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1.
BMC Med ; 22(1): 395, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39285313

RESUMEN

BACKGROUND: Transcervical resection of adhesions (TCRA) is the standard treatment for intrauterine adhesion (IUA). Previous studies have shown that postoperative oral estrogen or an intrauterine physical barrier could reduce the recurrence of IUA by promoting the proliferation of the endometrium or inhibiting the reformation of adhesions. Our team designed an intrauterine stent that can release estrogen within the uterine cavity slowly. In this study, we aimed to investigate the efficacy and safety of the estrogen-releasing intrauterine system in preventing the recurrence of moderate to severe IUA. METHODS: This was a multicenter prospective randomized controlled 2-arm parallel trial that included patients who were diagnosed with moderate to severe IUA and who received TCRA. A total of 250 patients were randomly assigned, at a 1:1 ratio, to receive the intrauterine estrogen-releasing system or a Foley catheter balloon combined with oral estrogen therapy after surgery. The primary outcome was the rate of adhesion reduction in the two groups. The secondary outcomes included endometrial thickness at the ovulation period, menstrual improvement rates, and other reported adverse events during follow-up. RESULTS: The average daily drug release amount for all the tested stents was 0.21 mg/day. At 60 days postoperatively, the rate of adhesion reduction was significantly greater in the experimental group than in the control group (93.33% vs. 58.56%, p < 0.001). The endometrium of the experimental group was thicker than that of the control group (p < 0.001). Consistently, the rate of improvement in menstruation was greater in the experimental group than in the control group (p = 0.010). No grade 3-4 adverse events were found in the two groups during the 1-year follow-up. CONCLUSIONS: In the cohort of patients with moderate to severe IUA, the intrauterine estrogen-releasing system was more effective at reducing adhesion than traditional oral estrogen combined with an intrauterine Foley catheter after TCRA. This novel intrauterine system provides a new option for the management of IUA after surgery. TRIAL REGISTRATION: The registration number is NCT04972032. Date of registration: August 15, 2021.


Asunto(s)
Estrógenos , Humanos , Femenino , Adherencias Tisulares/prevención & control , Estrógenos/administración & dosificación , Adulto , Estudios Prospectivos , Enfermedades Uterinas/cirugía , Resultado del Tratamiento , Prevención Secundaria/métodos , Recurrencia , Complicaciones Posoperatorias/prevención & control
2.
J Biol Chem ; 300(10): 107813, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39322015

RESUMEN

The formin protein Diaph3 is an actin nucleator that regulates numerous cytoskeleton-dependent cellular processes through the activation of actin polymerization. Expression and activity of Diaph3 is tightly regulated: lack of Diaph3 results in developmental defects and embryonic lethality in mice, while overexpression of Diaph3 causes auditory neuropathy. It is known that Diaph3 homophilic interactions include the intramolecular interaction of its Dia-inhibitory domain (DID)-diaphanous autoregulatory domain (DAD) domains and the intermolecular interactions of DD-DD domains or FH2-FH2 domains. However, the physiological significance of these interactions in Diaph3 protein stability and activity is not fully understood. In this study, we show that FH2-FH2 interaction promotes Diaph3 activity, while DID-DAD and DD-DD interactions inhibit Diaph3 activity through distinct mechanisms. DID-DAD interaction is responsible for the autoinhibition of Diaph3 protein, which is disrupted by binding of Rho GTPases. Interestingly, we find that DID-DAD interaction stabilizes the expression of each DID or DAD domain against proteasomal-mediated degradation. Disruption of DID-DAD interaction by RhoA binding or M1041A mutation causes increased Diaph3 activity and accelerated degradation of the activated Diaph3 protein. Further, the activated Diaph3 is ubiquitinated at K1142/1143/1144 lysine residues by the E3 ligase Stub1. Expression of Stub1 is causally related to the stability and activity of Diaph3. Knockdown of Stub1 in mouse cochlea results in hair cell stereocilia defects, neuronal degeneration, and hearing loss, resembling the phenotypes of mice overexpressing Diaph3. Thus, our study reports a novel regulatory mechanism of Diaph3 protein expression and activity whereby the active but not inactive Diaph3 is readily degraded to prevent excessive actin polymerization.

3.
Inorg Chem ; 63(41): 19450-19457, 2024 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-39333885

RESUMEN

The reasonable design and modulation of the electronic properties of Pd metallene are acknowledged as a promising avenue for enhancing the oxygen reduction reaction (ORR) in anion exchange membrane fuel cells (AEMFCs), yet they remain a formidable challenge. Herein, a thin-sheet structure of Zr-doped Pd metallene (PdZr metallene) with abundant defects is proposed using a facile wet-chemical approach for efficient and highly durable ORR electrocatalysis. Multiple microstructural analyses uncover that orchestrated electronic and oxophilic regulation of PdZr metallene via Lewis-acidic Zr site modulation could concurrently optimize the electronic configuration of Pd, downshift the d-band center of Pd, and, thus, promote the intrinsic activity. Benefiting from the unique two-dimensional morphology and electronic structure optimization facilitated by the Zr coupling effect, the resultant PdZr metallene demonstrates significantly enhanced ORR electrocatalytic performance in basic solutions, with a high half-wave potential (E1/2) of 0.87 V and commendable stability for 30 000 s, surpassing those of Pd metallene and various advanced Pd-based catalysts reported in the literature. Encouragingly, the PdZr metallene-based AEMFC achieves an increased maximum power density (90.4 mW cm-2) and impressive robustness over 12 h in an alkaline environment, manifesting the practical application of PdZr metallene in AEMFCs. This study showcases the applicability of PdZr metallene via Lewis acid site regulation for fabricating highly active electrocatalysts for high-performance AEMFCs.

4.
Arch Gynecol Obstet ; 310(4): 1945-1950, 2024 10.
Artículo en Inglés | MEDLINE | ID: mdl-39103619

RESUMEN

PURPOSES: This study aims to assess the effectiveness and safety of cervical polypectomy performed via vaginoscopy in pregnant women. METHODS: Pregnant patients diagnosed with cervical polyps were retrospectively included in Beijing Tiantan Hospital between April 2017 and April 2023. Group A underwent cervical polypectomy using a vaginoscopy technique without speculum, cervical forceps and anesthesia, while Group B received conservative management. The incidence of spontaneous abortion, preterm birth, preterm rupture of membranes (PROM), visual analog scale (VAS) scores, timing and method of delivery, and neonatal outcomes were analyzed. RESULTS: Of 90 pregnant patients included in the study, 48 patients receiving polypectomy under vaginoscopy were included into group A while 42 patients receiving conservative treatment were assigned into group B. At baseline, group A exhibited higher rates of vaginal bleeding pre-operation, as well as larger cervical polyp dimensions compared to group B. The median interval between vaginal bleeding and polypectomy was 3.5 weeks, with the median procedure typically performed at gestational week 19 in group A. There was no significant difference in the incidence of spontaneous abortion between the two groups (4.2% vs. 4.8%, p = 1.000). However, group A showed a significantly lower frequency of preterm birth (4.2% vs. 21.4%, p = 0.030) and premature rupture of membranes (PROM) (18.8% vs. 45.2%, p = 0.025) compared to group B. No disparities were observed in the timing, mode of delivery, and neonatal outcomes between the two groups. CONCLUSIONS: The utilization of vaginoscopy for cervical polypectomy has been shown to decrease the likelihood of preterm delivery and premature rupture of membranes in pregnant women with symptomatic cervical polyps. Therefore, performing cervical polypectomy via vaginoscopy without anesthesia provide a feasible and optimal ways in the management of this population.


Asunto(s)
Rotura Prematura de Membranas Fetales , Pólipos , Humanos , Femenino , Embarazo , Adulto , Estudios Retrospectivos , Pólipos/cirugía , Rotura Prematura de Membranas Fetales/etiología , Nacimiento Prematuro/prevención & control , Nacimiento Prematuro/etiología , Nacimiento Prematuro/epidemiología , Cuello del Útero/cirugía , Aborto Espontáneo/epidemiología , Aborto Espontáneo/etiología , Enfermedades del Cuello del Útero/cirugía , Hemorragia Uterina/etiología , Resultado del Tratamiento , Colposcopía/métodos , Colposcopía/efectos adversos
5.
Hum Genomics ; 18(1): 73, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956677

RESUMEN

Knockout of GAS2 (growth arrest-specific protein 2), causes disorganization and destabilization of microtubule bundles in supporting cells of the cochlear duct, leading to hearing loss in vivo. However, the molecular mechanism through which GAS2 variant results in hearing loss remains unknown. By Whole-exome sequencing, we identified a novel heterozygous splicing variant in GAS2 (c.616-2 A > G) as the only candidate mutation segregating with late-onset and progressive nonsyndromic hearing loss (NSHL) in a large dominant family. This splicing mutation causes an intron retention and produces a C-terminal truncated protein (named GAS2mu). Mechanistically, the degradation of GAS2mu via the ubiquitin-proteasome pathway is enhanced, and cells expressing GAS2mu exhibit disorganized microtubule bundles. Additionally, GAS2mu further promotes apoptosis by increasing the Bcl-xS/Bcl-xL ratio instead of through the p53-dependent pathway as wild-type GAS2 does, indicating that GAS2mu acts as a toxic molecule to exacerbate apoptosis. Our findings demonstrate that this novel variant of GAS2 promotes its own protein degradation, microtubule disorganization and cellular apoptosis, leading to hearing loss in carriers. This study expands the spectrum of GAS2 variants and elucidates the underlying pathogenic mechanisms, providing a foundation for future investigations of new therapeutic strategies to prevent GAS2-associated progressive hearing loss.


Asunto(s)
Sordera , Linaje , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Apoptosis/genética , Sordera/genética , Sordera/patología , Pueblos del Este de Asia/genética , Secuenciación del Exoma , Genes Dominantes , Microtúbulos/genética , Microtúbulos/metabolismo , Mutación/genética
6.
Rev Med Virol ; 34(3): e2539, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38719789

RESUMEN

The viral infection of the central nervous system is a significant public health concern. So far, most clinical cases of viral neuroinvasion are dealt with supportive and/or symptomatic treatments due to the unavailability of specific treatments. Thus, developing specific therapies is required to alleviate neurological symptoms and disorders. In this review, we shed light on molecular aspects of viruses' entry into the brain which upon targeting with specific drugs have shown promising efficacy in vitro and in preclinical in vivo model systems. Further assessing the therapeutic potential of these drugs in clinical trials may offer opportunities to halt viral neuroinvasion in humans.


Asunto(s)
Antivirales , Humanos , Animales , Antivirales/uso terapéutico , Antivirales/farmacología , Internalización del Virus/efectos de los fármacos , Encéfalo/virología , Encéfalo/patología , Encéfalo/efectos de los fármacos , Enfermedades Virales del Sistema Nervioso Central/tratamiento farmacológico , Enfermedades Virales del Sistema Nervioso Central/virología
7.
Molecules ; 29(10)2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38792110

RESUMEN

Flavonoids, a class of phenolic compounds, are one of the main functional components and have a wide range of molecular structures and biological activities in Polygonatum. A few of them, including homoisoflavonoids, chalcones, isoflavones, and flavones, were identified in Polygonatum and displayed a wide range of powerful biological activities, such as anti-cancer, anti-viral, and blood sugar regulation. However, few studies have systematically been published on the flavonoid biosynthesis pathway in Polygonatum cyrtonema Hua. Therefore, in the present study, a combined transcriptome and metabolome analysis was performed on the leaf, stem, rhizome, and root tissues of P. cyrtonema to uncover the synthesis pathway of flavonoids and to identify key regulatory genes. Flavonoid-targeted metabolomics detected a total of 65 active substances from four different tissues, among which 49 substances were first study to identify in Polygonatum, and 38 substances were flavonoids. A total of 19 differentially accumulated metabolites (DAMs) (five flavonols, three flavones, two dihydrochalcones, two flavanones, one flavanol, five phenylpropanoids, and one coumarin) were finally screened by KEGG enrichment analysis. Transcriptome analysis indicated that a total of 222 unigenes encoding 28 enzymes were annotated into three flavonoid biosynthesis pathways, which were "phenylpropanoid biosynthesis", "flavonoid biosynthesis", and "flavone and flavonol biosynthesis". The combined analysis of the metabolome and transcriptome revealed that 37 differentially expressed genes (DEGs) encoding 11 enzymes (C4H, PAL, 4CL, CHS, CHI, F3H, DFR, LAR, ANR, FNS, FLS) and 19 DAMs were more likely to be regulated in the flavonoid biosynthesis pathway. The expression of 11 DEGs was validated by qRT-PCR, resulting in good agreement with the RNA-Seq. Our studies provide a theoretical basis for further elucidating the flavonoid biosynthesis pathway in Polygonatum.


Asunto(s)
Vías Biosintéticas , Flavonoides , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Metabolómica , Polygonatum , Transcriptoma , Flavonoides/biosíntesis , Flavonoides/metabolismo , Flavonoides/genética , Polygonatum/genética , Polygonatum/metabolismo , Polygonatum/química , Metabolómica/métodos , Vías Biosintéticas/genética , Perfilación de la Expresión Génica/métodos , Metaboloma
8.
J Virol ; 98(5): e0011624, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38591880

RESUMEN

Flaviviruses in the Japanese encephalitis virus (JEV) serogroup, such as JEV, West Nile virus, and St. Louis encephalitis virus, can cause severe neurological diseases. The nonstructural protein 1 (NS1) is a multifunctional protein of flavivirus that can be secreted by infected cells and circulate in the host bloodstream. NS1' is an additional form of NS1 protein with 52 amino acids extension at its carboxy-terminal and is produced exclusively by flaviviruses in the JEV serogroup. In this study, we demonstrated that the secreted form of both NS1 and NS1' can disrupt the blood-brain barrier (BBB) of mice, with NS1' exhibiting a stronger effect. Using the in vitro BBB model, we found that treatment of soluble recombinant JEV NS1 or NS1' protein increases the permeability of human brain microvascular endothelial cells (hBMECs) and leads to the degradation of tight junction proteins through the autophagy-lysosomal pathway. Consistently, NS1' protein exhibited a more pronounced effect compared to NS1 in these cellular processes. Further research revealed that the increased expression of macrophage migration inhibitory factor (MIF) is responsible for triggering autophagy after NS1 or NS1' treatment in hBMECs. In addition, TLR4 and NF-κB signaling was found to be involved in the activation of MIF transcription. Moreover, administering the MIF inhibitor has been shown to decrease viral loads and mitigate inflammation in the brains of mice infected with JEV. This research offers a novel perspective on the pathogenesis of JEV. In addition, the stronger effect of NS1' on disrupting the BBB compared to NS1 enhances our understanding of the mechanism by which flaviviruses in the JEV serogroup exhibit neurotropism.IMPORTANCEJapanese encephalitis (JE) is a significant viral encephalitis worldwide, caused by the JE virus (JEV). In some patients, the virus cannot be cleared in time, leading to the breach of the blood-brain barrier (BBB) and invasion of the central nervous system. This invasion may result in cognitive impairment, behavioral disturbances, and even death in both humans and animals. However, the mechanism by which JEV crosses the BBB remains unclear. Previous studies have shown that the flavivirus NS1 protein plays an important role in causing endothelial dysfunction. The NS1' protein is an elongated form of NS1 protein that is particularly produced by flaviviruses in the JEV serogroup. This study revealed that both the secreted NS1 and NS1' of JEV can disrupt the BBB by breaking down tight junction proteins through the autophagy-lysosomal pathway, and NS1' is found to have a stronger effect compared to NS1 in this process. In addition, JEV NS1 and NS1' can stimulate the expression of MIF, which triggers autophagy via the ERK signaling pathway, leading to damage to BBB. Our findings reveal a new function of JEV NS1 and NS1' in the disruption of BBB, thereby providing the potential therapeutic target for JE.


Asunto(s)
Autofagia , Barrera Hematoencefálica , Virus de la Encefalitis Japonesa (Especie) , Encefalitis Japonesa , Proteínas no Estructurales Virales , Animales , Humanos , Ratones , Barrera Hematoencefálica/virología , Barrera Hematoencefálica/metabolismo , Encéfalo/virología , Encéfalo/metabolismo , Virus de la Encefalitis Japonesa (Especie)/fisiología , Encefalitis Japonesa/virología , Encefalitis Japonesa/metabolismo , Células Endoteliales/virología , Células Endoteliales/metabolismo , Factores Inhibidores de la Migración de Macrófagos/metabolismo , FN-kappa B/metabolismo , Proteínas no Estructurales Virales/metabolismo
9.
Front Microbiol ; 15: 1347204, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38559348

RESUMEN

Introduction: With the increasing demand for health products derived from Polygonati rhizoma (PR), people begin to artificially plant Polygonatum cyrtonema Hua (P. cyrtonema) in the middle and lower reaches of the Yangtze River. To promote P. cyrtonema cultivation and increase farmers' income, efforts are needed to understand the ways to obtain high-quality PR under artificial cultivation conditions. Methods: Rhizomes of artificial planting P. cyrtonema and rhizosphere soils were collected across five regions in Zhejiang Province, China. Subsequently, the contents of the main active ingredients of P. cyrtonema and soil properties were analyzed, and both rhizosphere and endophytic bacteria of P. cyrtonema were detected by 16S rDNA sequencing. The relationship between the active ingredients and soil properties, and the dominant bacteria were investigated by correlation analysis. Results: The content of active ingredients of P. cyrtonema from the five regions varied significantly, especially polysaccharides and saponins. High-throughput sequencing demonstrated that Proteobacteria was the dominant bacterial phylum in all samples, and Burkholderia-Caballeronia-Paraburkholderia was the main endophytic bacterial genus in rhizome. In addition, the bacterial diversity and richness of rhizosphere soil samples were higher than those of rhizome samples. Soil physicochemical properties and enzyme activities were significantly different across regions, leading to notable variations in the community structures of rhizosphere and endophytic bacteria. Redundancy analysis (RDA) displayed that pH and urease (UE) were the major factors altering shifting rhizosphere bacteria community structure. Moreover, the composition and diversity of rhizome endophytic bacteria were principally affected by both soil physicochemical properties and soil enzyme activities. Soil properties and bacteria from rhizosphere soil and rhizome had a considerable impact on certain active ingredients in P. cyrtonema under artificial cultivation conditions after Pearson correlation analysis. Polysaccharides were significantly correlated with nutrient-rich soil and endophytic bacteria, such as Burkholderia-Caballeronia-Paraburkholderia, Pseudomonas, Ralstonia, and Bacillus. However, flavonoids were associated with nutrient-poor soil. Saponins were positively correlated with OM and available phosphorous (AP) and were significantly negatively affected by rhizosphere bacterial communities. Conclusion: The study demonstrated that bacterial microorganisms were involved in the accumulation of active ingredients of P. cyrtonema together with soil physicochemical properties and enzyme activities, which provided a theoretical basis for the scientific and effective artificial cultivation of high-quality P. cyrtonema.

10.
Quant Imaging Med Surg ; 14(4): 3075-3085, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38617141

RESUMEN

Background: Primary dysmenorrhea (PDM) is the most common problem in menstruating women. A number of functional magnetic resonance imaging (fMRI) study have revealed that the brain plays a crucial role in the pathophysiology of PDM. However, these results have been inconsistent, and there is a lack of a comprehensive fMRI study to clarify the onset and long-term effects of PDM. The aim of this study was thus to investigate the onset and long-term effects of PDM in a cohort of patients with PDM. Methods: This study employed a cross-sectional design with prospective data collection, in which 25 patients with PDM and 20 healthy controls (HCs) were recruited. The patients with PDM underwent fMRI scans both during the PDM during the pain phase (PDM-P) and nonpain phase (PDM-NP). The long-term effects of PDM on the brain was assessed by comparing PDM-NP findings with those of HCs, and the central mechanism of PDM was assessed by comparing the PDM-P findings with those of PDM-NP. To identify changes in brain function, the amplitude of low-frequency fluctuations and the regional homogeneity (ReHo) were measured. To assess changes in brain structure, voxel-based morphometry (VBM) was applied. The periaqueductal gray (PAG) was set as a region of for conducting seed-based whole-brain functional connectivity (FC) analysis. Subsequently, Pearson correlation analyses were employed to evaluate the associations between the abnormal brain region and the clinical information of the patients. Results: There were neither functional nor structural differences between patients in the PDM-NP and HCs. Compared with those in PDM-NP, those in PDM-P showed increased ReHo in the left dorsolateral prefrontal cortex (DLPFC) but decreased FC between PAG and right superior parietal gyrus, bilateral inferior parietal gyrus, right calcarine gyrus, left superior occipital gyrus, left precentral gyrus, right DLPFC, and left crus I of the cerebellar hemisphere. Conclusions: The results from this study suggest that the mechanism of central pain hypersensitivity of PDM may be related to the disorder of the FC between the PAG and descending pain modulation system, default mode network (DMN), and occipital lobe. These findings could help us better understand the pathophysiology of PDM from a neuroimaging perspective.

11.
Foods ; 13(6)2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38540805

RESUMEN

Polygonatum cyrtonema Hua, an edible resource and medical material, is mainly consumed as a food in China. However, few published studies have comprehensively assessed its nutritional components. In this study, the proximate, carbohydrate, and dietary fiber contents as well as the mineral, vitamin, and amino acid compositions of five sources of P. cyrtomena grown in Yuhang district, Hangzhou city, Zhejiang province, were investigated. The nutritional profile of the five germplasms was investigated using analytical chemistry methods. All germplasms had a low starch content and contained greater amounts of carbohydrates (23.25-34.29%), protein (2.96-5.40%), Ca (195.08-282.08 mg/100 g), Fe (29.68-59.37 mg/100 g), and vitamin C (60.49-149.86 mg/100 g) in comparison to ginger, yam, and potatoes. The polysaccharide content ranged from 16.92% to 28.48%, representing the main source of carbohydrates. Fructose, a desirable sweetener, was the most abundant monosaccharide, representing 1.06% to 4.88% of the content. P. cyrtonema was found to be high in dietary fiber, with pectin and resistant starch being the major soluble components and hemicellulose being the dominant insoluble dietary fiber. A correlation analysis (CA) revealed significant correlations for the carbohydrate components and dietary fiber fractions with other nutrients. A principal component analysis (PCA) identified significant differences between the nutritional characteristics of the five germplasms, with Huanggang having the highest comprehensive quality scores. Moreover, ten nutrient components were selected as potential indicators that could be used to further evaluate the nutritional quality of P. cyrtomena. Our results demonstrate the rich nutrient composition and characteristics of P. cyrtonema and provide a valuable reference for the future development and utilization of Polygonatum.

12.
Int J Neural Syst ; 34(6): 2450023, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38490956

RESUMEN

Spiking neural membrane systems (SN P systems) are a class of bio-inspired models inspired by the activities and connectivity of neurons. Extensive studies have been made on SN P systems with synchronization-based communication, while further efforts are needed for the systems with rhythm-based communication. In this work, we design an asynchronous SN P system with resonant connections where all the enabled neurons in the same group connected by resonant connections should instantly produce spikes with the same rhythm. In the designed system, each of the three modules implements one type of the three operations associated with the edge detection of digital images, and they collaborate each other through the resonant connections. An algorithm called EDSNP for edge detection is proposed to simulate the working of the designed asynchronous SN P system. A quantitative analysis of EDSNP and the related methods for edge detection had been conducted to evaluate the performance of EDSNP. The performance of the EDSNP in processing the testing images is superior to the compared methods, based on the quantitative metrics of accuracy, error rate, mean square error, peak signal-to-noise ratio and true positive rate. The results indicate the potential of the temporal firing and the proper neuronal connections in the SN P system to achieve good performance in edge detection.


Asunto(s)
Potenciales de Acción , Algoritmos , Modelos Neurológicos , Neuronas , Neuronas/fisiología , Potenciales de Acción/fisiología , Redes Neurales de la Computación , Humanos , Relación Señal-Ruido
13.
J Vis Exp ; (204)2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38372363

RESUMEN

DNA double-strand breaks (DSBs) represent the most perilous DNA lesions, capable of inducing substantial genetic information loss and cellular demise. In response, cells employ two primary mechanisms for DSB repair: nonhomologous end joining (NHEJ) and homologous recombination (HR). Quantifying the efficiency of NHEJ and HR separately is crucial for exploring the relevant mechanisms and factors associated with each. The NHEJ assay and HR assay are established methods used to measure the efficiency of their respective repair pathways. These methods rely on meticulously designed plasmids containing a disrupted green fluorescent protein (GFP) gene with recognition sites for endonuclease I-SceI, which induces DSBs. Here, we describe the extrachromosomal NHEJ assay and HR assay, which involve co-transfecting HEK-293T cells with EJ5-GFP/DR-GFP plasmids, an I-SceI expressing plasmid, and an mCherry expressing plasmid. Quantitative results of NHEJ and HR efficiency are obtained by calculating the ratio of GFP-positive cells to mCherry-positive cells, as counted by flow cytometry. In contrast to chromosomally integrated assays, these extrachromosomal assays are more suitable for conducting comparative investigations involving multiple established stable cell lines.


Asunto(s)
Roturas del ADN de Doble Cadena , Reparación del ADN , Humanos , Proteínas Fluorescentes Verdes/genética , Células HEK293 , Recombinación Homóloga , Reparación del ADN por Unión de Extremidades
14.
CNS Neurosci Ther ; 30(2): e14585, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38421133

RESUMEN

INTRODUCTION: Serum response factor (SRF) is important in muscle development, tissue repair, and neuronal regulation. OBJECTIVES: This research aims to thoroughly examine the effects of SRF on spinal cord injury (SCI) and its ability to significantly impact the recovery and regeneration of neuronal axons. METHODS: The researchers created rat models of SCI and scratch injury to primary spinal cord neurons to observe the expression of relevant factors after neuronal injury. RESULTS: We found that the SRF, Ras, Raf, and cofilin levels increased after injury and gradually returned to normal levels. Afterward, researchers gave rats with SCI an SRF inhibitor (CCG1423) and studied the effects with nuclear magnetic resonance and transmission electron microscopy. The SRF inhibitor rodents had worse spinal cord recovery and axon regrowth than the control group. And the apoptosis of primary neurons after scratch injury was significantly higher in the SRF inhibitor group. Additionally, the researchers utilized lentiviral transfection to modify the SRF expression in neurons. SRF overexpression increased neuron migration while silencing SRF decreased it. Finally, Western blotting and RT-PCR were conducted to examine the expression changes of related factors upon altering SRF expression. The results revealed SRF overexpression increased Ras, Raf, and cofilin expression. Silencing SRF decreased Ras, Raf, and Cofilin expression. CONCLUSION: Based on our research, the SRF promotes axonal regeneration by activating the "Ras-Raf-Cofilin" signaling pathway.


Asunto(s)
Factores Despolimerizantes de la Actina , Traumatismos de la Médula Espinal , Ratas , Animales , Factores Despolimerizantes de la Actina/metabolismo , Factores Despolimerizantes de la Actina/farmacología , Factor de Respuesta Sérica/genética , Factor de Respuesta Sérica/metabolismo , Factor de Respuesta Sérica/farmacología , Traumatismos de la Médula Espinal/patología , Neuronas/metabolismo , Axones , Médula Espinal/metabolismo , Transducción de Señal , Regeneración Nerviosa , Recuperación de la Función/fisiología
15.
Inorg Chem ; 63(4): 2138-2147, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38237037

RESUMEN

Expediting the torpid kinetics of the oxygen reduction reaction (ORR) at the cathode with minimal amounts of Pt under acidic conditions plays a significant role in the development of proton exchange membrane fuel cells (PEMFCs). Herein, a novel Pt-N-C system consisting of Pt single atoms and nanoparticles anchored onto the defective carbon nanofibers is proposed as a highly active ORR catalyst (denoted as Pt-N-C). Detailed characterizations together with theoretical simulations illustrate that the strong coupling effect between different Pt sites can enrich the electron density of Pt sites, modify the d-band electronic environments, and optimize the oxygen intermediate adsorption energies, ultimately leading to significantly enhanced ORR performance. Specifically, the as-designed Pt-N-C demonstrates exceptional ORR properties with a high half-wave potential of 0.84 V. Moreover, the mass activity of Pt-N-C reaches 193.8 mA gPt-1 at 0.9 V versus RHE, which is 8-fold greater than that of Pt/C, highlighting the enormously improved electrochemical properties. More impressively, when integrated into a membrane electrode assembly as cathode in an air-fed PEMFC, Pt-N-C achieved a higher maximum power density (655.1 mW cm-2) as compared to Pt/C-based batteries (376.25 mW cm-2), hinting at the practical application of Pt-N-C in PEMFCs.

16.
Int Wound J ; 21(1): e14350, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37606302

RESUMEN

The present systematic review and meta-analysis aimed to determine the prevalence of surgical site infection (SSI) and related factors in patients after foot and ankle surgery. A comprehensive, systematic search was conducted in different international electronic databases, such as Scopus, PubMed, Web of Science and Persian electronic databases such as Iranmedex and Scientific Information Database (SID) using keywords extracted from Medical Subject Headings such as 'Prevalence', 'Surgical wound infection', 'Surgical site infection' and 'Orthopaedics' from the earliest to 1 June 2023. The appraisal tool for cross-sectional studies (AXIS tool) evaluates the quality of the included studies. A total of 10 447 patients undergoing foot and ankle surgery participated in nine studies. The pooled prevalence of SSI in patients who underwent foot and ankle surgery was reported in nine studies was 4.2% (95% CI: 2.4%-7.2%; I2 = 96.793%; p < 0.001). The odds ratio of SSI prevalence in men was higher than that of women and was significant (OR: 1.335; 95% CI: 1.106-1.612; Z = 3.009; p = 0.003). The pooled prevalence of SSI in patients with hindfoot fracture sites reported in five studies was 4.9% (95% CI: 2.6%-8.9%; I2 = 90.768%; p < 0.001). The pooled prevalence of SSI in patients with diabetes mellitus (DM) reported in six studies was 9.1% (95% CI: 5.6%-14.6%; I2 = 73.957%; p = 0.002). The pooled prevalence of SSI in patients with hypertension (HTN) reported in five studies was 5.5% (95% CI: 2.5%-11.6%; I2 = 91.346%; p < 0.001). The pooled prevalence of SSI in patients with tobacco use reported in eight studies was 6.6% (95% CI: 4.1%-10.4%; I2 = 85.379%; p < 0.001). In general, the existing differences in the prevalence of SSI after foot and ankle surgery in different studies can be based on different risk factors such as comorbidities and gender. Therefore, it is suggested to design appropriate interventions to reduce SSI in these patients.


Asunto(s)
Tobillo , Infección de la Herida Quirúrgica , Masculino , Humanos , Femenino , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Tobillo/cirugía , Prevalencia , Estudios Transversales , Factores de Riesgo
17.
DNA Repair (Amst) ; 133: 103603, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38029687

RESUMEN

Cytoplasmic FAM21 works as a guiding protein in Wiskott-Aldrich Syndrome Protein and SCAR Homolog (WASH) complex by linking WASH complex to endosomes through its interaction with retromer. Recently, we have reported that nuclear WASH localizes to DNA double strand break (DSB) sites to promote DNA repair through non-homologous end-joining (NHEJ). However, whether FAM21, the close partner of WASH, is involved in the nuclear WASH localization and DNA repair remains to be clarified. Here, we show that FAM21 interacts with Ku and the interaction between C-terminal FAM21 and Ku is essential for its recruitment to DSB sites. Moreover, FAM21 depletion led to decreases in WASH recruitment to damaged DNA and repair capacity upon DNA damage. Taken together, these results reveal that FAM21 promotes DNA repair by orchestrating the recruitment of WASH to DSB sites, providing a mechanistic insight into WASH-dependent DNA DSB repair.


Asunto(s)
Reparación del ADN , Proteínas , Reparación del ADN por Unión de Extremidades , Daño del ADN , ADN , Autoantígeno Ku
18.
Neurol Sci ; 45(1): 1-9, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38049550

RESUMEN

BACKGROUND: Evidence indicates that the SARS-CoV-2 virus can infect the brain, resulting in central nervous system symptoms. However, there is a lack of a longitudinal imaging study investigating the impact of Coronavirus disease 2019 (COVID-19) infection on brain function. Consequently, this study aimed to fill this knowledge gap using functional magnetic resonance imaging (fMRI). METHODS: Twenty-one participants underwent two resting-state fMRI scans before and after infection. The amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) were assessed to identify the brain function changes. Additionally, voxel-based morphometry (VBM) was utilized to assess changes in brain structure. Subsequently, brain regions that showed significant differences were identified as regions of interest (ROI) in functional connectivity analysis (FC). RESULTS: After infection, ALFF was increased in the bilateral paracentral lobe and postcentral gyrus while decreased in the bilateral precuneus. Moreover, ReHo was decreased in the cerebellar vermis, accompanied by a decrease in FC with the bilateral postcentral gyrus. Furthermore, gray matter volume (GMV) reduction was observed in the left thalamus. The results of the correlation analysis revealed a negative correlation between ALFF values in the bilateral precuneus and scores on the self-rating anxiety scale (SAS) in pre- and post-infection datasets. CONCLUSION: Neuroimaging alterations may occur before the manifestation of clinical symptoms, indicating that the functioning of the motor and sensory systems, as well as their connection, might be affected following infection. This alteration can potentially increase the potential of maladaptive responses to environmental stimuli. Furthermore, patients may be susceptible to future emotional disorders.


Asunto(s)
Mapeo Encefálico , COVID-19 , Humanos , Mapeo Encefálico/métodos , Estudios Longitudinales , COVID-19/patología , SARS-CoV-2 , Encéfalo , Imagen por Resonancia Magnética/métodos
19.
Artículo en Inglés | MEDLINE | ID: mdl-38064732

RESUMEN

Electrical impedance tomography (EIT) is a widely used functional imaging technology in the field of biomedical engineering with the characteristics of non-radiation, high temporal resolution, real-time, miniaturization, and low cost, but with relatively poor spatial resolution, which makes it become an effective complementary imaging alternative in conjunction with structural imaging technologies such as MRI and CT for bedside monitoring. The hardware systems and circuits (HSC) are the physical basis for EIT, and have major impacts on imaging speed, accuracy, cost and other key performance specifications. This review attempts to provide researchers with a relatively comprehensive picture of HSC for different EIT systems, which is organized as follows. Firstly, the general EIT hardware systems are classified as serial, fully parallel and semi-parallel types, respectively, according to their hardware architecture. Secondly, the main analogy front-end circuits of EIT hardware systems are summarized, in which the current drive circuits are divided into open loop, linear closed-loop and nonlinear closed-loop based on different feedback types. Thirdly, the common error sources and evaluation indicators on EIT measurements are summarized. Finally, the future development trends and research challenges of EIT are discussed. This review is expected to promote the development of EIT technology, especially on the design of HSC.

20.
Nurse Educ Pract ; 73: 103796, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37866273

RESUMEN

AIMS: To explore the relationship among a growth mindset, well-being and learning engagement of nursing students and the mediating effect of well-being. BACKGROUND: Reduced well-being and learning burnout are common among nursing students. From the perspective of positive psychology, a positive education can help students obtain well-being, improve their academic performance and be actively involved in learning. The core of positive education is a growth mindset. However, few studies have explored the causal relationship among a growth mindset, learning engagement and well-being. DESIGN: Correlational design based on cross-sectional data from a multicenter survey study. METHODS: A web-based survey was completed by 1065 nursing students from 5 schools in China between August 2022 and December 2022. The Growth Mindset Scale, the PERMA profiler and the Learning Engagement Scale were used to investigate the effect of a growth mindset on learning engagement and the mediating effect of well-being. RESULTS: Both a growth mindset (r = 0.272, p < 0.01) and well-being (r = 0.693, p < 0.01) were positively correlated with learning engagement, and a growth mindset (r = 0.363, p < 0.01) was positively correlated with well-being. Well-being completely mediated the relationship between a growth mindset and learning engagement. CONCLUSIONS: The growth mindset and well-being of nursing students are related to learning engagement. Therefore, schools can change students' thinking mode by carrying out positive education to enable students to acquire the ability to maintain their well-being and to improve their well-being and learning engagement.


Asunto(s)
Estudiantes de Enfermería , Humanos , Estudiantes de Enfermería/psicología , Estudios Transversales , Análisis de Clases Latentes , Aprendizaje , Instituciones Académicas
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