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1.
Clin Cancer Res ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38723277

RESUMO

PURPOSE: The rising global high incidence of differentiated thyroid carcinoma (DTC) has led to a significant increase in patients presenting with lung metastasis of DTC (LMDTC). This population poses a significant challenge in clinical practice, necessitating the urgent development of effective risk stratification methods and predictive tools for lung metastasis. EXPERIMENTAL DESIGN: Through proteomic analysis of large samples of primary lesion and dual validation employing parallel reaction monitoring and immunohistochemistry, we identified eight hub proteins as potential biomarkers. By expanding the sample size and conducting statistical analysis on clinical features and hub protein expression, we constructed three risk prediction models. RESULTS: This study identified eight hub proteins-SUCLG1/2, DLAT, IDH3B, ACSF2, ACO2, CYCS and VDAC2- as potential biomarkers for predicting DTC lung metastasis risk. We developed and internally validated three risk prediction models incorporating both clinical characteristics and hub protein expression. Our findings demonstrated that the combined prediction model exhibited optimal predictive performance, with the highest discrimination (AUC: 0.986) and calibration (Brier score: 0.043). Application of the combined prediction model within a specific risk threshold (0-0.97) yielded maximal clinical benefit. Finally, we constructed a nomogram based on the combined prediction model. CONCLUSIONS: As a large sample size study in lung metastatic DTC research, the identification of biomarkers through primary lesion proteomics and the development of risk prediction models integrating clinical features and hub protein biomarkers offer valuable insights for predicting DTC lung metastasis and establishing personalised treatment strategies.

2.
Small ; : e2402523, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38747010

RESUMO

A 44.610.8 topology hybrid ultramicroporous material (HUM), {[Cu1.5F(SiF6)(L)2.5]·G}n, (L = 4,4'-bisimidazolylbiphenyl, G = guest molecules), 1, formed by cross-linking interpenetrated 3D four-connected CdSO4-type nets with hexafluorosilicate anions is synthesized and evaluated in the context of gas sorption and separation herein. 1 is the first HUM functionalized with two different types of fluorinated sites (SiF6 2- and F- anions) lining along the pore surface. The optimal pore size (≈5 Å) combining mixed and high-density electronegative fluorinated sites enable 1 to preferentially adsorb C2H2 over CO2 and C2H4 by hydrogen bonding interactions with a high C2H2 isosteric heat of adsorption (Qst) of ≈42.3 kJ mol-1 at zero loading. The pronounced discriminatory sorption behaviors lead to excellent separation performance for C2H2/CO2 and C2H2/C2H4 that surpasses many well-known sorbents. Dynamic breakthrough experiments are conducted to confirm the practical separation capability of 1, which reveal an impressive separation factor of 6.1 for equimolar C2H2/CO2 mixture. Furthermore, molecular simulation and density functional theory (DFT) calculations validate the strong binding of C2H2 stems from the chelating fix of C2H2 between SiF6 2- anion and coordinated F- anion.

3.
Materials (Basel) ; 17(9)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38730785

RESUMO

Liquid metal (LM) is widely used in flexible electronic devices due to its excellent metallic conductivity and ductility. However, the fabrication of LM flexible strain sensors with high sensitivity and linearity is still a huge challenge, since the resistance of LM does not change much with strain. Here, a highly sensitive and linear fully flexible strain sensor with a resistive sensing function is proposed. The sensor comprises an Fe-doped liquid metal (Fe-LM) electrode for enhanced performance. The design and manufacturing of flexible strain sensors are based on the technology of controlling surface wettability by femtosecond laser micro/nano-processing. A supermetalphobic microstructure is constructed on a polydimethylsiloxane (PDMS) substrate to achieve the selection adhesion of Fe-LM on the PDMS substrate. The Fe-LM-based flexible strain sensor has high sensitivity and linearity, a gauge factor (GF) up to 1.18 in the strain range of 0-100%, excellent linearity with an R2 of 0.9978, a fast response time of 358 ms, and an excellent durability of more than 2400 load cycles. Additionally, the successful monitoring of human body signals demonstrates the potential of our developed flexible strain sensor in wearable monitoring applications.

4.
Plants (Basel) ; 13(9)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38732474

RESUMO

Genomic selection (GS) is a marker-based selection method used to improve the genetic gain of quantitative traits in plant breeding. A large number of breeding datasets are available in the soybean database, and the application of these public datasets in GS will improve breeding efficiency and reduce time and cost. However, the most important problem to be solved is how to improve the ability of across-population prediction. The objectives of this study were to perform genomic prediction (GP) and estimate the prediction ability (PA) for seed oil and protein contents in soybean using available public datasets to predict breeding populations in current, ongoing breeding programs. In this study, six public datasets of USDA GRIN soybean germplasm accessions with available phenotypic data of seed oil and protein contents from different experimental populations and their genotypic data of single-nucleotide polymorphisms (SNPs) were used to perform GP and to predict a bi-parent-derived breeding population in our experiment. The average PA was 0.55 and 0.50 for seed oil and protein contents within the bi-parents population according to the within-population prediction; and 0.45 for oil and 0.39 for protein content when the six USDA populations were combined and employed as training sets to predict the bi-parent-derived population. The results showed that four USDA-cultivated populations can be used as a training set individually or combined to predict oil and protein contents in GS when using 800 or more USDA germplasm accessions as a training set. The smaller the genetic distance between training population and testing population, the higher the PA. The PA increased as the population size increased. In across-population prediction, no significant difference was observed in PA for oil and protein content among different models. The PA increased as the SNP number increased until a marker set consisted of 10,000 SNPs. This study provides reasonable suggestions and methods for breeders to utilize public datasets for GS. It will aid breeders in developing GS-assisted breeding strategies to develop elite soybean cultivars with high oil and protein contents.

5.
Sci Data ; 11(1): 488, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734729

RESUMO

Domesticated herbivores are an important agricultural resource that play a critical role in global food security, particularly as they can adapt to varied environments, including marginal lands. An understanding of the molecular basis of their biology would contribute to better management and sustainable production. Thus, we conducted transcriptome sequencing of 100 to 105 tissues from two females of each of seven species of herbivore (cattle, sheep, goats, sika deer, horses, donkeys, and rabbits) including two breeds of sheep. The quality of raw and trimmed reads was assessed in terms of base quality, GC content, duplication sequence rate, overrepresented k-mers, and quality score distribution with FastQC. The high-quality filtered RNA-seq raw reads were deposited in a public database which provides approximately 54 billion high-quality paired-end sequencing reads in total, with an average mapping rate of ~93.92%. Transcriptome databases represent valuable resources that can be used to study patterns of gene expression, and pathways that are related to key biological processes, including important economic traits in herbivores.


Assuntos
Herbivoria , Transcriptoma , Animais , Bovinos/genética , Feminino , Coelhos/genética , Bases de Dados Genéticas , Cervos/genética , Equidae/genética , Cabras/genética , Cavalos/genética , Ovinos/genética
6.
Heliyon ; 10(9): e30179, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38737228

RESUMO

Self-health monitoring technologies have become increasingly popular in averting unanticipated health complications. However, the adoption rate of such technologies in developing countries is surprisingly low. Furthermore, empirical studies on the application of the value-belief-norm (VBN) model to elucidate intention to use IoT-enabled wearable fitness devices (IoT-enabled WFDs) are scarce. This study aimed to expand the VBN model by integrating health values, health consciousness, health knowledge-seeking, and social norms as influencing constructs. The proposed holistic framework was empirically tested to examine these constructs on users' decision-making process of adopting IoT-enabled WFDs. A web-based survey involving 866 adults in China aged 18-30 years was conducted. The gathered data were analysed using partial least squares-structural equation modeling. The results revealed the significant influence of health consciousness and health knowledge-seeking on personal health beliefs, as well as the favourable impact of personal health beliefs on personal norms and awareness of consequences. The results further demonstrated the substantial influence of awareness of consequences and ascription of responsibilities on personal norms. Besides that, personal norms and societal norms were found to have strong influence on the intention to adopt IoT-enabled WFDs, which was revealed to have significant influence on the actual usage. This study's findings offer novel theoretical insights on the behavioural characteristics of adopting IoT-enabled WFDs and serve as a practical guideline for industry experts and marketers to establish appropriate marketing strategies to support the IoT-enabled wearable sector. The findings also benefit policymakers in their efforts of developing strategies that emphasise the unique benefits of self-healthcare monitoring to encourage active lifestyle and decrease obesity and overweight-related health risks.

7.
Heliyon ; 10(9): e30408, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38726146

RESUMO

Background: Low-dose colchicine has been shown to lower major adverse cardiovascular events (MACE) among those with cardiovascular disease (CVD). It remains unclear how long a CVD patient needs to live to potentially benefit from colchicine. Our study aimed to determine the time to benefit (TTB) of colchicine in individuals with CVD. Methods: Literature searches were performed in PubMed for the cardiovascular outcome trial of colchicine in patients with CVD until October 12, 2023. The primary outcome measured was MACE. Reconstructed individual participant data (IPD) and the stratified Cox proportional hazards model were used to calculate the hazard ratio (HR) and 95 % confidence interval (CI) to estimate the efficacy of colchicine, and Weibull survival curves were fitted to estimate TTB for specific absolute risk reduction (ARR) thresholds (0.002, 0.005, and 0.01). Results: Four trials randomizing 11,594 adults aged between 59.8 and 66.5 years were included (follow-up duration: 12-28.6 months). Compared with placebo, colchicine reduced the risk of MACE (HR 0.68, 95 % CI: 0.60 to 0.78) but had no impact on cardiovascular and all-cause mortality. A TTB of 11.0 months (95 % CI: 0.59 to 21.3) was estimated to be needed to prevent 1 MACE in 100-colchicine-treated patients. The TTB for acute coronary syndrome was similar compared to stable coronary artery disease (10.7 vs. 11.2 months for ARR = 0.010). Conclusions: By using reconstructed IPD, this pooled analysis demonstrated that colchicine was associated with reduced nonfatal MACE, and the TTB was approximately 11.0 months to prevent 1 MACE per 100 patients.

8.
J Agric Food Chem ; 72(19): 10794-10804, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38711396

RESUMO

Chitin-degrading enzymes are critical components in regulating the molting process of the Asian corn borer and serve as potential targets for controlling this destructive pest of maize. Here, we used a scaffold-hopping strategy to design a series of efficient naphthylimide insecticides. Among them, compound 8c exhibited potent inhibition of chitinase from OfChi-h and OfChtI at low nanomolar concentrations (IC50 = 1.51 and 9.21 nM, respectively). Molecular docking simulations suggested that 8c binds to chitinase by mimicking the interaction of chitin oligosaccharide substrates with chitinase. At low ppm concentrations, compound 8c performed comparably to commercial insecticides in controlling the highly destructive plant pest, the Asian corn borer. Tests on a wide range of nontarget organisms indicate that compound 8c has very low toxicity. In addition, the effect of inhibitor treatment on the expression of genes associated with the Asian corn borer chitin-degrading enzymes was further investigated by quantitative real-time polymerase chain reaction. In conclusion, our study highlights the potential of 8c as a novel chitinase-targeting insecticide for effective control of the Asian corn borer, providing a promising solution in the quest for sustainable pest management.


Assuntos
Quitina , Quitinases , Proteínas de Insetos , Inseticidas , Simulação de Acoplamento Molecular , Mariposas , Zea mays , Animais , Quitinases/química , Quitinases/genética , Quitinases/metabolismo , Mariposas/enzimologia , Mariposas/efeitos dos fármacos , Mariposas/genética , Quitina/química , Quitina/metabolismo , Inseticidas/química , Inseticidas/farmacologia , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Proteínas de Insetos/química , Proteínas de Insetos/antagonistas & inibidores , Zea mays/química , Zea mays/parasitologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Desenho de Fármacos , Controle de Insetos , Larva/crescimento & desenvolvimento , Larva/efeitos dos fármacos , Relação Estrutura-Atividade
9.
Food Res Int ; 187: 114407, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38763661

RESUMO

Microalgae protein holds great potential for various applications in the food industry. However, the current knowledge regarding microalgae protein remains limited, with little information available on its functional properties. Furthermore, the relationship between its molecular structure and functional properties is not well defined, which limits its application in food processing. This study aims to addresses these gaps though an analysis of the emulsibility and foamability of various soluble protein isolates from two species of Spirulina (Arthospira platensis and Spirulina platensis), and the functional properties of Spirulina protein isolates in relation to its molecular structure and charge state. Results revealed that the degree of cross-linking and aggregation or folding and curling of protein tertiary structures was higher in the highly soluble Spirulina protein isolates (AP50% and SP50%) than in the low-solubility isolates (AP30% and SP30%). The foaming capacity (FC) of AP50% and SP50% was found to be lower than that of AP30% and SP30%. Spirulina protein isolates can stably adsorb at the air-water interface for at least 20 min and possessed good interfacial activity. A high pH value was found to promote cross-linking of protein particles at the oil-water interface, thereby reinforcing the internal network structure of emulsions and increasing viscosity. These findings provide preliminary insights for potential applications of Spirulina protein isolates in food production, especially towards quality improvement.


Assuntos
Proteínas de Bactérias , Emulsões , Solubilidade , Spirulina , Spirulina/química , Emulsões/química , Proteínas de Bactérias/química , Emulsificantes/química , Manipulação de Alimentos/métodos , Estrutura Molecular , Adsorção
10.
BMC Pediatr ; 24(1): 321, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724944

RESUMO

BACKGROUND: Radiologic volumetric evaluation of Wilms' tumor (WT) is an important indicator to guide treatment decisions. However, due to the heterogeneity of the tumors, radiologists have main-guard differences in diagnosis that can lead to misdiagnosis and poor treatment. The aim of this study was to explore whether CT-based outlining of WT foci can be automated using deep learning. METHODS: We included CT intravenous phase images of 105 patients with WT and double-blind outlining of lesions by two radiologists. Then, we trained an automatic segmentation model using nnUnet. The Dice similarity coefficient (DSC) and 95th percentile Hausdorff distance (HD95) were used to assess the performance. Next, we optimized the automatic segmentation results based on the ratio of the three-dimensional diameter of the lesion to improve the performance of volumetric assessment. RESULTS: The DSC and HD95 was 0.83 ± 0.22 and 10.50 ± 8.98 mm. The absolute difference and percentage difference in tumor size was 72.27 ± 134.84 cm3 and 21.08% ± 30.46%. After optimization according to our method, it decreased to 40.22 ± 96.06 cm3 and 10.16% ± 9.70%. CONCLUSION: We introduce a novel method that enhances the accuracy of predicting WT volume by integrating AI automated outlining and 3D tumor diameters. This approach surpasses the accuracy of using AI outcomes alone and has the potential to enhance the clinical evaluation of pediatric patients with WT. By intertwining AI outcomes with clinical data, this method becomes more interpretive and offers promising applications beyond Wilms tumor, extending to other pediatric diseases.


Assuntos
Neoplasias Renais , Tomografia Computadorizada por Raios X , Tumor de Wilms , Humanos , Tumor de Wilms/diagnóstico por imagem , Tumor de Wilms/patologia , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Tomografia Computadorizada por Raios X/métodos , Masculino , Feminino , Pré-Escolar , Lactente , Criança , Carga Tumoral , Aprendizado Profundo , Método Duplo-Cego , Imageamento Tridimensional , Estudos Retrospectivos
11.
ACS Omega ; 9(19): 21333-21345, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38764651

RESUMO

The solubility of eplerenone (EP) in 13 pure solvents (acetonitrile, N,N-dimethylformamide (DMF), acetone, 2-butanone, 4-methyl-2-pentanone, ethyl formate, methyl acetate, ethyl acetate, propyl acetate, butyl acetate, methyl propionate, ethyl propionate, ethanol, and 1-propanol) was determined by the gravimetric method at atmospheric pressure and various temperatures (from 283.15 to 323.15 K). The results showed that the solubility of EP in the selected solvents was positively correlated with the thermodynamic temperature, and the order of solubility of EP at 298.15 K was acetonitrile > DMF > 2-butanone > methyl acetate > 4-methyl-2-pentanone > methyl propionate > ethyl acetate > propyl acetate > ethyl formate > acetone > butyl acetate > ethanol >1-propanol. The modified Apelblat model, van't Hoff model, λh model, and polynomial empirical model were used for fitting the solubility data, and then the λh model was found to have the highest fitting accuracy with a minimum ARD of 7.0 × 10-3 and a minimum RMSD of 6.1 × 10-6. The solvent effect between the solute and the solvent was analyzed using linear solvation energy relationship (LSER), and the enthalpy of solvation (ΔsolH°), entropy of solvation (ΔsolS°), and Gibbs free energy of solvation (ΔsolG°) of the dissolution process of EP were calculated by the van't Hoff model, which indicated that the dissolution process of EP in the selected solvents was endothermic, nonspontaneous, and entropy-increasing. In this work, the solubility, dissolution characteristics, and thermodynamic parameters of EP were studied, which will provide data support for the production, crystallization, and purification of EP and will provide important guidance for the crystallization optimization of EP in industry.

12.
Food Chem X ; 22: 101431, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38764781

RESUMO

In the study, the effects of short-chain inulin (OP), natural inulin (OH), and long-chain inulin (OHP) at substitution levels of 3%, 6%, and 9%, as well as freezing of 0, 15, and 30 days, on the farinograph and extensograph characteristics of flour, the rheological properties, water distribution, and microstructure of dough, as well as the quality of the final steamed bread, were investigated. The findings revealed that inulin led to a reduction in the water absorption of the dough while increasing its stable time. Furthermore, inulin delayed the alteration of freezable water within the frozen dough. Notably, the addition of inulin resulted in a more cohesive and evenly arranged network structure within the frozen dough. Steamed bread supplemented with 6% OP, 6% OH, and 3% OHP consistently dislayed a higher specific volume and spread ratio. These findings offer valuable insights into the utilization of inulin in frozen wheat foods.

13.
Nat Commun ; 15(1): 4340, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773142

RESUMO

Macrophage-orchestrated inflammation contributes to multiple diseases including sepsis. However, the underlying mechanisms remain to be defined clearly. Here, we show that macrophage TP53-induced glycolysis and apoptosis regulator (TIGAR) is up-regulated in murine sepsis models. When myeloid Tigar is ablated, sepsis induced by either lipopolysaccharide treatment or cecal ligation puncture in male mice is attenuated via inflammation inhibition. Mechanistic characterizations indicate that TIGAR directly binds to transforming growth factor ß-activated kinase (TAK1) and promotes tumor necrosis factor receptor-associated factor 6-mediated ubiquitination and auto-phosphorylation of TAK1, in which residues 152-161 of TIGAR constitute crucial motif independent of its phosphatase activity. Interference with the binding of TIGAR to TAK1 by 5Z-7-oxozeaenol exhibits therapeutic effects in male murine model of sepsis. These findings demonstrate a non-canonical function of macrophage TIGAR in promoting inflammation, and confer a potential therapeutic target for sepsis by disruption of TIGAR-TAK1 interaction.


Assuntos
Proteínas Reguladoras de Apoptose , Modelos Animais de Doenças , Lipopolissacarídeos , MAP Quinase Quinase Quinases , Macrófagos , Sepse , Animais , Sepse/imunologia , Sepse/tratamento farmacológico , Sepse/metabolismo , MAP Quinase Quinase Quinases/metabolismo , MAP Quinase Quinase Quinases/genética , Masculino , Camundongos , Macrófagos/metabolismo , Macrófagos/imunologia , Macrófagos/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas Reguladoras de Apoptose/genética , Camundongos Endogâmicos C57BL , Fosforilação , Humanos , Ubiquitinação , Zearalenona/análogos & derivados , Zearalenona/farmacologia , Zearalenona/administração & dosagem , Fator 6 Associado a Receptor de TNF/metabolismo , Fator 6 Associado a Receptor de TNF/genética , Inflamação/metabolismo , Inflamação/patologia , Monoéster Fosfórico Hidrolases/metabolismo , Camundongos Knockout , Lactonas , Resorcinóis
14.
Minerva Urol Nephrol ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38757773

RESUMO

BACKGROUND: A three-dimensional (3D) reconstruction of the kidney, parapelvic cyst and the collecting system was conducted using the 3D Slicer software. The reconstructed image was used to form a virtual endoscope to assist flexible ureteroscopic incision and drainage was performed with a holmium laser for treating parapelvic cysts. The effectiveness of this assistive technique was assessed. METHODS: This was a retrospective cohort study. The clinical information of 59 patients undergoing flexible ureteroscopic incision and drainage for parapelvic cysts in two medical centers was collected. 3D Slicer software reconstruction and virtual endoscopic imaging were performed for 28 cases. Before the operation, the best point for incision on the collecting system's mucosa was assessed by virtual endoscope imaging. Propensity score matching was adopted for the reconstructive and non-reconstructive groups. RESULTS: After matching, the reconstructive group and non-reconstructive group both had 21 cases each. The operation time in the reconstructive and non-reconstructive groups was 38.81±5.01 and 51.00±18 minutes, respectively. Statistically significant differences existed between the two groups (t=7.024, P<0.001). No statistical significance was found in postoperative fever, immediate postoperative C reactive protein (CRP), length of postoperative hospital stay and cyst diameter three months after the operation. CONCLUSIONS: The operator was provided with a more direct and real vision when 3D Slicer software reconstruction was adopted via virtual endoscopic imaging to assist flexible ureteroscopic parapelvic cyst incision. This helped reduce the operation time. Further follow-ups and observations are required to assess the long-term efficacy of flexible ureteroscopic parapelvic cyst incision.

15.
Biochim Biophys Acta Mol Basis Dis ; 1870(6): 167223, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38718844

RESUMO

BACKGROUND: Erectile dysfunction (ED) seriously affects men's normal life, and obstructive sleep apnoea (OSA) has been diagnosed as a causative factor. Currently, exosomes secreted by adipose mesenchymal stem cells (ADSC) have been used in the non-clinical experimental treatment of ED disease with prominent efficacy due to the advantages of high stability and no immune exclusion. METHODS: In this study, chronic intermittent hypoxia (CIH) exposure was used to induce ED-corresponding phenotypes in Sprague Dawley (SD) rats as well as in cavernous smooth muscle cells (CCSMCs). ED symptoms were treated using exosomes secreted by ADSCs overexpressing circPIP5K1C (EXO-circ) injected into the rat corpus cavernosum. RESULTS: EXO-circ has the effect of ameliorating ED induced by CIH exposure in rats, the mechanism of which is to promote the expression of the downstream target gene SMURF1 after adsorption of miR-153-3p through the sponge so that SMURF1 and PFKFB3 occur protein-protein binding and ubiquitination degradation of PFKFB3 appears to inhibit the occurrence of spongiotic smooth muscle cells glycolysis, and to restore the function of the smooth muscle. CONCLUSIONS: These findings show that EXO-circ have a promising therapeutic potential in OSA-induced ED.

16.
Int J Oncol ; 64(6)2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38757347

RESUMO

Cellular senescence has a complex role in lymphocyte carcinogenesis and drug resistance of lymphomas. Senescent lymphoma cells combine with immunocytes to create an ageing environment that can be reprogrammed with a senescence­associated secretory phenotype, which gradually promotes therapeutic resistance. Certain signalling pathways, such as the NF­κB, Wnt and PI3K/AKT/mTOR pathways, regulate the tumour ageing microenvironment and induce the proliferation and progression of lymphoma cells. Therefore, targeting senescence­related enzymes or their signal transduction pathways may overcome radiotherapy or chemotherapy resistance and enhance the efficacy of relapsed/refractory lymphoma treatments. Mechanisms underlying drug resistance in lymphomas are complex. The ageing microenvironment is a novel factor that contributes to drug resistance in lymphomas. In terms of clinical translation, some senolytics have been used in clinical trials on patients with relapsed or refractory lymphoma. Combining immunotherapy with epigenetic drugs may achieve better therapeutic effects; however, senescent cells exhibit considerable heterogeneity and lymphoma has several subtypes. Extensive research is necessary to achieve the practical application of senolytics in relapsed or refractory lymphomas. This review summarises the mechanisms of senescence­associated drug resistance in lymphoma, as well as emerging strategies using senolytics, to overcome therapeutic resistance in lymphoma.


Assuntos
Senescência Celular , Resistencia a Medicamentos Antineoplásicos , Linfoma , Microambiente Tumoral , Humanos , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Senescência Celular/efeitos dos fármacos , Linfoma/tratamento farmacológico , Linfoma/patologia , Linfócitos/imunologia , Linfócitos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Carcinogênese/efeitos dos fármacos , Senoterapia/farmacologia , Senoterapia/uso terapêutico , Envelhecimento
17.
Artigo em Inglês | MEDLINE | ID: mdl-38700768

RESUMO

The combination of aerated flows and a high-pressure environment in a stilling basin can result in the supersaturation of total dissolved gas (TDG) downstream of hydraulic projects, posing an ecological risk to aquatic populations by inducing gas bubble disease (GBD) or other negative effects. There is limited literature reporting TDG mass transfer experiments on a complete physical dam model; most existing research is based on measurements in prototype tailwaters. In this study, TDG mass transfer experiments were conducted on a physical model of an under-constructed dam, with TDG-supersaturated water as the inflow, and TDG concentrations were meticulously monitored within the stilling basin. The measurements indicate that the TDG saturation at the outlet of the stilling basin decreased by 13.7% and 10.6% compared to the inlet for the two cases, respectively. Subsequently, an improved TDG prediction model was developed by incorporating a sub-grid air entrainment model and a phase-constrained scalar model. The numerical simulation results were compared with experimental data, indicating a maximum error in TDG saturation at all measured points of less than ± 3%. Moreover, the TDG saturation showed an error of only ± 0.3% at the outlet of the stilling basin. This model has broad applicability to various flow types for obtaining TDG mass transfer results and evaluating mitigation measures of TDG supersaturation to reduce the harmful effects on aquatic ecosystems.

18.
Int J Biol Macromol ; 268(Pt 2): 131938, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38692539

RESUMO

ING proteins display a high level of evolutionary conservation across various species, and play a crucial role in modulating histone acetylation levels, thus regulating various important biological processes in yeast and humans. Filamentous fungi possess distinct biological characteristics that differentiate them from yeasts and humans, and the specific roles of ING proteins in filamentous fungi remain largely unexplored. In this study, an ING protein, Fng2, orthologous to the yeast Pho23, has been identified in the wheat head blight fungus Fusarium graminearum. The deletion of the FNG2 gene resulted in defects in vegetative growth, conidiation, sexual reproduction, plant infection, and deoxynivalenol (DON) biosynthesis. Acting as a global regulator, Fng2 exerts negative control over histone H4 acetylation and governs the expression of over 4000 genes. Moreover, almost half of the differentially expressed genes in the fng3 mutant were found to be co-regulated by Fng2, emphasizing the functional association between these two ING proteins. Notably, the fng2 fng3 double mutant exhibits significantly increased H4 acetylation and severe defects in both fungal development and pathogenesis. Furthermore, Fng2 localizes within the nucleus and associates with the FgRpd3 histone deacetylase (HDAC) to modulate gene expression. Overall, Fng2's interaction with FgRpd3, along with its functional association with Fng3, underscores its crucial involvement in governing gene expression, thereby significantly influencing fungal growth, asexual and sexual development, pathogenicity, and secondary metabolism.

19.
Cardiovasc Diagn Ther ; 14(2): 240-250, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38716315

RESUMO

Background: Data on the associations of triglyceride (TG) levels with cardiovascular disease (CVD) and all-cause mortality mainly focused on the middle-aged or elderly population, with limited information available for younger adults. This study aimed to identify such associations among Chinese young adults. Methods: This study included Chinese adults younger than 40 years free of CVD, cancer, and lipid-lowering agents at baseline in the Kailuan study who were enrolled during 2006 through 2016. All participants were biennially followed up till December 2020. The enzymatic colorimetric method was used to measure baseline fasting TG. Participants were categorized into four groups by quartiles of TG, with the lowest quartile (Q1) as the reference group. The primary outcomes were CVD [composite of myocardial infarction (MI) and ischemic stroke] and all-cause mortality. CVD and mortality risks were estimated with Cox regression models. Results: A total of 43,882 participants were included. Their mean age was 30.6±5.56 years, and 80.2% were males. During a median follow-up of 11.2 years, 298 CVD events and 345 deaths occurred. The incidences of CVD and all-cause mortality were 0.67 and 0.76 per 1,000 person-years, respectively. Compared with individuals in the lowest quartile (Q1), participants in the highest quartile (Q4) showed a 126% higher risk of developing CVD [adjusted hazard ratio (HR) 2.26; 95% confidence interval (CI): 1.56 to 3.29; P=0.001] and a 61% higher risk of all-cause mortality (adjusted HR 1.61; 95% CI: 1.14 to 2.28; P=0.007). In addition, analyses of CVD subtypes showed that adjusted HRs (Q4 vs. Q1) were 3.25 (95% CI: 1.33 to 7.97; P=0.01) for MI, and 1.88 (95% CI: 1.16 to 3.04; P=0.01) for ischemic stroke. Conclusions: Among Chinese young adults, elevated fasting TG levels were associated with increased CVD and all-cause mortality risks.

20.
Research (Wash D C) ; 7: 0356, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38716471

RESUMO

Due to the breaking of time-reversal and parity symmetries and the presence of non-conservative microscopic interactions, active spinner fluids and solids respectively exhibit nondissipative odd viscosity and nonstorage odd elasticity, engendering phenomena unattainable in traditional passive or active systems. Here, we study the effects of odd viscosity and elasticity on phase behaviors of active spinner systems. We find the spinner fluid under a simple shear experiences an anisotropic gas-liquid phase separation driven by the odd-viscosity stress. This phase separation exhibits equilibrium-like behavior, with both binodal-like and spinodal curves and critical point. However, the formed dense liquid phase is unstable, since the odd elasticity instantly takes over the odd viscosity to condense the liquid into a solid-like phase. The unusual phase behavior essentially arises from the competition between thermal fluctuations and the odd response-induced effective attraction. Our results demonstrate that the cooperation of odd viscosity and elasticity can lead to exotic phase behavior, revealing their fundamental roles in phase transition.

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