•Motor incoordination in SCA17 mice was initiated at 6 weeks old.•The TBP nuclear aggregation and microglia activation occurred in the SCA17 mice at 4 weeks old.•Gliosis of astrocytes and Bergmann ...glia, pERK, Bax/Bcl2 ratio, and caspase-3 were increased at 6 weeks old.•The activation of pERK occurs in the cerebellar astrocytes and Bergmann glia might contribute to the elevated gliosis and the neuronal apoptosis in the SCA17 mice.
Spinocerebellar ataxia type 17 (SCA17) is an autosomal dominant neurodegenerative disease caused by CAG expansion in the gene encoding the TATA-binding protein (TBP). The neurological features of SCA17 are Purkinje cell loss and gliosis. We have generated SCA17 transgenic mice which recapitulate the patients’ phenotypes and are suitable for the study of the SCA17 pathomechanism. Our previous study identified the activation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) occurred in the SCA17 cerebella, this study aims to study the role of ERK activation in SCA17. The levels of pERK, calbindin, and gliosis markers on the mouse cerebellum at 4-8 weeks old were analyzed to elucidate the correlation among behavioral performance, ERK activation and Purkinje cell degeneration. The motor incoordination was initiated in SCA17 mice at 6 weeks old. We found that the presence of TBP nuclear aggregation and microglia activation were observed at 4 weeks old. Gliosis of astrocytes and Bergmann glia, pERK, Bax/Bcl2 ratio, and caspase-3 were significantly increased in the 6-week-old SCA17 mouse cerebellum. In addition to the polyglutamine-protein aggregation in Purkinje cells caused apoptosis cell-autonomously, a significant body of evidence have shown that ERK pathways involves in neuronal apoptosis. Our study showed that the activation of ERK in the astrocytes and Bergmann glia was identified as preceding motor deficits, which suggest the elevated gliosis by ERK activation may contribute to neuronal apoptosis in SCA17 mice.
Objective
To investigate and quantify age-related changes in lower limb muscle stiffness in typically developing children and adolescents using acoustic radiation force impulse shear wave ...elastography.
Materials and methods
Shear wave velocities of bilateral rectus femoris, tibialis anterior, and medial gastrocnemius muscles at rest were obtained in typically developing children and adolescents aged 3 to 18 years. The participants were classified into three age groups: Group 1 (children), 3 to 7 years old; Group 2, 8 to 12 (pre-adolescent); and Group 3 (adolescent), 13 to 18. The shear wave velocities of muscle were compared across the three age groups, as well as compared between right- and left-side limbs. The correlation between shear wave velocities and body weight or body mass index was assessed.
Results
Of the 47 participants, 21 were in Group 1, 17 in Group 2, and 9 in Group 3. There were no significant differences among the three age groups’ shear wave velocities of bilateral lower limb muscles, and no significant differences between right and left sides. There was no correlation between muscle stiffness and body weight or body mass index.
Conclusion
The present pilot study applied acoustic radiation force impulse shear wave elastography to quantify lower limb muscle stiffness in typically developing children and adolescents aged 3 to 18 years, suggesting no marked change in muscle stiffness occurs as they develop.
In this paper we present the laser nanowelding process of silver nanowires (AgNWs) deposited on flexible polymer substrates by continuous wave (CW) lasers. CW lasers are cost-effective and can ...provide moderate power density, somewhere between nanosecond pulsed lasers and flash lamps, which is just enough to perform the nanowelding process efficiently and does not damage the nanowires on the polymer substrates. Here, an Nd:YAG CW laser (wavelength 532 nm) was used to perform the nanowelding of AgNWs on polyethylene terephthalate (PET) substrates. Key process parameters such as laser power, scan speed, and number of scans were studied and optimized, and mechanisms of observed phenomena are discussed. Our best result demonstrates a sheet resistance of 12 ohm/squ with a transmittance at λ = 550 nm of 92% for AgNW films on PET substrates. A transparent resistive heater was made, and IR pictures were taken to show the high uniformity of the CW laser nanowelded AgNW film. Our findings show that highly effective and efficient nanowelding can be achieved without the need of expensive pulse lasers or light sources, which may contribute to lower the cost of mass producing AgNWs on flexible substrates.
With the rapid growth of battery-powered portable electronics, an efficient power management solution is necessary for extending battery life. Generally, basic switching regulators, such as buck and ...boost converters, may not be capable of using the entire battery output voltage range (e.g., 2.5-4.7 V for Li-ion batteries) to provide a fixed output voltage (e.g., 3.3 V). In this paper, an average-current-mode noninverting buck-boost dc-dc converter is proposed. It is not only able to use the full output voltage range of a Li-ion battery, but it also features high power efficiency and excellent noise immunity. The die area of this chip is 2.14 × 1.92mm ^2 , fabricated by using TSMC 0.35 μm 2P4M 3.3 V/5 V mixed-signal polycide process. The input voltage of the converter may range from 2.3 to 5 V with its output voltage set to 3.3 V, and its switching frequency is 500 kHz. Moreover, it can provide up to 400-mA load current, and the maximal measured efficiency is 92.01%.
Lung cancer is the leading cause of cancer-related death worldwide. Both diagnostic and prognostic biomarkers are urgently needed to increase patient survival. In this study, we identified/quantified ...1763 proteins from paired adenocarcinoma (ADC) tissues with different extents of lymph node (LN) involvement using an iTRAQ-based quantitative proteomic analysis. Based on a bioinformatics analysis and literature search, we selected six candidates (ERO1L, PABPC4, RCC1, RPS25, NARS, and TARS) from a set of 133 proteins that presented a 1.5-fold increase in expression in ADC tumors without LN metastasis compared with adjacent normal tissues. These six proteins were further verified using immunohistochemical staining and Western blot analyses. The protein levels of these six candidates were higher in tumor tissues compared with adjacent normal tissues. The ERO1L and NARS levels were positively associated with LN metastasis. Importantly, ERO1L overexpression in patients with early-stage ADC was positively correlated with poor survival, suggesting that ERO1L overexpression in primary sites of early-stage cancer tissues indicates a high risk for cancer micrometastasis. Moreover, we found that knockdown of either ERO1L or NARS reduced the viability and migration ability of ADC cells. Our results collectively provide a potential biomarker data set for ADC diagnosis/prognosis and reveal novel roles of ERO1L and NARS in ADC progression.
The purpose of this study is to explore the anti-inflammatory role of microRNAs (miR)-21 and miR-23 targeting the TLR/TNF-α pathway in response to chronic intermittent hypoxia with re-oxygenation ...(IHR) injury in patients with obstructive sleep apnea (OSA). Gene expression levels of the miR-21/23a, and their predicted target genes were assessed in peripheral blood mononuclear cells from 40 treatment-naive severe OSA patients, and 20 matched subjects with primary snoring (PS). Human monocytic THP-1 cell lines were induced to undergo apoptosis under IHR exposures, and transfected with miR-21-5p mimic. Both miR-21-5p and miR-23-3p gene expressions were decreased in OSA patients as compared with that in PS subjects, while
gene expression was increased. Both miR-21-5p and miR-23-3p gene expressions were negatively correlated with apnea hypopnea index and oxygen desaturation index, while
gene expression positively correlated with apnea hypopnea index. In vitro IHR treatment resulted in decreased miR-21-5p and miR-23-3p expressions. Apoptosis, cytotoxicity, and gene expressions of their predicted target genes-including
,
,
,
,
,
,
, and
-were all increased in response to IHR, while all were reversed with miR-21-5p mimic transfection under IHR condition. The findings provide biological insight into mechanisms by which IHR-suppressed miRs protect cell apoptosis via inhibit inflammation, and indicate that over-expression of the miR-21-5p may be a new therapy for OSA.
Objectives
Glymphatic system maintains brain fluid circulation via active transportation of astrocytic aquaporin-4 in perivascular space. The diffusion tensor imaging analysis along the perivascular ...space (DTI-ALPS) is an established method measuring perivascular glymphatic activity, but comprehensive investigations into its influential factors are lacking.
Methods
Community-dwelling older adults underwent brain MRI scans, neuropsychiatric, and multi-domain assessments. Blood biomarker tests included glial fibrillary acidic protein (GFAP) for astrocyte injury.
Results
In 71 enrolled participants, the DTI-ALPS index was associated with modifiable factors, including lipid profile (high-density lipoprotein,
r
= 0.396; very-low-density lipoprotein,
r
= − 0.342), glucose intolerance (diabetes mellitus, standardized mean difference (SMD) = 0.7662; glycated hemoglobin,
r
= − 0.324), obesity (body mass index,
r
= − 0.295; waist,
r
= − 0.455), metabolic syndrome (SMD = − 0.6068), cigarette-smoking (SMD = − 0.6292), and renal clearance (creatinine,
r
= − 0.387; blood urea nitrogen,
r
= − 0.303). Unmodifiable associative factors of DTI-ALPS were age (
r
= − 0.434) and sex (SMD = 1.0769) (all
p
< 0.05).
A correlation of DTI-ALPS and blood GFAP was noticed (
r
= − 0.201, one-tailed t-test for the assumption that astrocytic injury impaired glymphatic activity,
p
= 0.046). Their cognitive correlations diverged, domain-specific for DTI-ALPS (Facial Memory Test,
r
= 0.272,
p
= 0.022) but global cognition-related for blood GFAP (MoCA,
r
= − 0.264,
p
= 0.026; ADAS-cog,
r
= 0.304,
p
= 0.010).
Conclusion
This correlation analysis revealed multiple modifiable and unmodifiable association factors to the glymphatic image marker. The DTI-ALPS index correlated with various metabolic factors that are known to increase the risk of vascular diseases such as atherosclerosis. Furthermore, the DTI-ALPS index was associated with renal indices, and this connection might be a link of water regulation between the two systems. In addition, the astrocytic biomarker, plasma GFAP, might be a potential marker of the glymphatic system; however, more research is needed to confirm its effectiveness.
Building on previous studies of western North Pacific formation and intensity predictions along the ECMWF ensemble medium-range track forecasts, the first objective of this transition to the eastern ...North Pacific was to provide earlier forecasts of the Time-to-Formation (T2F) and Time-to-Hurricane (T2H) than are available from the National Hurricane Center Advisories. For the first six hurricanes of the 2021 season, the first detections in the ECMWF ensemble were 8 days to 12 days in advance of the T2F times and 9 days to 13 days in advance of the T2H times. The major advance in this study has been to document that the ECMWF ensemble is also capable of predicting Ending-T2H and Ending-T2F timings and positions along those 15-day ECMWF ensemble track forecasts. This study for the first time documents the opportunity for high wind warnings during the entire lifecycle of the 2021 season hurricanes even days in advance of formation. Validations of the pre-hurricane and Ending-hurricane tracks and timings are provided for the lifecycles of seven hurricanes and the “Almost-Hurricane Guillermo”. Because the technique has been accepted for operational testing at the Joint Typhoon Warning Center, a companion article has been submitted that will describe the flowchart methodology for evaluating the twice-daily ECMWF ensemble forecasts to select the most likely pre-hurricane circulation as early as possible while non-selecting the likely false alarm circulations.
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