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1.
Pediatr Blood Cancer ; : e30989, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38602300

RESUMEN

BACKGROUND: Infantile hemangiomas (IHs) are common benign vascular tumors in infants. Apelin, an endogenous cytokine, is implicated in the angiogenesis of neoplastic diseases. We aimed to explore the association between apelin and IHs, providing a foundation for clinical applications. METHODS: We identified differential expression of apelin in proliferative IHs compared to healthy controls (HCs) through bioinformatics analysis of publicly available databases and verified by Immunofluorescence. Enzyme-linked immunosorbent assay was used to quantify the serum levels of apelin and vascular endothelial growth factor (VEGF) in a cohort of 116 cases of proliferative IHs, 65 cases of capillary malformations (CMs), and 70 HCs. RESULTS: Apelin and APJ (APLNR, apelin receptor) were identified as the significantly upregulated differentially expressed genes (DEGs) in proliferative IHs. Immunofluorescence staining indicated high expression of apelin in proliferative IHs, while minimal expression in non-IH lesions. Apelin in IHs was reduced following 6 months of propranolol treatment. Serum apelin levels were significantly higher in the IH group compared to both the CM and HC groups. Moreover, apelin exhibited excellent discriminatory ability in distinguishing IHs from HCs, with an area under the curve (AUC) exceeding 0.90. A positive correlation was observed between the levels of apelin and the size of superficial IHs. The expression profiles of VEGF and apelin in IHs were found to be consistent. CONCLUSIONS: Apelin shows promise as a potential biomarker for IHs. The association between apelin and IH size, as well as its responsiveness to propranolol treatment, indicates its possible utility as a valuable indicator for the therapeutic evaluation of IHs.

2.
IEEE Trans Med Imaging ; PP2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38587957

RESUMEN

Accurate retinal layer segmentation on optical coherence tomography (OCT) images is hampered by the challenges of collecting OCT images with diverse pathological characterization and balanced distribution. Current generative models can produce high-realistic images and corresponding labels without quantitative limitations by fitting distributions of real collected data. Nevertheless, the diversity of their generated data is still limited due to the inherent imbalance of training data. To address these issues, we propose an image-label pair generation framework that generates diverse and balanced potential data from imbalanced real samples. Specifically, the framework first generates diverse layer masks, and then generates plausible OCT images corresponding to these layer masks using two customized diffusion probabilistic models respectively. To learn from imbalanced data and facilitate balanced generation, we introduce pathological-related conditions to guide the generation processes. To enhance the diversity of the generated image-label pairs, we propose a potential structure modeling technique that transfers the knowledge of diverse sub-structures from lowly- or non-pathological samples to highly pathological samples. We conducted extensive experiments on two public datasets for retinal layer segmentation. Firstly, our method generates OCT images with higher image quality and diversity compared to other generative methods. Furthermore, based on the extensive training with the generated OCT images, downstream retinal layer segmentation tasks demonstrate improved results. The code is publicly available at: https://github.com/nicetomeetu21/GenPSM.

3.
Stem Cell Res Ther ; 15(1): 100, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38589882

RESUMEN

BACKGROUND: Erythroid and myeloid differentiation disorders are commonly occurred in leukemia. Given that the relationship between erythroid and myeloid lineages is still unclear. To find the co-regulators in erythroid and myeloid differentiation might help to find new target for therapy of myeloid leukemia. In hematopoiesis, ALA (alpha lipoic acid) is reported to inhibit neutrophil lineage determination by targeting transcription factor ELK1 in granulocyte-monocyte progenitors via splicing factor SF3B1. However, further exploration is needed to determine whether ELK1 is a common regulatory factor for erythroid and myeloid differentiation. METHODS: In vitro culture of isolated CD34+, CMPs (common myeloid progenitors) and CD34+ CD371- HSPCs (hematopoietic stem progenitor cells) were performed to assay the differentiation potential of monocytes, neutrophils, and erythrocytes. Overexpression lentivirus of long isoform (L-ELK1) or the short isoform (S-ELK1) of ELK1 transduced CD34+ HSPCs were transplanted into NSG mice to assay the human lymphocyte and myeloid differentiation differences 3 months after transplantation. Knocking down of SRSF11, which was high expressed in CD371+GMPs (granulocyte-monocyte progenitors), upregulated by ALA and binding to ELK1-RNA splicing site, was performed to analyze the function in erythroid differentiation derived from CD34+ CD123mid CD38+ CD371- HPCs (hematopoietic progenitor cells). RNA sequencing of L-ELK1 and S-ELK1 overexpressed CD34+ CD123mid CD38+ CD371- HPCs were performed to assay the signals changed by ELK1. RESULTS: Here, we presented new evidence that ALA promoted erythroid differentiation by targeting the transcription factor ELK1 in CD34+ CD371- hematopoietic stem progenitor cells (HSPCs). Overexpression of either the long isoform (L-ELK1) or the short isoform (S-ELK1) of ELK1 inhibited erythroid-cell differentiation, but knockdown of ELK1 did not affect erythroid-cell differentiation. RNAseq analysis of CD34+ CD123mid CD38+ CD371- HPCs showed that L-ELK1 upregulated the expression of genes related to neutrophil activity, phosphorylation, and hypoxia signals, while S-ELK1 mainly regulated hypoxia-related signals. However, most of the genes that were upregulated by L-ELK1 were only moderately upregulated by S-ELK1, which might be due to a lack of serum response factor interaction and regulation domains in S-ELK1 compared to L-ELK1. In summary, the differentiation of neutrophils and erythrocytes might need to rely on the dose of L-ELK1 and S-ELK1 to achieve precise regulation via RNA splicing signals at early lineage commitment. CONCLUSIONS: ALA and ELK1 are found to regulate both human granulopoiesis and erythropoiesis via RNA spliceosome, and ALA-ELK1 signal might be the target of human leukemia therapy.


Asunto(s)
Leucemia , Ácido Tióctico , Humanos , Ratones , Animales , Eritropoyesis , Neutrófilos/metabolismo , Subunidad alfa del Receptor de Interleucina-3 , Proteína Elk-1 con Dominio ets/genética , Antígenos CD34/genética , Antígenos CD34/metabolismo , Diferenciación Celular/genética , Eritrocitos , Hipoxia , Isoformas de Proteínas
5.
Medicine (Baltimore) ; 103(15): e37744, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38608118

RESUMEN

RATIONALE: This report presents a unique case of a patient diagnosed with Primary Sjögren's syndrome and a relatively rare traditional Chinese medicine pattern, known as the combined cold and heat pattern and cold-dampness syndrome. The patient's condition was successfully managed using Chinese herbal medicine, specifically the modified Da-Chai-Hu decoction and Linggui Zhugan decoction. PATIENT CONCERNS: A 56-year-old woman had chronic dry eye and mouth for over 10 years. She was initially managed with traditional Chinese herbal medicine (TCHM) prescriptions, including the Zengye decoction, but the therapeutic effects were unsatisfactory. As the disease progressed, she was diagnosed with an anxiety disorder due to symptoms of vexation and insomnia. Treatment with alprazolam and venlafaxine failed to alleviate these symptoms. Recently, her general condition gradually worsened, with symptoms including a bitter taste in her mouth, dizziness, hot flashes, chills, poor appetite, chest discomfort, and constipation. DIAGNOSES: After a series of examinations, including a Schirmer test and labial gland biopsy, she was diagnosed with Sjögren's syndrome. INTERVENTIONS: Despite regular treatment with pilocarpine, sodium hyaluronate eye drops, venlafaxine, and alprazolam, the dry mouth symptoms intensified. Consequently, she sought further intervention through the TCHM. OUTCOMES: After 8 weeks of treatment with the modified Da-Chai-Hu decoction and Linggui Zhugan decoction, she reported a significant improvement in her dryness-related symptoms and sleep quality. LESSONS: This case report demonstrates that TCHM can effectively treat Primary Sjögren's syndrome, and should be considered for broader applications. Furthermore, this underscores the importance of tailoring treatment formulas to patients by identifying their specific syndrome differentiation in a clinical setting.


Asunto(s)
Medicamentos Herbarios Chinos , Síndrome de Sjögren , Humanos , Femenino , Persona de Mediana Edad , Alprazolam , Medicamentos Herbarios Chinos/uso terapéutico , Medicina Tradicional China , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/tratamiento farmacológico , Clorhidrato de Venlafaxina
6.
BMC Genomics ; 25(1): 363, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38609871

RESUMEN

BACKGROUND: Cold hardiness is fundamental for amphibians to survive during the extremely cold winter on the Qinghai-Tibet plateau. Exploring the gene regulation mechanism of freezing-tolerant Rana kukunoris could help us to understand how the frogs survive in winter. RESULTS: Transcriptome of liver and muscle of R. kukunoris collected in hibernation and spring were assisted by single molecule real-time (SMRT) sequencing technology. A total of 10,062 unigenes of R. kukunoris were obtained, and 9,924 coding sequences (CDS) were successfully annotated. Our examination of the mRNA response to whole body freezing and recover in the frogs revealed key genes concerning underlying antifreeze proteins and cryoprotectants (glucose and urea). Functional pathway analyses revealed differential regulated pathways of ribosome, energy supply, and protein metabolism which displayed a freeze-induced response and damage recover. Genes related to energy supply in the muscle of winter frogs were up-regulated compared with the muscle of spring frogs. The liver of hibernating frogs maintained modest levels of protein synthesis in the winter. In contrast, the liver underwent intensive high levels of protein synthesis and lipid catabolism to produce substantial quantity of fresh proteins and energy in spring. Differences between hibernation and spring were smaller than that between tissues, yet the physiological traits of hibernation were nevertheless passed down to active state in spring. CONCLUSIONS: Based on our comparative transcriptomic analyses, we revealed the likely adaptive mechanisms of R. kukunoris. Ultimately, our study expands genetic resources for the freezing-tolerant frogs.


Asunto(s)
Respuesta al Choque por Frío , Transcriptoma , Animales , Respuesta al Choque por Frío/genética , Tibet , Perfilación de la Expresión Génica , Ranidae/genética , Anuros
7.
Molecules ; 29(7)2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38611823

RESUMEN

(1) Background: Diabetes is a common metabolic disease that seriously endangers human health. In the present study, we investigated the therapeutic effects of the active ingredient Eleutheroside B (EB) from the traditional Chinese medicine Eleutheroside on diabetes mellitus in a zebrafish model. Concomitant hepatic injury was also analysed, along with the study of possible molecular mechanisms using metabolomics technology. This work should provide some theoretical references for future experimental studies. (2) Methods: A zebrafish diabetes model was constructed by soaking in a 1.75% glucose solution and feeding a high-fat diet. The intervention drug groups were metformin (100 µg∙mL-1) and EB (50, 100, and 150 µg∙mL-1) via water-soluble exposure for 30 days. Glucose, TG, TC, LDL-C, and HDL-C were evaluated in different treatment groups. GLUT4 protein expression was also evaluated in each group, and liver injury was observed by HE staining. Metabolomics techniques were used to investigate the mechanism by which EB regulates endogenous markers and metabolic pathways during the development of diabetes. (3) Results: All EB treatment groups in diabetic zebrafish showed significantly reduced body mass index (BMI) and improved blood glucose and lipid profiles. EB was found to upregulate GLUT4 protein expression and ameliorate the liver injury caused by diabetes. Metabolomics studies showed that EB causes changes in the metabolic profile of diabetic zebrafish. These were related to the regulation of purine metabolism, cytochrome P450, caffeine metabolism, arginine and proline metabolism, the mTOR signalling pathway, insulin resistance, and glycerophospholipid metabolism. (4) Conclusions: EB has a hypoglycaemic effect in diabetic zebrafish as well as significantly improving disorders of glycolipid metabolism. The mechanism of action of EB may involve regulation of the mTOR signalling pathway, purine metabolism, caffeine metabolism, and glycerophospholipid metabolism.


Asunto(s)
Diabetes Mellitus , Glucosa , Glucósidos , Fenilpropionatos , Humanos , Animales , Metabolismo de los Lípidos , Pez Cebra , Cafeína , Transportador de Glucosa de Tipo 4 , Serina-Treonina Quinasas TOR , Glicerofosfolípidos
8.
Infect Drug Resist ; 17: 1439-1445, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38628241

RESUMEN

Background: The HACEK group comprises Haemophilus spp., Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae, are Gram-negative bacteria that are slow-growing and fastidious. These organisms are common causes of culture-negative endocarditis. However, brain abscesses caused by Haemophilus aphrophilus and E. corrodens have been rarely reported. The case we describe, which was promptly identified and successfully treated, will be meaningful for the diagnosis and treatment of such infectious diseases. Case Presentation: Herein, we report a case of brain abscess in a young man who was infected with Haemophilus aphrophilus and E. corrodens. The patient was admitted to the hospital with sudden onset of vomiting, coma, and fever. Magnetic resonance imaging (MRI) of the brain and cerebrospinal fluid cell counts suggested cerebral abscess, he underwent drainage of the abscess and empirical antimicrobial therapy of meropenem (2 g every 8 hours) and linezolid (0.6 g every 12 hours) for more than 10 days without significant improvement. Metagenomic next-generation sequencing (mNGS) of drainage fluid and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) detection for isolated bacteria from samples suggested the presence of H. aphrophilus and E. corrodens. After 7 weeks of ceftriaxone (2 g every 12 hours) and meropenem (2 g every 8 hours) intravenously, the patient was discharged with a normal temperature and brain MRI showed improvement of the lesion. Conclusion: Similar cases reported in previous studies were always associated with bacterial blood dissemination after dental surgery or myocarditis; however, the patient in our case had no any associated risk factors. As far as we know, this is the only case of central nervous system infection caused by H. aphrophilus and E. corrodens that has utilized combined mNGS and MALDI-TOF MS in the diagnosis.

9.
BMJ Open ; 14(4): e080289, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38589257

RESUMEN

INTRODUCTION: Up to 78% of patients who had a stroke develop post-stroke dysphagia (PSD), a significant consequence. Life-threatening aspiration pneumonia, starvation, and water and electrolyte abnormalities can result. Several meta-analyses have shown that repeated transcranial magnetic stimulation (rTMS) improves swallowing in patients who had a stroke; however, the optimum model is unknown. This study will be the first Bayesian network meta-analysis (NMA) to determine the best rTMS modalities for swallowing of patients who had a stroke. METHODS AND ANALYSIS: PubMed, Web of Science, Embase, Google Scholar, Cochrane, the Chinese National Knowledge Infrastructure, the Chongqing VIP Database and WanFang Data will be searched from their creation to 2 September 2023. All randomised controlled trials associated with rTMS for PSD will be included. Only Chinese or English results will be studied. Two researchers will independently review the literature and extract data, then use the Cochrane Collaboration's Risk of Bias 2.0 tool to assess the included studies' methodological quality. The primary outcome is swallowing function improvement, whereas secondary outcomes include side effects (eg, paraesthesia, vertigo, seizures) and quality of life. A pairwise meta-analysis and NMA based on a Bayesian framework will be conducted using Stata and R statistical software. The Grading of Recommendations Assessment, Development, and Evaluation system will assess outcome indicator evidence quality. ETHICS AND DISSEMINATION: As all data in this study will be taken from the literature, ethical approval is not needed. We will publish our work in peer-reviewed publications and present it at academic conferences. PROSPERO REGISTRATION NUMBER: CRD42023456386.


Asunto(s)
Trastornos de Deglución , Accidente Cerebrovascular , Humanos , Estimulación Magnética Transcraneal/métodos , Trastornos de Deglución/terapia , Trastornos de Deglución/complicaciones , Metaanálisis en Red , Teorema de Bayes , Calidad de Vida , Accidente Cerebrovascular/complicaciones , Revisiones Sistemáticas como Asunto , Metaanálisis como Asunto
10.
BMJ Paediatr Open ; 8(1)2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38594193

RESUMEN

OBJECTIVE: To examine the association of cerebral palsy with autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), providing evidence for interdisciplinary medical service for children with cerebral palsy. DESIGN: A large-scale nationwide population-based study. SETTING: The National Health Interview Survey (NHIS). PATIENTS: 177 899 children aged 3-17 years among NHIS participants from 1997 to 2003 and 2008 to 2018. RESULTS: Among the 177 899 children included in this analysis, 602 (0.33%) had cerebral palsy, 1997 (1.16%) had ASD, and 13 697 (7.91%) had ADHD. Compared with children without cerebral palsy, children with cerebral palsy had a higher prevalence of ASD (6.09% vs 1.15%; p<0.001) and ADHD (15.91% vs 7.89%; p<0.001). After adjustment for age, sex, race/ethnicity, family highest education level, family income level and geographical region, the OR among children with cerebral palsy, compared with children without cerebral palsy, was 5.07 (95% CI 3.25 to 7.91) for ASD (p<0.001) and 1.95 (95% CI 1.43 to 2.66) for ADHD (p<0.001). Furthermore, the association of cerebral palsy with ASD and ADHD remained significant in all subgroups stratified by age, sex and race. CONCLUSION: In a large, nationally representative sample of US children, this study shows that children with cerebral palsy are at an increased risk of ASD and ADHD.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Trastorno del Espectro Autista , Parálisis Cerebral , Niño , Humanos , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno del Espectro Autista/epidemiología , Parálisis Cerebral/epidemiología , Prevalencia , Encuestas y Cuestionarios
11.
Polymers (Basel) ; 16(7)2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38611163

RESUMEN

Recently, the application of cryogenic hoses in the field of cryogenic media has become a hot topic, especially in the industry of offshore liquefied natural gas and aerospace field. However, the structure of cryogenic hoses is complex, and reasonable structural properties are required due to the harsh working conditions. There is still plenty of scope for further development to improve the performance in all aspects. In this paper, the current development status of cryogenic hoses for liquefied natural gas (LNG) transportation is reviewed first, including the types, manufacturers, structural forms, performance, and key technical challenges. And then, the recent progress and prospect of cryogenic hoses for cryogenic liquid transportation (such as LNG and liquid oxygen) are summarized, including structure design, low-temperature resistant polymers, liquid oxygen compatible polymers, and leakage monitoring technologies. This paper provides a comprehensive overview of the research development and application of cryogenic hoses. Moreover, future research directions have been proposed to facilitate its practical applications in aerospace.

12.
Diabetes Metab Syndr Obes ; 17: 1761-1767, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38645660

RESUMEN

Background: Type 2 diabetes mellitus (T2DM) poses a huge threat to population health globally, and more drugs need to be explored for treatment. In this study, we investigated the mechanism of active ingredient catalpol in Rehmannia glutinosa on reduces blood glucose in diabetic. Methods: The T2DM model was constructed by intraperitoneal injection of streptozotocin into Sprague-Dawley (SD) rats, which were randomly grouped into diabetes model group, pioglitazone group, Rehmannia glutinosa group, catalpol high-dose group, catalpol low-dose group and normal control group.The intervention was continued for 28 d, and changes in body weight, fasting blood glucose, insulin and lipid levels were observed. Results: Of all the drugs, pioglitazone had the most pronounced hypoglycemic effect, which began to decline after 2 weeks of treatment in the low-dose catalpol group and had no hypoglycemic effect in the high-dose catalpol group. Among them, Rehmannia glutinosa was able to increase serum triglyceride level, and pioglitazone effectively reduced total cholesterol level in rats. The low dose of catalpol decreased the concentration of low-density lipoprotein cholesterol (LDL), while the high dose of catalpol increased the concentration of LDL. Conclusion: As an active ingredient in Rehmannia glutinosa, catalpol has the potential to lower blood glucose and improve blood lipids in diabetes treatment, and its action may be achieved by regulating the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway, which provides a new idea for the development of new diabetes therapeutic approaches.

13.
ACS Appl Mater Interfaces ; 16(15): 18824-18832, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38566471

RESUMEN

Aqueous ammonium ion hybrid supercapacitor (A-HSC) is an efficient energy storage device based on nonmetallic ion carriers (NH4+), which combines advantages such as low cost, safety, and sustainability. However, unstable electrode structures are prone to structural collapse in aqueous electrolytes, leading to fast capacitance decay, especially in host materials represented by vanadium-based oxidation. Here, the Co2+ preintercalation strategy is used to stabilize the VO2 tunnel structure and improve the electrochemical stability of the fast NH4+ storage process. In addition, the understanding of the NH4+ storage mechanism has been deepened through ex situ structural characterization and electrochemical analysis. The results indicate that Co2+ preintercalation effectively enhances the conductivity and structural stability of VO2, and inhibits the dissolution of V in aqueous electrolytes. In addition, the charge storage mechanisms of NH4+ intercalation/deintercalation and the reversible formation/fracture of hydrogen bonds were revealed.

14.
Artículo en Inglés | MEDLINE | ID: mdl-38659271

RESUMEN

INTRODUCTION: Exosomes derived from Adipose-Derived Stem Cells (ADSCs-Exo) have been implicated in the enhancement of wound repair in Diabetic Foot Ulcers (DFU). OBJECTIVE: The current research was designed to explore the therapeutic potential and underlying mechanisms of ADSCs-Exo modified with microRNA-125b (miR-125b) in the context of DFU. METHODS: Rat models with DFU and human umbilical vein endothelial cells (HUVECs) subjected to high glucose (HG) conditions served as experimental systems and were administered miR-125b-engineered ADSCs-Exo. Then, the expressions of CD34, Ki-67, angiogenesis-related factors (VEGF and TGFß-1), angiogenesis inhibitor DLL-4, and inflammation-related proteins (TLR-4 and IL-6) were detected. RESULTS: MiR-125b was upregulated in ADSCs-Exo. MiR-125b-mimics transfection in ADSCs- Exo reduced inflammatory infiltration and promoted granulation formation and wound healing in wound tissues. MiR-125b-mimics-modified ADSCs-Exo injection increased the expression of CD34, Ki-67, VEGF, and TGFß-1, whereas decreased the expression of DLL-4, TLR-4, and IL-6 in wound tissues of DFU rats. In addition, miR-125b-mimics-ADSCs-Exo injection reversed the negative effects of HG on the proliferation, migration, and angiogenesis of HUVECs, as well as the positive effects of cell apoptosis. Moreover, miR-125b-inhibitor-ADSCs-Exo injection had the opposite effects to miR-125b-mimics-ADSCs-Exo. CONCLUSION: ADSCs-Exo promoted wound healing of DFU rats, especially when overexpressing miR-125b.

15.
J Chem Phys ; 160(16)2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38647312

RESUMEN

Understanding and further regulating the degradation of mandrel materials is a key aspect of target fabrication in inertial confinement fusion (ICF). Here, a quasi-one-dimensional confinement model is developed using a series of single-walled carbon nanotubes with varying diameters (Dm), and the degradation of poly-α-methylstyrene (PAMS) as a typical mandrel material is investigated under such confined conditions by using the combined method of quantum mechanics and molecular mechanics. In comparison to the isolated system, the calculations show that confinement can decrease or increase the energy barriers of PAMS degradation, which directly depends on Dm. Following which a clear exponential relationship between the degradation rate of PAMS and its own density is derived, indicating that the density of PAMS can be used to regulate mandrel degradation. This work highlights the important effects of confinement on degradation and provides a valuable reference for further development of polymer degradation technologies in ICF target fabrication and other fields.

16.
Structure ; 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38626767

RESUMEN

Nectin and nectin-like (Necl) co-receptor axis, comprised of receptors DNAM-1, TIGIT, CD96, PVRIG, and nectin/Necl ligands, is gaining prominence in immuno-oncology. Within this axis, the inhibitory receptor PVRIG recognizes Nectin-2 with high affinity, but the underlying molecular basis remains unknown. By determining the crystal structure of PVRIG in complex with Nectin-2, we identified a unique CC' loop in PVRIG, which complements the double-lock-and-key binding mode and contributes to its high affinity for Nectin-2. The association of the corresponding charged residues in the F-strands explains the ligand selectivity of PVRIG toward Nectin-2 but not for Necl-5. Moreover, comprehensive comparisons of the binding capacities between co-receptors and ligands provide innovative insights into the intra-axis immunoregulatory mechanism. Taken together, these findings broaden our understanding of immune recognition and regulation mediated by nectin/Necl co-receptors and provide a rationale for the development of immunotherapeutic strategies targeting the nectin/Necl axis.

17.
Cell Insight ; 3(3): 100170, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38590928

RESUMEN

The RNA-binding protein LUC7L3 is the human homolog of yeast U1 small nuclear RNA (snRNA)-related splicing factor Luc7p. While the primary function of LUC7L3 as an RNA-binding protein is believed to be involved in RNA metabolism, particularly in the splicing process, its exact role and other functions are still not fully understood. In this study, we aimed to elucidate the role of LUC7L3 and its impact on cell proliferation. Our study revealed that LUC7L3 depletion impairs cell proliferation compared to the other Luc7p paralogs, resulting in cell apoptosis and senescence. We explored the underlying mechanisms and found that LUC7L3 depletion leads to R-loop accumulation, DNA replication stress, and genome instability. Furthermore, we discovered that LUC7L3 depletion caused abnormalities in spindle assembly, leading to the formation of multinuclear cells. This was attributed to the dysregulation of protein translation of spindle-associated proteins. Additionally, we investigated the interplay between LUC7L3 and SRSF1 and identified SRSF1 as an upper stream regulator of LUC7L3, promoting the translation of LUC7L3 protein. These findings highlight the importance of LUC7L3 in maintaining genome stability and its relationship with SRSF1 in this regulatory pathway.

18.
Biomed Opt Express ; 15(3): 1831-1846, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38495723

RESUMEN

By incorporating multiple indicators that facilitate clinical decision making and effective management of diabetic retinopathy (DR), a comprehensive understanding of the progression of the disease can be achieved. However, the diversity of DR complications poses challenges to the automatic analysis of various information within images. This study aims to establish a deep learning system designed to examine various metrics linked to DR in ultra-widefield fluorescein angiography (UWFA) images. We have developed a unified model based on image generation that transforms input images into corresponding disease-free versions. By incorporating an image-level supervised training process, the model significantly reduces the need for extensive manual involvement in clinical applications. Furthermore, compared to other comparative methods, the quality of our generated images is significantly superior.

19.
ACS Appl Mater Interfaces ; 16(12): 15336-15347, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38485463

RESUMEN

Ionogels with excellent mechanical performance and conductivity have been considered as ideal candidates for flexible ionotronics. However, current ionogels suffer from the well-known trade-off between mechanical strength and conductivity. Herein, we construct an ionogel with bicontinuous phase structures, a polymer-rich phase, and a solvent-rich phase. The synergy of the polymer-rich phase as an energy dissipation mechanism and the solvent-rich phase as a conductive nanochannel enables the resultant bicontinuous ionogel to show comprehensive properties, a tensile strength of 4.2 MPa, a toughness of 14.4 MJ/m3, a conductivity of 4.3 mS/cm, excellent self-healing capability, and reprocessability. Benefiting from the remarkable mechanical performance and high conductivity, the integrated supercapacitor achieves a high specific capacitance of 118 mF/cm2 (at a current density of 0.2 mA/cm2) and a capacitance retention of up to 90% (1000 charge-discharge cycles). More significantly, the resultant supercapacitor retains outstanding electrochemical performance even after being subjected to various deformations and even under harsh conditions. This study provides a reliable strategy for developing a high-performance ionogel electrolyte and broadens its application in flexible ionotronics.

20.
BMC Microbiol ; 24(1): 98, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38528458

RESUMEN

OBJECTIVE: The association between heart failure (HF) and intestinal inflammation caused by a disturbed intestinal microbiota in infants with congenital heart disease (CHD) was investigated. METHODS: Twenty infants with HF and CHD who were admitted to our hospital between October 2021 and March 2022 were included in this study. Twenty age- and sex-matched infants without HF at our hospital were selected as the control group. Faecal samples were obtained from each participant and analysed by enzyme-linked immunoassay and 16 S rDNA sequencing to assess intestinal inflammatory factors and the microbiota. RESULTS: The levels of intestinal inflammatory factors, including IL-1ß, IL-4, IL-6, IL-17 A and TNF-α, were greatly increased, while the levels of IL-10 were significantly decreased in the HF group compared to the control group (p < 0.05). The intestinal microbial diversity of patients in the HF group was markedly lower than that in the control group (p < 0.05). The abundance of Enterococcus was significantly increased in the HF group compared to the control group (p < 0.05), but the abundance of Bifidobacterium was significantly decreased in the HF group compared to the control group (p < 0.05). The diversity of the intestinal microbiota was negatively correlated with the levels of IL-1ß, IL-4, IL-6 and TNF-α in the intestinal tract but was positively correlated with that of IL-10. The abundance of Enterococcus was positively associated with the levels of IL-1ß, IL-4, IL-6 and TNF-α in the intestinal tract but was negatively correlated with that of IL-10. NT-proBNP was positively associated with the levels of IL-1ß, IL-4, IL-6 and TNF-α in the HF group but was negatively correlated with that of IL-10. The heart function score was positively associated with the levels of IL-1ß, IL-4, IL-6 and TNF-α in the HF group but was negatively correlated with that of IL-10. CONCLUSIONS: Infants with CHD-related HF had a disordered intestinal microbiota, decreased diversity of intestinal microbes, increased levels of pathogenic bacteria and decreased levels of beneficial bacteria. The increased abundance of Enterococcus and the significant decrease in the diversity of the intestinal microbiota may exacerbate the intestinal inflammatory response, which may be associated with the progression of HF.


Asunto(s)
Cardiopatías Congénitas , Insuficiencia Cardíaca , Lactante , Humanos , Interleucina-10 , Factor de Necrosis Tumoral alfa , Interleucina-6 , Interleucina-4 , Insuficiencia Cardíaca/complicaciones , Cardiopatías Congénitas/complicaciones , Enterococcus/genética , Inflamación
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