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1.
Brief Bioinform ; 24(4)2023 07 20.
Artículo en Inglés | MEDLINE | ID: mdl-37193676

RESUMEN

Protein-deoxyribonucleic acid (DNA) interactions are important in a variety of biological processes. Accurately predicting protein-DNA binding affinity has been one of the most attractive and challenging issues in computational biology. However, the existing approaches still have much room for improvement. In this work, we propose an ensemble model for Protein-DNA Binding Affinity prediction (emPDBA), which combines six base models with one meta-model. The complexes are classified into four types based on the DNA structure (double-stranded or other forms) and the percentage of interface residues. For each type, emPDBA is trained with the sequence-based, structure-based and energy features from binding partners and complex structures. Through feature selection by the sequential forward selection method, it is found that there do exist considerable differences in the key factors contributing to intermolecular binding affinity. The complex classification is beneficial for the important feature extraction for binding affinity prediction. The performance comparison of our method with other peer ones on the independent testing dataset shows that emPDBA outperforms the state-of-the-art methods with the Pearson correlation coefficient of 0.53 and the mean absolute error of 1.11 kcal/mol. The comprehensive results demonstrate that our method has a good performance for protein-DNA binding affinity prediction. Availability and implementation: The source code is available at https://github.com/ChunhuaLiLab/emPDBA/.


Asunto(s)
Proteínas , Programas Informáticos , Proteínas/química , Biología Computacional/métodos , ADN/genética , Unión Proteica
2.
J Pathol ; 263(1): 8-21, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38332735

RESUMEN

Pompe disease is a lysosomal storage disorder that preferentially affects muscles, and it is caused by GAA mutation coding acid alpha-glucosidase in lysosome and glycophagy deficiency. While the initial pathology of Pompe disease is glycogen accumulation in lysosomes, the special role of the lysosomal pathway in glycogen degradation is not fully understood. Hence, we investigated the characteristics of accumulated glycogen and the mechanism underlying glycophagy disturbance in Pompe disease. Skeletal muscle specimens were obtained from the affected sites of patients and mouse models with Pompe disease. Histological analysis, immunoblot analysis, immunofluorescence assay, and lysosome isolation were utilized to analyze the characteristics of accumulated glycogen. Cell culture, lentiviral infection, and the CRISPR/Cas9 approach were utilized to investigate the regulation of glycophagy accumulation. We demonstrated residual glycogen, which was distinguishable from mature glycogen by exposed glycogenin and more α-amylase resistance, accumulated in the skeletal muscle of Pompe disease. Lysosome isolation revealed glycogen-free glycogenin in wild type mouse lysosomes and variously sized glycogenin in Gaa-/- mouse lysosomes. Our study identified that a defect in the degradation of glycogenin-exposed residual glycogen in lysosomes was the fundamental pathological mechanism of Pompe disease. Meanwhile, glycogenin-exposed residual glycogen was absent in other glycogen storage diseases caused by cytoplasmic glycogenolysis deficiencies. In vitro, the generation of residual glycogen resulted from cytoplasmic glycogenolysis. Notably, the inhibition of glycogen phosphorylase led to a reduction in glycogenin-exposed residual glycogen and glycophagy accumulations in cellular models of Pompe disease. Therefore, the lysosomal hydrolysis pathway played a crucial role in the degradation of residual glycogen into glycogenin, which took place in tandem with cytoplasmic glycogenolysis. These findings may offer a novel substrate reduction therapeutic strategy for Pompe disease. © 2024 The Pathological Society of Great Britain and Ireland.


Asunto(s)
Enfermedad del Almacenamiento de Glucógeno Tipo II , Glicoproteínas , Humanos , Ratones , Animales , Enfermedad del Almacenamiento de Glucógeno Tipo II/genética , Enfermedad del Almacenamiento de Glucógeno Tipo II/patología , Enfermedad del Almacenamiento de Glucógeno Tipo II/terapia , Glucógeno/análisis , Glucógeno/metabolismo , Glucosiltransferasas/metabolismo , Músculo Esquelético/patología , Lisosomas/metabolismo
3.
Brain ; 147(1): 100-108, 2024 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-37584389

RESUMEN

Recently, an astrocytic aquaporin 4-dependent drainage system, that is, the glymphatic system, has been identified in the live murine and human brain. Growing evidence suggests that glymphatic function is impaired in patients with several neurodegenerative diseases, including Alzheimer's and Parkinson's disease. As the third most common neurodegenerative disease, although animal studies have indicated that early glymphatic dysfunction is likely an important pathological mechanism underpinning amyotrophic lateral sclerosis (ALS), no available study has been conducted to thoroughly assess glymphatic function in vivo in ALS patients to date, particularly in patients with early-stage ALS. Thus, using diffusion tensor imaging analysis along the perivascular space (ALPS) index, an approximate measure of glymphatic function in vivo, we aimed to explore whether glymphatic function is impaired in patients with patients with early-stage ALS, and the diagnostic performance of the ALPS index in distinguishing between patients with early-stage ALS and healthy subjects. We also aimed to identify the relationships between glymphatic dysfunction and clinical disabilities and sleep problems in patients with early-stage ALS. In this retrospective study, King's Stage 1 ALS patients were defined as patients with early-stage ALS. We enrolled 56 patients with early-stage ALS and 32 age- and sex-matched healthy control subjects. All participants completed clinical screening, sleep assessment and ALPS index analysis. For the sleep assessment, the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and polysomnography were used. Compared with healthy control subjects, patients with early-stage ALS had a significantly lower ALPS index after family-wise error correction (P < 0.05). Moreover, receiver operating characteristic analysis showed that the area under the curve for the ALPS index was 0.792 (95% confidence interval 0.700-0.884). Partial correlation analyses showed that the ALPS index was significantly correlated with clinical disability and sleep disturbances in patients with early-stage ALS. Multivariate analysis showed that sleep efficiency (r = 0.419, P = 0.002) and periodic limb movements in sleep index (r = -0.294, P = 0.017) were significant predictive factors of the ALPS index in patients with early-stage ALS. In conclusion, our study continues to support an important role for glymphatic dysfunction in ALS pathology, and we provide additional insights into the early diagnostic value of glymphatic dysfunction and its correlation with sleep disturbances in vivo in patients with early-stage ALS. Moreover, we suggest that early improvement of glymphatic function may be a promising strategy for slowing the neurodegenerative process in ALS. Future studies are needed to explore the diagnostic and therapeutic value of glymphatic dysfunction in individuals with presymptomatic-stage neurodegenerative diseases.


Asunto(s)
Esclerosis Amiotrófica Lateral , Enfermedades Neurodegenerativas , Humanos , Animales , Ratones , Esclerosis Amiotrófica Lateral/complicaciones , Imagen de Difusión Tensora , Estudios Retrospectivos , Acuaporina 4
4.
Brief Bioinform ; 23(4)2022 07 18.
Artículo en Inglés | MEDLINE | ID: mdl-35536545

RESUMEN

The three-dimensional (3D) chromosomal structure plays an essential role in all DNA-templated processes, including gene transcription, DNA replication and other cellular processes. Although developing chromosome conformation capture (3C) methods, such as Hi-C, which can generate chromosomal contact data characterized genome-wide chromosomal structural properties, understanding 3D genomic nature-based on Hi-C data remains lacking. Here, we propose a persistent spectral simplicial complex (PerSpectSC) model to describe Hi-C data for the first time. Specifically, a filtration process is introduced to generate a series of nested simplicial complexes at different scales. For each of these simplicial complexes, its spectral information can be calculated from the corresponding Hodge Laplacian matrix. PerSpectSC model describes the persistence and variation of the spectral information of the nested simplicial complexes during the filtration process. Different from all previous models, our PerSpectSC-based features provide a quantitative global-scale characterization of chromosome structures and topology. Our descriptors can successfully classify cell types and also cellular differentiation stages for all the 24 types of chromosomes simultaneously. In particular, persistent minimum best characterizes cell types and Dim (1) persistent multiplicity best characterizes cellular differentiation. These results demonstrate the great potential of our PerSpectSC-based models in polymeric data analysis.


Asunto(s)
Cromosomas , Genómica , Diferenciación Celular , Cromosomas/genética , Genómica/métodos , Aprendizaje Automático , Conformación Molecular
5.
Physiol Plant ; 176(2): e14254, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38499939

RESUMEN

Together with rice, weeds strive for nutrients and space in farmland, resulting in reduced rice yield and quality. Planting herbicide-resistant rice varieties is one of the effective ways to control weeds. In recent years, a series of breakthroughs have been made to generate herbicide-resistant germplasm, especially the emergence of biotechnological tools such as gene editing, which provides an inherent advantage for the knock-out or knock-in of the desired genes. In order to develop herbicide-resistant rice germplasm resources, gene manipulation has been conducted to enhance the herbicide tolerance of rice varieties through the utilization of techniques such as physical and chemical mutagenesis, as well as genome editing. Based on the current research and persisting problems in rice paddy fields, research on the generation of herbicide-resistant rice still needs to explore genetic mechanisms, stacking multiple resistant genes in a single genotype, and transgene-free genome editing using the CRISPR system. Current rapidly developing gene editing technologies can be used to mutate herbicide target genes, enabling targeted genes to maintain their biological functions, and reducing the binding ability of target gene encoded proteins to corresponding herbicides, ultimately resulting in herbicide-resistant crops. In this review article, we have summarized the utilization of conventional and modern approaches to develop herbicide-resistant cultivars in rice as an effective strategy for weed control in paddy fields, and discussed the technology and research directions for creating herbicide-resistant rice in the future.


Asunto(s)
Herbicidas , Oryza , Oryza/genética , Herbicidas/farmacología , Malezas , Biotecnología , Productos Agrícolas/genética , Resistencia a los Herbicidas/genética
6.
Appl Opt ; 63(3): 708-713, 2024 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-38294383

RESUMEN

The Smith-Purcell radiation produced by electrons moving closely to a grating can be enhanced by resonances. Here, we show a method to manipulate the directionality of the resonance-enhanced radiation. Using the rigorous coupled-wave analysis method, we compare the radiation from symmetric and asymmetric gratings, showing that the enhanced Smith-Purcell radiation can become unilateral with a perturbation that breaks the structural symmetry. Our work provides an effective method for frequency-domain calculation of Smith-Purcell radiation and also an approach to realize more efficient use of the radiation.

7.
Nano Lett ; 23(11): 4778-4784, 2023 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-37252749

RESUMEN

Ferrimagnets are considered an excellent spintronic material candidate which combines ultrafast magnetic dynamics and straightforward electrical detectability. However, efficient routes toward magneto-ionic control of ferrimagnetic order remain elusive. In this study, a solid-state oxygen gating device was designed to control the magnetic properties of the ferrimagnetic CoTb alloy. Experimental results show that applying a small voltage can irreversibly tune a Tb-dominant device to a stable Co-dominant state and decrease the magnetization compensation temperature by 130 K. In addition, a reversible voltage control of the magnetization axis between out-of-plane and in-plane states is observed, which indicates that the migrated oxygen ions can bond to both Tb and Co sublattices. First-principles calculations indicate that voltage can dynamically control the flow-in and flow-out of oxygen ions that bond to the Co sublattice. Our work provides an effective means to manipulate ferrimagnetic order and contributes to the development of ultra-low-power spintronic devices.

8.
Small ; 19(50): e2305134, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37626457

RESUMEN

Phase change materials (PCMs) have great prospects in thermal management applications because they can store and release latent heat. However, they are not suitable for on-demand heating as they can only release heat once. Herein, this work reports the intermittent exothermic of PCMs based on a supersaturated salt solution, exhibiting fully controlled long-term storage of energy, releasing and suspending heat on demand. Due to the high energy barrier, it is difficult for the supersaturated salt solution to nucleate; thus, it can store energy for a long time. Contact with seeds or other foreign objects can destroy the metastable state of the supersaturated salt solution and promote the formation of crystal nuclei, enabling crystallization and heat release on demand. The release of crystallization heat can be interrupted using scissors dip in water. Additionally, self-healing behavior allows it to be recycled and last longer, due to the presence of Fe3+ , inducing strong dynamic reversible non-covalent crosslinking through metal coordination bonds. Furthermore, the hydrated salts gels are applied for thermal management of underfloor radiant heating system, demonstrating four types of intermittent exotherms sequences amazingly. Further, the intermittent exothermic hydrated salts gels provide a more user-friendly thermal management of underfloor radiant heating systems.

9.
Planta ; 257(2): 32, 2023 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-36602592

RESUMEN

MAIN CONCLUSION: A lncRNA MtCIR1 negatively regulates the response to salt stress in Medicago truncatula seed germination by modulating seedling growth and ABA metabolism and signaling by enhancing Na+ accumulation. Increasing evidence suggests that long non-coding RNAs (lncRNAs) are involved in the regulation of plant tolerance to varying abiotic stresses. A large number of lncRNAs that are responsive to abiotic stress have been identified in plants; however, the mechanisms underlying the regulation of plant responses to abiotic stress by lncRNAs are largely unclear. Here, we functionally characterized a salt stress-responsive lncRNA derived from the leguminous model plant M. truncatula, referred to as MtCIR1, by expressing MtCIR1 in Arabidopsis thaliana in which no such homologous sequence was observed. Expression of MtCIR1 rendered seed germination more sensitive to salt stress by enhanced accumulation of abscisic acid (ABA) due to suppressing the expression of the ABA catabolic enzyme CYP707A2. Expression of MtCIR1 also suppressed the expression of genes associated with ABA receptors and signaling. The ABA-responsive gene AtPGIP2 that was involved in degradation of cell wall during seed germination was up-regulated by expressing MtCIR1. On the other hand, expression of MtCIR1 in Arabidopsis thaliana enhanced foliar Na+ accumulation by down-regulating genes encoding Na+ transporters, thus rendering the transgenic plants more sensitive to salt stress. These results demonstrate that the M. truncatula lncRNA MtCIR1 negatively regulates salt stress response by targeting ABA metabolism and signaling during seed germination and foliar Na+ accumulation by affecting Na+ transport under salt stress during seedling growth. These novel findings would advance our knowledge on the regulatory roles of lncRNAs in response of plants to salt stress.


Asunto(s)
Medicago truncatula , ARN Largo no Codificante , Estrés Salino , Ácido Abscísico/metabolismo , Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas , Germinación/genética , Medicago truncatula/genética , Medicago truncatula/metabolismo , Plantas Modificadas Genéticamente/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Estrés Salino/genética , Plantones , Estrés Fisiológico/genética
10.
Plant Cell Environ ; 46(8): 2450-2469, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37249093

RESUMEN

Emerging evidence suggests that long noncoding RNAs (lncRNAs) are involved in regulation of plant response to environmental stress. CBF/DREB1s are highly conserved transcription factors that regulate response to cold stress in plants. However, very few lncRNAs were found to regulate expression of CBFs and cold tolerance in plant. Here, we identified a cold-responsive long intergenic noncoding RNA (MtCIR2) of CBF/DREB1 genes that were located in a major freezing tolerance QTL region of legume Medicago truncatula. We found that response of MtCIR2 transcription was more rapid than that of MtCBF/DREB1s during cold treatment. MtCIR2 positively regulated M. truncatula freezing tolerance, such that overexpression of MtCIR2 led to higher survival rate and lower cell membrane damage than wild-type plants, while mutation of MtCIR2 rendered the mutants more sensitive to cold stress. In addition, expression levels of MtCBF/DREB1s were up-regulated in the MtCIR2 overexpressing lines and down-regulated in the mutants. Among the MtCIR2-regulated genes, the strongest enriched genes were those involved in polysaccharide metabolic processes. In addition, we demonstrated that overexpression of MtCIR2 led to increases in contents of soluble sugars. These results highlight that MtCIR2 positively regulates tolerance to freezing by regulating MtCBF/DREB1s expression and glycometabolism in M. truncatula.


Asunto(s)
Proteínas de Arabidopsis , ARN Largo no Codificante , ARN Largo no Codificante/genética , Congelación , Factores de Transcripción/metabolismo , Familia de Multigenes , Regulación de la Expresión Génica de las Plantas , Frío , Proteínas de Arabidopsis/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
11.
J Chem Inf Model ; 63(18): 5847-5862, 2023 09 25.
Artículo en Inglés | MEDLINE | ID: mdl-37651308

RESUMEN

Within over 800 members of G-protein-coupled receptors, there are numerous orphan receptors whose endogenous ligands are largely unknown, providing many opportunities for novel drug discovery. However, the lack of an in-depth understanding of the intrinsic working mechanism for orphan receptors severely limits the related rational drug design. The G-protein-coupled receptor 52 (GPR52) is a unique orphan receptor that constitutively increases cellular 5'-cyclic adenosine monophosphate (cAMP) levels without binding any exogenous agonists and has been identified as a promising therapeutic target for central nervous system disorders. Although recent structural biology studies have provided snapshots of both active and inactive states of GPR52, the mechanism of the conformational transition between these states remains unclear. Here, an acceptable self-activation pathway for GPR52 was proposed through 6 µs Gaussian accelerated molecular dynamics (GaMD) simulations, in which the receptor spontaneously transitions from the active state to that matching the inactive crystal structure. According to the three intermediate states of the receptor obtained by constructing a reweighted potential of mean force, how the allosteric regulation occurs between the extracellular orthosteric binding pocket and the intracellular G-protein-binding site is revealed. Combined with the independent gradient model, several important microswitch residues and the allosteric communication pathway that directly links the two regions are both identified. Transfer entropy calculations not only reveal the complex allosteric signaling within GPR52 but also confirm the unique role of ECL2 in allosteric regulation, which is mutually validated with the results of GaMD simulations. Overall, this work elucidates the allosteric mechanism of GPR52 at the atomic level, providing the most detailed information to date on the self-activation of the orphan receptor.


Asunto(s)
Receptores Acoplados a Proteínas G , Transducción de Señal , Regulación Alostérica , Sitios de Unión , Comunicación
12.
Aesthetic Plast Surg ; 47(6): 2543-2551, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37535088

RESUMEN

BACKGROUND: Autologous cartilage grafts are increasingly used in the treatment of cleft lip nasal deformity, but nasal alar retraction caused by lining defects often occurs after surgery. We designed a new graft to treat unilateral cleft lip nasal deformity while avoiding nasal alar retraction. METHODS: Nineteen patients in our hospital underwent unilateral cleft lip nasal deformity repair surgery with an auricular cartilage-skin graft. The effect of surgery was evaluated in four aspects: satisfaction with postoperative appearance, nasal aesthetic subunit indices, position of the nasal alar rim and three-dimensional spatial difference. RESULTS: Overall satisfaction with each index was above 90%. The nasal tip angle and nasolabial angle of patients were significantly smaller after surgery than before surgery (P < 0.01). The height of the nostril on the affected side and the length of the nasal columella were greater after surgery than before surgery (P < 0.01). The spatial differences in soft tissue between the unaffected side and the affected side after surgery were significantly smaller than before surgery (P < 0.01). According to the follow-up results of 1-2 years, there were no significant retraction of the nasal alar rim (P > 0.05) and no obvious auricular deformity. All patients had a noticeable improvement in their nasal appearance. CONCLUSION: The auricular cartilage-skin graft, which can not only improve the appearance of the nose but also avoid nasal alar retraction, is an ideal graft to cure unilateral cleft lip nasal deformity. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Asunto(s)
Labio Leporino , Rinoplastia , Humanos , Labio Leporino/cirugía , Rinoplastia/métodos , Trasplante de Piel , Cartílago Auricular/cirugía , Nariz/cirugía , Tabique Nasal/cirugía , Resultado del Tratamiento
13.
J Sci Food Agric ; 103(12): 5883-5892, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37115015

RESUMEN

BACKGROUND: Cadmium (Cd), known as a vital contaminant in the environment, penetrates the blood-brain barrier and accumulates in the cerebrum. Acute toxicosis of Cd, which leads to lethal cerebral edema, intracellular accumulation and cellular dysfunction, remains to be illuminated with regard to the exact molecular mechanism of cerebral toxicity. Resveratrol (RES), present in the edible portions of numerous plants, is a simply acquirable and correspondingly less toxic natural compound with neuroprotective potential, which provides some theoretical bases for antagonizing Cd-induced cerebral toxicity. RESULTS: This work was executed to research the protective effects of RES against Cd-induced toxicity in chicken cerebrum. Markedly, these lesions were increased in the Cd group, which also exhibited a thinner cortex, reduced granule cells, vacuolar degeneration, and an enlarged medullary space in the cerebrum. Furthermore, Cd induced CYP450 enzyme metabolism disorders by disrupting the nuclear xenobiotic receptor response (NXRs), enabling the cerebrum to reduce the ability to metabolize exogenous substances, eventually leading to Cd accumulation. Meanwhile, accumulated Cd promoted oxidative damage and synergistically promoted the damage to neurons and glial cells. CONCLUSION: RES initiated NXRs (especially for aromatic receptor and pregnancy alkane X receptor), decreasing the expression of CYP450 genes, changing the content of CYP450, maintaining CYP450 enzyme normal activities, and exerting antagonistic action against the Cd-induced abnormal response of nuclear receptors. These results suggest that the cerebrum toxicity caused by Cd was reduced by pretreatment with RES. © 2023 Society of Chemical Industry.


Asunto(s)
Cadmio , Cerebro , Resveratrol/farmacología , Resveratrol/metabolismo , Cadmio/toxicidad , Cadmio/metabolismo , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Sistema Enzimático del Citocromo P-450/farmacología , Cerebro/metabolismo , Estrés Oxidativo , Microsomas/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo
14.
Opt Lett ; 47(11): 2911-2914, 2022 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-35648962

RESUMEN

Smith-Purcell radiation (SPR) is an important means of generating terahertz waves, and the enhancement of SPR is an attractive topic nowadays. Inspired by the phenomenon of special SPR, where the enhancement is achieved by using a high-duty-cycle grating, we describe a new, to the best of our knowledge, but more effective approach to this challenging problem. By deriving a simple analytical solution for the SPR from an annular electron beam passing through a cylindrical metallic grating, we show that the inverse structure, a low-duty-cycle grating can exhibit rather high SPR efficiencies in the presence of quasi-bound states in the continuum (quasi-BICs). The analytical prediction is supported by particle-in-cell simulations, which show that the quasi-BICs can enhance the superradiant SPR generated by a train of electron bunches by orders of magnitude. These results present an interesting mechanism for enhancing the SPR from metallic gratings, and may find applications in terahertz free-electron lasers.

15.
J Org Chem ; 87(12): 7658-7664, 2022 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-35658514

RESUMEN

The photoisomerization behavior of cyanostilbene molecules is a hotspot in supramolecular configuration transformation research. Here, we reported a cyanostilbene derivative that converted from the Z,Z-isomer to the E,E-isomer under UV light irradiation at 365 nm. This process can be reversibly converted only in the presence of cucurbit[8]uril under the same light source, accompanied by the reversible conversion of fluorescence from green to yellow. No effective configuration transformation occurred with guest molecules only or upon the addition of cucurbit[7]uril. The photoisomerization was fully characterized by UV-vis and fluorescence spectroscopy, NMR, high-resolution mass spectrometry, and transmission electron microscopy. This work provides a new method for the supramolecular macrocyclic-activated configuration transformation.

16.
J Nanobiotechnology ; 20(1): 512, 2022 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-36463157

RESUMEN

BACKGROUNDS: Reversing the immunosuppressive tumor microenvironment (TME) in the tumor is widely deemed to be an effective strategy to improve immune therapy. In particular, the redox balance in TME needs to be well controlled due to its critical role in mediating the functions of various cells, including cancer cells and immune-suppressive cells. RESULTS: Here, we propose an efficient strategy to reshape the redox homeostasis to reverse immunosuppressive TME. Specifically, we developed a microwave-chemo-immunostimulant CMMCP to promote the infiltration of the tumor-T cells by simultaneously reducing the reactive oxygen species (ROS) and glutathione (GSH) and improving the oxygen (O2) levels in TME. The CMMCP was designed by loading chemotherapy drugs cisplatin into the bimetallic Ce-Mn MOF nanoparticles coated with polydopamine. The Ce-Mn MOF nanoparticles can effectively improve the catalytic decomposition of ROS into O2 under microwave irradiation, resulting in overcoming hypoxia and limited ROS generation. Besides, the activity of intracellular GSH in TME was reduced by the redox reaction with Ce-Mn MOF nanoparticles. The reprogrammed TME not only boosts the immunogenic cell death (ICD) induced by cisplatin and microwave hyperthermia but also gives rise to the polarization of pro-tumor M2-type macrophages to the anti-tumor M1-type ones. CONCLUSION: Our in vivo experimental results demonstrate that the microwave-chemo-immunostimulant CMMCP significantly enhances the T cell infiltration and thus improves the antitumor effect. This study presents an easy, safe, and effective strategy for a whole-body antitumor effect after local treatment.


Asunto(s)
Adyuvantes Inmunológicos , Microondas , Cisplatino , Especies Reactivas de Oxígeno , Factores Inmunológicos , Inmunosupresores , Inmunoterapia , Oxidación-Reducción , Glutatión , Oxígeno
17.
Neurol Sci ; 43(5): 3201-3210, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34826032

RESUMEN

OBJECTIVE: We aim to investigate blood-brain barrier (BBB) dysfunction and myelin basic protein (MBP) in amyotrophic lateral sclerosis (ALS) with or without frontotemporal dementia (FTD) and further determine the effect of these factors on the survival of ALS. METHODS: This was a retrospective study of 113 ALS patients, 12 ALS-FTD patients, and 40 disease controls hospitalized between September 2013 and October 2020. CSF parameters including total protein (TP), albumin (Alb), immunoglobulin-G (IgG), and MBP were collected and compared between groups. The CSF-TP, CSF-Alb, CSF-IgG, and CSF/serum quotients of Alb and IgG (QAlb, QIgG) were used to reflect the BBB status. Patients were followed up until December 2020. Cox regression and Kaplan-Meier method were used for survival analysis. RESULTS: The CSF-TP, CSF-Alb, and CSF-IgG concentrations were significantly higher in patients than controls (p < 0.01). Increased CSF-TP and CSF-IgG was found in 45 (39.8%) and 27 (23.9%) ALS patients, while in 7 (58.3%) and 5 (41.7%) ALS-FTD patients. The level of CSF-Alb, CSF-IgG, and CSF-MBP were significantly higher in patients with ALS-FTD than ALS. MBP showed a moderate accuracy in the distinction between ALS-FTD and ALS (AUC = 0.715 ± 0.101). No difference in MBP was found between patients and controls. Kaplan-Meier analysis indicated that a higher CSF-TP, CSF-IgG, QIgG, or QAlb was significantly associated with shorter survival. Cox regression model showed that CSF-TP, CSF-IgG, and QIgG were independent predictors of survival. CONCLUSION: Our findings suggested that BBB dysfunction was more prominent in ALS-FTD than ALS and associated with a worse prognosis. Further studies are needed to determine the role of CSF-MBP as a biomarker in ALS.


Asunto(s)
Esclerosis Amiotrófica Lateral , Demencia Frontotemporal , Esclerosis Amiotrófica Lateral/metabolismo , Barrera Hematoencefálica/metabolismo , Humanos , Inmunoglobulina G/metabolismo , Proteína Básica de Mielina/metabolismo , Estudios Retrospectivos
18.
Arch Gynecol Obstet ; 305(5): 1193-1202, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34694432

RESUMEN

PURPOSE: Previous epidemiological data linking the C677T and A1298C MTHFR polymorphisms to gestational diabetes risk have been mixed and controversial. Therefore, we conducted this meta-analysis to derive a more precise estimation of the relationship between MTHFR polymorphisms and this pregnancy disorder. METHODS: A systematic literature search for original epidemiological studies was performed in the CNKI, WanFang, Cochrane Library, PubMed, and Web of Science databases. R language-based programs were employed for all statistical analyses. Odds ratios and corresponding 95% confidence intervals were calculated to estimate the effects of the variant allele on gestational diabetes risk. RESULTS: A summary of the estimates for the C677T polymorphism showed that the exposure cohorts were prone to gestational diabetes by a greater magnitude than the control groups. Further subgroup analysis by ethnicity showed that the Asians carrying the variant T allele were more susceptible to this pregnancy disorder. However, the pathogenic effect was not evident in the non-Asian subgroup. For the A1298C polymorphism, no statistical significance could be detected. CONCLUSION: This meta-analysis suggests that the T allele of the MTHFR gene C677T polymorphism tends to increase gestational diabetes susceptibility, especially for Asians. However, the A1298C polymorphism is not associated with an increased risk of this crippling pregnancy disorder.


Asunto(s)
Diabetes Gestacional , Alelos , Estudios de Casos y Controles , Diabetes Gestacional/epidemiología , Diabetes Gestacional/genética , Femenino , Predisposición Genética a la Enfermedad , Humanos , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Polimorfismo Genético , Polimorfismo de Nucleótido Simple , Embarazo , Prevalencia
19.
Eur Arch Otorhinolaryngol ; 279(3): 1341-1348, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34031750

RESUMEN

PURPOSE: To report our experience using endoscopic intranasal incision reduction (EIIR) for nasal fractures and to assess effectiveness of the method. METHODS: 30 patients who underwent EIIR were retrospectively analysed. All the patients were examined by three-dimensional computed tomography (3D CT), acoustic rhinometry and rhinomanometry, preoperatively and postoperatively at 1 month. The visual analogue scale (VAS) was used to assess the preoperative aesthetics and nasal airflow satisfaction and at 1, 3 and 6 months postoperatively. VAS aesthetic satisfaction was also scored by two junior doctors. RESULTS: 3D CT showed that the fracture fragments fitted well in 30 patients postoperatively at 1 month. VAS aesthetics and nasal airflow scores were significantly improved postoperatively at 1, 3 and 6 months compared with preoperative scores (P < 0.01). The VAS aesthetic scores from the two surgeons were also significantly improved (P < 0.01). The minimal cross-sectional area increased from 0.39 ± 0.13 to 0.64 ± 0.13 (P < 0.001), the nasal volume increased from 4.65 ± 0.86 to 6.37 ± 0.94 (P < 0.001) and the total inspiratory airway resistance of the bilateral nasal cavity median decreased from 0.467 Pa/mL/s to 0.193 Pa/mL/s (P < 0.001). There were no technique-related intraoperative complications. CONCLUSION: EIIR was a practical choice, and the aesthetics and nasal airflow were significantly improved in patients with overlapped and displaced bone fragments, patients with fractures of the frontal process of the maxilla (FFPM), patients who underwent failed CR and patients beyond the optimal temporal window.


Asunto(s)
Obstrucción Nasal , Rinometría Acústica , Endoscopía/métodos , Humanos , Cavidad Nasal/diagnóstico por imagen , Cavidad Nasal/cirugía , Obstrucción Nasal/etiología , Obstrucción Nasal/cirugía , Estudios Retrospectivos , Rinomanometría
20.
Appl Opt ; 60(13): 4034-4038, 2021 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-33983344

RESUMEN

According to the high-voltage and small-current characteristics for unbalanced current of high-voltage capacitors, a novel fiber optical filter unbalanced current transformer (FU-FOCT) is proposed, where an all-fiber temperature sensor based on the temperature birefringence effect of polarization-maintaining fiber is designed and integrated into an FU-FOCT for real-time temperature correction. The FU-FOCT prototype with a rated current of 1 A and a rated voltage of 258 kV is developed, and the accuracy, temperature, and frequency-response characteristics are tested. The results show that within the temperature range of ${-}{40}^\circ {\rm C} - 70^\circ {\rm C}$, the fluctuation range of the ratio error and phase error of the FU-FOCT at 1 A are ${-}{0.042}\% - 0.08\%$ and ${-}{0.16^\prime - 0.18^\prime}$, respectively, which meet the error limit requirements of class 0.2% specified in GB/T 20840.8-2007.

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