Anti-Inflammatory and Anticoagulative Effects of Paeonol on LPS-Induced Acute Lung Injury in Rats

Paeonol is an active component of Moutan Cortex Radicis and is widely used as an analgesic, antipyretic, and anti-inflammatory agent in traditional Chinese medicine. We wanted to determine the role of paeonol in treating adult respiratory distress syndrome (ARDS). We established an acute lung injury (ALI) model in Sprague-Dawley rats, which was similar to ARDS in humans, using intratracheal administration of lipopolysaccharide (LPS). The intraperitoneal administration of paeonol successfully reduced histopathological scores and attenuated myeloperoxidase-reactive cells as an index of polymorphonuclear neutrophils infiltration and also reduces inducible nitric oxide synthase expression in the lung tissue, at 16 h after LPS administration. In addition, paeonol reduced proinflammatory cytokines in bronchoalveolar lavage fluid, including tumor-necrosis factor-α, interleukin-1β, interleukin-6, and plasminogen-activated inhibition factor-1. These results indicated that paeonol successfully attenuates inflammatory and coagulation reactions to protect against ALI

Demography and welfare status of free-roaming dogs in Yangmingshan National Park, Taiwan

Free-roaming dogs (Canis familiaris) cause threats to native wildlife and public health and raise concerns for their welfare. Understanding the demography of free-roaming dog populations is essential for developing an effective management plan. An evaluation of their welfare status would be beneficial to earn public support for the management plan. In this study, we estimated the population size, survivorship, and health of a free-roaming dog population in Yangmingshan National Park (YMSNP), Taiwan, during 2016–2018. YMSNP is a rural area with human settlements but also a protected area of conservation concern. We identified 191, 176, 216 individuals at our sampling sites in 2016, 2017, and 2018, respectively. Using a photographic capture-recapture method and extrapolation, we estimated that there were 786–979 dogs in the park during this 3-year period. The annual apparent survival rate of identified dogs was 16.7% for 2016–2017 and 23.9% for 2017–2018. The dogs had a high rate of lameness and dermatosis of 5.1–8.8% and 14.2–18.1%, respectively. Thirty-five blood samples showed that 34.3% of the dogs were anemic, 37.1% showed abnormal white blood cell counts, and 68.6% exhibited abnormal platelet counts. These results suggested that the dogs were at high density with low survivorship and in poor health, and new individuals entered the population continuously. Interventions to manage this dog population and to improve their welfare must be carried out. Our study provides an example for monitoring and managing a free-roaming dog population in a rural, conservation area in Southeast Asia

A Study on the Effects of Lateral-Wedge Insoles on Plantar-Pressure Pattern for Medial Knee Osteoarthritis Using the Wearable Sensing Insole

Patients with knee osteoarthritis have a unique plantar-pressure pattern during walking, and lateral-wedge insoles are one of the treatment options. Participants were randomly assigned to either the lateral-wedge insole group or the ordinary insole group. The Visual Analog Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and plantar-pressure test scores were evaluated at the baseline and at 20 weeks. Plantar pressure data were collected using a pressure insole with 89 sensing locations. In the ordinary insole group, the function and total WOMAC scores decreased significantly (function score, 24.8 (baseline) to 16.5 (week 20); total score, 34.9 (baseline) to 24.6 (week 20)). During walking, the transverse width of the center of pressure as a percentage of foot width (%Trans) significantly increased in the ordinary insole group (baseline, 6.3%; week 20, 14.8%). In addition, the values of partial foot pressure as a percentage of body weight (%PFP) on the forefoot (baseline, 30.3%; week 20, 39.2%) and heel (baseline, 28.1%; week 20, 16.9%) also increased significantly in the ordinary insole group. Significant group-by-time interaction effects were observed for partial foot pressure per body weight in the forefoot (p = 0.031) and heel (p = 0.024). In the ordinary insole group, the plantar pressure on the heel significantly decreased (p = 0.011) and that on the forefoot significantly increased (p = 0.023). In contrast, plantar pressure remained stable in all regions in the lateral-wedge insole group. Thus, lateral-wedge insoles may protect against plantar pressure deterioration in patients with knee osteoarthritis

Impacts of Work Function Variation and Line-Edge Roughness on TFET and FinFET Devices and 32-Bit CLA Circuits

In this paper, we analyze the variability of III-V homojunction tunnel FET (TFET) and FinFET devices and 32-bit carry-lookahead adder (CLA) circuit operating in near-threshold region. The impacts of the most severe intrinsic device variations including work function variation (WFV) and fin line-edge roughness (fin LER) on TFET and FinFET device Ion, Ioff, Cg, 32-bit CLA delay and power-delay product (PDP) are investigated and compared using 3D atomistic TCAD mixed-mode Monte-Carlo simulations and HSPICE simulations with look-up table based Verilog-A models calibrated with TCAD simulation results. The results indicate that WFV and fin LER have different impacts on device Ion and Ioff. Besides, at low operating voltage (<0.3 V), the CLA circuit delay and power-delay product (PDP) of TFET are significantly better than FinFET due to its better Ion and Cg,ave and their smaller variability. However, the leakage power of TFET CLA is larger than FinFET CLA due to the worse Ioff variability of TFET devices

Pilot Study for Immunogenicity of SARS-CoV-2 Vaccine with Seasonal Influenza and Pertussis Vaccines in Pregnant Women

Background: It is well known that the implementation of routine immunizations to prevent vaccine-preventable diseases has a significant impact on the health and well-being of infants, children, and pregnant women. We aimed to evaluate the influence of influenza, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine on the immunogenicity of SARS-CoV-2 vaccine among pregnant women, the priority population recommended for vaccination. Methods: We conducted a prospective study among pregnant women without previous SARS-CoV-2 infection in Taiwan. Maternal and umbilical cord blood samples at delivery were analyzed for the percentage of inhibition of neutralizing antibodies (NAbs) against the original strain, Delta, and Omicron variants of SARS-CoV-2 as well as the total antibody to the SARS-CoV-2 spike protein. We examined the association between different doses of SARS-CoV-2 vaccine in combination with influenza and Tdap vaccination, and two-dose SARS-CoV-2 vaccination with or without influenza and Tdap vaccines via a two-sample t-test. Results of p < 0.05 were considered to be statistically significant. Results: 98 pregnant women were enrolled in our study, with 32 receiving two doses of SARS-CoV-2 mRNA-1273 vaccine, 60 receiving three-dose of mRNA-1273, and 6 receiving one-dose of ChAdOx1 and two-dose of mRNA-1273. Twenty-one participants were immunized with SARS-CoV-2, influenza, and Tdap vaccines. Of these 21 individuals, there were no significant NAbs levels in maternal and cord blood samples against the Omicron variant, regardless of doses or type of SARS-CoV-2 vaccine. However, antibody responses against the wild-type and Delta variant were significantly lower in all maternal sera in the two-dose SARS-CoV-2 vaccine group. Among 32 women receiving two-dose mRNA-1273, significantly lower levels of NAbs in maternal sera were observed against the Delta variant and total antibody both in maternal sera and cord blood were observed in individuals receiving SARS-CoV-2 and influenza vaccine. Conclusion: This is the pilot study to demonstrate the effects of influenza and the Tdap vaccine on the immunogenicity of the SARS-CoV-2 vaccine among pregnant women. These results suggest that combination vaccination during pregnancy may result in immunogenic interactions

Early Menarche and Ischemic Stroke Risk Among Postmenopausal Women

Background: Results from previous studies regarding relationships between age at menarche and cardiovascular disease remain controversial. This study investigated the association between endogenous estrogen exposure and ischemic stroke risk. Methods: A total of 189 ischemic stroke patients and 192 age-matched healthy postmenopausal women were recruited. Age at menarche and menopause and risk factors of ischemic stroke were recorded through structured questionnaires by well-trained research assistants. Lifetime estrogen exposure was calculated as the number of years between age of menarche and menopause. Results: Study subjects with a history of hypertension and diabetes mellitus have a 2.8- and 6.2-fold increased risk for ischemic stroke, respectively. In addition, study subjects with waist circumferences ≥ 80cm also have a 2.6-fold increased risk of ischemic stroke. Conversely, subjects who experienced menarche at an early age may have a significantly decreased risk of 0.3-fold for ischemic stroke. Moreover, there was a significant and joint protective effect for study subjects without any risk factors of ischemic stroke, including a history of hypertension and diabetes mellitus, late age at menarche, and shorter lifetime estrogen exposure; these subjects were found to have the lowest risk (0.03-fold) for the development of ischemic stroke. Conclusion: Our study provides strong evidence that a significant joint protective effect was observed for patients who undergo early menarche, have longer estrogen exposure and no history of hypertension or diabetes mellitus on the risk of ischemic stroke

Developing a Prognostic Gene Panel of Epithelial Ovarian Cancer Patients by a Machine Learning Model

Epithelial ovarian cancer patients usually relapse after primary management. We utilized the support vector machine algorithm to develop a model for the chemo-response using the Cancer Cell Line Encyclopedia (CCLE) and validated the model in The Cancer Genome Atlas (TCGA) and the GSE9891 dataset. Finally, we evaluated the feasibility of the model using ovarian cancer patients from our institute. The 10-gene predictive model demonstrated that the high response group had a longer recurrence-free survival (RFS) (log-rank test, p = 0.015 for TCGA, p = 0.013 for GSE9891 and p = 0.039 for NTUH) and overall survival (OS) (log-rank test, p = 0.002 for TCGA and p = 0.016 for NTUH). In a multivariate Cox hazard regression model, the predictive model (HR: 0.644, 95% CI: 0.436&#8315;0.952, p = 0.027) and residual tumor size &lt; 1 cm (HR: 0.312, 95% CI: 0.170&#8315;0.573, p &lt; 0.001) were significant factors for recurrence. The predictive model (HR: 0.511, 95% CI: 0.334&#8315;0.783, p = 0.002) and residual tumor size &lt; 1 cm (HR: 0.252, 95% CI: 0.128&#8315;0.496, p &lt; 0.001) were still significant factors for death. In conclusion, the patients of high response group stratified by the model had good response and favourable prognosis, whereas for the patients of medium to low response groups, introduction of other drugs or clinical trials might be beneficial

Activation of myeloid cell-specific adhesion class G protein-coupled receptor EMR2 via ligation-induced translocation and interaction of receptor subunits in lipid raft microdomains

The adhesion class G protein-coupled receptors (adhesion-GPCRs) play important roles in diverse biological processes ranging from immunoregulation to tissue polarity, angiogenesis, and brain development. These receptors are uniquely modified by selfcatalytic cleavage at a highly conserved GPCR proteolysis site (GPS) dissecting the receptor into an extracellular subunit (α) and a seven-pass transmembrane subunit (β) with cellular adhesion and signaling functions, respectively. Using the myeloid cellrestricted EMR2 receptor as a paradigm, we exam the mechanistic relevance of the subunit interaction and demonstrate a critical role for GPS autoproteolysis in mediating receptor signaling and cell activation. Interestingly, two distinct receptor complexes are identified as a result of GPS proteolysis: one consisting of a noncovalentα-β heterodimer and the other comprising two completely independent receptor subunits which distribute differentially in membrane raft microdomains. Finally, we show that receptor ligation induces subunit translocation and colocalization within lipid rafts, leading to receptor signaling and inflammatory cytokine production by macrophages. Our present data resolve earlier conflicting results and provide a new mechanism of receptor signaling, as well as providing a paradigm for signal transduction within the adhesion-GPCR family