Traumatic brain injury (TBI) is a principal cause of death and disability worldwide. Melatonin, a hormone made by the pineal gland, is known to have anti-inflammatory and antioxidant properties. In ...this study, using a weight-drop model of TBI, we investigated the protective effects of ramelteon, a melatonin MT1/MT2 receptor agonist, and its underlying mechanisms of action. Administration of ramelteon (10 mg/kg) daily at 10:00 a.m. alleviated TBI-induced early brain damage on day 3 and long-term neurobehavioral deficits on day 28 in C57BL/6 mice. Ramelteon also increased the protein levels of interleukin (IL)-10, IL-4, superoxide dismutase (SOD), glutathione, and glutathione peroxidase and reduced the protein levels of IL-1β, tumor necrosis factor, and malondialdehyde in brain tissue and serum on days 1, 3, and 7 post-TBI. Similarly, ramelteon attenuated microglial and astrocyte activation in the perilesional cortex on day 3. Furthermore, ramelteon decreased Keap 1 expression, promoted nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear accumulation, and increased levels of downstream proteins, including SOD-1, heme oxygenase-1, and NQO1 on day 3 post-TBI. However, in Nrf2 knockout mice with TBI, ramelteon did not decrease the lesion volume, neuronal degeneration, or myelin loss on day 3; nor did it mitigate depression-like behavior or most motor behavior deficits on day 28. Thus, timed ramelteon treatment appears to prevent inflammation and oxidative stress via the Nrf2-antioxidant response element pathway and might represent a potential chronotherapeutic strategy for treating TBI.
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•Ramelteon provided marked neuroprotection after TBI.•Ramelteon activated the Nrf2-ARE pathway in the brain after TBI.•The protection by ramelteon was partially lost in Nrf2-/- mice with TBI.
Ghrelin, a stomach-derived orexigenic hormone, has stimulated great interest as a potential target for obesity control. Pharmacological evidence indicates that ghrelin’s effects on food intake are ...mediated by neuropeptide Y (NPY) and agouti-related protein (AgRP) in the central nervous system. These include intracerebroventricular application of antibodies to neutralize NPY and AgRP, and the application of an NPY Y1 receptor antagonist, which blocks some of the orexigenic effects of ghrelin. Here we describe treatment of Agrp−/−;Npy−/− and Mc3r−/−;Mc4r−/− double knockout mice as well as Npy−/− and Agrp−/− single knockout mice with either ghrelin or an orally active nonpeptide ghrelin agonist. The data demonstrate that NPY and AgRP are required for the orexigenic effects of ghrelin, as well as the involvement of the melanocortin pathway in ghrelin signaling. Our results outline a functional interaction between the NPY and AgRP pathways. Although deletion of either NPY or AgRP caused only a modest or nondetectable effect, ablation of both ligands completely abolished the orexigenic action of ghrelin. Our results establish an in vivo orexigenic function for NPY and AgRP, mediating the effect of ghrelin.
Eight survey cruises in different seasons have been conducted in the Yellow Sea (YS) and East China Sea (ECS) during the period from 2000 to 2008. Suspended sediment concentration (SSC) and ...hydrological data were collected during each cruise. Data analysis showed that total suspended sediment mass was approximately 0.18 × 10
9 tons in the surveyed area during spring and autumn seasons. Highly turbid waters were found in the shallow waters between the Subei coast, the Changjiang estuary and the Zhejiang coast with seasonal variations.
The investigation provided convincing evidence that suspended sediments were transported from the Subei coast and the southern entrance of the Yellow Sea Trough to the central YS. Muddy patches were found at the sea bed when tidal currents were too weak to erode the bottom sediments and water column stratification and eddies provided favorable conditions for trapping the fine-grained suspended sediments.
The investigation indicated that the different front may have different effect on sediment transport during different seasons. The front between the Yellow Sea Cold Water and the coastal water in the Subei coast appeared to trap the high SSC sediments on the shallow water side of the front. During summer, the front along the Zhejiang coast seemed to prevent suspended sediments from transport across the front due to circulation in the front zone and upwelling along the Zhejiang coast. During winter, sediments were likely transported across the front to the central continental shelf of the ECS with the help of the downwelling and lateral Ekman transport driven by monsoon winds.
► We collect abundant in-situ data from 8 cruises during 2000–2008. ► We discuss the seasonal sediment transport and possible mechanism. ► Suspended sediments are transported from the Subei coast to the central Yellow Sea. ► A new explanation is given on the formation of muddy patches in the region. ► The different front may have different effect on sediment transport during different seasons.
Being a key feature of a glassy state, low temperature relaxation has important implications on the mechanical behavior of glasses; however, the mechanism of low temperature relaxation is still an ...open issue, which has been debated for decades. By systematically investigating the influences of cooling rate and pressure on low temperature relaxation in the Zr50Cu50 metallic glasses, it is found that even though pressure does induce pronounced local structural change, the low temperature-relaxation behavior of the metallic glass is affected mainly by cooling rate, not by pressure. According to the atomic displacement and connection mode analysis, we further demonstrate that the low temperature relaxation is dominated by the dispersion degree of fast dynamic atoms rather than the most probable atomic nonaffine displacement. Our finding provides the direct atomic-level evidence that the intrinsic heterogeneity is the key factor that determines the low temperature-relaxation behavior of the metallic glasses.
Abstract
In this paper, using a three-dimensional multispecies MHD model, we study the effect of the interplanetary magnetic field (IMF) intensity and orientation on the subsolar standoff distance of ...the Martian magnetic pileup boundary (
r
0
) and the pressure balance across it. The results show that: (1) with the increasing magnitude of the
Y-
or
Z-
component of the IMF,
B
Y
or
B
Z
,
r
0
increases, while the radial IMF component,
B
X
, has little effect. With the increasing magnitude of
B
Y
or
B
Z
, the compression degree of the magnetic field (
f
) increases, while the solar wind pressure coefficient (
k
) remains unchanged, resulting in the enhancement of
r
0
. (2) Under the same IMF intensity,
B
t
, the impact of the IMF cone angle on
r
0
and
f
is controlled by the ratio of the IMF
Y-
and
Z-
components to
B
t
,
B
Y
2
+
B
Z
2
/
B
t
. When the ratio is enhanced, both
r
0
and
f
increase, while
k
generally remains unchanged. Compared with the IMF cone angle, the influence of the IMF clock angle is relatively less. We suggest that the stronger magnetic pileup process controlled by the perpendicular IMFs (
B
Y
or
B
Z
) causes the larger
r
0
, while the weaker magnetic pileup under the radial IMF leads to the smaller
r
0
. The difference in the IMF effect on the size of the Martian magnetic pileup boundary and the terrestrial magnetopause reveals different solar wind interactions with a magnetized and unmagnetized planet. Last, the location of the intense crustal field can also affect
r
0
and the pressure balance condition, and the specific impact needs to be further studied.
The A1555 G mutation in mitochondrial 12S rRNA has been found to be associated with non-syndromic deafness and aminoglycoside-induced deafness. The sensitivity to the aminoglycoside paromomycin has ...been analyzed in lymphoblastoid cell lines derived from five deaf individuals and five hearing individuals from an Arab-Israeli family carrying the A1555G mutation, and three married-in controls from the same family. Exposure to a high concentration of paromomycin (2 mg/ml), which caused an 8% average increase in doubling time (DT) in the control cell lines, produced higher average DT increases (49 and 47%) in the A1555G mutation-carrying cell lines derived from symptomatic and asymptomatic individuals, respectively. The ratios of translation rates in the presence and absence of paromomycin, which reflected the effect of the drug on mitochondrial protein synthesis, were significantly decreased in the cell lines derived from symptomatic and asymptomatic individuals (by 30 and 28% on average, respectively), compared with the ratios in the control cell lines. These ratios showed, in both groups of mutant cell lines, a significant negative correlation with the ratios of DTs in the presence and absence of the antibiotic. These results have provided the first direct evidence that the mitochondrial 12S rRNA carrying the A1555G mutation is the main target of aminoglycosides. They suggest that these antibiotics exert their detrimental effect through an alteration of mitochondrial protein synthesis, which exacerbates the inherent defect caused by the mutation, reducing the overall translation rate down to and below the minimal level required for normal cellular function (40-50%).
We study the process e^{+}e^{-}→Λ_{c}^{+}Λover ¯_{c}^{-} at twelve center-of-mass energies from 4.6119 to 4.9509 GeV using data samples collected by the BESIII detector at the BEPCII collider. The ...Born cross sections and effective form factors (|G_{eff}|) are determined with unprecedented precision after combining the single and double-tag methods based on the decay process Λ_{c}^{+}→pK^{-}π^{+}. Flat cross sections around 4.63 GeV are obtained and no indication of the resonant structure Y(4630), as reported by Belle, is found. In addition, no oscillatory behavior is discerned in the |G_{eff}| energy dependence of Λ_{c}^{+}, in contrast to what is seen for the proton and neutron cases. Analyzing the cross section together with the polar-angle distribution of the Λ_{c}^{+} baryon at each energy point, the moduli of electric and magnetic form factors (|G_{E}| and |G_{M}|) are extracted and separated. For the first time, the energy dependence of the form factor ratio |G_{E}/G_{M}| is observed, which can be well described by an oscillatory function.
To explore and analyze the possible mechanism of liver injury in patients with coronavirus disease 2019 (novel coronavirus pneumonia, NCP).
The correlation between ALT, AST and other liver enzyme ...changes condition and NCP patients' disease status reported in the literature was comprehensively analyzed. ACE2 expression in liver tissue for novel coronavirus was analyzed based on single cell sequencing (GSE115469) data. RNA-Seq method was used to analyze Ace2 expression and transcription factors related to its expression in liver tissues at various time-points after hepatectomy in mouse model of acute liver injury with partial hepatectomy.
-test or Spearman rank correlation analysis was used for statistical analysis.
ALT and AST were abnormally elevated in some patients with novel coronavirus infection, and the rate and extent of ALT and AST elevation in severe NCP patients were higher than those in non-severe patients. Liver tissue results of single cell sequencing and immunohistochemistry showed that ACE2 was
The process e^{+}e^{-}→D_{s}^{*+}D_{s}^{*-} is studied with a semi-inclusive method using data samples at center-of-mass energies from threshold to 4.95 GeV collected with the BESIII detector ...operating at the Beijing Electron Positron Collider. The Born cross sections of the process are measured for the first time with high precision in this energy region. Two resonance structures are observed in the energy-dependent cross sections around 4.2 and 4.4 GeV. By fitting the cross sections with a coherent sum of three Breit-Wigner amplitudes and one phase-space amplitude, the two significant structures are assigned masses of (4186.8±8.7±30) and (4414.6±3.4±6.1) MeV/c^{2}, widths of (55±15±53) and (122.5±7.5±8.1) MeV, where the first errors are statistical and the second ones are systematic. The inclusion of a third Breit-Wigner amplitude is necessary to describe a structure around 4.79 GeV.
The destruction of lung parenchyma caused by TB can result in pulmonary sequelae that are classified as bronchiectasis due to traction (radiological sequelae), and bronchiectasis persisting with an ...inflammatory bronchial component and opportunistic bronchial infection. There is a lack of studies that comprehensively analyse whether post-TB bronchiectasis differs in clinical, prognostic or therapeutic aspects from bronchiectasis arising from other aetiologies. However, it has been noted that post-TB bronchiectasis tends to appear more frequently in the upper lung lobes. In many countries, TB is the most frequent known cause of bronchiectasis, but there is currently no targeted management of bronchiectasis due to TB as opposed to other aetiologies. It is imperative to first prevent TB, and when that fails to provide early diagnosis and adequate treatment for TB disease. In addition, efforts should be made to limit additional lung insults such as tobacco use and provide management of post TB bronchiectasis to minimise further pulmonary sequelae. The objective of this minireview was to provide an update on post-TB bronchiectasis, its definition, epidemiological data, pathophysiology, and clinical, diagnosis and therapeutic aspects.
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