Mitochondria take part in a network of intracellular processes that regulate homeostasis. Defects in mitochondrial function are key pathophysiological changes during AKI. Although Wnt/β-catenin ...signaling mediates mitochondrial dysfunction in chronic kidney fibrosis, little is known of the influence of β-catenin on mitochondrial function in AKI. To decipher this interaction, we generated an inducible mouse model of tubule-specific β-catenin overexpression (TubCat), and a model of tubule-specific β-catenin depletion (TubcatKO), and induced septic AKI in these mice with lipopolysaccharide (LPS) and aseptic AKI with bilateral ischemia-reperfusion. In both AKI models, tubular β-catenin stabilization in TubCat animals significantly reduced BUN/serum creatinine, tubular damage (NGAL-positive tubules), apoptosis (TUNEL-positive cells) and necroptosis (phosphorylation of MLKL and RIP3) through activating AKT phosphorylation and p53 suppression; enhanced mitochondrial biogenesis (increased PGC-1α and NRF1) and restored mitochondrial mass (increased TIM23) to re-establish mitochondrial homeostasis (increased fusion markers OPA1, MFN2, and decreased fission protein DRP1) through the FOXO3/PGC-1α signaling cascade. Conversely, kidney function loss and histological damage, tubular cell death, and mitochondrial dysfunction were all aggravated in TubCatKO mice. Mechanistically, β-catenin transfection maintained mitochondrial mass and activated PGC-1α via FOXO3 in LPS-exposed HK-2 cells. Collectively, these findings provide evidence that tubular β-catenin mitigates cell death and restores mitochondrial homeostasis in AKI through the common mechanisms associated with activation of AKT/p53 and FOXO3/PGC-1α signaling pathways.
A novel alkaline xylanase gene (
xyn
AI) from
Bacillus amyloliquefaciens
was highly expressed in
Pichia pastoris
, and the enzyme was purified and characterized. Sequence analysis indicated that ...XynAI belongs to xylanases family GH11 with 5 potential N-glycosylation sites and 3 salt bridges. The purified XynAI had molecular weight of 22 kDa, the optima temperature and pH of 55°C and pH 8.6, respectively. Furthermore, XynAI has high thermal (30–70°C) and pH (pH 5.0–10.0) stability.Mg
2+
, Ni
2+
, Ca
2+
and Fe
2+
at concentration of 1 mM enhanced the xylanase activity by 6.2, 6.5, 7.9 and 202.6%, respectively. Under optimal conditions, the
K
M
and
V
max
values of XynAI for beechwood xylan were 8 mg/mL and 83.3 µmol min
–1
mg of protein
–1
, respectively. In the culture supernatant, the maximal protein concentration and xylanase activity of XynAI reached 3.98 mg/mL and 292 U/mg, respectively. The biochemical properties of XynAI showed that it may be a promising candidate for industrial applications.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Purpose
To optimize and apply deep neural network based CEST (deepCEST) and apparent exchange dependent‐relaxation (deepAREX) for imaging the mouse brain with Alzheimer's disease (AD) at 3T MRI.
...Methods
CEST and T1 data of central and anterior brain slices of 10 AD mice and 10 age‐matched wild type (WT) mice were acquired at a 3T animal MRI scanner. The networks of deepCEST/deepAREX were optimized and trained on the WT data. The CEST/AREX contrasts of AD and WT mice predicted by the networks were analyzed and further validated by immunohistochemistry.
Results
After optimization and training on CEST data of WT mice, deepCEST/deepAREX could rapidly (~1 s) generate precise CEST and AREX results for unseen CEST data of AD mice, indicating the accuracy and generalization of the networks. Significant lower amide weighted (3.5 ppm) signal related to amyloid β‐peptide (Aβ) plaque depositions, which was validated by immunohistochemistry results, was detected in both central and anterior brain slices of AD mice compared to WT mice. Decreased magnetization transfer (MT) signal was also found in AD mice especially in the anterior slice.
Conclusion
DeepCEST/deepAREX could rapidly generate accurate CEST/AREX contrasts in animal study. The well‐optimized deepCEST/deepAREX have potential for AD differentiation at 3T MRI.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Rapid economic growth has given rise to a significant increase in ozone precursor emissions in many regions of China, especially in the densely populated North China Plain (NCP) and Yangtze River ...Delta (YRD). Improved understanding of ozone formation in response to different precursor emissions is imperative to address the highly nonlinear ozone problem and to provide a solid scientific basis for efficient ozone abatement in these regions. A comparative study on ozone photochemical production in summer has thus been carried out in the megacities of Tianjin (NCP) and Shanghai (YRD). Two intensive field campaigns were carried out respectively at an urban and a suburban site of Tianjin, in addition to routine monitoring of trace gases in Shanghai, providing data sets of surface ozone and its precursors including nitrogen oxides (NOx) and various non-methane hydrocarbons (NMHCs). Ozone pollution in summer was found to be more severe in the Tianjin region than in the Shanghai region, based on either the frequency or the duration of high ozone events. Such differences might be attributed to the large amount of highly reactive NMHCs in Tianjin. Industry related species like light alkenes were of particular importance in both urban and suburban Tianjin, while in Shanghai aromatics dominated. In general, the ozone problem in Shanghai is on an urban scale. Stringent control policies on local emissions would help reduce the occurrence of high ozone concentrations. By contrast, ozone pollution in Tianjin is probably a regional problem. Combined efforts to reduce ozone precursor emissions on a regional scale must be undertaken to bring the ozone problem under control.
Magnesium and its alloys are potential biodegradable implant materials due to their attractive biological property. But their poor corrosion resistance may result in the sudden failure of the ...implants. The bioactive hydroxyapatite (HA) coating was electrodeposited on AZ91D magnesium alloy surface to improve its biodegradation performance. The biodegradable behavior of HA coating was investigated by electrochemical tests and immersion tests. The experimental results indicated that the as-deposited coating consisting of dicalcium phosphate dehydrate ((DCPD, CaHPO
4 ·2H
2O) and β-tricalcium phosphate (β-TCP, Ca
3 (PO
4)
2) was transformed into uniform hydroxyapatite (HA, Ca
10 (PO
4)
6(OH)
2) coating after immersion in 1 M NaOH solution for 2 h. The HA coating can obviously slow down the biodegradation rate of AZ91D magnesium alloy in stimulated body fluid (SBF).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
A
bstract
Based on 4.5 fb
−
1
data taken at seven center-of-mass energies ranging from 4.600 to 4.699 GeV with the BESIII detector at the BEPCII collider, we measure the branching fractions of
Λ
c
+
...→
Σ
+
+
hadrons
relative to
Λ
c
+
→
Σ
+
π
+
π
−
. Combining with the world average branching fraction of
Λ
c
+
→
Σ
+
π
+
π
−
, their branching fractions are measured to be (0
.
377
±
0
.
042
±
0
.
020
±
0
.
021)% for
Λ
c
+
→
Σ
+
K
+
K
−
, (0
.
200
±
0
.
023
±
0
.
011
±
0
.
011)% for
Λ
c
+
→
Σ
+
K
+
π
−
, (0
.
414
±
0
.
080
±
0
.
030
±
0
.
023)% for
Λ
c
+
→
Σ
+
ϕ
and (0
.
197
±
0
.
036
±
0
.
009
±
0
.
011)% for
Λ
c
+
→ Σ
+
K
+
K
−
(non-
ϕ
). In all the above results, the first uncertainties are statistical, the second are systematic and the third are from external input of the branching fraction of
Λ
c
+
→
Σ
+
π
+
π
−
. Since no signal for
Λ
c
+
→
Σ
+
K
+
π
−
π
0
is observed, the upper limit of its branching fraction is determined to be 0.13% at the 90% confidence level.
The SOX4 transcription factor is involved in the development and cell fate decision. Although upregulation of SOX4 has been described in human prostate cancer (PCa), the prognostic value of SOX4 and ...its exact role in PCa progression remain unclear.
Three tissue microarrays were constructed from 241 Chinese PCa patients who underwent TURP. Immunohistochemistry (IHC) was used to detect the expression of SOX4. Genetic aberrations of epidermal growth factor receptor and HER2 were detected by fluorescence in situ hybridization. The effect of SOX4 on proliferation was evaluated by MTT (methyl thiazolyl tetrazelium), and cell migration and invasion were evaluated by transwell and wound-healing assays. The distribution of cell-cycle phase was analyzed by flow cytometry. Real-time PCR and western blot were used to study transcript and protein levels.
Using tissue microarray, we found that SOX4 was overexpressed in 33.0% (76/230) Chinese PCa patients by IHC. SOX4 overexpression was significantly associated with high Gleason scores (P=0.009) and the presence of distant metastasis (P=0.023). Additionally, SOX4 overexpression was significantly correlated with high Ki67 labeling index (P=0.005) and tended to associate with amplification of HER2 (P=0.052) in our cohort. Notably, SOX4 was correlated with cancer-specific mortality of PCa patients by Kaplan-Meier analysis (P=0.001). Multivariate Cox regression analysis indicated that SOX4 was an unfavorable independent prognostic factor in Chinese PCas (P=0.017). SOX4 overexpression enhanced proliferation of Vcap cells and siRNA knockdown of SOX4 significantly decreased Vcap cell migration and invasion, suggesting a role of SOX4 in cancer metastasis. Additionally, flow cytometry DNA analysis revealed that siRNA SOX4 leads to significant accumulation of cells in the S phase and marked decrease of cells in the G2/M phase. Further in vitro study revealed that SOX4 silencing could inhibit TGF-β (transforming growth factor-β)-induced epithelial-mesenchymal transition (EMT) in Vcap cells. Overexpression of SOX4 could promote the EMT phenotype in Vcap cells.
Our results define an important role for SOX4 in the progression of PCa by orchestrating EMT and may serve as a prognostic marker for PCa patients.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Polybrominated diphenyl ethers (PBDEs) have been commonly used as flame retardants and now become ubiquitous in the global environment. Using zebrafish as a model, we tested the hypothesis that PBDEs ...may affect the reproduction and development of fish. Zebrafish were exposed to environmentally relevant concentrations of DE-71 (a congener of PBDE commonly found in the environment) throughout their whole life cycle, and the effects of DE-71 on gonadal development, gamete quality, fertilization success, hatching success, embryonic development and sex ratio were investigated. Despite gonadal development was enhanced, reductions in spawning, fertilization success, hatching success and larval survival rate were evident, while significant increases in malformation and percentage of male were also observed in the F1 generation. Our laboratory results suggest that PBDEs may pose a risk to reproductive success and alter the sex ratio of fish in environments highly contaminated with PBDEs.
•Zebrafish were exposed to PBDE from eggs to adults.•An increase in Gonadal-Somatic Index and enhanced gonadal development was enhanced.•Fertilization and hatching successes were reduced, while malformation was increased.•PBDE alters sex differentiation, leading to a male biased F1 population.•Environmental relevant concentrations of PBDE threaten natural fish populations.
PBDE reduces fertilization and hatching successes, causes malformation and leads to a male biased F1 generation in fish.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
ABSTRACT
Based on Insight-HXMT data, we report on the pulse fraction evolution during the 2017–2018 outburst of the newly discovered first Galactic ultraluminous X-ray (ULX) source Swift ...J0243.6+6124. The pulse fractions of 19 observation pairs selected in the rising and fading phases with similar luminosity are investigated. The results show a general trend of the pulse fraction increasing with luminosity and energy at supercritical luminosity. However, the relative strength of the pulsation between each pair evolves strongly with luminosity. The pulse fraction in the rising phase is larger at luminosity below 7.71 × 1038 erg s−1, but smaller at above. A transition luminosity is found to be energy independent. Such a phenomenon is first confirmed by Insight-HXMT observations and we speculate that it may have relation with the radiation-pressure-dominated accretion disc.
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