Fibroblast growth factor 21 (FGF21) is a stress-inducible hormone that has important roles in regulating energy balance and glucose and lipid homeostasis through a heterodimeric receptor complex ...comprising FGF receptor 1 (FGFR1) and β-klotho. Administration of FGF21 to rodents or non-human primates causes considerable pharmacological benefits on a cluster of obesity-related metabolic complications, including a reduction in fat mass and alleviation of hyperglycaemia, insulin resistance, dyslipidaemia, cardiovascular disorders and non-alcoholic steatohepatitis (NASH). However, native FGF21 is unsuitable for clinical use owing to poor pharmacokinetic and biophysical properties. A large number of long-acting FGF21 analogues and agonistic monoclonal antibodies for the FGFR1-β-klotho receptor complexes have been developed. Several FGF21 analogues and mimetics have progressed to early phases of clinical trials in patients with obesity, type 2 diabetes mellitus and NASH. In these trials, the primary end points of glycaemic control have not been met, whereas substantial improvements were observed in dyslipidaemia, hepatic fat fractions and serum markers of liver fibrosis in patients with NASH. The complexity and divergence in pharmacology and pathophysiology of FGF21, interspecies variations in FGF21 biology, the possible existence of obesity-related FGF21 resistance and endogenous FGF21 inactivation enzymes represent major obstacles to clinical implementation of FGF21-based pharmacotherapies for metabolic diseases.
Within the chiral unitary approach and with the constraints of heavy quark spin symmetry, we study the coupled channel interactions of D (*) Σc (*) channels, close to whose thresholds three ...pentaquarklike P c states have been reported by the LHCb Collaboration. In the present work, we take into account the contributions of pion exchanges via box diagrams to the interaction potentials, and therefore lift the degeneracy in the masses of D ∗ Σc (*) spin multiplets. Fitting the J/ψp invariant mass distributions in the Λ0b → J/ψK − p decay, we find that the LHCb pentaquark states cannot be reproduced in the direct J/ψp production in the Λ0b decay, and can only be indirectly produced in the final state interactions of the Λ0b decay products, D (*) Σc (*), which further supports the nature of these states as D (*) Σc molecules. Based on the fit results obtained, we study the partial decay widths/branching ratios to the other decay channels, D ∗ Λc, D Λc, and ηcN, and the corresponding invariant mass distributions. The resonances with JP = 1/2 −, Pc (4312), Pc (4440) and the one of D ∗ Σ∗c around 4500 MeV, have large partial decay width into ηcN, and thus can be easily seen in the ηcN invariant mass distributions. By contrast, the states with JP = 3/2 −, Pc (4457), the (predicted) narrow Pc (4380), and the bound state of ¯ D∗Σ∗c with a mass of about 4520 MeV do not decay into ηcN. Therefore, the ηcN channel should be studied in the future to provide further insights into the nature of these states, especially that of Pc (4440) and Pc (4457) .
We revisit the classical relation between the strangeness content of the nucleon, the pion–nucleon sigma term and the SU(3)F breaking of the baryon masses in the context of Lorentz covariant chiral ...perturbation theory with explicit decuplet-baryon resonance fields. We find that a value of the pion–nucleon sigma term of ∼60 MeV is not necessarily at odds with a small strangeness content of the nucleon, in line with the fulfillment of the OZI rule. Moreover, this value is indeed favored by our next-to-leading order calculation. We compare our results with earlier ones and discuss the convergence of the chiral series as well as the uncertainties of chiral approaches to the determination of the sigma terms.
Increasing evidence suggests that large intervening non-coding RNAs (lincRNAs) regulate key pathways in cancer invasion and metastasis. In this observational retrospective study, the expression of ...the oncogenic lincRNA HOX transcript antisense RNA (HOTAIR) gene was measured in 63 patients with hepatocellular carcinoma (HCC) following hepatic resection. The HOTAIR gene was significantly overexpressed in HCC tissues compared with adjacent non-tumour tissues. Patients with high HOTAIR gene expression in their tumours had an increased risk of recurrence after hepatectomy. There was also a significant correlation between HOTAIR expression and lymph node metastasis. In vitro assays in the HCC cell line Bel7402 demonstrated that knockdown of HOTAIR lincRNA reduced cell proliferation and was associated with reductions in levels of matrix metalloproteinase-9 and vascular endothelial growth factor protein, which are important for cell motility and metastasis. In conclusion, HOTAIR lincRNA might be a potential biomarker for the existence of lymph node metastasis in HCC.
The nuclear shell structure, which originates in the nearly independent motion of nucleons in an average potential, provides an important guide for our understanding of nuclear structure and the ...underlying nuclear forces. Its most remarkable fingerprint is the existence of the so-called magic numbers of protons and neutrons associated with extra stability. Although the introduction of a phenomenological spin-orbit (SO) coupling force in 1949 helped in explaining the magic numbers, its origins are still open questions. Here, we present experimental evidence for the smallest SO-originated magic number (subshell closure) at the proton number six in
C obtained from systematic analysis of point-proton distribution radii, electromagnetic transition rates and atomic masses of light nuclei. Performing ab initio calculations on
C, we show that the observed proton distribution radii and subshell closure can be explained by the state-of-the-art nuclear theory with chiral nucleon-nucleon and three-nucleon forces, which are rooted in the quantum chromodynamics.
We study the ground-state octet baryon masses and sigma terms using the covariant baryon chiral perturbation theory (ChPT) with the extended-on-mass-shell (EOMS) renormalization scheme up to ...next-to-next-to-next-to-leading order (N
3
LO). By adjusting the available 19 low-energy constants (LECs), a reasonable fit of the
n
f
= 2+1 lattice quantum chromodynamics (LQCD) results from the PACS-CS, LHPC, HSC, QCDSF-UKQCD and NPLQCD collaborations is achieved. Finite-volume corrections to the lattice data are calculated self-consistently. Our study shows that the N
3
LO BChPT describes better the light quark mass evolution of the lattice data than the NNLO BChPT does and the various lattice simulations seem to be consistent with each other. We also predict the pion and strangeness sigma terms of the octet baryons using the LECs determined in the fit of their masses. The predicted pion- and strangeness-nucleon sigma terms are
σ
π
N
= 43(1)(6) MeV and
σ
sN
= 126(24)(54) MeV, respectively.
Abstract
Aims
Adipocyte fatty acid-binding protein (A-FABP) is an adipokine implicating in various metabolic diseases. Elevated circulating levels of A-FABP correlate positively with poor prognosis ...in ischaemic stroke (IS) patients. No information is available concerning the role of A-FABP in the pathogenesis of IS. Experiments were designed to determine whether or not A-FABP mediates blood–brain barrier (BBB) disruption, and if so, to explore the molecular mechanisms underlying this deleterious effects.
Methods and results
Circulating A-FABP and its cerebral expression were increased in mice after middle cerebral artery occlusion. Genetic deletion and pharmacological inhibition of A-FABP alleviated cerebral ischaemia injury with reduced infarction volume, cerebral oedema, neurological deficits, and neuronal apoptosis; BBB disruption was attenuated and accompanied by reduced degradation of tight junction proteins and induction of matrix metalloproteinases-9 (MMP-9). In patients with acute IS, elevated circulating A-FABP levels positively correlated with those of MMP-9 and cerebral infarct volume. Mechanistically, ischaemia-induced elevation of A-FABP selectively in peripheral blood monocyte-derived macrophages and cerebral resident microglia promoted MMP-9 transactivation by potentiating JNK/c-Jun signalling, enhancing degradation of tight junction proteins and BBB leakage. The detrimental effects of A-FABP were prevented by pharmacological inhibition of MMP-9.
Conclusion
A-FABP is a key mediator of cerebral ischaemia injury promoting MMP-9-mediated BBB disruption. Inhibition of A-FABP is a potential strategy to improve IS outcome.
We have identified the decay modes of the
D
s
+
→
π
+
K
∗
+
K
∗
-
,
π
+
K
∗
0
K
¯
∗
0
reactions producing a pion and two vector mesons. The posterior vector–vector interaction generates two ...resonances that we associate to the
f
0
(
1710
)
and the
a
0
(
1710
)
recently claimed, and they decay to the observed
K
+
K
-
or
K
S
0
K
S
0
pair, leading to the reactions
D
s
+
→
π
+
K
+
K
-
,
π
+
K
S
0
K
S
0
. The results depend on two parameters related to external and internal emission. We determine a narrow region of the parameters consistent with the large
N
c
limit within uncertainties which gives rise to decay widths in agreement with experiment. With this scenario we make predictions for the branching ratio of the
a
0
(
1710
)
contribution to the
D
s
+
→
π
0
K
+
K
S
0
reaction, finding values within the range of
(
1.3
±
0.4
)
×
10
-
3
. Comparison of these predictions with coming experimental results on that latter reaction will be most useful to deepen our understanding on the nature of these two resonances.
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