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1.
Artigo em Inglês | MEDLINE | ID: mdl-38953397

RESUMO

AIMS: The cerebellum is involved in higher-order mental processing as well as sensorimotor functions. Although structural abnormalities in the cerebellum have been demonstrated in schizophrenia, neuroimaging techniques are not yet applicable to identify them given the lack of biomarkers. We aimed to develop a robust diagnostic model for schizophrenia using radiomic features from T1-weighted magnetic resonance imaging (T1-MRI) of the cerebellum. METHODS: A total of 336 participants (174 schizophrenia; 162 healthy controls [HCs]) were allocated to training (122 schizophrenia; 115 HCs) and test (52 schizophrenia; 47 HCs) cohorts. We obtained 2568 radiomic features from T1-MRI of the cerebellar subregions. After feature selection, a light gradient boosting machine classifier was trained. The discrimination and calibration of the model were evaluated. SHapley Additive exPlanations (SHAP) was applied to determine model interpretability. RESULTS: We identified 17 radiomic features to differentiate participants with schizophrenia from HCs. In the test cohort, the radiomics model had an area under the curve, accuracy, sensitivity, and specificity of 0.89 (95% confidence interval: 0.82-0.95), 78.8%, 88.5%, and 75.4%, respectively. The model explanation by SHAP suggested that the second-order size zone non-uniformity feature from the right lobule IX and first-order energy feature from the right lobules V and VI were highly associated with the risk of schizophrenia. CONCLUSION: The radiomics model focused on the cerebellum demonstrates robustness in diagnosing schizophrenia. Our results suggest that microcircuit disruption in the posterior cerebellum is a disease-defining feature of schizophrenia, and radiomics modeling has potential for supporting biomarker-based decision-making in clinical practice.

2.
Small ; : e2402003, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38884191

RESUMO

Global healthcare based on the Internet of Things system is rapidly transforming to measure precise physiological body parameters without visiting hospitals at remote patients and associated symptoms monitoring. 2D materials and the prevailing mood of current ever-expanding MXene-based sensing devices motivate to introduce first the novel iridium (Ir) precious metal incorporated vanadium (V)-MXene via industrially favored emerging atomic layer deposition (ALD) techniques. The current work contributes a precise control and delicate balance of Ir single atomic forms or clusters on the V-MXene to constitute a unique precious metal-MXene embedded heterostructure (Ir-ALD@V-MXene) in practical real-time sensing healthcare applications to thermography with human-machine interface for the first time. Ir-ALD@V-MXene delivers an ultrahigh durability and sensing performance of 2.4% °C-1 than pristine V-MXene (0.42% °C-1), outperforming several conventionally used MXenes, graphene, underscoring the importance of the Ir-ALD innovative process. Aberration-corrected advanced ultra-high-resolution transmission/scanning transmission electron microscopy confirms the presence of Ir atomic clusters on well-aligned 2D-layered V-MXene structure and their advanced heterostructure formation (Ir-ALD@V-MXene), enhanced sensing mechanism is investigated using density functional theory (DFT) computations. A rational design empowering the Ir-ALD process on least explored V-MXene can potentially unfold further precious metals ALD-process developments for next-generation wearable personal healthcare devices.

3.
PLoS One ; 19(6): e0299345, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38870176

RESUMO

INTRODUCTION: Cervical cancer presents a significant global health challenge, disproportionately impacting underserved populations with limited access to healthcare. Early detection and effective management are vital in addressing this public health concern. This study focuses on Glyoxalase-1 (GLO1), an enzyme crucial for methylglyoxal detoxification, in the context of cervical cancer. METHODS: We assessed GLO1 expression in cervical cancer patient samples using immunohistochemistry. In vitro experiments using HeLa cells were conducted to evaluate the impact of GLO1 inhibition on cell viability and migration. Single-cell RNA sequencing (scRNA-seq) and gene set variation analysis were utilized to investigate the role of GLO1 in the metabolism of cervical cancer. Additionally, public microarray data were analyzed to determine GLO1 expression across various stages of cervical cancer. RESULTS: Our analysis included 58 cervical cancer patients, and showed that GLO1 is significantly upregulated in cervical cancer tissues compared to normal cervical tissues, independent of pathological findings and disease stage. In vitro experiments indicated that GLO1 inhibition by S-p-bromobenzylglutathione cyclopentyl diester decreased cell viability and migration in cervical cancer cell lines. Analyses of scRNA-seq data and public gene expression datasets corroborated the overexpression of GLO1 and its involvement in cancer metabolism, particularly glycolysis. An examination of expression data from precancerous lesions revealed a progressive increase in GLO1 expression from normal tissue to invasive cervical cancer. CONCLUSIONS: This study highlights the critical role of GLO1 in the progression of cervical cancer, presenting it as a potential biomarker and therapeutic target. These findings contribute valuable insights towards personalized treatment approaches and augment the ongoing efforts to combat cervical cancer. Further research is necessary to comprehensively explore GLO1's potential in clinical applications.


Assuntos
Biomarcadores Tumorais , Lactoilglutationa Liase , Neoplasias do Colo do Útero , Humanos , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Feminino , Lactoilglutationa Liase/metabolismo , Lactoilglutationa Liase/genética , Lactoilglutationa Liase/antagonistas & inibidores , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Células HeLa , Progressão da Doença , Movimento Celular , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Pessoa de Meia-Idade , Sobrevivência Celular/efeitos dos fármacos , Adulto , Linhagem Celular Tumoral
4.
bioRxiv ; 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38854035

RESUMO

Fungal plasma membrane proteins represent key therapeutic targets for antifungal agents, yet their structure and spatial distribution in the native context remain poorly characterized. Herein, we employ an integrative multimodal approach to elucidate the structural and functional organization of plasma membrane protein complexes in Candida glabrata , focusing on prominent and essential membrane proteins, the polysaccharide synthase ß-(1,3)-glucan synthase (GS) and the proton pump Pma1. Cryo-electron tomography (cryo-ET) and live cell imaging reveal that GS and Pma1 are heterogeneously distributed into distinct plasma membrane microdomains. Treatment with caspofungin, an echinocandin antifungal that targets GS, alters the plasma membrane and disrupts the native distribution of GS and Pma1. Based on these findings, we propose a model for echinocandin action that considers how drug interactions with the plasma membrane environment lead to inhibition of GS. Our work underscores the importance of interrogating the structural and dynamic characteristics of fungal plasma membrane proteins in situ to understand function and facilitate precisely targeted development of novel antifungal therapies.

5.
Nat Commun ; 15(1): 5446, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937458

RESUMO

Mitochondrial transcription factor A (TFAM) employs DNA bending to package mitochondrial DNA (mtDNA) into nucleoids and recruit mitochondrial RNA polymerase (POLRMT) at specific promoter sites, light strand promoter (LSP) and heavy strand promoter (HSP). Herein, we characterize the conformational dynamics of TFAM on promoter and non-promoter sequences using single-molecule fluorescence resonance energy transfer (smFRET) and single-molecule protein-induced fluorescence enhancement (smPIFE) methods. The DNA-TFAM complexes dynamically transition between partially and fully bent DNA conformational states. The bending/unbending transition rates and bending stability are DNA sequence-dependent-LSP forms the most stable fully bent complex and the non-specific sequence the least, which correlates with the lifetimes and affinities of TFAM with these DNA sequences. By quantifying the dynamic nature of the DNA-TFAM complexes, our study provides insights into how TFAM acts as a multifunctional protein through the DNA bending states to achieve sequence specificity and fidelity in mitochondrial transcription while performing mtDNA packaging.


Assuntos
Empacotamento do DNA , DNA Mitocondrial , Proteínas de Ligação a DNA , Transferência Ressonante de Energia de Fluorescência , Proteínas Mitocondriais , Conformação de Ácido Nucleico , Regiões Promotoras Genéticas , Fatores de Transcrição , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/química , Fatores de Transcrição/metabolismo , Fatores de Transcrição/química , Fatores de Transcrição/genética , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Humanos , Iniciação da Transcrição Genética , Mitocôndrias/metabolismo , Mitocôndrias/genética , Imagem Individual de Molécula , RNA Polimerases Dirigidas por DNA/metabolismo , RNA Polimerases Dirigidas por DNA/química , RNA Polimerases Dirigidas por DNA/genética , Sequência de Bases , Ligação Proteica
6.
Int J Mol Sci ; 25(10)2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38791285

RESUMO

Extracellular vesicles (EVs) have been found to have the characteristics of their parent cells. Based on the characteristics of these EVs, various studies on disease treatment using mesenchymal stem cell (MSC)-derived EVs with regenerative activity have been actively conducted. The therapeutic nature of MSC-derived EVs has been shown in several studies, but in recent years, there have been many efforts to functionalize EVs to give them more potent therapeutic effects. Strategies for functionalizing EVs include endogenous and exogenous methods. In this study, human umbilical cord MSC (UCMSC)-derived EVs were selected for optimum OA treatments with expectation via bioinformatics analysis based on antibody array. And we created a novel nanovesicle system called the IGF-si-EV, which has the properties of both cartilage regeneration and long-term retention in the lesion site, attaching positively charged insulin-like growth factor-1 (IGF-1) to the surface of the UCMSC-derived Evs carrying siRNA, which inhibits MMP13. The downregulation of inflammation-related cytokine (MMP13, NF-kB, and IL-6) and the upregulation of cartilage-regeneration-related factors (Col2, Acan) were achieved with IGF-si-EV. Moreover, the ability of IGF-si-EV to remain in the lesion site for a long time has been proven through an ex vivo system. Collectively, the final constructed IGF-si-EV can be proposed as an effective OA treatment through its successful MMP13 inhibition, chondroprotective effect, and cartilage adhesion ability. We also believe that this EV-based nanoparticle-manufacturing technology can be applied as a platform technology for various diseases.


Assuntos
Vesículas Extracelulares , Fator de Crescimento Insulin-Like I , Células-Tronco Mesenquimais , Osteoartrite , RNA Interferente Pequeno , Fator de Crescimento Insulin-Like I/metabolismo , Vesículas Extracelulares/metabolismo , Humanos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Osteoartrite/terapia , Osteoartrite/metabolismo , RNA Interferente Pequeno/genética , Animais , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 13 da Matriz/genética
7.
Gut Liver ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38712399

RESUMO

Background/Aims: : In 2019, the American Society for Gastrointestinal Endoscopy (ASGE) established clinical predictors for choledocholithiasis. Our study was designed to evaluate these predictors within the Korean clinical context, establish cutoff values, and develop a predictive model. Methods: : This retrospective study analyzed patients who underwent laparoscopic cholecystectomy. The relationships between choledocholithiasis and predictors including age, blood tests, and imaging findings were assessed through univariate and multivariate logistic regression analyses. We established Korean cutoff values for these predictors and developed a scoring system for choledocholithiasis using a multivariate logistic regression. The performance of this scoring system was then compared with that of the 2019 ASGE guidelines through a receiver operating characteristic curve. Results: : We established Korean cutoff values for age (>70 years), alanine aminotransferase (>26.5 U/L), aspartate aminotransferase (>28.5 U/L), gamma-glutamyl transferase (GGT; >82.5 U/L), alkaline phosphatase (ALP; >77.5 U/L), and total bilirubin (>0.95 mg/dL). In the multivariate analysis, only age >70 years, GGT >77.5 U/L, ALP >77.5 U/L, and common bile duct dilatation remained significant. We then developed a new Korean risk stratification model from the multivariate analysis, with an area under the curve of 0.777 (95% confidence interval, 0.75 to 0.81). Our model was stratified into the low-risk, intermediate-risk, and high-risk groups with the scores being <1.0, 1.0-5.5, and >5.5, respectively. Conclusions: : Predictors of choledocholithiasis in cholecystectomy patients and their cutoff values in Korean should be adjusted and further studies are needed to develop appropriate guidelines.

8.
Clin Psychopharmacol Neurosci ; 22(2): 345-353, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38627081

RESUMO

Objective: : Impulsivity can be observed in individuals with or without mental illness. The discovery of neural correlates responsible for trait impulsivity can therefore help to understand the severity of psychiatric symptoms, personality characteristics and social adjustment. In this study, we aimed to identify the gray matter substrates of trait impulsivity in healthy individuals. Methods: : Seventy-five healthy individuals were enrolled. At baseline, trait impulsivity was assessed using the Barratt Impulsiveness Scale (BIS) and all participants underwent T1-weighted magnetic resonance imaging scan. Beck Anxiety Inventory (BAI), World Health Organization Quality of Life (WHOQOL-BREF) and Connor-Davidson Resilience Scale (CD-RISC) were also assessed. Mean cortical thickness (CT) and the local gyrification index (LGI) were calculated to perform whole-brain vertex-wise correlation analysis, which were performed to investigate the relationship between BIS scores and CT or LGI in each brain region. We also revealed the relationship between brain regions and psychological measurements. Results: : Total BIS scores were significantly and negatively correlated with mean CT values in the left lateral occipital cortex (OC) and LGIs in the inferior frontal gyrus (IFG). Correlation analyses revealed that the lateral OC's mean CT values were negatively correlated with BAI scores and positively correlated with WHOQOL-BREF scores, while LGI in the IFG was positively correlated with CD-RISC scores. Conclusion: : Our study showed that trait impulsivity might be associated with the lateral OC and IFG in healthy individuals. Understanding the neural correlates of trait impulsivity could provide ways to expect high impulsivity, anxiety, and poor resilience in healthy adults.

9.
Comput Biol Med ; 174: 108436, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38643597

RESUMO

Great efforts have been made over the years to identify novel drug pairs with synergistic effects. Although numerous computational approaches have been proposed to analyze diverse types of biological big data, the pharmacogenomic profiles, presumably the most direct proxy of drug effects, have been rarely used due to the data sparsity problem. In this study, we developed a composite deep-learning-based model that predicts the drug synergy effect utilizing pharmacogenomic profiles as well as molecular properties. Graph convolutional network (GCN) was used to represent and integrate the chemical structure, genetic interactions, drug-target information, and gene expression profiles of cell lines. Insufficient amount of pharmacogenomic data, i.e., drug-induced expression profiles from the LINCS project, was resolved by augmenting the data with the predicted profiles. Our method learned and predicted the Loewe synergy score in the DrugComb database and achieved a better or comparable performance compared to other published methods in a benchmark test. We also investigated contribution of various input features, which highlighted the value of basal gene expression and pharmacogenomic profiles of each cell line. Importantly, DRSPRING (DRug Synergy PRediction by INtegrated GCN) can be applied to any drug pairs and any cell lines, greatly expanding its applicability compared to previous methods.


Assuntos
Sinergismo Farmacológico , Humanos , Transcriptoma/efeitos dos fármacos , Transcriptoma/genética , Aprendizado Profundo , Perfilação da Expressão Gênica/métodos , Biologia Computacional/métodos , Redes Neurais de Computação
10.
Sci Rep ; 14(1): 9875, 2024 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-38684873

RESUMO

Resilient individuals are less likely to develop psychiatric disorders despite extreme psychological distress. This study investigated the multimodal structural neural correlates of dispositional resilience among healthy individuals. Participants included 92 healthy individuals. The Korean version of the Connor-Davidson Resilience Scale and other psychological measures were used. Gray matter volumes (GMVs), cortical thickness, local gyrification index (LGI), and white matter (WM) microstructures were analyzed using voxel-based morphometry, FreeSurfer, and tract-based spatial statistics, respectively. Higher resilient individuals showed significantly higher GMVs in the inferior frontal gyrus (IFG), increased LGI in the insula, and lower fractional anisotropy values in the superior longitudinal fasciculus II (SLF II). These resilience's neural correlates were associated with good quality of life in physical functioning or general health and low levels of depression. Therefore, the GMVs in the IFG, LGI in the insula, and WM microstructures in the SLF II can be associated with resilience that contributes to emotional regulation, empathy, and social cognition.


Assuntos
Substância Cinzenta , Resiliência Psicológica , Substância Branca , Humanos , Masculino , Feminino , Adulto , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/fisiologia , Substância Cinzenta/anatomia & histologia , Substância Branca/diagnóstico por imagem , Substância Branca/fisiologia , Adulto Jovem , Imageamento por Ressonância Magnética , Voluntários Saudáveis , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , Qualidade de Vida
11.
Saf Health Work ; 15(1): 53-58, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38496277

RESUMO

Background: As social distancing persists and interest in work-life balance grows, more companies are adopting flexible work policies. While there have been studies on sleep disorders associated with different types of work, such as shift work, research exploring the relationship between flexible work schedules and sleep disorders is still limited, particularly among Korean workers. Methods: We performed a secondary analysis of the 6th Korean Working Conditions Survey, focusing on 31,243 paid workers out of a total of 50,538 participants. We defined flexible workers as those who set their own working hours. Sleep disorders were divided into three categories: 'difficulty falling asleep,' 'frequent waking during sleep,' and 'waking up feeling exhausted and fatigued.' Using scores derived from three specific symptoms, the Minimal Insomnia Symptoms Scale (MISS) was calculated to assess the prevalence of insomnia. We used chi-square tests to analyze demographic and job-related differences. A multivariate logistic regression analysis was employed to identify any relationship between flexible work schedules and sleep disorders. Results: Significant differences were found between flexible and non-flexible workers regarding age, income level, education level, and job type. Flexible workers reported sleep-related symptoms significantly more often. The odds ratio for insomnia was 1.40 (95% CI 1.21-1.61). For males, the odds ratio was 1.68 (1.36-2.08). Conclusion: This study establishes a correlation between flexible work schedules and sleep disorders among Korean salaried workers. Potential causes could include changes in circadian rhythm, increased work demands, and extended working hours. To precisely determine causality and associated diseases, further research is required.

12.
Schizophr Bull ; 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38300803

RESUMO

BACKGROUND AND HYPOTHESIS: Schizophrenia involves microstructural changes in white matter (WM) tracts. Oxidative stress is a key factor causing WM damage by hindering oligodendrocyte development and myelin maturation. Uric acid (UA), an endogenous antioxidant, may protect against oxidative stress. We investigated the effect of UA on WM connectivity in antipsychotic-naive or -free patients with early- or chronic-stage schizophrenia. STUDY DESIGN: A total of 192 patients with schizophrenia (122 recent-onset [ROS] and 70 chronic [CS]) and 107 healthy controls (HCs) participated in this study. Diffusion tensor imaging data and serum UA levels at baseline were obtained. STUDY RESULTS: Fractional anisotropy was lower in the widespread WM regions across the whole brain, and diffusivity measures were higher in both schizophrenia groups than in HCs. The CS group showed lower diffusivity in some WM tracts than the ROS or HC groups. The linear relationship of serum UA levels with axial and mean diffusivity in the right frontal region was significantly different between schizophrenia stages, which was driven by a negative association in the CS group. WM diffusivity associated with serum UA levels correlated with 8-week treatment responses only in patients with CS, suggesting UA to be protective against long-term schizophrenia. CONCLUSIONS: UA may protect against the WM damage associated with the progression of schizophrenia by reducing oxidative stress and supporting WM repair against oxidative damage. These results provide insights into the positive role of UA and may facilitate the development of novel disease-modifying therapies.

13.
J Clin Med ; 13(4)2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38398473

RESUMO

The diagnostic value of ileoscopy is not well established, and its routine practice is controversial. We aimed to investigate the diagnostic value of biopsy for macroscopically abnormal lesions in the terminal ileum and to identify the association between endoscopic indications and findings and the presence of significant disease. This retrospective study included 551 patients who underwent biopsy of abnormal lesions in the terminal ileum (TI) during colonoscopy between February 2000 and June 2019. Biopsy results were analyzed in relation to the endoscopic indications and gross findings. Significant disease was defined as a case in which a specific disease was suspected or confirmed by the biopsy results, requiring additional examination or treatment. Among the 551 biopsies from macroscopically abnormal lesions in the TI, 44 (8.0%) had significant diseases. The frequency of significant disease was high in patients with clinically suspected inflammatory bowel disease (IBD) (50.0%), anemia (31.6%), right lower quadrant (RLQ) pain (28.6%), and radiological abnormalities in the TI (27.5%). The frequency of Crohn's disease (CD) was high in patients with clinically suspected IBD. A concurrent abnormality in the ileocecal valve (ICV) (14.3%) and the presence of an ulcer (14.2%), mass, or polyp (25.4%) correlated with a high incidence of significant disease, particularly CD. In cases of suspected IBD, anemia, RLQ pain, and radiologic abnormalities in the TI, there is a high possibility of significant disease. Ulcers, masses, polyps, and concurrent abnormalities in the ICV were also associated with significant disease.

14.
Schizophrenia (Heidelb) ; 10(1): 11, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38280893

RESUMO

Although the role of the cerebellum in schizophrenia has gained attention, its contribution to cognitive impairment remains unclear. We aimed to investigate volumetric alterations in the cerebro-cerebellar gray matter (GM) in patients with recent-onset schizophrenia (ROS) and chronic schizophrenia (CS) compared with healthy controls (HCs). Seventy-two ROS, 43 CS, and 127 HC participants were recruited, and high-resolution T1-weighted structural magnetic resonance images of the brain were acquired. We compared cerebellar GM volumes among the groups using voxel-based morphometry and examined the cerebro-cerebellar GM volumetric correlations in participants with schizophrenia. Exploratory correlation analysis investigated the functional relevance of cerebro-cerebellar GM volume alterations to cognitive function in the schizophrenia group. The ROS and CS participants demonstrated smaller cerebellar GM volumes, particularly in Crus I and II, than HCs. Extracted cerebellar GM volumes demonstrated significant positive correlations with the cerebral GM volume in the fronto-temporo-parietal association areas engaged in higher-order association. The exploratory analysis showed that smaller cerebellar GM in the posterior lobe regions was associated with poorer cognitive performance in participants with schizophrenia. Our study suggests that cerebellar pathogenesis is present in the early stages of schizophrenia and interconnected with structural abnormalities in the cerebral cortex. Integrating the cerebellum into the pathogenesis of schizophrenia will help advance our understanding of the disease and identify novel treatment targets concerning dysfunctional cerebro-cerebellar interactions.

15.
Int J Biol Macromol ; 255: 128313, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37995783

RESUMO

Tyrosinase-mediated protein conjugation has recently drawn attention as a site-specific protein modification tool under mild conditions. However, the tyrosinases reported to date act only on extremely exposed tyrosine residues, which limits where the target tyrosine can be located. Herein, we report a tyrosinase from Streptomyces avermitilis (SaTYR), that exhibits a much higher activity against tyrosine residues on the protein surface than other tyrosinases. We determined the crystal structure of SaTYR and revealed that the enzyme has a relatively flat and shallow substrate-binding pocket to accommodate a protein substrate. We demonstrated SaTYR-mediated fluorescence dye tagging and PEGylation of a surface tyrosine residue that was unreacted by other tyrosinases with an approximately 95.2 % conjugation yield in 1 h. We also present a structural rationale that considers the steric hindrance from adjacent residues and surrounding structures along with the extent of solvent exposure of residues, as necessary when determining the optimal positions for introducing target tyrosine residues in SaTYR-mediated protein modification. The study demonstrated that the novel tyrosinase, SaTYR, extends the scope of tyrosinase-mediated protein modification, and we propose that site-specific tyrosine conjugation using SaTYR is a promising strategy for protein bioconjugation in various applications.


Assuntos
Monofenol Mono-Oxigenase , Streptomyces , Monofenol Mono-Oxigenase/metabolismo , Proteínas/metabolismo , Tirosina/química
16.
Sci Rep ; 13(1): 21822, 2023 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-38071248

RESUMO

Subthreshold social anxiety (SSA) is a condition in which individuals experience social anxiety that does not reach the threshold required for a clinical diagnosis of a social anxiety disorder (SAD). Although SSA may not impair lives as severely as SAD, it can affect social functioning. However, only a few studies focused on structural neural correlates of SSA. We recruited 65 individuals with SSA and used the Leibowitz Social Anxiety Scale to assess their social and performance anxiety levels and other relevant measures of social anxiety. Voxel-wise whole-brain correlational analyses showed a positive association between the cortical thickness (CT) of the superior frontal gyrus (SFG) and social anxiety levels and a negative correlation between the CT of the fusiform gyrus (FG) and performance anxiety levels in individuals with SSA. Exploratory Pearson's correlation analyses showed significant positive correlations between the CT of the SFG and Generalized Anxiety Disorder-7 total scores and negative associations between the CT of the FG and Beck Anxiety Inventory total scores. Our study provides insight into the neural basis of SSA, particularly performance anxiety, by highlighting the association between CT in specific brain regions and SSA characteristics.


Assuntos
Encéfalo , Ansiedade de Desempenho , Humanos , Lobo Temporal , Medo , Córtex Pré-Frontal , Imageamento por Ressonância Magnética
17.
Nat Commun ; 14(1): 7298, 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37949853

RESUMO

Chiral metamaterials have received significant attention due to their strong chiroptical interactions with electromagnetic waves of incident light. However, the fabrication of large-area, hierarchically manufactured chiral plasmonic structures with high dissymmetry factors (g-factors) over a wide spectral range remains the key barrier to practical applications. Here we report a facile yet efficient method to fabricate hierarchical chiral nanostructures over a large area (>11.7 × 11.7 cm2) and with high g-factors (up to 0.07 in the visible region) by imparting extrinsic chirality to nanostructured polymer substrates through the simple exertion of mechanical force. We also demonstrate the application of our approach in the polarized emission of quantum dots and information encryption, including chiral quick response codes and anti-counterfeiting. This study thus paves the way for the rational design and fabrication of large-area chiral nanostructures and for their application in quantum communications and security-enhanced optical communications.

18.
Int J Mol Sci ; 24(22)2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-38003216

RESUMO

The therapeutic potential of Mesenchymal stem cells (MSCs) for the treatment of Intervertebral disc (IVD) degeneration can be enhanced by amplifying specific cytokines and proteins. This study aimed to investigate the therapeutic potential of tetracycline-off system-engineered tonsil-derived mesenchymal stem cells (ToMSC-Tetoff-TGFß1-IGF1-BMP7) for treating intervertebral disc (IVD) degeneration. ToMSCs were isolated from a tonsillectomy patient and genetically modified with four distinct plasmids via CRISPR/Cas9-mediated knock-in gene editing. Transgene expression was confirmed through immunofluorescence, western blots, and an enzyme-linked immunosorbent assay for transforming growth factor beta 1 (TGFß1) protein secretion, and the effect of MSC-TetOff-TGFß1-IGF1-BMP7 on disc injury was assessed in a rat model. The ToMSC-Tetoff-TGFß1-IGF1-BMP7 treatment exhibited superior therapeutic effects compared to ToMSC-TGFß1, and ToMSC-SDF1α implantation groups, stimulating the regeneration of nucleus pulposus (NP) cells crucial for IVD. The treatment showed potential to restore the structural integrity of the extracellular matrix (ECM) by upregulating key molecules such as aggrecan and type II collagen. It also exhibited anti-inflammatory properties and reduced pain-inducing neuropeptides. ToMSC-Tetoff-TGFß1-IGF1-BMP7 holds promise as a novel treatment for IVD degeneration. It appears to promote NP cell regeneration, restore ECM structure, suppress inflammation, and reduce pain. However, more research and clinical trials are required to confirm its therapeutic potential.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Células-Tronco Mesenquimais , Núcleo Pulposo , Humanos , Ratos , Animais , Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/genética , Degeneração do Disco Intervertebral/terapia , Degeneração do Disco Intervertebral/metabolismo , Núcleo Pulposo/metabolismo , Tetraciclina/farmacologia , Antibacterianos/farmacologia , Células-Tronco Mesenquimais/metabolismo
19.
Psychiatry Investig ; 20(11): 1069-1076, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37997335

RESUMO

OBJECTIVE: This study investigated the impact of intolerance of uncertainty (IU) on structural changes in the brain and symptom severity in patients with panic disorder. METHODS: This study included 90 participants diagnosed with panic disorder. The IU Scale, Panic Disorder Severity Scale (PDSS), Beck Depression Inventory-II (BDI-II), Penn State Worry Questionnaire (PSWQ), Self-Forgiveness Scale (SFS), and Short Form 36 Health Survey (SF) were used. A voxel-wise correlation analysis was conducted to investigate the structural differences in the gray matter. RESULTS: As IU increased, the cortical thickness of the right lingual gyrus decreased significantly, while the gray matter volume of the right pars triangularis increased. The cortical thickness of the right lingual gyrus showed a significant negative correlation with the BDI-II score and a positive correlation with the SFS. Additionally, the gray matter volume of the right pars triangularis was positively correlated with the PDSS, PSWQ, and BDI-II scores and negatively correlated with the mental health domain of the SF. CONCLUSION: According to our findings, elevated IU in participants with panic disorder was associated with cortical thinning in the lingual gyrus and increased gray matter volume in the pars triangularis. These structural alterations may also have an impact on perceived quality of life, as well as high levels of depression and anxiety.

20.
Ann Occup Environ Med ; 35: e29, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37701491

RESUMO

Background: Lone workers are generally defined as individuals who work alone without supervision, including self-employed people. While lone workers are considered a vulnerable group in some countries, there is a lack of research on their health status in domestic studies. Globally, the number of lone workers has been increasing, and this trend has been further accelerated since the coronavirus disease 2019 (COVID-19) pandemic with the rise of remote work. Methods: The study analyzed data from 44,281 participants, excluding unpaid family workers, soldiers, and those with missing data. Lone workers were defined as individuals who reported having no colleagues with the same job at their current workplace. Self-rated health status was categorized as "good" or "poor." Results: This study found a statistically significant higher number of lone workers among women compare to men. The largest occupational category for lone workers was service and sales workers, followed by agriculture and fisheries workers. A majority of non-lone workers reported working 40 hours or less per week, while the majority of lone workers reported working 53 hours or more per week. In addition, lone workers had significantly poorer health status evaluations compared to non-lone workers (odds ratio: 1.297; 95% confidence interval: 1.165-1.444). Conclusions: Further research is needed to investigate the causal relationship between lone work and health, using data collected after the COVID-19 pandemic.

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