Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 666
Filtrar
1.
J Cancer ; 15(13): 4097-4112, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38947389

RESUMO

Ferroptosis has been characterized as non-apoptotic programmed cell death and is considered a novel strategy for antitumor treatment. The factor that binds to inducer of short transcripts-1 (FBI-1) is an important proto-oncogene playing multiple roles in human malignancies and the development of resistance to therapy. However, the roles of FBI-1 in ferroptosis of endocrine independent prostate carcinoma are still unknown. The results of this study showed that FBI-1 inhibited the ferroptosis of prostate carcinoma PC-3 cells (a typical endocrine-independent prostate carcinoma cell line) via the miR-324-3p/glutathione peroxidase 4 (miR-324-3p/GPX4) axis. Overexpression of FBI-1 enhanced the expression levels of GPX4. In contrast, knockdown of FBI-1 decreased the expression of GPX4 and induced the ferroptosis of PC-3 cells. The miR-324-3p decreased the expression of GPX4 by targeting the 3'-untranslated region of GPX4 to induce ferroptosis. Notably, FBI-1 increased the expression of GPX4 by repressing the levels of miR-324-3p. The transcription of miR-324-3p was mediated by specificity protein 1 (SP1), and FBI-1 repressed the expression of miR-324-3p by repressing the activation of SP1. In clinical specimens, the endogenous levels of FBI-1 were positively associated with Glutathione Peroxidase 4 (GPX4) and negatively related with the expression of miR-324-3p. Therefore, the results indicated that the miR-324-3p/GPX4 axis participates in the FBI-1-mediated ferroptosis of prostate carcinoma cells.

2.
BMC Infect Dis ; 24(1): 675, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38971721

RESUMO

Pleural empyema can lead to significant morbidity and mortality despite chest drainage and antibiotic treatment, necessitating novel and minimally invasive interventions. Fusobacterium nucleatum is an obligate anaerobe found in the human oral and gut microbiota. Advances in sequencing and puncture techniques have made it common to detect anaerobic bacteria in empyema cases. In this report, we describe the case of a 65-year-old man with hypertension who presented with a left-sided encapsulated pleural effusion. Initial fluid analysis using metagenomic next-generation sequencing (mNGS) revealed the presence of Fusobacterium nucleatum and Aspergillus chevalieri. Unfortunately, the patient experienced worsening pleural effusion despite drainage and antimicrobial therapy. Ultimately, successful treatment was achieved through intrapleural metronidazole therapy in conjunction with systemic antibiotics. The present case showed that intrapleural antibiotic therapy is a promising measure for pleural empyema.


Assuntos
Antibacterianos , Empiema Pleural , Fusobacterium nucleatum , Terapia de Salvação , Humanos , Masculino , Idoso , Empiema Pleural/tratamento farmacológico , Empiema Pleural/microbiologia , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Fusobacterium nucleatum/efeitos dos fármacos , Fusobacterium nucleatum/isolamento & purificação , Fusobacterium nucleatum/genética , Infecções por Fusobacterium/tratamento farmacológico , Infecções por Fusobacterium/complicações , Infecções por Fusobacterium/microbiologia , Metronidazol/uso terapêutico , Metronidazol/administração & dosagem , Sequenciamento de Nucleotídeos em Larga Escala , Resultado do Tratamento
3.
mSphere ; : e0043924, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39012105

RESUMO

Companion animals such as cats and dogs harbor diverse microbial communities that can potentially impact human health due to close and frequent contact. To better characterize their total infectomes and assess zoonotic risks, we characterized the overall infectomes of companion animals (cats and dogs) and evaluated their potential zoonotic risks. Meta-transcriptomic analyses were performed on 239 samples from cats and dogs collected across China, identifying 24 viral species, 270 bacterial genera, and two fungal genera. Differences in the overall microbiome and infectome composition were compared across different animal species (cats or dogs), sampling sites (rectal or oropharyngeal), and health status (healthy or diseased). Diversity analyses revealed that viral abundance was generally higher in diseased animals compared to healthy ones, while differences in microbial composition were mainly driven by sampling site, followed by animal species and health status. Disease association analyses validated the pathogenicity of known pathogens and suggested potential pathogenic roles of previously undescribed bacteria and newly discovered viruses. Cross-species transmission analyses identified seven pathogens shared between cats and dogs, such as alphacoronavirus 1, which was detected in both oropharyngeal and rectal swabs albeit with differential pathogenicity. Further analyses showed that some viruses, like alphacoronavirus 1, harbored multiple lineages exhibiting distinct pathogenicity, tissue, or host preferences. Ultimately, a systematic evolutionary screening identified 27 potential zoonotic pathogens in this sample set, with far more bacterial than viral species, implying potential health threats to humans. Overall, our meta-transcriptomic analysis reveals a landscape of actively transcribing microorganisms in major companion animals, highlighting key pathogens, those with the potential for cross-species transmission, and possible zoonotic threats. IMPORTANCE: This study provides a comprehensive characterization of the entire community of infectious microbes (viruses, bacteria, and fungi) in companion animals like cats and dogs, termed the "infectome." By analyzing hundreds of samples from across China, the researchers identified numerous known and novel pathogens, including 27 potential zoonotic agents that could pose health risks to both animals and humans. Notably, some of these zoonotic pathogens were detected even in apparently healthy pets, highlighting the importance of surveillance. The study also revealed key microbial factors associated with respiratory and gastrointestinal diseases in pets, as well as potential cross-species transmission events between cats and dogs. Overall, this work sheds light on the complex microbial landscapes of companion animals and their potential impacts on animal and human health, underscoring the need for monitoring and management of these infectious agents.

4.
Eur Radiol ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38981889

RESUMO

OBJECTIVES: This study examines the effectiveness of dual-energy CT (DECT) delayed-phase extracellular volume (ECV) fraction in predicting tumor regression grade (TRG) in far-advanced gastric cancer (FAGC) patients receiving preoperative immuno-chemotherapy. MATERIALS AND METHODS: A retrospective analysis was performed on far-advanced gastric adenocarcinoma patients treated with preoperative immuno-chemotherapy at our institution from August 2019 to March 2023. Patients were categorized based on their TRG into pathological complete response (pCR) and non-pCR groups. ECV was determined using the delayed-phase iodine maps. In addition, tumor iodine densities and standardized iodine ratios were meticulously analyzed using the triple-phase enhanced iodine maps. Univariate analysis with five-fold cross-validation and Spearman correlation determined DECT parameters and clinical indicators association with pCR. The predictive accuracy of these parameters for pCR was evaluated using a weighted logistic regression model with five-fold cross-validation. RESULTS: Of the 88 patients enrolled (mean age 60.8 ± 11.1 years, 63 males), 21 (23.9%) achieved pCR. Univariate analysis indicated ECV's significant role in differentiating between pCR and non-pCR groups (average p value = 0.021). In the logistic regression model, ECV independently predicted pCR with an average odds ratio of 0.911 (95% confidence interval, 0.798-0.994). The model, incorporating ECV, tumor area, and IDAV (the relative change rate of iodine density from venous phase to arterial phase), showed an average area under curves (AUCs) of 0.780 (0.770-0.791) and 0.766 (0.731-0.800) for the training and validation sets, respectively, in predicting pCR. CONCLUSION: DECT-derived ECV fraction is a valuable predictor of TRG in FAGC patients undergoing preoperative immuno-chemotherapy. CLINICAL RELEVANCE STATEMENT: This study demonstrates that DECT-derived extracellular volume fraction is a reliable predictor for pathological complete response in far-advanced gastric cancer patients receiving preoperative immuno-chemotherapy, offering a noninvasive tool for identifying potential treatment beneficiaries.

5.
BMC Med Imaging ; 24(1): 159, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926711

RESUMO

BACKGROUND: To assess the improvement of image quality and diagnostic acceptance of thinner slice iodine maps enabled by deep learning image reconstruction (DLIR) in abdominal dual-energy CT (DECT). METHODS: This study prospectively included 104 participants with 136 lesions. Four series of iodine maps were generated based on portal-venous scans of contrast-enhanced abdominal DECT: 5-mm and 1.25-mm using adaptive statistical iterative reconstruction-V (Asir-V) with 50% blending (AV-50), and 1.25-mm using DLIR with medium (DLIR-M), and high strength (DLIR-H). The iodine concentrations (IC) and their standard deviations of nine anatomical sites were measured, and the corresponding coefficient of variations (CV) were calculated. Noise-power-spectrum (NPS) and edge-rise-slope (ERS) were measured. Five radiologists rated image quality in terms of image noise, contrast, sharpness, texture, and small structure visibility, and evaluated overall diagnostic acceptability of images and lesion conspicuity. RESULTS: The four reconstructions maintained the IC values unchanged in nine anatomical sites (all p > 0.999). Compared to 1.25-mm AV-50, 1.25-mm DLIR-M and DLIR-H significantly reduced CV values (all p < 0.001) and presented lower noise and noise peak (both p < 0.001). Compared to 5-mm AV-50, 1.25-mm images had higher ERS (all p < 0.001). The difference of the peak and average spatial frequency among the four reconstructions was relatively small but statistically significant (both p < 0.001). The 1.25-mm DLIR-M images were rated higher than the 5-mm and 1.25-mm AV-50 images for diagnostic acceptability and lesion conspicuity (all P < 0.001). CONCLUSIONS: DLIR may facilitate the thinner slice thickness iodine maps in abdominal DECT for improvement of image quality, diagnostic acceptability, and lesion conspicuity.


Assuntos
Meios de Contraste , Aprendizado Profundo , Interpretação de Imagem Radiográfica Assistida por Computador , Radiografia Abdominal , Imagem Radiográfica a Partir de Emissão de Duplo Fóton , Tomografia Computadorizada por Raios X , Humanos , Estudos Prospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Tomografia Computadorizada por Raios X/métodos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Radiografia Abdominal/métodos , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/métodos , Adulto , Iodo , Idoso de 80 Anos ou mais
6.
J Stroke Cerebrovasc Dis ; 33(8): 107811, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38866118

RESUMO

OBJECTIVES: Embolic Stroke of Undetermined Source (ESUS) is a distinct stroke entity that disproportionately affects young adults. We sought to describe characteristics, workup and outcomes of young adult ESUS patients who underwent thrombectomy, and compare outcomes to those reported in different age groups. MATERIALS AND METHODS: Young-ESUS is a multicenter longitudinal cohort study that enrolled consecutive patients aged 21-50 years at 41 stroke centers in 13 countries between 2017- 2019. Between-group comparisons were performed using Wilcoxon rank sum test for continuous variables or Fisher's exact test for binary variables. Distribution of functional outcomes after thrombectomy for our young adult cohort versus pediatric and older adult cohorts reported in the literature were described using the Kruskal-Wallis test. RESULTS: Of 535 patients enrolled in Young-ESUS, 65 (12.1%) were treated with endovascular thrombectomy. Patients who underwent thrombectomy were more likely to undergo in-depth cardiac testing than those who did not, but cardiac abnormalities were not detected more often in this group. Among thrombectomy patients, 35/63 (55.6%) had minimal to no functional disability at follow up. When adjusted for age, stroke severity and IV alteplase, the odds of achieving favorable outcome did not differ between treated versus untreated patients. CONCLUSIONS: Thrombectomy is not rare in young adults with ESUS. Despite extensive workup, cardiac abnormalities were not more prevalent in the thrombectomy group. More research to determine optimal workup, etiologic factors and favorable outcome of stroke across the lifespan is needed.

7.
Phys Chem Chem Phys ; 26(23): 16838-16846, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38832413

RESUMO

As a key configuration, hard carbon (HC) is widely regarded as a promising cathode for rechargeable aluminum batteries (RABs), because of its enlarged interlayer spacing and well-developed pore structures. However, the trade-off between the pore structure, interlayer spacing and conductivity easily leads to an unsatisfactory electrochemical performance in terms of capacity and cycling stability. Hence, N-doped hard carbon (P-M) is synthesized at a relatively low temperature (700 °C) and anion intercalation associated with the energy storage process is investigated. The results demonstrate that the introduction of a N-doping agent not only expands the layer spacing and creates rich pore structures, but also boosts the conductivity. Compared with HC without N-doping, the expanded interlayer spacing in P-M can increase ion storage ability, and the rich pore channels contribute to electron transfer. Besides, compared with HC annealed at a higher temperature (900 °C), the enhanced conductivity in P-M is conducive to accelerating ion diffusion. Benefiting from these structure merits, the optimized P-M cathode delivers a high capacity (323 mA h g-1 at 500 mA g-1) and a prolonged cycle lifespan over 1000 cycles at 1 A g-1 retaining 109 mA h g-1. This work can provide a guidance for developing other high-performance hard carbon cathodes.

8.
Can J Cardiol ; 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38914270

RESUMO

BACKGROUND: Individuals with frailty are at higher risk of adverse cardiovascular outcomes and bleeding. The objective of this study was to determine whether the effects of rivaroxaban 2.5mg twice daily in addition to low-dose aspirin are similar among frail compared with non-frail patients with chronic atherosclerotic vascular disease. METHODS: In the COMPASS trial (ClinicalTrials.gov number NCT01776424), patients with chronic atherosclerotic vascular disease were randomized to receive aspirin 100mg daily, aspirin 100mg daily and rivaroxaban 2.5mg twice daily or rivaroxaban 5mg twice daily. In this post hoc analysis, frailty was evaluated by constructing a cumulative deficit index from 37 diseases, signs, and symptoms. The frailty index for each participant was calculated as the proportion of the 37 deficits exhibited, with values >0.2 considered frail. The primary outcome was the composite of cardiovascular death, myocardial infarction, or stroke. Hazard ratios (HR) and 95% confidence intervals (CI) are reported. RESULTS: Frailty was present in 13% of the trial population. In non-frail individuals, adding rivaroxaban 2.5mg twice daily to aspirin reduced the primary outcome (HR, 95% CI: 0.69, 0.59-0.80) and mortality (0.75, 0.63-0.90) but increased major bleeding (1.87, 1.51-2.31); however, its effects on the primary outcome (1.06, 0.79-1.42), mortality (1.08, 0.80-1.46) and major bleeding (1.10, 0.71-1.70) were not evident among participants with frailty (respective interaction p-values 0.011, 0.049 and 0.032). CONCLUSIONS: In adults with chronic atherosclerotic vascular disease, the benefit of adding rivaroxaban 2.5mg twice daily to aspirin was not evident in patients with frailty.

9.
PLoS One ; 19(5): e0301610, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38743774

RESUMO

In the process of horizontal well construction, the working environment in the well is very complicated. It is difficult to determine the actual deformation and force of the coiled tubing in the wellbore from the load change at the wellhead along. In addition, the coiled tubing wrapped around the reel and entering the wellbore through the injection head may cause an initial residual bending. In this paper, the mathematical model of the coiled tubing under axial load during buckling deformation is established, and the analytical solution with the time term is derived by reasonable simplification of the model. The effect of residual bending on the post-sinusoidal buckling of the coiled tubing in the horizontal well was investigated using the separation variable method. The effect of residual bending variations on the well wall contact forces is analyzed. The research shows that the initial parameter Г is the main factor influencing the post-sinusoidal buckling of the coiled tubing with residual bending. The larger the parameter value Г, the greater the effect of the residual bending on the post-sinusoidal buckling deformation of the coiled tubing, and the earlier the critical point of the mixed sinusoidal-helical buckling of the coiled tubing appears. The compression velocity of the coiled tubing has a significant effect on the well wall contact force. The faster the compression, the greater the contact force. By introducing the time term and the separation variable, this paper provides a new method and theoretical basis for further study of the process of entering sinusoidal-helical buckling of the coiled tubing with initial residual bending.


Assuntos
Modelos Teóricos , Estresse Mecânico
10.
Proc Natl Acad Sci U S A ; 121(19): e2322934121, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38701119

RESUMO

EPH receptors (EPHs), the largest family of tyrosine kinases, phosphorylate downstream substrates upon binding of ephrin cell surface-associated ligands. In a large cohort of endometriotic lesions from individuals with endometriosis, we found that EPHA2 and EPHA4 expressions are increased in endometriotic lesions relative to normal eutopic endometrium. Because signaling through EPHs is associated with increased cell migration and invasion, we hypothesized that chemical inhibition of EPHA2/4 could have therapeutic value. We screened DNA-encoded chemical libraries (DECL) to rapidly identify EPHA2/4 kinase inhibitors. Hit compound, CDD-2693, exhibited picomolar/nanomolar kinase activity against EPHA2 (Ki: 4.0 nM) and EPHA4 (Ki: 0.81 nM). Kinome profiling revealed that CDD-2693 bound to most EPH family and SRC family kinases. Using NanoBRET target engagement assays, CDD-2693 had nanomolar activity versus EPHA2 (IC50: 461 nM) and EPHA4 (IC50: 40 nM) but was a micromolar inhibitor of SRC, YES, and FGR. Chemical optimization produced CDD-3167, having picomolar biochemical activity toward EPHA2 (Ki: 0.13 nM) and EPHA4 (Ki: 0.38 nM) with excellent cell-based potency EPHA2 (IC50: 8.0 nM) and EPHA4 (IC50: 2.3 nM). Moreover, CDD-3167 maintained superior off-target cellular selectivity. In 12Z endometriotic epithelial cells, CDD-2693 and CDD-3167 significantly decreased EFNA5 (ligand) induced phosphorylation of EPHA2/4, decreased 12Z cell viability, and decreased IL-1ß-mediated expression of prostaglandin synthase 2 (PTGS2). CDD-2693 and CDD-3167 decreased expansion of primary endometrial epithelial organoids from patients with endometriosis and decreased Ewing's sarcoma viability. Thus, using DECL, we identified potent pan-EPH inhibitors that show specificity and activity in cellular models of endometriosis and cancer.


Assuntos
Inibidores de Proteínas Quinases , Humanos , Feminino , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Endometriose/tratamento farmacológico , Endometriose/metabolismo , Endometriose/patologia , DNA/metabolismo , Receptores da Família Eph/metabolismo , Receptores da Família Eph/antagonistas & inibidores , Receptor EphA2/metabolismo , Receptor EphA2/antagonistas & inibidores , Bibliotecas de Moléculas Pequenas/farmacologia , Bibliotecas de Moléculas Pequenas/química , Movimento Celular/efeitos dos fármacos
11.
Pain Manag Nurs ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38609805

RESUMO

OBJECTIVE: To assess the effect of a teach-back educational intervention using Behavior Change Wheel (BCW) framework on perioperative pain among patients with lung cancer. METHODS: A prospective quasi-experimental study was conducted in 88 patients with lung cancer from a tertiary hospital in China. According to the order of admission, they were allocated to either control group or intervention group, with 44 patients in each group. Patients in the control group received routine nursing care, while patients in the intervention group were given a teach-back education program based on BCW framework. The visual analog scale (VAS) was adopted to evaluate patients' pain on the day of surgery (T0), 1 (T1), 2 (T2), and 3 (T3) days after surgery. We also recorded the use of patient-controlled analgesia (PCA), the length of hospital stay, and the degree of patients' satisfaction. RESULTS: Rest pain, pain when coughing, and pain during activity that patients in the intervention group experienced were significantly less severe than those in the control group on T0 and T1. The pain when coughing in the intervention group was also significantly milder on T2 and T3. In addition, the number of self-control time, use duration, and total dose of PCA were significantly lower in the intervention group. Moreover, patients' satisfaction of nursing service was significantly higher in the intervention group. CONCLUSION: A teach-back education program based on BCW framework was effective in pain management among the perioperative patients with lung cancer. This study demonstrates the application of teach-back method and the BCW in the development of patient education intervention to mitigate perioperative pain.

12.
J Acoust Soc Am ; 155(4): 2503-2516, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38587432

RESUMO

Passive acoustic monitors analyze sound signals emitted by seafloor gas bubbles to measure leakage rates. In scenarios with low-flux gas leaks, individual bubble sounds are typically non-overlapping. Measurement methods for these bubble streams aim to estimate the frequency peak of each bubble sound, which correlates with the bubble's size. However, the presence of ocean ambient noise poses challenges to accurately estimating these frequency peaks, thereby affecting the measurement of gas leakage rates in shallow sea environments using passive acoustic monitors. To address this issue, we propose a robust measurement method that includes a noise-robust sparse time-frequency representation algorithm and an adaptive thresholding approach for detecting bubble frequencies. We demonstrate the effectiveness of our proposed method using experimental data augmented with ocean ambient noise and ship-transit noise recorded from a bay area.

13.
Arch Gynecol Obstet ; 309(5): 2167-2173, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38503849

RESUMO

OBJECTIVE: The purpose of this study is to compare the clinical efficacy of oral dydrogesterone and micronized vaginal progesterone (MVP) gel during the first HRT-FET cycle. METHODS: A retrospective cohort study based on a total of 344 women undergoing their first HRT-FET cycles without Gonadotropin-Releasing Hormone agonist (GnRH-a) pretreatment was conducted. All the cycles were allocated to two groups in the reproductive medical center at the University of Hong Kong-Shenzhen Hospital. One group (n = 193) received oral dydrogesterone 30 mg/d before embryo transfer, while the other group (n = 151) received MVP gel 180 mg/d. RESULTS: The demographics and baseline characteristics of two groups were comparable. We found no statistically significant difference in live birth rate (24.35% vs. 31.13%, P = 0.16), clinical pregnancy rate (34.72% vs. 36.42%, P = 0.74), embryo implantation rate (25.09% vs. 28.36%, P = 0.43), positive pregnancy rate (42.49% vs 38.41%, P = 0.45), miscarriage rate (9.33% vs 3.97%, P = 0.05), or ectopic pregnancy rate (0.52% vs. 0.66%, P = 0.86) between the oral dydrogesterone group and MVP gel group. In the multivariate logistic regression analysis for covariates, medication used for luteal support was not associated with live birth rate (OR = 0.73, 95% CI: 0.32-1.57, P = 0.45). And the different luteal support medication did not have a significant positive association with the live birth rate in the cycles with day 2 embryo transferred (OR = 1.39, 95% CI:0.66-2.39, P = 0.39) and blastocyst transferred (OR = 1.31 95% CI:0.64-2.69, P = 0.46). CONCLUSION: 30 mg/d oral dydrogesterone and 180 mg/d MVP gel revealed similar reproductive outcomes in HRT-FET cycles in the study.


Assuntos
Didrogesterona , Progesterona , Gravidez , Feminino , Humanos , Progesterona/uso terapêutico , Estudos Retrospectivos , Taxa de Gravidez , Transferência Embrionária , Luteína
14.
Cancer Lett ; 588: 216768, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38453045

RESUMO

Hedgehog signaling is activated in response to liver injury, and modulates organogenesis. However, the role of non-canonical hedgehog activation via TGF-ß1/SMAD3 in hepatic carcinogenesis is poorly understood. TGF-ß1/SMAD3-mediated non-canonical activation was found in approximately half of GLI2-positive hepatocellular carcinoma (HCC), and two new GLI2 isoforms with transactivating activity were identified. Phospho-SMAD3 interacted with active GLI2 isoforms to transactivate downstream genes in modulation of stemness, epithelial-mesenchymal transition, chemo-resistance and metastasis in poorly-differentiated hepatoma cells. Non-canonical activation of hedgehog signaling was confirmed in a transgenic HBV-associated HCC mouse model. Inhibition of TGF-ß/SMAD3 signaling reduced lung metastasis in a mouse in situ hepatic xenograft model. In another cohort of 55 HCC patients, subjects with high GLI2 expression had a shorter disease-free survival than those with low expression. Moreover, co-positivity of GLI2 with SMAD3 was observed in 87.5% of relapsed HCC patients with high GLI2 expression, indicating an increased risk of post-resection recurrence of HCC. The findings underscore that suppressing the non-canonical hedgehog signaling pathway may confer a potential strategy in the treatment of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Humanos , Camundongos , Carcinoma Hepatocelular/patologia , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Neoplasias Hepáticas/patologia , Camundongos Transgênicos , Proteínas Nucleares/metabolismo , Transdução de Sinais , Proteína Smad3/genética , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Proteína Gli2 com Dedos de Zinco/genética , Proteína Gli2 com Dedos de Zinco/metabolismo
15.
Nat Ecol Evol ; 8(5): 947-959, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38519631

RESUMO

Mosquito transmitted viruses are responsible for an increasing burden of human disease. Despite this, little is known about the diversity and ecology of viruses within individual mosquito hosts. Here, using a meta-transcriptomic approach, we determined the viromes of 2,438 individual mosquitoes (81 species), spanning ~4,000 km along latitudes and longitudes in China. From these data we identified 393 viral species associated with mosquitoes, including 7 (putative) species of arthropod-borne viruses (that is, arboviruses). We identified potential mosquito species and geographic hotspots of viral diversity and arbovirus occurrence, and demonstrated that the composition of individual mosquito viromes was strongly associated with host phylogeny. Our data revealed a large number of viruses shared among mosquito species or genera, enhancing our understanding of the host specificity of insect-associated viruses. We also detected multiple virus species that were widespread throughout the country, perhaps reflecting long-distance mosquito dispersal. Together, these results greatly expand the known mosquito virome, linked viral diversity at the scale of individual insects to that at a country-wide scale, and offered unique insights into the biogeography and diversity of viruses in insect vectors.


Assuntos
Culicidae , Mosquitos Vetores , Viroma , Animais , Culicidae/virologia , China , Mosquitos Vetores/virologia , Metagenômica , Arbovírus/genética , Arbovírus/classificação , Filogenia , Biodiversidade
16.
Pharmacol Res ; 203: 107137, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38522761

RESUMO

Peptide stapling, by employing a stable, preformed alpha-helical conformation, results in the production of peptides with improved membrane permeability and enhanced proteolytic stability, compared to the original peptides, and provides an effective solution to accelerate the rapid development of peptide drugs. Various reviews present peptide stapling chemistries, anchoring residues and one- or two-component cyclization, however, therapeutic stapled peptides have not been systematically summarized, especially focusing on various disease-related targets. This review highlights the latest advances in therapeutic peptide drug development facilitated by the application of stapling technology, including different stapling techniques, synthetic accessibility, applicability to biological targets, potential for solving biological problems, as well as the current status of development. Stapled peptides as therapeutic drug candidates have been classified and analysed mainly by receptor- and ligand-based stapled peptide design against various diseases, including cancer, infectious diseases, inflammation, and diabetes. This review is expected to provide a comprehensive reference for the rational design of stapled peptides for different diseases and targets to facilitate the development of therapeutic peptides with enhanced pharmacokinetic and biological properties.


Assuntos
Peptídeos , Humanos , Animais , Peptídeos/uso terapêutico , Peptídeos/química , Peptídeos/farmacologia , Desenho de Fármacos
17.
Sci Rep ; 14(1): 6766, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38514692

RESUMO

The basic principle of multi-view stereo (MVS) is to perform 3D reconstruction by extracting depth information from multiple views. Most current SOTA MVS networks are based on Vision Transformer, which usually means expensive computational complexity. To reduce computational complexity and improve depth map accuracy, we propose a MVS network with Bidirectional Semantic Information (BSI-MVS). Firstly, we design a Multi-Level Spatial Pyramid module to generate multiple layers of feature map for extracting multi-scale information. Then we propose a 2D Bidirectional-LSTM module to capture bidirectional semantic information at different time steps in the horizontal and vertical directions, which contains abundant depth information. Finally, cost volumes are built based on various levels of feature maps to optimize the final depth map. We experiment on the DTU and BlendedMVS datasets. The result shows that our network, in terms of overall metrics, surpasses TransMVSNet, CasMVSNet, CVP-MVSNet, and AACVP-MVSNet respectively by 17.84%, 36.42%, 14.96%, and 4.86%, which also shows a noticeable performance enhancement in objective metrics and visualizations.

18.
Dement Geriatr Cogn Disord ; 53(2): 74-82, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38408448

RESUMO

INTRODUCTION: Previous studies have indicated a correlation between perceived stress and cognitive decline. However, it remains unknown whether high levels of perceived stress can result in motoric cognitive risk (MCR) syndrome. This study investigated the relationship between perceived stress and MCR in a community-based population. METHODS: The study cohort comprised 852 elderly individuals from the Rugao Longitudinal Aging Cohort. Perceived stress was assessed using the 10-item Perceived Stress Scale (PSS-10), while MCR was defined as the coexistence of subjective memory complaints (SMCs) and slow gait speed. RESULTS: The average age of the study participants is 79.84 ± 4.34 years. The mean score of PSS-10 among participants is 10.32 (range = 0-33; [SD] = 5.71), with a median score of 10.00 (6.00, 14.00). The prevalence of MCR is 9.3%. In the logistic regression analysis, for each 1-SD (5.71) increase in the global PSS-10 score, the risk of MCR increased by 40% (95% CI 1.09-1.80). Additionally, in the aspect of two components of MCR, with a 1-SD increase (5.71) in the global PSS-10 score, there was a 50% (95% CI 1.29-1.75) increase in the risk of SMCs and a 27% (95% CI 1.04-1.55) increase in the risk of slow gait speed. In terms of specific walking speed, there was a reverse correlation between the global PSS-10 score and walking speed (r = -0.14, p < 0.001). CONCLUSIONS: This study provided preliminary evidence that high levels of perceived stress were associated with the risk of MCR in a community-dwelling population.


Assuntos
Envelhecimento , Disfunção Cognitiva , Estresse Psicológico , Humanos , Masculino , Idoso , Feminino , Estresse Psicológico/epidemiologia , Estresse Psicológico/psicologia , Idoso de 80 Anos ou mais , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/psicologia , Envelhecimento/fisiologia , Envelhecimento/psicologia , Estudos Longitudinais , Velocidade de Caminhada , Longevidade , Fatores de Risco , Prevalência , Estudos de Coortes , Transtornos da Memória/epidemiologia , Transtornos da Memória/psicologia , Testes Neuropsicológicos
19.
Invest Ophthalmol Vis Sci ; 65(2): 23, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38345554

RESUMO

Purpose: Choroidal neovascularization (CNV) can constitute the final pathology of many ocular diseases and result in severe vision loss. Studies have demonstrated that DNA methylation is critical in retinal development, aging, and disorders. The current work investigated the effects and underlying mechanism of 5-Aza-2'-deoxycytidine (5-aza-dC), a suppressor of DNA methylation, in the pathological progression of CNV. Methods: The DNA methylation profiles of retinal pigment epithelial (RPE)/choroidal complexes in normal and laser-induced CNV mice were assessed by Arraystar Mouse RefSeq Promoter Arrays. The CNV area and blood flow density and intensity were observed by optical coherence tomography angiography, and fluorescence leakage was examined by fundus fluorescein angiography in CNV mice with systemic administration of 5-aza-dC. The effects of 5-aza-dC on the biological functions of bEnd.3 cells were estimated by related assays. Notum gene promoter methylation was measured using bisulfite sequencing PCR. Methyltransferases and Wnt signaling-related genes were detected in animal and cell culture experiments by real-time PCR and immunoblot. Results: Methyltransferases were upregulated, but Notum (a secretion inhibitor of Wnt signaling) was downregulated in the RPE/choroidal complexes of mice with experimental CNV. Intraperitoneal injection of 5-aza-dC inactivated the Wnt pathway and ameliorated the lesion area and the intensity and density of blood flow, as well as the degree of leakage in CNV. In vitro, vascular endothelial growth factor A (VEGFA) stimulation promoted methyltransferases expression and suppressed Notum expression, consequently activating Wnt signaling, whereas exogenous 5-aza-dC reversed VEGFA-induced hyperpermeability, proliferation, migration, and tube formation in bEnd.3 cells via demethylation of Notum promoter. Conclusions: We observed that 5-aza-dC attenuates the growth of CNV by inhibiting the Wnt signaling pathway via promoter demethylation of the Wnt antagonist Notum. These findings provide a theoretical basis for methylation-based treatment with the Notum gene as a potential target for CNV treatment.


Assuntos
Neovascularização de Coroide , Via de Sinalização Wnt , Camundongos , Animais , Via de Sinalização Wnt/genética , Decitabina/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Células Endoteliais/metabolismo , Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/genética , Neovascularização de Coroide/metabolismo , Azacitidina/farmacologia , Metiltransferases , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
20.
Med Sci Monit ; 30: e942832, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38321725

RESUMO

BACKGROUND Hypertriglyceridemia-induced acute pancreatitis (HTG-AP), representing 10% of all acute pancreatitis cases, is characterized by younger onset age and more severe progression, often leading to higher ICU admission rates. This condition poses a significant challenge due to its rapid progression and the potential for severe complications, including multiple organ failure. HTG-AP is distinct from other forms of pancreatitis, such as those caused by cholelithiasis or alcohol, in terms of clinical presentation and outcomes. It's essential to identify early markers that can predict the severity of HTG-AP to improve patient management and outcomes. MATERIAL AND METHODS This study divided 127 HTG-AP patients into mild acute pancreatitis (MAP, n=71) and moderate-to-severe acute pancreatitis (MSAP/SAP, n=56) groups. Blood biological indicators within the first 24 hours of admission were analyzed. Risk factors for HTG-AP progression were determined using binary logistic regression and ROC curves. RESULTS Elevated levels of HCT, NLR, TBI, DBI, AST, Cre, and AMS were noted in the MSAP/SAP group, with lower levels of LYM, Na⁺, Ca²âº, ApoA, and ApoB compared to the MAP group (p<0.05). NEUT%, Ca²âº, ApoA, and ApoB were significantly linked with HTG-AP severity. Their combined ROC analysis yielded an area of 0.81, with a sensitivity of 61.8% and specificity of 90%. CONCLUSIONS NEUT%, Ca²âº, ApoA, and ApoB are significant risk factors for progressing to MSAP/SAP in HTG-AP. Their combined assessment provides a reliable predictive measure for early intervention in patients at risk of severe progression.


Assuntos
Hipertrigliceridemia , Pancreatite , Humanos , Cálcio , Neutrófilos , Doença Aguda , Estudos Retrospectivos , Hipertrigliceridemia/complicações , Apolipoproteínas , Apolipoproteínas A , Apolipoproteínas B
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...