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1.
Transl Lung Cancer Res ; 13(8): 2023-2037, 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39263021

RESUMO

Background: Notwithstanding the rapid developments in precision medicine in recent years, lung cancer still has a low survival rate, especially lung squamous cell cancer (LUSC). The tumor microenvironment (TME) plays an important role in the progression of lung cancer, in which high neutrophil levels are correlated with poor prognosis, potentially due to their interactions with tumor cells via pro-inflammatory cytokines and chemokines. However, the precise mechanisms of how neutrophils influence lung cancer remain unclear. This study aims to explore these mechanisms and develop a prognosis predictive model in LUSC, addressing the knowledge gap in neutrophil-related cancer pathogenesis. Methods: LUSC datasets from the Xena Hub and Gene Expression Omnibus (GEO) databases were used, comprising 473 tumor samples and 195 tumor samples, respectively. Neutrophil contents in these samples were estimated using CIBERSORT, xCell, and microenvironment cell populations (MCP) counter tools. Differentially expressed genes (DEGs) were identified using DEseq2, and a weighted gene co-expression network analysis (WGCNA) was performed to identify neutrophil-related genes. A least absolute shrinkage and selection operator (LASSO) Cox regression model was constructed for prognosis prediction, and the model's accuracy was validated using Kaplan-Meier survival curves and time-dependent receiver operating characteristic (ROC) curves. Additionally, genomic changes, immune correlations, drug sensitivity, and immunotherapy response were analyzed to further validate the model's predictive power. Results: Neutrophil content was significantly higher in adjacent normal tissue compared to LUSC tissue (P<0.001). High neutrophil content was associated with worse overall survival (OS) (P=0.02), disease-free survival (DFS) (P=0.02), and progression-free survival (PFS) (P=0.03) using different software estimates. Nine gene modules were identified, with blue and yellow modules showing strong correlations with neutrophil prognosis (P<0.001). Eight genes were selected for the prognostic model, which accurately predicted 1-, 3-, and 5-year survival in both the training set [area under the curve (AUC) value =0.60, 0.63, 0.66, respectively] and validation set (AUC value =0.58, 0.58, 0.59, respectively), with significant prognosis differences between high- and low-risk groups (P<0.001). The model's independent prognostic factors included risk group, pathologic M stage, and tumor stage (P<0.05). A further molecular mechanism analysis revealed differences between risk groups were revealed in immune checkpoint and human leukocyte antigen (HLA) gene expression, hallmark pathways, drug sensitivity, and immunotherapy responses. Conclusions: This study established a risk-score model that effectively predicts the prognosis of LUSC patients and sheds light on the molecular mechanisms involved. The findings enhance the understanding of neutrophil-tumor interactions, offering potential targets for personalized treatments. However, further experimental validation and clinical studies are required to confirm these findings and address study limitations, including reliance on public databases and focus on a specific lung cancer subtype.

2.
Biochim Biophys Acta Mol Cell Res ; 1871(7): 119817, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39159683

RESUMO

Intermittent fasting exerts a profound beneficial influence on a spectrum of diseases through various mechanisms including regulation of immune responses, elimination of senescent- and pathogenic cells and improvement of stem cell-based tissue regeneration in a disease- and tissue-dependent manner. Our previous study demonstrated that alternate-day fasting (ADF) led to alleviation of xerostomia and sialadenitis in non-obese diabetic (NOD) mice, a well-defined model of Sjögren's syndrome (SS). This present study delved into the previously unexplored impacts of ADF in this disease setting and revealed that ADF increases the proportion of salivary gland stem cells (SGSCs), defined as the EpCAMhi cell population among the lineage marker negative submandibular gland (SMG) cells. Furthermore, ADF downregulated the expression of p16INK4a, a cellular senescence marker, which was concomitant with increased apoptosis and decreased expression and activity of NLRP3 inflammasomes in the SMGs, particularly in the SGSC-residing ductal compartments. RNA-sequencing analysis of purified SGSCs from NOD mice revealed that the significantly downregulated genes by ADF were mainly associated with sugar metabolism, amino acid biosynthetic process and MAPK signaling pathway, whereas the significantly upregulated genes related to fatty acid metabolic processes, among others. Collectively, these findings indicate that ADF increases the SGSC proportion, accompanied by a modulation of the SGSC property and a switch from sugar- to fatty acid-based metabolism. These findings lay the foundation for further investigation into the functionality of SGSCs influenced by ADF and shed light on the cellular and molecular mechanisms by which ADF exerts beneficial actions on salivary gland restoration in SS.


Assuntos
Jejum , Camundongos Endogâmicos NOD , Glândulas Salivares , Síndrome de Sjogren , Células-Tronco , Animais , Síndrome de Sjogren/metabolismo , Síndrome de Sjogren/patologia , Síndrome de Sjogren/genética , Camundongos , Glândulas Salivares/metabolismo , Glândulas Salivares/patologia , Células-Tronco/metabolismo , Glândula Submandibular/metabolismo , Glândula Submandibular/patologia , Modelos Animais de Doenças , Feminino , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Inflamassomos/metabolismo , Apoptose
3.
Mol Immunol ; 174: 47-56, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39197397

RESUMO

SjÓ§gren's syndrome (SS), also known as Sjögren's disease, is a chronic autoimmune condition predominantly affecting the salivary and lacrimal glands. The disease is driven by autoimmune responses involving the activation and actions of major innate- and adaptive immune cell subsets. However, the specific characteristics and roles of regulatory T cells (Tregs) in SS remain elusive. This study seeks to clarify the main phenotypic and functional attributes of Tregs in the salivary glands and their draining lymph nodes in murine models of SS. Our flow cytometric analysis revealed that Tregs in the salivary gland-draining lymph nodes of female non-obese diabetic (NOD) mice, a spontaneous model of SS, exhibited a greater proportion of activated Tregs and fewer resting Tregs compared to Balb/c mice. Furthermore, Tregs from the salivary gland-draining lymph nodes of female C57BL/6.NOD-Aec1Aec2 (B6.NOD-Aec) mice, a model for primary SS, demonstrated significantly lower IL-10 production but markedly higher IFNγ- and IL-17 production than their C57BL/6 counterparts. Additionally, treatment of C57BL/6 Tregs with IL-7, a cytokine critical for SS pathogenesis, resulted in diminished IL-10 production and enhanced IFNγ and IL-17 production in these cells. Notably, the alterations in B6.NOD-Aec Tregs also included an increased expression of the immune-inhibitory molecule CTLA-4 compared to the C57BL/6 Tregs. Intriguingly, in vitro co-cultures of Tregs with conventional CD4 T cells and other key immune populations from lymph nodes indicated that Tregs from salivary gland-draining lymph nodes of both B6.NOD-Aec and C57BL/6 strains exhibited comparable and limited immunosuppressive effects on the proliferation and function of conventional CD4 T cells. The ability of B6.NOD-Aec Tregs to directly inflict damages to salivary gland epithelial tissues and contribute to SS pathologies through IFNγ and IL-17 that they produce warrants further investigations. In addition, enhancing the relatively weak immunosuppressive capacities of these Tregs may also serve as a viable strategy to alleviate the SS phenotype in the mouse models and potentially in patients.


Assuntos
Modelos Animais de Doenças , Linfonodos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Glândulas Salivares , Síndrome de Sjogren , Linfócitos T Reguladores , Animais , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/patologia , Linfócitos T Reguladores/imunologia , Feminino , Camundongos , Glândulas Salivares/imunologia , Glândulas Salivares/patologia , Linfonodos/imunologia , Linfonodos/patologia , Interferon gama/imunologia , Interferon gama/metabolismo , Interleucina-17/imunologia , Interleucina-10/imunologia , Interleucina-7/imunologia
4.
Adv Mater ; : e2408681, 2024 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-39155581

RESUMO

Direct production of high-purity ethylene from acetylene using renewable energy through electrocatalytic semi-hydrogenation presents a promising alternative to traditional thermocatalytic processes. However, the low conversion of acetylene results in a significant amount of acetylene impurities in the product, necessitating additional purification steps. Herein, a tandem electrocatalytic system that integrates acetylene electrolyzer and zinc-acetylene battery units for high-purity ethylene production is designed. The ultrathin CuO nanoribbons with enriched oxygen vacancies (CuO1-x NRs) as electrocatalysts achieve a remarkable 93.2% Faradaic efficiency of ethylene at an ampere-level current density of 1.0 A cm-2 in an acetylene electrolyzer, and the power density reaches 3.8 mW cm-2 in a zinc-acetylene battery under acetylene stream. Moreover, the tandem electrocatalysis system delivers a single-pass acetylene conversion of 99.998% and ethylene selectivity of 96.1% at a high current of 1.4 A. Experimental data and calculations demonstrate that the presence of oxygen vacancies accelerates water dissociation to produce active hydrogen atoms while preventing the over-hydrogenation of ethylene. Furthermore, techno-economic analysis reveals that the tandem system can dramatically reduce the overall ethylene production cost compared to the conventional thermocatalytic processes. A novel strategy for complete acetylene-to-ethylene conversion under mild conditions, establishing a non-petroleum route for the production of ethylene is reported.

5.
Front Vet Sci ; 11: 1424073, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39109341

RESUMO

Introduction: As effective growth-promoters and immune-modulators, yeast fermented products have shown positive effects in ruminants. To explore the mechanisms of yeast culture promoting growth and regulating immunity, this study investigated the effects of yeast culture, and ß-glucan as one of its main active ingredients, on the growth performance, immune function, antioxidant capacity and hormonal profile in Mongolian ram lambs. Methods: One hundred and five Mongolian ram lambs were randomly assigned to 3 groups, with 35 replicates in each group. The dietary treatments were: total mixed ration (TMR) as the control group, TMR supplemented with 50-70 g/kg yeast culture (YC) or 75 mg/kg ß-glucan. The test period was 137 days. All the sheep were weighed and 6 serum samples were collected in each group on days 0, 30, 60, 90 and 130, respectively. Results: The results showed that both YC and ß-glucan could promote the growth performance with increased average daily gain and decreased feed to weight gain ratio. Moreover, these two feed additives facilitated the immune function by selectively increasing the serum levels of lysozyme, IgG, IgM, INF-γ, TNF-α and some interleukins (IL-1ß, IL-2, IL-6 and IL-8); ameliorated the antioxidant capacity with higher total antioxidant capacity and enzyme activities of catalase and glutathione peroxidase; altered the metabolism-associated hormone levels with higher growth hormone and thyroid hormone T3 but lower cortisol and insulin. Discussion: In conclusion, both YC and ß-glucan could improve the growth performance, immune function and antioxidant capacity, and regulate the serum levels of metabolism-associated hormones, thus exerting effects of promoting growth and improving immune function. Therefore, YC could be considered as a suitable potential alternative strategy to antibiotics and be used as an animal feed additive. This article provides a theoretical basis for the clinical application of such yeast fermented preparations in mutton sheep husbandry.

6.
ACS Appl Mater Interfaces ; 16(26): 33917-33927, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961575

RESUMO

Despite the remarkable progress of perovskite solar cells (PSCs), the substantial inherent defects within perovskites restrict the achievement of higher efficiency and better long-term stability. Herein, we introduced a novel multifunctional imidazole analogue, namely, 1-benzyl-3-methylimidazolium bromide (BzMIMBr), into perovskite precursors to reduce bulk defects and inhibit ion migration in inverted PSCs. The electron-rich environment of -N- in the BzMIMBr structure, which is attributed to the electron-rich adjacent benzene ring-conjugated structure, effectively passivates the uncoordinated Pb2+ cations. Moreover, the interaction between the BzMIMBr additive and perovskite can effectively hinder the deprotonation of formamidinium iodide/methylammonium iodide (FAI/MAI), extending the crystallization time and improving the quality of the perovskite precursors and films. This interaction also effectively inhibits ion migration to subsequent deposited films, leading to a noteworthy decrease in trap states. Various characterization studies show that the BzMIMBr-doped films exhibit superior film morphology and surface uniformity and reduced nonradiative carrier recombination, consequently enhancing crystallinity by reducing bulk/surface defects. The PSCs fabricated on the BzMIMBr-doped perovskite thin film exhibit a power conversion efficiency of 23.37%, surpassing that of the pristine perovskite device (20.71%). Additionally, the added BzMIMBr substantially increased the hydrophobicity of perovskite, as unencapsulated devices still retained 93% of the initial efficiency after 1800 h of exposure to air (45% relative humidity).

7.
Mol Immunol ; 173: 20-29, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39018744

RESUMO

SjÓ§gren's syndrome is a systemic autoimmune disease primarily targeting the salivary and lacrimal glands. Our previous investigations have shown that administration of interleukin-22 (IL-22), an IL-10 family cytokine known for its complex and context-dependent effects on tissues, either protective- or detrimental, to salivary glands leads to hypofunction and pathological changes of salivary glands in C57BL/6 mice and in non-obese diabetic (NOD) mice, the latter being a commonly used model of SjÓ§gren's syndrome. This study aims to delineate the pathophysiological roles of endogenously produced IL-22 in the development of salivary gland pathologies and dysfunction associated with SjÓ§gren's disease in the NOD mouse model. Our results reveal that neutralizing IL-22 offered a protective effect on salivary gland function without significantly affecting the immune cell infiltration of salivary glands or the autoantibody production. Blockade of IL-22 reduced the levels of phosphorylated STAT3 in salivary gland tissues of NOD mice, while its administration to salivary glands had the opposite effect. Correspondingly, the detrimental impact of exogenously applied IL-22 on salivary glands was almost completely abrogated by a specific STAT3 inhibitor. Moreover, IL-22 blockade led to a downregulation of protein amounts of Ten-Eleven-Translocation 2, a methylcytosine dioxygenase critical for mediating interferon-induced responses, in salivary gland epithelial cells. IL-22 neutralization also exerted a protective effect on the salivary gland epithelial cells that express high levels of surface EpCAM and bear the stem cell potential, and IL-22 treatment in vitro hampered the survival/expansion of these salivary gland stem cells, indicating a direct negative impact of IL-22 on these cells. In summary, this study has uncovered a critical pathogenic role of the endogenous IL-22 in the pathogenesis of Sjögren's disease-characteristic salivary gland dysfunction and provided initial evidence that this effect is dependent on STAT3 activation and potentially achieved through fostering Tet2-mediated interferon responses in salivary gland epithelial cells and negatively affecting the EpCAMhigh salivary gland stem cells.


Assuntos
Interleucina 22 , Glândulas Salivares , Síndrome de Sjogren , Animais , Feminino , Humanos , Camundongos , Modelos Animais de Doenças , Interleucinas/imunologia , Interleucinas/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Glândulas Salivares/patologia , Glândulas Salivares/imunologia , Glândulas Salivares/metabolismo , Síndrome de Sjogren/imunologia , Fator de Transcrição STAT3/metabolismo
8.
Bio Protoc ; 14(12): e5016, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38948263

RESUMO

Human babesiosis is a tick-borne disease caused by Babesia pathogens. The disease, which presents with malaria-like symptoms, can be life-threatening, especially in individuals with weakened immune systems and the elderly. The worldwide prevalence of human babesiosis has been gradually rising, prompting alarm among public health experts. In other pathogens, genetic techniques have proven to be valuable tools for conducting functional studies to understand the importance of specific genes in development and pathogenesis as well as to validate novel cellular targets for drug discovery. Genetic manipulation methods have been established for several non-human Babesia and Theileria species and, more recently, have begun to be developed for human Babesia parasites. We have previously reported the development of a method for genetic manipulation of the human pathogen Babesia duncani. This method is based on positive selection using the hDHFR gene as a selectable marker, whose expression is regulated by the ef-1aB promoter, along with homology regions that facilitate integration into the gene of interest through homologous recombination. Herein, we provide a detailed description of the steps needed to implement this strategy in B. duncani to study gene function. It is anticipated that the implementation of this method will significantly improve our understanding of babesiosis and facilitate the development of novel and more effective therapeutic strategies for the treatment of human babesiosis. Key features This protocol provides an effective means of transfection of B. duncani, enabling genetic manipulation and editing to gain further insights into its biology and pathogenesis. The protocol outlined here for the electroporation of B. duncani represents an advancement over previous methods used for B. bovis [1]. Improvements include higher volume of culture used during the electroporation step and an enhancement in the number of electroporation pulses. These modifications likely enhance the efficiency of gene editing in B. duncani, allowing for quicker and more effective selection of transgenic parasites.

9.
Microorganisms ; 12(6)2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38930523

RESUMO

Babesia duncani (B. duncani), a protozoan parasite prevalent in North America, is a significant threat for human health. Given the regulatory role of pyruvate kinase I (PyK I) in glycolytic metabolism flux and ATP generation, PyK I has been considered the target for drug intervention for a long time. In this study, B. duncani PyK I (BdPyK I) was successfully cloned, expressed, and purified. Polyclonal antibodies were confirmed to recognize the native BdPyK I protein (56 kDa) using Western blotting. AlphaFold software predicted the three-dimensional structure of BdPyK I, and molecular docking with small molecules was conducted to identify potential binding sites of inhibitor on BdPyK I. Moreover, inhibitory effects of six inhibitors (tannic acid, apigenin, shikonin, PKM2 inhibitor, rosiglitazone, and pioglitazone) on BdPyK I were examined under the optimal enzymatic conditions of 3 mM PEP and 3 mM ADP, and significant activity reduction was found. Enzyme kinetics and growth inhibition assays further confirmed the reliability of these inhibitors, with PKM2 inhibitor, tannic acid, and apigenin exhibiting the highest selectivity index as specific inhibitors for B. duncani. Subsequently, key amino acid residues were mutated in both BdPyK I and Homo sapiens pyruvate kinase I (HPyK I), and two differential amino acid residues (isoleucine and phenylalanine) were identified between HPyK I and BdPyK I through PyK activity detection experiments. These findings lay foundation for understanding the role of PyK I in the growth and development of B. duncani, providing insights for babesiosis prevention and drug development.

10.
Nat Commun ; 15(1): 5238, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898098

RESUMO

While sanguinarine has gained recognition for antimicrobial and antineoplastic activities, its complex conjugated structure and low abundance in plants impede broad applications. Here, we demonstrate the complete biosynthesis of sanguinarine and halogenated derivatives using highly engineered yeast strains. To overcome sanguinarine cytotoxicity, we establish a splicing intein-mediated temperature-responsive gene expression system (SIMTeGES), a simple strategy that decouples cell growth from product synthesis without sacrificing protein activity. To debottleneck sanguinarine biosynthesis, we identify two reticuline oxidases and facilitated functional expression of flavoproteins and cytochrome P450 enzymes via protein molecular engineering. After comprehensive metabolic engineering, we report the production of sanguinarine at a titer of 448.64 mg L-1. Additionally, our engineered strain enables the biosynthesis of fluorinated sanguinarine, showcasing the biotransformation of halogenated derivatives through more than 15 biocatalytic steps. This work serves as a blueprint for utilizing yeast as a scalable platform for biomanufacturing diverse benzylisoquinoline alkaloids and derivatives.


Assuntos
Benzofenantridinas , Isoquinolinas , Engenharia Metabólica , Saccharomyces cerevisiae , Temperatura , Isoquinolinas/metabolismo , Isoquinolinas/química , Benzofenantridinas/metabolismo , Benzofenantridinas/biossíntese , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Engenharia Metabólica/métodos , Halogenação , Sistema Enzimático do Citocromo P-450/metabolismo , Sistema Enzimático do Citocromo P-450/genética
11.
Am J Ophthalmol ; 266: 37-45, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38735449

RESUMO

PURPOSE: To evaluate the recurrence characteristics on optical coherence tomography and clinical outcomes after phototherapeutic keratectomy (PTK) or penetrating keratoplasty (PKP) in patients with Reis-Bücklers corneal dystrophy (RBCD). DESIGN: Retrospective interventional case series. METHODS: Seventeen patients with RBCD (31 eyes, including 6 surgery-naïve eyes and 25 surgical eyes) received 44 surgical interventions from 1996 through 2022. PTK or PKP was performed as the initial surgical procedure. Significant recurrence was determined when best spectacle-corrected visual acuity decreased at least 2 lines with increased opacity in the superficial cornea. Repeated PTK or PTK on the corneal graft (CG-PTK) was considered if patients could not endure poor vision due to significant recurrence. Recurrence depth and annual increase in thickness of the central cornea and subepithelial deposits were assessed by anterior segment optical coherence tomography. RESULTS: The mean follow-up time was 12.8 ± 8.5 years (range, 2.0-25.5 years). The mean logMAR best spectacle-corrected visual acuity improved from 1.24 ± 0.48 preoperatively to 0.27 ± 0.09 postoperatively in the initial PTK group (13 eyes, P < .001), from 1.84 ± 0.69 to 0.40 ± 0.13 in the PKP group (12 eyes, P < .001), from 1.04 ± 0.46 to 0.30 ± 0.07 in the repeated PTK group (12 times in 7 eyes, P < .001), and from 1.29 ± 0.43 to 0.39 ± 0.11 in the CG-PTK group (7 times in 5 eyes, P = .001). The median significant recurrence time was 27 months (95% confidence interval 23.9-30.1), 96 months (84.1-107.9), 31 months (28.8-33.1), and 24 months (19.8-28.2), respectively (P < .001). The depth of superficial deposits located between the epithelium and the anterior stroma was approximately 115 µm (85-159 µm). The annual thickening of subepithelial deposits was 14 ± 2 µm after initial PTK, 7 ± 3 µm after PKP, 14 ± 3 µm after repeated PTK, and 30 ± 11 µm after CG-PTK, compared to 4 ± 2 µm in surgery-naïve eyes (P = .002, .515, .002, <.001). The thickness of the central cornea increased by 15 ± 2 µm, 7 ± 2 µm, 15 ± 3 µm, and 31 ± 10 µm per year in the 4 surgery groups, respectively, compared to 5 ± 2 µm in surgery-naïve eyes (P = .001, .469, .001, <.001). CONCLUSIONS: Better visual acuity can be achieved after PTK than PKP for treatment of RBCD. The annual thickening of subepithelial deposits may approximate an increase in central corneal thickness. The superficial distribution of subepithelial deposits makes it feasible to perform repeated PTK, even on the corneal allograft, for recurrent RBCD.


Assuntos
Distrofias Hereditárias da Córnea , Ceratoplastia Penetrante , Ceratectomia Fotorrefrativa , Recidiva , Tomografia de Coerência Óptica , Acuidade Visual , Humanos , Tomografia de Coerência Óptica/métodos , Ceratectomia Fotorrefrativa/métodos , Masculino , Feminino , Estudos Retrospectivos , Acuidade Visual/fisiologia , Adulto , Distrofias Hereditárias da Córnea/cirurgia , Distrofias Hereditárias da Córnea/fisiopatologia , Distrofias Hereditárias da Córnea/diagnóstico , Pessoa de Meia-Idade , Seguimentos , Adulto Jovem , Adolescente , Lasers de Excimer/uso terapêutico , Córnea/cirurgia , Córnea/patologia , Córnea/diagnóstico por imagem , Idoso
12.
Sci Rep ; 14(1): 11865, 2024 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-38789592

RESUMO

Chest X-ray (CXR) is an extensively utilized radiological modality for supporting the diagnosis of chest diseases. However, existing research approaches suffer from limitations in effectively integrating multi-scale CXR image features and are also hindered by imbalanced datasets. Therefore, there is a pressing need for further advancement in computer-aided diagnosis (CAD) of thoracic diseases. To tackle these challenges, we propose a multi-branch residual attention network (MBRANet) for thoracic disease diagnosis. MBRANet comprises three components. Firstly, to address the issue of inadequate extraction of spatial and positional information by the convolutional layer, a novel residual structure incorporating a coordinate attention (CA) module is proposed to extract features at multiple scales. Next, based on the concept of a Feature Pyramid Network (FPN), we perform multi-scale feature fusion in the following manner. Thirdly, we propose a novel Multi-Branch Feature Classifier (MFC) approach, which leverages the class-specific residual attention (CSRA) module for classification instead of relying solely on the fully connected layer. In addition, the designed BCEWithLabelSmoothing loss function improves the generalization ability and mitigates the problem of class imbalance by introducing a smoothing factor. We evaluated MBRANet on the ChestX-Ray14, CheXpert, MIMIC-CXR, and IU X-Ray datasets and achieved average AUCs of 0.841, 0.895, 0.805, and 0.745, respectively. Our method outperformed state-of-the-art baselines on these benchmark datasets.


Assuntos
Radiografia Torácica , Humanos , Radiografia Torácica/métodos , Redes Neurais de Computação , Doenças Torácicas/diagnóstico por imagem , Doenças Torácicas/diagnóstico , Algoritmos , Diagnóstico por Computador/métodos
13.
Int Ophthalmol ; 44(1): 203, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671195

RESUMO

PURPOSE: This study aimed to observe the tilt and decentration of multifocal intraocular lens (IOL) with optic capture in Berger space within 2 years after pediatric cataract surgery. METHODS: This is a prospective observational study. The implantation of multifocal IOL (Tecnis ZMB00) with optic capture in Berger space was performed on 33 patients (48 eyes) with pediatric cataract at Qingdao Eye Hospital. Tilt and decentration of IOL was measured using Scheimpflug system (Pentacam) at 1 month and 2 years postoperatively. RESULTS: All the multifocal IOLs were successfully implanted in Berger space with optic capture and no visually significant complications were detected during the follow-up. The mean tilt of IOLs was 2.779° ± 0.950° in the vertical plane and 2.399° ± 0.898° in the horizontal plane at 1 month postoperatively, and the mean length of the decentration was 0.207 ± 0.081 mm in vertical plane and 0.211 ± 0.090 mm in the horizontal plane. Compared with 1 month after surgery, the angle of tilt decreased by a mean of 0.192° and decentration increased by a mean of 0.014 mm at the vertical meridian at 2 years postoperatively (P = 0.37 and P = 0.27, respectively), meanwhile, tilt increased by 0.265° and decentration increased by 0.012 mm at the horizontal meridian (P = 0.11 and P = 0.22, respectively). CONCLUSIONS: The follow-up results suggest the tilt and decentration of multifocal IOL implantation with optic capture in Berger space remain stable in an acceptable range within 2 years after cataract surgery in children above the age of 5. TRIAL REGISTRATION: The study was approved by the Ethics Committee of Qingdao Eye Hospital, and registered on Chinese Clinical Trial Registry (ChiCTR identifier: 1900023155).


Assuntos
Extração de Catarata , Catarata , Lentes Intraoculares Multifocais , Acuidade Visual , Humanos , Masculino , Feminino , Estudos Prospectivos , Catarata/complicações , Catarata/fisiopatologia , Pré-Escolar , Criança , Extração de Catarata/métodos , Extração de Catarata/efeitos adversos , Seguimentos , Desenho de Prótese , Migração do Implante de Lente Intraocular/diagnóstico , Migração do Implante de Lente Intraocular/fisiopatologia , Migração do Implante de Lente Intraocular/etiologia , Migração do Implante de Lente Intraocular/cirurgia , Implante de Lente Intraocular/métodos , Lactente
14.
Artigo em Inglês | MEDLINE | ID: mdl-38558277

RESUMO

Polyvinyl chloride (PVC) waste is a major environmental challenge. In this study, we found that a PVC-eating insect, Tenebrio molitor, could survive by consuming PVC as a dietary supplement. To understand the gut symbiotic community, metagenomic analysis was performed to reveal the biodiversity of a symbiotic community in the midgut of Tenebrio molitor. Among them, seven genera were enriched from the midgut of the insect under culture conditions with PVC as carbon source. A strain of Stenotrophomonas maltophilia was isolated from the midgut symbiotic community of the plastic-eating Tenebrio molitor. To unravel the functional gene for the biodegradation enzyme, we sequenced the whole genome of Stenotrophomonas maltophilia and found that orf00390, annotated as a hydrolase, was highly expressed in the PVC culture niche.

15.
Opt Express ; 32(2): 1501-1511, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38297700

RESUMO

In this study, we designed a self-focused ultrasonic transducer made of polyvinylidene fluoride (PVDF). This transducer involves a back-reflector, which is modeled after tapetum lucidum in the eyes of some nocturnal animals. The bionic structure reflects the ultrasound, which passes through the PVDF membrane, back to PVDF and provides a second chance for the PVDF to convert the ultrasound to electric signals. This design increases the amount of ultrasound absorbed by the PVDF, thereby improving the detection sensitivity. Both ultrasonic and photoacoustic (PA) experiments were conduct to characterize the performance of the transducer. The results show that the fabricated transducer has a center frequency of 13.07 MHz, and a bandwidth of 96% at -6 dB. With an acoustic numerical aperture (NA) of 0.64, the transducer provides a lateral resolution of 140µm. Importantly, the bionic design improves the detection sensitivity of the transducer about 30%. Finally, we apply the fabricated transducer to optical-resolution (OR) and acoustic-resolution photoacoustic microscopy (AR-PAM) to achieve multiscale-resolution PA imaging. Imaging of the bamboo leaf and the leaf skeleton demonstrates that the proposed transducer can provide high spatial resolution, better imaging intensity and contrast. Therefore, the proposed transducer design will be useful to enhance the performance of multiscale-resolution PAM.

16.
Exp Ther Med ; 27(2): 79, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38264431

RESUMO

Dystrophic epidermolysis bullosa (DEB) is a rare disease and the associated esophageal stricture is frequently complicated by the lack of clinical experience. The present study reported a very rare case of DEB in a 37-year-old male, who was admitted to Shenzhen Hospital (Shenzhen, China) due to an esophageal stricture. The patient received esophageal dilation under digital subtraction angiography. In this patient, dilation therapy was effective and safe. The patient underwent skin biopsies, and histological examination of the resected tissue specimens confirmed DEB diagnosis. The patient was followed up in the Department of Thoracic Surgery, Shenzhen Hospital, for 2 years without any recurrence of esophageal stricture. This is the first case report of dilation therapy in a very rare case of DEB with a satisfactory outcome, but the long-term efficacy needs further observation. In addition, the latest relevant literature was reviewed and it was found that this treatment is uncommonly reported, as is the condition.

17.
Neurosci Lett ; 822: 137648, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38246407

RESUMO

Converging evidence from behavioral and neuroscience studies demonstrated that our attention to the external world is influenced by emotion, especially anxiety. However, little is known about how trait anxiety influences neural and behavioral responses during mind wandering. The present study aimed to examine the neural and cognitive time courses of how trait anxiety affects mind wandering. Event-related potentials (ERPs) were recorded from 20 individuals with high trait anxiety and 20 with low trait anxiety when they performed the Sustained Attention to Response Task (SART) in which they were asked to respond to frequent ''nontargets'' (digits 0-6, 8-9) but withhold responses to infrequent ''targets'' (the digit 7). We compared the behavioral performance and electroencephalographic waves between the high and low trait anxiety groups during states of "mind wandering" (fail to withhold a response to the target number) and being "on-task" (correctly withhold a response to the target number). Results showed that a larger late positive component (LPC, 400-950 ms) was elicited when participants were "on task" than when they were mind wandering. Additionally, a larger late slow waveform (LSW, 950-1050 ms) was elicited in the high trait anxiety group than in the low trait anxiety group. Moreover, there was a positive correlation between self-reported trait anxiety scores and the LSW amplitudes during mind wandering. It was proposed that the effect of trait anxiety on the cognitive neural mechanism underlying attentional processing was primarily reflected in a later process involving the redistribution of cognitive resources.


Assuntos
Eletroencefalografia , Potenciais Evocados , Humanos , Transtornos de Ansiedade , Cognição/fisiologia , Ansiedade
18.
Med Clin (Barc) ; 162(1): 35-38, 2024 01 12.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-37517931

RESUMO

BACKGROUND: Leucine-rich glioma inactivated 1 (LGI1) antibody-related autoimmune encephalitis is easily misdiagnosed clinically because of its complex and diverse clinical manifestations. We present two cases of LGI1 antibody-related encephalitis with negative imaging findings and perform a literature review on this disease entity. CASE DESCRIPTION: The first case was that of a 60-year-old man who presented with involuntary movement of the paroxysmal right limb. The second case was that of a 66-year-old man who presented with hearing hallucinations, involuntary shaking of the right limb, and progressive cognitive impairment. Both patients in this study showed negative magnetic resonance imaging (MRI) results. Routine cerebrospinal fluid (CSF) and biochemical examinations showed no significant abnormalities, and positive LGI1 antibodies were detected in both the CSF and serum. CONCLUSION: Based on our experience and the literature review, we recommend that LGI1 antibody-related encephalitis should be considered when faciobrachial dystonic seizures, acute and subacute-onset seizures, low serum sodium (possibly with low CSF chloride), and cognitive-psychiatric disorders are encountered, even in the absence of specific radiographic and altered CSF findings.


Assuntos
Doenças Autoimunes do Sistema Nervoso , Encefalite , Glioma , Encefalite Límbica , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Leucina , Peptídeos e Proteínas de Sinalização Intracelular , Autoanticorpos , Encefalite Límbica/diagnóstico por imagem , Encefalite/diagnóstico por imagem , Imageamento por Ressonância Magnética/efeitos adversos , Convulsões/etiologia , Doenças Autoimunes do Sistema Nervoso/diagnóstico por imagem , Doenças Autoimunes do Sistema Nervoso/complicações , Glioma/complicações
19.
Virol Sin ; 39(1): 134-143, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38070873

RESUMO

The monkeypox virus (MPXV) has triggered a current outbreak globally. Genome sequencing of MPXV and rapid tracing of genetic variants will benefit disease diagnosis and control. It is a significant challenge but necessary to optimize the strategy and application of rapid full-length genome identification and to track variations of MPXV in clinical specimens with low viral loads, as it is one of the DNA viruses with the largest genome and the most AT-biased, and has a significant number of tandem repeats. Here we evaluated the performance of metagenomic and amplicon sequencing techniques, and three sequencing platforms in MPXV genome sequencing based on multiple clinical specimens of five mpox cases in Chinese mainland. We rapidly identified the full-length genome of MPXV with the assembly of accurate tandem repeats in multiple clinical specimens. Amplicon sequencing enables cost-effective and rapid sequencing of clinical specimens to obtain high-quality MPXV genomes. Third-generation sequencing facilitates the assembly of the terminal tandem repeat regions in the monkeypox virus genome and corrects a common misassembly in published sequences. Besides, several intra-host single nucleotide variations were identified in the first imported mpox case. This study offers an evaluation of various strategies aimed at identifying the complete genome of MPXV in clinical specimens. The findings of this study will significantly enhance the surveillance of MPXV.


Assuntos
Monkeypox virus , Mpox , Humanos , Monkeypox virus/genética , Mpox/diagnóstico
20.
PLoS One ; 18(12): e0292506, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38096197

RESUMO

BACKGROUND: Individuals with chronic kidney disease (CKD) are at a substantially higher risk for stroke, which may predispose individuals to cognitive impairment. However, the association of low estimated glomerular filtration rate (eGFR) and albuminuria with poorer cognitive performance in patients with stroke is not fully understood, and the current evidence for this association is contradictory. Our aim was to retrospectively investigate whether low eGFR and albuminuria, as indicated by the urine albumin-creatinine ratio (UACR), are independently or jointly associated with worse cognitive performance in patients with ischemic stroke. METHODS: This retrospective study included 608 patients with acute ischemic stroke. Their UACR and eGFR values were obtained from inpatient medical records. Global cognitive function was assessed with the mini-mental state exam (MMSE) and Montreal Cognitive Assessment (MoCA) one month after hospital discharge. The relationship between renal measures and cognitive performance was assessed using univariate and multiple linear regression analyses. Potential confounders included age, gender, BMI, education, diabetes and hypertension history, NIHSS score, smoking and alcohol consumption status, serum total cholesterol, triglyceride, fasting glucose, uric acid, homocysteine, systolic blood pressure, and either eGFR or UACR. RESULTS: Patients had an average age of 66.6±4.1 years, and 48% were females. Average eGFR and UACR were 88.4±12.9 ml/min/1.73m2 and 83.6±314.2 mg/g, respectively. The number of patients with eGFR ≥90, 60-89, and <60 ml/min/1.73 m2 was 371 (61%), 207 (34%), and 30 (5%), respectively, and the percentage of patients with UACR <30 mg/g, 30-300 mg/g, and >300 mg/g was 56%, 39%, and 5%, respectively. Multivariate adjusted models showed that eGFR was independently associated with MMSE (ß = -0.4; 95% CI = -0.5,-0.4; p <0.001) and MoCA (ß = -0.6; 95% CI = -0.7,-0.5; p <0.001). However, UACR was not significantly correlated with MMSE or MoCA. CONCLUSION: In patients with ischemic stroke, reduced eGFR but not albuminuria was associated with lower cognitive performance. These results show that the eGFR decline could be an effective indicator of cognitive impairment after a stroke. Therefore, regular monitoring and early detection of mild renal dysfunction in patients with acute ischemic stroke might be needed.


Assuntos
AVC Isquêmico , Insuficiência Renal Crônica , Acidente Vascular Cerebral , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Masculino , AVC Isquêmico/complicações , Estudos Retrospectivos , Albuminúria/complicações , Rim , Taxa de Filtração Glomerular/fisiologia , Insuficiência Renal Crônica/complicações , Acidente Vascular Cerebral/complicações , Cognição , Creatinina
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