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1.
Discov Med ; 36(185): 1250-1259, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38926111

RESUMO

BACKGROUND: Cigarette smoke (CS) induces autophagy and endoplasmic reticulum (ER) stress in the lungs. Research suggests that maternal exposure to CS during pregnancy leads to decreased lung function in offspring. However, the effects of maternal CS exposure on lung autophagy and ER stress in offspring during pregnancy remain unclear. METHODS: C57BL/6J female mice were divided into the AA (air treatment during both pre-pregnancy and pregnancy), AS (air treatment during pre-pregnancy and CS treatment during pregnancy), SA (CS treatment during pre-pregnancy and air treatment during pregnancy), and SS (CS treatment during both pre-pregnancy and pregnancy) groups. The male offspring mice were selected to the study and euthanized 49 days after birth for the study. Hematoxylin and eosin (HE) staining was employed to observe pathological alterations, while transmission electron microscopy (TEM) was utilized to examine ultrastructure and autophagic vesicles. Additionally, the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method was applied to identify apoptosis in lung tissues. Immunofluorescence, Real-Time PCR, and Western Blot analyses were conducted to assess the expression of ER stress and autophagy-related markers in lung tissues. RESULTS: The findings revealed that exposure to CS heightened the extent of pathological damage and the abundance of autophagosomes in the lungs of offspring mice. TUNEL results indicated an increased fluorescence intensity in the AS, SA and SS groups, with the most significant in AS and SS groups. Furthermore, CS exposure augmented the fluorescence intensity and expression of ER stress and autophagy-related proteins. The expression of C/EBP-homologous protein (CHOP) exhibited no discernible difference between the SA and SS groups but showed a significant increase in the AS group. Conversely, the expression levels of glucose-regulated protein 78 (GRP78), Caspase-12, Beclin-1, and microtubule-associated protein 1 light chain 3 (LC3) exhibited no significant difference between the AS and SA groups, whereas they were significantly upregulated in the SS group. CONCLUSIONS: Preconceptional and gestational exposure to CS heightened ER stress and autophagy in the lungs of mouse offspring. However, in mothers who smoked, withdrawal from CS during pregnancy led to a reduction in ER stress and autophagy in the lungs of their offspring.


Assuntos
Autofagia , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático , Pulmão , Exposição Materna , Camundongos Endogâmicos C57BL , Efeitos Tardios da Exposição Pré-Natal , Animais , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Feminino , Gravidez , Camundongos , Pulmão/patologia , Pulmão/metabolismo , Exposição Materna/efeitos adversos , Masculino , Efeitos Tardios da Exposição Pré-Natal/patologia , Apoptose , Poluição por Fumaça de Tabaco/efeitos adversos
2.
Parkinsonism Relat Disord ; 125: 107037, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38878445

RESUMO

PURPOSE: To investigate interocular asymmetry (IA) of retinal structure and vessel density in patients with Parkinson's disease (PD) and normal controls (NC). METHODS: Seventy-eight subjects including 40 PD patients and 38 NC had completed optical coherence tomography angiography (OCTA) and neurological examinations for three rating scales (UPDRS-III, MMSE and MoCA). The IA was calculated by the absolute value of difference in right and left eyes. The IA of thickness in macular ganglion cell inner-plexiform layer (GCIPL), peripapillary retinal nerve fiber layer (pRNFL), and vessel density of superficial capillary plexus (SCP), deep capillary plexus (DCP), radial peripapillary capillary (RPC) were obtained from OCTA. RESULTS: The motor-symptom-onset side of eyes showed lower vessel density in parafovea of SCP (51.09 ± 3.46 vs 49.81 ± 4.16, P = 0.03) and superior hemi of perifovea DCP (49.55 ± 5.81 vs 47.33 ± 5.71, = 0.04). The PD patients showed larger IA in thickness of superior half of pRNFL (5.27 [2.67, 10.87] vs 3.08 [1.62, 5.61], P = 0.02) and parafovea GCIPL (2.40[1.25, 6.35] vs 1.40[0.50, 2.45], P = 0.02). No significant interocular asymmetry was found in vessel density between PD and NC. A higher UPDRS-III scale was associated with larger IA in GCIPL (ß = 0.093, P = 0.001) and smaller IA in DCP (ß = -0.065, P = 0.037). CONCLUSION: The motor-symptom-onset side of eyes showed more severe loss of macular vessel density than the other side of eyes. The PD patients showed asymmetrical structural change in GCIPL and pRNFL, which showed the potential as the diagnostic biomarker for PD.

3.
Reprod Toxicol ; 128: 108646, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38880403

RESUMO

OBJECTIVE: To investigate the impact of maternal smoking on chronic obstructive pulmonary disease (COPD) progression in offspring. METHODS: Using female C57BL/6 J mice, a maternal cigarette smoke exposure (CSE) model was established. Mice were exposed to cigarette smoke for 2 hours/day, 7 days/week, with a minimum 4-hour interval between exposures. Experimental groups included control (Con), pregnancy exposure (AS), pre-pregnancy exposure (SA), and pre-pregnancy + pregnancy exposure (SS). Lung function tests (Penh, PAU, TVb, EF50, Tr) were conducted on male offspring at 7 weeks. Histopathology, electron microscopy, and protein level changes were examined. RESULTS: Lung function tests revealed significant impairments in Penh, PAU, TVb, EF50, and Tr in offspring across all exposure scenarios. Specifically, AS experienced significant lung function impairment and mitochondrial dysfunction in offspring, with noticeable pulmonary lesions and increased apoptosis. SA showed similar or even more severe lung function impairment and cellular apoptosis. SS exhibited the most pronounced effects, with the highest levels of lung dysfunction, mitochondrial damage, and apoptosis. Histopathological analysis showed pulmonary lesions in offspring exposed to maternal CSE. Flow cytometry revealed increased apoptosis and reduced mitochondrial membrane potential in offspring lung cells. Electron microscopy confirmed mitochondrial dysfunction. Upregulation of apoptotic proteins and downregulation of anti-apoptotic protein Bcl-2 were found in offspring lung tissue exposed to maternal CSE. CONCLUSION: Maternal smoking induces impaired lung function, pulmonary lesions, and mitochondrial dysfunction in offspring, regardless of exposure timing and duration. Additionally, it alters expression of apoptosis-related proteins in offspring lung tissue, potentially contributing to COPD susceptibility.

4.
Front Microbiol ; 15: 1384027, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38803370

RESUMO

Cordyceps cicadae, as a new food ingredient, is a valuable edible and medicinal fungi. However, its resources are severely depleted due to environmental limitations and excessive harvesting practices. N6-(2-hydroxyethyl) adenosine (HEA), as an important product of Cordyceps cicadae, has the potential to be used in medical industry due to its diverse disease curing potential. However, the disclosure of HEA synthesis still severely limited its application until now. In this study, the kinetic curves for adenosine and HEA under shaker fermentation were explored. The kinetics of HEA and adenosine production exhibited a competitive pattern, implicating a possibility of sharing a same step during their synthesis. Due to HEA as a derivative of nitrogen metabolism, the effect of different nitrogen sources (peptone, yeast extract, ammonium sulfate, diammonium oxalate monohydrate, ammonium citrate dibasic, and ammonium citrate tribasic) on HEA production in Cordyceps cicadae strain AH 10-4 had been explored under different incubation conditions (shaker fermentation, stationary fermentation, and submerged fermentation). Our results indicated that the complex organic nitrogen sources were found to improve the accumulation of HEA content under shaker fermentation. In contrast, the optimal nitrogen source for the accumulation of HEA under stationary fermentation and submerged fermentation was ammonium citrate tribasic. But submerged fermentation obviously shortened the incubation time and had a comparable capacity of HEA accumulation by 2.578 mg/g compared with stationary fermentation of 2.535 mg/g, implicating a possibility of scaled-up production of HEA in industry by submerged fermentation. Based on the dramatic HEA production by ammonium sulfate as nitrogen resources between stationary and shaker fermentations, alanine, aspartate and glutamate as well as arginine metabolic pathway were related to the production of HEA by comparative transcriptome. Further investigation indicated that glutamic acid, which is an analog of Asp, showed an optimum production of HEA in comparison with other amino acids.

5.
J Hazard Mater ; 472: 134440, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38723480

RESUMO

N6-methyladenosine (m6A) is the most common form of internal post-transcriptional methylation observed in eukaryotic mRNAs. The abnormally increased level of m6A within the cells can be catalyzed by specific demethylase fat mass and obesity-associated protein (FTO) and stay in a dynamic and reversible state. However, whether and how FTO regulates oxidative damage via m6A modification remain largely unclear. Herein, by using both in vitro and in vivo models of oxidative damage induced by arsenic, we demonstrated for the first time that exposure to arsenic caused a significant increase in SUMOylation of FTO protein, and FTO SUMOylation at lysine (K)- 216 site promoted the down-regulation of FTO expression in arsenic target organ lung, and therefore, remarkably elevating the oxidative damage via an m6A-dependent pathway by its specific m6A reader insulin-like growth factor-2 mRNA-binding protein-3 (IGF2BP3). Consequently, these findings not only reveal a novel mechanism underlying FTO-mediated oxidative damage from the perspective of m6A, but also imply that regulation of FTO SUMOylation may serve as potential approach for treatment of oxidative damage.


Assuntos
Adenosina , Dioxigenase FTO Dependente de alfa-Cetoglutarato , Estresse Oxidativo , Proteínas de Ligação a RNA , Sumoilação , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Sumoilação/efeitos dos fármacos , Animais , Estresse Oxidativo/efeitos dos fármacos , Adenosina/análogos & derivados , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Humanos , Arsênio/toxicidade , Camundongos , Masculino , Pulmão/efeitos dos fármacos , Pulmão/metabolismo
6.
Microb Cell Fact ; 23(1): 154, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38796463

RESUMO

Microbial cell factories serve as pivotal platforms for the production of high-value natural products, which tend to accumulate on the cell membrane due to their hydrophobic properties. However, the limited space of the cell membrane presents a bottleneck for the accumulation of these products. To enhance the production of intracellular natural products and alleviate the burden on the cell membrane caused by product accumulation, researchers have implemented various membrane engineering strategies. These strategies involve modifying the membrane components and structures of microbial cell factories to achieve efficient accumulation of target products. This review summarizes recent advances in the application of membrane engineering technologies in microbial cell factories, providing case studies involving Escherichia coli and yeast. Through these strategies, researchers have not only improved the tolerance of cells but also optimized intracellular storage space, significantly enhancing the production efficiency of natural products. This article aims to provide scientific evidence and references for further enhancing the efficiency of similar cell factories.


Assuntos
Membrana Celular , Escherichia coli , Membrana Celular/metabolismo , Escherichia coli/metabolismo , Escherichia coli/genética , Produtos Biológicos/metabolismo , Engenharia Metabólica/métodos , Saccharomyces cerevisiae/metabolismo
7.
Front Microbiol ; 15: 1375120, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38605715

RESUMO

Filamentous fungi play a crucial role in environmental pollution control, protein secretion, and the production of active secondary metabolites. The evolution of gene editing technology has significantly improved the study of filamentous fungi, which in the past was laborious and time-consuming. But recently, CRISPR-Cas systems, which utilize small guide RNA (sgRNA) to mediate clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas), have demonstrated considerable promise in research and application for filamentous fungi. The principle, function, and classification of CRISPR-Cas, along with its application strategies and research progress in filamentous fungi, will all be covered in the review. Additionally, we will go over general matters to take into account when editing a genome with the CRISPR-Cas system, including the creation of vectors, different transformation methodologies, multiple editing approaches, CRISPR-mediated transcriptional activation (CRISPRa) or interference (CRISPRi), base editors (BEs), and Prime editors (PEs).

8.
High Alt Med Biol ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38682426

RESUMO

Xiong, Shiqiang, Jun Hou, Haixia Yang, Meiting Gong, Xin Ma, Xuhu Yang, Hongyang Zhang, Yao Ma, Liang Gao, and Haifeng Pei. The profiles of venous thromboembolism at different high altitudes High Alt Med Biol. 00:000-000, 2024.-This study investigated the incidence of venous thromboembolism (VTE) in high altitude (HA) and very HA areas. Patients with deep vein thrombosis (DVT) or pulmonary embolism (PE) diagnosed between 2004 and 2022 in Yecheng, China, were retrospectively analyzed. The results showed that patients with PE at very HA had a higher risk of lower extremity DVT (OR 16.3 [95% CI 1.2-223.2], p = 0.036), than those at HA, especially in the early stages of very HA entry, and the harsh environment of very HA further exacerbated the risk of VTE. These findings emphasize the higher risk of PE development in very HA and the need for enhanced prevention and treatment in this area.

9.
Neuron ; 112(9): 1498-1517.e8, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38430912

RESUMO

Recognizing the affective states of social counterparts and responding appropriately fosters successful social interactions. However, little is known about how the affective states are expressed and perceived and how they influence social decisions. Here, we show that male and female mice emit distinct olfactory cues after experiencing distress. These cues activate distinct neural circuits in the piriform cortex (PiC) and evoke sexually dimorphic empathic behaviors in observers. Specifically, the PiC → PrL pathway is activated in female observers, inducing a social preference for the distressed counterpart. Conversely, the PiC → MeA pathway is activated in male observers, evoking excessive self-grooming behaviors. These pathways originate from non-overlapping PiC neuron populations with distinct gene expression signatures regulated by transcription factors and sex hormones. Our study unveils how internal states of social counterparts are processed through sexually dimorphic mechanisms at the molecular, cellular, and circuit levels and offers insights into the neural mechanisms underpinning sex differences in higher brain functions.


Assuntos
Empatia , Caracteres Sexuais , Animais , Masculino , Feminino , Camundongos , Empatia/fisiologia , Córtex Piriforme/fisiologia , Córtex Piriforme/metabolismo , Sinais (Psicologia) , Camundongos Endogâmicos C57BL , Afeto/fisiologia , Neurônios/fisiologia , Neurônios/metabolismo , Comportamento Animal/fisiologia
10.
World J Clin Cases ; 12(7): 1339-1345, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38524509

RESUMO

BACKGROUND: Bradycardia-induced cardiomyopathy (BIC), which is a disease resulting from bradycardia, is characterized by cardiac chamber enlargement and diminished cardiac function. The correction of bradycardia can allow for significant improvements in both cardiac function and structure; however, this disease has been infrequently documented. In this case, we conducted a longitudinal follow-up of a patient who had been enduring BIC for more than 40 years to heighten awareness and prompt timely diagnosis and rational intervention. CASE SUMMARY: A woman who presented with postactivity fatigue and dyspnea was diagnosed with bradycardia at the age of 7. Since she had no obvious symptoms, she did not receive any treatment to improve her bradycardia during the 42-year follow-up, except for the implantation of a temporary pacemaker during labor induction surgery. As time progressed, the patient's heart gradually expanded due to her low ventricular rate, and she was diagnosed with BIC. In 2014, the patient developed atrial fibrillation, her ventricular rate gradually increased, and her heart shape gradually returned to normal. This report describes the cardiac morphological changes caused by the heart rate changes in BIC patients older than 40 years, introduces another possible outcome of BIC, and emphasizes the importance of early intervention in treating BIC. CONCLUSION: BIC can induce atrial fibrillation, causing an increased ventricular rate and leading to positive cardiac remodeling.

11.
BMC Ophthalmol ; 24(1): 108, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448910

RESUMO

BACKGROUND: To compare the bleb morphologies of phacoemulsification combined with Ex-PRESS implantation (Phaco-ExPRESS), phaco trabeculectomy (Phaco-Trab), and trabeculectomy (Trab) in postoperative two years. METHODS: Patients with primary open-angle glaucoma (POAG) with or without cataracts were included in this study. All patients underwent surgeries of either Phaco-ExPRESS, Phaco-Trab, or Trab. The morphologic structures of the filtering bleb, including microcysts area, hyperreflective dot density, and stromal connective tissue under in vivo confocal microscope (IVCM), were compared between the three groups. The data were collected preoperatively and postoperatively at 2 weeks, 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months. RESULTS: Eighty-nine eyes from 89 patients were enrolled, including 32 in the Phaco-ExPRESS group, 25 in the Phaco-Trab group, and 32 in the Trab group. In a 24-month follow-up, bleb morphologies in Phaco-ExPRESS were similar to the Trab group. The area of epithelial microcysts was significantly increased in Phaco-ExPRESS and Trab groups while significantly decreased in Phaco-Trab. At postoperative 24 months, the complete success rate was 65.1% in Phaco-ExPRESS, 32.0% in Phaco-Trab, and 59.4% in the Trab group (P = 0.03). The phaco-Trab group had more postoperative anti-glaucoma medications than the other two groups (P < 0.05). CONCLUSIONS: Phaco-ExPRESS group and Trab group had similar blebs morphologies in IVCM, with larger microcyst area, looser connective tissue, and less inflammation than Phaco-Trab, indicating that the function of blebs in the Phaco-ExPRESS and Trab group, was more potent than that of Phaco-Trab. All these surgical methods provided adequate IOP control, but Phaco-Trab required more anti-glaucoma medications.


Assuntos
Cistos , Glaucoma de Ângulo Aberto , Facoemulsificação , Trabeculectomia , Humanos , Agentes Antiglaucoma , Glaucoma de Ângulo Aberto/complicações , Glaucoma de Ângulo Aberto/cirurgia , Estudos Retrospectivos , Microscopia Confocal
12.
Sensors (Basel) ; 24(4)2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38400268

RESUMO

Street trees are of great importance to urban green spaces. Quick and accurate segmentation of street trees from high-resolution remote sensing images is of great significance in urban green space management. However, traditional segmentation methods can easily miss some targets because of the different sizes of street trees. To solve this problem, we propose the Double-Branch Multi-Scale Contextual Network (DB-MSC Net), which has two branches and a Multi-Scale Contextual (MSC) block in the encoder. The MSC block combines parallel dilated convolutional layers and transformer blocks to enhance the network's multi-scale feature extraction ability. A channel attention mechanism (CAM) is added to the decoder to assign weights to features from RGB images and the normalized difference vegetation index (NDVI). We proposed a benchmark dataset to test the improvement of our network. Experimental research showed that the DB-MSC Net demonstrated good performance compared with typical methods like Unet, HRnet, SETR and recent methods. The overall accuracy (OA) was improved by at least 0.16% and the mean intersection over union was improved by at least 1.13%. The model's segmentation accuracy meets the requirements of urban green space management.

13.
Front Endocrinol (Lausanne) ; 15: 1295745, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38344662

RESUMO

Purpose: To assess the differences in the measurement of central foveal thickness (CFT) in patients with macular edema (ME) between two display modes (1:1 pixel and 1:1 micron) on optical coherence tomography (OCT). Design: This is a retrospective, cross-sectional study. Methods: Group A consisted of participants with well-horizontal OCT B-scan images and group B consisted of participants with tilted OCT B-scan. We manually measured the CFT under the two display modes, and the values were compared statistically using the paired t-test. Spearman's test was used to assess the correlations between the OCT image tilting angle (OCT ITA) and the differences in CFT measurement. The area under the curve (AUC) was calculated to define the OCT ITA cutoff for a defined CFT difference. Results: In group A, the mean CFT in the 1:1 pixel display mode was 420.21 ± 130.61 µm, similar to the mean CFT of 415.27 ± 129.85 µm in the 1:1 micron display mode. In group B, the median CFT in the 1:1 pixel display mode is 409.00 µm (IQR: 171.75 µm) and 368.00 µm (IQR: 149.00 µm) in the 1:1 micron display mode. There were significant differences between the two display modes with the median (IQR) absolute difference and median (IQR) relative difference of 38.00 µm (75.00 µm) and 10.19% (21.91%) (all p = 0.01). The differences in CFT measurement between the two display modes were correlated with the OCT ITA (absolute differences, r = 0.88, p < 0.01; relative differences, r = 0.87, p < 0.01). The AUC for a predefined CFT difference was 0.878 (10 µm), 0.933 (20 µm), 0.938 (30 µm), 0.961 (40 µm), 0.962 (50 µm), and 0.970 (60 µm). Conclusion: In patients with DM, when the OCT B-scan images were well-horizontal, manual CFT measurements under the two display modes were similar, but when the B-scan images were tilted, the CFT measurements were different under the two display modes, and the differences were correlated to the OCT ITA.


Assuntos
Edema Macular , Humanos , Edema Macular/diagnóstico por imagem , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Estudos Transversais
14.
World J Surg Oncol ; 22(1): 37, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38287354

RESUMO

BACKGROUND: Ovarian clear cell carcinoma (OCCC) shares treatment strategies with epithelial ovarian cancer (EOC). Due to OCCC's rarity, there's a lack of prospective studies on its surgery, resulting in heterogeneous and limited existing data. This study aims to clarify the prognostic significance of lymphadenectomy in OCCC patients. METHODS: We systematically searched Web of Science, Scopus, PubMed, and Google Scholar until July 2023 for studies investigating lymphadenectomy's effects on OCCC patients. We calculated pooled hazard ratios (HR) with 95% confidence intervals (CI). This study is registered in PROSPERO (CRD42021270460). RESULTS: Among 444 screened articles, seven studies (2883 women) met inclusion criteria. Our analysis revealed that lymphadenectomy significantly improved disease-specific survival (DSS) (HR = 0.76, 95%CI = 0.60-0.95, P = 0.02) and disease-free survival (DFS) (HR = 0.58, 95%CI = 0.34-0.99, P = 0.05). However, it did not significantly affect overall survival (OS) (HR = 0.80, 95%CI = 0.60-1.06, P = 0.12) or progression-free survival (PFS) (HR = 0.95, 95%CI = 0.64-1.42, P = 0.79). Notably, some earlier studies reported no survival benefit, warranting cautious interpretation. CONCLUSION: Lymphadenectomy does not significantly enhance OS and PFS for OCCC but does improve DFS and DSS. Tailoring treatment to individual patient profiles is imperative for optimal outcomes. Precise preoperative or intraoperative lymph node metastasis detection is essential for identifying candidates benefiting from lymphadenectomy. Collaborative international efforts and an OCCC database are pivotal for refining future treatment strategies.


Assuntos
Adenocarcinoma de Células Claras , Neoplasias Ovarianas , Humanos , Feminino , Excisão de Linfonodo/métodos , Carcinoma Epitelial do Ovário/cirurgia , Adenocarcinoma de Células Claras/cirurgia , Adenocarcinoma de Células Claras/patologia , Prognóstico , Neoplasias Ovarianas/patologia
15.
Mol Genet Genomic Med ; 12(1): e2357, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38284445

RESUMO

BACKGROUND: Newborn screening (NBS) aims to detect congenital anomalies, and next-generation sequencing (NGS) has shown promise in this aspect. However, the NBS strategy for monogenic inherited diseases in China remains insufficient. METHODS: We developed a NeoEXOME panel comprising 601 genes that are relevant to the Chinese population found through extensive research on available databases. An interpretation system to grade the results into positive (high-risk, moderate-risk, and low-risk genotypes), negative, and carrier according to the American College of Medical Genetics (ACMG) guidelines was also developed. We validated the panel to evaluate its efficacy by using data from the "1000 Genomes Project" and conducted a pilot multicenter study involving 3423 neonates. RESULTS: The NGS positive rate in the 1000 Genomes Project was 7.6% (23/301), whereas the rate was 12.0% in the multicenter study, including 3249 recruited neonates. Notably, in 200 neonates, positive per conventional NBS, 58.5% (69/118) showed results consistent with NGS. In the remaining 3049 neonates showing negative results in conventional NBS, 271 (8.9%) were positive per NGS, and nine of them were clinically diagnosed with diseases in the follow-up. CONCLUSION: We successfully designed a NeoEXOME panel for targeted sequencing of monogenic inherited diseases in NBS. The panel demonstrated high performance in the Chinese population, particularly for the early detection of diseases with no biochemical markers.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Triagem Neonatal , Humanos , Recém-Nascido , Projetos Piloto , Sequenciamento do Exoma , Triagem Neonatal/métodos , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala/métodos
16.
J Chromatogr A ; 1713: 464521, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-37992598

RESUMO

Long-term intake of animal-derived foods with excessive fluoroquinolones (FQs) will cause damage to human health, so it is critical to establish a feasible approach for sensitive and rapid monitoring of FQs residues. In this study, a new cyclodextrin modified magnetic metal-organic frameworks (Fe3O4@UiO-66-CD) was successfully synthesized by amidation reaction and applied to magnetic solid phase extraction (MSPE) for FQs analysis. The adsorption behavior of Fe3O4@UiO-66-CD was consistent with the pseudo-second-order kinetics and Freundlich isothermal adsorption model, which indicated that the designed material had various interactions on FQs, such as host-guest interaction and π-π interaction. The parameters of MSPE were optimized and the determination method of norfloxacin, enrofloxacin, lomefloxacin and gatifloxacin was established by using MSPE combined with ultra-high performance liquid chromatography (UHPLC) and fluorescence detector (FLD). The method validation results displayed that the detection limits were 0.02-0.09 ng/mL, and the RSDs of intra-day and inter-day precision were less than 4.1 and 6.4 %, respectively. In the target FQs analysis of real honey and milk samples, the recoveries at different fortified concentrations were in the ranges of 88.4 % to 108.6 % with RSD ≤ 5.7 %. The results showed that the proposed method was sensitive, accurate and reliable for the determination of trace FQs in animal-derived foods.


Assuntos
Ciclodextrinas , Mel , Estruturas Metalorgânicas , Animais , Humanos , Estruturas Metalorgânicas/química , Cromatografia Líquida de Alta Pressão/métodos , Leite/química , Mel/análise , Fluoroquinolonas/análise , Extração em Fase Sólida/métodos , Fenômenos Magnéticos
17.
ACS Omega ; 8(48): 45801-45816, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38075842

RESUMO

Hydrogen has been regarded as an important type of renewable energy; however, the usage of pure hydrogen remains a challenge due to the difficulty of transportation and storage. To facilitate the hydrogen usage, it has been proposed to add hydrogen into the existing natural gas pipeline and storage systems, and therefore, the blended hydrogen is injected into the underground gas reservoirs, which is often used for the seasonal storage of natural gas. However, the mechanism of the H2/CH4 mixture storage in the porous formations of underground reservoirs still remains unclear. In this work, we have used molecular simulations to study the storage of the H2/CH4 mixture in dry and wet kaolinite pores of gibbsite and siloxane structures aiming at the clays in the underground porous reservoirs. The results showed that the hydrogen storage density increases as the injected H2 fraction increases in the dry pores but is nearly not affected by the pore size in the range of 5-200 nm. For the H2 fraction below 20%, the percentage of the H2 stored in the pores from the injected gas mixture is higher than that of CH4, and the larger pores are more preferential for H2 storage, but the H2 molecule distribution is more diffused than that of CH4 across the pore. The CH4 molecules adopt the tripod and inclined configurations with an angle of 110° or 70° toward the surface, while the H2 molecules are perpendicular to the surface. But both the molecular structures of H2 and CH4 are not affected by the gibbsite/siloxane structure or water content. However, the siloxane pores have a better selective storage capacity for H2 from the H2/CH4 mixture. The existence of water in the formation weakens both the H2 and CH4 storage densities. For gibbsite pores, the water molecules form a film on the surface, driving the H2 and CH4 molecules to the middle of the pore. But for siloxane pores, the water molecules form water cluster across the pore, leaving less pore volumes for H2 and CH4 storage, which causes a weaker H2 storage capacity than that of the gibbsite pores.

18.
Ophthalmic Res ; 66(1): 1159-1168, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38130005

RESUMO

INTRODUCTION: The aim of the study was to investigate the clinical characteristics and treatment outcomes of the pseudophakic eyes with malignant glaucoma (MG). METHODS: This retrospective case-control study enrolled 53 eyes of 47 patients with primary angle-closure glaucoma having cataract surgery history, including 19 patients (25 eyes) diagnosed with MG and 28 patients (28 eyes) without MG as the match. Among patients diagnosed with MG, 14 patients (18 eyes) underwent zonulo-hyaloido-vitrectomy (ZHV) and the other 5 patients (7 eyes) received conservative treatments. The visual acuity, refraction status, intraocular pressure (IOP), extent of peripheral anterior synechia, classes of anti-glaucoma medications, and ultrasound biomicroscopy (UBM) examination were recorded before cataract surgery, at the diagnosis of MG, and 3 months after ZHV or atropine application, respectively. RESULTS: In the pseudophakic eyes with MG, the IOP cannot be well controlled compared to the matched eyes (27.24 ± 8.72 mm Hg vs. 14.30 ± 2.63 mm Hg, p < 0.001). In addition, there was a difference in the average spherical equivalent refractive error between 2 groups of patients (-2.23 ± 0.84 D in MG vs. -0.12 ± 0.64 D in the matched eyes, p < 0.001). By UBM analysis, the anterior chamber depth (ACD) was shallower in MG than that in the matched eyes (2.34 ± 0.20 mm vs. 3.47 ± 0.29 mm, p < 0.001). The difference between the anterior vault distance of the pseudophakic eyes with MG and that of the matched eyes was also significant (p < 0.001). After treated with ZHV, the IOP was greatly decreased from 27.84 ± 10.14 mm Hg to 15.85 ± 4.41 mm Hg (p < 0.001). The refractive error also changed from -2.11 ± 0.91 D to +0.42 ± 0.99 D (p < 0.001). At the same time, the central ACD was significantly deepened from 2.30 ± 0.39 mm to 3.30 ± 0.31 mm (p < 0.001). CONCLUSION: Uncontrolled IOP and shallow anterior chamber both centrally and peripherally are the primary clinical characteristics for the pseudophakic eyes with MG. An unexpected refractive error or myopic shift for the eyes with PACG after cataract surgery can be an important hint for diagnosis of MG. The typical UBM image is an anterior displacement of the lens-iris diaphragm and a bow-shaped change of the intraocular lens. It is an effective way to treat pseudophakic MG with the ZHV through a peripheral iridectomy.


Assuntos
Catarata , Glaucoma de Ângulo Fechado , Glaucoma , Miopia , Facoemulsificação , Humanos , Estudos Retrospectivos , Estudos de Casos e Controles , Glaucoma de Ângulo Fechado/complicações , Glaucoma de Ângulo Fechado/diagnóstico , Glaucoma de Ângulo Fechado/cirurgia , Glaucoma/cirurgia , Pressão Intraocular , Miopia/cirurgia
19.
J Inflamm Res ; 16: 4885-4898, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37920240

RESUMO

Objective: The mechanisms underlying the chronic rhinosinusitis with nasal polyps (CRSwNP) remained unclear. This study aimed to identify differentially expressed genes (DEGs) in nasal polyps from CRSwNP patients compared to healthy controls and explore key genes and pathways associated with CRSwNP pathophysiology and prognosis. Methods: Three datasets were obtained from the Gene Expression Omnibus database and the intersecting DEGs were identified in CRSwNP patients. Gene Ontology (GO) and protein-protein interaction (PPI) network analysis were applied to investigate the function of DEGs. Nasal specimens from 90 CRSwNP and 45 controls were further collected and qRT-PCR was applied to verify the mRNA expression of hub genes, and moreover, their association with tissue eosinophilia and clinical characteristics in CRSwNP were analyzed. Results: Sixty-eight co-DEGs including 8 upregulated and 60 downregulated genes were identified and GO analyses identified the terms including positive regulation of ERK1 and ERK2 cascade, transforming growth factor beta receptor signaling pathway. PPI networks identified hub genes including EGF, ERBB4, AZGP1, CRISP3 and PIP which were validated to be significantly down-regulated in CRSwNP and showed well diagnostic prediction quality. In addition, lower mRNA expressions level of EGF and AZGP1 in eosinophilic CRSwNP compared with non-eosinophilic CRSwNP were found. Aberrant low expressions of EGF and AZGP1 protein in CRSwNP were identified, and there was good consistency between their mRNA expression level and protein relative expression level. Furthermore, the expressions of EGF and AZGP1 mRNA were significantly correlated with clinical severity parameters. Conclusion: Integrated analysis revealed 68 co-DEGs between nasal polyps and controls and identified hub genes, of which EGF and AZGP1 expression was significantly downregulated in eosinophilic CRSwNP and correlated with disease severity. Downregulation of EGF and AZGP1 may contribute to epithelial barrier dysfunction and type 2 inflammation in CRSwNP, suggesting them as potential diagnostic biomarkers and therapeutic targets.

20.
Nat Prod Res ; : 1-8, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38031803

RESUMO

Callicarpa nudiflora (C. nudiflora) is widely used in the treatment of bleeding related diseases. However, its main material basis has not been fully defined which limits the in-depth study of screening out the material basis of hemostasis and coagulation from C. nudiflor. In this study, the method of spectrum-effect relationship was used to quickly screen the material basis of hemostasis and coagulation. The five compounds related to hemostasis and coagulation were screened as Alyssonoside (P24), Luteolin (P25), Quercetin (P26), Apigenin (P28), Isorhamnetin (P29). And the contribution of these five peaks to hemostasis and coagulation efficacy was P24 > P25 > P28 > P26 > P29.

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