Zinc ions (Zn2+) are important messenger molecules involved in various physiological functions. To maintain the homeostasis of cytosolic Zn2+ concentration (Zn2+c), Zrt/Irt-related proteins (ZIPs) ...and Zn2+ transporters (ZnTs) are the two families of proteins responsible for decreasing and increasing the Zn2+c, respectively, by fluxing Zn2+ across the membranes of the cell and intracellular compartments in opposite directions. Most studies focus on the cytotoxicity incurred by a high concentration of Zn2+c and less investigate the Zn2+c at physiological levels. Zinc oxide-nanoparticle (ZnO-NP) is blood brain barrier-permeable and elevates the Zn2+c to different levels according to the concentrations of ZnO-NP applied. In this study, we mildly elevated the Zn2+c by ZnO-NP at concentrations below 1 μg/ml, which had little cytotoxicity, in cultured human neuroblastoma SH-SY5Y cells and characterized the importance of Zn2+ transporters in 6-hydroxy dopamine (6-OHDA)-induced cell death. The results show that ZnO-NP at low concentrations elevated the Zn2+c transiently in 6 hr, then declined gradually to a basal level in 24 hr. Knocking down the expression levels of ZnT1 (located mostly at the plasma membrane) and ZIP8 (present in endosomes and lysosomes) increased and decreased the ZnO-NP-induced elevation of Zn2+c, respectively. ZnO-NP treatment reduced the basal levels of reactive oxygen species and Bax/Bcl-2 mRNA ratios; in addition, ZnO-NP decreased the 6-OHDA-induced ROS production, p53 expression, and cell death. These results show that ZnO-NP-induced mild elevation in Zn2+c activates beneficial effects in reducing the 6-OHDA-induced cytotoxic effects. Therefore, brain-delivery of ZnO-NP can be regarded as a potential therapy for neurodegenerative diseases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is associated with insulin resistance, lipid metabolism, and tumorigenesis. However, the association between the IGF2BP2 polymorphism and ...oral cancer risk remains unclear. We recruited 1349 male patients with oral cancer and 1198 cancer-free controls. Three single nucleotide polymorphisms IGF2BP2 rs11705701, rs4402960, and rs1470579 were assessed using real-time polymerase chain reaction. The results indicate that the male patients with oral cancer and with the rs11705701 GA+AA, rs4402960 GT+TT, and rs1470579 AC+CC genotypes had increased risk of advanced clinical stage, larger tumor, and progression of lymph node metastasis compared with those with wild-type IGF2BP2. Moreover, according to The Cancer Genome Atlas dataset, high expression of the IGF2BP2 gene is associated with poor survival in patients with head and neck squamous cell carcinoma. In conclusion, our results suggest that IGF2BP2 polymorphisms are associated with less favorable oral cancer clinical characteristics.
A multi-omics quantitative integrative analysis of lignin biosynthesis can advance the strategic engineering of wood for timber, pulp, and biofuels. Lignin is polymerized from three monomers ...(monolignols) produced by a grid-like pathway. The pathway in wood formation of Populus trichocarpa has at least 21 genes, encoding enzymes that mediate 37 reactions on 24 metabolites, leading to lignin and affecting wood properties. We perturb these 21 pathway genes and integrate transcriptomic, proteomic, fluxomic and phenomic data from 221 lines selected from ~2000 transgenics (6-month-old). The integrative analysis estimates how changing expression of pathway gene or gene combination affects protein abundance, metabolic-flux, metabolite concentrations, and 25 wood traits, including lignin, tree-growth, density, strength, and saccharification. The analysis then predicts improvements in any of these 25 traits individually or in combinations, through engineering expression of specific monolignol genes. The analysis may lead to greater understanding of other pathways for improved growth and adaptation.
Abstract
The zero echo time (ZTE) technique has improved the detection of lung nodules in PET/MRI but respiratory motion remains a challenge in lung scan. We investigated the feasibility and ...performance of fractionated deep-inspiration breath-hold (FDIBH) three-dimensional (3D) ZTE FDG PET/MRI for assessing lung nodules in patients with proved malignancy. Sixty patients who had undergone ZTE FDG PET/MRI and chest CT within a three-day interval were retrospectively included. Lung nodules less than 2 mm were excluded for analysis. Two physicians checked the adequacy of FDIBH ZTE and compared the lung nodule detection rates of FDIBH 3D ZTE and free-breathing (FB) four-dimensional (4D) ZTE, with chest CT as the reference standard. FDIBH resolved the effect of respiratory motion in 49 patients. The mean number and size of the pulmonary nodules identified in CT were 15 ± 31.3 per patient and 5.9 ± 4.6 mm in diameter. The overall nodule detection rate was 71% for FDIBH 3D ZTE and 70% for FB 4D ZTE (
p
= 0.73). FDIBH 3D ZTE significantly outperformed FB 4DZTE in detecting lung base nodules (72% and 68%;
p
= 0.03), especially for detecting those less than 6 mm (61% and 55%;
p
= 0.03). High inter-rater reliability for FDIBH 3D ZTE and FB 4D ZTE (k = 0.9 and 0.92) was noted. In conclusion, the capability of FDIBH 3D ZTE in respiratory motion resolution was limited with a technical failure rate of 18%. However, it could provide full expansion of the lung in a shorter scan time which enabled better detection of nodules (< 6 mm) in basal lungs, compared to FB 4D ZTE.
DNMT3A mutations are associated with poor prognosis in acute myeloid leukemia (AML), but the stability of this mutation during the clinical course remains unclear. In the present study of 500 ...patients with de novo AML, DNMT3A mutations were identified in 14% of total patients and in 22.9% of AML patients with normal karyotype. DNMT3A mutations were positively associated with older age, higher WBC and platelet counts, intermediate-risk and normal cytogenetics, FLT3 internal tandem duplication, and NPM1, PTPN11, and IDH2 mutations, but were negatively associated with CEBPA mutations. Multivariate analysis demonstrated that the DNMT3A mutation was an independent poor prognostic factor for overall survival and relapse-free survival in total patients and also in normokaryotype group. A scoring system incorporating the DNMT3A mutation and 8 other prognostic factors, including age, WBC count, cytogenetics, and gene mutations, into survival analysis was very useful in stratifying AML patients into different prognostic groups (P < .001). Sequential study of 138 patients during the clinical course showed that DNMT3A mutations were stable during AML evolution. In conclusion, DNMT3A mutations are associated with distinct clinical and biologic features and poor prognosis in de novo AML patients. Furthermore, the DNMT3A mutation may be a potential biomarker for monitoring of minimal residual disease.
The objective of this study was to examine associations of daily averages and daily variations in ambient relative humidity (RH), temperature, and PM2.5 on the obstructive sleep apnea (OSA) severity.
...A case-control study was conducted to retrospectively recruit 8628 subjects in a sleep center between January 2015 and December 2021, including 1307 control (apnea-hypopnea index (AHI) < 5 events/h), 3661 mild-to-moderate OSA (AHI of 5–30 events/h), and 3597 severe OSA subjects (AHI > 30 events/h). A logistic regression was used to examine the odds ratio (OR) of outcome variables (daily mean or difference in RH, temperature, and PM2.5 for 1, 7, and 30 days) with OSA severity (by the groups). Two-factor logistic regression models were conducted to examine the OR of RH with the daily mean or difference in temperature or PM2.5 with OSA severity. An exposure-response relationship analysis was conducted to examine the outcome variables with OSA severity in all, cold and warm seasons.
We observed associations of mean PM2.5 and RH with respective increases of 0.04–0.08 and 0.01–0.03 events/h for the AHI in OSA patients. An increase in the daily difference of 1 % RH increased the AHI by 0.02–0.03 events/h in OSA patients. A daily PM2.5 decrease of 1 μg/m3 reduced the AHI by 0.03 events/h, whereas a daily decrease in the RH of 1 % reduced the AHI by 0.03–0.04 events/h. The two-factor model confirmed the most robust associations of ambient RH with AHI in OSA patients. The exposure-response relationship in temperature and RH showed obviously seasonal patterns with OSA severity.
Short-term ambient variations in RH and PM2.5 were associated with changes in the AHI in OSA patients, especially RH in cold season. Reducing exposure to high ambient RH and PM2.5 levels may have protective effects on the AHI in OSA patients.
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•Associations of environmental factors with OSA severity were examined.•Ambient RH-dependent AHI was observed in OSA patients.•Decreased levels of PM2.5 and RH were associated with lower AHI values in OSA patients.•Patients staying in low-level PM2.5 and RH outdoor environments may reverse OSA severity.•Exposure of extreme weather could increase the risk of OSA severity.
Abstract
In this study, we analyze the influences of carbon nanotube (CNT) addition on the martensite transformation and internal friction of Cu–Al–Ni shape-memory alloys (SMAs). X-ray diffraction ...and differential scanning calorimetry results demonstrate that Cu–13.5Al–4Ni–
x
CNT (
x
= 0, 0.2, 0.4, 0.6, and 0.8 wt%) SMA/CNT composites exhibit a
$${\upbeta }_{1}({\mathrm{DO}}_{3})\rightleftarrows {\upbeta }_{1}^{\mathrm{^{\prime}}}(18\mathrm{R})$$
β
1
(
DO
3
)
⇄
β
1
′
(
18
R
)
martensitic transformation. The martensitic transformation temperatures and transformation enthalpies of the martensitic transformation peaks for the Cu–13.5Al–4Ni–
x
CNT (
x
= 0–0.8 wt%) composites gradually decrease with the increase in the amount of CNT addition. Compared to the Cu–13.5Al–4Ni SMA, the Cu–13.5Al–4Ni–
x
CNT (
x
= 0.2–0.8 wt%) SMA/CNT composites exhibit significant improvements in the amount of dissipation of energy (storage modulus (
$${E}^{\prime}))$$
E
′
)
)
and mechanical strength. However, the tan δ of the internal friction peak gradually decreases with the increase in the CNT content above 0.6 wt%. The reduction in tan
δ
is attributed to the decrease in the magnitude of the austenite-to-martensite transformation and precipitation of γ
2
(Cu
9
Al
4
) phase particles, which impede the interface motion in between the parent/martensitic phase and martensitic phase.
A recently developed bootstrap autoregressive-distributed lag test with structural breaks has been used to test the cointegration and causality regarding major economies worldwide, in order to ...investigate the relationship between electricity and economic growth during the period 1971–2014. Although a long-run cointegrating relationship between the time series of real GDP and electricity consumption per capita cannot be sufficiently detected, the results of this research show the contingency of causality. In India, the past histories of electricity consumption serve as a predictive indicator influencing the present states of economic growth. Positive and negative feedback exists in the United States and China, respectively. The results of the growth hypothesis support the government in India budgeting an enormous amount of money for its infrastructural development in the fiscal year 2017–2018. The government in the United States continues to investigate modern methods of developing the supply of electricity, such as renewable energy technologies. After the economic growth in China, Chinese citizens live in better conditions and garner a higher level of culture. Thus, they may pursue lower-energy-consuming products to strive for a better environment. Based on empirical analysis, certain policy and managerial implications have been addressed by decision-makers at the macroeconomic and microeconomic levels.
•Bootstrap ARDL test with structural breaks uses to test the cointegration.•No cointegration between real GDP and electricity consumption in China, the United States, and India.•Positive and negative feedback exists in the United States and China.•Positive unidirectional causality running from electricity consumption to economic growth in India.
Mutations of nicotinamide adenine dinucleotide phosphate-dependent isocitrate dehydrogenase gene (IDH1) have been identified in patients with gliomas. Recent genome-wide screening also revealed IDH1 ...mutation as a recurrent event in acute myeloid leukemia (AML), but its clinical implications in AML are largely unknown. We analyzed 493 adult Chinese AML patients in Taiwan and found 27 patients (5.5%) harboring this mutation. IDH1 mutation was strongly associated with normal karyotype (8.4%, P = .002), isolated monosomy 8 (P = .043), NPM1 mutation (P < .001), and French-American-British M1 subtype (P < .001), but inversely associated with French-American-British M4 subtype (P = .030) and expression of HLA-DR, CD13, and CD14 (P = .002, .003, and .038, respectively). There was no impact of this mutation on patient survival. Sequential analysis of IDH1 mutation was performed in 130 patients during follow-ups. None of the 112 patients without IDH1 mutation at diagnosis acquired this mutation at relapse. In all 18 IDH1-mutated patients studied, the mutation disappeared in complete remission; the same mutation reappeared in all 11 samples obtained at relapse. We conclude that IDH1 is associated with distinct clinical and biologic characteristics and seems to be very stable during disease evolution.
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