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1.
Neural Regen Res ; 20(3): 740-750, 2025 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38886939

RESUMEN

Lipid droplets serve as primary storage organelles for neutral lipids in neurons, glial cells, and other cells in the nervous system. Lipid droplet formation begins with the synthesis of neutral lipids in the endoplasmic reticulum. Previously, lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis; however, recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous system. In addition to their role in regulating cell metabolism, lipid droplets play a protective role in various cellular stress responses. Furthermore, lipid droplets exhibit specific functions in neurons and glial cells. Dysregulation of lipid droplet formation leads to cellular dysfunction, metabolic abnormalities, and nervous system diseases. This review aims to provide an overview of the role of lipid droplets in the nervous system, covering topics such as biogenesis, cellular specificity, and functions. Additionally, it will explore the association between lipid droplets and neurodegenerative disorders. Understanding the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.

2.
Microbiol Spectr ; : e0043624, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39162553

RESUMEN

The intact immune system of mice exhibits resistance to colonization by exogenous microorganisms, but the gut microbiota profiles of the humanized mice and the patterns of human fecal microbiota colonization remain unexplored. Humanized NCG (huNCG) mice were constructed by injected CD34 +stem cells. 16S rRNA sequencing and fecal microbiota transplantation (FMT) technologies were used to detect the differences in microbiota and selective colonization ability for exogenous community colonization among three mice cohorts (C57BL/6J, NCG, and huNCG). Flow cytometry analysis showed that all huNCG mice had over 25% hCD45 +in peripheral blood. 16S rRNA gene sequence analysis showed that compared with NCG mice, the gut microbiota of huNCG mice were significantly altered. After FMT, the principal coordinates analysis (PCoA) showed that the gut microbial composition of huNCG mice (huNCG-D9) was similar to that of donors. The relative abundance of Firmicutes and Bacteroidetes were significantly increased in huNCG mice compared to NCG mice. Further comparison of ASV sequences revealed that Bacteroides plebeius, Bacteroides finegoldii, Escherichia fergusonii, Escherichia albertii, Klebsiella pneumoniae, and Klebsiella variicola exhibited higher abundance and stability in huNCG mice after FMT. Furthermore, PICRUSt2 analysis showed that huNCG mice had significantly enhanced metabolism and immunity. This study demonstrated that humanized mice are more conducive to colonization within the human gut microbiota, which provides a good method for studying the association between human diseases and microbiota.IMPORTANCEThe gut microbiota and biomarkers of humanized mice are systematically revealed for the first time. The finding that human fecal microbiota colonize humanized mice more stably provides new insights into the study of interactions between immune responses and gut microbiota.

3.
Anal Methods ; 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39140766

RESUMEN

The early detection of bacterial species plays a crucial role in patient prognosis and the development of effective therapeutic regimens. This study introduces an accessible and promising colorimetric sensor array designed to classify gram-positive (G+) and gram-negative (G-) bacterial species. The classification relies on 6 chemical ligands with dimethylamino/amino groups as sensing elements and silver nanotriangles as colorimetric probes. Using these specific sensor arrays, we successfully differentiated G- and G+ bacterial species and discriminated individual bacterial strains, and the sensors exhibited remarkable reproducibility and high sensitivity. Moreover, the sensor array can identify bacterial mixtures and bacteria at varying concentrations, underscoring its versatility. In summary, this sensor array offers an effective tool for bacterial analysis with promising applications in the field of biomedical diagnostics.

4.
Arch Sex Behav ; 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39134736

RESUMEN

In addition to describing sexual partner preferences, sexual self-labels in gay and bisexual (henceforth, sexual minority) men, such as top, bottom, and versatile, are associated with psychological characteristics (e.g., gendered personality traits). No research has explored the association between sexual self-labels and eating and body image disturbances in sexual minority men. Research in sexual minority men from China is particularly valuable and needed due to recent rises in rates of eating and body image disturbances and unique, minority-specific stressors experienced by Chinese sexual minority populations. We adopted an online, cross-sectional study in a sample of sexual minority men from China (N = 403; tops, n = 256, bottoms, n = 95, versatiles, n = 52). Bottoms reported higher thinness internalization, lower muscularity internalization, higher body fat dissatisfaction, and higher psychological distress than tops. Bottoms' weight bias internalization was higher than tops' and versatiles' reports and, compared to versatiles, bottoms also reported higher psychosocial impairment related to eating disorder psychopathology. Compared to versatiles, tops reported higher drive for muscularity and muscularity-oriented disordered eating. Adjusting for age, psychological distress, and psychosocial impairment, tops reported higher muscularity internalization than bottoms and higher drive for muscularity and muscularity-oriented disordered eating than both bottoms and versatiles. Findings suggested unique relations between sexual self-labels and eating and body image disturbances in Chinese sexual minority men. Replication and validation of the temporal order between sexual self-labels and eating and body image disturbances is needed, including assessment of social factors (e.g., femmephobia, minority stress) that may help explain the links between sexual self-labels and eating pathology.

5.
Food Chem ; 460(Pt 3): 140689, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39116767

RESUMEN

Residues of pesticides in milk may pose a threat to human health. This study aimed to develop a liquid-phase microextraction (LPME) method using hexafluoroisopropanol (HFIP)-based supramolecular solvent (SUPRAS) for the simultaneous extraction and purification of four pesticides (boscalid, novaluron, cypermethrin and bifenthrin) in milk. Pesticides were extracted using SUPRAS prepared with nonanol and HFIP, and the extraction efficiency was analyzed. Results showed satisfactory recoveries ranging from 80.8%-111.0%, with relative standard deviations (RSDs) of <6.4%. Additionally, satisfactory linearities were observed, with correlation coefficients >0.9952. The limits of quantification (LOQs) were in the range of 1.8 µg·L-1-14.0 µg·L-1. The established method demonstrated high extraction efficiency with a short operation time (15 mins) and low solvent consumption (2.7 mL). The HFIP-based SUPRAS LPME method offers a convenient and efficient approach for the extraction of pesticides from milk, presenting a promising alternative to conventional techniques.

6.
Orthop Surg ; 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39139066

RESUMEN

OBJECTIVES: Cervical spondylosis may lead to changes in the sagittal parameters of the neck and trigger compensatory alterations in systemic sagittal parameters. However, there is currently a dearth of comparative research on the changes and compensatory alterations to sagittal parameters resulting from different types of cervical spondylosis. This study compared the preoperative sagittal alignment sequences among patients with cervical spondylotic radiculopathy (CSR), ossification of the posterior longitudinal ligament (OPLL), and cervical spondylotic myelopathy (CSM) caused by factors resulting from non-OPLL factors. MATERIALS AND METHODS: Full length lateral X-ray of the spine and cervical computed tomography (CT) of 256 patients (134 men, 122 women; mean age, 56.9 ± 9.5 years) were analyzed retrospectively. A total of 4096 radiomics features were measured through the lateral X-ray by two spinal surgeons with extensive experience. The clinical symptoms measures were the Japanese Orthopaedic Association (JOA) score, number of hand actions in 10 s, hand-grip strength, visual analog scale (VAS) score. Normally distributed data was compared using one-way analysis of variance (ANOVA) for parametric variables and χ2 test were used to analyze the categorical data. RESULTS: In the OPLL group, the C2-C7 Cobb angle was greater than in the CSR and CSM groups (19.8 ± 10.4°, 13.3 ± 10.3°, and 13.9 ± 9.9°, respectively, p < 0.001). Additionally, the C7-S1 SVA measure was found to be situated in the anterior portion with regards to the CSM and CSR groups (19.7 ± 58.4°, -6.3 ± 34.3° and -26.3 ± 32.9°, p < 0.001). Moreover, the number of individuals with C7-S1 SVA >50 mm was significantly larger than the CSM group (26/69, 11/83, p < 0.001). In the CSR group, the TPA demonstrated smaller values compared to the OPLL group (8.8 ± 8.5°, 12.7 ± 10.2°, p < 0.001). Furthermore, the SSA was comparatively smaller as opposed to both the OPLL and CSM groups (49.6 ± 11.2°, 54.2 ± 10.8° and 54.3 ± 9.3°, p < 0.05). CONCLUSION: Patients with OPLL exhibit greater cervical lordosis than those with CSR and CSM. However, OPLL is more likely to result in spinal imbalance when compared to the CSM group. Furthermore, OPLL and CSM patients exhibit anterior trunk inclination and worse global spine sagittal parameters in comparison to CSR patients.

7.
Clin Transl Sci ; 17(8): e13896, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39119977

RESUMEN

Ruzotolimod (Toll-like receptor 7 (TLR7) agonist, RG7854) is an oral, small molecule immuno-modulator activating the TLR 7 and is being evaluated in patients with CHB. As with other TLR7 agonists, the study drug-related adverse events of flu-like symptoms have been reported in some participants during phase I studies with ruzotolimod. An exploratory analysis of the relationship between pharmacokinetic (PK)/pharmacodynamic (PD) and flu-like symptoms was performed in participants from two phase I studies including both healthy volunteers and NUC-suppressed CHB patients who received either single or multiple ascending doses of orally administered ruzotolimod. Linear and logistic regression were used to explore potential relationships between dose, flu-like symptoms, PK, and PD. Generalized linear regression was performed to predict the probability of flu-like symptoms of all intensities at different RO7011785 (the active metabolite of the double prodrug ruzotolimod) PK exposure. This analysis showed that single or multiple doses of ruzotolimod at ⩾100 mg, the immune PD (IFN-α, neopterin, IP-10, and the transcriptional expression of ISG15, OAS-1, MX1, and TLR7) responses increase with the RO7011785 PK exposure, which increases linearly with the doses from 3 mg to 170 mg of ruzotolimod. The analysis also showed that the probability of flu-like symptoms occurrence increases with PD responses (IFN-α and IP-10). Dose reduction of ruzotolimod can be an effective way to reduce the magnitude of PD response, thus reducing the probability of study drug-related flu-like symptoms occurrence at all intensity in the participants who are highly sensitive to PD activation and intolerant to flu-like symptoms.


Asunto(s)
Voluntarios Sanos , Hepatitis B Crónica , Receptor Toll-Like 7 , Humanos , Receptor Toll-Like 7/agonistas , Masculino , Adulto , Femenino , Persona de Mediana Edad , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/inmunología , Hepatitis B Crónica/virología , Hepatitis B Crónica/sangre , Adulto Joven , Antivirales/farmacocinética , Antivirales/administración & dosificación , Antivirales/efectos adversos , Gripe Humana/tratamiento farmacológico , Gripe Humana/inmunología , Relación Dosis-Respuesta a Droga , Adolescente , Administración Oral , Compuestos Orgánicos
8.
Chem Biodivers ; : e202400818, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39110524

RESUMEN

Insect infestations continually endanger stored goods, underscoring the significance of discovering eco-friendly insecticides for pest management. Essential oils (EOs) from different parts of Toddalia asiatica (leaf, fruit and branch) were extracted by hydrodistillation and analyzed by GC-MS. Carvene, p-cymene and muurolene are the principal compounds of T. asiatica leaf (TAL), T. asiatica fruit (TAF) and T. asiatica branch (TAB) EO respectively. Our work aimed to assess the contact toxicity and repellent effects of EOs on two storage pests, Tribolium castaneum and Lasioderma serricorne. All tested EOs exhibited obvious contact toxicity, especially, TAL EO against T. castaneum (33.48 µg/adult) and TAF EO against L. serricorne (16.42 µg/adult). Repellency tests revealed that TAL and TAF EOs, at a concentration of 78.63 nL/cm2, achieved nearing 100% efficiency against T. castaneum. These results suggest that EOs of T. asiatica could be used as effective botanical insecticides for managing stored-product insects.

9.
Plants (Basel) ; 13(15)2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39124162

RESUMEN

The mechanism by which nitrate inhibits nitrogen fixation in soybean (Glycine max L.) is not fully understood. Accumulation of ureide in soybean plant tissues may regulate the nitrogen fixation capacity through a feedback pathway. In this study, unilaterally nodulated dual-root soybeans prepared by grafting were grown in sand culture. They were subjected to the removal of the nodulated side roots, and were given either nitrate supply or no supply to the non-nodulated side roots for 3 days (experiment I). Additionally, they received nitrate supply to the non-nodulated side roots for 1-14 days (experiment II). The results showed that nitrate supply increased the levels of asparagine and ureide in soybean shoots (Experiment I). In Experiment II, nodule dry weight, nodule number, nodule nitrogenase activity, and nodule urate oxidase activity decreased significantly after 3, 7, and 14 days of nitrate supply. Ureide content in the shoots and nodules increased after 1, 3, and 7 days of nitrate supply, but decreased after 14 days of nitrate supply. There was a significant positive correlation between urate oxidase activity and nitrogenase activity. Hence, we deduced that nitrate supply increased the asparagine content in soybean shoots, likely inhibiting ureide degradation, which induced the accumulation of ureide in soybean shoots and nodules, and, in turn, feedback inhibited the nodule nitrogen fixation. In addition, urate oxidase activity can be used to assess the nitrogen fixation capacity of nodules.

10.
Front Immunol ; 15: 1400722, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39170612

RESUMEN

Background: Although neoadjuvant therapy has brought numerous benefits to patients, not all patients can benefit from it. Chemokines play a crucial role in the tumor microenvironment and are closely associated with the prognosis and treatment of colorectal cancer. Therefore, constructing a prognostic model based on chemokines will help risk stratification and providing a reference for the personalized treatment. Methods: Employing LASSO-Cox predictive modeling, a chemokine-based prognostic model was formulated, harnessing the data from TCGA and GEO databases. Then, our exploration focused on the correlation between the chemokine signature and elements such as the immune landscape, somatic mutations, copy number variations, and drug sensitivity. CXCL10+M1 macrophages identified via scRNA-seq. Monocle2 showed cell pseudotime trajectories, CellChat characterized intercellular communication. CytoTRACE analyzed neoadjuvant therapy stemness, SCENIC detected cell type-specific regulation. Lastly, validation was performed through multiplex immunofluorescence experiments. Results: A model based on 15 chemokines was constructed and validated. High-risk scores correlated with poorer prognosis and advanced TNM and clinical stages. Individuals presenting elevated risk scores demonstrated an increased propensity towards the development of chemotherapy resistance. Subsequent scRNA-seq data analysis indicated that patients with higher presence of CXCL10+ M1 macrophages in tumor tissues are more likely to benefit from neoadjuvant therapy. Conclusion: We developed a chemokine-based prognostic model by integrating both single-cell and bulk RNA-seq data. Furthermore, we revealed epithelial cell heterogeneity in neoadjuvant outcomes and identified CXCL10+ M1 macrophages as potential therapy response predictors. These findings could significantly contribute to risk stratification and serve as a key guide for the advancement of personalized therapeutic approaches.


Asunto(s)
Quimiocina CXCL10 , Neoplasias Colorrectales , Terapia Neoadyuvante , Microambiente Tumoral , Humanos , Neoplasias Colorrectales/terapia , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/mortalidad , Quimiocina CXCL10/genética , Quimiocina CXCL10/metabolismo , Terapia Neoadyuvante/métodos , Pronóstico , Microambiente Tumoral/inmunología , Biomarcadores de Tumor , Macrófagos/inmunología , Macrófagos/metabolismo , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/metabolismo , Femenino , Masculino , Resultado del Tratamiento , Quimiocinas/metabolismo , Quimiocinas/genética
11.
Talanta ; 280: 126720, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39173245

RESUMEN

Water constitutes the most prevalent impurity in organic solvents, exerting significant influence on chemical reactions and potentially leading to fires and explosions, even in minute quantities. Thus, the development of convenient, rapid, and cost effective fluorescent probes for real-time monitoring of water content in organic solvents is imperative. Although some fluorescent materials have been synthesized for this purpose, most suffer from laborious preparation processes and poor cycling performance, constraining their practical application. This study investigates the impact of hydrogen bonding on the aggregation-induced emission (AIE) properties of quinoline derivatives, leveraging quinoline as the foundational scaffold and its nitrogen atom as the hydrogen bond acceptor. Research findings elucidate that intermolecular hydrogen bonding of quinoline is the primary determinant of their AIE behaviors. By harnessing the phenomenon of water molecules forming intermolecular hydrogen bonds with quinoline nitrogen atoms, we devised a straightforward and rapid method to fabricate a fluorescent test paper for real-time monitoring of water content in organic solvents. Experimental results demonstrate that even minute changes in water content, down to concentrations as low as 0.5 % by volume in organic solvents, can induce fluorescence changes in the test paper, which also exhibits favorable cycling performance. This study not only explores the influence of hydrogen bonds on the AIE properties of quinoline derivatives but also pioneers the development of a cost-effective, rapid, and recyclable test paper for real-time monitoring of water content fluctuations in organic solvents.

13.
J Med Biochem ; 43(4): 587-596, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-39139162

RESUMEN

Background: To explore the correlation between left atrial appendage morphology, blood flow velocity and plasma galectin-3 and thrombosis in patients with atrial fibrillation. Methods: Patients with atrial fibrillation who received treatment and completed ultrasound examination in hospital from 2022 to December 2023 were enrolled. According to whether there was left atrial appendage thrombosis, the patients were divided into a control group (no left atrial appendage thrombosis was found) and a study group (left atrial appendage thrombosis was found). The morphology and structure of the left atrial appendage, blood flow velocity and plasma galectin-3 level were recorded exploring its correlation with left atrium thrombosis. Results: A total of 330 patients with atrial fibrillation were enrolled, including 278 in the control group and 52 in the study group. Left group and the control group of morphological structure differences (P < 0.05). The main lobe length, ostial area, longest diameter, shortest diameter, left atrial appendage volume and left atrial volume in the study group were higher than those in the control group (P < 0.05). The left atrial appendage emptying velocity, filling velocity and left ventricular ejection fraction of the study group were lower than those of the control group, and the left ventricular end-diastolic diameter was higher than that of the control group (P < 0.05). Group of white blood cell count, neutrophils/lymphocyte ratio, plasma galactose lectin-3 levels were higher than control group (P < 0.05). ROC curve analysis of left atrial appendage emptying velocity, left atrial appendage filling velocity, left atrial enddiastolic diameter and left atrial ejection fraction had higher diagnostic value (P < 0.05). Conclusions: Left atrial appendage morphology, blood flow velocity and plasma galectin-3 level are important factors to evaluate the risk of left atrial appendage thrombosis in patients with atrial fibrillation. This study improves the understanding of thrombosis, further elucidates the risk factors for thrombosis, and improves patient prognosis.

14.
Intensive Crit Care Nurs ; 84: 103744, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39089198

RESUMEN

OBJECTIVES: To assess the efficacy of early rehabilitation program for VV-ECMO patients and observe the influence on the respiratory and skeletal muscles. DESIGN: A cohort study. SETTING: The study was conducted with VVECMO patients in a comprehensive ICU with 32 beds. MAIN OUTCOME MEASURES: Ultrasound measurements were performed on each patients on day 1, 4, 7, 10, and 14, including diaphragmatic excursion (DE), diaphragmatic thickening fraction (DTF), intercostal muscle thickening fraction (ICMTF), thickness of the rectus femoris (RF), thickness of vastus intermedius (VI), and rectus femoris cross-sectional area (RF-CSA). Data on basic characteristics, results of ultrasound measurements, patients outcomes and adverse events were collected. RESULTS: 22 patients received usual rehabilitation measures were set as the control group and 23 patients underwent early rehabilitation program were set as the study group. There were no differences in diaphragmatic excursion, diaphragmatic thickening fraction, intercostal muscle thickening fraction, thickness of rectus femoris, thickness of vastus intermedius, rectus femoris cross-sectional area between two groups on day 1 after VV-ECMO treatment (P > 0.05). The variation of diaphragmatic thickening fraction and intercostal muscle thickening fraction decreased on the day 7 and 14 after treatment (P < 0.05). The variation of vastus intermedius thickness and rectus femoris cross-sectional area in the study group was less compared with those in the control group on day 4, 7, 10 and 14. The ECMO duration in the study group was shorter than that in the control group (12.00 [10.00-16.25] days vs. 8.00 [6.00-12.25] days, P = 0.002), but there was no difference in the duration of mechanical ventilation. CONCLUSION: Early rehabilitation program can ameliorate muscle atrophy. We recommend implementation of our rehabilitation program in VV-ECMO patients. This program can improve skeletal muscle atrophy and dysfunction in patients with VV-ECMO effectively and perhaps improve quality of life for patients in the future. IMPLICATIONS FOR CLINICAL PRACTICE: Early rehabilitation program put higher demands bedside nurses. It requires them to observe conditions of VVECMO patients closely, assess the feasibility of rehabilitation promptly, and monitor for any adverse reactions. Ultrasound measurement is a noninvasive and useful tool to assess muscle atrophy in ICU patients. Early rehabilitation program can improve skeletal muscle atrophy and dysfunction in patients with VV-ECMO effectively.


Asunto(s)
Oxigenación por Membrana Extracorpórea , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios de Cohortes , Oxigenación por Membrana Extracorpórea/métodos , Oxigenación por Membrana Extracorpórea/estadística & datos numéricos , Adulto , Unidades de Cuidados Intensivos/organización & administración , Unidades de Cuidados Intensivos/estadística & datos numéricos , Ultrasonografía/métodos
15.
J Med Chem ; 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39140772

RESUMEN

Various small molecule GLP1R agonists have been developed and tested for treating type 2 diabetes (T2DM) and obesity. However, many of these new compounds have drawbacks, such as potential hERG inhibition, lower activity compared to natural GLP-1, limited oral bioavailability in cynomolgus monkeys, and short duration of action. Recently, a new category of 3-phenyloxetane derivative GLP1R agonists with enhanced hERG inhibition has been discovered. Using an AIDD/CADD method, compound 14 (DD202-114) was identified as a potent and selective GLP1R agonist, which was chosen as a preclinical candidate (PCC). Compound 14 demonstrates full agonistic efficacy in promoting cAMP accumulation and possesses favorable drug-like characteristics compared to the clinical drug candidate Danuglipron. Additionally, in hGLP-1R knock-in mice, compound 14 displayed a sustained pharmacological effect, effectively reducing blood glucose levels and food intake. These findings suggest that compound 14 holds promise as a future treatment option for T2DM and obesity, offering improved properties.

16.
Biochem Pharmacol ; 227: 116466, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39102989

RESUMEN

Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma with limited response to chemotherapy. Histone acetylation is reduced in DLBCL. Chidamide, a histone deacetylase inhibitor, shows promise in lymphomas but needs further investigation for DLBCL. Our study indicated that chidamide effectively suppresses DLBCL both in vitro and in vivo. High-throughput RNA sequencing analysis provided comprehensive evidence that chidamide markedly influences crucial signaling pathways in DLBCL, including the MAPK, MYC and p53 pathway. Additionally, we observed substantial variability in the sensitivity of DLBCL cells to chidamide, and identified that elevated expression of BCL6 might confer resistance to chidamide in DLBCL. Moreover, our investigations revealed that BCL6 inhibited chidamide-induced histone acetylation by recruiting histone deacetylase (HDACs), leading to drug resistance in DLBCL cells. Furthermore, we found that lenalidomide targeted BCL6 degradation through the ubiquitination pathway and restore the sensitivity of drug-resistant DLBCL to chidamide. Collectively, these findings provided valuable insights into the global impact of chidamide on DLBCL and highlight the potential of targeting HDACs as a therapeutic strategy for DLBCL. Identifying BCL6 as a biomarker for predicting the response to chidamide and the combination therapy with BCL6 inhibition has the potential to lead to more personalized and effective treatments for DLBCL patients.


Asunto(s)
Aminopiridinas , Benzamidas , Resistencia a Antineoplásicos , Inhibidores de Histona Desacetilasas , Linfoma de Células B Grandes Difuso , Proteínas Proto-Oncogénicas c-bcl-6 , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/genética , Inhibidores de Histona Desacetilasas/farmacología , Proteínas Proto-Oncogénicas c-bcl-6/genética , Proteínas Proto-Oncogénicas c-bcl-6/metabolismo , Resistencia a Antineoplásicos/efectos de los fármacos , Benzamidas/farmacología , Línea Celular Tumoral , Animales , Ratones , Aminopiridinas/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto/métodos , Femenino , Lenalidomida/farmacología , Lenalidomida/uso terapéutico , Antineoplásicos/farmacología , Ratones SCID
17.
Soft Robot ; 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39078729

RESUMEN

Soft actuators offer numerous potential applications; however, challenges persist in achieving a high driving force and fast response speed. In this work, we present the design, fabrication, and analysis of a soft pneumatic bistable actuator (PBA) mimicking jellyfish subumbrellar muscle motion for waterjet propulsion. Drawing inspiration from the jellyfish jet propulsion and the characteristics of bistable structure, we develop an elastic band stretch prebending PBA with a simple structure, low inflation cost, exceptional driving performance, and stable driving force output. Through a bionic analysis of jellyfish body structure and motion, we integrate the PBA into a jellyfish-like prototype, enabling it to achieve jet propulsion. To enhance the swimming performance, we introduce a skin-like structure for connecting the soft actuator to the jellyfish-like soft robot prototype. This skin-like structure optimizes the fluid dynamics during jet propulsion, resulting in improved efficiency and maneuverability. Our study further analyzes the swimming performance of the jellyfish-like prototype, demonstrating a swimming speed of 3.8 cm/s (0.32 body length/s, BL/s) for the tethered prototype and 4.7 cm/s (0.38 BL/s) for the untethered prototype. Moreover, we showcase the jellyfish-like prototype's notable load-bearing capacity and fast-forward swimming performance compared to other driving methods for underwater biomimetic robots. This work provides valuable insights for the development of highly agile and fast responsive soft robots that imitate the subumbrellar muscle of jellyfish for efficient water-jet propulsion, utilizing skin-like structures to enhance swimming performance.

18.
Transl Lung Cancer Res ; 13(6): 1420-1425, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38973944

RESUMEN

Background: Malignant pleural mesothelioma (MPM) is a rare thoracic malignancy with high morbidity and mortality. A combination of systemic therapy and surgery may be a promising modality for the treatment of MPM, but evidence-based medicine is still lacking. Case Description: Here we report a case of MPM. The patient presented to hospital with cough and sputum. After ineffective symptomatic treatment, computed tomography (CT) examination suggested a malignant tumor of pleural origin. Positron emission tomography/computed tomography (PET/CT) examination suggested no lymph node metastasis or distant metastasis. The pathologic diagnosis of MPM was confirmed after CT-guided puncture biopsy. Next, she underwent 3 courses of neoadjuvant chemotherapy combined with dual immunotherapy (carboplatin and pemetrexed combined with anti-CTLA4 and anti-PD-1), resulting in significant tumor shrinkage. After obtaining the patient's consent and completing a preoperative evaluation, we modified the extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) by performing a lower lobe resection and partial pleurectomy of the left lung. Intraoperative rapid frozen pathology suggested that the margins of the tumor were negative and complete resection was achieved. The postoperative pathology report showed 10% residual viable tumor, so the major pathological response (MPR) was achieved after treatment. Conclusions: MPM might respond well to neoadjuvant chemotherapy and dual immunotherapy, improving the probability of complete surgical resection and attaining an encouraging pathologic response.

19.
Front Nutr ; 11: 1363299, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38978702

RESUMEN

Objective: Selenium is an essential micronutrient and a type of dietary antioxidant. This study aimed to investigate the associations of dietary selenium intake with the risk of human chronic disease [cardiovascular disease (CVD), diabetes mellitus (DM), and cancer] and mortality among US general adults. Methods: The dietary and demographic data in this study were collected from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. Death outcomes were determined by associating with the National Death Index (NDI) records as of December 31, 2019. Logistic regression analyses were used to investigate the relationship of selenium intake with the risk of CVD, DM, and cancer. The effect of dietary selenium on all-cause and disease-specific mortality was estimated with restricted cubic spline (RCS) curves based on the univariate and multivariate Cox proportional hazard models. Results: Among the 25,801 participants, dietary selenium intake was divided into quintiles (Q1-Q5). After covariate adjustment, the results showed that the participants with higher quintiles (Q4 and Q5) of selenium intake tended to have a low risk of CVD (OR = 0.97, 95% CI: 0.96, 0.99; OR = 0.98, 95% CI: 0.97, 1.00, respectively). Moreover, the RCS curves showed a significant nonlinear association between selenium intake and the risk of all-cause (with a HR of 0.82, 95% CI: 0.68, 0.99) and DM-specific mortality (with the lowest HR of 0.30; 95% CI, 0.12-0.75). Furthermore, we conducted a subgroup analysis and found a negative correlation between the highest quartile of selenium intake and all-cause mortality among participants aged 50 and above (HR = 0.75, 95% CI: 0.60-0.93, p = 0.009). Conclusion: Our results indicated that a moderate dietary selenium supplement decreased the risk of CVD and displayed a nonlinear trend in association with the risk of all-cause and DM-specific mortality among US adults. In addition, we found that participants aged 50 and older may benefit from higher selenium intake. However, these findings still need to be confirmed through further mechanism exploration.

20.
Exp Aging Res ; : 1-12, 2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39003730

RESUMEN

BACKGROUND: Cognitive models of depression assert that attentional biases play an important role in the maintenance of depression. However, few studies have explored attentional bias in depressed older adults, and no consistent conclusions have been reached. METHODS: In the current study, we investigated attentional bias in older adults with non-clinical depression. Older adults aged over 60 with non-clinical depression and without depression were instructed to perform a free viewing task while their eye movements were tracked. RESULTS: The results showed that, compared to older adults without depression, non-clinically depressed older adults had longer total fixation durations and a greater number of fixations on sad stimuli. Moreover, non-depressed older adults exhibited a preference for pleasant images, whereas this effect was not observed in older adults with non-clinical depression. CONCLUSION: This study suggested that non-clinically depressed older adults have attentional bias, which is manifested as increased attention to sad stimuli and decreased attention to pleasant stimuli.The current study has functional and potential functional implications.

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