Cholesterol profiling reveals 7ß-hydroxycholesterol as a pathologically relevant peripheral biomarker of Alzheimer's disease.

AIM: Cholesterol homeostasis is associated with Alzheimer's disease (AD). Despite the multitude of cholesterol metabolites, little is known about which metabolites are directly involved in AD pathogenesis and can serve as its potential biomarkers. METHODS: To identify "hit" metabolites, steroid profiling was conducted in mice with different age, diet, and genotype and also in humans with normal cognition, mild cognitive impairment, and AD using gas chromatography-mass spectrometry. Then, using one of the "hit" molecules (7ß-hydroxycholesterol; OHC), molecular and histopathological experiment and behavioral testing were conducted in normal mice following its intracranial stereotaxic injection to see whether this molecule drives AD pathogenesis and causes cognitive impairment. RESULTS: The serum levels of several metabolites, including 7ß-OHC, were increased by aging in the 3xTg-AD unlike normal mice. Consistently, the levels of 7ß-OHC were increased in the hairs of patients with AD and were correlated with clinical severity. We found that 7ß-OHC directly affects AD-related pathophysiology; intrahippocampal injection of 7ß-OHC induced astrocyte and microglial cell activation, increased the levels of pro-inflammatory cytokines (TNF-alpha, IL-1ß, IL-6), and enhanced amyloidogenic pathway. Mice treated with 7ß-OHC also exhibited deficits in memory and frontal/executive functions assessed by object recognition and 5-choice serial reaction time task, respectively. CONCLUSIONS: Our results suggest that 7ß-OHC could serve as a convenient, peripheral biomarker of AD. As directly involved in AD pathogenesis, 7ß-OHC assay may help actualize personalized medicine in a way to identify an at-risk subgroup as a candidate population for statin-based AD treatment.

Primed IFN-γ-Umbilical Cord Stem Cells Ameliorate Temporomandibular Joint Osteoarthritis.

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disorder affecting the temporomandibular joint (TMJ), marked by persistent inflammation and structural damage to the joint. Only symptomatic treatment is available for managing TMJOA. Human umbilical cord mesenchymal stem cells (hUC-MSCs) show potential for treating TMJOA via their immune-modulating actions in the disease area. In addition, stimulation of inflammatory cytokines such as interferon-gamma in hUC-MSCs improves the therapeutic activity of naïve stem cells. Emerging evidence indicates that macrophages play significant roles in regulating joint inflammation through diverse secreted mediators in the pathogenesis of TMJOA. This study was conducted to evaluate the effects of inflammatory cytokine-stimulated hUC-MSCs in repairing TMJOA-induced cartilage lesions and the role of macrophages in the disease. Our in vitro data showed that stimulated hUC-MSCs induce M2 polarization of macrophages and enhance the expression of anti-inflammatory molecules. These effects were subsequently validated in vivo. In a rat model of TMJOA, stimulated hUC-MSCs ameliorated inflammation and increased M2 macrophages ratio. Our results indicate that hUC-MSCs stimulated by inflammatory cytokines modulate the activation of M2 macrophages, thereby shifting the local osteoarthritis microenvironment toward a prochondrogenic state and facilitating cartilage repair in inflammatory conditions. Stimulating hUC-MSCs with inflammatory cytokines could potentially offer an effective therapeutic approach for TMJOA, with macrophages playing a pivotal role in immune modulation.

Particulate matter (PM10) exacerbates on MK-801-induced schizophrenia-like behaviors through the inhibition of ERK-CREB-BDNF signaling pathway.

Particulate matter (PM), released into the air by a variety of natural and human activities, is a key indicator of air pollution. Although PM is known as the extensive health hazard to affect a variety of illness, few studies have specifically investigated the effects of PM10 exposure on schizophrenic development. In the present study, we aimed to investigate the impact of PM10 on MK-801, N-methyl-D-aspartate (NMDA) receptor antagonist, induced schizophrenia-like behaviors in C57BL/6 mouse. Preadolescent mice were exposed PM10 to 3.2 mg/m3 concentration for 4 h/day for 2 weeks through a compartmentalized whole-body inhalation chamber. After PM10 exposure, we conducted behavioral tests during adolescence and adulthood to investigate longitudinal development of schizophrenia. We found that PM10 exacerbated schizophrenia-like behavior, such as psychomotor agitation, social interaction deficits and cognitive deficits at adulthood in MK-801-induced schizophrenia animal model. Furthermore, the reduced expression levels of brain-derived neurotrophic factor (BDNF) and the phosphorylation of BDNF related signaling molecules, extracellular signal-regulated kinase (ERK) and cAMP response element-binding protein (CREB), were exacerbated by PM10 exposure in the adult hippocampus of MK-801-treated mice. Thus, our present study demonstrates that exposure to PM10 in preadolescence exacerbates the cognitive impairment in animal model of schizophrenia, which are considered to be facilitated by the decreased level of BDNF through reduced ERK-CREB expression.

Locomotion Techniques for Dynamic Environments: Effects on Spatial Knowledge and User Experiences.

Various locomotion techniques are used to navigate and find way through space in virtual environments (VE), and each technique provides different experiences and performances to users. Previous studies have primarily focused on static environments, whereas there is a need for research from a different perspective of dynamic environments because there are many moving objects in VE, such as other users. In this study, we compare the effects of different locomotion techniques on the user's spatial knowledge and experience, depending on whether the virtual objects are moving or not. The investigated locomotion techniques include joystick, teleportation, and redirected walking (RDW), all commonly used for VR navigation. The results showed that the differences in spatial knowledge and user experience provided by different locomotion techniques can vary depending on whether the environment is static or dynamic. Our results also showed that for a given VE, there are different locomotion techniques that induce fewer collisions between the user and other objects, or reduce the time it takes the user to perform a given task. This study suggests that when designing a locomotion interface for a specific VR application, it is possible to improve the user's spatial knowledge and experience by recommending different locomotion techniques depending on the degree of environment dynamism and and type of task.

Efficacy of IFN-γ-Primed Umbilical Cord-Derived Mesenchymal Stem Cells on Temporomandibular Joint Osteoarthritis.

BACKGROUND: Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease affecting the cartilage and subchondral bone, leading to temporomandibular joint pain and dysfunction. The complex nature of TMJOA warrants effective alternative treatments, and mesenchymal stem cells (MSCs) have shown promise in regenerative therapies. The aim of this study is twofold: firstly, to ascertain the optimal interferon-gamma (IFN-γ)-primed MSC cell line for TMJOA treatment, and secondly, to comprehensively evaluate the therapeutic efficacy of IFN-γ-primed mesenchymal stem cells derived from the human umbilical cord matrix in a rat model of TMJOA. METHODS: We analyzed changes in the expression of several key genes associated with OA protection in MSC-secreted compounds. Following this, we performed co-culture experiments using a transwell system to predict gene expression changes in primed MSCs in the TMJOA environment. Subsequently, we investigated the efficacy of the selected IFN-γ-primed human umbilical cord matrix-derived MSCs (hUCM-MSCs) for TMJOA treatment in a rat model. RESULTS: IFN-γ-primed MSCs exhibited enhanced expression of IDO, TSG-6, and FGF-2. Moreover, co-culturing with rat OA chondrocytes induced a decrease in pro-inflammatory and extracellular matrix degradation factors. In the rat TMJOA model, IFN-γ-primed MSCs with elevated IDO1, TSG-6, and FGF2 expression exhibited robust anti-inflammatory and therapeutic capacities, promoting the improvement of the inflammatory environment and cartilage regeneration. CONCLUSION: These findings underscore the importance of prioritizing the mitigation of the inflammatory milieu in TMJOA treatment and highlight IFN-γ-primed MSCs secreting these three factors as a promising, comprehensive therapeutic strategy.

The First Report on the Complete Sequence Characterization of Bluetongue Virus Serotype 3 in the Republic of Korea.

The bluetongue virus (BTV) is a significant animal pathogen with economic implications in the ruminant industry. Despite global reports on BTV detection and epidemiologic investigations, limited studies have focused on the virus in the ROK. In this study, BTV epidemiological research was conducted on blood samples from cattle and goat farms across nine regions during 2013-2014. The results showed that 3.33% of bovine blood samples (194/5824) and 0.19% of goat blood samples (2/1075) tested positive for BTV antibodies using ELISA. In Jeju-do, BTV RNA amplification occurred in 51 of 422 samples (12.1%) using real-time reverse transcription (RT-qPCR). The isolation of one sample revealed it as serotype 3, as indicated by the sequence of segments 2 (Seg-2) and 6 (Seg-6), associated with the eastern BTV topotype. However, based on Seg-1, -3, -4, -5, -7, -8, -9, and -10 analyses, the BTV-3/JJBB35 strain is more closely related to distinct BTV strains. These findings imply BTV circulation and that the Korean-isolated BTV might originate from Asian BTV strains due to multiple reassortment events. This study provides foundational data for ongoing BTV monitoring and disease-control policies in the ROK.

Reconsidering repurposing: long-term metformin treatment impairs cognition in Alzheimer's model mice.

Metformin, a primary anti-diabetic medication, has been anticipated to provide benefits for Alzheimer's disease (AD), also known as "type 3 diabetes". Nevertheless, some studies have demonstrated that metformin may trigger AD pathology and even elevate AD risk in humans. Despite this, limited research has elucidated the behavioral outcomes of metformin treatment, which would hold significant translational value. Thus, we aimed to perform thorough behavioral research on the prolonged administration of metformin to mice: We administered metformin (300 mg/kg/day) to transgenic 3xTg-AD and non-transgenic (NT) C57BL/6 mice over 1 and 2 years, respectively, and evaluated their behaviors across multiple domains via touchscreen operant chambers, including motivation, attention, memory, visual discrimination, and cognitive flexibility. We found metformin enhanced attention, inhibitory control, and associative learning in younger NT mice (≤16 months). However, chronic treatment led to impairments in memory retention and discrimination learning at older age. Furthermore, metformin caused learning and memory impairment and increased levels of AMPKα1-subunit, ß-amyloid oligomers, plaques, phosphorylated tau, and GSK3ß expression in AD mice. No changes in potential confounding factors on cognition, including levels of motivation, locomotion, appetite, body weight, blood glucose, and serum vitamin B12, were observed in metformin-treated AD mice. We also identified an enhanced amyloidogenic pathway in db/db mice, as well as in Neuro2a-APP695 cells and a decrease in synaptic markers, such as PSD-95 and synaptophysin in primary neurons, upon metformin treatment. Our findings collectively suggest that the repurposing of metformin should be carefully reconsidered when this drug is used for individuals with AD.

Genomic surveillance of genes encoding the SARS-CoV-2 spike protein to monitor for emerging variants on Jeju Island, Republic of Korea.

Introduction: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been fueled by new variants emerging from circulating strains. Here, we report results from a genomic surveillance study of SARS-CoV-2 on Jeju Island, Republic of Korea, from February 2021 to September 2022. Methods: A total of 3,585 SARS-CoV-2 positive samples were analyzed by Sanger sequencing of the gene encoding the spike protein before performing phylogenetic analyses. Results: We found that the Alpha variant (B.1.1.7) was dominant in May 2021 before being replaced by the Delta variant (B.1.617.2) in July 2021, which was dominant until December 2021 before being replaced by the Omicron variant. Mutations in the spike protein, including N440K and G446S, have been proposed to contribute to immune evasion, accelerating the spread of Omicron variants. Discussion: Our results from Juju Island, Republic of Korea, are consistent with and contribute to global surveillance efforts crucial for identifying new variants of concern of SARS-CoV-2 and for monitoring the transmission dynamics and characteristics of known strains.

Elucidating Primary Degradation Mechanisms in High-Cycling-Capacity, Compositionally Tunable High-Entropy Hydrides.

The hydrogen sorption properties of single-phase bcc (TiVNb)100-xCrx alloys (x = 0-35) are reported. All alloys absorb hydrogen quickly at 25 °C, forming fcc hydrides with storage capacity depending on the Cr content. A thermodynamic destabilization of the fcc hydride is observed with increasing Cr concentration, which agrees well with previous compositional machine learning models for metal hydride thermodynamics. The steric effect or repulsive interactions between Cr-H might be responsible for this behavior. The cycling performances of the TiVNbCr alloy show an initial decrease in capacity, which cannot be explained by a structural change. Pair distribution function analysis of the total X-ray scattering on the first and last cycled hydrides demonstrated an average random fcc structure without lattice distortion at short-range order. If the as-cast alloy contains a very low density of defects, the first hydrogen absorption introduces dislocations and vacancies that cumulate into small vacancy clusters, as revealed by positron annihilation spectroscopy. Finally, the main reason for the capacity drop seems to be due to dislocations formed during cycling, while the presence of vacancy clusters might be related to the lattice relaxation. Having identified the major contribution to the capacity loss, compositional modifications to the TiVNbCr system can now be explored that minimize defect formation and maximize material cycling performance.

PAIP 2020: Microsatellite instability prediction in colorectal cancer.

Microsatellite instability (MSI) refers to alterations in the length of simple repetitive genomic sequences. MSI status serves as a prognostic and predictive factor in colorectal cancer. The MSI-high status is a good prognostic factor in stage II/III cancer, and predicts a lack of benefit to adjuvant fluorouracil chemotherapy in stage II cancer but a good response to immunotherapy in stage IV cancer. Therefore, determining MSI status in patients with colorectal cancer is important for identifying the appropriate treatment protocol. In the Pathology Artificial Intelligence Platform (PAIP) 2020 challenge, artificial intelligence researchers were invited to predict MSI status based on colorectal cancer slide images. Participants were required to perform two tasks. The primary task was to classify a given slide image as belonging to either the MSI-high or the microsatellite-stable group. The second task was tumor area segmentation to avoid ties with the main task. A total of 210 of the 495 participants enrolled in the challenge downloaded the images, and 23 teams submitted their final results. Seven teams from the top 10 participants agreed to disclose their algorithms, most of which were convolutional neural network-based deep learning models, such as EfficientNet and UNet. The top-ranked system achieved the highest F1 score (0.9231). This paper summarizes the various methods used in the PAIP 2020 challenge. This paper supports the effectiveness of digital pathology for identifying the relationship between colorectal cancer and the MSI characteristics.

Effective Technical Protocol for Producing a Mono-Iodoacetate-Induced Temporomandibular Joint Osteoarthritis in a Rat Model.

An animal model of osteoarthritis (OA) induced by monosodium iodoacetate (MIA) can be effectively adjusted based on the concentration of MIA to control the onset, progression, and severity of OA as required. The rat temporomandibular joint osteoarthritis (TMJOA) model using MIA is a useful tool for studying the effectiveness of disease-modifying OA drugs in TMJOA research. However, the intricate and complex anatomy of the rat TMJ often poses challenges in achieving consistent TMJOA induction during experiments. In the previous article, a reference point was established by drawing parallel lines based on the line connecting the external ear and the zygomatic arch. However, this is not suitable for the anatomical characteristics of the rat. We used the zygomatic arch as a reference, which is a technical protocol that considers it. In our protocol, we designated a point ∼1 mm away from the point where the zygomatic arch bends toward the ear as the injection site. To ensure precise injection of MIA and increase the likelihood of inducing OA, it is recommended to insert the needle at a 45° angle so that the needle tip contacts the joint projection. To confirm TMJOA induction, we identified changes in the condyle using in vivo microcomputed tomography (CT) in a rat model of MIA-induced OA and measured the degree of pain-related inflammation using head withdrawal threshold (HWT) measurements. Micro-CT scanning revealed typical OA-like lesions, including degenerative changes and subchondral bone remodeling induced by MIA in the TMJ. Pain, a major clinical feature of OA, showed an appropriate response corresponding to the structural changes shown in micro-CT scanning. In addition, the MIA concentration suitable for long-term observation of lesions was determined through ex vivo micro-CT imaging and HWT measurements. The 8 mg concentration exhibited a significant difference compared with others, confirming the sustained presence of lesions, particularly through changes in subchondral bone over an extended period. Consequently, we have successfully established a reliable rat TMJOA induction model and identified the MIA concentration suitable for long-term observation of subchondral bone research, which will greatly contribute to the study of TMJOA-an incurable disease lacking specific treatment options. The Clinical Trial Registration number is 2021-12-208.

The Anti-Atopic Dermatitis Effects of Mentha arvensis Essential Oil Are Involved in the Inhibition of the NLRP3 Inflammasome in DNCB-Challenged Atopic Dermatitis BALB/c Mice.

The NLRP3 inflammasome is upregulated by various agents, such as nuclear factor-kappa B (NF-κB), lipopolysaccharide (LPS), and adenosine triphosphate (ATP). The NLRP3 inflammasome facilitations the maturation of interleukin (IL)-1ß, a proinflammatory cytokine that is critically involved in the pathogenesis of atopic dermatitis (AD). Although the NLRP3 inflammasome clearly exacerbates AD symptoms such as erythema and pruritus, drugs for AD patients targeting the NLRP3 inflammasome are still lacking. Based on the previous findings that Mentha arvensis essential oil (MAEO) possesses strong anti-inflammatory and anti-AD properties through its inhibition of the ERK/NF-κB signaling pathway, we postulated that MAEO might be capable of modulating the NLRP3 inflammasome in AD. The aim of this research was to investigate whether MAEO affects the inhibition of NLRP3 inflammasome activation in murine bone marrow-derived macrophages (BMDMs) stimulated with LPS + ATP in vitro and in a murine model displaying AD-like symptoms induced by 2,4-dinitrochlorobenzene (DNCB) in vivo. We found that MAEO inhibited the expression of NLRP3 and caspase-1, leading to the suppression of NLRP3 inflammasome activation and IL-1ß production in BMDMs stimulated with LPS + ATP. In addition, MAEO exhibited efficacy in ameliorating AD symptoms in a murine model induced by DNCB, as indicated by the reduction in dermatitis score, ear thickness, transepidermal water loss (TEWL), epidermal thickness, and immunoglobulin E (IgE) levels. Furthermore, MAEO attenuated the recruitment of NLRP3-expressing macrophages and NLRP3 inflammasome activation in murine dorsal skin lesions induced by DNCB. Overall, we provide evidence for the anti-AD effects of MAEO via inhibition of NLRP3 inflammasome activation.

Paeonol, the active component of Cynanchum paniculatum, ameliorated schizophrenia-like behaviors by regulating the PI3K-Akt-GSK3ß-NF-κB signalling pathway in MK-801-treated mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Cynanchum paniculatum (Bunge) Kitag. ex H. Hara (Asclepiadaceae) have been traditionally used in East Asia as analgesic or antiviral agents. Interestingly, some Chinese and Korean traditional medicinal books reported that the use of C. paniculatum in the treatment of psychotic symptoms, such as hallucinations and delusions. AIM OF THE STUDY: In this study, we aimed to investigate whether C. paniculatum could improve sensorimotor gating disruption in mice with MK-801-induced schizophrenia-like behaviors. We also aimed to identify the active component of C. paniculatum that could potentially serve as a treatment for schizophrenia and found that paeonol, the major constituent compound of C. paniculatum, showed potential as a treatment for schizophrenia. MATERIALS AND METHODS: To assess the effect of paeonol on mice with MK-801-induced schizophrenia-like behaviors, we carried out a series of behavioral tests related with symptoms of schizophrenia. In addition, we utilized Western blotting and ELISA techniques to investigate the antipsychotic actions of paeonol. RESULT: C. paniculatum extract (100 or 300 mg/kg) and paenol (10 or 30 mg/kg) significantly reversed MK-801-induced prepulse deficits in acoustic startle response test. In addition, paeonol (10 or 30 mg/kg) attenuated social novelty preference and novel object recognition memory on MK-801-induced schizophrenia-like behaviour in mice. Furthermore, the phosphorylation levels of PI3K, Akt, GSK3ß and NF-κB, as well as related pro-inflammatory cytokine, such as IL-1ß and TNF-α, were significantly reversed by the administration of paeonol (10 or 30 mg/kg) in the prefrontal cortex of MK-801-treated mice. CONCLUSIONS: Collectively, these data show that paeonol can potentially be used as an agent for treating sensorimotor gating deficits, negative symptoms, and cognitive deficits, such as those observed in schizophrenia with few adverse effects.

Triazine-Based Small Molecules: A Potential New Class of Compounds in the Antifungal Toolbox.

Invasive fungal infections caused by Candida species remain a significant public health problem worldwide. The increasing prevalence of drug-resistant infections and a limited arsenal of antifungal drugs underscore the need for novel interventions. Here, we screened several classes of pharmacologically active compounds against mammalian diseases for antifungal activity. We found that the synthetic triazine-based compound melanogenin (Mel) 56 is fungicidal in Candida albicans laboratory and clinical strains with minimal inhibitory concentrations of 8−16 µg/mL. Furthermore, Mel56 has general antifungal activity in several non-albicans Candida species and the non-pathogenic yeast Saccharomyces cerevisiae. Surprisingly, Mel56 inhibited the yeast-to-hyphae transition at sublethal concentrations, revealing a new role for triazine-based compounds in fungi. In human cancer cell lines, Mel56 targets the inner mitochondrial integral membrane prohibitin proteins, PHB1 and PHB2. However, Mel56 treatment did not impact C. albicans mitochondrial activity, and antifungal activity was similar in prohibitin single, double, and triple homozygous mutant strains compared to the wild-type parental strain. These results suggests that Mel56 has a novel mechanism-of-action in C. albicans. Therefore, Mel56 is a promising antifungal candidate warranting further analyses.

Relationship Between Adipokines, Cognition, and Brain Structures in Old Age Depending on Obesity.

BACKGROUND: Adipokines such as leptin and adiponectin are associated with cognitive function. Although adiposity crucially affects adipokine levels, it remains unclear whether the relationship between adipokines and cognition is influenced by obesity. METHODS: We enrolled 171 participants and divided them into participants with obesity and without obesity to explore the effect of obesity on the relationship between adipokines and cognition. In addition to plasma levels of leptin and adiponectin, multidomain cognitive functions and brain structures were assessed using neuropsychological testing and magnetic resonance imaging. Association between levels of these adipokines and Alzheimer's disease (AD) was then assessed by logistic regression. RESULTS: We found that cognitive function was negatively associated with leptin levels and leptin-to-adiponectin ratio (LAR). Such correlations between leptin and cognitive domains were prominent in participants with obesity but were not observed in those without obesity. Leptin levels were associated with lower hippocampal volumes in participants with obesity. A significant interaction of leptin and obesity was found mostly in the medial temporal lobe. Both leptin and LAR were positively associated with insulin resistance and inflammation markers in all participants. Of note, LAR was associated with a higher risk of AD after adjusting for demographic variables, Apolipoprotein E genotype, and body mass index. CONCLUSIONS: Obesity might be a factor that determines how adipokines affect brain structure and cognition. Leptin resistance might influence the relationship between adipokines and cognition. In addition, LAR rather than each adipokine levels alone may be a better indicator of AD risk in older adults with metabolic stress.

Anti-Inflammatory Effects of the LK5 Herbal Complex on LPS- and IL-4/IL-13-Stimulated HaCaT Cells and a DNCB-Induced Animal Model of Atopic Dermatitis in BALB/c Mice.

Atopic dermatitis (AD) is a chronic inflammatory skin disease influenced by a complex interplay of genetic and environmental factors. The activation of the JAK-STAT pathway increases the expression of inflammatory cytokines such as IL-4 and IL-13, further deteriorating AD. Therefore, for the treatment of AD, the JAK-STAT pathway is emerging as a significant target, alongside inflammatory cytokines. This study investigates the potential therapeutic effects of a novel herbal complex, LK5, composed of Scutellaria baicalensis, Liriope platyphylla, Sophora flavescens, Dictammus dasycarpus, and Phellodendron schneider, known for their anti-inflammatory and immune-modulating properties. We examined the anti-inflammatory and anti-AD effects of the LK5 herbal complex in HaCaT cells stimulated by LPS and IL-4/IL-13, as well as in a mouse model of AD induced by DNCB. In HaCaT cells stimulated with LPS or IL-4/IL-13, the LK5 herbal complex demonstrated anti-inflammatory effects by inhibiting the expression of inflammatory cytokines including TNF-α, IL-6, and IL-1ß, and downregulating the phosphorylation of STAT proteins. In a murine AD-like model induced by DNCB, administration of the LK5 herbal complex significantly ameliorated clinical symptoms, including dermatitis, ear thickness, and TEWL. Histological analysis revealed a reduction in epidermal thickness and mast cell infiltration. The LK5 herbal complex also inhibited pruritus induced by compound 48/80. Furthermore, the LK5 herbal complex treatment significantly decreased the levels of inflammatory cytokines such as TSLP, IL-6, and IgE in plasma and ear tissue of AD-induced mice. These findings suggest that the LK5 herbal complex may modulate the immune response and alleviate AD symptoms by inhibiting STAT pathways.

Pressure cells for in situ neutron total scattering: time and real-space resolution during deuterium absorption.

In situ gas-loading sample holders for two-dimensionally arranged detectors in time-of-flight neutron total scattering experiments have been developed to investigate atomic arrangements during deuterium absorption using time and real-space resolution. A single-crystal sapphire container was developed that allows conditions of 473 K and 10 MPa hydrogen gas pressure. High-resolution transient measurements detected deuterium absorption by palladium that proceeded within a few seconds. A double-layered container with thick- and thin-walled vanadium allowed conditions of 423 K and 10 MPa hydrogen gas pressure. The deuterium occupation sites of a lanthanum-nickel-aluminium alloy are discussed in detail on the basis of real-space high-resolution data obtained from in situ neutron scattering measurements and reverse Monte Carlo structural modeling.

Plasma adiponectin levels predict cognitive decline and cortical thinning in mild cognitive impairment with beta-amyloid pathology.

BACKGROUND: Blood adiponectin and leptin are adipokines that emerged as potential biomarkers for predicting Alzheimer's disease (AD) owing to their strong connection with obesity. Although obesity affects the relation between beta-amyloid (Aß) aggregation and cognitive decline, the longitudinal interactive effect of adipokines and Aß on cognition and brain structures in humans remains unexplored. Hence, we investigated whether plasma levels of adiponectin and leptin are associated with future cognitive decline and cortical thinning across Aß conditions (Aß [+] and Aß [-]) in individuals with mild cognitive impairment (MCI). METHODS: Of 156 participants with MCI from the longitudinal cohort study of Alzheimer's Disease Neuroimaging Initiative (ADNI), 31 were Aß (-) and 125 were Aß (+) as determined by CSF analysis. The Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores and the thickness of the parahippocampal and entorhinal cortices were used to evaluate cognition and brain structure, respectively. After stratifying groups by Aß conditions, the association of cognitive and brain structural changes with baseline plasma levels of adiponectin and leptin was examined. RESULTS: Of the total 156 participants, 51 were women (32.7%). The mean age of participants was 74.5 (standard deviation 7.57), and the mean follow-up period was 54.3 months, without a difference between the Aß (+) and (-) groups. After adjustment for confounders, higher plasma adiponectin levels were associated with a faster increase in ADAS-Cog scores, indicating faster cognitive decline under the Aß (+) condition (beta = 0.224, p = 0.018). Likewise, participants with higher plasma adiponectin presented faster cortical thinning in the bilateral parahippocampal cortices under the Aß (+) condition (beta = - 0.004, p = 0.012 for the right side; beta = - 0.004, p = 0.025 for the left side). Interestingly, plasma adiponectin levels were not associated with longitudinal ADAS-Cog scores or cortical thickness in the Aß (-) condition. Plasma leptin levels were not predictive of cognition or cortical thickness regardless of Aß status. CONCLUSION: Plasma adiponectin can be a potential biomarker for predicting the speed of AD progression in individuals with Aß (+) MCI.

Comparison of the Virulence of Korean African Swine Fever Isolates from Pig Farms during 2019-2021.

African swine fever (ASF) was first reported in South Korea in September 2019, and as of 31 December 2021, a total of 21 cases in domestic pig farms and 1875 ASFV-infected wild boars have been confirmed in the country. With the continued circulation of ASF in wild boars, and subsequent outbreaks in domestic pigs, concerns were raised about the possible changes in virulence occurring among African swine fever viruses (ASFV) circulating in South Korea. In this study, four Korean ASFV strains isolated from domestic pig farms at different time points between 2019 and 2021 were chosen, and used to experimentally infect domestic pigs by intramuscular inoculation to compare their virulence. All challenged pigs died at 4-9 days post-inoculation, with many showing clinical symptoms of fever, depression, loss of appetite, and recumbency. Gross lesions observed at necropsy included enlargement and hemorrhage of the lymph nodes and hydropericardium. The study showed that all four Korean ASFV isolates caused acute forms of illness, which supports the view that virulence among the circulating ASFV isolates in South Korea remained unchanged and highly virulent during this period.