Gestational diabetes mellitus (GDM) is known as different degree glucose intolerance that is initially identified during pregnancy. MicroRNAs (miRs) may be a potential candidate for treatment of GDM. ...Herein, we suggested that miR‐351 could be an inhibitor in the progression of GDM via the phosphoinositide 3‐kinase/protein kinase B (PI3K/AKT) pathway. Microarray analysis was used to identify differentially expressed genes and predict miRs regulating flotillin 2 (FLOT2). Target relationship between miR‐351 and FLOT2 was verified. Gestational diabetes mellitus mice were treated with a series of mimic, inhibitor and small interfering RNA to explore the effect of miR‐351 on insulin resistance (IR), cell apoptosis in pancreatic tissues and liver gluconeogenesis through evaluating GDM‐related biochemical indexes, as well as expression of miR‐351, FLOT2, PI3K/AKT pathway‐, IR‐ and liver gluconeogenesis‐related genes. MiR‐351 and FLOT2 were reported to be involved in GDM. FLOT2 was the target gene of miR‐351. Gestational diabetes mellitus mice exhibited IR and liver gluconeogenesis, up‐regulated FLOT2, activated PI3K/AKT pathway and down‐regulated miR‐351 in liver tissues. Additionally, miR‐351 overexpression and FLOT2 silencing decreased the levels of FLOT2, phosphoenolpyruvate carboxykinase, glucose‐6‐phosphatase, fasting blood glucose, fasting insulin, total cholesterol, triglyceride, glyeosylated haemoglobin and homeostasis model of assessment for IR index (HOMA‐IR), extent of PI3K and AKT phosphorylation, yet increased the levels of HOMA for islet β‐cell function, HOMA for insulin sensitivity index and glucose transporter 2 expression, indicating reduced cell apoptosis in pancreatic tissues and alleviated IR and liver gluconeogenesis. Our results reveal that up‐regulation of miR‐351 protects against IR and liver gluconeogenesis by repressing the PI3K/AKT pathway through regulating FLOT2 in GDM mice, which identifies miR‐351 as a potential therapeutic target for the clinical management of GDM.
Press-hardened steels (PHS) with a 1.5-mm-thick coated Al⁻Si layer is welded using an IPG YLS6000 continuous fiber laser in the air atmosphere. An SU5000 scanning electron microscope (SEM) and an ...Oxford EDS X-Max20 energy spectrometer are used to characterize the microstructure, which consists of delta (δ)-ferrite and lath martensite. It is similar to that of the welding performed in the Ar atmosphere, but the content of δ-ferrite is less. The reason is the formation of Al₂O₃ inclusions in the molten pool, which reacts with oxygen from the air ambient and the Al from the molten Al⁻Si coating of PHS. The oxygen content is measured with an ONH-3000 analyzer. An HV-1000 microhardness tester and DNS-100 universal material test equipment are performed to test the hardness and tensile strength. Similar hardness and strength of welded joints are achieved welding in the air atmosphere compared to that of the Ar atmosphere. Fracture was initialed in the fusion line of overlapping zone and propagated along the interface of two plates and fusion line due to the Al segregation.
A
bstract
In this paper, we calculate the matrix element and form factors of vector-to- vector (
V
I
→ V
II
) transition within the standard light-front (SLF) and covariant light- front (CLF) quark ...models (QMs), and investigate the self-consistency and Lorentz covari- ance of the CLF QM within two types of correspondences between the manifest covariant Bethe-Salpeter approach and the LF approach. The zero-mode and valence contributions to the form factors of
V
I
→ V
II
transition in the CLF QM and their relation to the SLF results are analyzed, and the main conclusions obtained via the decay constants of vector and axial-vector mesons and the form factors of
P → V
transition in the previous works are confirmed again. Furthermore, we present our numerical predictions for the form factors of
c →
(
q, s
) (
q
=
u, d
) induced
D
*
→
(
K
*
, ρ
),
D
∗
→
(
ϕ, K
*
),
J/
Ψ
→
D
s
∗
D
∗
,
B
c
∗
→
B
s
∗
B
∗
transitions and
b →
(
c, s, q
) induced
B
∗
→ (
D
∗
,
K
∗
,
ρ
),
B
s
∗
→
D
s
∗
ϕ
K
∗
,
B
c
∗
→
J
/
Ψ
D
s
∗
D
∗
,
ϒ
1
S
→
B
c
∗
B
s
∗
B
∗
the relevant phenomenological studies of meson decays.
•FAN1 protects against repeat expansions in a mouse model of the FXDs.•Protection is seen in somatic tissues, including brain, but is not seen for intergenerational expansions.•As GWAS suggest, FAN1 ...mutations may affect the age at onset of some Repeat Expansion Diseases.
The Fragile X-related disorders (FXDs) are members of a large group of human neurological or neurodevelopmental conditions known as the Repeat Expansion Diseases. The mutation responsible for all of these diseases is an expansion in the size of a disease-specific tandem repeat tract. However, the underlying cause of this unusual mutation is unknown. Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) in the vicinity of the FAN1 (MIM* 613534) gene that are associated with variations in the age at onset of a number of Repeat Expansion Diseases. FAN1 is a nuclease that has both 5′-3′ exonuclease and 5′ flap endonuclease activities. Here we show in a model for the FXDs that Fan1−/− mice have expansions that, in some tissues including brain, are 2–3 times as extensive as they are in Fan1+/+ mice. However, no effect of the loss of FAN1 was apparent for germ line expansions. Thus, FAN1 plays an important role in protecting against somatic expansions but is either not involved in protecting against intergenerational repeat expansions or is redundant with other related enzymes. However, since loss of FAN1 results in increased expansions in brain and other somatic tissue, FAN1 polymorphisms may be important disease modifiers in those Repeat Expansion Diseases in which somatic expansion contributes to age at onset or disease severity.
Cell-free DNA is naturally degraded in various bodily fluids. The aim of this study was to determine the degradation kinetics of DNA, with and without protein, in serum, urine and saliva.
Naked DNA ...and DNA-protein complex were prepared, added to the samples to be analysed and incubated at 37°C and room temperature for various lengths of time. Alleles of 20 short tandem repeat loci were amplified from the incubated samples, and clearance models were generated from the mean peak areas.
Plotting the natural logarithm of DNA concentration against the incubation time produced a linear relationship. The half-lives of DNA with and without protein in serum were 157.6min and 30.8min at 37°C, 330.5min and 70.5min at room temperature, respectively. The half-lives of DNA with protein in saliva were 175.6min and 251.3min at 37°C and room temperature, respectively. However, the half-lives of DNA in urine (both with and without protein) were too short to detect.
The kinetics of DNA degradation in serum and saliva followed a first-order clearance model. Urine had the strongest effect on DNA degradation, and the half-lives of DNA with protein were relatively longer than those of naked DNA.
•DNA degradations were qualitatively observed in serum, saliva and urine.•DNA degradation followed a first-order clearance model in these samples.•The half-lives of DNA with protein were relatively longer than those of naked DNA.•The half-lives were around 3h in 37°C and 5h in 24°C for serum and saliva.•The half-lives of DNA in urine were too short to detect in room temperature.
X-linked inhibitor of apoptosis protein (XIAP) possesses a critical role in promotion of cell survival and maintenance of cellular homeostasis. In cancer, elevated XIAP expression has been associated ...with malignancy, poor prognosis, and treatment resistance. However, the underlying mechanisms of these effects remain unclear. XIAP has previously been proposed to promote tumor growth through suppression of autophagy. In this study, we examined the expression of XIAP and p62, two critical mediators of autophagy, in breast and colon cancer. We observed a negative correlation between XIAP and p62 expression in normal and cancer tissues of breast and colon, and that the ratio of XIAP and p62 expression determines the cancer phenotype. In vitro, we observed that XIAP interacted with p62 and also that XIAP depletion resulted in increased expression of p62. XIAP functioned as an ubiquitination E3 ligase towards p62 and suppressed p62 expression through ubiquitin-proteasomal degradation. Furthermore, XIAP enhanced cancer cell proliferation, viability, and colony formation in vitro via suppression of p62. In addition, we demonstrated that XIAP-enhanced tumor growth is dependent on depletion of p62 in vivo. Herein, we have therefore delineated a novel mechanism by which XIAP contributes to development and progression of breast and colon carcinoma.
Hematopoietic bone marrow stem cell transplantation has been regularly used in clinical practice for over 40 years. Further research indicates that bone marrow stromal cells are also stem cells that ...are capable of self-renewal, proliferation and differentiation. With appropriate induction, the bone marrow stromal cells can differentiate into bone, cartilage, tendon, adipose tissue and fibrous tissue, which would potentially be applied for treating bone loss diseases. This review outlines research in understanding role of bone marrow stem cells and stem cells from other origins in bone repair, and highlight the current and potential stem cell based treatment for bone loss diseases in the future.
We report a new strategy for synthesizing two-dimensional (2D) hierarchically porous carbon (HPC) based on soft pitch as the carbon source and oyster shell as both the template and activation agent ...precursor. The confined space of the sheet-like CaCO3 in oyster shell allows the soft pitch to diffuse and coat the in-built template, and the resultant 2D carbon derived from pyrolysis of the pitch inherited the sheet-like morphology of the template. Furthermore, CaCO3 can be easily converted into CaO, which acts as the self-activation agent to produce interconnected micro-, meso-, and macroporous carbon networks. The specific surface area of the resultant HPC was tuned from 612 to 1258 m2 g−1 by varying the pyrolysis time at 900 °C, and the resulting micro/meso-pore sizes were in the range of 0.7–9.5 nm. When used as the electrode of a lithium ion battery (LIB), the HPC exhibited a high reversible capacity of 1251 mAh g−1 at 0.1 A g−1 with excellent cycle stability. These results indicate that the 2D layered structure might effectively shorten the solid-state diffusion distance for Li ions in a LIB during the charging and discharging process. The interconnected hierarchical porous structure also improved the capacitance.
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Both phototropins (phot1 and phot2) and cryptochromes (cry1 and cry2) were proven as the Arabidopsis thaliana blue light receptors. Phototropins predominately function in photomovement, and ...cryptochromes play a role in photomorphogenesis. Although cryptochromes have been proposed to serve as positive modulators of phototropic responses, the underlying mechanism remains unknown. Here, we report that depleting sucrose from the medium or adding gibberellic acids (GAs) can partially restore the defects in phototropic curvature of the phot1 phot2 double mutants under high‐intensity blue light; this restoration does not occur in phot1 phot2 cry1 cry2 quadruple mutants and nph3 (nonphototropic hypocotyl 3) mutants which were impaired phototropic response in sucrose‐containing medium. These results indicate that GAs and sucrose antagonistically regulate hypocotyl phototropism in a cryptochromes dependent manner, but it showed a crosstalk with phototropin signaling on NPH3. Furthermore, cryptochromes activation by blue light inhibit GAs synthesis, thus stabilizing DELLAs to block hypocotyl growth, which result in the higher GAs content in the shade side than the lit side of hypocotyl to support the asymmetric growth of hypocotyl. Through modulation of the abundance of DELLAs by sucrose depletion or added GAs, it revealed that cryptochromes have a function in mediating phototropic curvature.
The concluded function of cryptochromes in hypocotyls phototropism is controversial. By phenotypic analysis of mutant lines grown on sucrose free medium or medium with added gibberellic acids, we demonstrated that cryptochromes‐mediated hypocotyl phototropism was regulated antagonistically by gibberellin and sugar. This process showed a crosstalk with phototropin signaling on NPH3.
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