Previous studies presumed that the disturbed neurovascular coupling to be a critical risk factor of cognitive impairments in type 2 diabetes mellitus (T2DM), but distinct clinical manifestations were ...lacked. Consequently, we decided to investigate the neurovascular coupling in T2DM patients by exploring the MRI relationship between neuronal activity and the corresponding cerebral blood perfusion.
Degree centrality (DC) map and amplitude of low-frequency fluctuation (ALFF) map were used to represent neuronal activity. Cerebral blood flow (CBF) map was used to represent cerebral blood perfusion. Correlation coefficients were calculated to reflect the relationship between neuronal activity and cerebral blood perfusion.
At the whole gray matter level, the manifestation of neurovascular coupling was investigated by using 4 neurovascular biomarkers. We compared these biomarkers and found no significant changes. However, at the brain region level, neurovascular biomarkers in T2DM patients were significantly decreased in 10 brain regions. ALFF-CBF in left hippocampus and fractional ALFF-CBF in left amygdala were positively associated with the executive function, while ALFF-CBF in right fusiform gyrus was negatively related to the executive function. The disease severity was negatively related to the memory and executive function. The longer duration of T2DM was related to the milder depression, which suggests T2DM-related depression may not be a physiological condition but be a psychological condition.
Correlations between neuronal activity and cerebral perfusion maps may be a method for detecting neurovascular coupling abnormalities, which could be used for diagnosis in the future. Trial registry number: This study has been registered in ClinicalTrials.gov (NCT02420470) on April 2, 2015 and published on July 29, 2015.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Sperm cryopreservation and artificial insemination are important methods for giant panda breeding and preservation of extant genetic diversity. Lower conception rates limit the use of artificial ...insemination with frozen-thawed giant panda sperm, due to the lack of understanding of the cryodamaging or cryoinjuring mechanisms in cryopreservation. Long non-coding RNAs (lncRNAs) are involved in regulating spermatogenesis. However, their roles during cryopreservation remain largely unexplored. Therefore, this study aimed to identify differentially expressed lncRNAs and mRNAs associated with cryodamage or freeze tolerance in frozen-thawed sperm through high throughput sequencing. A total of 61.05 Gb clean reads and 22,774 lncRNA transcripts were obtained. From the sequencing results, 1477 significantly up-regulated and 1,396 significantly down-regulated lncRNA transcripts from fresh and frozen-thawed sperm of giant panda were identified. GO and KEGG showed that the significantly dysregulated lncRNAs and mRNAs were mainly involved in regulating responses to cold stress and apoptosis, such as the integral component of membrane, calcium transport, and various signaling pathways including PI3K-Akt, p53 and cAMP. Our work is the first systematic profiling of lncRNA and mRNA in fresh and frozen-thawed giant panda sperm, and provides valuableinsights into the potential mechanism of cryodamage in sperm.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Ruthenium-containing complexes have emerged as good alternative to the currently used platinum-containing drugs for malignant tumor therapy. In this work, cytotoxic effects of recently synthesized ...ruthenium polypyridyl complexes Ru(bpy)2(CFPIP)(ClO4)2 (bpy = 2,2′-bipyridine, CFPIP = (E)-2-(4-fluorostyryl)-1H-imidazo4,5-f1,10phenanthroline, Ru(II)-1), Ru(phen)2(CFPIP)(ClO4)2 (phen = 1,10-phenanthroline, Ru(II)-2) and Ru(dmb)2(CFPIP)(ClO4)2 (dmb = 4,4′-dimethyl-2,2′-bipyridine, Ru(II)-3) toward different tumor cells were investigated in vitro and compared with cisplatin, the most widely used chemotherapeutic drug against hepatocellular carcinoma (HepG-2). The results demonstrate that target complexes show excellent cytotoxicity against HepG-2 cells with low IC50 value of 21.4 ± 1.5, 18.0 ± 2.1 and 22.3 ± 1.7 μM, respectively. It was important noting that target Ru(II) complexes exhibited better antitumor activity than cisplatin (IC50 = 28.5 ± 2.4 μM) against HepG-2 cells, and has no obvious toxicity to normal cell LO2. DNA binding results suggest that Ru(II)-1, Ru(II)-2 and Ru(II)-3 interact with CT DNA (calf thymus DNA) through intercalative mode. Complexes exerted its antitumor activity through increasing anti-migration and inducing cell cycle arrest at the S phase. In addition, the apoptosis was tested by AO (acridine orange)/EB (ethidium bromide) staining and flow cytometry. Mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and colocalization tests were also evaluated by ImageXpress Micro XLS system. Overall, the results show that the ruthenium polypyridyl complexes induce apoptosis in HepG-2 cells through ROS-mediated mitochondria dysfunction pathway.
DNA-binding behaviors and antitumor activity of the Ru(II) complexes were investigated. Complexes exerted its antitumor activity through increasing anti-migration and inducing cell cycle arrest at the S phase. In addition, mitochondrial membrane potential, reactive oxygen species, and colocalization tests were also evaluated by ImageXpress Micro XLS system. Display omitted
•Cinnamaldehyde-derived Ru(II) complexes were designed and synthesized.•In vitro antitumor activity screening of the Ru(II) complexes were investigated.•The desired Ru(II) complexes localizes in mitochondria.•Ru(II) complexes induce apoptosis of HepG-2 cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
MicroRNAs (miRNAs) function as potential diagnostic biomarkers in various cancers. This study aimed to evaluate the roles of miR‐205‐5p in lung cancer progression and diagnosis.
Materials ...and Methods
MiR‐205‐5p was detected by quantitative real‐time PCR. The effect of miR‐205‐5p on cell proliferation and metastasis was estimated by MTT and flow cytometry. The expression of TP53INP1 and related genes was analyzed by immunoblotting. The diagnostic value of miR‐205‐5p was analyzed using receiver operating characteristic (ROC) curve analysis, sensitivity, and specificity.
Results
The miR‐205‐5p was increased in lung cancer tissues. MiR‐205‐5p mimics were promoted but its inhibitor suppressed cell proliferation and metastasis compared with control treatment in vitro and in vivo. By regulating the 3′ untranslated region, miR‐205‐5p could negatively regulate TP53INP1 expression, which further inhibited the expression of RB1 and P21, but increased that of cyclinD1. Moreover, the serum miR‐205‐5p levels of patients with lung cancer were significantly higher than those of normal controls, and they were correlated with patients' gender, drinking status, and clinical stage. The area under the ROC curve of serum miR‐205‐5p in the diagnosis of non‐small‐cell lung cancer was 0.8250, respectively. The finding supported its possession of high diagnostic efficiency for lung cancer.
Conclusions
MiR‐205‐5p promoted lung cancer cell proliferation and metastasis by negatively regulating the novel target TP53INP1, which further affected the expression of P21, RB1, and cyclin D1. Serum miR‐205‐5p is a novel and valuable biomarker for lung cancer diagnosis.
MiR‐205‐5p was upregulated in lung cancer and promoted lung cancer cell proliferation by negatively regulating a novel target TP53INP1, which further affected the expression of P21, RB1, and cyclin D1. A high level of serum miR‐205‐5p is a valuable biomarker for the diagnosis of patients with lung cancer.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Objective
To explore the characteristics and risk factors for major mediastinal vessel invasion in different risk grades of thymic epithelial tumors (TETs) based on computed tomography (CT) imaging, ...and to develop prediction models of major mediastinal artery and vein invasion.
Methods
One hundred and twenty-two TET patients confirmed by histopathological analysis who underwent thorax CT were enrolled in this study. Clinical and CT data were retrospectively reviewed for these patients. According to the abutment degree between the tumor and major mediastinal vessels, the arterial invasion was divided into grade I, II, and III (< 25%, 25 – 49%, and ≥ 50%, respectively); the venous invasion was divided into grade I and II (< 50% and ≥ 50%). The degree of vessel invasion was compared among different defined subtypes or stages of TETs using the chi-square tests. The risk factors associated with TET vascular invasion were identified using multivariate logistic regression analysis.
Results
Based on logistic regression analysis, male patients (β = 1.549; odds ratio, 4.824) and the pericardium or pleural invasion (β = 2.209; odds ratio, 9.110) were independent predictors of 25% artery invasion, and the midline location (β = 2.504; odds ratio, 12.234) and mediastinal lymphadenopathy (β = 2.490; odds ratio, 12.06) were independent predictors of 50% artery invasion. As for 50% venous invasion, the risk factors include midline location (β = 2.303; odds ratio, 10.0), maximum tumor diameter larger than 5.9 cm (β = 4.038; odds ratio, 56.736), and pericardial or pleural effusion (β = 1.460; odds ratio, 4.306). The multivariate logistic model obtained relatively high predicting efficacy, and the area under the curve (AUC), sensitivity, and specificity were 0.944, 84.6%, and 91.7% for predicting 50% artery invasion, and 0.913, 81.8%, and 86.0% for 50% venous invasion in TET patients, respectively.
Conclusion
Several CT features can be used as independent predictors of ≥50% artery or venous invasion. A multivariate logistic regression model based on CT features is helpful in predicting the vascular invasion grades in patients with TET.
•SsC4H has 1849-bp with a 1518-bp open reading frame encoding 505-amino acid protein.•SsC4H protein have structural features of CYP450 and trans-cinnamate 4-monooxygenase.•Recombinant SsC4H protein ...catalyzed trans-cinnamic acid to p-coumaric acid.•NO delayed wax apple fruit softening by inhibiting SsC4H, C4H and lignin synthesis.
Cottony softening of harvested wax apple fruit is characterized by lignin accumulation, and it involves the activity of cinnamate-4-hydroxylase (C4H) and its encoding gene. This work investigated the characteristics and function of the C4H gene of wax apple fruit and discussed its relationship with lignin biosynthesis during nitric oxide (NO)-delayed cottony softening of harvested wax apple fruit. The C4H gene cloned from wax apple fruit was named SsC4H, and it has a length of 1849 bp and a 1518 bp open reading frame encoding 505 amino acids. The sequence of SsC4H-encoded amino acids contained typical C4H domains and shared high sequence similarity and close evolutionary relationships with C4H from other plants; in vitro catalytic activity of C4H was observed in the expressed and purified recombined SsC4H protein. Moreover, the SsC4H expression and C4H activities were inhibited in NO-treated wax apple fruit compared with control fruit, with lower lignin content and cottony softening index. Therefore, SsC4H was confirmed as the C4H gene for wax apple fruit, and the NO-retarded cottony softening of harvested wax apple fruit may be attributed to inhibited expression of SsC4H and C4H activity, delaying lignin biosynthesis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Phosphates are essential for modern metabolisms. A recent study reported a phosphate-free metabolic network and suggested that thioesters, rather than phosphates, could alleviate thermodynamic ...bottlenecks of network expansion. As a result, it was considered that a phosphorus-independent metabolism could exist before the phosphate-based genetic coding system. To explore the origin of phosphorus-dependent metabolism, the present study constructs a protometabolic network that contains phosphates prebiotically available using computational systems biology approaches. It is found that some primitive phosphorylated intermediates could greatly alleviate thermodynamic bottlenecks of network expansion. Moreover, the phosphorus-dependent metabolic network exhibits several ancient features. Taken together, it is concluded that phosphates played a role as important as that of thioesters during the origin and evolution of metabolism. Both phosphorus and sulfur are speculated to be critical to the origin of life.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•Neurovascular coupling dysfunction was found in chronic migraine.•Visual language related gyri were involved in neurovascular coupling dysfunction.•Sensory system and pain transmitting network ...related gyri were also involved.
Previous studies reported that long-term nociceptive stimulation could result in neurovascular coupling (NVC) dysfunction in brain, but these studies were based mainly on unimodal imaging biomarkers, thus could not comprehensively reflect NVC dysfunction. We investigated the potential NVC dysfunction in chronic migraine by exploring the relationship between neuronal activity and cerebral perfusion maps. The Pearson correlation coefficients between these 2 maps were defined as the NVC biomarkers. NVC biomarkers in migraineurs were significantly lower in left inferior parietal gyrus (IPG), left superior marginal gyrus (SMG) and left angular gyrus (AG), but significantly higher in right superior occipital gyrus (SOG), right superior parietal gyrus (SPG), and precuneus. These brain regions were located mainly in parietal or occipital lobes and were related to visual or sensory information processing. ALFF-CBF in right SPG was positively correlated with disease history and that in right precuneus was negatively correlated with migraine persisting time. fALFF-CBF in left SMG and AG were negatively related to headache frequency and positively related to health condition and disease history. In conclusion, multi-modal MRI could be used to detect NVC dysfunction in chronic migraine patients, which is a new method to assess the impact of chronic pain on the brain.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The (1 −
x
)(Bi
0.5
Na
0.42
K
0.08
)
0.96
Sr
0.04
Ti
0.975
Nb
0.025
O
3
–
x
BiAlO
3
(
x
= 0, 0.01, 0.02, 0.03, 0.05) lead-free ceramics were synthesized by means of the traditional solid-state ...reaction method. Influences of the BiAlO
3
doping on structure, dielectric, and ferroelectric properties of the ceramics were systematically investigated. The X-ray diffraction (XRD) measurement was used to detect phase structure. The samples exhibit pseudocubic symmetry and dense microstructures. All of the ceramics, whether they were poled or unpoled, exhibit two dielectric anomalies on the dielectric spectra between room temperature and 350 °C, and no dielectric anomaly related to depolarization behavior was observed. The polarization loops and strain curves exhibit pinching-type shape and sprout shape, respectively. The corresponding mechanism was also discussed.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ