The macroscale routing mechanism of structural brain connectivity related to body mass index.

Understanding the brain's mechanisms in individuals with obesity is important for managing body weight. Prior neuroimaging studies extensively investigated alterations in brain structure and function related to body mass index (BMI). However, how the network communication among the large-scale brain networks differs across BMI is underinvestigated. This study used diffusion magnetic resonance imaging of 290 young adults to identify links between BMI and brain network mechanisms. Navigation efficiency, a measure of network routing, was calculated from the structural connectivity computed using diffusion tractography. The sensory and frontoparietal networks indicated positive associations between navigation efficiency and BMI. The neurotransmitter association analysis identified that serotonergic and dopaminergic receptors, as well as opioid and norepinephrine systems, were related to BMI-related alterations in navigation efficiency. The transcriptomic analysis found that genes associated with network routing across BMI overlapped with genes enriched in excitatory and inhibitory neurons, specifically, gene enrichments related to synaptic transmission and neuron projection. Our findings suggest a valuable insight into understanding BMI-related alterations in brain network routing mechanisms and the potential underlying cellular biology, which might be used as a foundation for BMI-based weight management.

Mortality of very low birth weight infants by neonatal intensive care unit workload and regional group status.

Background: Very low birth weight infants (VLBWIs) continue to face high mortality risk influenced by the care quality of neonatal intensive care units (NICUs). Understanding the impact of workload and regional differences on these rates is crucial for improving outcomes. Purpose: This study aimed to assess how the structural and staffing attributes of NICUs influence the mortality rates of VLBWIs, emphasizing the significance of the availability of medical personnel and the regional distribution of care facilities. Methods: Data from 69 Korean NICUs collected by the Korean Neonatal Network between January 2015 and December 2016 were retrospectively analyzed. The NICUs were classified by various parameters: capacity (small, medium, large), nurse-to-bed ratio (1-4), and regional location (A, B, C). Pediatrician staffing was also analyzed and NICUs categorized by beds per pediatrician into low (≤10), medium (11-15), and high (≥16). The NICUs were classified by mortality rates into high-performance (1st and 2nd quartiles) and low-performance (3rd and 4th quartiles). Demographic, perinatal, and neonatal outcomes were analyzed using multivariate logistic regression to explore the association between NICU characteristics and mortality rates. Results: This study included 4,745 VLBWIs (mean gestational age, 28.4 weeks; mean birth weight, 1,088 g; 55.4% male) and found significant variations in survival rates across NICUs linked to performance and staffing levels. High-performing NICUs, often with lower bed-to-staff ratios and advanced care levels, had higher survival rates. Notably, NICUs with two rather than one neonatologist were associated with reduced mortality rates. The study also underscored regional disparities, with NICUs in certain areas showing less favorable survival rates. Conclusion: Adequate NICU staffing and proper facility location are key to lowering the number of VLBWI deaths. Enhancing staffing and regional healthcare equity is crucial for improving the survival of this population.

Health Literacy and Health-Related Quality of Life in Older Adults With Mild Cognitive Impairment.

OBJECTIVES: Health literacy is considered crucial in health status outcomes, but little is known about the association among cognitively impaired persons. This study investigated the association between health literacy and health-related quality of life (HRQoL) in older adults with mild cognitive impairment (MCI). We further examined whether the association between health literacy and HRQoL depends on age, sex, and educational attainment. DESIGN: A cross-sectional study was conducted between January and December 2022. SETTING AND PARTICIPANTS: The study population was 233 older adults with MCI who visited the Veterans Health Service Medical Center in Korea. METHODS: The diagnosis of MCI was confirmed by a physician based on clinical and neuropsychological assessments. The European Health Literacy Survey Questionnaire and EuroQol Five Dimensions Questionnaire were used to measure the health literacy and HRQoL of the participants. RESULTS: HRQoL was significantly correlated with health literacy (r = 0.25, P ≤ .001) and its 3 subdomains (r = 0.27, P ≤ .001 for health care; r = 0.19, P = .004 for disease prevention; and r = 0.18, P = .005 for health promotion). After adjustment for potential covariates, older adults with higher levels of health literacy were significantly associated with better HRQoL: ß = 0.02 (P = .0021) for health literacy, ß = 0.07 (P = .0001) for health care, and ß = 0.04 (P = .0443) for disease prevention. The interactions between HRQoL and health literacy with the specific variables of age, sex, and education demonstrated a statistical significance (ß = 0.02 with age, ß = 0.03 with sex, and ß = 0.06 with education). CONCLUSIONS AND IMPLICATIONS: There was a significant association between health literacy and HRQoL among older adults with MCI. This finding suggests that improving health literacy of older adults with MCI may enhance HRQoL. An education intervention is recommended to reduce the existing health disparities due to low health literacy.

Comparison of two crystal polymorphs of NowGFP reveals a new conformational state trapped by crystal packing.

Crystal polymorphism serves as a strategy to study the conformational flexibility of proteins. However, the relationship between protein crystal packing and protein conformation often remains elusive. In this study, two distinct crystal forms of a green fluorescent protein variant, NowGFP, are compared: a previously identified monoclinic form (space group C2) and a newly discovered orthorhombic form (space group P212121). Comparative analysis reveals that both crystal forms exhibit nearly identical linear assemblies of NowGFP molecules interconnected through similar crystal contacts. However, a notable difference lies in the stacking of these assemblies: parallel in the monoclinic form and perpendicular in the orthorhombic form. This distinct mode of stacking leads to different crystal contacts and induces structural alteration in one of the two molecules within the asymmetric unit of the orthorhombic crystal form. This new conformational state captured by orthorhombic crystal packing exhibits two unique features: a conformational shift of the ß-barrel scaffold and a restriction of pH-dependent shifts of the key residue Lys61, which is crucial for the pH-dependent spectral shift of this protein. These findings demonstrate a clear connection between crystal packing and alternative conformational states of proteins, providing insights into how structural variations influence the function of fluorescent proteins.

AB001. Development of tumour-targeted therapy for the treatment of adult and paediatric high-grade gliomas.

BACKGROUND: Brain cancer patients, especially those suffering from high-grade gliomas (HGGs) face a bleak future with very dismal long-term disease-free survival outcomes due to the limited treatment options currently available. Therefore, there is an unmet need for new therapeutic intervention that extends patients' progress-free survival and improves their quality of life. A significant hurdle is the inability of current chemotherapy agents to cross the blood-brain barrier (BBB). BBB acts as a protective shield that filters the blood to ensure nothing harmful makes it to the brain. This protection is usually good, but it becomes a problem if you want to deliver therapeutic cancer drugs through it. This barrier blocks 98% of drugs from entering the brain. Even the ones that cross BBB are unevenly distributed in the normal brain and tumour tissue, resulting in mediocre treatment and severe side effects. METHODS: We are developing drug delivery systems that can cross the BBB and facilitate the specific accumulation of drugs in the tumour tissue. This will significantly improve the efficacy of anticancer drugs in treating various brain cancers and reduce systemic toxicity. Our group has explored and developed BBB crossing and tumour targeting near infra-red dyes, which can be covalently attached to Food and Drug Administration (FDA)-approved chemotherapy agents (drug-dye conjugates), thereby delivering it to the tumour tissue. RESULTS: We synthesized such drug-dye conjugates to target various aberrant pathways in HGG and tested these conjugates against patient-derived HGG cell lines. One such conjugate was tested on a mouse model of glioblastoma, an aggressive form of HGG, and shown to cross the BBB and specifically accumulate in tumour tissue, bringing forth tumour burden reduction. CONCLUSIONS: The results obtained from this work serve as proof of principle that enables tumour-specific drug delivery to treat HGG. This work also paves the way for treating other brain cancers and central nervous system (CNS) disorders like Parkinson's and Alzheimer's disease, for which no adequate therapy exists.

Detection of sow pregnancy in day-20 urine samples using monoclonal antibody against synthesized porcine early pregnancy factor: Preliminary results.

Early diagnosis of pregnancy is directly related to cost-effective livestock production. We produced a rat monoclonal antibody (mAb) against synthesized porcine early pregnancy factor (pEPF) using conventional hybridoma technology and used it as a tool for the detection of early pregnancy in Duroc sows. The rat pEPF-mAb showed reactivity to uterine tissues of pregnant sows 20 or 30 days post-mating (day 0 defined as the day of mating) and non-pregnant sows (confirmed signs of estrus) in western blotting. Immunohistochemical analysis confirmed that pEPF was located in the stromal and grand epithelial tissues of pregnant sows 20 or 30 days post-mating. In the enzyme-linked immunosorbent assay, pEPF expression in urine and blood showed similar results, with the highest expression observed in pregnant sows 20 days post-mating, whereas there was no significant difference in expression levels between non-pregnant sows and pregnant sows 30 days post-mating. The pEPF-mAb-based pregnancy diagnostic kit can be applied to pig urine samples non-invasively collected at 20 days post-mating with 70 % accuracy. Further improvements to the kit's diagnostic performance may lead to substantial benefits for the swine industry, facilitating more efficient and accurate reproductive management.

The expression of PD-L1 on tumor-derived exosomes enhances infiltration and anti-tumor activity of αCD3 × αPD-L1 bispecific antibody-armed T cells.

Anti-cluster of differentiation (CD) 3 × α programmed death-ligand 1 (PD-L1) bispecific T-cell engager (BsTE)-bound T-cells (BsTE:T) are a promising new cancer treatment agent. However, the mechanisms of action of bispecific antibody-armed activated T-cells are poorly understood. Therefore, this study aimed to investigate the anti-tumor mechanism and efficacy of BsTE:T. The BsTE:T migration was assessed in vivo and in vitro using syngeneic and xenogeneic tumor models, flow cytometry, immunofluorescence staining, transwell migration assays, microfluidic chips, Exo View R100, western blotting, and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 technology. In murine B16 melanoma, MC38 colon cancer, and human multiple myeloma cells, BsTE:T exhibited superior tumor elimination relative to that of T-cells or BsTE alone. Moreover, BsTE:T migration into tumors was significantly enhanced owing to the presence of PD-L1 in tumor cells and secretion of PD-L1-containing exosomes. Furthermore, increased infiltration of CD44highCD62Llow effector memory CD8+ T-cells into tumors was closely associated with the anti-tumor effect of BsTE:T. Therefore, BsTE:T is an innovative potential anti-tumor therapy, and exosomal PD-L1 plays a crucial role both in vitro and in vivo in the anti-tumor activity of BsTE:T.

Role of induction chemotherapy in advanced-stage olfactory neuroblastoma.

OBJECTIVES: To evaluate the treatment outcomes in patients with advanced-stage olfactory neuroblastoma (ONB) who received induction chemotherapy (IC). MATERIALS AND METHODS: The clinical data of 38 patients with advanced-stage ONB who received initial IC were retrospectively analyzed. The response was defined using the Response Evaluation Criteria in Solid Tumors version 1.1. Patients with complete remission or partial remission were defined as responders. RESULTS: Seventeen (44.7%) patients responded to IC. The response rate was higher in patients with high Hyams grade tumor (III/IV) compared to those with low-grade tumors (I/II) (60% vs. 22.2%, p = 0.038). Overall, the 5-year cancer-specific survival (CSS) rate was 76.0%. Among nonresponders to IC, a significant difference in 5-year CSS rates was observed between surgery with adjuvant radiotherapy (RT) (100%) versus definitive RT or chemoradiotherapy (CRT) (68.6%) (log-rank p = 0.006). However, for responders, there was no significant difference in 5-year CSS rates between surgery with adjuvant therapy (75%) and definitive RT or CRT (51.1%) (log-rank p = 0.536). When only high-grade tumors were considered among responders, the 5-year CSS rate was significantly higher in patients who received RT or CRT (51.4%) compared to those who underwent surgery with adjuvant therapy (0%) (log-rank p = 0.008). CONCLUSION: In advanced-stage ONB, RT or CRT may be preferable for high-grade tumor responding to IC. Higher response rate and a potential role for induction IC in determining the optimal definitive treatment modality suggest a positive role for advanced-stage high-grade ONB.

Negligible additive effect of environmental concentrations of fragmented polyethylene terephthalate microplastics on the growth and reproductive performance of Java medaka exposed to 17ß-estradiol and bisphenol A.

To investigate whether environmental concentrations of fragmented polyethylene terephthalate (PET) microplastics (MPs) have additional or combined effects on endocrine-disrupting activity, Java medaka (Oryzias javanicus) were exposed to 17ß-estradiol (E2; 5, 10, 50, and 100 ng L-1), bisphenol A (BPA; 5, 10, 50, and 100 µg L-1), and E2 and BPA combined with PET MPs (1 and 100 particles L-1) for 200 days. The growth parameters, such as body length and weight, were significantly decreased by the highest concentrations of E2 and BPA. A significant reduction in egg production was observed in female fish exposed to BPA, with an additive toxic effect of PET MPs. A female-biased sex ratio was observed in fish exposed to both chemicals. Exposure to E2 significantly increased the hepatosomatic index (HSI) in both sexes, while no significant effect was observed in the gonadosomatic index (GSI). Exposure to BPA significantly increased the HSI in female fish and decreased the GSI in both sexes of fish. An additive effect of PET MPs was observed on the GSI value of female exposed to BPA. Significant elevations in vitellogenin (VTG) levels were observed in both sexes due to exposure to E2 and BPA. Additive effects of PET MPs were observed on VTG levels in males exposed to E2 and BPA. Taken together, even long-term treatment with PET MPs induced only a negligible additive effect on the endocrine-disrupting activity in Java medaka at environmentally relevant concentrations.

Advancing the early detection of canine cognitive dysfunction syndrome with machine learning-enhanced blood-based biomarkers.

Up to half of the senior dogs suffer from canine cognitive dysfunction syndrome (CCDS), the diagnosis method relies on subjective questionnaires such as canine cognitive dysfunction rating (CCDR) scores. Therefore, the necessity of objective diagnosis is emerging. Here, we developed blood-based biomarkers for CCDS early detection. Blood samples from dogs with CCDR scores above 25 were analyzed, and the biomarkers retinol-binding protein 4 (RBP4), C-X-C-motif chemokine ligand 10 (CXCL10), and NADPH oxidase 4 (NOX4) were validated against neurodegenerative models. Lower biomarker levels were correlated with higher CCDR scores, indicating cognitive decline. Machine-learning analysis revealed the highest predictive accuracy when analyzing the combination of RBP4 and NOX4 using the support vector machine algorithm and confirmed potential diagnostic biomarkers. These results suggest that blood-based biomarkers can notably improve CCDS early detection and treatment, with implications for neurodegenerative disease management in both animals and humans.

Raepenol™ Cream, a Complex of Natural Compounds, Promotes Wound Healing and Relieves Pruritus In Vivo.

BACKGROUND/AIM: Skin wound healing is a physiological process restoring the structural and functional integrity of injured skin. During this process, wound management preventing bacterial infection and complications is important for the regeneration of skin layers and adnexa, as well as the protective function of the skin. Therefore, the development of an effective ointment to promote wound healing without complications is beneficial. MATERIALS AND METHODS: This study developed Raepenol™ cream, comprising a base cream and natural compounds including paeonol, D-panthenol and extract of Centella asiatica, and assessed its therapeutic effect in wound healing. A rat model of skin wound healing and a mouse model of imiquimod-induced pruritus were employed. The effect of Raepenol™ cream was evaluated by wound size and histological analysis, including the integrity of skin structures and inflammatory response. RESULTS: Raepenol™ cream treatment effectively restored the structural integrity of the skin in rats, including wound closure, regeneration of skin adnexa, and reconstitution of collagen, comparable to commercial ointment. Additionally, Raepenol™ cream significantly suppressed pruritus by inhibiting mast cell infiltration or retention in the inflammatory site of mouse ears. CONCLUSION: Raepenol™ cream effectively promoted wound healing and relieved pruritus in animal models. These results suggest that it could be a promising option for wound care and pruritus relief, offering potential advantages over current ointments.

Protective Effects of Imatinib on a DSS-induced Colitis Model Through Regulation of Apoptosis and Inflammation.

BACKGROUND/AIM: Inflammatory bowel disease (IBD) is characterized by dysregulated immune responses and a multifactorial etiology. While imatinib has demonstrated efficacy in the treatment of immune-related diseases, its potential effects in IBD treatment remain underexplored. MATERIALS AND METHODS: This study aimed to investigate the therapeutic effects of imatinib in colitis treatment. A dextran sulfate sodium (DSS)-induced colitis model was used to mimic IBD in mice. Imatinib was administered orally to mice simultaneously with DSS treatment. The effects of imatinib on DSS-induced colitis were evaluated by analyzing colitis-related pathology, including the disease activity index (DAI), histological lesions, inflammatory markers, and tight junction integrity. Additionally, western blot analysis and quantitative real-time polymerase chain reaction were used to assess inflammatory markers, tight-junction proteins, and cell death. RESULTS: In the DSS-induced colitis model, imatinib treatment exerted protective effects by attenuating weight loss, restoring colon length, reducing spleen weight, and improving the DAI score and histological lesions. Additionally, imatinib reduced the level of proinflammatory cytokines, including TNF-α, IL-6, and IL-1ß. Furthermore, imatinib treatment restored tight-junction integrity and decreased the expression of apoptosis marker proteins. CONCLUSION: Overall, imatinib treatment significantly alleviated the symptoms of DSS-induced colitis by influencing the expression of proinflammatory cytokines, tight junction proteins, and apoptotic markers in mice. These findings highlight imatinib as a potential therapeutic candidate for IBD.

Deficits of Facial Emotion Recognition in Elderly Individuals with Mild Cognitive Impairment.

INTRODUCTION: The study of facial emotion recognition is under-explored in subjects with mild cognitive impairment (MCI). We investigated whether deficits in facial emotion recognition are present in patients with MCI. We also analyzed the relationship between facial emotion recognition and different domains of cognitive function. METHODS: This study included 300 participants aged 60 years or older with cognitive decline. We evaluated 181 MCI and 119 non-MCI subjects using the Seoul Neuropsychological Screening Battery-Core (SNSB-C) and facial emotion recognition task using six facial expressions (anger, disgust, fear, happiness, sadness and surprise). A Generalized Linear Model (GLM) was used to assess the association between cognitive performance and accuracy of facial emotion recognition and to compare facial emotion recognition in the MCI group based on the impairment of five different domains of cognitive function. The model was adjusted for age, sex, years of education, and depressive symptoms. RESULTS: Patients with MCI had a lower score for accurately recognizing total facial emotion (0.48 vs. 0.53; ρ = 0.0003) and surprise (0.73 vs. 0.81; ρ = 0.0215) when compared to cognitively healthy subjects. We also discovered that frontal/executive function domain (Digit Symbol Coding [DSC, 0.38 vs. 0.49; p < 0.0001], Controlled Oral Word Association Test [COWAT, 0.42 vs. 0.49; p = 0.0001], Korean-Trail Making Test [K-TMT, 0.37 vs. 0.48; p = 0.0073], Korean-Color Word Stroop Test [K-CWST, 0.43 vs. 0.49; p = 0.0219]) and language domain (Korean-Boston Naming Test [S-K-BNT, 0.46 vs. 0.47; p = 0.003]) were statistically associated with the deficits of facial emotion recognition in patients with MCI. CONCLUSION: We observed a significant association between deficits in facial emotion recognition and cognitive impairment in elderly individuals.

Neuropathologically directed profiling of PRNP somatic and germline variants in sporadic human prion disease.

Creutzfeldt-Jakob Disease (CJD), the most common human prion disease, is associated with pathologic misfolding of the prion protein (PrP), encoded by the PRNP gene. Of human prion disease cases, < 1% were transmitted by misfolded PrP, ~ 15% are inherited, and ~ 85% are sporadic (sCJD). While familial cases are inherited through germline mutations in PRNP, the cause of sCJD is unknown. Somatic mutations have been hypothesized as a cause of sCJD, and recent studies have revealed that somatic mutations accumulate in neurons during aging. To investigate the hypothesis that somatic mutations in PRNP may underlie sCJD, we performed deep DNA sequencing of PRNP in 205 sCJD cases and 170 age-matched non-disease controls. We included 5 cases of Heidenhain variant sporadic CJD (H-sCJD), where visual symptomatology and neuropathology implicate localized initiation of prion formation, and examined multiple regions across the brain including in the affected occipital cortex. We employed Multiple Independent Primer PCR Sequencing (MIPP-Seq) with a median depth of > 5000× across the PRNP coding region and analyzed for variants using MosaicHunter. An allele mixing experiment showed positive detection of variants in bulk DNA at a variant allele fraction (VAF) as low as 0.2%. We observed multiple polymorphic germline variants among individuals in our cohort. However, we did not identify bona fide somatic variants in sCJD, including across multiple affected regions in H-sCJD, nor in control individuals. Beyond our stringent variant-identification pipeline, we also analyzed VAFs from raw sequencing data, and observed no evidence of prion disease enrichment for the known germline pathogenic variants P102L, D178N, and E200K. The lack of PRNP pathogenic somatic mutations in H-sCJD or the broader cohort of sCJD suggests that clonal somatic mutations may not play a major role in sporadic prion disease. With H-sCJD representing a localized presentation of neurodegeneration, this serves as a test of the potential role of clonal somatic mutations in genes known to cause familial neurodegeneration.

Fasudil and viscosity of gelatin promote hepatic differentiation by regulating organelles in human umbilical cord matrix-mesenchymal stem cells.

BACKGROUND: Human mesenchymal stem cells originating from umbilical cord matrix are a promising therapeutic resource, and their differentiated cells are spotlighted as a tissue regeneration treatment. However, there are limitations to the medical use of differentiated cells from human umbilical cord matrix-mesenchymal stem cells (hUCM-MSCs), such as efficient differentiation methods. METHODS: To effectively differentiate hUCM-MSCs into hepatocyte-like cells (HLCs), we used the ROCK inhibitor, fasudil, which is known to induce endoderm formation, and gelatin, which provides extracellular matrix to the differentiated cells. To estimate a differentiation efficiency of early stage according to combination of gelatin and fasudil, transcription analysis was conducted. Moreover, to demonstrate that organelle states affect differentiation, we performed transcription, tomographic, and mitochondrial function analysis at each stage of hepatic differentiation. Finally, we evaluated hepatocyte function based on the expression of mRNA and protein, secretion of albumin, and activity of CYP3A4 in mature HLCs. RESULTS: Fasudil induced endoderm-related genes (GATA4, SOX17, and FOXA2) in hUCM-MSCs, and it also induced lipid droplets (LDs) inside the differentiated cells. However, the excessive induction of LDs caused by fasudil inhibited mitochondrial function and prevented differentiation into hepatoblasts. To prevent the excessive LDs formation, we used gelatin as a coating material. When hUCM-MSCs were induced into hepatoblasts with fasudil on high-viscosity (1%) gelatin-coated dishes, hepatoblast-related genes (AFP and HNF4A) showed significant upregulation on high-viscosity gelatin-coated dishes compared to those treated with low-viscosity (0.1%) gelatin. Moreover, other germline cell fates, such as ectoderm and mesoderm, were repressed under these conditions. In addition, LDs abundance was also reduced, whereas mitochondrial function was increased. On the other hand, unlike early stage of the differentiation, low viscosity gelatin was more effective in generating mature HLCs. In this condition, the accumulation of LDs was inhibited in the cells, and mitochondria were activated. Consequently, HLCs originated from hUCM-MSCs were genetically and functionally more matured in low-viscosity gelatin. CONCLUSIONS: This study demonstrated an effective method for differentiating hUCM-MSCs into hepatic cells using fasudil and gelatin of varying viscosities. Moreover, we suggest that efficient hepatic differentiation and the function of hepatic cells differentiated from hUCM-MSCs depend not only on genetic changes but also on the regulation of organelle states.

Prevention of UVB-Induced Photoaging by an Ethyl Acetate Fraction from Allomyrina dichotoma Larvae and Its Potential Mechanisms in Human Dermal Fibroblasts.

Allomyrina dichotoma larvae (ADL) is an insect type that is used ethnopharmacologically to treat various diseases; however, its use as an antiaging treatment has not been widely studied. Previously, we found that an ethyl acetate (EA) fraction derived from an ADL extract (ADLE) has a high polyphenol content and antioxidant properties. In this study, we identified the underlying molecular mechanism for the protective effect of the EA fraction against UVB-induced photodamage in vitro and ex vivo. UVB treatment increased intracellular reactive oxygen species levels and DNA damage; the latter of which was significantly decreased following cotreatment with the EA fraction. Biological markers of aging, such as p16INK4a, p21WAF1, and senescence-associated ß-gal levels, were induced by UVB treatment but significantly suppressed following EA-fraction treatment. UVB-induced upregulation of matrix metalloproteinase (MMP)-1 and downregulation of COL1A1 were also reversed by EA-fraction treatment in both cells and a 3D skin model, which resulted in increased keratin and collagen deposition. Moreover, EA-fraction treatment inhibited the phosphorylation of MAPKs (p38, ERK, and JNK) and nuclear factor (NF-)-kB and decreased the levels of inflammatory cytokines in UVB-treated cells. The results indicate that an EA fraction from ADLE ameliorates UVB-induced degradation of COL1A1 by inhibiting MMP expression and inactivating the MAPK/NF-κB p65/AP-1 signaling pathway involved in this process.

Effect of Thermal Oxidation of Carbon Nanotubes during Wet Spinning into Fibers Using Sodium Cholate Surfactant in Aqueous Dispersion.

Surfactant-based wet spinning is a promising route toward the eco-friendly production of carbon nanotube fibers (CNTFs). However, currently, the properties of surfactant-based wet-spun CNTFs lag behind those produced by other methods, indicating the need for further understanding and research. Here, we explored the surface characteristics of carbon nanotubes (CNTs) that are advantageous for the properties of CNTFs produced by wet spinning, using sodium cholate as a surfactant. Our finding indicates that appropriate thermal oxidation of CNTs enhances the fiber properties, while excessive oxidation undermines them. This implies that the bonding mechanism between CNTs and sodium cholate involves hydrophobic interaction and π-π interaction. Therefore, it is crucial to preserve a clean surface of CNTs in wet spinning using sodium cholate. We believe our research will contribute to the advancement of surfactant-based wet spinning of CNTFs.

Neuropathologically-directed profiling of PRNP somatic and germline variants in sporadic human prion disease.

Creutzfeldt-Jakob Disease (CJD), the most common human prion disease, is associated with pathologic misfolding of the prion protein (PrP), encoded by the PRNP gene. Of human prion disease cases, ~1% were transmitted by misfolded PrP, ~15% are inherited, and ~85% are sporadic (sCJD). While familial cases are inherited through germline mutations in PRNP, the cause of sCJD is unknown. Somatic mutations have been hypothesized as a cause of sCJD, and recent studies have revealed that somatic mutations accumulate in neurons during aging. To investigate the hypothesis that somatic mutations in PRNP may underlie sCJD, we performed deep DNA sequencing of PRNP in 205 sCJD cases and 170 age-matched non-disease controls. We included 5 cases of Heidenhain variant sporadic CJD (H-sCJD), where visual symptomatology and neuropathology implicate focal initiation of prion formation, and examined multiple regions across the brain including in the affected occipital cortex. We employed Multiple Independent Primer PCR Sequencing (MIPP-Seq) with a median depth of >5,000X across the PRNP coding region and analyzed for variants using MosaicHunter. An allele mixing experiment showed positive detection of variants in bulk DNA at a variant allele fraction (VAF) as low as 0.2%. We observed multiple polymorphic germline variants among individuals in our cohort. However, we did not identify bona fide somatic variants in sCJD, including across multiple affected regions in H-sCJD, nor in control individuals. Beyond our stringent variant-identification pipeline, we also analyzed VAFs from raw sequencing data, and observed no evidence of prion disease enrichment for the known germline pathogenic variants P102L, D178N, and E200K. The lack of PRNP pathogenic somatic mutations in H-sCJD or the broader cohort of sCJD suggests that clonal somatic mutations may not play a major role in sporadic prion disease. With H-sCJD representing a focal presentation of neurodegeneration, this serves as a test of the potential role of clonal somatic mutations in genes known to cause familial neurodegeneration.

The Biological Roles of microRNAs in Drosophila Development.

Drosophila is a well-established insect model system for studying various physiological phenomena and developmental processes, with a focus on gene regulation. Drosophila development is controlled by programmed regulatory mechanisms specific to individual tissues. When key developmental processes are shared among various insects, the associated regulatory networks are believed to be conserved across insects. Thus, studies of developmental regulation in Drosophila have substantially contributed to our understanding of insect development. Over the past two decades, studies on microRNAs (miRNAs) in Drosophila have revealed their crucial regulatory roles in various developmental processes. This review focuses on the biological roles of miRNAs in specific tissues and processes associated with Drosophila development. Additionally, as a future direction, we discuss sequencing technologies that can analyze the interactions between miRNAs and their target genes, with the aim of enhancing miRNA studies in Drosophila development.

Differences in cortical microstructure according to body mass index in neurologically healthy populations using structural magnetic resonance imaging.

Associations between brain structure and body mass index (BMI) are increasingly gaining attention. Although BMI-related regional alterations in brain morphology have been previously reported, the effect of BMI on the microstructural profiles, which provide information on the proxy of neuronal density within the cortex, is unexplored. In this study, we investigated the links between cortical layer-specific microstructural profiles and BMI in 302 neurologically healthy young adults. Using the microstructure-sensitive proxy based on the T1-and T2-weighted ratio, we estimated microstructural profile covariance (MPC) by calculating linear correlations of cortical depth-wise intensity profiles between different brain regions. Then, low-dimensional gradients of the MPC matrix were estimated using dimensionality reduction techniques, and the gradients were associated with BMI. Significant effects in the heteromodal association areas were observed. The BMI-gradient association map was related to the geodesic distance along the cortical surface, curvature, and sulcal depth, suggesting that the microstructural alterations occurred along the cortical topology. The BMI-gradient association map was further linked to cognitive states related to negative emotions. Our findings may provide insights into understanding the atypical cortical microstructure associated with BMI.