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1.
Front Endocrinol (Lausanne) ; 15: 1301213, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38742199

RESUMO

Purpose: To investigate the relationship between bone turnover markers (BTMs) and thyroid indicators in Graves' disease (GD) and to further assess predictive value of changes in early stage retrospectively. Methods: We studied 435 patients with GD and 113 healthy physical examiners retrospectively and followed up these two groups of patients after 6 months. We investigated the correlations between BTMs and other 15 observed factors, and analyzed the predictive value of FT3 and FT4 before and after treatment (FT3-P/FT3-A, FT4-P/FT4-A) on whether BTMs recovered. Results: The levels of thyroid hormones and BTMs in GD group were significantly higher than those in control group (P < 0.05) and decreased after 6 months of treatment. FT3, W, Ca and ALP were independent factors in predicting the elevation of OST. Duration of disease, FT3, TSH and ALP were independent factors in predicting the elevation of P1NP. Age, duration of disease, TRAb and ALP were independent factors in predicting the elevation of CTX-1. The AUC of FT3-P/FT3-A and FT4-P/FT4-A for predicting OST recovery were 0.748 and 0.705 (P < 0.05), respectively, and the cut-off values were 0.51 and 0.595. There was no predictive value for P1NP and CTX-1 recovery (P > 0.05). Conclusion: BTMs were abnormally elevated in GD and were significantly correlated with serum levels of FT3, FT4, TRAb, Ca, and ALP. FT3 decreased more than 51% and FT4 dropped more than 59.5% after 6 months of treatment were independent predictors for the recovery of BTMs in GD.


Assuntos
Biomarcadores , Remodelação Óssea , Doença de Graves , Valor Preditivo dos Testes , Humanos , Masculino , Feminino , Doença de Graves/sangue , Doença de Graves/tratamento farmacológico , Doença de Graves/metabolismo , Adulto , Biomarcadores/sangue , Estudos Retrospectivos , Pessoa de Meia-Idade , Glândula Tireoide/metabolismo , Osso e Ossos/metabolismo , Hormônios Tireóideos/sangue , Estudos de Casos e Controles , Prognóstico , Antitireóideos/uso terapêutico , Tiroxina/sangue , Tri-Iodotironina/sangue , Seguimentos
2.
Artigo em Inglês | MEDLINE | ID: mdl-38695117

RESUMO

Aqueous zinc-ion batteries (ZIBs) are regarded as a type of promising energy-storage device because of their high safety and low cost, and polyaniline (PANI) is normally employed as a cathode material for ZIBs owing to its unique electrochemical properties and high environmental stability. However, a low specific capacity and a short cycle life limit the development and applications of PANI-based electrodes. Herein, we have developed a novel type of highly stable PANI-based cathode material enabled by phosphene (PR) for aqueous Zn-PANI batteries through in situ chemical oxidative polymerization. The introduction of PR nanoflakes not only inhibits the degradation of PANI and generates more active sites for Zn2+ storage but also enables a synergistic effect of the Zn2+ insertion/extraction and P-Zn alloying reaction. This promotes a high reversible specific capacity of 240.2 mAh g-1 at 0.2 A g-1 and excellent rate performance for the PR/PANI nanocomposite cathode material. Compared to the pristine PANI cathode material, the PR/PANI nanocomposite cathode material is more suitable for the Zn-PANI battery, thanks to its higher specific capacity and better cycle stability. This study provides an innovative approach for developing the next generation of reliable PR-based electrode materials for aqueous energy-storage devices.

3.
Mol Cell ; 84(9): 1684-1698.e9, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38593805

RESUMO

The Bloom syndrome (BLM) helicase is critical for alternative lengthening of telomeres (ALT), a homology-directed repair (HDR)-mediated telomere maintenance mechanism that is prevalent in cancers of mesenchymal origin. The DNA substrates that BLM engages to direct telomere recombination during ALT remain unknown. Here, we determine that BLM helicase acts on lagging strand telomere intermediates that occur specifically in ALT-positive cells to assemble a replication-associated DNA damage response. Loss of ATRX was permissive for BLM localization to ALT telomeres in S and G2, commensurate with the appearance of telomere C-strand-specific single-stranded DNA (ssDNA). DNA2 nuclease deficiency increased 5'-flap formation in a BLM-dependent manner, while telomere C-strand, but not G-strand, nicks promoted ALT. These findings define the seminal events in the ALT DNA damage response, linking aberrant telomeric lagging strand DNA replication with a BLM-directed HDR mechanism that sustains telomere length in a subset of human cancers.


Assuntos
Dano ao DNA , Replicação do DNA , RecQ Helicases , Homeostase do Telômero , Telômero , RecQ Helicases/metabolismo , RecQ Helicases/genética , Humanos , Telômero/metabolismo , Telômero/genética , DNA de Cadeia Simples/metabolismo , DNA de Cadeia Simples/genética , Proteína Nuclear Ligada ao X/genética , Proteína Nuclear Ligada ao X/metabolismo , DNA Helicases/metabolismo , DNA Helicases/genética , Síndrome de Bloom/genética , Síndrome de Bloom/metabolismo , Síndrome de Bloom/enzimologia , Síndrome de Bloom/patologia , Linhagem Celular Tumoral
4.
Langmuir ; 40(19): 9892-9910, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38685830

RESUMO

Nowadays, high-phase-inversion in situ emulsification technology has shown great potential in enhancing oil recovery from high-water-cut thin-oil reservoirs. However, emulsification characteristics, interfacial properties, and the mechanism of high phase inversion have not been systematically described. In this study, an emulsification experiment was conducted to investigate the effects of shear time, shear rate, and temperature on the phase inversion of thin oil. Furthermore, the influence of resin and wax on the dispersion of asphaltene was studied through microscopic morphology analysis. Interfacial tension measurement and interfacial viscoelasticity analysis were carried out to determine the interaction characteristics of asphaltene, resin, and wax at the interface. The results showed that, at 50 °C, the phase-inversion point of thin oil reached as high as 75%, and even at 60 °C, it remained at 70%. The shear time and shear rate did not affect the phase-inversion point of thin oil, while an increase in temperature led to a decrease in the phase-inversion point. Moreover, compared to the 20% phase-inversion point of base oil, the phase-inversion point increased with different proportions of asphaltene, resin, and wax. Particularly, at the ratio of asphaltene/resin/wax = 1:5:9, the phase-inversion point reached as high as 80%, indicating the optimal state. In this proportion, asphaltene aggregates exhibited the smallest and most uniform size, best dispersion, lower interfacial tension, and higher interfacial modulus. These findings provide reference and guidance for further enhancing oil recovery in medium-to-high-water-cut thin-oil reservoirs.

5.
BMC Cancer ; 24(1): 445, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600469

RESUMO

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9), the last member of the proprotein convertase family, functions as a classic regulator of low-density lipoprotein (LDL) by interacting with low-density lipoprotein receptor (LDLR). Recent studies have shown that PCSK9 can affect the occurrence and development of tumors and can be used as a novel therapeutic target. However, a comprehensive pan-cancer analysis of PCSK9 has yet to be conducted. METHODS: The potential oncogenic effects of PCSK9 in 33 types of tumors were explored based on the datasets of The Cancer Genome Atlas (TCGA) dataset. In addition, the immune regulatory role of PCSK9 inhibition was evaluated via in vitro cell coculture and the tumor-bearing mouse model. Finally, the antitumor efficacy of targeted PCSK9 combined with OVA-II vaccines was verified. RESULTS: Our results indicated that PCSK9 was highly expressed in most tumor types and was significantly correlated with late disease stage and poor prognosis. Additionally, PCSK9 may regulate the tumor immune matrix score, immune cell infiltration, immune checkpoint expression, and major histocompatibility complex expression. Notably, we first found that dendritic cell (DC) infiltration and major histocompatibility complex-II (MHC-II) expression could be upregulated by PCSK9 inhibition and improve CD8+ T cell activation in the tumor immune microenvironment, thereby achieving potent tumor control. Combining PCSK9 inhibitors could enhance the efficacies of OVA-II tumor vaccine monotherapy. CONCLUSIONS: Conclusively, our pan-cancer analysis provided a more comprehensive understanding of the oncogenic and immunoregulatory roles of PCSK9 and demonstrated that targeting PCSK9 could increase the efficacy of long peptide vaccines by upregulating DC infiltration and MHC-II expression on the surface of tumor cells. This study reveals the critical oncogenic and immunoregulatory roles of PCSK9 in various tumors and shows the promise of PCSK9 as a potent immunotherapy target.


Assuntos
Genes MHC da Classe II , Imunoterapia , Neoplasias , Pró-Proteína Convertase 9 , Pró-Proteína Convertases , Animais , Camundongos , Antígenos de Histocompatibilidade , Lipoproteínas LDL , Neoplasias/genética , Neoplasias/terapia , Pró-Proteína Convertase 9/metabolismo , Pró-Proteína Convertases/antagonistas & inibidores , Receptores de LDL/genética , Microambiente Tumoral
6.
Expert Opin Drug Saf ; : 1-8, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38602862

RESUMO

BACKGROUND: Lanthanum carbonate is widely used to manage serum phosphate and calcium levels in end-stage kidney disease (ESKD) patients, yet comprehensive long-term safety data are lacking. This study leverages the FDA Adverse Event Reporting System (FAERS) to assess the extended safety profile of lanthanum carbonate. RESEARCH DESIGN AND METHODS: We analyzed FAERS data (2004-2022) to study the association between lanthanum carbonate and adverse events (AEs). Using MedDRA v25.0, we identified risk signals through System Organ Classes (SOCs) and Preferred Terms (PTs). Disproportionality analyzes quantified lanthanum carbonate-associated AE signals. RESULTS: Among 3,284 reports, 2,466 were primary suspected AEs linked to lanthanum carbonate. Males reported AEs more frequently than females. Patients aged over 64 represented the majority. Median onset time for lanthanum carbonate-related AEs was 146 days. Gastrointestinal disorders were prevalent. We identified 16 new signals, including stress, abnormal hepatic function, cholelithiasis, bile duct stone, gastric cancer, and adenocarcinoma gastric. Stress was notable, particularly in male patients over 65 and those with lower weight. CONCLUSIONS: This study affirms lanthanum carbonate's long-term safety for reducing elevated blood phosphorus levels. While gastrointestinal disorders were common, attention must focus on emerging AEs, particularly stress, especially in elderly patients.

7.
J Chem Phys ; 160(13)2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38557844

RESUMO

The moisture with salt ions adsorbed on the mineral soil surface is crucial to the cohesion process when the media is exposed to marine or coastal environments. However, the impact of salinity on the cohesion of soils is not well studied at the nanoscale. In this study, the salinity effect was investigated by studying the wettability and capillary force of NaCl solutions on quartz substrates via a molecular dynamics-based approach. Besides, a new visualization method was proposed to measure the contact angle of liquid droplets from the aspect of nanoscale. The results indicated that salt ions can weaken the wettability of the liquid on the quartz surface and inhibit the capillary force. Compared with water, the liquid with a 10% NaCl solution can achieve a capillary force reduction of around 70%, resulting in a detrimental effect on the cohesion of soils. Overall, this study enhanced the understanding of the nanoscale salinity effect on the cohesion process and provided insights into the modification of the mechanical properties of soils from the aspect of nanoscale.

8.
Exp Ther Med ; 27(5): 221, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38590563

RESUMO

Ischemic cardiomyopathy (ICM) is a serious cardiac disease with a very high mortality rate worldwide, which causes myocardial ischemia and hypoxia as the main damage. Further understanding of the underlying pathological processes of cardiomyocyte injury is key to the development of cardioprotective strategies. Ferroptosis is an iron-dependent form of regulated cell death characterized by the accumulation of lipid hydroperoxides to lethal levels, resulting in oxidative damage to the cell membrane. The current understanding of the role and regulation of ferroptosis in ICM is still limited, especially in the absence of evidence from large-scale transcriptomic data. Through comprehensive bioinformatics analysis of human ICM transcriptome data obtained from the Gene Expression Omnibus database, the present study identified differentially expressed ferroptosis-related genes (DEFRGs) in ICM. Subsequently, their potential biological mechanisms and cross-talk were analyzed, and hub genes were identified by constructing protein-protein interaction networks. Ferroptosis features such as reactive oxygen species generation, changes in ferroptosis marker proteins, iron ion aggregation and lipid oxidation, were identified in the H9c2 anoxic reoxygenation injury model. Finally, the diagnostic ability of Gap junction alpha-1 (GJA1), Solute carrier family 40 member 1 (SLC40A1), Alpha-synuclein (SNCA) were identified through receiver operating characteristic curves and the expression of DEFRGs was verified in an in vitro model. Furthermore, potential drugs (retinoic acid) that could regulate ICM ferroptosis were predicted based on key DEFRGs. The present article presents new insights into the role of ferroptosis in ICM, investigating the regulatory role of ferroptosis in the pathological process of ICM and advocating for ferroptosis as a potential novel therapeutic target for ICM based on evidence from the ICM transcriptome.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38607748

RESUMO

BACKGROUND: The effect of anti-osteoporosis treatment in elderly patients with osteoporosis and lumbar discectomy and fusion (LIF) for lumbar degenerative diseases is not well known. OBJECTIVE: This study aimed to evaluate the effect of perioperative anti-osteoporosis treatment in the patients with osteoporosis and LIF. METHODS: From January to December 2022, patients were divided into three groups according to the inclusive criteria: the normal group (Group A), the osteopenia group (Group B) and the osteoporosis group (Group C). Quantitative computed tomography (QCT), height of the intervertebral space (HIS), segmental sagittal angle (SSA), visual analogue scale (VAS) score and Oswestry Disability Index (ODI) were compared between the groups at the follow-up time. The serum Ca2 + , osteocalcin (OC), propeptide of type I procollagen (PINP) C-terminal cross-linking telopeptide of type I collagen (ß-CTX) and 25-OH vitamin D (25-OH VD) levels were compared between the groups at the time of follow-up. Interbody fusion was graded on the X-ray and CT images at the follow-up time. RESULTS: There were 165 patients in this study. There were significant differences in the mean age, mean score, HIS and SSA between the groups at the different follow-up times. There were significant differences in the concentrations of serum Ca2 + , OC, ß-CTX, 25-OH VD and PINP at the sixth month after surgery between the groups. There were significant differences in the concentrations of serum Ca2 + , ß-CTX and 25-OH VD between the pre-surgery and at six months after surgery in Group B and ß-CTX and 25-OH VD in Group C. There was a significant difference in the degree of fusion between Group B and C (χ2= 5.6243, P< 0.05). CONCLUSION: In elderly patients with LIF and osteoporosis, anti-osteoporosis therapy could reduce bone resorption and thus facilitate fusion. Anti-osteoporosis medication tends to enhance radiological, functional, and fusion short-term outcomes.

10.
Talanta ; 274: 126004, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38564824

RESUMO

Reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive sulfur species (RSS) serve as vital mediators essential for preserving intracellular redox homeostasis within the human body, thereby possessing significant implications across physiological and pathological domains. Nevertheless, deviations from normal levels of ROS, RNS, and RSS disturb redox homeostasis, leading to detrimental consequences that compromise bodily integrity. This disruption is closely linked to the onset of various human diseases, thereby posing a substantial threat to human health and survival. Small-molecule fluorescent probes exhibit considerable potential as analytical instruments for the monitoring of ROS, RNS, and RSS due to their exceptional sensitivity and selectivity, operational simplicity, non-invasiveness, localization capabilities, and ability to facilitate in situ optical signal generation for real-time dynamic analyte monitoring. Due to their distinctive transition from their spirocyclic form (non-fluorescent) to their ring-opened form (fluorescent), along with their exceptional light stability, broad wavelength range, high fluorescence quantum yield, and high extinction coefficient, rhodamine fluorophores have been extensively employed in the development of fluorescent probes. This review primarily concentrates on the investigation of fluorescent probes utilizing rhodamine dyes for ROS, RNS, and RSS detection from the perspective of different response groups since 2016. The scope of this review encompasses the design of probe structures, elucidation of response mechanisms, and exploration of biological applications.


Assuntos
Corantes Fluorescentes , Espécies Reativas de Nitrogênio , Espécies Reativas de Oxigênio , Rodaminas , Corantes Fluorescentes/química , Rodaminas/química , Espécies Reativas de Nitrogênio/análise , Humanos , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/análise , Imagem Óptica , Animais , Enxofre/química , Enxofre/análise
11.
Micromachines (Basel) ; 15(3)2024 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-38542651

RESUMO

As a core component of power conversion systems, insulated gate bipolar transistor (IGBT) modules continually suffer from severe thermal damage caused by temperature swings and shear stress, resulting in fatigue failure. Bond wires falling off is one of the failure modes of IGBT modules. Given that the number of fallen-off bond wires is a significant parameter to evaluate the health status of the IGBT modules, this paper proposes an online identification model to recognize the number of fallen-off bond wires during normal operation. Firstly, a database containing datum Vce,on-Tj-IC (collector-emitter on-state voltage Vce,on, chip junction temperature Tj, collector current IC) planes with different fallen-off bond wires is built based on an offline aging test. Secondly, a Foster network model and a special circuit are designed to measure the junction temperature Tj and the collector-emitter on-state voltage Vce,on, respectively. Thirdly, the feature points of the IGBT module represented by Vce,on, Tj, and IC are given to the database to recognize the number of fallen-off bond wires according to the position of the feature points in the datum plane. The experimental results show that the proposed method can determine the fallen-off bond wires under the operation condition.

12.
Heart Vessels ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38502317

RESUMO

BACKGROUND: The prognostic nutritional index (PNI) and serum chloride level are related to adverse outcomes in patients with heart failure. However, little is known about the relationship between the PNI and serum chloride level in predicting the poor prognosis of patients with acute decompensated heart failure (ADHF). METHODS AND RESULTS: We reviewed 1221 consecutive patients with ADHF admitted to the First Affiliated Hospital of Kunming Medical University from January 2017 to October 2021. After excluding patients with in hospital death, missing follow-up data, missing chloride data, missing lymphocyte (LYM) count data, or missing serum albumin data, 805 patients were included. PNI was calculated using the formula: serum albumin (ALB) (g/L) + 5 × LYM count (10^9/L). Patients were divided into 4 groups according to the quartiles of the PNI, and the highest PNI quartile (PNI Q4: PNI ≥ 47.3) was set as the reference group. The patients in the lowest PNI quartile (PNI Q1: PNI < 40.8) had the lowest cumulative survival rate, and mortality risk decreased progressively through the quartiles (log-rank χ2 142.283, P < 0.0001). Patients with ADHF were divided into 8 groups by quartiles of PNI and median levels of serum chloride. After adjustment, the hazard ratio (HR) for all-cause mortality in ADHF patients in Group 1 was 8.7 times higher than that in the reference Group 8. Furthermore, the addition of serum chloride level and PNI quartile to the Cox model increased the area under the Receiver operating characteristic (ROC) curve by 0.05, and the area under the ROC curve of the new model was higher than that of the original model with traditional risk factors. CONCLUSIONS: Both the lowest PNI quartiles and low chloride level indicate a higher risk of all-cause death in patients with ADHF.

13.
Int J Biol Macromol ; 265(Pt 2): 131091, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38521319

RESUMO

Acetaldehyde dehydrogenase 2 (ALDH2) is a crucial enzyme in alcohol metabolism, and oral administration of ALDH2 is a promising method for alcohol detoxification. However, recombinant ALDH2 is susceptible to hydrolysis by digestive enzymes in the gastrointestinal tract and is expressed as inactive inclusion bodies in E. coli. In this study, we performed three rounds of rational design to address these issues. Specifically, the surface digestive sites of pepsin and trypsin were replaced with other polar amino acids, while hydrophobic amino acids were incorporated to reshape the catalytic cavity of ALDH2. The resulting mutant DE2-852 exhibited a 45-fold increase in soluble expression levels, while its stability against trypsin and pepsin increased by eightfold and twofold, respectively. Its catalytic efficiency (kcat/Km) at pH 7.2 and 3.2 improved by more than four and five times, respectively, with increased Vmax and decreased Km values. The enhanced properties of DE2-852 were attributed to the D457Y mutation, which created a more compact protein structure and facilitated a faster collision between the substrate and catalytic residues. These results laid the foundation for the oral administration and mass preparation of highly active ALDH2 and offered insights into the oral application of other proteins.


Assuntos
Aldeído Desidrogenase , Pepsina A , Humanos , Aldeído-Desidrogenase Mitocondrial/genética , Aldeído-Desidrogenase Mitocondrial/química , Aldeído Desidrogenase/genética , Aldeído Desidrogenase/metabolismo , Tripsina , Escherichia coli/genética , Escherichia coli/metabolismo , Aminoácidos
14.
BMC Musculoskelet Disord ; 25(1): 233, 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38521928

RESUMO

BACKGROUND: Osteosarcoma is one of the most common cancers worldwide. Intense efforts have been made to elucidate the pathogeny, but the mechanisms of osteosarcoma are still not well understood. We aimed to investigate the potential biomarker, allograft inflammatory factor-1 (AIF1), affecting the progression and prognosis of osteosarcoma. METHODS: Three microarray datasets were downloaded from GEO datasets and one was obtained from the TCGA dataset. The differentially expressed genes (DEGs) were identified. GO and KEGG functional enrichment analyses of overlapped DEGs were performed. The PPI network of overlapped DEGs was constructed by STRING and visualized with Cytoscape. Overall survival (OS) and Metastasis free survival (MFS) were analyzed from GSE21257. Finally, the effect of the most relevant core gene affecting the progression of osteosarcoma was examined in vitro. RESULTS: One hundred twenty six DEGs were identified, consisting of 65 upregulated and 61 downregulated genes. Only AIF1 was significantly associated with OS and MFS. It was found that AIF1 could be enriched into the NF-κB signaling pathway. GSEA and ssGSEA analyses showed that AIF1 was associated with the immune invasion of tumors. Cell experiments showed that AIF1 was underexpressed in osteosarcoma cell lines, while the malignant propriety was attenuated after overexpressing the expression of AIF1. Moreover, AIF1 also affects the expression of the NF-κB pathway. CONCLUSION: In conclusion, DEGs and hub genes identified in the present study help us understand the molecular mechanisms underlying the carcinogenesis and progression of osteosarcoma, and provide candidate targets for diagnosis and treatment of osteosarcoma.


Assuntos
Proteínas de Ligação ao Cálcio , Perfilação da Expressão Gênica , Proteínas dos Microfilamentos , Osteossarcoma , Humanos , Biologia Computacional , Redes Reguladoras de Genes , NF-kappa B , Osteossarcoma/genética , Osteossarcoma/patologia , Prognóstico , Proteínas de Ligação ao Cálcio/genética , Proteínas dos Microfilamentos/genética
15.
Hum Genet ; 143(3): 293-309, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38456936

RESUMO

Auditory neuropathy (AN) is a unique type of language developmental disorder, with no precise rate of genetic contribution that has been deciphered in a large cohort. In a retrospective cohort of 311 patients with AN, pathogenic and likely pathogenic variants of 23 genes were identified in 98 patients (31.5% in 311 patients), and 14 genes were mutated in two or more patients. Among subgroups of patients with AN, the prevalence of pathogenic and likely pathogenic variants was 54.4% and 56.2% in trios and families, while 22.9% in the cases with proband-only; 45.7% and 25.6% in the infant and non-infant group; and 33.7% and 0% in the bilateral and unilateral AN cases. Most of the OTOF gene (96.6%, 28/29) could only be identified in the infant group, while the AIFM1 gene could only be identified in the non-infant group; other genes such as ATP1A3 and OPA1 were identified in both infant and non-infant groups. In conclusion, genes distribution of AN, with the most common genes being OTOF and AIFM1, is totally different from other sensorineural hearing loss. The subgroups with different onset ages showed different genetic spectrums, so did bilateral and unilateral groups and sporadic and familial or trio groups.


Assuntos
Perda Auditiva Central , Mutação , Humanos , Feminino , Masculino , Perda Auditiva Central/genética , Lactente , Criança , Pré-Escolar , Estudos Retrospectivos , Adolescente , Proteínas de Membrana/genética , Estudos de Coortes
16.
Braz J Cardiovasc Surg ; 39(2): e20220185, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38426429

RESUMO

INTRODUCTION: Inflammatory and immunological factors play pivotal roles in the prognosis of acute type A aortic dissection. We aimed to evaluate the prognostic values of immune-inflammatory parameters in acute type A aortic dissection patients after surgery. METHODS: A total of 127 acute type A aortic dissection patients were included. Perioperative clinical data were collected through the hospital's information system. The outcomes studied were delayed extubation, reintubation, and 30-day mortality. Multivariate logistic regression analysis and receiver operating characteristic analysis were used to screen the risk factors of poor prognosis. RESULTS: Of all participants, 94 were male, and mean age was 51.95±11.89 years. The postoperative prognostic nutritional indexes were lower in delayed extubation patients, reintubation patients, and patients who died within 30 days. After multivariate regression analysis, the postoperative prognostic nutritional index was a protective parameter of poor prognosis. The odds ratios (95% confidence interval) of postoperative prognostic nutritional index were 0.898 (0.815, 0.989) for delayed extubation and 0.792 (0.696, 0.901) for 30-day mortality. Low postoperative fibrinogen could also well predict poor clinical outcomes. The odds ratios (95% confidence interval) of postoperative fibrinogen were 0.487 (0.291, 0.813) for delayed extubation, 0.292 (0.124, 0.687) for reintubation, and 0.249 (0.093, 0.669) for 30-day mortality. CONCLUSION: Postoperative prognostic nutritional index and postoperative fibrinogen could be two promising markers to identify poor prognosis of acute type A aortic dissection patients after surgery.


Assuntos
Dissecção Aórtica , Fibrinogênio , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Feminino , Prognóstico , Avaliação Nutricional , Estudos Retrospectivos , Dissecção Aórtica/cirurgia , Fatores de Risco
17.
Hum Mol Genet ; 33(10): 905-918, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38449065

RESUMO

Mutations in AIFM1, encoding for apoptosis-inducing factor (AIF), cause AUNX1, an X-linked neurologic disorder with late-onset auditory neuropathy (AN) and peripheral neuropathy. Despite significant research on AIF, there are limited animal models with the disrupted AIFM1 representing the corresponding phenotype of human AUNX1, characterized by late-onset hearing loss and impaired auditory pathways. Here, we generated an Aifm1 p.R450Q knock-in mouse model (KI) based on the human AIFM1 p.R451Q mutation. Hemizygote KI male mice exhibited progressive hearing loss from P30 onward, with greater severity at P60 and stabilization until P210. Additionally, muscle atrophy was observed at P210. These phenotypic changes were accompanied by a gradual reduction in the number of spiral ganglion neuron cells (SGNs) at P30 and ribbons at P60, which coincided with the translocation of AIF into the nucleus starting from P21 and P30, respectively. The SGNs of KI mice at P210 displayed loss of cytomembrane integrity, abnormal nuclear morphology, and dendritic and axonal demyelination. Furthermore, the inner hair cells and myelin sheath displayed abnormal mitochondrial morphology, while fibroblasts from KI mice showed impaired mitochondrial function. In conclusion, we successfully generated a mouse model recapitulating AUNX1. Our findings indicate that disruption of Aifm1 induced the nuclear translocation of AIF, resulting in the impairment in the auditory pathway.


Assuntos
Fator de Indução de Apoptose , Núcleo Celular , Modelos Animais de Doenças , Animais , Fator de Indução de Apoptose/genética , Fator de Indução de Apoptose/metabolismo , Camundongos , Humanos , Núcleo Celular/metabolismo , Núcleo Celular/genética , Masculino , Mutação , Gânglio Espiral da Cóclea/metabolismo , Gânglio Espiral da Cóclea/patologia , Perda Auditiva/genética , Perda Auditiva/patologia , Perda Auditiva/metabolismo , Técnicas de Introdução de Genes , Transporte Proteico , Células Ciliadas Auditivas Internas/metabolismo , Células Ciliadas Auditivas Internas/patologia , Atrofia Muscular/genética , Atrofia Muscular/patologia , Atrofia Muscular/metabolismo
18.
Heliyon ; 10(3): e24578, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38327458

RESUMO

Background: Myocardial injury has been regarded as a major cause of several heart diseases. Long non-coding RNA (lncRNA) has emerged as a key regulator in a wide array of diseases. Aim of the study: This study aims to explore the role of Zfas1 in myocardial injury. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was adopted to evaluate the proliferative capability of H9c2 cells. Terminal deoxynucleotidyltransferase dUTP nick end labeling (TUNEL) and flow cytometry assays were employed to measure cell apoptosis. The expression of proteins related to apoptosis and autophagy was examined by Western blot. Immunofluorescence (IF) assay was performed to monitor the process of autophagy. Real-time reverse-transcription polymerase chain reaction (RT-qPCR) was employed to determine the expressions of autophagy-related gene 10 (ATG10), miR-383-5p and Zfas1. The interacting relationship between miR-383-5p and ATG10 (or Zfas1) was assessed by luciferase reporter and RNA-binding protein immunoprecipitation (RIP) assays. Results: The treatment of hypoxia hindered cell proliferation but accelerated cell apoptosis and autophagy. ATG10 exhibited higher mRNA and protein expression in H9c2 cells induced by hypoxia. MiR-383-5p was revealed to be the upstream gene of ATG10 and could interact with ATG10. Zfas1 was validated to sponge miR-383-5p and positively regulated ATG10 expression. Zfas1 knockdown-mediated cellular proliferation, apoptosis and autophagy phenotypes were counteracted by ATG10 abundance. Conclusions: LncRNA Zfas1 boosts cell apoptosis and autophagy in myocardial injury induced by hypoxia via miR-383-5p/ATG10 axis, indicating that Zfas1 may be utilized as a therapeutic target for myocardial injury.

19.
ACS Appl Mater Interfaces ; 16(8): 10180-10195, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38362656

RESUMO

To realize highly efficient solar-thermo-electric energy conversion for clean electricity power generation, we have developed a new type of unidirectionally structured magnetic phase-change composite comprising a carbonized polyimide (C-PI)/Kevlar nanofiber (KNF) complex aerogel as a 3D carbon skeleton porous supporting material, CoFe2O4 nanoparticles as a magnetic additive, polyethylene glycol (PEG) as a phase-change material, and polypyrrole as a photothermal absorption coating layer. The as-fabricated C-PI/KNF complex aerogel exhibits a unidirectional microstructure, high porosity, robust skeleton frame, ultralight weight, and high thermal conductance. Featured with such unique structure and characteristics, the complex aerogel can offer an effective heat and electron transfer method to ensure highly efficient solar-thermal conversion and photothermal energy storage of the developed composite. The developed composite exhibits a high latent heat capacity of over 150 J g-1, outstanding shape stability along with a low leakage of 0.2 wt %, good thermal cycling stability, and high photothermal conversion efficiency of 84.8%. Based on the Seebeck effect, a solar thermoelectric generation system (STEGS) was constructed with the hot side coupled with the developed composite and the cold side immersed in air and ice water. Under 2.0 kW m-2 solar irradiation, the developed STEGS in ice water obtained maximum output voltage and current of 259.7 mV and 27.1 mA, respectively, which are significantly higher than those in air. The output power of the developed STEGS in an ice water environment is 50.6% higher than that in air under 4.0 kW m-2 solar irradiation. More importantly, the developed STEGS in ice water continuously generated output voltage and current for about 810 s without solar irradiation thanks to the latent heat release by the PEG component within the developed composite. In addition, the introduction of magnetic CoFe2O4 can accelerate solar-thermal conversion through periodic electron motion by the Néel relaxation or Brownian relaxation. This resulted in an increase in the maximum output voltage and current by 13.7 and 11.5%, respectively, under an alternating magnetic field as a result of the magnetism-accelerated solar-thermo-electric conversion. This study offers an innovative approach for developing PCM-based advanced functional materials for solar energy utilization in clean and sustainable electricity generation.

20.
Nature ; 626(7998): 283-287, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38297128

RESUMO

Ultracold polyatomic molecules offer opportunities1 in cold chemistry2,3, precision measurements4 and quantum information processing5,6, because of their rich internal structure. However, their increased complexity compared with diatomic molecules presents a challenge in using conventional cooling techniques. Here we demonstrate an approach to create weakly bound ultracold polyatomic molecules by electroassociation7 (F.D. et al., manuscript in preparation) in a degenerate Fermi gas of microwave-dressed polar molecules through a field-linked resonance8-11. Starting from ground-state NaK molecules, we create around 1.1 × 103 weakly bound tetratomic (NaK)2 molecules, with a phase space density of 0.040(3) at a temperature of 134(3) nK, more than 3,000 times colder than previously realized tetratomic molecules12. We observe a maximum tetramer lifetime of 8(2) ms in free space without a notable change in the presence of an optical dipole trap, indicating that these tetramers are collisionally stable. Moreover, we directly image the dissociated tetramers through microwave-field modulation to probe the anisotropy of their wavefunction in momentum space. Our result demonstrates a universal tool for assembling weakly bound ultracold polyatomic molecules from smaller polar molecules, which is a crucial step towards Bose-Einstein condensation of polyatomic molecules and towards a new crossover from a dipolar Bardeen-Cooper-Schrieffer superfluid13-15 to a Bose-Einstein condensation of tetramers. Moreover, the long-lived field-linked state provides an ideal starting point for deterministic optical transfer to deeply bound tetramer states16-18.

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