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Neuroinflammation plays a critical role in the neurological recovery of spinal cord injury (SCI). Adenosine can modulate neuroinflammation, whose uptake is mediated by nucleoside transporters. This study aimed to investigate the roles of equilibrative nucleoside transporter 1 (Ent1) in the inflammatory responses and functional recovery of SCI. Spinal cord contusion at the T10 dorsal portion was induced in mice to cause partial paralysis of the hindlimbs. Genetic deletion and pharmacological inhibition of Ent1 were used to evaluate the role of Ent1 in SCI. The outcomes were evaluated in terms of the Basso Mouse Scale (BMS), gait analysis, astrogliosis, microgliosis, and cytokine levels on day 14 post-injury. As a result, Ent1 deletion reduced neuroinflammation and improved the BMS score (4.88 ± 0.35 in Ent1

Purpose To propose hybrid predicting models integrating clinical and magnetic resonance imaging (MRI) features to diagnose lumbar vertebral osteopenia (LvOPI) in premenopausal women. Methods This prospective study enrolled 101 Taiwanese women, including 53 before and 48 women after menopause. Clinical information, including age, body height, body weight and body mass index (BMI), were recorded. Bone mineral density (BMD) was measured by the dual-energy X-ray absorptiometry. Lumbar vertebral fat fraction (LvFF) was measured by MRI. LvOPI scores (LvOPISs) comprising different clinical features and LvFF were constructed to diagnose LvOPI. Statistical analyses included normality tests, linear regression analyses, logistic regression analyses, group comparisons, and diagnostic performance. A P value less than 0.05 was considered as statistically significant. Results The post-menopausal women had higher age, body weight, BMI, LvFF and lower BMD than the pre-menopausal women (all P P P P = 0.0566), BMI (0.737; P P P P Conclusion The diagnostic accuracy of the LvOPI can be improved by using our proposed hybrid predicting models in Taiwanese premenopausal women.

The performance enhancement of integrated circuits relying on dimension scaling (i.e., following Moore’s Law) is more and more challenging owing to the physical limit of Si materials. Monolithic three-dimensional (M3D) integration has been considered as a powerful scheme to further boost up the system performance. Two-dimensional (2D) materials such as MoS2 are potential building blocks for constructing upper-tier transistors owing to their high mobility, atomic thickness, and back-end-of-line (BEOL) compatible processes. The concept to integrate 2D material-based devices with Si field-effect transistor (FET) is technologically important but the compatibility is yet to be experimentally demonstrated. Here, we successfully integrated an n-type monolayer MoS2 FET on a p-type Si fin-shaped FET with 20 nm fin width via an M3D integration technique to form a complementary inverter. The integration was enabled by deliberately adopting industrially matured techniques, such as chemical mechanical planarization and e-beam evaporation, to ensure its compatibility with the existing 3D integrated circuit process and the semiconductor industry in general. The 2D FET is fabricated using low-temperature sequential processes to avoid the degradation of lower-tier Si devices. The MoS2 n-FETs and Si p-FinFETs display symmetrical transfer characteristics and the resulting 3D complementary metal-oxide-semiconductor inverter show a voltage transfer characteristic with a maximum gain of ~38. This work clearly proves the integration compatibility of 2D materials with Si-based devices, encouraging the further development of monolithic 3D integrated circuits.

Objectives This population-based study aimed to collect, analyze, and summarize the long-term trends in medical imaging use in Taiwan. Methods A retrospective cohort population-based study of medical imaging usage for the individuals who received care under the National Health Insurance system from 2000 to 2017. CT and MRI utilization rates were determined overall as well as across certain variables including patient age, hospital type, health care type, hospital characteristics, and geographic area. Results Individuals registered in our health insurance system have received 21,766,745 CT scans and 7,520,088 MRI scans from 2000 to 2017. Annual growth rates for both imaging types were positive over that period, though growth rates have slowed in recent years. The growth rate for CT use was greatest (9–12%) between 2001 and 2004, dropped to 2% in 2005, then generally rose thereafter, reaching 3% in 2017. Similarly, MRI use growth peaked at 24% between 2001 and 2003, dropped to 4% in 2005, then increased in a fluctuating manner, reaching 2% in 2017. Conclusion Over the past 2 decades, CT and MRI use in Taiwan has increased sharply, especially in the oldest age group (≥ 60 years old), but growth rates have slowed in recent years. Increases in imaging use have corresponded with improved clinical outcomes, including greater life expectancy and reduced mortality rates, though further assessment is required to demonstrate a direct link with imaging. Nevertheless, the better clinical outcomes are also predisposed by the comprehensive care covered by the NHI system.

Understanding the structural diversity of honeybee-infecting viruses is critical to maintain pollinator health and manage the spread of diseases in ecology and agriculture. We determine cryo-EM structures of T = 4 and T = 3 capsids of virus-like particles (VLPs) of Lake Sinai virus (LSV) 2 and delta-N48 LSV1, belonging to tetraviruses, at resolutions of 2.3–2.6 Å in various pH environments. Structural analysis shows that the LSV2 capsid protein (CP) structural features, particularly the protruding domain and C-arm, differ from those of other tetraviruses. The anchor loop on the central β-barrel domain interacts with the neighboring subunit to stabilize homo-trimeric capsomeres during assembly. Delta-N48 LSV1 CP interacts with ssRNA via the rigid helix α1’, α1’–α1 loop, β-barrel domain, and C-arm. Cryo-EM reconstructions, combined with X-ray crystallographic and small-angle scattering analyses, indicate that pH affects capsid conformations by regulating reversible dynamic particle motions and sizes of LSV2 VLPs. C-arms exist in all LSV2 and delta-N48 LSV1 VLPs across varied pH conditions, indicating that autoproteolysis cleavage is not required for LSV maturation. The observed linear domino-scaffold structures of various lengths, made up of trapezoid-shape capsomeres, provide a basis for icosahedral T = 4 and T = 3 architecture assemblies. These findings advance understanding of honeybee-infecting viruses that can cause Colony Collapse Disorder.

Pentraxin 3 (PTX3) has been shown to be a predictor of endothelial dysfunction in patients with increased risk of cardiovascular disease (CVD) (e.g., obesity). Circulating PTX3 concentrations are dysregulated in obese individuals and are elevated following acute aerobic exercise. High-intensity interval exercise (HIIE) has been demonstrated to be as effective as continuous moderate-intensity exercise in improving endothelial function, as indicated by brachial artery flow-mediated dilation (BAFMD), in patients with CVD. Therefore, the purpose of this study was to examine the effect of acute HIIE on plasma PTX3 and BAFMD responses in obese individuals. Eight obese and six normal-weight young males participated in acute HIIE (4 intervals of 4 min at 80–90% of VO2max; 3 min of active recovery at 50–60% VO2max). Plasma PTX3 and BAFMD were measured prior to, immediately following exercise, and one and 2 hours into recovery. Plasma PTX3 concentrations significantly increased following HIIE, yet the PTX3 response to HIIE was significantly blunted in obese compared to normal-weight participants. While the kinetic responses of BAFMD were also significantly different in obese compared to normal-weight participants, similar increases above the baseline were observed 2 hours into recovery in both groups. Finally, plasma PTX3 concentrations were not associated with BAFMD at baseline or in response to HIIE. The utilization of HIIE may serve as a time-efficient exercise prescription strategy to transiently improve endothelial function, independent of elevated plasma PTX3 concentrations, in obese individuals.

Generation and maintenance of antigen-specific effector and memory T cells are central events in immune responses against infections. We show that TNF receptor-associated factor 2 (TRAF2) maintains a survival signaling axis in effector and memory CD8 T cells required for immune responses against infections. This signaling axis involves activation of Tpl2 and its downstream kinase ERK by NF-κB-inducing kinase (NIK) and degradation of the proapoptotic factor Bim. NIK mediates Tpl2 activation by stimulating the phosphorylation and degradation of the Tpl2 inhibitor p105. Interestingly, while NIK is required for Tpl2-ERK signaling under normal conditions, uncontrolled NIK activation due to loss of its negative regulator, TRAF2, causes constitutive degradation of p105 and Tpl2, leading to severe defects in ERK activation and effector/memory CD8 T cell survival. Thus, TRAF2 controls a previously unappreciated signaling axis mediating effector/memory CD8 T cell survival and protective immunity.

Purpose The aim of this study was to use the computational fluid dynamics (CFD) method, patient-specific electrocardiogram (ECG) signals, and computed tomography three-dimensional image reconstruction technique to investigate the blood flow in coronary arteries during cardiac arrhythmia. Methods Two patients with premature ventricular contraction-type cardiac arrhythmia and one with atrial fibrillation-type cardiac arrhythmia were investigated. The inlet velocity of the coronary artery in simulation was applied with the measured velocity profile of the left ventricular outflow tract (LVOT) from the Doppler echocardiography. The measured patient central aortic blood pressure waveform was employed for the coronary artery outlet in simulation. The no-slip boundary condition was applied to the arterial wall. Results For the patient with irregular cardiac rhythms (Case I), the coronary blood flow rate under the shortened and lengthened cardiac rhythms were 0.66 and 0.96 mL/s, respectively. In Case II, the maximum velocity at the LVOT under a normal heartbeat was found to be 101 cm/s, whereas the average value was 73 cm/s. In Case III, the patient was also diagnosed with a congenital stenosis problem at the myocardial bridge (MCB) at the LAD. The measured blood flow rate at the MCB of the LAD for the three heartbeats in Case III was found to be 0.68, 1.08, and 1.14 mL/s. Conclusion The integration of patient-specific ECG signals and image-based CFD methods can clearly analyze hemodynamic information for patients during cardiac arrhythmia. The cardiac arrhythmia can reduce the blood flow in the coronary arteries.

TANK-binding kinase 1 (TBK1) responds to microbial stimuli and mediates the induction of type I interferon (IFN). Here, we show that TBK1 is also a central mediator of growth factor signalling; this function of TBK1 relies on a specific adaptor—TBK-binding protein 1 (TBKBP1). TBKBP1 recruits TBK1 to protein kinase C-theta (PKCθ) through a scaffold protein, CARD10. This enables PKCθ to phosphorylate TBK1 at Ser 716, a crucial step for TBK1 activation by growth factors but not by innate immune stimuli. Although the TBK1–TBKBP1 signalling axis is not required for the induction of type I IFN, it mediates mTORC1 activation and oncogenesis. Conditional deletion of either TBK1 or TBKBP1 in lung epithelial cells inhibits tumourigenesis in a mouse model of lung cancer. In addition to promoting tumour growth, the TBK1–TBKBP1 axis facilitates tumour-mediated immunosuppression through a mechanism that involves induction of the checkpoint molecule PD-L1 and stimulation of glycolysis. These findings suggest a PKCθ–TBKBP1–TBK1 growth factor signalling axis that mediates both tumour growth and immunosuppression. Zhu et al. show that, in response to growth factors, TBKBP1 recruits TBK1 to promote its activation by PKCθ, thereby facilitating mTORC1 activation, tumour-mediated immunosuppression and tumourigenesis.

The technology for scraped surface detection remains experimental. It is mainly performed visually by experienced technicians, which is neither objective nor standardized. Since the scraping technique is the key to the accuracy and the performance of the machine, a method to determine the characteristics of the scraping surface in a quick, objective way is proposed, in order to ensure the quality of scraping. The scraping surface is photographed using a smartphone, and an Android application is developed using a Java image processing algorithm. A square inch of image is then captured on the screen, the RGB image is isolated, and its histogram is read. Using a watershed algorithm, the background image is calculated from the boundary, and then binary, filter and morphological image processing algorithms are used. If the light is uniform, a split binary technique is used. The scraping appearance is then calculated and analyzed in points per inch (PPI) and percentage of points (POP). The experimental results indicated that the total area for recognition was approximately 1-in2; PPI = 13; and POP = 30.9%, and recognition time was less than 1 sec. The experimental analysis results in this study were compared to those of two scraping experts; the two errors were both lower than 5%.

Background Dysregulation of pericellular proteolysis usually accounts for cancer cell invasion and metastasis. Isolation of a cell-surface protease system for lung cancer metastasis is an important issue for mechanistic studies and therapeutic target identification. Methods Immunohistochemistry of a tissue array (n = 64) and TCGA database (n = 255) were employed to assess the correlation between serine protease inhibitors (SPIs) and lung adenocarcinoma progression. The role of SPI in cell motility was examined using transwell assays. Pulldown and LC/MS/MS were performed to identify the SPI-modulated novel protease(s). A xenografted mouse model was harnessed to demonstrate the role of the SPI in lung cancer metastasis. Results Hepatocyte growth factor activator inhibitor-2 (HAI-2) was identified to be downregulated following lung cancer progression, which was related to poor survival and tumour invasion. We further isolated a serum-derived serine protease, plasmin, to be a novel target of HAI-2. Downregulation of HAI-2 promotes cell surface plasmin activity, EMT, and cell motility. HAI-2 can suppress plasmin-mediated activations of HGF and TGF-β1, EMT and cell invasion. In addition, downregulated HAI-2 increased metastasis of lung adenocarcinoma via upregulating plasmin activity. Conclusion HAI-2 functions as a novel inhibitor of plasmin to suppress lung cancer cell motility, EMT and metastasis.

Two-dimensional semiconductors, such as MoS2 are known to be highly susceptible to diverse molecular adsorbates on the surface during fabrication, which could adversely affect device performance. To ensure high device yield, uniformity and performance, the semiconductor industry has long employed wet chemical cleaning strategies to remove undesirable surface contaminations, adsorbates, and native oxides from the surface of Si wafers. A similarly effective surface cleaning technique for two-dimensional materials has not yet been fully developed. In this study, we propose a wet chemical cleaning strategy for MoS2 by using N-methyl-2-pyrrolidone. The cleaning process not only preserves the intrinsic properties of monolayer MoS2, but also significantly improves the performance of monolayer MoS2 field-effect-transistors. Superior device on current of 12 μA·μm–1 for a channel length of 400 nm, contact resistance of 15 kΩ·μm, field-effect mobility of 15.5 cm2·V–1·s–1, and the average on–off current ratio of 108 were successfully demonstrated