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1.
iScience ; 27(7): 110137, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39006481

ABSTRACT

Pituitary adenoma-induced excess endocrine growth hormone (GH) secretion can lead to breast cancer development and metastasis. Herein, we used an acromegaly mouse model to investigate the role of excess endocrine GH on triple-negative breast cancer (TNBC) growth and metastasis. Additionally, we aimed to elucidate the molecular mechanism of transcription factor 20 (TCF20)/nuclear factor erythroid 2-related factor 2 (NRF2) signaling-mediated aggressiveness and metastasis of TNBC. Excess endocrine GH induced TCF20 activates the transcription of NRF2 and NRF2-target genes to facilitate TNBC metastasis. Inhibition of GH receptor (GHR) and TCF20 activity using the GHR antagonist or small-interfering RNA-induced gene knockdown resulted in reduced tumor volume and metastasis, suggesting that excess endocrine GH stimulates TCF20/NRF2 pathways in TNBC and promotes metastasis to the lung. GHR inhibitors present an effective therapeutic strategy to prevent TNBC cell growth and metastasis. Our findings revealed functional and mechanistic roles of the GH-TCF20-NRF2 signaling axis in TBNC progression.

2.
Cancer Res Treat ; 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38853539

ABSTRACT

Purpose: In 2024, medical researchers in the Republic of Korea were invited to amend the health and medical data utilization guidelines (Government Publications Registration Number: 11-1352000-0052828-14). This study aimed to show the overall impact of the guideline revision, with a focus on clinical genomic data. Materials and Methods: This study amended the pseudonymization of genomic data defined in the previous version through a joint study led by the Ministry of Health and Welfare, the Korea Health Information Service, and the Korea Genome Organization. To develop the previous version, we held three conferences with four main medical research institutes and seven academic societies. We conducted two surveys targeting special genome experts in academia, industry, and institutes. Results: We found that cases of pseudonymization in the application of genome data were rare and that there was ambiguity in the terminology used in the previous version of the guidelines. Most experts (> ~90%) agreed that the 'reserved' condition should be eliminated to make genomic data available after pseudonymization. In this study, the scope of genomic data was defined as clinical next generation sequencing data, including FASTQ, BAM/SAM, VCF, and medical records. Pseudonymization targets genomic sequences and metadata, embedding specific elements, such as germline mutations, short tandem repeats, single-nucleotide polymorphisms, and identifiable data (for example, ID or environmental values). Expression data generated from multi-omics can be used without pseudonymization. Conclusion: This amendment will not only enhance the safe use of healthcare data but also promote advancements in disease prevention, diagnosis, and treatment.

3.
Biochem Biophys Res Commun ; 726: 150280, 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-38909534

ABSTRACT

Esophageal epithelium is one of the most proliferative and regenerative epithelia in our body, indicating robust stem cell activity. However, the underlying mechanisms regulating the self-renewal and differentiation of esophageal stem cells need to be more elucidated. Here, we identify the role of YAP1 in esophageal stem cells. YAP1 is differentially expressed in the nuclei of esophageal basal cells. Furthermore, the treatment of verteporfin, a YAP1 inhibitor, interfered with esophageal organoid formation. Consistently, YAP1 deletion decreased esophageal organoid formation and the expression of basal genes while increasing the expression of suprabasal genes. Finally, global transcriptomic analysis revealed that YAP1 inhibition induced a significant enrichment of gene sets related to keratinization and cornification, while depleting gene sets related to DNA repair and chromosome maintenance. Our data uncover a novel regulatory mechanism for esophageal stem cells, which could provide a potential strategy for esophageal regenerative medicine.


Subject(s)
Adaptor Proteins, Signal Transducing , Cell Differentiation , Cell Self Renewal , Esophagus , Stem Cells , YAP-Signaling Proteins , YAP-Signaling Proteins/metabolism , Stem Cells/metabolism , Stem Cells/cytology , Esophagus/cytology , Esophagus/metabolism , Animals , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Mice , Humans , Organoids/metabolism , Organoids/cytology
4.
J Lipid Atheroscler ; 13(2): 184-193, 2024 May.
Article in English | MEDLINE | ID: mdl-38826178

ABSTRACT

Objective: Serum hemoglobin (Hb) level affects the viscosity of blood. Several studies have reported that Hb level is associated with adverse cardiovascular outcome. However, there is a paucity of evidence on the association between serum Hb level and the risk of subclinical atherosclerosis. Thus, the objective of this study was to investigate the relationship between Hb level and risk of carotid plaque in a health checkup cohort. Methods: This retrospective study analyzed a total of 3,805 individuals without history of cardiovascular disease (CVD) who underwent carotid ultrasonography (USG) between January 2016 and June 2018. Participants were divided into 4 groups based on Hb quartiles in each of male and female. Carotid plaque score was calculated based on USG reports. Multivariable logistic regression analysis was performed for each index of quartile groups regarding the risk of carotid plaque. Results: Of 3,805 individuals (mean age, 52.62±10.25 years; 2,674 [70.28%] males), mean Hb level was 15.11±0.75 g/dL in male and 13.35±0.74 g/dL in female. When the Q1 group was compared to the Q4, increasing quartile of Hb was associated with the presence of significant carotid plaque (plaque score ≥3) in male (adjusted odds ratio [OR], 1.538; 95% confidence interval [CI], 1.182-2.001; p=0.001) and female (adjusted OR, 1.749; 95% CI, 1.058-2.676; p=0.01). Conclusion: A high Hb level is associated with an increased risk of carotid plaques in individuals without history of CVD. This finding may support the need for early screening of CVD in individuals with high Hb levels.

5.
J Alzheimers Dis Rep ; 8(1): 863-876, 2024.
Article in English | MEDLINE | ID: mdl-38910943

ABSTRACT

Background: Application of visual scoring scales for regional atrophy in Alzheimer's disease (AD) in clinical settings is limited by their high time cost and low intra/inter-rater agreement. Objective: To provide automated atrophy scoring using objective volume driven from deep-learning segmentation methods for AD subtype classification using magnetic resonance imaging (MRI). Methods: We enrolled 3,959 participants (1,732 cognitively normal [CN], 1594 with mild cognitive impairment [MCI], and 633 with AD). The occupancy indices for each regional volume were calculated by dividing each volume by the size of the lateral and inferior ventricular volumes. MR images from 355 participants (119 CN, 119 MCI, and 117 AD) from three different centers were used for validation. Two neuroradiologists performed visual assessments of the medial temporal, posterior, and global cortical atrophy scores in the frontal lobe using T1-weighted MR images. Images were also analyzed using the deep learning-based segmentation software, Neurophet AQUA. Cutoff values for the three scores were determined using the data distribution according to age. The scoring results were compared for consistency and reliability. Results: Four volumetric-driven scoring results showed a high correlation with the visual scoring results for AD, MCI, and CN. The overall agreement with human raters was weak-to-moderate for atrophy scoring in CN participants, and good-to-almost perfect in AD and MCI participants. AD subtyping by automated scores also showed usefulness as a research tool. Conclusions: Determining AD subtypes using automated atrophy scoring for late-MCI and AD could be useful in clinical settings or multicenter studies with large datasets.

6.
RSC Adv ; 14(28): 19718-19725, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38899034

ABSTRACT

The mechanical strength of magnesium implants undergoes a rapid decline after implantation due to bioabsorption, which can lead to the risk of rupture. To ensure sustained mechanical strength and initiate bioabsorption selectively upon specific external stimuli until the bone regains sufficient support, we developed a biosafe near-infrared light (NIR)-sensitive polymer coating using polycaprolactone (PCL) and Ti3C2 (MXenes). The synthetic MXene powders were characterized using SEM, EDS, and XRD, and the amount of MXenes had a proliferation-promoting effect on MC3T3-E1, as observed through cell assays. The PCL-MXene coating was successfully prepared on the magnesium surface using the casting coating method, and it can protect the magnesium surface for up to 28 days by decreasing the corrosion ratio. However, the coating can be easily degraded after exposure to NIR light for 20 minutes to expose the magnesium substrate, especially in a liquid environment. Meanwhile, the magnesium implant with the PCL-MXene coating has no cytotoxicity toward MC3T3-E1. These findings can provide a new solution for the development of controlled degradation implants.

7.
BMC Med ; 22(1): 212, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38807210

ABSTRACT

BACKGROUND: To examine the effectiveness and safety of a data sharing and comprehensive management platform for institutionalized older patients. METHODS: We applied information technology-supported integrated health service platform to patients who live at long-term care hospitals (LTCHs) and nursing homes (NHs) with cluster randomized controlled study. We enrolled 555 patients aged 65 or older (461 from 7 LTCHs, 94 from 5 NHs). For the intervention group, a tablet-based platform comprising comprehensive geriatric assessment, disease management, potentially inappropriate medication (PIM) management, rehabilitation program, and screening for adverse events and warning alarms were provided for physicians or nurses. The control group was managed with usual care. Co-primary outcomes were (1) control rate of hypertension and diabetes, (2) medication adjustment (PIM prescription rate, proportion of polypharmacy), and (3) combination of potential quality-of-care problems (composite quality indicator) from the interRAI assessment system which assessed after 3-month of intervention. RESULTS: We screened 1119 patients and included 555 patients (control; 289, intervention; 266) for analysis. Patients allocated to the intervention group had better cognitive function and took less medications and PIMs at baseline. The diabetes control rate (OR = 2.61, 95% CI 1.37-4.99, p = 0.0035), discontinuation of PIM (OR = 4.65, 95% CI 2.41-8.97, p < 0.0001), reduction of medication in patients with polypharmacy (OR = 1.98, 95% CI 1.24-3.16, p = 0.0042), and number of PIMs use (ꞵ = - 0.27, p < 0.0001) improved significantly in the intervention group. There was no significant difference in hypertension control rate (OR = 0.54, 95% CI 0.20-1.43, p = 0.2129), proportion of polypharmacy (OR = 1.40, 95% CI 0.75-2.60, p = 0.2863), and improvement of composite quality indicators (ꞵ = 0.03, p = 0.2094). For secondary outcomes, cognitive and motor function, quality of life, and unplanned hospitalization were not different significantly between groups. CONCLUSIONS: The information technology-supported integrated health service effectively reduced PIM use and controlled diabetes among older patients in LTCH or NH without functional decline or increase of healthcare utilization. TRIAL REGISTRATION: Clinical Research Information Service, KCT0004360. Registered on 21 October 2019.


Subject(s)
Delivery of Health Care, Integrated , Long-Term Care , Humans , Aged , Male , Female , Aged, 80 and over , Long-Term Care/methods , Information Technology , Nursing Homes , Polypharmacy
8.
Sci Rep ; 14(1): 12276, 2024 05 29.
Article in English | MEDLINE | ID: mdl-38806509

ABSTRACT

Alzheimer's disease (AD) accounts for 60-70% of the population with dementia. Mild cognitive impairment (MCI) is a diagnostic entity defined as an intermediate stage between subjective cognitive decline and dementia, and about 10-15% of people annually convert to AD. We aimed to investigate the most robust model and modality combination by combining multi-modality image features based on demographic characteristics in six machine learning models. A total of 196 subjects were enrolled from four hospitals and the Alzheimer's Disease Neuroimaging Initiative dataset. During the four-year follow-up period, 47 (24%) patients progressed from MCI to AD. Volumes of the regions of interest, white matter hyperintensity, and regional Standardized Uptake Value Ratio (SUVR) were analyzed using T1, T2-weighted-Fluid-Attenuated Inversion Recovery (T2-FLAIR) MRIs, and amyloid PET (αPET), along with automatically provided hippocampal occupancy scores (HOC) and Fazekas scales. As a result of testing the robustness of the model, the GBM model was the most stable, and in modality combination, model performance was further improved in the absence of T2-FLAIR image features. Our study predicts the probability of AD conversion in MCI patients, which is expected to be useful information for clinician's early diagnosis and treatment plan design.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Disease Progression , Machine Learning , Magnetic Resonance Imaging , Positron-Emission Tomography , Humans , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/diagnosis , Female , Male , Aged , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/diagnosis , Magnetic Resonance Imaging/methods , Positron-Emission Tomography/methods , Aged, 80 and over , Neuroimaging/methods , Dementia/diagnostic imaging , Dementia/diagnosis
9.
Anal Sci ; 40(5): 907-915, 2024 May.
Article in English | MEDLINE | ID: mdl-38598050

ABSTRACT

Lateral flow assays have been widely used for detecting coronavirus disease 2019 (COVID-19). A lateral flow assay consists of a Nitrocellulose (NC) membrane, which must have a specific lateral flow rate for the proteins to react. The wicking rate is conventionally used as a method to assess the lateral flow in membranes. We used multiple regression and artificial neural networks (ANN) to predict the wicking rate of NC membranes based on membrane recipe data. The developed ANN predicted the wicking rate with a mean square error of 0.059, whereas the multiple regression had a square error of 0.503. This research also highlighted the significant impact of the water content on the wicking rate through images obtained from scanning electron microscopy. The findings of this research can cut down the research and development costs of novel NC membranes with a specific wicking rate significantly, as the algorithm can predict the wicking rate based on the membrane recipe.

10.
J Phys Chem Lett ; 15(16): 4437-4443, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38626458

ABSTRACT

Water molecules confined between biological membranes exhibit a distinctive non-Gaussian displacement distribution, far different from that of bulk water. Here, we introduce a new transport equation for water molecules in the intermembrane space, quantitatively explaining molecular dynamics simulation results. We find that the unique transport dynamics of water molecules stems from the lateral diffusion coefficient fluctuation caused by their longitudinal motion in the direction perpendicular to the membranes. We also identify an interfacial region where water possesses distinct physical properties, which is unaffected by changes in the intermembrane separation.

11.
Insects ; 15(3)2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38535377

ABSTRACT

Nippolachnus Matsumura, 1917 is a small aphid genus from the tribe Tuberolachnini (Hemiptera: Lachninae) occurring in Southeast Asia. Species from this genus are quite characteristic and stand out among lachnids for their morphology and ecological associations. We have performed a revision and phylogenetic analyses to elucidate the relationships within Nippolachnus and other representatives of Tuberolachnini. Here, the taxonomy of the genus is revised based on morphological data to include seven species, three of them newly described: Nippolachnus chakrabartiisp. nov. from India, Nippolachnus sinensissp. nov. from China, and Nippolachnus malayaensissp. nov. from Indonesia. Nippolachnus appear to be non monophyletic genus and a new genus, Indolachnusgen. nov., is described to accommodate Nippolachnus himalayensis (van der Goot, 1917) as Indolachnus himalayensis (van der Goot, 1917) comb. nov. The new genus is a sister group to the remaining Nippolachnus species, which created a monophyletic clade. Neonippolachnus Shinji, 1924 syn. nov. is recognised as a synonym of Nippolachnus, and Neonippolachnus betulae Shinji, 1924 syn. nov. as a synonym of Nippolachnus micromeli Shinji, 1924. For the first time, a scanning electron microscopy study of the sexual generation of N. piri Matsumura, 1917 has been performed. Apterous and alate viviparous females of N. bengalensis Basu and Hille Ris Lambers, 1968, N. piri, and N. micromeli, and alate viviparous females of N. xitianmushanus Zhang and Zhong, 1982 are re-described and illustrated, as well as apterous and alate viviparous females of I. himalayensiscomb. nov. Hitherto unknown morphs of N. micromeli, N. piri, and N. xitianmushanus are described. A lectotype and paralectotypes of N. xitianmushanus are designated herein. Notes on distribution and host plants are given, and keys to apterous and alate viviparous females of the genera Nippolachnus and Indolachnus are also provided.

12.
Heart ; 110(10): 718-725, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38286514

ABSTRACT

OBJECTIVE: It is uncertain whether percutaneous coronary intervention (PCI) in addition to optimal medical therapy (OMT) can reduce adverse clinical events in the long term as compared with OMT alone in patients with pure stable angina. METHODS: We enrolled patients from 2006 to 2010 using the Korean national insurance data. 58 742 patients with pure stable angina with no history of myocardial infarction (MI) nor PCI were candidate, and finally, 5673 patients in the PCI plus OMT group and 5673 in the OMT alone group were selected with 1:1 propensity matching. They were followed up for 9.3 years. RESULTS: Primary endpoint, a composite of MI, stroke and cardiac death rate was significantly higher in the PCI group than in the OMT group, 13.5/1000 vs 11.5/1000 person-year with HR of 1.18 (95% CI 1.06 to 1.32, p=0.003). Individual event rate of MI and cardiac death rate was higher in the PCI group than in the OMT group at 9.3 years, 2.9 vs 2.1 (HR 1.38, 95% CI 1.09 to 1.7, p=0.009) and 4.8 vs 3.4/1000 person-year (HR 1.40, 95% CI 1.16 to 1.69, p=0.001), respectively. Revascularisation and total death occurred more in the PCI group as compared with the OMT group, 30.3 vs 8.2 (HR 3.64, 95% CI 3.27 to 4.05, p<0.001) and 13.5 vs 10.6/1000 person-year (HR 1.23, 95% CI 1.12 to 1.40, p<0.001), respectively. In subgroup analysis, the same trend of more event in the PCI group was detected. CONCLUSIONS: PCI plus OMT was associated with higher rate of primary endpoint of MI, stroke, cardiac death as compared with OMT alone in patients with pure stable angina at 9.3-year follow-up in large population.


Subject(s)
Angina, Stable , Percutaneous Coronary Intervention , Humans , Angina, Stable/therapy , Angina, Stable/mortality , Male , Female , Percutaneous Coronary Intervention/statistics & numerical data , Middle Aged , Republic of Korea/epidemiology , Aged , Treatment Outcome , Myocardial Infarction/mortality , Myocardial Infarction/therapy , Stroke/epidemiology , Propensity Score , Cardiovascular Agents/therapeutic use , Time Factors , Risk Factors , Retrospective Studies , Follow-Up Studies
13.
Nanomicro Lett ; 16(1): 83, 2024 Jan 12.
Article in English | MEDLINE | ID: mdl-38214803

ABSTRACT

Composite solid electrolytes (CSEs) have emerged as promising candidates for safe and high-energy-density solid-state lithium metal batteries (SSLMBs). However, concurrently achieving exceptional ionic conductivity and interface compatibility between the electrolyte and electrode presents a significant challenge in the development of high-performance CSEs for SSLMBs. To overcome these challenges, we present a method involving the in-situ polymerization of a monomer within a self-supported porous Li6.4La3Zr1.4Ta0.6O12 (LLZT) to produce the CSE. The synergy of the continuous conductive LLZT network, well-organized polymer, and their interface can enhance the ionic conductivity of the CSE at room temperature. Furthermore, the in-situ polymerization process can also construct the integration and compatibility of the solid electrolyte-solid electrode interface. The synthesized CSE exhibited a high ionic conductivity of 1.117 mS cm-1, a significant lithium transference number of 0.627, and exhibited electrochemical stability up to 5.06 V vs. Li/Li+ at 30 °C. Moreover, the Li|CSE|LiNi0.8Co0.1Mn0.1O2 cell delivered a discharge capacity of 105.1 mAh g-1 after 400 cycles at 0.5 C and 30 °C, corresponding to a capacity retention of 61%. This methodology could be extended to a variety of ceramic, polymer electrolytes, or battery systems, thereby offering a viable strategy to improve the electrochemical properties of CSEs for high-energy-density SSLMBs.

14.
J Microbiol ; 62(1): 33-48, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38182942

ABSTRACT

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a globally recognized foodborne pathogen that affects both animals and humans. Endoribonucleases mediate RNA processing and degradation in the adaptation of bacteria to environmental changes and have been linked to the pathogenicity of S. Typhimurium. Not much is known about the specific regulatory mechanisms of these enzymes in S. Typhimurium, particularly in the context of environmental adaptation. Thus, this study carried out a comparative transcriptomic analysis of wild-type S. Typhimurium SL1344 and its mutant (∆rnc), which lacks the rnc gene encoding RNase III, thereby elucidating the detailed regulatory characteristics that can be attributed to the rnc gene. Global gene expression analysis revealed that the ∆rnc strain exhibited 410 upregulated and 301 downregulated genes (fold-change > 1.5 and p < 0.05), as compared to the wild-type strain. Subsequent bioinformatics analysis indicated that these differentially expressed genes are involved in various physiological functions, in both the wild-type and ∆rnc strains. This study provides evidence for the critical role of RNase III as a general positive regulator of flagellar-associated genes and its involvement in the pathogenicity of S. Typhimurium.


Subject(s)
Ribonuclease III , Salmonella typhimurium , Humans , Animals , Ribonuclease III/genetics , Ribonuclease III/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Gene Expression Profiling , Transcriptome , Gene Expression Regulation, Bacterial
15.
Med Image Anal ; 91: 103029, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37988921

ABSTRACT

Imaging markers of cerebral small vessel disease provide valuable information on brain health, but their manual assessment is time-consuming and hampered by substantial intra- and interrater variability. Automated rating may benefit biomedical research, as well as clinical assessment, but diagnostic reliability of existing algorithms is unknown. Here, we present the results of the VAscular Lesions DetectiOn and Segmentation (Where is VALDO?) challenge that was run as a satellite event at the international conference on Medical Image Computing and Computer Aided Intervention (MICCAI) 2021. This challenge aimed to promote the development of methods for automated detection and segmentation of small and sparse imaging markers of cerebral small vessel disease, namely enlarged perivascular spaces (EPVS) (Task 1), cerebral microbleeds (Task 2) and lacunes of presumed vascular origin (Task 3) while leveraging weak and noisy labels. Overall, 12 teams participated in the challenge proposing solutions for one or more tasks (4 for Task 1-EPVS, 9 for Task 2-Microbleeds and 6 for Task 3-Lacunes). Multi-cohort data was used in both training and evaluation. Results showed a large variability in performance both across teams and across tasks, with promising results notably for Task 1-EPVS and Task 2-Microbleeds and not practically useful results yet for Task 3-Lacunes. It also highlighted the performance inconsistency across cases that may deter use at an individual level, while still proving useful at a population level.


Subject(s)
Cerebral Small Vessel Diseases , Magnetic Resonance Imaging , Humans , Magnetic Resonance Imaging/methods , Reproducibility of Results , Cerebral Small Vessel Diseases/diagnostic imaging , Cerebral Hemorrhage , Computers
16.
J Alzheimers Dis ; 97(1): 259-271, 2024.
Article in English | MEDLINE | ID: mdl-38143346

ABSTRACT

BACKGROUND: Brain volume is associated with cognitive decline in later life, and cortical brain atrophy exceeding the normal range is related to inferior cognitive and behavioral outcomes in later life. OBJECTIVE: To investigate the likelihood of cognitive decline, mild cognitive impairment (MCI), or dementia, when regional atrophy is present in participants' magnetic resonance imaging (MRI). METHODS: Multi-center MRI data of 2,545 adults were utilized to measure regional volumes using NEUROPHET AQUA. Four lobes (frontal, parietal, temporal, and occipital), four Alzheimer's disease-related regions (entorhinal, fusiform, inferior temporal, and middle temporal area), and the hippocampus in the left and right hemispheres were measured and analyzed. The presence of regional atrophy from brain MRI was defined as ≤1.5 standard deviation (SD) compared to the age- and sex-matched cognitively normal population. The risk ratio for cognitive decline was investigated for participants with regional atrophy in contrast to those without regional atrophy. RESULTS: The risk ratio for cognitive decline was significantly higher when hippocampal atrophy was present (MCI, 1.84, p < 0.001; dementia, 4.17, p < 0.001). Additionally, participants with joint atrophy in multiple regions showed a higher risk ratio for dementia, e.g., 9.6 risk ratio (95% confidence interval, 8.0-11.5), with atrophy identified in the frontal, temporal, and hippocampal gray matter, than those without atrophy. CONCLUSIONS: Our study showed that individuals with multiple regional atrophy (either lobar or AD-specific regions) have a higher likelihood of developing dementia compared to the age- and sex-matched population without atrophy. Thus, further consideration is needed when assessing MRI findings.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Humans , Cognitive Dysfunction/pathology , Brain/diagnostic imaging , Brain/pathology , Alzheimer Disease/pathology , Gray Matter/diagnostic imaging , Gray Matter/pathology , Magnetic Resonance Imaging , Atrophy/pathology
17.
PLoS One ; 18(12): e0289072, 2023.
Article in English | MEDLINE | ID: mdl-38051731

ABSTRACT

Heterogeneity of ribosomal RNA (rRNA) sequences has recently emerged as a mechanism that can lead to subpopulations of specialized ribosomes. Our previous study showed that ribosomes containing highly divergent rRNAs expressed from the rrnI operon (I-ribosomes) can preferentially translate a subset of mRNAs such as hspA and tpiA in the Vibrio vulnificus CMCP6 strain. Here, we explored the functional conservation of I-ribosomes across Vibrio species. Exogenous expression of the rrnI operon in another V. vulnificus strain, MO6-24/O, and in another Vibrio species, V. fischeri (strain MJ11), decreased heat shock susceptibility by upregulating HspA expression. In addition, we provide direct evidence for the preferential synthesis of HspA by I-ribosomes in the V. vulnificus MO6-24/O strain. Furthermore, exogenous expression of rrnI in V. vulnificus MO6-24/O cells led to higher mortality of infected mice when compared to the wild-type (WT) strain and a strain expressing exogenous rrnG, a redundant rRNA gene in the V. vulnificus CMCP6 strain. Our findings suggest that specialized ribosomes bearing heterogeneous rRNAs play a conserved role in translational regulation among Vibrio species. This study shows the functional importance of rRNA heterogeneity in gene expression control by preferential translation of specific mRNAs, providing another layer of specialized ribosome system.


Subject(s)
Vibrio vulnificus , Vibrio , Mice , Animals , Vibrio/genetics , RNA, Ribosomal/genetics , Ribosomes/genetics , Ribosomes/metabolism , Vibrio vulnificus/genetics , Operon/genetics
18.
Plants (Basel) ; 12(24)2023 Dec 05.
Article in English | MEDLINE | ID: mdl-38140402

ABSTRACT

The study aimed to investigate the antioxidant and antidiabetic activity of Brugmansia arborea L. flower extracts, solvent fractions, and isolated compounds. B. arborea L flowers were extracted with aqueous methanol, and concentrated extract was successively partitioned into EtOAc, n-BuOH, and H2O fractions. Repeated silica gel and octadecyl silica gel column chromatographies for EtOAc and n-BuOH fractions led to the isolation of a new phenylalkyl glycoside (6), along with five known ones. Several spectroscopic data led to the structure determination of one new phenylalky glycoside as brugmansioside C (named) (6) and five known ones as benzyl-O-ß-D-glucopyranoside (1), benzyl-O-ß-D-glucosyl-(1→6)-ß-D-glucopyranoside (2), 2-phenylethyl-O-ß-D-glucopyranoside (3), 2-phenylethyl-O-ß-D-glucosyl-(1→6)-ß-D-glucopyranoside (4), and 3-phenylpropyl-O-ß-D-glucopyranoside (5). The five known ones (1-5) were isolated from B. arborea flowers for the first time in this study. The extract, solvent fractions, and all isolated compounds showed radical scavenging activities using ABTS radical, and EtOAc fraction showed the highest scavenging capacity, whereas compounds 2, 4, and 6 did not display the capacity to use the DPPH radical. The extract, solvent fractions, and all isolated compounds showed a protective effect on pancreatic islets damaged by alloxan treatment in zebrafish larvae. The pancreatic islet size treated with EtOAc, n-BuOH fractions, and all compounds significantly increased by 64.0%, 69.4%, 82.0%, 89.8%, 80.0%, 97.8%, 103.1%, and 99.6%, respectively, compared to the alloxan-induced group. These results indicate that B. arborea flowers and their isolated compounds are useful as potential antioxidant and antidiabetic agents.

19.
RSC Adv ; 13(50): 35766-35772, 2023 Nov 30.
Article in English | MEDLINE | ID: mdl-38115984

ABSTRACT

The significance of developing a selective and sensitive sensor for quality control purposes is underscored by the prevalent use of kojic acid (KA) in cosmetics, pharmaceuticals, and food items. KA's utility stems from its ability to inhibit tyrosinase activity. However, the instability of KA and its potential adverse effects have created a pressing need for accurate and sensitive sensors capable of analyzing real samples. This research introduces an electrochemical ratiometric sensor designed to accurately detect KA in actual cosmetic and food samples. The ratiometric sensor offers distinct advantages such as enhanced selectivity, reproducibility, and sensitivity. It achieves this by leveraging the ratio between two output signals, thereby producing reliable and undistorted results. The sensor is constructed by modifying a Glassy Carbon Electrode (GCE) with a nanocomposite consisting of Ti3C2 MXene, Prussian blue, and gold nanoparticles. The incorporation of MXene and gold nanoparticles heightens sensitivity and reduces impedance. Meanwhile, the Prussian blue signal diminishes proportionally with increasing KA concentration, forming the basis for the ratiometric sensing mechanism. The outcomes of the study reveal a broad linear range (1-600 µM), a low detection limit (1 µM), and strong selectivity for KA. These findings suggest the sensor's potential efficacy in quality control across cosmetics, pharmaceuticals, and food products.

20.
Heliyon ; 9(11): e21377, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38027863

ABSTRACT

Advanced Persistent Threat (APT) attacks pose significant challenges for AI models in detecting and mitigating sophisticated and highly effective cyber threats. This research introduces a novel concept called Hybrid HHOSSA which is the grouping of Harris Hawk Optimization (HHO) and Sparrow Search Algorithm (SSA) characteristics for optimizing the feature selection and data balancing in the context of APT detection. In addition, the light GBM as well as the weighted average Bi-LSTM are optimized by the proposed hybrid HHOSSA optimization. The HHOSSA-based attribute selection is used to choose the most important attributes from the provided dataset in the early step of the quasi-identifier detection. The HHOSSA-SMOTE algorithm effectively balances the unbalanced data, such as the lateral movements and the data exfiltration in the DAPT 2020 database, which further improves the classifier performance. The light GBM and the Bi-LSTM classifier hyperparameters are well attuned and classified by the HHOSSA optimization for the precise classification of the attacks. The outcome of both the optimized light GBM and the Bi-LSTM classifier generates the final prediction of the attacks existing in the network. According to the research findings, the HHOSSA-hybrid classifier achieves high accuracy in detecting attacks, with an accuracy rate of 94.468 %, a sensitivity of 94.650 %, and a specificity of 95.230 % with a K-fold value of 10. Also, the HHOSSA-hybrid classifier achieves the highest AUC percentage of 97.032, highlighting its exceptional performance in detecting APT attacks.

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