sequence identification, they belonged to 7 genera and 12 species, including Aspergillus, Fusarium, Colletotrichum, Penicillium, Diaporthe, Geotrichum, and Metarhizium. According to the identification and drought stress results, 12 strains of endophytic fungi with better drought tolerance were selected to study their abilities of dissolving inorganic phosphorus and potassium feldspar powder and producing indole-3-acetic acid (IAA). It was found that the amount of dissolved phosphorus in 7 strains of endophytic fungi was significantly higher than that of CK, and the content of soluble phosphorus was 101.98-414.51 µg. ml-1; 6 endophytic fungi had significantly higher potassium solubilization than CK, and the content of water-soluble potassium ranged from 19.17 to 30.94 mg·l-1; 6 strains have the ability to produce IAA, and the yield of IAA ranged between 0.04 and 0.42 mg. ml-1. This study for the first time identified the existence of endophytic fungi with drought tolerance and growth-promoting function in C. multiflorus, which could provide new direction for plant drought tolerance and growth promotion fungi strain resources. It also provides a theoretical basis for the subsequent application of endophytic fungi of C. multiflorus in agricultural and forestry production to improve plant tolerance.

20.
Chem Soc Rev ; 52(24): 8481-8499, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-37929845

RESUMO

Nanomedicine, as an interdisciplinary discipline involving the development and application of nanoscale materials and technologies, is rapidly developing under the impetus of bionanotechnology and has attracted a great deal of attention from researchers. Especially, with the global outbreak of COVID-19, the in-depth investigation of the infection mechanism of the viruses has made the study of virus-mimicking nanosystems (VMNs) a popular research topic. In this review, we initiate with a brief historical perspective on the emergence and development of VMNs for providing a comprehensive view of the field. Next, we present emerging design principles and functionalization strategies for fabricating VMNs in light of viral infection mechanisms. Then, we describe recent advances in VMNs in biology, with a major emphasis on representative examples. Finally, we summarize the opportunities and challenges that exist in this field, hoping to provide new insights and inspiration to develop VMNs for disease diagnosis and treatment and to attract the interest of more researchers from different fields.


Assuntos
COVID-19 , Vírus , Humanos , Nanomedicina , COVID-19/diagnóstico
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