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1.
J Agric Food Chem ; 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39231315

RESUMEN

Plants have complex detoxification and metabolic systems that enable them to deal with environmental pollutants. We report accumulation of the pesticide isoproturon (IPU) in a BR signaling pathway for mutant bzr4-3/5 rice to be significantly higher than in wild-type (WT) rice controls and for exogenous 24-epibrassinolide to reverse toxic symptoms in WT rice but not in mutants. A genome-wide RNA sequencing study of WT/bzr4 rice is performed to identify transcriptomic changes and metabolic mechanisms under IPU exposure. Three differentially expressed genes in yeast cells increase the degradation rate of IPU in a growth medium by factors of 1.61, 1.51, and 1.29 after 72 h. Using UPLC/Q-TOF-MS/MS, five phase I metabolites and five phase II conjugates are characterized in rice grains, with concentrations generally decreasing in bzr4 rice grains. OsBZR4, a regulator of IPU degradation in rice, may eliminate IPU from edible parts of food crops by regulating downstream metabolic genes.

2.
J Agric Food Chem ; 72(34): 19143-19154, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39105716

RESUMEN

Starch was mixed with a gel to produce a starch-based gel ink, which exhibited favorable printing characteristics. Through the optimization of infill density, 3D-printed scaffolds with 50% infill density and a highly ordered microstructure were successfully fabricated. The addition of calcium carbonate nanoparticles-glucono delta lactone (CaCO3 NPs-GDL) had notable effects on the swelling degree, in vitro digestion, water stability, and pore distribution of the scaffolds. When the amount of CaCO3 NPs in the starch-based gel was 0.075 g, the resulting 3D-printed gel scaffold with a 50% infill density proved to be the most suitable for cultivating cell-based meat. It featured pore sizes ranging from 80 to 120 µm and a compression modulus of 246.76 Pa. After 7 days of proliferation, the C2C12 mouse skeletal myoblasts exhibited an approximately 2.81-fold increase in cell numbers. The fusion index and maturation index of C2C12 cells on the scaffolds were 57.00 ± 0.45% and 34.56 ± 0.56%, respectively. The starch-based gel scaffolds demonstrated excellent water stability and in vitro degradability. Moreover, C2C12 cells exhibited successful proliferation and differentiation on the starch-based scaffolds, ultimately leading to the production of cell-based meat. This study developed a starch-based composite gel scaffold for the manufacture of cell-based meat.


Asunto(s)
Geles , Carne , Impresión Tridimensional , Almidón , Andamios del Tejido , Almidón/química , Animales , Ratones , Andamios del Tejido/química , Geles/química , Carne/análisis , Línea Celular , Proliferación Celular/efectos de los fármacos , Ingeniería de Tejidos , Mioblastos/citología , Mioblastos/metabolismo , Carbonato de Calcio/química , Diferenciación Celular/efectos de los fármacos , Carne in Vitro
3.
Anim Nutr ; 18: 27-38, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39026602

RESUMEN

In nature, aflatoxins, especially aflatoxin B1 (AFB1), are the common mycotoxins, which cause serious health problems for humans and animals. This paper aimed to study the effects of AFB1 on flesh flavor and muscle development of grass carp (Ctenopharyngodon idella) and its mechanism. There were 1440 individual fish in total, with 6 treatments and each treatment replicated 3 times. The 6 treatments were fed a control diet with different doses of AFB1 (0.04, 29.48, 58.66, 85.94, 110.43 and 146.92 µg/kg diet) for 60 d. AFB1 increased myofiber diameter, as well as decreased myofiber density of grass carp muscle (P < 0.05). The contents of free amino acid decreased gradually (P < 0.05) as dietary AFB1 increased in the muscle of grass carp. The levels of reactive oxygen species, malonaldehyde and protein carbonyl (PC) were increased (P < 0.05) with the dietary AFB1 increased. The levels of antioxidant enzyme (glutathione peroxidase, glutathione, glutathione reductase, total antioxidant capacity, anti-superoxide anion, and anti-hydroxyl radical) were decreased (P < 0.05) with the dietary AFB1 increased. In addition, dietary AFB1 decreased the content of collagen, and downregulated the mRNA and protein levels of transforming growth factor-ß (TGF-ß)/Smads signaling pathway in grass carp muscle (P < 0.05). The mRNA and protein levels of myogenic regulatory factors were downregulated in grass carp muscle (P < 0.05). Furthermore, the activities of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) were increased (P < 0.05), and the protein levels of phosphorylate-38 mitogen-activated protein kinase (p-p38MAPK), phosphorylate-c-Jun N-terminal kinase, urokinase-type plasminogen activator (uPA), MMP-2 and MMP-9 were upregulated (P < 0.05), but collagen Ⅰ, laminin ß1 and fibronectin were downregulated (P < 0.05) with the dietary AFB1 increased in the muscle of grass carp. Based on the results of this study, we can draw the following conclusion: dietary AFB1 might damage flesh flavor and inhibit the muscle development through MAPK/uPA/MMP/extracellular matrix (ECM) signaling pathway in grass carp. Moreover, the recommended safe limit of AFB1 in feed is no more than 26.77 µg/kg diet according to the PC levels in grass carp muscle.

4.
Int J Mol Sci ; 25(14)2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39062957

RESUMEN

The AT-hook motif nuclear-localized (AHL) family is pivotal for the abiotic stress response in plants. However, the function of the cassava AHL genes has not been elucidated. Promoters, as important regulatory elements of gene expression, play a crucial role in stress resistance. In this study, the promoter of the cassava MeAHL31 gene was cloned. The MeAHL31 protein was localized to the cytoplasm and the nucleus. qRT-PCR analysis revealed that the MeAHL31 gene was expressed in almost all tissues tested, and the expression in tuber roots was 321.3 times higher than that in petioles. Promoter analysis showed that the MeAHL31 promoter contains drought, methyl jasmonate (MeJA), abscisic acid (ABA), and gibberellin (GA) cis-acting elements. Expression analysis indicated that the MeAHL31 gene is dramatically affected by treatments with salt, drought, MeJA, ABA, and GA3. Histochemical staining in the proMeAHL31-GUS transgenic Arabidopsis corroborated that the GUS staining was found in most tissues and organs, excluding seeds. Beta-glucuronidase (GUS) activity assays showed that the activities in the proMeAHL31-GUS transgenic Arabidopsis were enhanced by different concentrations of NaCl, mannitol (for simulating drought), and MeJA treatments. The integrated findings suggest that the MeAHL31 promoter responds to the abiotic stresses of salt and drought, and its activity is regulated by the MeJA hormone signal.


Asunto(s)
Arabidopsis , Regulación de la Expresión Génica de las Plantas , Manihot , Reguladores del Crecimiento de las Plantas , Proteínas de Plantas , Plantas Modificadas Genéticamente , Regiones Promotoras Genéticas , Estrés Fisiológico , Arabidopsis/genética , Arabidopsis/metabolismo , Plantas Modificadas Genéticamente/genética , Estrés Fisiológico/genética , Manihot/genética , Manihot/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Reguladores del Crecimiento de las Plantas/farmacología , Sequías , Ciclopentanos/farmacología , Ciclopentanos/metabolismo , Ácido Abscísico/farmacología , Ácido Abscísico/metabolismo , Oxilipinas/farmacología , Oxilipinas/metabolismo , Acetatos/farmacología
5.
Environ Sci Technol ; 58(29): 13056-13064, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-38900493

RESUMEN

Rubber-derived chemicals (RDCs) originating from tire and road wear particles are transported into road stormwater runoff, potentially threatening organisms in receiving watersheds. However, there is a lack of knowledge on time variation of novel RDCs in runoff, limiting initial rainwater treatment and subsequent rainwater resource utilization. In this study, we investigated the levels and time-concentration profiles of 35 target RDCs in road stormwater runoff from eight functional areas in the Greater Bay Area, South China. The results showed that the total concentrations of RDCs were the highest on the expressway compared with other seven functional areas. N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), 6PPD-quinone, benzothiazole, and 1,3-diphenylguanidine were the top four highlighted RDCs (ND-228840 ng/L). Seasonal and spatial differences revealed higher RDC concentrations in the dry season as well as in less-developed regions. A lag effect of reaching RDC peak concentrations in road stormwater runoff was revealed, with a lag time of 10-90 min on expressways. Small-intensity rainfall triggers greater contamination of rubber-derived chemicals in road stormwater runoff. Environmental risk assessment indicated that 35% of the RDCs posed a high risk, especially PPD-quinones (risk quotient up to 2663). Our findings contribute to a better understanding of managing road stormwater runoff for RDC pollution.


Asunto(s)
Lluvia , Goma , Ciudades , Contaminantes Químicos del Agua/análisis , Monitoreo del Ambiente , China
6.
Neurosci Bull ; 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38819707

RESUMEN

Knowledge about the neuronal dynamics and the projectome are both essential for understanding how the neuronal network functions in concert. However, it remains challenging to obtain the neural activity and the brain-wide projectome for the same neurons, especially for neurons in subcortical brain regions. Here, by combining in vivo microscopy and high-definition fluorescence micro-optical sectioning tomography, we have developed strategies for mapping the brain-wide projectome of functionally relevant neurons in the somatosensory cortex, the dorsal hippocampus, and the substantia nigra pars compacta. More importantly, we also developed a strategy to achieve acquiring the neural dynamic and brain-wide projectome of the molecularly defined neuronal subtype. The strategies developed in this study solved the essential problem of linking brain-wide projectome to neuronal dynamics for neurons in subcortical structures and provided valuable approaches for understanding how the brain is functionally organized via intricate connectivity patterns.

7.
Br J Cancer ; 130(11): 1819-1827, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38594370

RESUMEN

BACKGROUND: Although DHFR gene amplification has long been known as a major mechanism for methotrexate (MTX) resistance in cancer, the early changes and detailed development of the resistance are not yet fully understood. METHODS: We performed genomic, transcriptional and proteomic analyses of human colon cancer cells with sequentially increasing levels of MTX-resistance. RESULTS: The genomic amplification evolved in three phases (pre-amplification, homogenously staining region (HSR) and extrachromosomal DNA (ecDNA)). We confirm that genomic amplification and increased expression of DHFR, with formation of HSRs and especially ecDNAs, is the major driver of resistance. However, DHFR did not play a detectable role in the early phase. In the late phase (ecDNA), increase in FAM151B protein level may also have an important role by decreasing sensitivity to MTX. In addition, although MSH3 and ZFYVE16 may be subject to different posttranscriptional regulations and therefore protein expressions are decreased in ecDNA stages compared to HSR stages, they still play important roles in MTX resistance. CONCLUSION: The study provides a detailed evolutionary trajectory of MTX-resistance and identifies new targets, especially ecDNAs, which could help to prevent drug resistance. It also presents a proof-of-principal approach which could be applied to other cancer drug resistance studies.


Asunto(s)
Resistencia a Antineoplásicos , Amplificación de Genes , Metotrexato , Tetrahidrofolato Deshidrogenasa , Humanos , Metotrexato/farmacología , Resistencia a Antineoplásicos/genética , Tetrahidrofolato Deshidrogenasa/genética , Tetrahidrofolato Deshidrogenasa/metabolismo , Línea Celular Tumoral , Neoplasias del Colon/genética , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Antimetabolitos Antineoplásicos/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Genómica/métodos
8.
Foods ; 13(7)2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38611353

RESUMEN

AIMS: The study aimed to evaluate the effects of dietary folic acid (FA) on the production performance of laying hens, egg quality, and the nutritional differences between eggs fortified with FA and ordinary eggs. METHODS: A total of 288 26-week-old Hy-Line Brown laying hens (initial body weights 1.65 ± 0.10 kg) with a similar weight and genetic background were used. A completely randomized design divided the birds into a control group and three treatment groups. Each group consisted of six replicates, with twelve chickens per replicate. Initially, all birds were fed a basal diet for 1 week. Subsequently, they were fed a basal diet supplemented with 0, 5, 10, or 15 mg/kg FA in a premix for a duration of 6 weeks. RESULTS: Supplementation of FA could significantly (p < 0.05) enhance the FA content in egg yolks, particularly when 10 mg/kg was used, as it had the most effective enrichment effect. Compared to the control group, the Glu content in the 10 and 15 mg/kg FA groups showed a significant (p < 0.05) decrease. Additionally, the contents of Asp, Ile, Tyr, Phe, Cys, and Met in the 15 mg/kg FA group were significantly (p < 0.05) lower compared to the other groups. Adding FA did not have significant effects on the levels of vitamin A and vitamin E in egg yolk, but the vitamin D content in the 5 and 10 mg/kg FA groups showed a significant (p < 0.05) increase. Furthermore, the addition of FA did not have a significant effect on the levels of Cu, Fe, Mn, Se, and Zn in egg yolk. The dietary FA did not have a significant effect on the total saturated fatty acids (SFA) and polyunsaturated fatty acid (PUFA) content in egg yolk. However, the total monounsaturated fatty acid (MUFA) content in the 5 and 10 mg/kg groups significantly (p < 0.05) increased. These changes in nutritional content might be attributed to the increased very low-density lipoprotein (VLDL) protein content. The significant decrease in solute carrier family 1 Member 1 (SLC1A1), solute carrier family 1 Member 2 (SLC1A2), and solute carrier family 1 Member 3 (SLC1A3) gene expression compared to the control group appeared to be the reason for the decrease in amino acid content in egg yolk within the dietary FA group. CONCLUSION: The findings suggest that the appropriate addition of FA can enhance the levels of MUFA and vitamin D in egg yolks, thereby improving their nutritional value. Excessive intake of FA can decrease the effectiveness of enriching FA in egg yolk and impact the enrichment of certain amino acids. The yolk of eggs produced by adding 10 mg/kg of FA to the feed contains the optimal amount of nutrients. This study informs consumers purchasing FA-fortified eggs.

9.
Ecotoxicol Environ Saf ; 276: 116332, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38626608

RESUMEN

According to the International Agency for Research on Cancer (IARC), aflatoxin B1 (AFB1) has been recognized as a major contaminant in food and animal feed and which is a common mycotoxin with high toxicity. Previous research has found that AFB1 inhibited zebrafish muscle development. However, the potential mechanism of AFB1 on fish muscle development is unknown, so it is necessary to conduct further investigation. In the present research, the primary myoblast of grass carp was used as a model, we treated myoblasts with AFB1 for 24 h. Our results found that 5 µM AFB1 significantly inhibited cell proliferation and migration (P < 0.05), and 10 µM AFB1 promoted lactate dehydrogenase (LDH) release (P < 0.05). Reactive oxygen species (ROS), protein carbonyl (PC) and malondialdehyde (MDA) levels were increased in 15, 5 and 10 µM AFB1 (P < 0.05), respectively. Catalase (CAT), glutathione peroxidase (GPx) and total superoxide dismutase (T-SOD) activities were decreased in 10, 10 and 15 µM AFB1 (P < 0.05), respectively. Furthermore, 15 µM AFB1 induced oxidative damage by Nrf2 pathway, also induced apoptosis in primary myoblast of grass carp. Meanwhile, 15 µM AFB1 decreased MyoD gene and protein expression (P < 0.05). Importantly, 15 µM AFB1 decreased the protein expression of collagen Ⅰ and fibronectin (P < 0.05), and increased the protein levels of urokinase plasminogen activator (uPA), matrix metalloproteinase 9 (MMP-9), matrix metalloproteinase 2 (MMP-2), and p38 mitogen-activated protein kinase (p38MAPK) (P < 0.05). As a result, our findings suggested that AFB1 damaged the cell morphology, induced oxidative damage and apoptosis, degraded ECM components, in turn inhibiting myoblast development by activating the p38MAPK/urokinase-type plasminogen activator (uPA)/matrix metalloproteinase (MMPs)/extracellular matrix (ECM) signaling pathway.


Asunto(s)
Aflatoxina B1 , Carpas , Proliferación Celular , Matriz Extracelular , Mioblastos , Especies Reactivas de Oxígeno , Animales , Aflatoxina B1/toxicidad , Mioblastos/efectos de los fármacos , Matriz Extracelular/efectos de los fármacos , Matriz Extracelular/metabolismo , Proliferación Celular/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Estrés Oxidativo/efectos de los fármacos , Movimiento Celular/efectos de los fármacos
10.
J Acoust Soc Am ; 155(4): 2646-2658, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38634662

RESUMEN

This study discusses acoustic dissipation, which contributes to inaccuracies in impedance tube measurements. To improve the accuracy of these measurements, this paper introduces a transfer function model that integrates diverse dissipation prediction models. Bayesian inference is used to estimate the important parameters included in these models, describing dissipation originating from various mechanisms, sound speed, and microphone positions. By using experimental measurements and considering a hypothetical air layer in front of a rigid termination as the material under test, Bayesian parameter estimation allows a substantial enhancement in characterization accuracy by incorporating the dissipation and sound speed estimates. This approach effectively minimizes residual absorption coefficients attributed to both boundary-layer effects and air medium relaxation. The incorporation of dissipation models leads to a substantial reduction (to 1%) in residual absorption coefficients. Moreover, the use of accurately estimated parameters further enhances the accuracy of actual tube measurements of materials using the two-microphone transfer function method.

11.
Acta Pharmacol Sin ; 45(6): 1252-1263, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38360931

RESUMEN

Although ALK tyrosine kinase inhibitors (ALK-TKIs) have shown remarkable benefits in EML4-ALK positive NSCLC patients compared to conventional chemotherapy, the optimal sequence of ALK-TKIs treatment remains unclear due to the emergence of primary and acquired resistance and the lack of potential prognostic biomarkers. In this study, we systematically explored the validity of sequential ALK inhibitors (alectinib, lorlatinib, crizotinib, ceritinib and brigatinib) for a heavy-treated patient with EML4-ALK fusion via developing an in vitro and in vivo drug testing system based on patient-derived models. Based on the patient-derived models and clinical responses of the patient, we found that crizotinib might inhibit proliferation of EML4-ALK positive tumors resistant to alectinib and lorlatinib. In addition, NSCLC patients harboring the G1269A mutation, which was identified in alectinib, lorlatinib and crizotinib-resistant NSCLC, showed responsiveness to brigatinib and ceritinib. Transcriptomic analysis revealed that brigatinib suppressed the activation of multiple inflammatory signaling pathways, potentially contributing to its anti-tumor activity. Moreover, we constructed a prognostic model based on the expression of IL6, CXCL1, and CXCL5, providing novel perspectives for predicting prognosis in EML4-ALK positive NSCLC patients. In summary, our results delineate clinical responses of sequential ALK-TKIs treatments and provide insights into the mechanisms underlying the superior effects of brigatinib in patients harboring ALKG1269A mutation and resistant towards alectinib, lorlatinib and crizotinib. The molecular signatures model based on the combination of IL6, CXCL1 and CXCL5 has the potential to predict prognosis of EML4-ALK positive NSCLC patients.


Asunto(s)
Adenocarcinoma del Pulmón , Antineoplásicos , Neoplasias Pulmonares , Proteínas de Fusión Oncogénica , Compuestos Organofosforados , Inhibidores de Proteínas Quinasas , Pirimidinas , Humanos , Compuestos Organofosforados/uso terapéutico , Compuestos Organofosforados/farmacología , Pirimidinas/uso terapéutico , Pirimidinas/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo , Animales , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Pronóstico , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Resistencia a Antineoplásicos , Lactamas/uso terapéutico , Carbazoles/uso terapéutico , Carbazoles/farmacología , Sulfonas/uso terapéutico , Sulfonas/farmacología , Crizotinib/uso terapéutico , Crizotinib/farmacología , Línea Celular Tumoral , Piperidinas/uso terapéutico , Piperidinas/farmacología , Femenino , Ratones , Inflamación/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Pirazoles/uso terapéutico , Pirazoles/farmacología , Masculino , Quinasa de Linfoma Anaplásico/genética , Quinasa de Linfoma Anaplásico/antagonistas & inhibidores , Quinasa de Linfoma Anaplásico/metabolismo , Proliferación Celular/efectos de los fármacos , Mutación , Aminopiridinas/uso terapéutico , Aminopiridinas/farmacología
12.
Mol Ther ; 32(4): 1110-1124, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38341612

RESUMEN

Whether and how tumor intrinsic signature determines macrophage-elicited metastasis remain elusive. Here, we show, in detailed studies of data regarding 7,477 patients of 20 types of human cancers, that only 13.8% ± 2.6%/27.9% ± 3.03% of patients with high macrophage infiltration index exhibit early recurrence/vascular invasion. In parallel, although macrophages enhance the motility of various hepatoma cells, their enhancement intensity is significantly heterogeneous. We identify that the expression of malignant Dicer, a ribonuclease that cleaves miRNA precursors into mature miRNAs, determines macrophage-elicited metastasis. Mechanistically, the downregulation of Dicer in cancer cells leads to defects in miRNome targeting NF-κB signaling, which in turn enhances the ability of cancer cells to respond to macrophage-related inflammatory signals and ultimately promotes metastasis. Importantly, transporting miR-26b-5p, the most potential miRNA targeting NF-κB signaling in hepatocellular carcinoma, can effectively reverse macrophage-elicited metastasis of hepatoma in vivo. Our results provide insights into the crosstalk between Dicer-elicited miRNome and cancer immune microenvironments and suggest that strategies to remodel malignant cell miRNome may overcome pro-tumorigenic activities of inflammatory cells.


Asunto(s)
Carcinoma Hepatocelular , MicroARNs , Humanos , FN-kappa B/genética , FN-kappa B/metabolismo , Carcinoma Hepatocelular/patología , Transducción de Señal/fisiología , MicroARNs/genética , MicroARNs/metabolismo , Macrófagos/metabolismo , Línea Celular Tumoral , Microambiente Tumoral/genética
13.
Int J Ophthalmol ; 17(2): 324-330, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38371262

RESUMEN

AIM: To present the 1-year results of a prospective cohort study investigating the efficacy, potential mechanism, and safety of orthokeratology (ortho-k) with different back optic zone diameters (BOZD) for myopia control in children. METHODS: This randomized clinical study was performed between Dec. 2020 and Dec. 2021. Participants were randomly assigned to three groups wearing ortho-k: 5 mm BOZD (5-MM group), 5.5 mm BOZD (5.5-MM group), and 6 mm BOZD (6-MM group). The 1-year data were recorded, including axial length, relative peripheral refraction (RPR, measured by multispectral refractive topography, MRT), and visual quality. The contrast sensitivity (CS) was evaluated by CSV-1000 instrument with spatial frequencies of 3, 6, 12, and 18 cycles/degree (c/d); the corneal higher-order aberrations (HOAs) were measured by iTrace aberration analyzer. The one-way ANOVA was performed to assess the differences between the three groups. The correlation between the change in AL and RPR was calculated by Pearson's correlation coefficient. RESULTS: The 1-year results of 20, 21, and 21 subjects in the 5-MM, 5.5-MM, and 6-MM groups, respectively, were presented. There were no statistical differences in baseline age, sex, or ocular parameters between the three groups (all P>0.05). At the 1-year visit, the 5-MM group had lower axial elongation than the 6-MM group (0.07±0.09 vs 0.18±0.11 mm, P=0.001). The 5-MM group had more myopic total RPR (TRPR, P=0.014), with RPR in the 15°-30° (RPR 15-30, P=0.015), 30°-45° (RPR 30-45, P=0.011), temporal (RPR-T, P=0.008), and nasal area (RPR-N, P<0.001) than the 6-MM group. RPR 15-30 in the 5.5-MM group was more myopic than that in the 6-MM group (P=0.002), and RPR-N in the 5-MM group was more myopic than that in the 5.5-MM group (P<0.001). There were positive correlations between the axial elongation and the change in TRPR (r=0.756, P<0.001), RPR 15-30 (r=0.364, P=0.004), RPR 30-45 (r=0.306, P=0.016), and RPR-N (r=0.253, P=0.047). The CS decreased at 3 c/d (P<0.001), and the corneal HOAs increased in the 5-MM group (P=0.030). CONCLUSION: Ortho-k with 5 mm BOZD can control myopia progression more effectively. The mechanism may be associated with greater myopic shifts in RPR.

14.
Cancer Res ; 84(6): 841-854, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38231484

RESUMEN

Triggering ferroptosis, an iron-dependent form of cell death, has recently emerged as an approach for treating cancer. A better understanding of the role and regulation of ferroptosis is needed to realize the potential of this therapeutic strategy. Here, we observed extensive activation of ferroptosis in hepatoma cells and human hepatocellular carcinoma (HCC) cases. Patients with low to moderate activation of ferroptosis in tumors had the highest risk of recurrence compared to patients with no or high ferroptosis. Upon encountering ferroptotic liver cancer cells, aggregated macrophages efficiently secreted proinflammatory IL1ß to trigger neutrophil-mediated sinusoidal vascular remodeling, thereby creating favorable conditions for aggressive tumor growth and lung metastasis. Mechanistically, hyaluronan fragments released by cancer cells acted via an NF-κB-dependent pathway to upregulate IL1ß precursors and the NLRP3 inflammasome in macrophages, and oxidized phospholipids secreted by ferroptotic cells activated the NLRP3 inflammasome to release functional IL1ß. Depleting either macrophages or neutrophils or neutralizing IL1ß in vivo effectively abrogated ferroptosis-mediated liver cancer growth and lung metastasis. More importantly, the ferroptosis-elicited inflammatory cellular network served as a negative feedback mechanism that led to therapeutic resistance to sorafenib in HCC. Targeting the ferroptosis-induced inflammatory axis significantly improved the therapeutic efficacy of sorafenib in vivo. Together, this study identified a role for ferroptosis in promoting HCC by triggering a macrophage/IL1ß/neutrophil/vasculature axis. SIGNIFICANCE: Ferroptosis induces a favorable tumor microenvironment and supports liver cancer progression by stimulating an inflammatory cellular network that can be targeted to suppress metastasis and improve the efficacy of sorafenib.


Asunto(s)
Carcinoma Hepatocelular , Ferroptosis , Neoplasias Hepáticas , Neoplasias Pulmonares , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Sorafenib/farmacología , Proteína con Dominio Pirina 3 de la Familia NLR , Inflamasomas , Neoplasias Hepáticas/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Línea Celular Tumoral , Microambiente Tumoral
15.
Anticancer Drugs ; 35(3): 219-226, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-37948336

RESUMEN

After an initial positive response to chemotherapy, cancer patients often become resistant and experience relapse. Our previous research identified eukaryotic translation initiation factor 4E (eIF4E) as a crucial target to overcome chemoresistance. In this study, we delved further into the role and therapeutic potential of myeloid cell leukemia 1 (Mcl-1), an eIF4E-mediated target, in chemoresistance. We showed that the levels of phosphor and total eIF4E, as well as Mcl-1, were elevated in chemoresistant cervical but not colon cancer cells. Mcl-1 inhibitor S64315 decreased Mcl-1 levels in chemoresistant cancer cells, regardless of Mcl-1 upregulation, decreased viability in chemoresistant cancer cells and acted synergistically with chemotherapy drugs. The combined inhibition of Mcl-1 and B-cell lymphoma 2 (Bcl-2), employing both genetic and pharmacological approaches, led to a markedly more substantial decrease in viability compared with the inhibition of either target individually. The combination of S64315 and Bcl-2 inhibitors reduced tumor growth in chemoresistant cervical and colon cancer models without causing general toxicity in mice. This combination also prolonged overall survival compared with using S64315 or venetoclax alone. Our research highlights the therapeutic potential of inhibiting Mcl-1 and Bcl-2 simultaneously in chemoresistant cancers and provides a rationale for initiating clinical trials to investigate the combination of S64315 and venetoclax for the treatment of advanced colon and cervical cancer.


Asunto(s)
Neoplasias del Colon , Resistencia a Antineoplásicos , Sulfonamidas , Animales , Humanos , Ratones , Apoptosis , Compuestos Bicíclicos Heterocíclicos con Puentes , Línea Celular Tumoral , Neoplasias del Colon/tratamiento farmacológico , Factor 4E Eucariótico de Iniciación , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-bcl-2/antagonistas & inhibidores
16.
Clin Immunol ; 258: 109857, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38043757

RESUMEN

Systemic lupus erythematosus (SLE) is a typical systemic autoimmune disease that manifests as skin rash, arthritis, lymphadenopathy, and multiple organ lesions. Epigenetics, including DNA methylation, histone modification, and non-coding RNA regulation, mainly affect the function and characteristics of cells through the regulation of gene transcription or translation. Increasing evidence indicates that there are a variety of complex epigenetic effects in patients with SLE, which interfere with the differentiation and function of T, and B lymphocytes, monocytes, and neutrophils, and enhance the expression of SLE-associated pathogenic genes. This paper summarizes our currently knowledge regarding pathogenesis of SLE, and introduces current advances in the epigenetic regulation of SLE from three aspects: immune function, inflammatory response, and lupus complications. We propose that epigenetic changes could be used as potential biomarkers and therapeutic targets of SLE.


Asunto(s)
Artritis , Lupus Eritematoso Sistémico , Humanos , Epigénesis Genética , Metilación de ADN , Artritis/genética , Diferenciación Celular
17.
Curr Eye Res ; 49(4): 410-416, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38116796

RESUMEN

PURPOSE: To evaluate the prevalence and types of artifacts in ultrawide-field swept-source optical coherence tomography angiography (SS-OCTA) scans of diabetic retinopathy (DR) patients. METHODS: This study was a prospective, observational study conducted from May 2022 to October 2022. Participants comprised individuals with proliferative diabetic retinopathy (PDR), nonproliferative diabetic retinopathy (NPDR), no diabetic retinopathy, and healthy controls. SS-OCTA imaging was performed, and a 5-scan composite with a larger field of view (23.5 mm × 17.5 mm) was captured using built-in software. Two experienced ophthalmologists analyzed the images independently, and the image quality and artifact prevalence were recorded and analyzed. RESULTS: The study included 70 eyes (16 with PDR, 24 with NPDR, 12 eyes of diabetic patients without DR, and 18 healthy eyes) in 70 subjects. Imaging artifacts were observed in a high percentage of eyes, with 98.57% of eyes presenting at least one type of artifact. A significant proportion of eyes (58.57%) exhibited a severe degree of artifacts. The most prevalent artifacts were loss of signal in 63 eyes (90%) and displacement artifact and masking artifact in 43 eyes (61.4%). Patients with more severe stages of DR had higher artifact scores (p < 0.05). Multivariate regression analysis indicated that DR severity was the most important factor influencing artifact scores (p < 0.05). CONCLUSIONS: In OCTA photos, various artifacts arise at different frequencies. It is crucial to qualitatively evaluate the images to ensure their quality. The results demonstrate that DR severity has a significant correlation with artifact scores.


Asunto(s)
Diabetes Mellitus , Retinopatía Diabética , Humanos , Retinopatía Diabética/diagnóstico , Artefactos , Tomografía de Coherencia Óptica/métodos , Estudios Prospectivos , Retina , Angiografía con Fluoresceína/métodos , Vasos Retinianos
18.
J Acoust Soc Am ; 154(6): 3941-3942, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38133512

RESUMEN

This special issue on three-dimensional (3D) sound reconstruction for virtual auditory displays: applications in buildings contains six research papers. Among them, three articles describe virtual reconstruction of important theatres and opera houses. The remaining articles focus on theoretical approaches of virtual sound localization or auralization.

19.
J Biol Chem ; 299(11): 105329, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37805139

RESUMEN

Prion diseases are a group of transmissible neurodegenerative diseases primarily caused by the conformational conversion of prion protein (PrP) from α-helix-dominant cellular prion protein (PrPC) to ß-sheet-rich pathological aggregated form of PrPSc in many mammalian species. Dogs exhibit resistance to prion diseases, but the mechanism behind the phenomenon remains poorly understood. Compared with human PrP and mouse PrP, dog PrP has two unique amino acid residues, Arg177 and Asp159. Because PrPC contains a low-complexity and intrinsically disordered region in its N-terminal domain, it undergoes liquid-liquid phase separation (LLPS) in vitro and forms protein condensates. However, little is known about whether these two unique residues modulate the formation of PrPC condensates. Here, using confocal microscopy, fluorescence recovery after photobleaching assays, thioflavin T binding assays, and transmission electron microscopy, we report that Arg177 and Asp159 from the dog PrP slow the LLPS of full-length human PrPC, shifting the equilibrium phase boundary to higher protein concentrations and inhibit amyloid formation of the human protein. In sharp contrast, His177 and Asn159 from the human PrP enhance the LLPS of full-length dog PrPC, shifting the equilibrium phase boundary to lower protein concentrations, and promote fibril formation of the canid protein. Collectively, these results demonstrate how LLPS and amyloid formation of PrP are inhibited by a single residue Arg177 or Asp159 associated with prion disease resistance, and how LLPS and fibril formation of PrP are promoted by a single residue His177 or Asn159. Therefore, Arg177/His177 and Asp159/Asn159 are key residues in modulating PrPC liquid-phase condensation.


Asunto(s)
Enfermedades por Prión , Priones , Ratones , Perros , Humanos , Animales , Proteínas Priónicas/metabolismo , Priones/metabolismo , Amiloide/química , Proteínas Amiloidogénicas , Mamíferos/metabolismo
20.
J Agric Food Chem ; 2023 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-37905821

RESUMEN

The rice cytochrome P450 gene has been comprehensively studied in the present study. This gene encodes CYP90D5 in promoting the degradation of isoproturon (IPU) and acetochlor (ACT) in rice tissues and grains. It has here been found that CYP90D5 improved the resistance of the plant to IPU and ACT, which was reflected in the improvement of the growth of the overexpression (OE) lines. CYP90D5 also reduced the levels of IPU and ACT accumulation in rice, and the CRISPR-Cas9 (Cas9) lines displayed the opposite effects. This function of CYP90D5 for pesticide degradation was also confirmed by the transformation of CYP90D5 in Pichia pastoris. Compared with the control yeast, it grew better and could degrade more pesticides. In addition, the relative contents of the IPU and ACT derivatives increased in the OE rice, while they decreased in the Cas9 rice. This suggested that CYP90D5 plays a pivotal role in the pesticide detoxification and degradation.

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