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1.
Nucleic Acids Res ; 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38709875

RESUMEN

Over 150 types of chemical modifications have been identified in RNA to date, with pseudouridine (Ψ) being one of the most prevalent modifications in RNA. Ψ plays vital roles in various biological processes, and precise, base-resolution detection methods are fundamental for deep analysis of its distribution and function. In this study, we introduced a novel base-resolution Ψ detection method named pseU-TRACE. pseU-TRACE relied on the fact that RNA containing Ψ underwent a base deletion after treatment of bisulfite (BS) during reverse transcription, which enabled efficient ligation of two probes complementary to the cDNA sequence on either side of the Ψ site and successful amplification in subsequent real-time quantitative PCR (qPCR), thereby achieving selective and accurate Ψ detection. Our method accurately and sensitively detected several known Ψ sites in 28S, 18S, 5.8S, and even mRNA. Moreover, pseU-TRACE could be employed to measure the Ψ fraction in RNA and explore the Ψ metabolism of different pseudouridine synthases (PUSs), providing valuable insights into the function of Ψ. Overall, pseU-TRACE represents a reliable, time-efficient and sensitive Ψ detection method.

2.
Cell Mol Life Sci ; 81(1): 209, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38710967

RESUMEN

As an integral lysosomal transmembrane protein, transmembrane protein 106B (TMEM106B) regulates several aspects of lysosomal function and is associated with neurodegenerative diseases. The TMEM106B gene mutations lead to lysosomal dysfunction and accelerate the pathological progression of Neurodegenerative diseases. Yet, the precise mechanism of TMEM106B in Neurodegenerative diseases remains unclear. Recently, different research teams discovered that TMEM106B is an amyloid protein and the C-terminal domain of TMEM106B forms amyloid fibrils in various Neurodegenerative diseases and normally elderly individuals. In this review, we discussed the physiological functions of TMEM106B. We also included TMEM106B gene mutations that cause neurodegenerative diseases. Finally, we summarized the identification and cryo-electronic microscopic structure of TMEM106B fibrils, and discussed the promising therapeutic strategies aimed at TMEM106B fibrils and the future directions for TMEM106B research in neurodegenerative diseases.


Asunto(s)
Proteínas de la Membrana , Mutación , Proteínas del Tejido Nervioso , Enfermedades Neurodegenerativas , Humanos , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/química , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neurodegenerativas/genética , Enfermedades Neurodegenerativas/patología , Proteínas del Tejido Nervioso/metabolismo , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/química , Animales , Lisosomas/metabolismo , Lisosomas/genética , Amiloide/metabolismo , Amiloide/genética , Amiloide/química
3.
Biosens Bioelectron ; 257: 116345, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38692247

RESUMEN

Nitrite (NO2-) is present in a variety of foods, but the excessive intake of NO2- can indirectly lead to carcinogenic, teratogenic, mutagenicity and other risks to the human body. Therefore, the detection of NO2- is crucial for maintaining human health. In this study, an integrated array sensor for NO2- detection is developed based on molybdenum single atom material (IMSMo-SAC) using high-resolution electrohydrodynamic (EHD) printing technology. The sensor comprises three components: a printed electrode array, multichannels designed on polydimethylsiloxane (PDMS) and an electronic signal process device with bluetooth. By utilizing Mo-SAC to facilitate electron transfer during the redox reaction, rapid and efficient detection of NO2- can be achieved. The sensor has a wide linear range of 0.1 µM-107.8 mM, a low detection limit of 33 nM and a high sensitivity of 0.637 mA-1mM-1 cm-2. Furthermore, employing this portable array sensor allows simultaneously measurements of NO2- concentrations in six different foods samples with acceptable recovery rates. This array sensor holds great potential for detecting of small molecules in various fields.


Asunto(s)
Técnicas Biosensibles , Diseño de Equipo , Análisis de los Alimentos , Límite de Detección , Molibdeno , Nitritos , Molibdeno/química , Técnicas Biosensibles/instrumentación , Nitritos/análisis , Análisis de los Alimentos/instrumentación , Humanos , Dimetilpolisiloxanos/química , Electrodos , Técnicas Electroquímicas/métodos , Técnicas Electroquímicas/instrumentación , Contaminación de Alimentos/análisis
4.
J Diabetes Investig ; 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38741389

RESUMEN

AIMS/INTRODUCTION: To estimate the prevalence, awareness, treatment, control rate, and influence factors of type 2 diabetes in Fujian province and provide the scientific basic for prevention. MATERIALS AND METHODS: A population-based study with the analysis of binary logistic regression was carried out to estimate the odds ratios of the influencing factor on type 2 diabetes. Data of the Patient-Centered Evaluative Assessment of Cardiac Events (PEACE) in southeast China were used. The study sample originated from 12 counties in Fujian province and included 135,352 permanent residents aged 35-75 years in 2021. RESULTS: The prevalence of type 2 diabetes was 18.32% (24,801/135,352). Among them, 13,921 (56.13%) were aware of their condition, 11,894 (47.96%) were receiving treatment, and 4,537 (18.29%) had achieved control of blood glucose. Multivariate logistic regression analysis showed that older age, men, low-family income, low-education level, urban locality, no medical insurance, and histories of myocardial infarction, stroke, dyslipidemia, hypertension, alcohol consumption, and obesity were associated with a higher prevalence of type 2 diabetes. CONCLUSIONS: The prevalence of type 2 diabetes among residents aged 35-75 years in southeast China is high, whereas the status of its low awareness, treatment and control is severe, warranting a broad-based global strategy, including greater efforts in earlier screening, and more effective and affordable treatment is essential.

5.
Chem Sci ; 15(20): 7659-7666, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38779171

RESUMEN

The development of high-quality organic scintillators encounters challenges primarily associated with the weak X-ray absorption ability resulting from the presence of low atomic number elements. An effective strategy involves the incorporation of halogen-containing molecules into the system through co-crystal engineering. Herein, we synthesized a highly fluorescent dye, 2,5-di(4-pyridyl)thiazolo[5,4-d]thiazole (Py2TTz), with a fluorescence quantum yield of 12.09%. Subsequently, Py2TTz was co-crystallized with 1,4-diiodotetrafluorobenzene (I2F4B) and 1,3,5-trifluoro-2,4,6-triiodobenzene (I3F3B) obtaining Py2TTz-I2F4 and Py2TTz-I3F3. Among them, Py2TTz-I2F4 exhibited exceptional scintillation properties, including an ultrafast decay time (1.426 ns), a significant radiation luminescence intensity (146% higher than Bi3Ge4O12), and a low detection limit (70.49 nGy s-1), equivalent to 1/78th of the detection limit for medical applications (5.5 µGy s-1). This outstanding scintillation performance can be attributed to the formation of halogen-bonding between I2F4B and Py2TTz. Theoretical calculations and single-crystal structures demonstrate the formation of halogen-bond-induced rather than π-π-induced charge-transfer cocrystals, which not only enhances the X-ray absorption ability and material conductivity under X-ray exposure, but also constrains molecular vibration and rotation, and thereby reducing non-radiative transition rate and sharply increasing its fluorescence quantum yields. Based on this, the flexible X-ray film prepared based on Py2TTz-I2F4 achieved an ultrahigh spatial resolution of 26.8 lp per mm, underscoring the superiority of this strategy in developing high-performance organic scintillators.

6.
Cell Rep Med ; 5(5): 101573, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38776874

RESUMEN

Epstein-Barr virus (EBV) is linked to various malignancies and autoimmune diseases, posing a significant global health challenge due to the lack of specific treatments or vaccines. Despite its crucial role in EBV infection in B cells, the mechanisms of the glycoprotein gp42 remain elusive. In this study, we construct an antibody phage library from 100 EBV-positive individuals, leading to the identification of two human monoclonal antibodies, 2B7 and 2C1. These antibodies effectively neutralize EBV infection in vitro and in vivo while preserving gp42's interaction with the human leukocyte antigen class II (HLA-II) receptor. Structural analysis unveils their distinct binding epitopes on gp42, different from the HLA-II binding site. Furthermore, both 2B7 and 2C1 demonstrate potent neutralization of EBV infection in HLA-II-positive epithelial cells, expanding our understanding of gp42's role. Overall, this study introduces two human anti-gp42 antibodies with potential implications for developing EBV vaccines targeting gp42 epitopes, addressing a critical gap in EBV research.


Asunto(s)
Anticuerpos Monoclonales , Epítopos , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Humanos , Herpesvirus Humano 4/inmunología , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/virología , Anticuerpos Monoclonales/inmunología , Epítopos/inmunología , Animales , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Ratones , Antígenos de Histocompatibilidad Clase II/inmunología , Antígenos de Histocompatibilidad Clase II/metabolismo , Proteínas Virales/inmunología , Linfocitos B/inmunología
7.
Arch Toxicol ; 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38758406

RESUMEN

Endometrial carcinoma is one of most common malignant tumors in women, and ferroptosis is closely related to the development and treatment of endometrial carcinoma. The aim of this study was to screen ferroptosis-related genes associated with endometrial carcinoma and predict targeted drugs through bioinformatics. 761 differentially expressed genes were obtained by the dataset GSE63678 from the GEO database, and most of the genes were enriched in the KEGG_CELL_CYCLE and KEGG_OOCYTE_MEIOSIS signaling pathways. 22 ferroptosis-differentially expressed genes were obtained by intersection with the FerrDb database. These genes were involved in biological processes including macromolecular complex assembly and others, and involved in signal pathways including glutathione metabolism, p53 signaling pathway and others. CDKN2A, IDH1, NRAS, TFRC and GOT1 were obtained as hub genes by PPI network analysis. GEPIA showed that CDKN2A, IDH1, NRAS and TFRC were significantly expressed in endometrial carcinoma. Immunohistochemical results showed that CDKN2A, NRAS and TFRC were significantly expressed in endometrial carcinoma clinical tissue samples. The ROC constructed by TCGA database showed that CDKN2A, NRAS and TFRC had significant value in the diagnosis of endometrial carcinoma, and all had prognostic efficacy. 136,572-09-3 BOSS and others were identified as potential targeted drugs for endometrial carcinoma targeting ferroptosis. Our study has shown that ferroptosis-related genes CDKN2A, NRAS and TFRC are diagnostic markers of endometrial carcinoma, and 136,572-09-3 BOSS, methyprylon BOSS, daunorubicin CTD 00005752, nitroglycerin BOSS and dUTP BOSS, IRON BOSS, Imatinib mesylate BOSS, 2-Butanone BOSS, water BOSS, and L-thyroxine BOSS may be potential therapeutic drugs.

8.
Int J Mol Sci ; 25(8)2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38673832

RESUMEN

Phytophthora root rot is a devastating disease of soybean caused by Phytophthora sojae. However, the resistance mechanism is not yet clear. Our previous studies have shown that GmAP2 enhances sensitivity to P. sojae in soybean, and GmMYB78 is downregulated in the transcriptome analysis of GmAP2-overexpressing transgenic hairy roots. Here, GmMYB78 was significantly induced by P. sojae in susceptible soybean, and the overexpressing of GmMYB78 enhanced sensitivity to the pathogen, while silencing GmMYB78 enhances resistance to P. sojae, indicating that GmMYB78 is a negative regulator of P. sojae. Moreover, the jasmonic acid (JA) content and JA synthesis gene GmAOS1 was highly upregulated in GmMYB78-silencing roots and highly downregulated in overexpressing ones, suggesting that GmMYB78 could respond to P. sojae through the JA signaling pathway. Furthermore, the expression of several pathogenesis-related genes was significantly lower in GmMYB78-overexpressing roots and higher in GmMYB78-silencing ones. Additionally, we screened and identified the upstream regulator GmbHLH122 and downstream target gene GmbZIP25 of GmMYB78. GmbHLH122 was highly induced by P. sojae and could inhibit GmMYB78 expression in resistant soybean, and GmMYB78 was highly expressed to activate downstream target gene GmbZIP25 transcription in susceptible soybean. In conclusion, our data reveal that GmMYB78 triggers soybean sensitivity to P. sojae by inhibiting the JA signaling pathway and the expression of pathogenesis-related genes or through the effects of the GmbHLH122-GmMYB78-GmbZIP25 cascade pathway.


Asunto(s)
Ciclopentanos , Resistencia a la Enfermedad , Regulación de la Expresión Génica de las Plantas , Glycine max , Oxilipinas , Phytophthora , Enfermedades de las Plantas , Proteínas de Plantas , Factores de Transcripción , Glycine max/genética , Glycine max/microbiología , Glycine max/parasitología , Glycine max/metabolismo , Phytophthora/patogenicidad , Resistencia a la Enfermedad/genética , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/parasitología , Enfermedades de las Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ciclopentanos/metabolismo , Oxilipinas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Plantas Modificadas Genéticamente , Raíces de Plantas/microbiología , Raíces de Plantas/genética , Raíces de Plantas/parasitología , Raíces de Plantas/metabolismo
9.
Toxicol Sci ; 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38565259

RESUMEN

Peritubular macrophages (PTMφ) are predominantly localized near spermatogonial stem cells in the testis. We previously revealed that exposure of peripubertal male Fischer rats to mono-(2-ethylhexyl) phthalate (MEHP) leads to increased PTMφs in the testis. The mechanisms that trigger increases in PTMφs in the testis are poorly understood. However, MEHP exposure is known to both induce spermatocyte apoptosis and to perturb the blood-testis barrier (BTB). This study aims to elucidate the association between the disruption of BTB and the increases of PTMφs in the testis by comparing the effects observed with MEHP to two other testicular toxicants with variable effects on the BTB and subtype of germ cell undergoing apoptosis. Methoxyacetic acid (MAA) acts directly on spermatocytes and does not affect BTB function, while cadmium chloride (CdCl2) induces profound injury to BTB. The results indicated that MAA exposure significantly increased spermatocyte apoptosis, while no significant changes in the numbers of PTMφs in the testis occurred. In contrast, CdCl2 exposure disrupted BTB function and increased the abundance of PTMφs in the testis. To further investigate whether MEHP-induced changes in BTB integrity accounted for the increase in PTMφs, a plasmid for LG3/4/5, the functional component of laminin-alpha 2, was overexpressed in the testis to stabilize BTB integrity before MEHP exposure. The results showed that LG3/4/5 overexpression substantially reduced the ability of MEHP to compromise BTB integrity and prevented the increase in PTMφ numbers after MEHP exposure. These results indicate that BTB disruption is necessary to increase PTMφs in the testis induced by toxicants.

10.
Front Plant Sci ; 15: 1361959, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38576787

RESUMEN

Artemisinin biosynthesis, unique to Artemisia annua, is suggested to have evolved from the ancestral costunolide biosynthetic pathway commonly found in the Asteraceae family. However, the evolutionary landscape of this process is not fully understood. The first oxidase in artemisinin biosynthesis, CYP71AV1, also known as amorpha-4,11-diene oxidase (AMO), has specialized from ancestral germacrene A oxidases (GAOs). Unlike GAO, which exhibits catalytic promiscuity toward amorpha-4,11-diene, the natural substrate of AMO, AMO has lost its ancestral activity on germacrene A. Previous studies have suggested that the loss of the GAO copy in A. annua is responsible for the abolishment of the costunolide pathway. In the genome of A. annua, there are two copies of AMO, each of which has been reported to be responsible for the different product profiles of high- and low-artemisinin production chemotypes. Through analysis of their tissue-specific expression and comparison of their sequences with those of other GAOs, it was discovered that one copy of AMO (AMOHAP) exhibits a different transcript compared to the reported artemisinin biosynthetic genes and shows more sequence similarity to other GAOs in the catalytic regions. Furthermore, in a subsequent in vitro enzymatic assay, the recombinant protein of AMOHAP unequivocally demonstrated GAO activity. This result clearly indicates that AMOHAP is a GAO rather than an AMO and that its promiscuous activity on amorpha-4,11-diene has led to its misidentification as an AMO in previous studies. In addition, the divergent expression pattern of AMOHAP compared to that of the upstream germacrene A synthase may have contributed to the abolishment of costunolide biosynthesis in A. annua. Our findings reveal a complex evolutionary landscape in which the emergence of a new metabolic pathway replaces an ancestral one.

11.
Prev Med Rep ; 41: 102697, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38560595

RESUMEN

Background: Healthy lifestyles are effective means to reduce major cardiovascular events. However, little is known about the association of healthy lifestyles with development of carotid atherosclerosis at the early stage of cardiovascular diseases (CVDs). Methods: We enrolled participants from Fujian province in the China PEACE MPP project. We calculated a healthy lifestyle score by adherence to non-smoking, sufficient physical activity, healthy diet and healthy body mass index. Cox proportional hazards regression models and restricted cubic splines (RCS) were used to explore the association between the healthy lifestyles and rapid progression of carotid plaque. Results: 8379 participants were included (mean age: 60.6 ± 8.3 years, 54.6 % female), with a median follow-up of 1.2 years (inter quartile range: 1.0-1.6). RCS showed a significant inverse association between the healthy lifestyle score and progression of carotid plaque. Participants with "intermediate" (HR: 0.72 [95 % confidence interval (CI): 0.65-0.80]) or "ideal" (HR: 0.68 [0.59-0.78]) adherence to healthy lifestyles had a lower risk of progression of carotid plaque compared to those with "poor" adherence. Age, sex, occupation, income, residence type and metabolic status were significant factors influencing the relationship. Farmers benefited more in non-smoking and sufficient physical activity compared to non-farmers, and participants with lower income or without dyslipidaemia benefited more in sufficient physical activity and healthy diet compared to their counterparts (p-for-interaction < 0.05). Conclusions: Healthy lifestyles were associated with lower risk of progression of carotid plaque in populations with atherosclerosis. Promotion of healthy lifestyles from the early stage of carotid atherosclerosis could reduce the burden of CVDs in China.

12.
Opt Express ; 32(7): 11583-11599, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38571002

RESUMEN

A multiple sub-pupil ultra-spectral imaging system designed with a single spectrometer and detector can simultaneously detect multiple-channel spectra with ultra-high spectral resolution. However, due to using a prism in the system's front end, the nonlinear dispersion introduces spectral line tilt in the imaging spectra. This phenomenon can lead to bias in the final spectral data. To eliminate this issue, we propose a new design by introducing a second prism to correct this spectral tilt in the system. The angle of spectral line tilt generated by the nonlinear dispersion of the first prism is derived. It provides the theoretical basis for characterizing the second complementary prism. Finally, a UV multiple sub-pupil ultra-spectral imaging system is designed. The system employs two pupil separation prisms and one flat panel array to segment the pupil in three channels, each operating within spectral ranges of 180∼210 nm, 275∼305 nm, and 370∼400 nm, respectively. The spectral resolutions in all three channels are better than 0.1 nm. The corrected spectral line tilt is less than 1/3 of a pixel in the two channels with pupil separation prisms. At a Nyquist frequency of 30 lp/mm, the modulation transfer functions of all three channels are greater than 0.7, ensuring imaging quality. The design results indicate that the method proposed in this paper, utilizing complementary prisms, can effectively correct the spectral line tilt caused by the nonlinear dispersion of the pupil separation prisms. This design approach can be a reference for developing multiple sub-pupil ultra-spectral imaging systems.

13.
Chem Commun (Camb) ; 60(33): 4479-4482, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38564258

RESUMEN

We found that the N6 methyl group of N6-methyladenine is able to hinder the methylation of N6-methyladenine at the N1 position by DMS. Based on this, we have devised a novel method for detecting N6-methyladenine, which was successfully applied to identify specific m6A loci in 28S rRNA.


Asunto(s)
Metilación , ARN Ribosómico 28S
14.
J Org Chem ; 89(8): 5905-5910, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38579179

RESUMEN

The total syntheses of (±)-quebrachamine and (±)-kopsiyunnanine D are reported. Key transformations include an intermolecular Horner-Wadsworth-Emmons olefination to merge the two fragments convergently and an intramolecular Mitsunobu reaction to introduce the synthetically challenging nine-membered azonane ring efficiently.

15.
PLoS One ; 19(4): e0301986, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38626158

RESUMEN

The production of sludge-based biochar to recover phosphorus (P) from wastewater and reuse the recovered phosphorus as agricultural fertilizer is a preferred process. This article mainly studied the removal of phosphate (PO4-P) from aqueous solution by synthesizing sludge-based biochar (MgSBC-0.1) from anaerobic fermentation sludge treated with magnesium (Mg)-loading-modification, and compared it with unmodified sludge-based biochar (SBC). The physicochemical properties, adsorption efficiency, and adsorption mechanism of MgSBC-0.1 were studied. The results showed that the surface area of MgSBC-0.1 synthesized increased by 5.57 times. The material surface contained MgO, Mg(OH)2, and CaO nanoparticles. MgSBC-0.1 can effectively remove phosphate in the initial solution pH range of 3.00-7.00, with a fitted maximum phosphorus adsorption capacity of 379.52 mg·g-1. The adsorption conforms to the pseudo second-order kinetics model and Langmuir isotherm adsorption curve. The characterization of the adsorbed composite material revealed the contribution of phosphorus crystal deposition and electrostatic attraction to phosphorus absorption.


Asunto(s)
Fosfatos , Contaminantes Químicos del Agua , Fosfatos/química , Magnesio , Aguas del Alcantarillado , Adsorción , Carbón Orgánico , Fósforo/química , Cinética , Contaminantes Químicos del Agua/análisis
16.
Mol Plant Pathol ; 25(4): e13452, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38619823

RESUMEN

Phytophthora root and stem rot of soybean (Glycine max), caused by the oomycete Phytophthora sojae, is an extremely destructive disease worldwide. In this study, we identified GmEIL1, which encodes an ethylene-insensitive3 (EIN3) transcription factor. GmEIL1 was significantly induced following P. sojae infection of soybean plants. Compared to wild-type soybean plants, transgenic soybean plants overexpressing GmEIL1 showed enhanced resistance to P. sojae and GmEIL1-silenced RNA-interference lines showed more severe symptoms when infected with P. sojae. We screened for target genes of GmEIL1 and confirmed that GmEIL1 bound directly to the GmERF113 promoter and regulated GmERF113 expression. Moreover, GmEIL1 positively regulated the expression of the pathogenesis-related gene GmPR1. The GmEIL1-regulated defence response to P. sojae involved both ethylene biosynthesis and the ethylene signalling pathway. These findings suggest that the GmEIL1-GmERF113 module plays an important role in P. sojae resistance via the ethylene signalling pathway.


Asunto(s)
Fabaceae , Phytophthora , Factores de Transcripción/genética , Glycine max/genética , Etilenos , Plantas Modificadas Genéticamente
17.
Quant Imaging Med Surg ; 14(4): 2816-2827, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38617137

RESUMEN

Background: Osteoporosis, a disease stemming from bone metabolism irregularities, affects approximately 200 million people worldwide. Timely detection of osteoporosis is pivotal in grappling with this public health challenge. Deep learning (DL), emerging as a promising methodology in the field of medical imaging, holds considerable potential for the assessment of bone mineral density (BMD). This study aimed to propose an automated DL framework for BMD assessment that integrates localization, segmentation, and ternary classification using various dominant convolutional neural networks (CNNs). Methods: In this retrospective study, a cohort of 2,274 patients underwent chest computed tomography (CT) was enrolled from January 2022 to June 2023 for the development of the integrated DL system. The study unfolded in 2 phases. Initially, 1,025 patients were selected based on specific criteria to develop an automated segmentation model, utilizing 2 VB-Net networks. Subsequently, a distinct cohort of 902 patients was employed for the development and testing of classification models for BMD assessment. Then, 3 distinct DL network architectures, specifically DenseNet, ResNet-18, and ResNet-50, were applied to formulate the 3-classification BMD assessment model. The performance of both phases was evaluated using an independent test set consisting of 347 individuals. Segmentation performance was evaluated using the Dice similarity coefficient; classification performance was appraised using the receiver operating characteristic (ROC) curve. Furthermore, metrics such as the area under the curve (AUC), accuracy, and precision were meticulously calculated. Results: In the first stage, the automatic segmentation model demonstrated excellent segmentation performance, with mean Dice surpassing 0.93 in the independent test set. In the second stage, both the DenseNet and ResNet-18 demonstrated excellent diagnostic performance in detecting bone status. For osteoporosis, and osteopenia, the AUCs were as follows: DenseNet achieved 0.94 [95% confidence interval (CI): 0.91-0.97], and 0.91 (95% CI: 0.87-0.94), respectively; ResNet-18 attained 0.96 (95% CI: 0.92-0.98), and 0.91 (95% CI: 0.87-0.94), respectively. However, the ResNet-50 model exhibited suboptimal diagnostic performance for osteopenia, with an AUC value of only 0.76 (95% CI: 0.69-0.80). Alterations in tube voltage had a more pronounced impact on the performance of the DenseNet. In the independent test set with tube voltage at 100 kVp images, the accuracy and precision of DenseNet decreased on average by approximately 14.29% and 18.82%, respectively, whereas the accuracy and precision of ResNet-18 decreased by about 8.33% and 7.14%, respectively. Conclusions: The state-of-the-art DL framework model offers an effective and efficient approach for opportunistic osteoporosis screening using chest CT, without incurring additional costs or radiation exposure.

18.
Int J Biol Macromol ; 267(Pt 1): 131372, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38580024

RESUMEN

Clinically, open wounds caused by accidental trauma and surgical lesion resection are easily infected by external bacteria, hindering wound healing. Antibacterial photodynamic therapy has become a promising treatment strategy for wound infection. In this study, a novel antibacterial nanocomposite material (QMC NPs) was synthesized by curcumin, quaternized chitosan and mesoporous polydopamine nanoparticles. The results showed that 150 µg/mL QMC NPs had good biocompatibility and exerted excellent antibacterial activity against Staphylococcus aureus and Escherichia coli after blue laser irradiation (450 nm, 1 W/cm2). In vivo, QMC NPs effectively treated bacterial infection and accelerated the healing of infected wounds in mice.


Asunto(s)
Antibacterianos , Quitosano , Curcumina , Escherichia coli , Indoles , Nanopartículas , Polímeros , Staphylococcus aureus , Quitosano/química , Quitosano/farmacología , Indoles/química , Indoles/farmacología , Curcumina/farmacología , Curcumina/química , Polímeros/química , Polímeros/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Nanopartículas/química , Animales , Ratones , Staphylococcus aureus/efectos de los fármacos , Porosidad , Escherichia coli/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Cicatrización de Heridas/efectos de los fármacos , Infecciones Bacterianas/tratamiento farmacológico
19.
Microbiol Res ; 284: 127728, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38643523

RESUMEN

The continued rise of drug-resistant bacterial infections heightens a threat of a pandemic of antimicrobial resistance to the global health. The urgency of infection control against antimicrobial-resistant bacteria is evident. Ferroptosis, a newly defined form of iron-dependent cell death characterized by lipid peroxidation, has garnered substantial interest since this programmed cell death was associated with pathophysiological processes of many diseases. Exploring whether ferroptosis could be utilized in infectious diseases holds significant importance for discovering novel antimicrobial approaches. Recent years have witnessed significant progress with respect to elucidating the mechanisms that govern ferroptosis induction and its roles in bacterial pathogenesis and host-pathogen interactions. In this review, we discuss the mechanisms of targeting ferroptosis and/or iron homeostasis for the control of antimicrobial-resistant bacterial infections. These implications may inform and enable effective therapeutic strategies against pathogen infection and provide novel insights into the potential applications of ferroptosis to address the global bacterial resistance crisis.


Asunto(s)
Antibacterianos , Bacterias , Infecciones Bacterianas , Ferroptosis , Interacciones Huésped-Patógeno , Hierro , Ferroptosis/efectos de los fármacos , Humanos , Infecciones Bacterianas/microbiología , Hierro/metabolismo , Bacterias/efectos de los fármacos , Bacterias/metabolismo , Antibacterianos/farmacología , Peroxidación de Lípido , Animales , Farmacorresistencia Bacteriana , Homeostasis
20.
J Nat Med ; 78(3): 664-676, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38427210

RESUMEN

This study investigates the cardioprotective effects of Paeoniflorin (PF) on left ventricular remodeling following acute myocardial infarction (AMI) under conditions of hypobaric hypoxia. Left ventricular remodeling post-AMI plays a pivotal role in exacerbating heart failure, especially at high altitudes. Using a rat model of AMI, the study aimed to evaluate the cardioprotective potential of PF under hypobaric hypoxia. Ninety male rats were divided into four groups: sham-operated controls under normoxia/hypobaria, an AMI model group, and a PF treatment group. PF was administered for 4 weeks after AMI induction. Left ventricular function was assessed using cardiac magnetic resonance imaging. Biochemical assays of cuproptosis, oxidative stress, apoptosis, inflammation, and fibrosis were performed. Results demonstrated PF significantly improved left ventricular function and remodeling after AMI under hypobaric hypoxia. Mechanistically, PF decreased FDX1/DLAT expression and serum copper while increasing pyruvate. It also attenuated apoptosis, inflammation, and fibrosis by modulating Bcl-2, Bax, NLRP3, and oxidative stress markers. Thus, PF exhibits therapeutic potential for left ventricular remodeling post-AMI at high altitude by inhibiting cuproptosis, inflammation, apoptosis and fibrosis. Further studies are warranted to optimize dosage and duration and elucidate PF's mechanisms of action.


Asunto(s)
Glucósidos , Hipoxia , Monoterpenos , Infarto del Miocardio , Estrés Oxidativo , Ratas Sprague-Dawley , Remodelación Ventricular , Animales , Glucósidos/farmacología , Glucósidos/uso terapéutico , Remodelación Ventricular/efectos de los fármacos , Masculino , Ratas , Monoterpenos/farmacología , Monoterpenos/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Hipoxia/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Modelos Animales de Enfermedad , Función Ventricular Izquierda/efectos de los fármacos
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