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1.
J Virol ; : e0019524, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38656209

RESUMO

The host cytoskeleton plays crucial roles in various stages of virus infection, including viral entry, transport, replication, and release. However, the specific mechanisms by which intermediate filaments are involved in orthoflavivirus infection have not been well understood. In this study, we demonstrate that the Japanese encephalitis virus (JEV) remodels the vimentin network, resulting in the formation of cage-like structures that support viral replication. Mechanistically, JEV NS1 and NS1' proteins induce the translocation of CDK1 from the nucleus to the cytoplasm and interact with it, leading to the phosphorylation of vimentin at Ser56. This phosphorylation event recruits PLK1, which further phosphorylates vimentin at Ser83. Consequently, these phosphorylation modifications convert the typically filamentous vimentin into non-filamentous "particles" or "squiggles." These vimentin "particles" or "squiggles" are then transported retrogradely along microtubules to the endoplasmic reticulum, where they form cage-like structures. Notably, NS1' is more effective than NS1 in triggering the CDK1-PLK1 cascade response. Overall, our study provides new insights into how JEV NS1 and NS1' proteins manipulate the vimentin network to facilitate efficient viral replication. IMPORTANCE: Japanese encephalitis virus (JEV) is a mosquito-borne orthoflavivirus that causes severe encephalitis in humans, particularly in Asia. Despite the availability of a safe and effective vaccine, JEV infection remains a significant public health threat due to limited vaccination coverage. Understanding the interactions between JEV and host proteins is essential for developing more effective antiviral strategies. In this study, we investigated the role of vimentin, an intermediate filament protein, in JEV replication. Our findings reveal that JEV NS1 and NS1' proteins induce vimentin rearrangement, resulting in the formation of cage-like structures that envelop the viral replication factories (RFs), thus facilitating efficient viral replication. Our research highlights the importance of the interplay between the cytoskeleton and orthoflavivirus, suggesting that targeting vimentin could be a promising approach for the development of antiviral strategies to inhibit JEV propagation.

2.
Plant J ; 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38430515

RESUMO

Host-induced gene silencing (HIGS) is an inherent mechanism of plant resistance to fungal pathogens, resulting from cross-kingdom RNA interference (RNAi) mediated by small RNAs (sRNAs) delivered from plants into invading fungi. Introducing artificial sRNA precursors into crops can trigger HIGS of selected fungal genes, and thus has potential applications in agricultural disease control. To investigate the HIGS of apple (Malus sp.) during the interaction with Botryosphaeria dothidea, the pathogenic fungus causing apple ring rot disease, we evaluated whether apple miRNAs can be transported into and target genes in B. dothidea. Indeed, miR159a from Malus hupehensis, a wild apple germplasm with B. dothidea resistance, silenced the fungal sugar transporter gene BdSTP. The accumulation of miR159a in extracellular vesicles (EVs) of both infected M. hupehensis and invading B. dothidea suggests that this miRNA of the host is transported into the fungus via the EV pathway. Knockout of BdSTP caused defects in fungal growth and proliferation, whereas knockin of a miR159a-insensitive version of BdSTP resulted in increased pathogenicity. Inhibition of miR159a in M. hupehensis substantially enhanced plant sensitivity to B. dothidea, indicating miR159a-mediated HIGS against BdSTP being integral to apple immunity. Introducing artificial sRNA precursors targeting BdSTP and BdALS, an acetolactate synthase gene, into M. hupehensis revealed that double-stranded RNAs were more potent than engineered MIRNAs in triggering HIGS alternative to those natural of apple and inhibiting infection. These results provide preliminary evidence for cross-kingdom RNAi in the apple-B. dothidea interaction and establish HIGS as a potential disease control strategy in apple.

3.
Radiology ; 310(3): e232255, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38470237

RESUMO

Background Large language models (LLMs) hold substantial promise for medical imaging interpretation. However, there is a lack of studies on their feasibility in handling reasoning questions associated with medical diagnosis. Purpose To investigate the viability of leveraging three publicly available LLMs to enhance consistency and diagnostic accuracy in medical imaging based on standardized reporting, with pathology as the reference standard. Materials and Methods US images of thyroid nodules with pathologic results were retrospectively collected from a tertiary referral hospital between July 2022 and December 2022 and used to evaluate malignancy diagnoses generated by three LLMs-OpenAI's ChatGPT 3.5, ChatGPT 4.0, and Google's Bard. Inter- and intra-LLM agreement of diagnosis were evaluated. Then, diagnostic performance, including accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC), was evaluated and compared for the LLMs and three interactive approaches: human reader combined with LLMs, image-to-text model combined with LLMs, and an end-to-end convolutional neural network model. Results A total of 1161 US images of thyroid nodules (498 benign, 663 malignant) from 725 patients (mean age, 42.2 years ± 14.1 [SD]; 516 women) were evaluated. ChatGPT 4.0 and Bard displayed substantial to almost perfect intra-LLM agreement (κ range, 0.65-0.86 [95% CI: 0.64, 0.86]), while ChatGPT 3.5 showed fair to substantial agreement (κ range, 0.36-0.68 [95% CI: 0.36, 0.68]). ChatGPT 4.0 had an accuracy of 78%-86% (95% CI: 76%, 88%) and sensitivity of 86%-95% (95% CI: 83%, 96%), compared with 74%-86% (95% CI: 71%, 88%) and 74%-91% (95% CI: 71%, 93%), respectively, for Bard. Moreover, with ChatGPT 4.0, the image-to-text-LLM strategy exhibited an AUC (0.83 [95% CI: 0.80, 0.85]) and accuracy (84% [95% CI: 82%, 86%]) comparable to those of the human-LLM interaction strategy with two senior readers and one junior reader and exceeding those of the human-LLM interaction strategy with one junior reader. Conclusion LLMs, particularly integrated with image-to-text approaches, show potential in enhancing diagnostic medical imaging. ChatGPT 4.0 was optimal for consistency and diagnostic accuracy when compared with Bard and ChatGPT 3.5. © RSNA, 2024 Supplemental material is available for this article.


Assuntos
Nódulo da Glândula Tireoide , Humanos , Feminino , Adulto , Nódulo da Glândula Tireoide/diagnóstico por imagem , Estudos Retrospectivos , Idioma , Redes Neurais de Computação , Curva ROC
4.
Cell Rep Med ; 5(2): 101415, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38382467

RESUMO

Immune checkpoint inhibitors, particularly PD-1/PD-L1 blockades, have been approved for unresectable hepatocellular carcinoma (HCC). However, high resistance rates still limit their efficacy, highlighting the urgent need to understand the underlying mechanisms and develop strategies for overcoming the resistance. In this study, we demonstrate that HCC with high MER proto-oncogene tyrosine kinase (MerTK) expression exhibits anti-PD-1/PD-L1 resistance in two syngeneic mouse models and in patients who received anti-PD-1/PD-L1 therapy. Mechanistically, MerTK renders HCC resistant to anti-PD-1/PD-L1 by limiting ferroptosis with the upregulation of SLC7A11 via the ERK/SP1 pathway and facilitating the development of an immunosuppressive tumor microenvironment (TME) with the recruitment of myeloid-derived suppressor cells (MDSCs). Sitravatinib, an inhibitor of MerTK, sensitizes resistant HCC to anti-PD-L1 therapy by promoting tumor ferroptosis and decreasing MDSC infiltration into the TME. In conclusion, we find that MerTK could serve as a predictive biomarker for patient stratification and as a promising target to overcome anti-PD-1/PD-L1 resistance in HCC.


Assuntos
Carcinoma Hepatocelular , Ferroptose , Neoplasias Hepáticas , Animais , Humanos , Camundongos , Antígeno B7-H1 , c-Mer Tirosina Quinase/genética , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Imunidade , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Microambiente Tumoral
5.
Plant Sci ; 341: 112008, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38307352

RESUMO

miRNAs govern gene expression and regulate plant defense. Alternaria alternata is a destructive fungal pathogen that damages apple. The wild apple germplasm Malus hupehensis is highly resistant to leaf spot disease caused by this fungus. Herein, we elucidated the regulatory and functional role of miR393a in apple resistance against A. alternata by targeting Transport Inhibitor Response 1. Mature miR393 accumulation in infected M. hupehensis increased owing to the transcriptional activation of MIR393a, determined to be a positive regulator of A. alternata resistance to either 'Orin' calli or 'Gala' leaves. 5' RLM-RACE and co-transformation assays showed that the target of miR393a was MhTIR1, a gene encoding a putative F-box auxin receptor that compromised apple immunity. RNA-seq analysis of transgenic calli revealed that MhTIR1 upregulated auxin signaling gene transcript levels and influenced phytohormone pathways and plant-pathogen interactions. miR393a compromised the sensitivity of several auxin-signaling genes to A. alternata infection, whereas MhTIR1 had the opposite effect. Using exogenous indole-3-acetic acid or the auxin synthesis inhibitor L-AOPP, we clarified that auxin enhances apple susceptibility to this pathogen. miR393a promotes SA biosynthesis and impedes pathogen-triggered ROS bursts by repressing TIR1-mediated auxin signaling. We uncovered the mechanism underlying the miR393a-TIR1 module, which interferes with apple defense against A. alternata by modulating the auxin signaling pathway.


Assuntos
Malus , Malus/metabolismo , Alternaria/fisiologia , Ácidos Indolacéticos/metabolismo , Transdução de Sinais , Regulação da Expressão Gênica de Plantas
6.
Int Immunopharmacol ; 126: 111202, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37988908

RESUMO

OBJECTIVE: Gadd45ß have a regulatory role in cellular inflammation, proliferation and migration. However, the role of Gadd45ß in synovial inflammation in osteoarthritis (OA) remains to be explored. This study aimed to ascertain whether Gadd45ß is involved in OA synovial inflammation. METHODS: The rat model was induced by sodium iodoacetate and the cellular model was constructed with lipopolysaccharide (LPS)-induced fibroblast-like synoviocytes (FLSs). siRNA was applied to interfere with the expression of intracellular Gadd45ß. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to detect the expression of Gadd45ß mRNA and protein. The inflammation, proliferation, and migration of OA-FLSs were detected by enzyme-linked immunosorbent assay, cell scratch assay, 5-ethynyl-2'-deoxyuridine assay, etc. The effect of downregulation of Gadd45ß on the nuclear factor-κB (NF-κB) pathway was investigated. RESULTS: Expression of Gadd45ß in OA rat synovial tissues and OA-FLSs was increased, and LPS treatment promoted cell proliferation and enhanced cell migration. Gadd45ß interference inhibited the inflammation, proliferation and migration of cells induced by LPS. LPS promoted P65 expression in the nucleus and activated the NF-κB signaling pathway, whereas si-Gadd45ß reversed this situation. CONCLUSIONS: si-Gadd45ß inhibited the inflammatory response, proliferation and migration of FLSs, and activation of the NF-κB signaling pathway, which could delay the progression of OA. Hence, it may become a potential therapeutic target for OA.


Assuntos
Osteoartrite , Sinoviócitos , Animais , Ratos , Proliferação de Células , Células Cultivadas , Regulação para Baixo , Fibroblastos , Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo , Osteoartrite/metabolismo
7.
Front Bioeng Biotechnol ; 11: 1260204, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38026869

RESUMO

Background and objective: Cervical fusion with vertebral body screw (VBS)-plate systems frequently results in limited biomechanical stability. To address this issue, anterior transpedicular screw (ATPS) fixation has been developed and applied preliminarily to multilevel spinal fusion, osteoporosis, and three-column injury of the cervical spine. This study aimed to compare the biomechanical differences between unilateral ATPS (UATPS), bilateral ATPS (BATPS), and VBS fixation using finite element analysis. Materials and methods: A C6 corpectomy model was performed and a titanium mesh cage (TMC) and bone were implanted, followed by implantation of a novel ATPS-plate system into C5 and C7 to simulate internal fixation with UATPS, BATPS, and VBS. Internal fixation with UATPS comprises ipsilateral transpedicular screw-contralateral vertebral body screw (ITPS-CVBS) and cross transpedicular screw-vertebral body screw (CTPS-VBS) fixations. Mobility, the maximal von Mises stress on TMC, the stress distribution and maximal von Mises stress on the screws, and the maximum displacement of the screw were compared between the four groups. Results: Compared with the original model, each group had a reduced range of motion (ROM) under six loads. After ACCF, the stress was predominantly concentrated at two-thirds of the length from the tail of the screw, and it was higher on ATPS than on VBS. The stress of the ATPS from the cranial part was higher than that of the caudal part. The similar effect happened on VBS. The screw stress cloud maps did not show any red areas reflective of a concentration of the stress on VBS. Compared with VBS, ATPS can bear a greater stress from cervical spine movements, thus reducing the stress on TMC. The maximal von Mises stress was the lowest with bilateral transpedicular TMC and increased with cross ATPS and with ipsilateral ATPS. ITPS-CVBS, CTPS-VBS, and BATPS exhibited a reduction of 2.3%-22.1%, 11.9%-2.7%, and 37.9%-64.1% in the maximum displacement of screws, respectively, compared with that of VBS. Conclusion: In FEA, the comprehensive stability ranked highest for BATPS, followed by CTPS-VBS and ITPS-CVBS, with VBS demonstrating the lowest stability. Notably, utilizing ATPS for fixation has the potential to reduce the occurrence of internal fixation device loosening after ACCF when compared to VBS.

8.
Reprod Sci ; 30(9): 2829-2841, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37016173

RESUMO

This study was aimed to identify a novel metastasis-promoting molecule and elucidate its functional and prognostic roles in cervical cancer. DDIT4 (DNA-damage-inducible transcript 4), a hypoxia-inducible gene, was identified by analyzing multiple microarray databases. The correlation between DDIT4 expression in immunohistochemistry and clinicopathological characteristics in the public database and our cohort was evaluated by statistical analysis. Transwell® assay and wound-healing assay to determine cell migration and invasion were performed. DDIT4 was knocked down using siRNA or lentiviral vectors. The potential downstream pathways of DDIT4 were explored and verified by a gene set enrichment analysis and western blotting. The in vivo metastatic capability was determined with the use of an intraperitoneal injection mouse model. In the analysis of the public database and our cohort, DDIT4 high expression was significantly related to short overall survival and lymph node metastasis in patients with early-stage cervical cancer. The knockdown of DDIT4 attenuated the migration and invasion activity of tumor cells in vitro and reduced the expression of epithelial-mesenchymal transition (EMT)-related proteins and the NF-κB pathway in cervical cancer cells. DDIT4 also promoted tumor progression in the mouse model. Our results indicate that DDIT4 can be a prognostic indicator in cervical cancer and promote lymph node metastasis, augmenting malignancy via the EMT and NF-kB pathways.


Assuntos
NF-kappa B , Neoplasias do Colo do Útero , Humanos , Animais , Feminino , Camundongos , NF-kappa B/metabolismo , Metástase Linfática , Transdução de Sinais , Transição Epitelial-Mesenquimal/genética , Neoplasias do Colo do Útero/genética , Linhagem Celular Tumoral , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Proliferação de Células , Fatores de Transcrição/metabolismo
9.
Front Neurosci ; 17: 1118650, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36950128

RESUMO

Rumination is closely related to mental disorders and can thus be used as a marker of their presence or a predictor of their development. The presence of masking and fabrication in psychological selection can lead to inaccurate detection of psychological disorders. Human language is considered crucial in eliciting specific conscious activities, and the use of natural language processing (NLP) in the development of questionnaires for psychological tests has the potential to elicit immersive ruminative thinking, leading to changes in neural activity. Electroencephalography (EEG) is commonly used to detect and record neural activity in the human brain and is sensitive to changes in brain activity. In this study, we used NLP to develop a questionnaire to induce ruminative thinking and then recorded the EEG signals in response to the questionnaire. The behavioral results revealed that ruminators exhibited higher arousal rates and longer reaction times, specifically in response to the ruminative items of the questionnaire. The EEG results showed no significant difference between the ruminators and the control group during the resting state; however, a significant alteration in the coherence of the entire brain of the ruminators existed while they were answering the ruminative items. No differences were found in the control participants while answering the two items. These behavioral and EEG results indicate that the questionnaire elicited immersive ruminative thinking, specifically in the ruminators. Therefore, the questionnaire designed using NLP is capable of eliciting ruminative thinking in ruminators, offering a promising approach for the early detection of mental disorders in psychological selection.

10.
Front Public Health ; 11: 1129322, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36908472

RESUMO

Introduction: With the COVID-19 pandemic in China, a large number of mild or ordinary confirmed cases have been sent to Fangcang shelter hospitals for treatment. We aimed to investigate the mental health condition of Fangcang patients 2 years after the pandemic when patients knew more about COVID-19 and the virus was less virulent. We focused on the effect of dysfunctional beliefs and attitudes about sleep on depression, anxiety, and insomnia. Methods: A total of 1,014 patients from two large Fangcang shelter hospitals in Shanghai between 22 April and 8 May 2022 completed a set of questionnaires comprising: the Dysfunctional Beliefs and Attitudes about Sleep scale, the Generalized Anxiety Disorder scale, the Patient Health Questionnaire, and the Insomnia Severity Index scale. Results: Results show that the positive screening rates for anxiety, depression, and insomnia among tested patients were 55.3, 27.0, and 47.8%, respectively. Patients were more likely to report higher anxiety, depression, and insomnia, and to endorse affective and sleep disorders if they were: female, aged 18-40 years, with undergraduate course or above, white-collar employees, or those who thought the pandemic would have severe economic effects. About 51.4% of the participants had dysfunctional beliefs about sleep to varying degrees. Compared with patients who had accurate beliefs about sleep, the ratios of insomnia, anxiety, and depression were significantly higher among patients with dysfunctional beliefs about sleep. Discussion: Attention should be paid to the mental health problems of patients in Fangcang shelter hospitals. The results indicate that dysfunctional beliefs about sleep significantly increased anxiety, depression, and insomnia of Fangcang patients.


Assuntos
COVID-19 , Distúrbios do Início e da Manutenção do Sono , Humanos , Feminino , Saúde Mental , Qualidade do Sono , Pandemias , Hospitais Especializados , Depressão/psicologia , Unidades Móveis de Saúde , China , Sono
11.
Cureus ; 15(1): e33464, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36751208

RESUMO

INTRODUCTION: The purpose of this study is to investigate the effects of sleep deprivation on individual attentional function and related electrophysiological mechanisms. METHODS: Twenty healthy men who were deprived of sleep for 24 h were evaluated by selective attention test, persistent attention test, and event-related potentials (ERP) experiment. RESULTS: After 24 h of sleep deprivation, the subjects' selective attention decreased, mainly manifested as prolonged response time, decreased motion stability, increased rate of neglect error, decreased sustained attention, prolonged latency of P300 at Cz (p=0.001), and decreased amplitude (p=0.000). CONCLUSION: After 24 h of sleep deprivation, the attentional ability decreased significantly, and behavioral and ERP indicators showed certain changes.

12.
Clin Neurophysiol ; 147: 1-10, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36608385

RESUMO

OBJECTIVE: The dorsolateral prefrontal cortex (DLPFC) has been increasingly used as a neuromodulatory target in pain management. Transcranial random noise stimulation (tRNS) was shown to effectively elevate cortical excitability. Hence, this study aimed to characterize how tRNS over the left DLPFC affects pain expectation and perception, as well as the efficacy of conditioned-pain modulation (CPM) that reflects the function of the endogenous pain-inhibitory pathway. METHODS: Using a randomized, double-blinded, and sham-controlled design, healthy participants were randomly recruited to receive tRNS with a direct current offset or sham stimulation. Their expectations and perceptions of painful electrocutaneous stimuli, as well as CPM efficacy were assessed before, immediately after, and 30 min after tRNS. RESULTS: Compared with sham stimulation, perceived-pain ratings to the painful stimuli, and expected-pain ratings before painful stimuli, attenuated immediately after tRNS, whereas this analgesic effect was ineffective 30 min after tRNS. Importantly, the immediate analgesia induced by tRNS could be accounted for by tRNS effect on attenuating expected-pain ratings before certain painful stimuli. However, CPM efficacy was not significantly affected by tRNS. CONCLUSIONS: These results demonstrate analgesia immediately after applying tRNS over the left DLPFC. SIGNIFICANCE: This study provides evidence for analgesia of DLPFC-tRNS on an experimental pain model.


Assuntos
Estimulação Transcraniana por Corrente Contínua , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Córtex Pré-Frontal Dorsolateral , Motivação , Córtex Pré-Frontal/fisiologia , Dor , Percepção
13.
PeerJ ; 11: e14563, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36655043

RESUMO

Osteoarthritis (OA) is the most common joint disease in the world, characterized by pain and loss of joint function, which has led to a serious reduction in the quality of patients' lives. In this work, ultrahigh performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-QToF/MS) in conjunction with multivariate pattern recognition methods and an univariate statistical analysis scheme were applied to explore the serum metabolic signatures within OA group (n = 31), HC (healthy controls) group (n = 57) and non-OA group (n = 19) for early diagnosis and differential diagnosis of OA. Based on logistic regression analysis and receiver operating characteristic (ROC) curve analysis, seven metabolites, including phosphatidylcholine (18:0/22:6), p-cresol sulfate and so on, were identified as critical metabolites for the diagnosis of OA and HC and yielded an area under the curve (AUC) of 0.978. The other panel of unknown m/z 239.091, phosphatidylcholine (18:0/18:0) and phenylalanine were found to distinguish OA from non-OA and achieved an AUC of 0.888. These potential biomarkers are mainly involved in lipid metabolism, glucose metabolism and amino acid metabolism. It is expected to reveal new insight into OA pathogenesis from changed metabolic pathways.


Assuntos
Metabolômica , Osteoartrite , Humanos , Metabolômica/métodos , Cromatografia Líquida , Biomarcadores , Osteoartrite/diagnóstico , Lecitinas
14.
Redox Biol ; 59: 102601, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36630819

RESUMO

Hydrogen sulfide (H2S) is an important signaling molecule in colorectal cancer (CRC). It is produced in the colon by the catalytic synthesis of the colonocytes' enzymatic systems and the release of intestinal microbes, and is oxidatively metabolized in the colonocytes' mitochondria. Both endogenous H2S in colonic epithelial cells and exogenous H2S in intestinal lumen contribute to the onset and progression of CRC. The up-regulation of endogenous synthetases is thought to be the cause of the elevated H2S levels in CRC cells. Different diagnostic probes and combination therapies, as well as tumor treatment approaches through H2S modulation, have been developed in recent years and have become active area of investigation for the diagnosis and treatment of CRC. In this review, we focus on the specific mechanisms of H2S production and oxidative metabolism as well as the function of H2S in the occurrence, progression, diagnosis, and treatment of CRC. We also discuss the present challenges and provide insights into the future research of this burgeoning field.


Assuntos
Neoplasias Colorretais , Sulfeto de Hidrogênio , Humanos , Sulfeto de Hidrogênio/metabolismo , Mitocôndrias/metabolismo , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/tratamento farmacológico
15.
Cell Rep Med ; 4(2): 100912, 2023 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-36669488

RESUMO

Medical artificial intelligence (AI) has been moving from the research phase to clinical implementation. However, most AI-based models are mainly built using high-quality images preprocessed in the laboratory, which is not representative of real-world settings. This dataset bias proves a major driver of AI system dysfunction. Inspired by the design of flow cytometry, DeepFundus, a deep-learning-based fundus image classifier, is developed to provide automated and multidimensional image sorting to address this data quality gap. DeepFundus achieves areas under the receiver operating characteristic curves (AUCs) over 0.9 in image classification concerning overall quality, clinical quality factors, and structural quality analysis on both the internal test and national validation datasets. Additionally, DeepFundus can be integrated into both model development and clinical application of AI diagnostics to significantly enhance model performance for detecting multiple retinopathies. DeepFundus can be used to construct a data-driven paradigm for improving the entire life cycle of medical AI practice.


Assuntos
Inteligência Artificial , Citometria de Fluxo , Curva ROC , Área Sob a Curva
16.
Pharmazie ; 78(11): 217-224, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38178286

RESUMO

The global pandemic of COVID-19 disease is caused by the pathogenic factor called SARS-CoV-2. Meanwhile, a series of vaccines and small-molecule drugs, including the mRNA vaccines and Paxlovid®, have been approved, but their efficacy is decreased significantly due to the constant emergence of mutant viral strains. The R&D of host-directed therapeutics has great potential to overcome such limitations and provide new prevention and therapy options for patients with COVID-19 or high-risk group for SARS-CoV-2 infections. Transmembrane serine protease 2 (TMPRSS2) is belonging to a protein family with highly conserved serine protease domain whose crucial role in viral entry is to activate the spike protein of viruses to induce the fusion between host cells and viruses. In this review, we sketch the critical position of TMPRSS2 in the SARS-CoV-2 viral entry and summarize the advanced research and development of TMPRSS2 inhibitors, including repurposed drugs, as a new way to fight COVID-19.


Assuntos
COVID-19 , Reposicionamento de Medicamentos , Inibidores de Serino Proteinase , Humanos , Serina Endopeptidases , Serina Proteases , Inibidores de Serino Proteinase/uso terapêutico
17.
Front Neurosci ; 16: 992537, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36419460

RESUMO

Job burnout is one of the most widespread mental problems in today's society and seriously affects the mental health and combat effectiveness of soldiers and officers. Herein, the effect of burnout on individual attention is studied from the perspective of neuroelectrophysiology. A total of 1,155 army soldiers and officers were included in this investigation and completed the Job Burnout Scale for Military Personnel. A total of 42 soldiers and officers were randomly selected from those with and without burnout to participate in an event-related potential (ERP) study using a visual oddball task. The characteristics of visual P3a and P3b at Fz, FCz, Cz, CPz, and Pz were recorded and analyzed by repeated-measures analysis of variance (ANOVA). P < 0.05 was the criterion for a significant difference. The total average score on the Job Burnout Scale for Military Personnel among the participants was 0.74 ± 0.46, and the detection rate of job burnout was 29.85%. In the Oddball task, the average number of target stimuli counted in the burnout group was lower than that in the control group, but no significant difference was found. For P3a, the Fz, FCz, Cz, CPz, and Pz amplitudes in the burnout group were significantly lower than those in the control group. The average amplitude of P3a evoked in the central parietal area was larger than that in the prefrontal area. For P3b, the amplitudes of the five electrodes in the burnout group were significantly lower than those in the control group. The average amplitude of P3b evoked in the parietal region was larger than those in the prefrontal and central parietal regions. A certain degree of job burnout is evident in army soldiers and officers. The voluntary attention and involuntary attention of individuals with burnout are both affected to some extent, as reflected by the lower amplitudes of P3a and P3b. The results suggest that P3a and P3b can be used as indicators to monitor cognitive neural function in soldiers and officers with burnout and can also be used as references for evaluating the effects of cognitive training and screening methods. In this study, ERP was used to research the attention ability of soldiers and officers with job burnout, and related issues were discussed from the aspects of the burnout results, behavioral results, ERP results, compensation effect of cognitive resources, application in the military field, limitations, and prospects.

18.
Artigo em Inglês | MEDLINE | ID: mdl-36142002

RESUMO

This study aims to map the knowledge structure and themes trends of primary ovarian insufficiency (POI) therapy to help researchers rapidly master the hotspots and prospects of POI therapy from the increasing number of publications. The literature search and bibliometric analyses were performed by using Web of Science Core Collection and VOSviewer. Annual publications from 2000 to 2022 continued to increase with some fluctuations. The most productive country, organization, and journal were the USA, Shanghai Jiao Tong University, and Human Reproduction, respectively. Harvard University was the organization with the highest citation. Fertility and Sterility and Nelson, L.M. were the most influential journal and author, respectively. Seven clusters separated by keywords association showed the extensive scope of POI therapy. The hotspots of POI therapy were hormone replacement therapy and fertility preservation, and the innovative treatment strategies including in vitro activation and mesenchymal stem cells had development potential. In addition, our result showed that the high-cited articles were published in journals with high impact factors. The paper provides a comprehensive overview of the development and hotspots of POI therapy, allowing researchers to recognize the current status and future directions of POI therapy.


Assuntos
Pesquisa Biomédica , Bibliometria , China , Eficiência , Humanos , Publicações
19.
Ann N Y Acad Sci ; 1517(1): 286-299, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35976662

RESUMO

Autistic traits-subclinical forms of characteristics associated with autism spectrum disorders-are associated with poor social interactions and high risks for mental health disorders. We hypothesized that altered sensitivity to social rejection is an important contributor to psychological distress observed among individuals with high autistic traits. Experiment 1 adopted a social-judgment task and compared behavioral and neural activity in response to social rejection between participants exhibiting either high or low autistic traits (HAT and LAT, respectively). Rejection-induced hurt feelings, P3 amplitudes, and θ-oscillation magnitudes were greater in the HAT group than in the LAT group. Mediation analysis indicated that autistic traits heighten rejection-induced social pain through increasing frontal-midline θ-oscillations. Responses to nonsocial feedback in the age-judgment task were comparable, confirming that the between-group differences were specific to social negative feedback. Experiment 2 assessed the association between autistic traits, rejection sensitivity, and psychological distress among randomly recruited participants. Results showed that autistic traits affected depressive/anxious symptomatology partially through heightened rejection sensitivity. Therefore, autistic traits heighten sensitivity to rejection-induced social pain that leads to psychological distress. This finding will help facilitate the development of strategies for coping with social pain and improving mental health for individuals with high autistic traits.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Humanos , Julgamento/fisiologia , Dor , Ansiedade
20.
Brain Sci ; 12(7)2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35884692

RESUMO

(1) Background: The combined n-back + Go/NoGo paradigm was used to investigate whether audiovisual interactions interfere with or facilitate WM. (2) Methods: College students were randomly assigned to perform the working memory task based on either a single (visual or auditory) or dual (audiovisual) stimulus. Reaction times, accuracy, and WM performance were compared across the two groups to investigate effects of audiovisual interactions. (3) Results: With low cognitive load (2-back), auditory stimuli had no effect on visual working memory, whereas visual stimuli had a small effect on auditory working memory. With high cognitive load (3-back), auditory stimuli interfered (large effect size) with visual WM, and visual stimuli interfered (medium effect size) with auditory WM. (4) Conclusions: Audiovisual effects on WM follow the resource competition theory, and the cognitive load of a visual stimulus is dominated by competition; vision always interferes with audition, and audition conditionally interferes with vision. With increased visual cognitive load, competitive effects of audiovisual interactions were more obvious than those with auditory stimuli. Compared with visual stimuli, audiovisual stimuli showed significant interference only when visual cognitive load was high. With low visual cognitive load, the two stimulus components neither facilitated nor interfered with the other in accordance with a speed-accuracy trade-off.

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