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1.
Cancer Sci ; 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39038928

RESUMO

Sorafenib, an anticancer drug, has been shown to induce ferroptosis in cancer cells. However, resistance to sorafenib greatly limits its therapeutic efficacy, and the exact mechanism of resistance is not fully understood. This study investigated the role of N-Acetyltransferase 10 (NAT10) in influencing the anticancer activity of sorafenib in nasopharyngeal carcinoma (NPC) and its molecular mechanism. NAT10 expression was significantly upregulated in NPC. Mechanistically, NAT10 promotes proteins of solute carrier family 7 member 11 (SLC7A11) expression through ac4C acetylation, inhibiting sorafenib-induced ferroptosis in NPC cells. The combined application of sorafenib and the NAT10 inhibitor remodelin significantly inhibits SLC7A11 expression and promotes ferroptosis in NPC cells. In vivo knockout of NAT10 inhibited the growth of sorafenib-resistant NPC. Our findings suggest that NAT10 inhibition might be a promising therapeutic approach to enhance the anticancer activity of sorafenib.

2.
Environ Geochem Health ; 46(9): 350, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39073511

RESUMO

Dissolved organic matter (DOM), a pivotal component in the global carbon cycle, plays a crucial role in maintaining the productivity and functionality of aquatic ecosystems. However, the driving factors of variations in the properties of riverine DOM in tropical islands still remain unclear. In this study, the spatiotemporal response of the optical characteristics of riverine DOM to seasonality and land use on Hainan Island in southern China was investigated. Our results revealed that DOM in the rivers of Hainan Island exhibited a relatively high proportion of fulvic acid and demonstrated strong terrestrial sources. The optical properties of DOM exhibited significant variations both seasonally and spatially. Land use exerted a dominant influence on riverine DOM. Specifically, during the wet season, riverine DOM exhibited larger molecular weight, increased chromophoric DOM (CDOM) abundance, and higher Fmax compared to the dry season. Furthermore, riverine DOM influenced by grassland and farmland showed higher CDOM abundance, Fmax, and humification degree in contrast to those impacted by forest and urban. Random forest and correlation analysis results indicated that grassland and farmland enhanced the Fmax of DOM by increasing levels of TP, NO3--N, Chl a, and NH4+-N in the dry season. However, during the wet season, the increased Fmax of DOM induced by grassland and farmland relied on the increments of Chl a and TP concentrations. This study improves our understanding of the spatiotemporal fluctuations of DOM in the rivers of Hainan Island, highlighting the effects of season and land use on DOM. It offers valuable support for improving water quality and contributes to enhancing human comprehension of the global carbon cycle.


Assuntos
Monitoramento Ambiental , Rios , Estações do Ano , Rios/química , China , Monitoramento Ambiental/métodos , Ilhas , Clima Tropical , Análise Espaço-Temporal , Substâncias Húmicas/análise , Agricultura , Compostos Orgânicos/análise , Benzopiranos/análise
3.
Surg Open Sci ; 20: 98-100, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39006205

RESUMO

Subcutaneous injection of unfractionated heparin (UH) or low molecular weight heparin (LMWH) is frequently utilized for venous thromboembolism chemoprophylaxis. We previously discovered that nurses believe patients experience more pain with UH compared to the LMWH enoxaparin; however, no published studies that are appropriately powered exist comparing pain associated with subcutaneous chemoprophylaxis. Our objective was to assess if differences exist in pain associated with subcutaneous administration of UH and enoxaparin. We conducted an observational study of patients who underwent major abdominal surgery between 11/2017-4/2019. All patients received one of three prophylactic regimens: (1) UH only, (2) Initial dose of UH followed by enoxaparin, or (3) enoxaparin only. Of the 74 patients observed, 40 patients received UH followed by enoxaparin, 17 received UH only, and 17 received enoxaparin only. There was a significant difference in patients' mean perceived pain between subcutaneous UH and enoxaparin injections (mean post-injection pain after UH 3.3 vs. enoxaparin 1.5; p < 0.001). There was no significant difference in perceived pain for patients who received consecutive UH or enoxaparin injections. Differences in pain associated with different chemoprophylaxis agents may be an unrecognized driver of patient refusals of VTE chemoprophylaxis and may lead to worse VTE outcomes.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38889040

RESUMO

High-fidelity online 3D scene reconstruction from monocular videos continues to be challenging, especially for coherent and fine-grained geometry reconstruction. The previous learning-based online 3D reconstruction approaches with neural implicit representations have shown a promising ability for coherent scene reconstruction, but often fail to consistently reconstruct fine-grained geometric details during online reconstruction. This paper presents a new on-the-fly monocular 3D reconstruction approach, named GP-Recon, to perform high-fidelity online neural 3D reconstruction with fine-grained geometric details. We incorporate geometric prior (GP) into a scene's neural geometry learning to better capture its geometric details and, more importantly, propose an online volume rendering optimization to reconstruct and maintain geometric details during the online reconstruction task. The extensive comparisons with state-of-the-art approaches show that our GP-Recon consistently generates more accurate and complete reconstruction results with much better fine-grained details, both quantitatively and qualitatively.

5.
Kaohsiung J Med Sci ; 40(7): 631-641, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38826147

RESUMO

Autophagy is a self-recycling machinery to maintain cellular homeostasis by degrading harmful materials in the cell. Autophagy-related gene 5 (Atg5) is required for autophagosome maturation. However, the role of Atg5 in tumorigenesis under autophagy deficient conditions remains unclear. This study focused on the autophagy-independent role of Atg5 and the underlying mechanism in tumorigenesis. We demonstrated that knockout of autophagy-related genes including Atg5, Atg7, Atg9, and p62 in mouse embryonic fibroblast (MEF) cells consistently decreased cell proliferation and motility, implying that autophagy is required to maintain diverse cellular functions. An Atg7 knockout MEF (Atg7-/- MEF) cell line representing deprivation of autophagy function was used to clarify the role of Atg5 transgene in tumorigenesis. We found that Atg5-overexpressed Atg7-/-MEF (clone A) showed increased cell proliferation, colony formation, and migration under autophagy deficient conditions. Accordingly, rescuing the autophagy deficiency of clone A by overexpression of Atg7 gene shifts the role of Atg5 from pro-tumor to anti-tumor status, indicating the dual role of Atg5 in tumorigenesis. Notably, the xenograft mouse model showed that clone A of Atg5-overexpressed Atg7-/- MEF cells induced temporal tumor formation, but could not prolong further tumor growth. Finally, biomechanical analysis disclosed increased Wnt5a secretion and p-JNK expression along with decreased ß-catenin expression. In summary, Atg5 functions as a tumor suppressor to protect the cell under normal conditions. In contrast, Atg5 shifts to a pro-tumor status under autophagy deprivation conditions.


Assuntos
Proteína 5 Relacionada à Autofagia , Proteína 7 Relacionada à Autofagia , Autofagia , Carcinogênese , Proliferação de Células , Animais , Autofagia/genética , Proteína 5 Relacionada à Autofagia/genética , Proteína 5 Relacionada à Autofagia/metabolismo , Camundongos , Proteína 7 Relacionada à Autofagia/genética , Proteína 7 Relacionada à Autofagia/metabolismo , Carcinogênese/genética , Carcinogênese/patologia , Movimento Celular/genética , Humanos , Fibroblastos/metabolismo , Camundongos Knockout
6.
Microcirculation ; 31(5): e12853, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38690605

RESUMO

OBJECTIVE: Both low serum albumin (SA) concentration and coronary microvascular dysfunction (CMD) are risk factors for the development of heart failure (HF). We hypothesized that SA concentration is associated with myocardial flow reserve (MFR) and implicated in pathophysiological mechanism of HF. METHODS: We retrospectively studied 454 patients undergoing dynamic cardiac cadmium-zinc-telluride myocardial perfusion imaging from April 2018 to February 2020. The population was categorized into three groups according to SA level (g/dL): Group 1: >4, Group 2: 3.5-4, and Group 3: <3.5. Myocardial blood flow (MBF) and myocardial flow reserve (MFR, defined as stress/rest MBF ratio) were compared. RESULTS: The mean age of the whole cohort was 66.2 years, and 65.2% were men. As SA decreased, stress MBF (mL min-1 g-1) and MFR decreased (MBF: 3.29 ± 1.03, MFR: 3.46 ± 1.33 in Group 1, MBF: 2.95 ± 1.13, MFR: 2.51 ± 0.93 in Group 2, and MBF: 2.64 ± 1.16, MFR: 1.90 ± 0.50 in Group 3), whereas rest MBF (mL min-1 g-1) increased (MBF: 1.05 ± 0.42 in Group 1, 1.27 ± 0.56 in Group 2, and 1.41 ± 0.61 in Group 3). After adjusting for covariates, compared with Group 1, the odds ratios for impaired MFR (defined as MFR < 2.5) were 3.57 (95% CI: 2.32-5.48) for Group 2 and 34.9 (95% CI: 13.23-92.14) for Group 3. The results would be similar if only regional MFR were assessed. The risk prediction for CMD using SA was acceptable, with an AUC of 0.76. CONCLUSION: Low SA concentration was associated with the severity of CMD in both global and regional MFR as well as MBF.


Assuntos
Cádmio , Circulação Coronária , Telúrio , Tomografia Computadorizada de Emissão de Fóton Único , Zinco , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Zinco/sangue , Cádmio/sangue , Microcirculação , Imagem de Perfusão do Miocárdio/métodos , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico por imagem , Compostos de Zinco , Albumina Sérica
7.
Front Biosci (Landmark Ed) ; 29(5): 167, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38812318

RESUMO

BACKGROUND: Ovarian cancer is a highly lethal gynecologic malignancy. ARHGAP10, a member of Rho GTPase-activating proteins, is a potential tumor suppressor in ovarian cancer. However, its role and the involved mechanism need further examination. Here, we investigated whether ARHGAP10 is also associated with ferroptosis. METHODS: Lentivirus infection was used for gene overexpression or silencing. Real-time polymerase chain reaction (RT-PCR) and Western blot were used to assess mRNA and protein levels, respectively. Cell viability was assessed by Cell Counting Kit-8 (CCK-8) assay. Lipid reactive oxygen species level was measured by flow cytometry. A tumorigenicity assay was performed to evaluate tumor growth in vivo, and sections of mouse tumor tissues were examined by immunofluorescence microscopy. Chromatin Immunoprecipitation (ChIP) assay was used to assess the binding of H3K9ac to the promoter region of ARHGAP10. RESULTS: ARHGAP10 overexpression promoted ferroptosis in ovarian cancer cells, resulting in decreased cell viability, and increased lipid reactive oxygen species (ROS) level. Further, it decreased and increased GPX4 and PTGS2 expression, respectively, and also induced suppression of tumor growth in mice. Fer-1, a potent inhibitor of ferroptosis, suppressed the above effects of ARHGAP10. Contrarily, ARHGAP10 silencing alleviated ferroptosis in ovarian cancer cells, which was reversed by RSL3, a ferroptosis-inducing agent. Lastly, sodium butyrate (SB) was found to transcriptionally regulate ARHGAP10, thereby also contributing to the ferroptosis of ovarian cancer cells. CONCLUSIONS: Our results suggest that SB/ARHGAP10/GPX4 is a new signaling axis involved in inducing ferroptosis in ovarian cancer cells and suppressing tumor growth, which has potential clinical significance.


Assuntos
Ácido Butírico , Ferroptose , Proteínas Ativadoras de GTPase , Regulação Neoplásica da Expressão Gênica , Neoplasias Ovarianas , Espécies Reativas de Oxigênio , Ferroptose/efeitos dos fármacos , Ferroptose/genética , Feminino , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/tratamento farmacológico , Humanos , Animais , Proteínas Ativadoras de GTPase/genética , Proteínas Ativadoras de GTPase/metabolismo , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Ácido Butírico/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Camundongos , Camundongos Nus , Sobrevivência Celular/efeitos dos fármacos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética
9.
JAMA Netw Open ; 7(4): e246721, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38619839

RESUMO

Importance: Delayed appendicitis diagnosis is associated with worse outcomes. Appendicitis hospital care costs associated with delayed diagnosis are unknown. Objective: To determine whether delayed appendicitis diagnosis was associated with increased appendicitis hospital care costs. Design, Setting, and Participants: This cohort study used data from patients receiving an appendectomy aged 18 to 64 years in 5 states (Florida, Maryland, Massachusetts, New York, Wisconsin) that were captured in the Healthcare Cost and Utilization Project State Inpatient and Emergency Department databases for the years 2016 and 2017 with no additional follow-up. Data were analyzed January through April 2023. Exposures: Delayed diagnosis was defined as a previous emergency department or inpatient hospital encounter with an abdominal diagnosis other than appendicitis, and no intervention 7 days prior to appendectomy encounter. Main Outcomes and Measures: The main outcome was appendicitis hospital care costs. This was calculated from aggregated charges of encounters 7 days prior to appendectomy, the appendectomy encounter, and 30 days postoperatively. Cost-to-charge ratios were applied to charges to obtain costs, which were then adjusted for wage index, inflation to 2022 US dollar, and with extreme outliers winsorized. A multivariable Poisson regression estimated appendicitis hospital care costs associated with a delayed diagnosis while controlling for age, sex, race and ethnicity, insurance status, care discontinuity, income quartile, hospital size, teaching status, medical school affiliation, percentage of Black and Hispanic patient discharges, core-based statistical area, and state. Results: There were 76 183 patients (38 939 female [51.1%]; 2192 Asian or Pacific Islander [2.9%], 14 132 Hispanic [18.5%], 8195 non-Hispanic Black [10.8%], 46 949 non-Hispanic White [61.6%]) underwent appendectomy, and 2045 (2.7%) had a delayed diagnosis. Delayed diagnosis patients had median (IQR) unadjusted cost of $11 099 ($6752-$17 740) compared with $9177 ($5575-$14 481) for nondelayed (P < .001). Patients with delayed diagnosis had 1.23 times (95% CI, 1.16-1.28 times) adjusted increased appendicitis hospital care costs. The mean marginal cost of delayed diagnosis was $2712 (95% CI, $2083-$3342). Even controlling for delayed diagnosis, non-Hispanic Black patients had 1.22 times (95% CI, 1.17-1.28 times) the adjusted increased appendicitis hospital care costs compared with non-Hispanic White patients. Conclusions and Relevance: In this cohort study, delayed diagnosis of appendicitis was associated with increased hospital care costs.


Assuntos
Apendicite , Humanos , Feminino , Apendicite/diagnóstico , Apendicite/cirurgia , Estudos de Coortes , Diagnóstico Tardio , Hospitalização , Pacientes Internados
10.
IEEE Trans Pattern Anal Mach Intell ; 46(9): 5986-6000, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38564349

RESUMO

Texture synthesis is a fundamental problem in computer graphics that would benefit various applications. Existing methods are effective in handling 2D image textures. In contrast, many real-world textures contain meso-structure in the 3D geometry space, such as grass, leaves, and fabrics, which cannot be effectively modeled using only 2D image textures. We propose a novel texture synthesis method with Neural Radiance Fields (NeRF) to capture and synthesize textures from given multi-view images. In the proposed NeRF texture representation, a scene with fine geometric details is disentangled into the meso-structure textures and the underlying base shape. This allows textures with meso-structure to be effectively learned as latent features situated on the base shape, which are fed into a NeRF decoder trained simultaneously to represent the rich view-dependent appearance. Using this implicit representation, we can synthesize NeRF-based textures through patch matching of latent features. However, inconsistencies between the metrics of the reconstructed content space and the latent feature space may compromise the synthesis quality. To enhance matching performance, we further regularize the distribution of latent features by incorporating a clustering constraint. In addition to generating NeRF textures over a planar domain, our method can also synthesize NeRF textures over curved surfaces, which are practically useful. Experimental results and evaluations demonstrate the effectiveness of our approach.

11.
Artigo em Inglês | MEDLINE | ID: mdl-38640055

RESUMO

Interactive image restoration aims to construct an interactive pathway between users and restoration networks, which empowers users to modulate the restoration results according to their own demands. However, existing methods are primarily limited to training their networks with predefined and simplistic synthetic degradations. Consequently, these methods often encounter significant performance degradation when confronted with real-world degradations that deviate from their assumptions. Furthermore, existing interactive image restoration approaches solely support global modulation, wherein a single modulation factor governs the reconstruction process for the entire image. In this paper, we propose a novel method to perform real-world and intricate image super-resolution in an interactive manner. Specifically, we propose a metric-learning-based degradation estimation strategy to estimate not only the overall degradation level of the entire image but also the finer-grained, pixel- wise degradation within real-world scenarios. This enables local control over the restoration results by selectively modulating the corresponding regions based on the densely-estimated degradation map. Additionally, a new metric-argumented loss is proposed to further enhance the performance of real-world image super-resolution. Through extensive experimentation, we demonstrate the efficacy of our method in achieving exceptional modulation and restoration performance in real-world image super-resolution tasks, all while maintaining an appealing model complexity.

13.
BMC Infect Dis ; 24(1): 427, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649864

RESUMO

BACKGROUND: COVID-19 has been shown to increase the risk of extracorporeal coagulation during hemodialysis in patients, but the underlying mechanism remains unclear. This study aimed to investigate the effect and mechanism of COVID-19 on the risk of extracorporeal coagulation in patients with chronic kidney disease undergoing hemodialysis. METHODS: A retrospective analysis of the extracorporeal coagulation status of 339 hemodialysis patients at our center before and after COVID-19 infection was performed, including subgroup analyses. Post-infection blood composition was analyzed by protein spectrometry and ELISA. RESULTS: Compared to the pre-COVID-19 infection period, COVID-19-induced extracorporeal coagulation predominantly occurred in patients with severe/critical symptoms. Further proteomic analysis demonstrated that in patients with severe/critical symptoms, the coagulation cascade reaction, platelet activation, inflammation, and oxidative stress-related pathways were significantly amplified compared to those in patients with no/mild symptoms. Notably, the vWF/FBLN5 pathway, which is associated with inflammation, vascular injury, and coagulation, was significantly upregulated. CONCLUSIONS: Patients with severe/critical COVID-19 symptoms are at a higher risk of extracorporeal coagulation during hemodialysis, which is associated with the upregulation of the vWF/FBLN5 signaling pathway. These findings highlight the importance of early anticoagulant therapy initiation in COVID-19 patients with severe/critical symptoms, particularly those undergoing hemodialysis. Additionally, vWF/FBLN5 upregulation may be a novel mechanism for virus-associated thrombosis/coagulation.


Assuntos
COVID-19 , Diálise Renal , SARS-CoV-2 , Transdução de Sinais , Regulação para Cima , Fator de von Willebrand , Humanos , COVID-19/sangue , COVID-19/metabolismo , Diálise Renal/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fator de von Willebrand/metabolismo , Fator de von Willebrand/análise , Idoso , Coagulação Sanguínea , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/sangue , Adulto
14.
Vet Microbiol ; 292: 110065, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38564904

RESUMO

Porcine epidemic diarrhea virus (PEDV) is an enteric coronavirus that causes acute enteric disease in piglets and severely threatens the pig industry all over the world. Death domain-associated protein (DAXX) is a classical chaperone protein involved in multiple biological processes, such as cell apoptosis, transcriptional regulation, DNA damage repair, and host innate immunity. However, whether DAXX functions in the anti-PEDV innate immune responses remains unclear. In this study, we found that PEDV infection upregulated DAXX expression and induced its nucleocytoplasmic translocation in IPEC-J2 cells. Furthermore, we found that DAXX overexpression was inhibitory to PEDV replication, while downregulation of DAXX by RNA interference facilitated PEDV replication. The antiviral activity of DAXX was due to its positive effect on IFN-λ3-STAT1 signaling, as DAXX positively regulated STAT1 activation through their interaction in cytoplasm and enhancing the downstream ISG15 expression. Mutation of tryptophan at 621 to alanine in DAXX increased its abundance in the cytoplasm, leading to the upregulation of STAT1 phosphorylation and ISG15 expression. It indicated that cytoplasmic fraction of DAXX was advantageous for the STAT1-ISG15 signaling axis and PEDV inhibition. In summary, these results show that DAXX inhibits PEDV infection by increasing IFN-λ3-induced STAT1 phosphorylation and the downstream ISG15 expression.


Assuntos
Infecções por Coronavirus , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Animais , Suínos , Linhagem Celular , Fator de Transcrição STAT1/genética , Domínio de Morte , Infecções por Coronavirus/veterinária , Replicação Viral
15.
PLoS One ; 19(3): e0298375, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38512875

RESUMO

BACKGROUND AND AIMS: Few studies have examined the relationship between daytime napping and risk of kidney diseases. We aimed to investigate the association of daytime napping with the incidence of chronic kidney disease (CKD) and end-stage kidney disease (ESKD). We also examined whether sleep duration modified the association of nap with CKD or ESKD. METHODS: We recruited 460,571 European middle- to older-aged adults without prior CKD or ESKD between March 13, 2006, and October 1, 2010, in the UK Biobank. Sleep behavior data were obtained through questionnaires administered during recruitment. The analysis of the relationship between napping and the occurrence of CKD and ESKD utilized Cox proportional hazards regression models. The modification role of sleep duration on the effect of nap on CKD and ESKD was also examined. RESULTS: After a mean follow-up of 11.1 (standard deviation 2.2) years, we observed 28,330 incident CKD cases and 927 ESKD cases. The daytime napping was associated with incident CKD (P for trend = .004). After fully adjusted, when compared with participants who did not take nap, those in sometimes and usually nap groups had higher risk of CKD. Nevertheless, the available evidence did not support a link between daytime napping and ESKD (P for trend = .06). Simultaneously, there was insufficient evidence suggesting that sleeping duration modified the association of daytime napping with incident CKD or ESKD. CONCLUSION: Daytime napping was associated with an increased risk of CKD. However, the absence of conclusive evidence did not indicate a connection between daytime napping and ESKD.


Assuntos
Falência Renal Crônica , Insuficiência Renal Crônica , Humanos , Pessoa de Meia-Idade , Incidência , Falência Renal Crônica/epidemiologia , Estudos Prospectivos , Insuficiência Renal Crônica/epidemiologia , Sono , Idoso
16.
J Clin Lab Anal ; 38(7): e25031, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38514901

RESUMO

BACKGROUND: Primary cilia are static microtubule-based structures protruding from the cell surface and present on most vertebrate cells. The appropriate localization of phospholipids is essential for cilia formation and stability. INPP5E is a cilia-localized inositol 5-phosphatase; its deletion alters the phosphoinositide composition in the ciliary membrane, disrupting ciliary function. METHODS: The EGFP-2xP4MSidM, PHPLCδ1-EGFP, and SMO-tRFP plasmids were constructed by the Gateway system to establish a stable RPE1 cell line. The INPP5E KO RPE1 cell line was constructed with the CRISPR/Cas9 system. The localization of INPP5E and the distribution of PI(4,5)P2 and PI4P were examined by immunofluorescence microscopy. The fluorescence intensity co-localized with cilia was quantified by ImageJ. RESULTS: In RPE1 cells, PI4P is localized at the ciliary membrane, whereas PI(4,5)P2 is localized at the base of cilia. Knocking down or knocking out INPP5E alters this distribution, resulting in the distribution of PI(4,5)P2 along the ciliary membrane and the disappearance of PI4P from the cilia. Meanwhile, PI(4,5)P2 is located in the ciliary membrane labeled by SMO-tRFP. CONCLUSIONS: INPP5E regulates the distribution of phosphoinositide on cilia. PI(4,5)P2 localizes at the ciliary membrane labeled with SMO-tRFP, indicating that ciliary pocket membrane contains PI(4,5)P2, and phosphoinositide composition in early membrane structures may differ from that in mature ciliary membrane.


Assuntos
Cílios , Monoéster Fosfórico Hidrolases , Cílios/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Monoéster Fosfórico Hidrolases/genética , Humanos , Linhagem Celular , Fosfatidilinositol 4,5-Difosfato/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/citologia , Fosfatos de Fosfatidilinositol/metabolismo , Sistemas CRISPR-Cas , Fosfolipídeos/metabolismo
17.
Artigo em Inglês | MEDLINE | ID: mdl-38354074

RESUMO

Creating a vivid video from the event or scenario in our imagination is a truly fascinating experience. Recent advancements in text-to-video synthesis have unveiled the potential to achieve this with prompts only. While text is convenient in conveying the overall scene context, it may be insufficient to control precisely. In this paper, we explore customized video generation by utilizing text as context description and motion structure (e.g. frame- wise depth) as concrete guidance. Our method, dubbed Make-Your-Video, involves joint-conditional video generation using a Latent Diffusion Model that is pre-trained for still image synthesis and then promoted for video generation with the introduction of temporal modules. This two-stage learning scheme not only reduces the computing resources required, but also improves the performance by transferring the rich concepts available in image datasets solely into video generation. Moreover, we use a simple yet effective causal attention mask strategy to enable longer video synthesis, which mitigates the potential quality degradation effectively. Experimental results show the superiority of our method over existing baselines, particularly in terms of temporal coherence and fidelity to users' guidance. In addition, our model enables several intriguing applications that demonstrate potential for practical usage. The code, model weights, and videos are publicly available at our project page: https://doubiiu.github.io/projects/Make-Your-Video/.

18.
IEEE Trans Pattern Anal Mach Intell ; 46(7): 5192-5208, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38354071

RESUMO

Previous work for video captioning aims to objectively describe the video content but the captions lack human interest and attractiveness, limiting its practical application scenarios. The intention of video title generation (video titling) is to produce attractive titles, but there is a lack of benchmarks. This work offers CREATE, the first large-scale Chinese shoRt vidEo retrievAl and Title gEneration dataset, to assist research and applications in video titling, video captioning, and video retrieval in Chinese. CREATE comprises a high-quality labeled 210 K dataset and two web-scale 3 M and 10 M pre-training datasets, covering 51 categories, 50K+ tags, 537K+ manually annotated titles and captions, and 10M+ short videos with original video information. This work presents ACTEr, a unique Attractiveness-Consensus-based Title Evaluation, to objectively evaluate the quality of video title generation. This metric measures the semantic correlation between the candidate (model-generated title) and references (manual-labeled titles) and introduces attractive consensus weights to assess the attractiveness and relevance of the video title. Accordingly, this work proposes a novel multi-modal ALignment WIth Generation model, ALWIG, as one strong baseline to aid future model development. With the help of a tag-driven video-text alignment module and a GPT-based generation module, this model achieves video titling, captioning, and retrieval simultaneously. We believe that the release of the CREATE dataset, ACTEr metric, and ALWIG model will encourage in-depth research on the analysis and creation of Chinese short videos.

19.
Autophagy ; 20(6): 1444-1446, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38294001

RESUMO

Macroautophagy/autophagy acts as an anti-tumor mechanism in early cancer stages but promotes growth in established tumors. Similarly, miRNAs function as tumor suppressors or oncogenes, depending on their target genes. This reciprocal relationship between autophagy and miRNAs is a well-studied area, primarily focused on how miRNAs regulate autophagy-related genes. Our research provides innovative insights into how autophagy selectively controls miRNAs. For instance, MIR224 is preferentially degraded within autophagosomes, leading to the upregulation of SMAD4 and suppressing hepatocellular carcinoma (HCC) tumorigenesis. Conversely, autophagy positively regulates MIR449A by degrading EP300/p300 to activate FOXO1 and facilitate MIR449A transcription in colorectal cancer (CRC). In conclusion, our findings reveal the role of autophagy in maintaining the cellular balance of two miRNAs to mitigate tumorigenic stresses and highlight that autophagy-regulated miRNA profiles may serve as diagnostic and therapeutic markers for cancer development.


Assuntos
Autofagia , Homeostase , MicroRNAs , Neoplasias , Autofagia/genética , Autofagia/fisiologia , MicroRNAs/metabolismo , MicroRNAs/genética , Humanos , Neoplasias/genética , Neoplasias/patologia , Neoplasias/metabolismo , Animais , Carcinogênese/genética , Carcinogênese/patologia , Regulação Neoplásica da Expressão Gênica
20.
J Clin Periodontol ; 51(1): 97-107, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37850252

RESUMO

AIM: To investigate the association between periodontal diseases, airflow limitation and incident chronic obstructive pulmonary disease (COPD) in a large-scale prospective UK Biobank cohort. MATERIALS AND METHODS: Our approach comprised a cross-sectional study and a prospective cohort. Periodontal diseases were determined based on the participants' self-reported dental symptoms, including painful gums, bleeding gums and loose teeth. Logistic regression and Cox proportional hazards models were used to evaluate the association of periodontal diseases with airflow limitation and incident COPD in the cross-sectional study and the prospective cohort, respectively. RESULTS: The cross-sectional study involved 495,610 participants. Multivariable analysis found that periodontal diseases were significantly associated with airflow limitation (odds ratio = 1.036, 95% confidence interval [CI]: 1.015-1.059). The cohort study included 379,266 participants with a median follow-up period of 12.68 years. An elevated risk of incident COPD was associated with the presence of periodontal diseases (hazard ratio: 1.248, 95% CI: 1.174-1.326). The effect was consistent among subgroups, including baseline age (≤65 or >65 years), sex, smoking status and diabetes mellitus. CONCLUSIONS: Periodontal diseases are associated with airflow limitation and elevated COPD incidence. Maintaining good periodontal health in patients with chronic bronchitis and emphysema may help prevent the onset of COPD.


Assuntos
Doenças Periodontais , Doença Pulmonar Obstrutiva Crônica , Humanos , Idoso , Estudos Transversais , Estudos Prospectivos , Biobanco do Reino Unido , Estudos de Coortes , Bancos de Espécimes Biológicos , Fatores de Risco , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doenças Periodontais/complicações , Doenças Periodontais/epidemiologia
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