The electrical performances of gate-recessed AlGaN/GaN high-electron mobility transistors (HEMTs) fabricated using the damage-free neutral beam etching (NBE) method are demonstrated. The NBE method ...could eliminate the plasma-induced defects generated by irradiating ultraviolet/VUV photons in the conventional inductively coupled plasma reactive ion etching method. The AlGaN/GaN HEMT device fabricated using the new gate recess process exhibited superior electrical performances, including a maximum drain current density (I DS,max ) of 1.54 A/mm, low 1/f noise, a current-gain cutoff frequency (fT) of 153 GHz, a maximum frequency of oscillation (f MAX ) of 167 GHz, and a minimum noise figure (NF min ) of 3.28 dB with an associated gain (G AS ) of 5.06 dB at 54 GHz. Such superior characteristics confirm the inherent advantages of adopting the damage-free NBE process in fabricating GaN devices for millimeter-wave applications.
Currently, there is a significant unmet need for novel analgesics with fewer side effects. In this study, we carried out structural modification of a hit compound previously identified in an ...artificial-intelligence (AI) virtual screening and discovered the potent analgesic, benzobthiophene-2-carboxamide analog (compound 25) with new structural scaffold. We investigated the signaling pathways of opioid receptors mediated by compound 25, and found this racemic compound activated mu-opioid receptor through the cyclic adenosine monophosphate (cAMP) and β-arrestin-2-mediated pathways with strong potency and efficacy, and accompanying nociceptin-orphanin FQ opioid peptide and delta-opioid receptors through the cAMP pathway with weak potencies. Compound 25 elicited potent antinociception in thermal-stimulated pain (ED50 value of 127.1 ± 34.65 μg/kg) and inflammatory-induced allodynia models with less gastrointestinal transit inhibition and antinociceptive tolerance than morphine. Overall, this study revealed a novel analgesic with reduced risks of side effects.
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•Benzobthiophene-2-carboxamides were identified as potent opioid receptor agonists.•Compound 25 demonstrates potent antinociception in thermal nociceptive mouse model.•Compound 25 exerts less potent constipation than antinociception.•Compound 25 demonstrates less antinociceptive tolerance than morphine.
Glioblastoma multiforme (GBM) is a cancer of the central nervous system with limited therapeutic outcomes. Infiltrating cancer cells are the contributing factor to high GBM malignancy. The ...intracranial brain cancer cell infiltration is a complex cascade involving adhesion, migration, and invasion. An arsenal of natural products has been under exploration to overcome GBM malignancy. This study applied the antimicrobial peptide tilapia piscidin 3 (TP3) to GBM8401, U87MG, and T98G cells. The cellular assays and microscopic observations showed that TP3 significantly attenuated cell adhesion, migration, and invasion. A live‐cell video clip showed the inhibition of filopodia protrusions and cell attachment. Probing at the molecular levels showed that the proteolytic activities (from secretion), the mRNA and protein expression levels of matrix metalloproteinases‐2 and ‐9 were attenuated. This result strongly evidenced that both invasion and metastasis were inhibited, although metastatic GBM is rare. Furthermore, the protein expression levels of cell‐mobilization regulators focal adhesion kinase and paxillin were decreased. Similar effects were observed in small GTPase (RAS), phosphorylated protein kinase B (AKT) and MAP kinases such as extracellular signal‐regulated kinases (ERK), JNK, and p38. Overall, TP3 showed promising activities to prevent cell infiltration and metastasis through modulating the tumor microenvironment balance, suggesting that TP3 merits further development for use in GBM treatments.
We first describe the anti‐cancer activities of the antimicrobial peptide tilapia piscidin 3 which inhibits infiltration and motility of glioblastoma multiforme cells.
This study examined variation between users of ‘club’ and ‘hard’ drugs in Taiwan in terms of prevalence of use and demographics and psychosocial characteristics.
Data were derived from a survey of ...17,837 Taiwanese civilians, aged 12–64 years, using stratified, multi-stage, random sampling. Participants completed a computer-assisted self-interview on tablet computers which covered use of legal substances, sedatives/hypnotics and prescription analgesics; use of illicit drugs/inhalants, risky sexual experiences; expectations of drugs; and psychological distress.
Approximately 1.29% of respondents reported ever using an illicit drug in their lifetime; prevalence estimates of club drugs (mainly ketamine, marijuana, and ecstasy) were slightly higher than hard drugs (mainly methamphetamine and heroin). Concurrent use of legal substances, particularly problematic use of alcohol and tobacco, as well as non-medical use of prescription drugs, were strong correlates of illicit drug use in general, with club drug use exhibiting an extremely strong association with alcohol use. Club drug users were demographically different from hard drug users, including in terms of their gender, age, and level of educational attainment. They were also more likely to be divorced or widowed, to report risky sexual partnerships and more depressive symptoms than hard drug users.
Our findings indicate drug type specific distinct psychosocial characteristics, which may warrant further attention in the design of treatment and intervention programs.
Face recognition segmentation is very important for symptom detection, especially in the case of complex image backgrounds or noise. The complexity of the photo background, the clarity of the facial ...expressions, or the interference of other people's faces can increase the difficulty of detection. Therefore, in this paper, we have proposed a method to combine mask region-based convolutional neural networks (Mask R-CNN) with you only look once version 4 (YOLOv4) to identify facial symptoms by this new method. We use the face image dataset from the public image databases DermNet and Freepic as the training source for the model. Face segmentation was first applied with Mask R-CNN. Then the images were imported into ResNet-101, and the facial features were fused with region of interest (RoI) in the feature pyramid networks (FPN) structures. After removing the non-face features and noise, the face region has been accurately obtained. Next, the recognized face area and RoI data were used to identify facial symptoms (acne, freckle, and wrinkles) with YOLOv4. Finally, we use Mask R-CNN, and you only look once version 3 (YOLOv3) and YOLOv4 are matched to perform the performance analysis. Although, the facial images with symptoms are relatively few. We still use a limited amount of data to train the model. The experimental results show that our proposed method still achieves 57.73%, 60.38%, and 59.75% of mean average precision (mAP) for different amounts of data. Compared with other methods, the mAP was more than about 3%. Consequently, using the method proposed in this paper, facial symptoms can be effectively and accurately identified.
Background: Older patients with cancer receive anticancer therapy in outpatient settings, and care-related issues may occur after discharge, which often requires family caregivers (FCs) to play a ...significant role in providing cancer care at home. However, relatively few studies have been focused on exploring the care experiences of these FCs. Purpose: The aim of this study was to explore the care experiences of FCs caring for older family members with cancer at home. Methods: A qualitative study design and in-depth individual interviews were used to explore the at-home care experiences of FCs of older patients with cancer. The research was conducted in chemotherapy outpatient settings of a medical center in northern Taiwan. Content analysis was used to analyze data. The analyses focused on first extracting meaningful units from the text and then inducting categories from these units and determining the major themes. Results: Twenty FCs were interviewed. The three themes identified included (a) increased information needs and challenges in diet preparation and treatment decision making, (b) personal and patient-induced emotional stress, and (c) life rebalancing through the care experience. Conclusions/Implications for Practice: The findings highlight the educational requirements, especially related to meeting personal dietary needs and obtaining psychological support, for FCs caring for older patients with cancer to help them rebalance their life.
The comorbidity of obesity and major depressive disorder (MDD) may be attributable to a bidirectional relationship and shared genetic influence. We aimed to examine the polygenic associations between ...obesity and MDD and to characterize their corresponding impacts on the obesity mechanism.
Genome-wide genotyping was available in 106,604 unrelated individuals from Taiwan Biobank. Polygenic risk score (PRS) for body mass index (BMI) and MDD was derived to evaluate their effects on obesity-related traits. Stratified analyses were performed for the modified effect of depression on the polygenic associations.
The MDD PRS was positively associated with waistline (beta in per SD increase in PRS = 0.12), hipline (beta = 0.08), waist-hip ratio (WHR) (beta = 0.05), body fat rate (beta = 0.08), BMI (beta = 0.05), overweight (OR = 1.02 for BMI ≥ 25), and obesity (OR = 1.05 for BMI ≥ 30). For the synergism between depression and BMI PRS, the presence of active depression symptoms defined by the PHQ-4 (p for interaction < 0.05 for waistline, WHR, and BMI) was more salient than lifetime MDD.
Limitations include recall bias for MDD due to a retrospective self-reporting questionnaire, a low response rate of the PHQ-4 for evaluating active psychological symptoms, and limited generalizability to non-Taiwanese ancestries.
The shared genetic etiology of obesity and depression was demonstrated. The amplified effect of BMI polygenic effect on obesity for individuals with active depressive symptoms was also characterized. The study may be helpful for designing public health interventions to reduce the disease burden caused by obesity and depression.
•Polygenic risk for depression was positively associated with obesity.•Depression amplified the effect of polygenic risk for obesity.•No synergism of polygenic risks for depression and for obesity•Shared genetic etiology between depression and obesity
Glioblastoma multiforme (GBM) is a cancer of largely unknown cause that leads to a 5-year survival rate of approximately 7% in the United States. Current treatment strategies are not effective, ...indicating a strong need for the development of novel therapies. In this study, the outcomes of sinularin, a marine-derived product, were evaluated against GBM. Our cellular studies using GBM cells revealed that sinularin induces cell death. The measured half maximal inhibitory concentrations (IC50) values ranged from 30 to 6 μM at 24–72 h. Cell death was induced via the generation of ROS leading to mitochondria-mediated apoptosis. This was evidenced by annexin V/propidium iodine staining and an upregulation of cleaved forms of the pro-apoptotic proteins caspase 9, 3, and PARP, and supported by CellROXTM Green, MitoSOXTM Red, and CM-H2DCFDA staining methods. In addition, we observed a downregulation of the antioxidant enzymes SOD1/2 and thioredoxin. Upon treatment with sinularin at the ~IC50 concentration, mitochondrial respiration capacities were significantly reduced, as shown by measuring the oxygen consumption rates and enzymatic complexes of oxidative phosphorylation. Intriguingly, sinularin significantly inhibited indicators of angiogenesis such as vessel tube formation, cell migration, and cell mobility in human umbilical vein endothelial cells or the fusion cell line EA.Hy926. Lastly, in a transgenic zebrafish model, intersegmental vessel formation was also significantly inhibited by sinularin treatment. These findings indicate that sinularin exerts anti-brain cancer properties that include apoptosis induction but also antiangiogenesis.
Non-tuberculous mycobacterial (NTM) lung disease (NTM-LD) prevalence is increasing worldwide. In this study, we aimed to evaluate the clinical significance of NTM pulmonary isolates (NTM-PI) and ...NTM-LD in patients with systemic autoimmune disease (SAD) who had a concurrent interstitial lung disease (ILD) diagnosis.
We retrospectively identified patients with SAD who had a concurrent ILD diagnosis (SAD-ILD) and from whom clinically indicated sputum specimens were collected for NTM culture between 2003 and 2018 at a tertiary referral hospital. We analysed the prevalence and risk factors of NTM pulmonary isolates (NTM-PI; ≥1 positive culture) and NTM-LD (≥2 positive cultures).
This study included 258 patients. Rheumatoid arthritis and Sjögren's syndrome were the most common SADs (32.2% and 26.7%, respectively). The NTM-negative subgroup had 204 patients (79.1%) and the NTM-PI subgroup had 54 patients (20.9%). In the NTM-PI subgroup, 33 patients had one NTM positive set of specimens (NTM 1+, 12.8% of the entire sample) and 21 had NTM-LD (8.1% of the entire sample). In a multivariable analysis, chronic kidney disease (CKD; adjusted odds ratio aOR: 3.10 1.53, 6.29) and chronic obstructive pulmonary disease (COPD; aOR: 2.59 1.16, 5.78) were significantly associated with NTM-PI. For NTM-LD, CKD (aOR: 2.79 1.00, 7.76) and COPD (aOR: 3.70 1.23, 10.72) remained significant risk factors.
In patients with SAD-ILD, the NTM-PI and NTM-LD prevalence rates were 20.9% and 8.1%, respectively. COPD and CKD were independent risk factors of both NTM-PI and NTM-LD. Previous use of biological agents was associated with NTM-PI.
Ineffective site-specific delivery has seriously impeded the efficacy of nanoparticle-based drugs to a disease site. Here, we report the preparation of three different shapes (sphere, scroll, and ...oblate) to systematically evaluate the impact of the marginative delivery on the efficacy of magnetic resonance (MR) imaging-guided X-ray irradiation at a low dose of 1 Gy. In addition to the shape effect, the therapeutic efficacy is investigated for the first time to be strongly related to the structure effect that is associated with the chemical activity. The enhanced particle–vessel wall interaction of both the flat scroll and oblate following margination dynamics leads to greater accumulation in the lungs, resulting in superior performance over the sphere against lung tumor growth and suppression of lung metastasis. Furthermore, the impact of the structural discrepancy in nanoparticles on therapeutic efficacy is considered. The tetragonal oblate reveals that the feasibility of the charge-transfer process outperforms the orthorhombic scroll and cubic sphere to suppress tumors. Finally, surface area is also a crucial factor affecting the efficacy of X-ray treatments from the as-prepared particles.
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