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1.
Environ Pollut ; 357: 124467, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38950850

RESUMO

The 31st FISU Summer World University Games (SWUG) was held in Chengdu, southwestern China, from July 22 to August 8, 2023. A series of control measures were carried out to ensure good air quality during the SWUG, providing an opportunity to investigate the atmospheric behaviors of light-absorbing aerosols under such a substantial disturbance caused by the control measures. To assess the impacts of emission controls on primary pollutants, a field campaign was conducted at a rural site in Chengdu to investigate the characterization of equivalent black carbon (eBC). The changes of eBC concentrations before, during, and after the SWUG were characterized. The sources of eBC were resolved, and the impacts of atmospheric processes on the absorption capacity were also investigated. During the SWUG, the eBC concentration decreased by 12.1 % and 25.3 % compared with those before and after the SWUG. A fossil fuel combustion (eBCff) and a biomass burning (eBCbb) originated eBC were resolved using the aethalometer model. Both eBCff and eBCbb decreased during the SWUG, indicating the effectiveness of control measures. After the SWUG, the influence of biomass burning emissions became more and more significant, and the contribution of brown carbon (BrC) to light absorption at 370-660 nm increased by 52, 19, 7, 6, and 17 % compared to those during the SWUG. As the biomass burning emitted aerosols aged, the absorption Ångström exponent and babs(BrC370nm) decreased gradually, which was mainly due to the photobleaching of the chromophores during the daytime. eBCff was mainly affected by strong wind, while high eBCbb concentration was mainly attributed to the gradual accumulation of biomass-burning emissions near the observation site. The results show the significant reduction of eBC with the implementation of the air pollution mitigation campaign, and provide insights on the impacts of atmospheric processes on BC optical properties during summertime.

2.
Echocardiography ; 41(7): e15876, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38980981

RESUMO

OBJECTIVES: To assess the ability of left atrial (LA) strain parameters to discriminate patients with elevated left atrial pressure (LAP) from patients with atrial fibrillation (AF). METHODS AND RESULTS: A total of 142 patients with non-valvular AF who underwent first catheter ablation (CA) between November 2022 and November 2023 were enrolled in the study. Conventional and speckle-tracking echocardiography (STE) were performed in all patients within 24 h before CA, and LAP was invasively measured during the ablation procedure. According to mean LAP, the study population was classified into two groups of normal LAP (LAP < 15 mmHg, n = 101) and elevated LAP (LAP ≥ 15 mmHg, n = 41). Compared with the normal LAP group, elevated LAP group showed significantly reduced LA reservoir strain (LASr) [9.14 (7.97-11.80) vs. 20 (13.59-26.96), p < .001], and increased LA filling index [9.60 (7.15-12.20) vs. 3.72 (2.17-5.82), p < .001], LA stiffness index [1.13 (.82-1.46) vs. .47 (.30-.70), p < .001]. LASr, LA filling index and LA stiffness index were independent predictors of elevated LAP after adjusted by the type of AF, EDT, E/e', mitral E, and peak acceleration rate of mitral E velocity. The receiver-operating characteristic curve (ROC) analysis showed LA strain parameters (area under curve [AUC] .794-.819) could provide similar or greater diagnostic accuracy for elevated LAP, as compared to conventional echocardiographic parameters. Furthermore, the novel algorithms built by LASr, LA stiffness index, LA filling index, and left atrial emptying fraction (LAEF), was used to discriminate elevated LAP in AF with good accuracy (AUC .880, accuracy of 81.69%, sensitivity of 80.49%, and specificity of 82.18%), and much better than 2016 ASE/EACVI algorithms in AF. CONCLUSION: In patients with AF, LA strain parameters could be useful to predict elevated LAP and non-inferior to conventional echocardiographic parameters. Besides, the novel algorithm built by LA strain parameters combined with conventional parameters would improve the diagnostic efficiency.


Assuntos
Fibrilação Atrial , Função do Átrio Esquerdo , Pressão Atrial , Ecocardiografia , Átrios do Coração , Humanos , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/cirurgia , Feminino , Masculino , Pessoa de Meia-Idade , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/fisiopatologia , Ecocardiografia/métodos , Pressão Atrial/fisiologia , Função do Átrio Esquerdo/fisiologia , Valor Preditivo dos Testes , Ablação por Cateter/métodos , Reprodutibilidade dos Testes , Idoso
3.
J Med Chem ; 67(13): 10848-10874, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38912753

RESUMO

Bifunctional conjugates targeting PD-L1/PARP7 were designed, synthesized, and evaluated for the first time. Compounds B3 and C6 showed potent activity against PD-1/PD-L1 interaction (IC50 = 0.426 and 0.342 µM, respectively) and PARP7 (IC50 = 2.50 and 7.05 nM, respectively). They also displayed excellent binding affinity with hPD-L1, approximately 100-200-fold better than that of hPD-1. Both compounds restored T-cell function, leading to the increase of IFN-γ secretion. In the coculture assay, B3 and C6 enhanced the killing activity of MDA-MB-231 cells by Jurkat T cells in a concentration-dependent manner. Furthermore, B3 and C6 displayed significant in vivo antitumor efficacy in a melanoma B16-F10 tumor mouse model, more than 5.3-fold better than BMS-1 (a PD-L1 inhibitor) and RBN-2397 (a PARP7i clinical candidate) at the dose of 25 mg/kg, without observable side effects. These results provide valuable insight and understanding for developing bifunctional conjugates for potential anticancer therapy.


Assuntos
Antineoplásicos , Antígeno B7-H1 , Imunoterapia , Humanos , Animais , Antígeno B7-H1/metabolismo , Antígeno B7-H1/antagonistas & inibidores , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Antineoplásicos/uso terapêutico , Imunoterapia/métodos , Linhagem Celular Tumoral , Camundongos Endogâmicos C57BL , Feminino , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/química , Inibidores de Poli(ADP-Ribose) Polimerases/síntese química , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/patologia , Melanoma Experimental/terapia
4.
Acta Pharm Sin B ; 14(6): 2786-2789, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38828158

RESUMO

The current status of clinical trials utilizing nanoparticle drug delivery system (NDDS) for brain tumors was summarized.Image 1.

5.
Fundam Res ; 4(1): 95-102, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38933850

RESUMO

Iconic memory and short-term memory are not only crucial for perception and cognition, but also of great importance to mental health. Here, we first showed that both types of memory could be improved by improving limiting processes in visual processing through perceptual learning. Normal adults were trained in a contrast detection task for ten days, with their higher-order aberrations (HOA) corrected in real-time. We found that the training improved not only their contrast sensitivity function (CSF), but also their iconic memory and baseline information maintenance for short-term memory, and the relationship between memory and CSF improvements could be well-predicted by an observer model. These results suggest that training the limiting component of a cognitive task with visual perceptual learning could improve visual cognition. They may also provide an empirical foundation for new therapies to treat people with poor sensory memory.

6.
Cancer Lett ; 597: 217021, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38876388

RESUMO

The purpose of this study was to present the preliminary results of the PLATFORM Study, which aimed to evaluate the effectiveness of precision treatment for rare tumors in China. This study involved a phase II, open-label, non-randomized, multi-arm, single-center clinical trial. Patients with advanced rare solid tumors, who had not responded to standard treatment, were enrolled. The primary objective was to assess the safety and efficacy of targeted therapies in patients with actionable genetic alterations and immune checkpoint inhibitors in patients lacking actionable genetic alterations. Out of the 922 cases screened, 107 patients underwent mutation detection, with a final enrollment of 64 cases for the study. Among these, 26 cases received targeted therapy, and 38 cases underwent immunotherapy. The study encompassed over 40 types of rare tumors. The overall objective response rate (ORR) was 7.0%, with a disease control rate (DCR) of 70%. Targeted therapy showed a higher ORR of 17.8% and a DCR of 100%. The median progression-free survival (PFS) was 4 months overall, with targeted therapy showing a median PFS of 5 months and immunotherapy showing a median PFS of 3 months. In conclusion, from this preliminary analysis, targeted therapy within the precision medicine framework demonstrated promising therapeutic potential for rare tumors. However, monotherapy immunotherapy exhibited limited efficacy, highlighting the challenges in overcoming tumor-specific variations. These findings underscore the importance of further research and the exploration of combination therapies to improve outcomes for patients with rare tumors.

7.
J Steroid Biochem Mol Biol ; 243: 106560, 2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38917955

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a debilitating and progressive lung disease with an unknown cause that has few treatment options. 18ß-Glycyrrhetinic acid (18ß-GA) is the main bioactive component in licorice, exhibiting anti-inflammatory and antioxidant effects, while also holding certain application value in the metabolism and regulation of steroids. In this study, we demonstrated that 18ß-GA effectively alleviates bleomycin (BLM)-induced IPF by inhibiting the TGF-ß1/JAK2/STAT3 signaling axis. In vivo experiments demonstrate that 18ß-GA significantly attenuates pulmonary fibrosis progression by reducing lung inflammation, improving lung function, and decreasing collagen deposition. In vitro experiments reveal that 18ß-GA inhibits the activation and migration of TGF-ß1-induced fibroblasts. Furthermore, it regulates the expression of vimentin, N-cadherin and E-cadherin proteins, thereby inhibiting TGF-ß1-induced epithelial-mesenchymal transition (EMT) in lung alveolar epithelial cells. Mechanistically, 18ß-GA ameliorates pulmonary fibrosis by modulating the TGF-ß1/JAK2/STAT3 signaling pathway in activated fibroblasts. Taken together, our findings demonstrate the potential and underlying mechanisms of 18ß-GA in ameliorating IPF, emphasizing its potential as a novel therapeutic drug for the treatment of this devastating disease.

8.
Mol Omics ; 20(6): 417-429, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38940931

RESUMO

Objective: this study evaluates the prognostic relevance of gene subtypes and the role of kinesin family member 2C (KIF2C) in lung cancer progression. Methods: high-expression genes linked to overall survival (OS) and progression-free interval (PFI) were selected from the TCGA-LUAD dataset. Consensus clustering analysis categorized lung adenocarcinoma (LUAD) patients into two subtypes, C1 and C2, which were compared using clinical, drug sensitivity, and immunotherapy analyses. A random forest algorithm pinpointed KIF2C as a prognostic hub gene, and its functional impact was assessed through various assays and in vivo experiments. Results: The study identified 163 key genes and distinguished two LUAD subtypes with differing OS, PFI, pathological stages, drug sensitivity, and immunotherapy response. KIF2C, highly expressed in the C2 subtype, was associated with poor prognosis, promoting cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), with knockdown reducing tumor growth in mice. Conclusion: The research delineates distinct LUAD subtypes with significant clinical implications and highlights KIF2C as a potential therapeutic target for personalized treatment in LUAD.


Assuntos
Adenocarcinoma de Pulmão , Transição Epitelial-Mesenquimal , Cinesinas , Neoplasias Pulmonares , Cinesinas/genética , Cinesinas/metabolismo , Humanos , Animais , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/metabolismo , Camundongos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Transição Epitelial-Mesenquimal/genética , Prognóstico , Regulação Neoplásica da Expressão Gênica , Proliferação de Células/genética , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Perfilação da Expressão Gênica , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Head Neck ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38887926

RESUMO

BACKGROUND: To establish and validate a machine learning model using pretreatment multiparametric magnetic resonance imaging-based radiomics data with clinical data to predict radiation-induced temporal lobe injury (RTLI) in patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT). METHODS: Data from 230 patients with NPC who received IMRT (130 with RTLI and 130 without) were randomly divided into the training (n = 161) and validation cohort (n = 69) with a ratio of 7:3. Radiomics features were extracted from pretreatment apparent diffusion coefficient (ADC) map, T2-weighted imaging (T2WI), and CE-T1-weighted imaging (CE-T1WI). T-test, spearman rank correlation, and least absolute shrinkage and selection operator (LASSO) algorithm were employed to identify significant radiomics features. Clinical features were selected with univariate and multivariate analyses. Radiomics and clinical models were constructed using multiple machine learning classifiers, and a clinical-radiomics nomogram that combined clinical with radiomics features was developed. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were drawn to compare and verify the predictive performances of the clinical model, radiomics model, and clinical-radiomics nomogram. RESULTS: A total of 5064 radiomics features were extracted, from which 52 radiomics features were selected to construct the radiomics signature. The AUC of the radiomics signature based on multiparametric MRI was 0.980 in the training cohort and 0.969 in the validation cohort, outperforming the radiomics signature only based on T2WI and CE-T1WI (p < 0.05), which highlighted the significance of the DWI sequence in the prediction of temporal lobe injury. The area under the curve (AUC) of the clinical model was 0.895 in the training cohort and 0.905 in the validation cohort. The nomogram, which integrated radiomics and clinical features, demonstrated an impressive AUC value of 0.984 in the validation set; however, no statistically significant difference was observed compared to the radiomics model. The calibration curve and decision curve analysis of the nomogram demonstrated excellent predictive performance and clinical feasibility. CONCLUSIONS: The clinical-radiomics nomogram, integrating clinical features with radiomics features derived from pretreatment multiparametric MRI, exhibits compelling predictive performance for RTLI in patients diagnosed with NPC.

10.
Gene ; 927: 148634, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38848880

RESUMO

BACKGROUND: B cell exhaustion (BEX) refers to the impairment of normal B cell functions and decreased proliferation capability. However, the prognostic value of BEX-related genes in bladder cancer (BLCA) remains unclear. METHODS: BLCA cases from TCGA were used for training, while GSE5287, GSE13507, GSE31684, and GSE32894 cohorts from GEO were used for external validation. BEX-related genes were identified through literature retrieval, unsupervised clustering, and genomic difference detection. Gene pairing, LASSO, random forest, and Cox regression were employed to construct a predictive model. B cell samples from scRNAseqDB, GSE111636, and IMvigor210 were utilized to explore immunoprofiles and the predictive ability of the model in immunotherapeutic response. Additionally, 21 pairs of BLCA and paracarcinoma samples from Nanfang Hospital were used to re-confirm our findings through RT-qPCR, immunofluorescence, and flow cytometry. RESULTS: 39 BEX-related genes were identified. A 4-gene-pair signature was constructed and served as a reliable prognostic predictor across multiple datasets (pooled HR = 2.32; 95 % CI = 1.81-2.98). The signature reflected the BEX statuses of B cells (FDR < 0.05) and showed promise in evaluating immunotherapeutic sensitivity (P < 0.001). In the local cohort, CD52, TUBB6, and CAV1 were down-regulated in BLCA tissues, while TGFBI, UBE2L6, TINAGL1, and IL32 were up-regulated (all P < 0.05). Furthermore, the infiltration levels of CD19 + CD52 + and CD19 + TUBB6 + B cells in paracarcinoma samples were higher than those in BLCA samples (all P < 0.05). CONCLUSION: A BEX-related gene signature was developed to predict prognosis and immunotherapeutic sensitivity in BLCA, providing valuable guidance for personalized treatment.

11.
Funct Integr Genomics ; 24(4): 118, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38935217

RESUMO

Lung adenocarcinoma (LUAD) has a malignant characteristic that is highly aggressive and prone to metastasis. There is still a lack of suitable biomarkers to facilitate the refinement of precision-based therapeutic regimens. We used a combination of 10 known clustering algorithms and the omics data from 4 dimensions to identify high-resolution molecular subtypes of LUAD. Subsequently, consensus machine learning-related prognostic signature (CMRS) was developed based on subtypes related genes and an integrated program framework containing 10 machine learning algorithms. The efficiency of CMRS was analyzed from the perspectives of tumor microenvironment, genomic landscape, immunotherapy, drug sensitivity, and single-cell analysis. In terms of results, through multi-omics clustering, we identified 2 comprehensive omics subtypes (CSs) in which CS1 patients had worse survival outcomes, higher aggressiveness, mRNAsi and mutation frequency. Subsequently, we developed CMRS based on 13 key genes up-regulated in CS1. The prognostic predictive efficiency of CMRS was superior to most established LUAD prognostic signatures. CMRS demonstrated a strong correlation with tumor microenvironmental feature variants and genomic instability generation. Regarding clinical performance, patients in the high CMRS group were more likely to benefit from immunotherapy, whereas low CMRS were more likely to benefit from chemotherapy and targeted drug therapy. In addition, we evaluated that drugs such as neratinib, oligomycin A, and others may be candidates for patients in the high CMRS group. Single-cell analysis revealed that CMRS-related genes were mainly expressed in epithelial cells. The novel molecular subtypes identified in this study based on multi-omics data could provide new insights into the stratified treatment of LUAD, while the development of CMRS could serve as a candidate indicator of the degree of benefit of precision therapy and immunotherapy for LUAD.


Assuntos
Adenocarcinoma de Pulmão , Imunoterapia , Neoplasias Pulmonares , Aprendizado de Máquina , Microambiente Tumoral , Humanos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/terapia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Prognóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Genômica , Multiômica
12.
Clin Pharmacol Ther ; 116(2): 415-425, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38751031

RESUMO

Bispecific T-cell engagers (bsTCEs) have emerged as a promising class of cancer immunotherapy. BsTCEs enable physical connections between T cells and tumor cells to enhance T-cell activity against cancer. Despite several marketing approvals, the development of bsTCEs remains challenging, especially at early clinical translational stages. The intricate design of bsTCEs makes their pharmacologic effects and safety profiles highly dependent on patient's immunological and tumor conditions. Such context-dependent pharmacology introduces considerable uncertainty into translational efforts. In this study, we developed a Quantitative Systems Pharmacology (QSP) model, through context unification, that can facilitate the translation of bsTCEs preclinical data into clinical activity. Through characterizing the formation dynamics of immunological synapse (IS) induced by bsTCEs, this model unifies a broad range of contexts related to target affinity, tumor characteristics, and immunological conditions. After rigorous calibration using both experimental and clinical data, the model enables consistent translation of drug potency observed under diverse experimental conditions into predictable exposure-response relationships in patients. Moreover, the model can help identify optimal target-binding affinities and minimum efficacious concentrations across different clinical contexts. This QSP approach holds significant promise for the future development of bsTCEs.


Assuntos
Anticorpos Biespecíficos , Neoplasias , Linfócitos T , Pesquisa Translacional Biomédica , Humanos , Linfócitos T/imunologia , Linfócitos T/efeitos dos fármacos , Pesquisa Translacional Biomédica/métodos , Anticorpos Biespecíficos/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Imunoterapia/métodos , Farmacologia em Rede , Sinapses Imunológicas/imunologia , Animais
14.
Urol Oncol ; 42(9): 275-287, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38806387

RESUMO

Prostate cancer (PCa) is one of the most common tumors affecting men all over the world. PCa has brought a huge health burden to men around the world, especially for elderly men, but its pathogenesis is unclear. In prostate cancer, epigenetic inheritance plays an important role in the development, progression, and metastasis of the disease. An important role in cancer invasion and metastasis is played by matrix metalloproteinases (MMPs), zinc-dependent proteases that break down extracellular matrix. We review two important forms of epigenetic modification and the role of matrix metalloproteinases in tumor regulation, both of which may be of significant value as novel biomarkers for early diagnosis and prognosis monitoring. The author considers that both mechanisms have promising therapeutic applications for therapeutic agent research in prostate cancer, but that efforts should be made to mitigate or eliminate the side effects of drug therapy in order to maximize quality of life of patients. The understanding of epigenetic modification, MMPs, and their inhibitors in the functional regulation of prostate cancer is gradually advancing, it will provide a new technical means for the prevention of prostate cancer, early diagnosis, androgen-independent prostate cancer treatment, and drug research.


Assuntos
Epigênese Genética , Metaloproteinases da Matriz , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Metaloproteinases da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz/uso terapêutico , Inibidores de Metaloproteinases de Matriz/farmacologia , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética
16.
Cell Mol Biol Lett ; 29(1): 65, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714951

RESUMO

The engineered clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein (Cas) system is currently widely applied in genetic editing and transcriptional regulation. The catalytically inactivated CasRx (dCasRx) has the ability to selectively focus on the mRNA coding region without disrupting transcription and translation, opening up new avenues for research on RNA modification and protein translation control. This research utilized dCasRx to create a translation-enhancement system for mammals called dCasRx-eIF4GI, which combined eukaryotic translation initiation factor 4G (eIF4GI) to boost translation levels of the target gene by recruiting ribosomes, without affecting mRNA levels, ultimately increasing translation levels of different endogenous proteins. Due to the small size of dCasRx, the dCasRx-eIF4GI translation enhancement system was integrated into a single viral vector, thus optimizing the delivery and transfection efficiency in subsequent applications. Previous studies reported that ferroptosis, mediated by calcium oxalate (CaOx) crystals, significantly promotes stone formation. In order to further validate its developmental potential, it was applied to a kidney stone model in vitro and in vivo. The manipulation of the ferroptosis regulatory gene FTH1 through single-guide RNA (sgRNA) resulted in a notable increase in FTH1 protein levels without affecting its mRNA levels. This ultimately prevented intracellular ferroptosis and protected against cell damage and renal impairment caused by CaOx crystals. Taken together, this study preliminarily validated the effectiveness and application prospects of the dCasRx-eIF4GI translation enhancement system in mammalian cell-based disease models, providing novel insights and a universal tool platform for protein translation research and future therapeutic approaches for nephrolithiasis.


Assuntos
Sistemas CRISPR-Cas , Oxalato de Cálcio , Rim , Animais , Humanos , Masculino , Camundongos , Oxalato de Cálcio/metabolismo , Sistemas CRISPR-Cas/genética , Fator de Iniciação Eucariótico 4G/metabolismo , Fator de Iniciação Eucariótico 4G/genética , Ferritinas , Ferroptose/genética , Edição de Genes/métodos , Células HEK293 , Rim/metabolismo , Rim/patologia , Cálculos Renais/genética , Cálculos Renais/metabolismo , Oxirredutases/metabolismo , Oxirredutases/genética , Biossíntese de Proteínas/genética , RNA Guia de Sistemas CRISPR-Cas/genética , RNA Guia de Sistemas CRISPR-Cas/metabolismo
17.
iScience ; 27(6): 109879, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38812554

RESUMO

Within the population of humans with otherwise normal vision, there exists some proportion whose ability to perceive depth from binocular disparity is poor or absent. The prevalence of this "stereo-anomaly" has been reported to be as small as 2%, or as great as 30%. We set out to investigate this discrepancy. We used a digital tool to measure stereoacuity in tasks requiring either the detection of disparity or the discrimination of the direction of disparity. In a cohort of 228 participants, we found that 98% were able to consistently perform the detection task. Of these, only 69% consistently performed the discrimination task. The 31% of participants who had difficulty with the discrimination task could further be divided into 17% who were consistently unable to perform the task and 14% who showed limited ability. This suggests that identification of the direction of disparity requires further processing beyond merely detecting its presence.

18.
BMC Cancer ; 24(1): 648, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802747

RESUMO

BACKGROUND: This study aimed to assess the long-term effect of level IIb clinical target volume (CTV) optimisation on survival, xerostomia, and dysphagia in patients with nasopharyngeal carcinoma (NPC). METHODS: Clinical data of 415 patients with NPC treated with intensity-modulated radiotherapy between December 2014 and October 2018 were retrospectively analysed. The patients were categorised into modified and comparison groups. Late xerostomia and dysphagia were evaluated using Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer scoring. Survival analysis was performed using the Kaplan-Meier method. Differences in late toxicity and dose parameters between both groups were compared. Prognostic factors for survival and late toxicity were assessed using regression analyses. RESULTS: Patients in the modified group developed late xerostomia and dysphagia less frequently than those in the comparison group did (P < 0.001). The mean dose (Dmean) and V26 of parotid glands; Dmean and V39 of submandibular glands; and Dmean of sublingual glands, oral cavity, larynx, and superior, middle, and lower pharyngeal constrictor muscles were lower in the modified group than those in the comparison group (all P < 0.001). Both groups had no significant differences in overall, local recurrence-free, distant metastasis-free, or progression-free survival. The Dmean of the parotid and sublingual glands was a risk factor for xerostomia. The Dmean of the parotid and sublingual glands and middle pharyngeal constrictor muscle was a risk factor for dysphagia. CONCLUSIONS: Level IIb optimisation in NPC patients who meet certain criteria specially the exclusion of positive retropharyngeal nodes treated with intensity-modulated radiotherapy has the potential to better protect the salivary and swallowing structures, decreasing the development of late radiation-induced xerostomia and dysphagia while maintaining long-term survival.


Assuntos
Transtornos de Deglutição , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Radioterapia de Intensidade Modulada , Xerostomia , Humanos , Transtornos de Deglutição/etiologia , Masculino , Xerostomia/etiologia , Feminino , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/complicações , Carcinoma Nasofaríngeo/patologia , Pessoa de Meia-Idade , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos , Seguimentos , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/complicações , Adulto , Idoso , Lesões por Radiação/etiologia , Lesões por Radiação/prevenção & controle , Deglutição , Glândulas Salivares/efeitos da radiação , Glândulas Salivares/patologia , Glândulas Salivares/diagnóstico por imagem , Dosagem Radioterapêutica , Prognóstico , Adulto Jovem
19.
EClinicalMedicine ; 72: 102622, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38745965

RESUMO

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

20.
Plant Physiol Biochem ; 211: 108694, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38714131

RESUMO

Using natural clinoptilolite (NCP) as a carrier and alginate (Alg)-calcium as an active species, the porous silicon calcium alginate nanocomposite (Alg-Ca-NCP) was successfully fabricated via adsorption-covalence-hydrogen bond. Its structural features and physicochemical properties were detailed investigated by various characterizations. The results indicated that Alg-Ca-NCP presented the disordered lamellar structures with approximately uniform particles in size of 300-500 nm. Specially, their surface fractal evolutions between the irregular roughness and dense structures were demonstrated via the SAXS patterns. The results elucidated that the abundant micropores of NCP were beneficial for unrestricted diffusing of Alg-Ca, which was conducive to facilitate a higher loading and sustainable releasing. The Ca content of leaf mustard treated with Alg-Ca-NCP-0.5 was 484.5 mg/100g on the 21st day, higher than that by water (CK) and CaCl2 solution treatments, respectively. Meanwhile, the prepared Alg-Ca-NCPs presented the obvious anti-aging effects on peroxidase drought stress of mustard leaves. These demonstrations provided a simple and effective method to synthesize Alg-Ca-NCPs as delivery nanocomposites, which is useful to improve the weak absorption and low utilization of calcium alginate by plants.


Assuntos
Alginatos , Mostardeira , Zeolitas , Alginatos/química , Alginatos/farmacologia , Zeolitas/química , Zeolitas/farmacologia , Mostardeira/metabolismo , Mostardeira/efeitos dos fármacos , Mostardeira/química , Folhas de Planta/metabolismo , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/química , Porosidade , Brassica/metabolismo , Brassica/efeitos dos fármacos , Brassica/crescimento & desenvolvimento , Ácido Glucurônico/química , Nanocompostos/química , Difração de Raios X , Ácidos Hexurônicos/química , Ácidos Hexurônicos/metabolismo
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