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1.
Methods Mol Biol ; 2854: 127-141, 2025.
Artículo en Inglés | MEDLINE | ID: mdl-39192125

RESUMEN

Luciferase reporter systems are commonly used in scientific research to investigate a variety of biological processes, including antiviral innate immunity. These systems employ the use of luciferase enzymes derived from organisms such as fireflies or renilla reniformis, which emit light upon reaction with a substrate. In the context of antiviral innate immunity, the luciferase reporter systems offer a noninvasive and highly sensitive approach for real-time monitoring of immune responses in vitro and in vivo, enabling researchers to delve into the intricate interactions and signaling pathways involved in host-virus dynamic interactions. Here, we describe the methods of the promoter-luciferase reporter and enhancer-luciferase reporter, which provide insights into the transcriptional and post-transcriptional regulation of antiviral innate immunity. Additionally, we outline the split-luciferase complementary reporter method, which was designed to explore protein-protein interactions associated with antiviral immunity. These methodologies offer invaluable knowledge regarding the molecular mechanisms underlying antiviral immune pathways and have the potential to support the development of effective antiviral therapies.


Asunto(s)
Genes Reporteros , Inmunidad Innata , Luciferasas , Humanos , Luciferasas/metabolismo , Luciferasas/genética , Animales , Interferones/metabolismo , Interferones/inmunología , Regiones Promotoras Genéticas , Antivirales/farmacología , Células HEK293 , Interacciones Huésped-Patógeno/inmunología , Interacciones Huésped-Patógeno/genética
2.
Chem Sci ; 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39355224

RESUMEN

Developing p-type polymeric semiconductors with exceptional electrical performance, heat tolerance, and cost-effectiveness is pivotal for advancing the practical application of n-i-p perovskite solar cells. Here, we employed direct arylation polycondensation to synthesize an alternating copolymer of phenothiazine and 3,4-ethylenedioxythiophene, featuring a high glass transition temperature (175 °C). In addition to the alternation of conjugated units within the main chain, the copolymer features alternating flexible (2-octyldodecyl) and rigid (trimethylphenyl) substituents at the nitrogen positions of the phenothiazine moiety. Compared to reference polymers with solely flexible or rigid substituents, the alternating use of these moieties resulted in the polymeric semiconductor composite film with smoother morphology and enhanced hole mobility. By employing this polymer with a distinct distribution of substituents and an innovative main chain structure as a hole transport material, we fabricated perovskite solar cells achieving an average efficiency of 25.1%. These cells also exhibited excellent stabilities under conditions of 85 °C thermal storage and 45 °C operation.

3.
J Neurosci Methods ; : 110296, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39357604

RESUMEN

OBJECTIVE: Adipose-derived stromal cells (ADSCs) have shown promise as a potential source of neural differentiation. In this study, we investigated the morphological, molecular and ultrastructural features of ADSCs during neuronal differentiation. METHODS: ADSCs were induced in vitro and their differentiation was examined at different time points. Immunocytochemical staining was performed to detect the expression of neuron-specific markers NSE and MAP-2. Immunofluorescence double labeling and Western blot detected the co-expression of presynaptic markers (CaMKII, SynCAM1, SYN) and postsynaptic markers (PSD-95, Synapsin I). Scanning electron microscopy (SEM) was performed to detect the synaptic structural features of differentiated neurons. RESULTS: ADSCs showed diverse morphological features during differentiation, gradually acquiring a neuron-like spindle shape and organized arrangement. The expression of neuron-specific markers and synaptic markers peaked at 5h of induction. Scanning electron microscopy showed polygonal protrusions of ADSC-derived neurons, and transmission electron microscopy showed characteristic ultrastructures such as nidus, synaptic vesicle-like structures, and tight junctions. CONCLUSION: Our findings suggest that ADSCs differentiated for 5h have neuronal features, including morphological, molecular, and ultrastructural resemblance to neurons, as well as the formation of synaptic structures. These insights contribute to a better understanding of ADSC-based neuronal differentiation and pave the way for future applications in regenerative medicine and neurodegenerative diseases.

4.
J Plast Reconstr Aesthet Surg ; 98: 331-336, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39326095

RESUMEN

BACKGROUND: Urethral plate (UP) reserved Onlay urethroplasty is currently used widely in mid-distal hypospadias. However, for children with 15-30° residual curvature after degloving, only dorsal tunica albuginea plication is performed to correct penile ventral curvature (VC), and long-term follow-up showed a high recurrence rate of penile curvature. We developed a modified Onlay urethroplasty, which dissociates the UP and completely removes the tissue beneath the UP to fully correct penile curvature. Furthermore, we compared it with the standard Onlay urethroplasty to explore its rationality and feasibility. METHODS: We prospectively collected clinical data from 68 children with hypospadias who underwent standard or modified Onlay urethroplasty between September 2019 and June 2021, and evaluated the interim outcomes to identify the complications between the two groups. Additionally, we conducted histological examination of the tissue beneath the UP. RESULTS: A total of 32 patients underwent modified Onlay urethroplasty. Intraoperative curvature measurements showed that 37.5% (12/32) of the patients had completely straightened their penis after UP dissection and removal of the fibrous tissue beneath it. A total of 36 patients underwent standard Onlay urethroplasty. Totally, five fistulas each were reported in the first and second groups, and the complication rates were 15.6% and 13.9%, respectively (P > 0.05). The histological results showed that the tissue below the UP contains a large amount of collagen, mainly type I collagen. CONCLUSION: The dissociated UP Onlay urethroplasty can maximally remove factors limiting penis growth and completely correct penile curvature, without increasing the incidence of postoperative complications. Therefore, we recommend the application of the improved Onlay urethroplasty in children with mid-distal hypospadias.

5.
Environ Sci Technol ; 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39329193

RESUMEN

Gaseous oxygenated organic molecules (OOMs) are crucial precursors of atmospheric organic aerosols. OOMs in urban atmospheres have complex compositions, posing challenges to understanding their formation, evolution, and influences. In this study, we identify 2403 atmospheric gaseous OOMs in urban Beijing using online nitrate-based chemical ionization Orbitrap mass spectrometry based on one-year atmospheric measurements. We find that OOMs in urban atmospheres can be identified with higher accuracy and wider coverage, compared to previously used online mass spectrometry. With optimized OOM resolving capabilities, previous knowledge of OOMs in urban atmospheres can be expanded. First, clear homologous and oxygen-addition characteristics of the OOMs are revealed. Second, OOMs with lower concentrations or higher masses are identified and characterized with high confidence, e.g., OOMs with masses above 350 Da. In particular, dimers of OOMs (e.g., C20H32O8-15N2), crucial species for organic nucleation, are identified. During four seasons, nitrogen-containing OOMs dominate the total concentration of OOMs, and OOMs are mainly from aromatic and aliphatic oxidation. Additionally, radicals with similar composition as OOMs, intermediates for OOM formation, are identified with clear diurnal variation, e.g., CnH2n-5O6 radicals (n = 8-10) and CmH2m-4NO9 radicals (m = 9-10), peak during the daytime and nighttime, respectively, previously having scarce measurement evidence in urban atmospheres.

6.
Hepatology ; 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39302977

RESUMEN

BACKGROUND AND AIMS: Hyperactivated inflammatory responses induced by cytokine release syndrome (CRS) are the primary causes of tissue damage and even death. The translation process is precisely regulated to control the production of proinflammatory cytokines. However, it is largely unknown whether targeting translation can effectively limit the hyperactivated inflammatory responses during acute hepatitis and graft-versus-host disease (GVHD). APPROACH AND RESULTS: By using in vitro translation and cellular overexpression systems, we have found that the non-structural protein gene NS2A of Zika virus (ZIKV) functions as RNA molecules to suppress the translation of both ectopic genes and endogenous proinflammatory cytokines. Mechanistically, results from RNA pulldown and co-immunoprecipitation (Co-IP) assays have demonstrated that NS2A RNA interacts with the translation initiation factor eIF2α to disrupt the dynamic balance of the eIF2/eIF2B complex and translation initiation, which is the rate-limiting step during the translation process. In the acetaminophen (APAP)-, LPS/D-galactosamine (D-GalN)-, viral infection-induced acute hepatitis, and GVHD mouse models, mice with myeloid cell-specific knock-in of NS2A show decreased levels of serum proinflammatory cytokines and reduced tissue damage. CONCLUSIONS: ZIKV NS2A dampens the production of proinflammatory cytokines and alleviates inflammatory injuries by interfering translation process as RNA molecules, which suggests that NS2A RNA is potentially used to treat numerous acute inflammatory diseases characterized by CRS.

7.
Neuroimage ; 299: 120841, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39244077

RESUMEN

Working memory in attention deficit hyperactivity disorder (ADHD) is closely related to cortical functional network connectivity (CFNC), such as abnormal connections between the frontal, temporal, occipital cortices and with other brain regions. Low-intensity transcranial ultrasound stimulation (TUS) has the advantages of non-invasiveness, high spatial resolution, and high penetration depth and can improve ADHD memory behavior. However, how it modulates CFNC in ADHD and the CFNC mechanism that improves working memory behavior in ADHD remain unclear. In this study, we observed working memory impairment in ADHD rats, establishing a corresponding relationship between changes in CFNCs and the behavioral state during the working memory task. Specifically, we noted abnormalities in the information transmission and processing capabilities of CFNC in ADHD rats while performing working memory tasks. These abnormalities manifested in the network integration ability of specific areas, as well as the information flow and functional differentiation of CFNC. Furthermore, our findings indicate that TUS effectively enhances the working memory ability of ADHD rats by modulating information transmission, processing, and integration capabilities, along with adjusting the information flow and functional differentiation of CFNC. Additionally, we explain the CFNC mechanism through which TUS improves working memory in ADHD. In summary, these findings suggest that CFNCs are important in working memory behaviors in ADHD.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Memoria a Corto Plazo , Animales , Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Trastorno por Déficit de Atención con Hiperactividad/terapia , Ratas , Memoria a Corto Plazo/fisiología , Masculino , Modelos Animales de Enfermedad , Corteza Cerebral/fisiopatología , Corteza Cerebral/diagnóstico por imagen , Ratas Sprague-Dawley , Red Nerviosa/fisiopatología , Red Nerviosa/diagnóstico por imagen
8.
Front Neurol ; 15: 1358859, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39346768

RESUMEN

Background: Cancer patients frequently suffer pain as one of their symptoms. It includes acute and chronic pain and is one of the most feared symptoms for patients. About one-third of adults actively undergoing cancer treatment suffer from pain related to their condition. Cancer pain control remains suboptimal due to a lack of assessment, knowledge, and access. Fire needle therapy, a traditional Chinese medicine, offers a potentially beneficial addition to current pain management approaches. This protocol outlines a systematic review and meta-analysis to compile evidence and examine the pain-relieving effects and safety of fire needle therapy for cancer patients. Methods and analysis: We will systematically search China National Knowledge Infrastructure (CNKI), Wanfang Database, China Biology Medicine disc (CBM), China Science and Technology Journal Database (CSTJ or VIP), PubMed, Web of Science, Embase, Cochrane Central Registry of Controlled Trials (CENTRAL), Chinese Clinical Trial Registry (Chictr), Opengrey, Worldcat, and Scopus from inception through July 2023. Random control trials (RCTs) include all types of cancer patients (age ≥ 18 years) complaining of pain. The primary outcome will be changes in pain intensity measured by Visual Analogue Scale (VAS), Numerical Rating Scale (NRS), Neuropathic Pain Scale (NPS), or Brief Pain Inventory (BPI). Secondary outcomes include quality of life (EORTC QLQ-C30 and GCQ), performance status (KPS), times of burst pain, treatment response rate, the dose reduction of analgesic drugs, and side effects rates. Utilizing the Cochrane risk bias measurement tool: Risk of Bias 2 (RoB 2), the trials' quality will be evaluated, and meta-analysis will be performed using RevMan software (version 5.4). Discussion: This systematic review will be the first comprehensive review of the literature to provide a meta-analysis of fire needle therapy for cancer pain, including only Random control trials (RCTs). For the sake of transparency and to avoid future duplication, the publication of this protocol offers a clear illustration of the procedures utilized in this evaluation. The results of our future studies may provide a new approach and theoretical basis for the treatment of cancer pain by medical oncology professionals. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023418609.

9.
Nat Cell Biol ; 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39300312

RESUMEN

Endocytosis and recycling control the uptake and retrieval of various materials, including membrane proteins and lipids, in all eukaryotic cells. These processes are crucial for cell growth, organization, function and environmental communication. However, the mechanisms underlying efficient, fast endocytic recycling remain poorly understood. Here, by utilizing a biosensor and imaging-based screening, we uncover a recycling mechanism that couples endocytosis and fast recycling, which we name the clathrin-associated fast endosomal recycling pathway (CARP). Clathrin-associated tubulovesicular carriers containing clathrin, AP1, Arf1, Rab1 and Rab11, while lacking the multimeric retrieval complexes, are generated at subdomains of early endosomes and then transported along actin to cell surfaces. Unexpectedly, the clathrin-associated recycling carriers undergo partial fusion with the plasma membrane. Subsequently, they are released from the membrane by dynamin and re-enter cells. Multiple receptors utilize and modulate CARP for fast recycling following endocytosis. Thus, CARP represents a previously unrecognized endocytic recycling mechanism with kiss-and-run membrane fusion.

10.
Medicine (Baltimore) ; 103(22): e38094, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-39259103

RESUMEN

Patients with diabetes have physical and psychological issues due to chronic illness. According to the guidelines of the Chinese Diabetes Society, after the diagnosis of patients with diabetes, they should receive routine health education, but this is the passive installation method of education. Nurses have made important contributions to the follow-up, education, and support of patients with diabetes and their families. The objective of this study was to evaluate the effectiveness of nurse-led follow-up care in routine health education and follow-up for patients with diabetes. Medical records of 721 patients with type 1 and type 2 diabetes were reviewed. Patients received nurse-led follow-up care including educational programs + Tai Chi exercises (patients received nurse-led follow-up care including educational programs for 6 months, n = 108), routine health education and follow-up + Tai Chi exercises (patients received routine health education and follow-up for 6 months, n = 205), or Tai Chi exercises only, but did not receive nurse-led follow-up care or routine health education and follow-up (patients received Tai Chi exercises only for 6 months, n = 408) for 6-months. The Zung Self-Rating Depression and Anxiety Scale and Summary of Diabetes Self-Care Activities were used to evaluate anxiety, depression, and self-care activities, respectively. Before the start of follow-up care (BFC), knowledge regarding diabetes and its threat was ≤1.75, anxiety and depression scores were ≥52 each, and self-care activities were ≤37. After 6 months of follow-up care, patients in the patients received nurse-led follow-up care including educational programs for 6 months improved their knowledge regarding diabetes and its threat, anxiety, depression, and self-care activities as compared to their before the start of follow-up care conditions and patients in the RF and patients received Tai Chi exercises only for 6 months at after 6 months of follow-up care conditions (P < .001 for all). Chinese type 1 or 2 diabetes patients had worse physical and psychological conditions and less knowledge regarding diabetes and its threat. Nurse-led aftercare, including educational programs with Tai Chi exercises for 6 months, decreased anxiety and depression and improved knowledge regarding diabetes and its threat and self-care activities in diabetic patients (Level of Evidence: IV; Technical Efficacy: Stage 5).


Asunto(s)
Diabetes Mellitus Tipo 2 , Educación del Paciente como Asunto , Autocuidado , Humanos , Masculino , Femenino , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/enfermería , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/psicología , Autocuidado/métodos , Educación del Paciente como Asunto/métodos , Adulto , Taichi Chuan/métodos , Anciano , Educación en Salud/métodos , Diabetes Mellitus Tipo 1/enfermería , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 1/psicología , Ansiedad/etiología , Estudios de Seguimiento , Cuidados Posteriores/métodos
11.
Chem Sci ; 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39246348

RESUMEN

In the quest to enhance the efficiency and durability of n-i-p perovskite solar cells (PSCs), engineering hole-transporting conjugated polymers with well-matched energy levels, exceptional film-forming properties, rapid hole transport, and superior moduli is paramount. Here, we present a novel approach involving the customization of a conjugated polymer, designated as p-DTPF4-EBEH, comprising alternating units of an oxa[5]helicene-based polycyclic heteroaromatic (DTPF4) and 5,5'-(2,5-di(hexyloxy)-1,4-phenylene)bis(3,4-ethylenedioxythiophene) (EBEH), synthesized through palladium-catalyzed direct arylation. Relative to homopolymers p-DTPF4 and p-EBEH, p-DTPF4-EBEH demonstrates a proper HOMO energy level, hole density, and hole mobility, alongside superior film-forming capabilities. Remarkably, compared to the commonly used hole transport material spiro-OMeTAD, p-DTPF4-EBEH not only exhibits superior film-forming property and hole mobility but also offers increased modulus and improved waterproofing. Incorporating p-DTPF4-EBEH as the hole transport material in PSCs results in an average power conversion efficiency of 25.8%, surpassing the 24.3% achieved with spiro-OMeTAD. Importantly, devices utilizing p-DTPF4-EBEH demonstrate enhanced thermal storage stability at 85 °C, along with operational robustness.

13.
Invest Ophthalmol Vis Sci ; 65(10): 36, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39186261

RESUMEN

Purpose: Keratoconus (KC), characterized by progressive corneal protrusion and thinning, is a complex disease influenced by the combination of genetic and environmental factors. The purpose of this study was to explore potential gene‒environment interaction between the calpastatin (CAST) gene and eye-rubbing in KC. Methods: A case-only study including 930 patients (676 patients with eye-rubbing and 254 patients without eye-rubbing) from the Chinese Keratoconus (CKC) cohort study was performed in the present study. Genotyping of single nucleotide polymorphism (SNP) was conducted using the Illumina Infinium Human Asian Screening Array (ASA) Beadchip. The gene‒environment interactions between CAST gene and eye-rubbing were analyzed using PLINK version 1.90. The interactions between CAST genotypes and eye-rubbing were analyzed by logistic regression models. The SNP-SNP-environment interactions were analyzed using generalized multifactor dimensionality reduction (GMDR). Results: Three SNPs in CAST gene, namely, rs26515, rs27991, and rs9314177, reached the significance threshold for interactions (defined as P < 2.272 × 10-3). Notably, the minor alleles of these three SNPs exhibited negative interactions with eye-rubbing in KC. The results of logistic regression models revealed that the minor allele homozygotes and heterozygotes of rs26515, rs27991, and rs9314177 also exhibited negative interactions with eye-rubbing. Furthermore, GMDR analysis revealed the significant SNP-SNP-environment interactions among rs26515, rs27991, rs9314177, and eye-rubbing in KC. Conclusions: This study identified rs26515, rs27991, and rs9314177 in CAST gene existed gene-environment interactions with eye-rubbing in KC, which is highly important for understanding the underlying biological mechanisms of KC and guiding precision prevention and proper management.


Asunto(s)
Proteínas de Unión al Calcio , Interacción Gen-Ambiente , Queratocono , Polimorfismo de Nucleótido Simple , Adulto , Femenino , Humanos , Masculino , Adulto Joven , Proteínas de Unión al Calcio/genética , China/epidemiología , Pueblos del Este de Asia/genética , Predisposición Genética a la Enfermedad , Genotipo , Queratocono/genética
14.
Neurobiol Dis ; 200: 106635, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39128813

RESUMEN

Early-onset epilepsy following ischemic stroke is a severe neurological condition, the pathogenesis of which remains incompletely understood. Recent studies suggest that Neural stem/progenitor cells (NSPCs) play a crucial role in the disease process, yet the precise molecular mechanisms regulating NSPCs have not been thoroughly investigated. This study utilized single-cell transcriptome sequencing and bioinformatics analysis to identify disease-related genes, which were subsequently validated in both in vitro and in vivo experiments. The findings revealed that Hsp90aa1 (heat shock protein 90 kDa alpha, class A member 1), Jun proto-oncogene (JUN), and CC Motif Ligation 2 (Ccl2) constitute an important regulatory axis influencing the migration and differentiation of NSPCs, potentially impacting the onset and progression of early-onset epilepsy post-ischemic stroke. Additionally, the expression of Hsp90aa1 was found to influence the likelihood of seizure occurrence and the severity of brain ischemia.


Asunto(s)
Diferenciación Celular , Movimiento Celular , Epilepsia , Proteínas HSP90 de Choque Térmico , Accidente Cerebrovascular Isquémico , Células-Madre Neurales , Animales , Masculino , Ratones , Diferenciación Celular/fisiología , Movimiento Celular/fisiología , Progresión de la Enfermedad , Epilepsia/metabolismo , Epilepsia/genética , Proteínas HSP90 de Choque Térmico/metabolismo , Proteínas HSP90 de Choque Térmico/genética , Accidente Cerebrovascular Isquémico/metabolismo , Accidente Cerebrovascular Isquémico/patología , Ratones Endogámicos C57BL , Células-Madre Neurales/metabolismo , Proteínas Proto-Oncogénicas c-jun
15.
Cell Insight ; 3(5): 100186, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39144257

RESUMEN

Enhanced glutamine catabolism is one of the main metabolic features of cancer, providing energy and intermediate metabolites for cancer progression. However, the functions of glutamine catabolism in cancer under nutrient deprivation need to be further clarified. Here, we discovered that deacetylation of glutamate dehydrogenase 1 (GLUD1), one of the key enzymes in glutamine catabolism, maintains the survival of lung adenocarcinoma (LUAD) cells under glucose starvation by inhibiting autophagic cell death. We found that glucose starvation increased GLUD1 activity by reducing its acetylation on Lys84 and promoted its active hexamer formation. Besides, deacetylation of GLUD1 induced its cytoplasmic localization, where GLUD1 was ubiquitinated in K63-linkage by TRIM21, leading to the binding of GLUD1 with cytoplasmic glutaminase KGA. These two effects enhanced glutamine metabolism both in mitochondria and cytoplasm, increased the production of alpha-ketoglutarate (α-KG). Meanwhile, cytoplasmic GLUD1 also interacted with p62 and prevented its acetylation, leading to the inhibition of p62 body formation. All these effects blocked autophagic cell death of LUAD cells under glucose starvation. Taken together, our results reveal a novel function of GLUD1 under glucose deprivation in LUAD cells and provide new insights into the functions of glutamine catabolism during cancer progression.

16.
Artículo en Inglés | MEDLINE | ID: mdl-39162400

RESUMEN

SnTe, an environmentally friendly thermoelectric material, has garnered widespread scholarly interest owing to its lead-free nature; however, its intrinsic thermoelectric performance is constrained by a relatively low Seebeck coefficient and an extremely high lattice thermal conductivity. In this investigation, we employ the alloying of Ge and AgSbTe2 to enhance the zT value of SnTe. The study found that Ge, Ag, and Sb can effectively enhance the Seebeck coefficient and power factor of SnTe by utilizing band convergence. At the same time, a multitude of point defects induce phonon scattering, consequently decreasing the lattice thermal conductivity of SnTe. Collectively, these synergistic effects result in Sn0.75Ge0.25Te-15% AgSbTe2 achieving its highest zT value of 1.28 at 823 K, with an average zT value of 0.77 between 400 and 823 K. Such high zT values of the SnTe-based thermoelectric material provide the potential for applications in high-performance solid-state thermoelectric devices.

17.
Food Chem X ; 23: 101668, 2024 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-39139487

RESUMEN

Yuling paste, a traditional Chinese health food derived from longan pulp and American ginseng, undergoes a unique processing method involving nine cycles of steaming and sun-drying. Ultra-high-performance liquid chromatography tandem mass spectrometry combined with widely targeted metabolomics has been used to examine the dynamic change in metabolite profiles through the processing. A total of 758 metabolites were identified. Processing significantly affects metabolite changes, and network pharmacology is subsequently used to explore potential pharmacological ingredients. After processing, the contents of active ingredients such as ginsenoside rh2, oleanolic acid, choline, d-glucose, and D-galacturonic acid were found to increase significantly. These increases can be correlated to the enhancement of five distinct pathways, and the contents of naringenin-7-O-glucoside, adenosine, pantothenic acid, and D-sucrose decreased after the processing, correlating with decreases in two different pathways. This study provides a comprehensive reference and scientific basis for understanding the health benefits associated with this traditional health food.

18.
J Nanobiotechnology ; 22(1): 495, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39164753

RESUMEN

BACKGROUND: The Hippo pathway is a conserved tumour suppressor signalling pathway, and its dysregulation is often associated with abnormal cell growth and tumorigenesis. We previously revealed that the transcriptional coactivator Yes-associated protein (YAP), the key effector of the Hippo pathway, is a molecular target for glioblastoma (GBM), the most common malignant brain tumour. Inhibiting YAP with small interfering RNA (siYAP) or the specific inhibitor verteporfin (VP) can diminish GBM growth to a certain degree. RESULTS: In this study, to enhance the anti-GBM effect of siYAP and VP, we designed stepwise-targeting and hypoxia-responsive liposomes (AMVY@NPs), which encapsulate hypoxia-responsive polymetronidazole-coated VP and DOTAP adsorbed siYAP, with angiopep-2 (A2) modification on the surface. AMVY@NPs exhibited excellent blood‒brain barrier crossing, GBM targeting, and hypoxia-responsive and efficient siYAP and VP release properties. By inhibiting the expression and function of YAP, AMVY@NPs synergistically inhibited both the growth and stemness of GBM in vitro. Moreover, AMVY@NPs strongly inhibited the growth of orthotopic U87 xenografts and improved the survival of tumour-bearing mice without adverse effects. CONCLUSION: Specific targeting of YAP with stepwise-targeting and hypoxia-responsive liposome AMVY@NPs carrying siYAP and VP efficiently inhibited GBM progression. This study provides a valuable drug delivery platform and creative insights for molecular targeted treatment of GBM in the future.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Liposomas , Ratones Desnudos , ARN Interferente Pequeño , Verteporfina , Glioblastoma/tratamiento farmacológico , Glioblastoma/metabolismo , Glioblastoma/patología , Liposomas/química , Verteporfina/farmacología , Verteporfina/uso terapéutico , Animales , Humanos , Línea Celular Tumoral , Ratones , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/metabolismo , Proteínas Señalizadoras YAP , Nanopartículas/química , Ratones Endogámicos BALB C , Factores de Transcripción/metabolismo , Angiomotinas , Ensayos Antitumor por Modelo de Xenoinjerto , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/efectos de los fármacos , Péptidos
19.
Angew Chem Int Ed Engl ; : e202412680, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39166757

RESUMEN

Designing highly active and cost-effective electrocatalysts for the alkaline hydrogen oxidation reaction (HOR) is critical for advancing anion-exchange membrane fuel cells (AEMFCs). While dilute metal alloys have demonstrated substantial potential in enhancing alkaline HOR performance, there has been limited exploration in terms of rational design, controllable synthesis, and mechanism study. Herein, we developed a series of dilute Pd-Ni alloys, denoted as x% Pd-Ni, based on a trace-Pd decorated Ni-based coordination polymer through a facile low-temperature pyrolysis approach. The x% Pd-Ni alloys exhibit efficient electrocatalytic activity for HOR in alkaline media. Notably, the optimal 0.5% Pd-Ni catalyst demonstrates high intrinsic activity with an exchange current density of 0.055 mA cm-2, surpassing that of many other alkaline HOR catalysts. The mechanism study reveals that the strong synergy between Pd single atoms (SAs)/Pd dimer and Ni substrate can modulate the binding strength of proton (H)/hydroxyl (OH), thereby significantly reducing the activation energy barrier of a decisive reaction step. This work offers new insights into designing advanced dilute metal or single-atom-alloys (SAAs) for alkaline HOR and potentially other energy conversion processes.

20.
Int J Surg ; 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-39167041

RESUMEN

BACKGROUND: We seek to compare the early and late outcomes of reperfusion-first versus central repair-first strategies in patients with acute type A dissection (ATAAD) complicated by mesenteric malperfusion. METHODS: Among 68 patients, reperfusion-first strategy with superior mesenteric artery (SMA) stenting was adopted in 31 and central repair-first in 37, based on rupture risk and circulatory compromise, severity, time and mechanisms of mesenteric ischemia. Early and late outcomes were compared between two strategies. Follow-up was 100% at 3.3±1.4 years. RESULTS: Mean age was 50.6±11.4 years (59 males, 86.8%). The reperfusion-first group had more celiac artery involvement (74.2% vs. 48.6%) and peritoneal irritation signs (19.4% vs. 2.7%), while central repair-first group had more tamponade (27% vs. 3.2%). Early mortality was 48.6% (18/37) with central repair-first strategy versus 19.4% (6/31) in reperfusion-first group (P=0.012). Reperfusion-first patients had fewer gastrointestinal complications (12.9% vs. 54.1%, P<0.001) and respiratory failure (3.2% vs. 24.3%, P=0.017). At 5 years, SMA stent patency was 84%, and survival was significantly higher in reperfusion-first patients (80.6% vs. 45.9%, P=0.009), with similar freedom from adverse events between two groups (74.9% vs. 76.0%, P=0.812). Tamponade (hazard ratio [HR], 3.093; P=0.023), peritoneal irritation signs (HR, 8.559; P=0.006), and lactate (mmol/L) (HR, 1.279; P<0.001) were predictors for all-cause mortality. CONCLUSIONS: In this series of ATAAD patients with mesenteric malperfusion, the reperfusion-first strategy with SMA stenting could significantly reduce the mortality risk and achieved favorable late survival and freedom from adverse events. These results argue favorably for the use of the reperfusion-first strategy in such patients.

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