MR-GGI: accurate inference of gene-gene interactions using Mendelian randomization.

BACKGROUND: Researchers have long studied the regulatory processes of genes to uncover their functions. Gene regulatory network analysis is one of the popular approaches for understanding these processes, requiring accurate identification of interactions among the genes to establish the gene regulatory network. Advances in genome-wide association studies and expression quantitative trait loci studies have led to a wealth of genomic data, facilitating more accurate inference of gene-gene interactions. However, unknown confounding factors may influence these interactions, making their interpretation complicated. Mendelian randomization (MR) has emerged as a valuable tool for causal inference in genetics, addressing confounding effects by estimating causal relationships using instrumental variables. In this paper, we propose a new statistical method, MR-GGI, for accurately inferring gene-gene interactions using Mendelian randomization. RESULTS: MR-GGI applies one gene as the exposure and another as the outcome, using causal cis-single-nucleotide polymorphisms as instrumental variables in the inverse-variance weighted MR model. Through simulations, we have demonstrated MR-GGI's ability to control type 1 error and maintain statistical power despite confounding effects. MR-GGI performed the best when compared to other methods using the F1 score on the DREAM5 dataset. Additionally, when applied to yeast genomic data, MR-GGI successfully identified six clusters. Through gene ontology analysis, we have confirmed that each cluster in our study performs distinct functional roles by gathering genes with specific functions. CONCLUSION: These findings demonstrate that MR-GGI accurately inferences gene-gene interactions despite the confounding effects in real biological environments.

Numerical modeling of sneeze airflow and its validation with an experimental dataset.

In this study, we aimed at providing datasets using experimental results to validate the sneeze airflow. In addition, the boundary conditions for the sneeze simulation that could reproduce the sneeze airflow in the experimental results are presented and reviewed. The validation datasets were created by performing ensemble-average analysis with the experimental results of particle image velocimetry, and these were used to explore the boundary conditions to reproduce the sneeze airflow. As a result of the sneeze airflow reproduced by computational fluid dynamics simulation, the magnitude ranges of maximum velocity at the interface were observed to be 21.1-23.9 m/s for males and 17.9-20.3 m/s for females, which were higher than those of coughing. Compared with the experimental results, the root-mean-square error range for the overall airflow distribution was 0.19-0.23 m/s, whereas the error range for the magnitude of the maximum velocity at a criterion point was 0.03-0.08 m/s. The total sneezing airflow volume was in the range of 0.36-0.48 L, which was relatively low compared with that of coughing. Thus, this study provides important fundamental boundary conditions for computational fluid dynamics analysis, validated by experimental results, to interpret the spread of infectious particles by sneezing.

Effects of Environmental Features in Small Public Urban Green Spaces on Older Adults' Mental Restoration: Evidence from Tokyo.

Exposure to small public urban green spaces (SPUGS) has been demonstrated to have mental benefits for older adults. However, studies on identifying the objective environmental features of SPUGS and their effects on mental restoration for older adults remain limited. This study employed a multilevel regression model to investigate the restorative and vitalizing effects of the environmental features of 11 SPUGS in Tokyo. Onsite measurements were conducted in Kita-Ku, and 202 older adults were surveyed. The results showed that: (1) The fitting curve of the green view index and Restoration Outcome Scale (ROS) score showed an inverted U shape-both green view index and boundary enclosure had a strong impact on the mental restoration of older adults; (2) The colorfulness index showed the strongest relationship with the vitalizing effect. (3) The sky view factor and number of seats only influenced the ROS score, while the results of revitalization suggest that large areas of water should be avoided. (4) Physiological Equivalent Temperature (PET) was also confirmed to have negative effects on the mental restoration of older adults in autumn. These empirical findings can be used as a resource to promote the mental health of older adults in the design of SPUGS in high-density Asian countries.

Lemon Balm and Corn Silk Mixture Alleviates Metabolic Disorders Caused by a High-Fat Diet.

We recently reported that varying combination ratios of lemon balm (Mellissa officinalis L.) and corn silk extracts (Stigma of Zea mays L. fruit) could reduce the obesity caused by a high-fat diet (HFD). The present study investigated the dose-dependent effect of a 1:1 (w:w) mixture of lemon balm and corn silk extracts (M-LB/CS) on HFD-mediated metabolic disorders and compared the effect with metformin. Oral administration of 50-200 mg/kg of M-LB/CS for 84 days significantly inhibited HFD-induced body weight gain, adipocyte hypertrophy, and lipogenic gene induction without affecting food consumption in mice. Biochemical analyses showed that M-LB/CS blocked abnormal lipid accumulation in the blood by escalating fecal lipid excretion. In addition, M-LB/CS prevented HFD-mediated pancreatic atrophy, decreased the number of insulin- and glucagon-immunoreactive cells, and inhibited increases in glycated hemoglobin, glucose, and insulin. Moreover, M-LB/CS also reduced hepatic injury, lipid accumulation, gluconeogenesis, and lipid peroxidation in parallel with the induction of AMP-activated protein kinase and antioxidant enzymes. Furthermore, M-LB/CS protected the kidney by inhibiting tubular vacuolation and reducing serum creatinine and blood urea nitrogen levels. The prophylactic effect of 100 mg/kg M-LB/CS-administration was comparable to that of metformin. Therefore, M-LB/CS may be an alternative option for managing obesity and its related metabolic disorders.

Amlodipine decreases mitral regurgitation volume in dogs over 7 days: A study of 24 dogs with myxomatous mitral valve degeneration.

Background: Amlodipine, a dihydropyridine calcium-channel blocker, is currently being investigated as a treatment for myxomatous mitral valvular degeneration (MMVD). However, the effects of amlodipine on moderate or severe spontaneous MMVD, based on changes in echocardiographic indices, remain unclear. Animals: Client-owned small-breed dogs (n = 24) with naturally occurring MMVD of the American College of Veterinary Internal Medicine (ACVIM) stage B2 or higher. Methods: Basic dog information including previous medication treatments were recorded. All subjects received amlodipine 0.1 mg/kg, administered per os, twice daily for 7 days, in addition to their existing medication. We measured systolic blood pressure, obtained x-ray, echocardiography, blood test data before and after 1 week of amlodipine administration. Results: Left ventricular end-diastolic internal diameter, left atrial diameter and E wave reduced statistically after 1 week of amlodipine treatment (all p < 0.001). No adverse effects were reported. Conclusions: These findings suggest that low-dose amlodipine should be considered as treatment for dogs with ACVIM stage B2‒C MMVD.

Experimental measurements of airflow features and velocity distribution exhaled from sneeze and speech using particle image velocimetry.

Airflow exhaled from sneeze and speech is an important source of viruses and droplets in daily life and may cause imperceptible virus propagation. The velocities of sneeze and speech airflow exhaled from 10 healthy young participants repeatedly using high-frequency (2986 Hz) particle image velocimetry are measured. The parameters for describing the dynamic process of sneeze airflow, such as sneeze duration time (SDT), peak velocity time (PVT), maximum velocities, and sneeze spread angle, are analyzed. The sneeze airflow lasts 430 ms (SDT) and reaches the peak velocity in the first 20 ms (PVT). The maximum sneeze airflow velocity is approximately 15.9 m/s. The temporal variation of the sneeze velocity exhibits the gamma distribution. For speech airflow, the maximum instantaneous velocity and maximum time-averaged velocity are reported. The maximum instantaneous velocity is approximately 6.25 m/s, whereas the time-averaged value is only 0.208 m/s owing to the extremely small airflow velocity among syllables. The vertical/horizontal spread angles of the airflow are 15.1°/15.4° for sneeze and 52.9°/42.9° for speech. The difference in airflow features based on gender is generally slight for both sneeze and speech. Subsequently, an ensemble-average operation is conducted to obtain the general and representative velocity distributions. We report each component of the temporal and spatial velocity distributions of the sneeze airflow and the time-averaged velocity distribution of the speech airflow. These detailed distribution data can provide a comprehensive understanding of sneeze and speech airflow movement mechanisms as well as a detailed database for future sneeze and speech computational fluid dynamics simulations.

Lemon Balm and Corn Silk Extracts Mitigate High-Fat Diet-Induced Obesity in Mice.

Lemon balm and corn silk are valuable medicinal herbs, which exhibit variety of beneficial effects for human health. The present study explored the anti-obesity effects of a mixture of lemon balm and corn silk extracts (M-LB/CS) by comparison with the effects of single herbal extracts in high-fat diet (HFD)-induced obesity in mice. HFD supplementation for 84 days increased the body weight, the fat mass density, the mean diameter of adipocytes, and the thickness of fat pads. However, oral administration of M-LB/CS significantly alleviated the HFD-mediated weight gain and adipocyte hypertrophy without affecting food consumption. Of the various combination ratios of M-LB/CS tested, the magnitude of the decreases in weight gain and adipocyte hypertrophy by administration of 1:1, 1:2, 2:1, and 4:1 (w/w) M-LB/CS was more potent than that by single herbal extracts alone. In addition, M-LB/CS reduced the HFD-mediated increases in serum cholesterol, triglyceride, and low-density lipoprotein, prevented the reduction in serum high-density lipoprotein, and facilitated fecal excretion of cholesterol and triglyceride. Moreover, M-LB/CS mitigated the abnormal changes in specific mRNAs associated with lipogenesis and lipolysis in the adipose tissue. Furthermore, M-LB/CS reduced lipid peroxidation by inhibiting the HFD-mediated reduction in glutathione, catalase, and superoxide dismutase. Therefore, M-LB/CS is a promising herbal mixture for preventing obesity.

Recent research on expiratory particles in respiratory viral infection and control strategies: A review.

The global spread of coronavirus disease 2019 poses a significant threat to human health. In this study, recent research on the characteristics of expiratory particles and flow is reviewed, with a special focus on different respiratory activities, to provide guidance for reducing the viral infection risk in the built environment. Furthermore, environmental influence on particle evaporation, dispersion, and virus viability after exhalation and the current methods for infection risk assessment are reviewed. Finally, we summarize promising control strategies against infectious expiratory particles. The results show that airborne transmission is a significant viral transmission route, both in short and long ranges, from infected individuals. Relative humidity affects the evaporation and trajectories of middle-sized droplets most, and temperature accelerates the inactivation of SARS-CoV-2 both on surfaces and in aerosols. Future research is needed to improve infection risk models to better predict the infection potential of different transmission routes. Moreover, further quantitative studies on the expiratory flow features after wearing a mask are needed. Systematic investigations and the design of advanced air distribution methods, portable air cleaners, and ultraviolet germicidal irradiation systems, which have shown high efficacy in removing contaminants, are required to better control indoor viral infection.

Measurements of exhaled airflow velocity through human coughs using particle image velocimetry.

The sudden outbreak of coronavirus (COVID-19) has infected over 100 million people and led to over two million deaths (data in January 2021), posing a significant threat to global human health. As a potential carrier of the novel coronavirus, the exhaled airflow of infected individuals through coughs is significant in virus transmission. The research of detailed airflow characteristics and velocity distributions is insufficient because most previous studies utilize particle image velocimetry (PIV) with low frequency. This study measured the airflow velocity of human coughs in a chamber using PIV with high frequency (interval: 1/2986 s) to provide a detailed validation database for droplet propagation CFD simulation. Sixty cough cases for ten young healthy nonsmoking volunteers (five males and five females) were analyzed. Ensemble-average operations were conducted to eliminate individual variations. Vertical and horizontal velocity distributions were measured around the mouth area. Overall cough characteristics such as cough duration time (CDT), peak velocity time (PVT), maximum velocities, and cough spread angle were obtained. The CDT of the cough airflow was 520-560 m s, while PVT was 20 m s. The male/female averaged maximum velocities were 15.2/13.1 m/s. The average vertical/horizontal cough spread angle was 15.3°/13.3° for males and 15.6°/14.2° for females. In addition, the spatial and temporal distributions of ensemble-averaged velocity profiles were obtained in the vertical and horizontal directions. The experimental data can provide a detailed validation database the basis for further study on the influence of cough airflow on virus transmission using computational fluid dynamic simulations.

Experimental assessment of convective and radiative heat transfer coefficients for various clothing ensembles.

The convective and radiative heat transfer coefficients of clothing are important parameters for human thermoregulation and comfort models. Many researchers have studied convective and radiative heat transfer coefficients of the naked human body. However, there is limited information on convective and radiative heat transfer coefficients for the clothed human body. Therefore, this study aims to confirm whether the convective and radiative heat transfer coefficients vary with different clothing ensembles in addition to clarifying how the difference in clothing heat transfer coefficients affects the prediction of thermal comfort index, such as the predicted mean vote (PMV) index. The convective and radiative heat transfer coefficients for eight sets of clothing ensembles were measured through a manikin experiment. The results demonstrated that (1) the largest difference between convective heat transfer coefficients for various clothing ensembles was 32%, and (2) PMV values differed between the clothing ensembles with the largest value being approximately 0.2, which corresponds nearly 1 °C change in the indoor temperature. Therefore, it is necessary to consider the actual clothing convective heat transfer coefficient for the precise prediction of thermal comfort.

Protective effects of fermented rice extract on ulcerative colitis induced by dextran sodium sulfate in mice.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD), characterized by the gut mucosal ulceration. Growing evidence indicates that dysregulation of immune response to the commensal microbiota involves the pathogenesis of IBD. Previous studies have demonstrated the favorable probiotic effects of fermented rice extracts through triple fermentation with Saccharomyces cerevisiae and Weissella cibaria (FRe). Thus, the therapeutic potential of FRe for UC was examined. Dextran sodium sulfate UC mice model was orally administered distilled water as a control, sulfasalazine, or FRe at 300, 200, and 100 mg/kg, once a day for a week. The UC control exhibited body weight loss, bloody stools, and colonic shortening. However, the FRe, especially at 300 mg/kg, led to a reduction in weight loss, disease activity index scores, and colon weight, and an increase in colorectal length. The histopathological analyses revealed mild changes involved in the colonic crypt and mucosal damages in the FRe groups, along with inhibited inflammation. Indeed, the FRe reduced neutrophil infiltration and production of proinflammatory cytokines (i.e., tumor necrosis factor-α, interleukin-6/-8). This was accompanied by the down-regulation of nuclear factor-kappa B. The gene expression responsible for the intestinal barrier integrity (i.e., Zonna occludens-1/-2, Claudin-1, Occludin, Mucin-1/-2) was up-regulated in the FRe groups. In addition, the FRe reduced lipid peroxidation and enhanced antioxidant activity. Interestingly, the microbiota dysbiosis was attenuated in the FRe groups, and the number of beneficial bacteria, Lactobacilli and Bifidobacteria, was increased. It suggests that the FRe potently ameliorate UC as a functional food.

Anti-Photoaging Effects of Low Molecular-Weight Fucoidan on Ultraviolet B-Irradiated Mice.

Ultraviolet (UV) B exposure induces DNA damage and production of reactive oxygen species (ROS), which causes skin photoaging through signaling pathways of inflammation and modulation of extracellular matrix remodeling proteins, collagens, and matrix metalloproteinase (MMP). As low molecular-weight fucoidan (LMF) has potential antioxidant and anti-inflammatory properties, we examined the protective effects of LMF against UVB-induced photoaging. A UVB-irradiated mouse model was topically treated with myricetin or LMF at 2.0, 1.0 and 0.2 mg/cm² (LMF2.0, LMF1.0 and LMF0.2, respectively) once a day for 15 weeks. Wrinkle formation, inflammation, oxidative stress, MMP expression, and apoptosis in the treated regions were compared with those in a distilled water-treated photoaging model (UVB control). LMF treatments, particularly LMF2.0 and LMF1.0, significantly inhibited the wrinkle formation, skin edema, and neutrophil recruitment into the photo-damaged lesions, compared with those in the UVB control. While LMF decreased interleukin (IL)-1ß release, it increased IL-10. The LMF treatment inhibited the oxidative stresses (malondialdehyde and superoxide anion) and enhanced endogenous antioxidants (glutathione). Additionally, LMF reduced the mRNA expression of MMP-1, 9, and 13. The histopathological analyses revealed the anti-photoaging effects of LMF exerted via its antioxidant, anti-apoptotic, and MMP-9-inhibiting effects. These suggest that LMF can be used as a skin-protective remedy for photoaging.

Recurrent sebaceous carcinoma in an African hedgehog (Atelerix albiventris).

A 1.5-year-old intact male African hedgehog (Atelerix albiventris) was presented with a firm, non-movable subcutaneous mass on ventral chest area. Microscopically, the tumor was un-encapsulated, invasive up to the muscle layer, and composed of highly pleomorphic polygonal cells arranged in variably-sized lobules. The neoplastic cells had abundant cytoplasm with vacuolation and a large pleomorphic nucleus with prominent nucleoli. Mitotic figures were frequently observed with atypical mitoses. Immunohistochemically, the neoplastic cells were strongly positive for cytokeratin, but negative for vimentin. Based on these findings, a diagnosis of sebaceous carcinoma was made. Three months after the surgery, a recurrent mass was found at the surgical site. On necropsy, the mass has penetrated the underlying intercostal musculature, without metastasis to distant organs. This is the first report of a sebaceous carcinoma in an African hedgehog.

Mapping of the dog skin based on biophysical measurements.

Trans epidermal water loss (TEWL), skin hydration status and pH were determined in 14 skin regions of five healthy male Beagle dogs (2-4 years) both before and after anaesthesia. Trans epidermal water loss was highest for the footpad and head and lowest for the inguinal region. Skin hydration status was higher in the ear but did not vary significantly in other regions. Skin pH was usually alkaline with the highest values on the lower back and tail. Following anaesthesia, TEWL and skin hydration were significantly lower on the head, upper back and footpad, and upper back and elbow respectively, while skin pH was unaffected by this procedure. While measurement of pH would seem to be valid anywhere on the body in anaesthetized dogs, regional factors should be considered when interpreting TEWL and skin hydration values and when treating regional skin diseases in veterinary practice.