Genomic instability caused by mutation of the checkpoint molecule TP53 may endow cancer cells with the ability to undergo genomic evolution to survive stress and treatment. We attempted to gain ...insight into the potential contribution of ovarian cancer genomic instability resulted from TP53 mutation to the aberrant expression of multidrug resistance gene MDR1.
TP53 mutation status was assessed by performing nucleotide sequencing and immunohistochemistry. Ovarian cancer cell DNA ploidy was determined using Feulgen-stained smears or flow cytometry. DNA copy number was analyzed by performing fluorescence in situ hybridization (FISH).
In addition to performing nucleotide sequencing for 5 cases of ovarian cancer, TP53 mutations were analyzed via immunohistochemical staining for P53. Both intensive P53 immunohistochemical staining and complete absence of signal were associated with the occurrence of TP53 mutations. HE staining and the quantification of DNA content indicated a significantly higher proportion of polyploidy and aneuploidy cells in the TP53 mutant group than in the wild-type group (p < 0.05). Moreover, in 161 epithelial ovarian cancer patients, multivariate logistic analysis identified late FIGO (International Federation of Gynecology and Obstetrics) stage, serous histotype, G3 grade and TP53 mutation as independent risk factors for ovarian cancer recurrence. In relapse patients, the proportion of chemoresistant cases in the TP53 wild-type group was significantly lower than in the mutant group (63.6% vs. 91.8%, p < 0.05). FISH results revealed a higher percentage of cells with >6 MDR1 copies and chromosome 7 amplication in the TP53 mutant group than in the wild-type group 11.7 ± 2.3% vs. 3.0 ± 0.7% and 2.1 ± 0.7% vs. 0.3 ± 0.05%, (p < 0.05), respectively. And we observed a specific increase of MDR1 and chromosome 7 copy numbers in the TP53 mutant group upon disease regression (p < 0.01).
TP53 mutation-associated genomic instability may promote chromosome 7 accumulation and MDR1 amplification during ovarian cancer chemoresistance and recurrence. Our findings lay the foundation for the development of promising chemotherapeutic approaches to treat aggressive and recurrent ovarian cancer.
The binding mode and stoichiometry of the cationic porphyrin TMPyP4 to G-quadruplex structure are still controversial to date, mainly due to the intricate polymorphism of G-rich sequences in the ...different conditions of solution. Here in the presence of the molecular crowding agent PEG, the binding interaction of TMPyP4 and another porphyrin derivative TPrPyP4 with four-stranded parallel (G
4T
4G
4)4 G-quadruplex was studied systematically using circular dichroism, visible absorption titration, and steady-state and time-resolved fluorescence spectroscopies. The results show that each (G
4T
4G
4)4 molecule is able to bind four TMPyP4 or TPrPyP4 molecules. Two types of independent and nonequivalent binding sites with the higher and lower binding affinity are confirmed, and the stronger and weaker binding constants are 2.74
×
10
8 and 8.21
×
10
5
M
−
1
for (G
4T
4G
4)4-TMPyP4, 2.05
×
10
8 and 1.05
×
10
6
M
−
1
for (G
4T
4G
4)4-TPrPyP4, respectively. The two porphyrin molecules stack on the two ends of G-quadruplex with the higher binding affinity, another two porphyrins bind weakly to the two external grooves.
Microbial evolution-mediated CO
2
from litter has aroused widespread concern, and knowing the factors controlling litter-derived CO
2
is important when considering the effects of accumulative CO
2
...release from litter on the global greenhouse. We conducted a short-term N addition (6, 16, and 24 g N m
‒2
yr
‒1
) experiment in
Cyperus malaccensis
var.
brevifolius
(shichito matgrass) litter decomosition. Phospholipid fatty acid (PLFA) method and enzyme method were used to analysis litter microbial community composition and enzymatic activity. During a 220-day decomposition period, there was little effect of the N amendments on litter CO
2
evolution rates (9.97‒307.54 μg C g
−1
h
−1
) with a notable exception regarding the increase of the high-N treatment at day 20. The accumulative CO
2
release significantly increased after N addition in the medium and late phases. The facilitation effect on accumulative CO
2
release by N amendments was more and more obvious over the decomposition time, especially for the low- and intermediate-N treatments. At the end of our experiment, compared with the control treatment, accumulative CO
2
release increased 69.75%, 76.62%, and 39.93% for low-, intermediate-, and high-N treatments, respectively. These observations highlight that N deposition could cause high losses of litter C as CO
2
.
Hepatocellular carcinoma is the fifth most common malignancy and the third leading cause of cancer-related death worldwide. Dysregulation of HomeoboxD10 (HOXD10) was found to suppress or promote ...cancer progression in different cancer types. The function and regulation of HOXD10 remain unclear in human hepatocellular carcinoma (HCC).
Primary HCC samples (117), normal liver tissue samples (15), and 13 HCC cell lines (SNU182, SNU449, HBXF344, SMMC7721, Huh7, HepG2, LM3, PLC/PRF/5, BEL7402, SNU387, SNU475, QGY7703, and Huh1) were included in this study. Methylation-specific PCR, flow cytometry, western blot, transwell, siRNA, and chromatin immunoprecipitation assays were employed.
HOXD10 was methylated in 76.9% (90/117) of human primary HCC samples. HOXD10 methylation was significantly associated with vessel cancerous embolus, tumor cell differentiation, and the 3-year overall survival rate (all
< 0.05). The expression of HOXD10 was regulated by promoter region methylation. HOXD10 suppressed colony formation, cell proliferation, cell invasion and migration, and induced G2/M phase arrest and apoptosis in HCC cells. HOXD10 suppressed HCC cell xenograft growth in mice. HOXD10 suppresses HCC growth by inhibiting ERK signaling.
HOXD10 is frequently methylated in human HCC, and the expression of HOXD10 is regulated by promoter region methylation. HOXD10 suppresses HCC cell growth both in vitro and in vivo. HOXD10 suppresses human HCC by inhibiting ERK signaling.
is a new member of the Ras gene family. It was described as a potential tumor suppressor in human glioblastomas and esophageal cancer. The role of
in colorectal cancer remains unclear.
To explore the ...epigenetic changes and function of
in human colorectal cancer, we studied ten colorectal cancer cell lines and 146 primary colorectal cancer samples and 50 matched adjacent samples using semi-quantitative reverse transcription PCR, immunohistochemistry, methylation-specific PCR and bisulfite sequencing, western blot, flow cytometry, and transwell assays.
expression was found in DKO and HCT116 cells, while reduced expression was detected in LoVo, SW48, LS180, and SW620 cells, and there was no expression detected in DLD1, HT29, RKO, and SW480 cells. Complete methylation was found in the promoter region of DLD1, HT29, RKO, and SW480 cells. Partial methylation was detected in LoVo, LS180, SW48, and SW620 cells, and unmethylation was found in DKO and HCT116 cells. These results indicate that promoter region methylation correlated with loss of/reduced expression of
. Re-expression of
was induced by 5-aza-2'-deoxycytidine, suggesting that the expression of
is regulated by promoter region methylation.
was methylated in 47.3% (69/146) of primary colorectal cancer samples, no methylation was found in non-cancerous colonic tissue samples. Methylation of
was significantly associated with TNM stage (
0.05) and short survival time (
0.0121).
induced apoptosis and inhibited cell proliferation, migration, and invasion in colorectal cancer. Finally,
suppressed colorectal cancer cell xenograft growth in nude mice.
is frequently methylated in human colorectal cancer and the expression of
is regulated by promoter region methylation. Methylation of
is a marker of poor prognosis in human colorectal cancer.
Influenza A virus (IAV) has been raising public health and safety concerns worldwide. Cyanovirin-N (CVN) is a prominent anti-IAV candidate, but both cytotoxicity and immunogenicity have hindered the ...development of this protein as a viable therapy. In this article, linker-CVN (LCVN) with a flexible and hydrophilic polypeptide at the N-terminus was efficiently produced from the cytoplasm of Escherichia coli at a >15-l scale. PEGylation at the N-terminal α-amine of LCVN was also reformed as 20 kDa PEGylated linkered Cyanovirin-N (PEG20k-LCVN). The 50% effective concentrations of PEG20k-LCVN were 0.43 ± 0.11 µM for influenza A/HK/8/68 (H3N2) and 0.04 ± 0.02 µM for A/Swan/Hokkaido/51/96 (H5N3), dramatically lower than that of the positive control, Ribavirin (2.88 ± 0.66 × 10(3) µM and 1.79 ± 0.62 × 10(3) µM, respectively). A total of 12.5 µM PEG20k-LCVN effectively inactivate the propagation of H3N2 in chicken embryos. About 2.0 mg/kg/day PEG20k-LCVN increased double the survival rate (66.67%, P = 0.0378) of H3N2 infected mice, prolonged the median survival period, downregulated the mRNA level of viral nuclear protein and decreased (attenuated) the pathology lesion in mice lung. A novel PEGylated CVN derivative, PEG20k-LCVN, exhibited potent and strain-dependent anti-IAV activity in nanomolar concentrations in vitro, as well as in micromolar concentration in vivo.
Wireless powered communication (WPC) has been considered as one of the key technologies in the Internet of Things (IoT) applications. In this paper, we study a wireless powered time-division duplex ...(TDD) multiuser multiple-input multiple-output (MU-MIMO) system, where the base station (BS) has its own power supply and all users can harvest radio frequency (RF) energy from the BS. We aim to maximize the users' information rates by jointly optimizing the duration of users' time slots and the signal covariance matrices of the BS and users. Different to the commonly used sum rate and max-min rate criteria, the proportional fairness of users' rates is considered in the objective function. We first study the ideal case with the perfect channel state information (CSI), and show that the non-convex proportionally fair rate optimization problem can be transformed into an equivalent convex optimization problem. Then we consider practical systems with imperfect CSI, where the CSI mismatch follows a Gaussian distribution. A chance-constrained robust system design is proposed for this scenario, where the Bernstein inequality is applied to convert the chance constraints into the convex constraints. Finally, we consider a more general case where only partial knowledge of the CSI mismatch is available. In this case, the conditional value-at-risk (CVaR) method is applied to solve the distributionally robust system rate optimization problem. Simulation results are presented to show the effectiveness of the proposed algorithms.
Low bandgap lead–tin (Pb–Sn) mixed perovskite solar cells have achieved high power conversion efficiency in excess of 17%. However, methylammonium (MA) cation is usually contained, and the thermal ...stability of MA is always a great concern. In this work, according to composition engineering, a nearly formamidinium (FA) based low‐bandgap Pb–Sn mixed perovskite FAPb0.75Sn0.25I3 is being tried to explore as the absorber layer. Combined with interface engineering by replacing poly(3,4‐ethylenedioxythiophene)‐polystyrenesulfonic acid (PEDOT:PSS), layer with NiOx as hole transport layer, a power conversion efficiency of 17.25% is obtained. This low‐bandgap perovskite solar cell maintains about 91% of its original efficiency at 80 °C for 20 h, and 92% of its initial performance after 46 days storage at the room temperature. The good thermal stability of nearly FA based low‐bandgap perovskite could be good for delivering efficient and stable perovskite‐perovskite tandem solar cells.
A nearly formamidinium (FA) lead–tin (Pb–Sn) mixed perovskite FAPb0.75Sn0.25I3 is exploited to fabricate a low‐bandgap perovskite solar cell. By combination with a NiOx hole transport layer, a power conversion efficiency of 17.25% is obtained. This low‐bandgap perovskite solar cell maintains about 91% of its original efficiency at 80 °C for 20 h, which demonstrates good thermal stability.
The retrogradation of gelatinized starch is primarily responsible for the decreased qualities and shelf-lives of starch-based foods. Inspired by the mixture of rice flour and infant milk powder in ...daily life and the inhibition on retrogradation of gelatinized starch by protein hydrolysate, the purpose of this study was to provide scientific insights into whey protein hydrolysate (WPH) as a potential anti-retrogradation additive for gelatinized rice starch (RS). The addition of WPH restricted the amylose leaching and swelling of RS, resulting in decreased peak viscosity and peak storage modulus, and the setback values reduced as well. The combinations between WPH and starch polymer chains reduced the action site of the enzyme, increasing the resistant starch content. On retrogradation (storage at 4 °C for 14 days), compared with RS, the hardness and water mobility significantly decreased with the addition of WPH; the relative crystallinity decreased from 13.82 to 10.44%, while the 1047 cm−1/1022 cm−1 ratios reduced from 0.925 to 0.822, which may be attributed to the fact that WPH prevented the molecular associations and formation of hydrogen bonds among the starch polymer chains. The retrogradation kinetics was determined using the Avrami model and indicated that WPH could effectively inhibit the recrystallization of RS. These results above demonstrated WPH could be a potential anti-retrogradation additive for prolonging the shelf-life of rice-based foods.
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•Whey protein hydrolysate (WPH) decreased the retrogradation of rice starch (RS).•Effects on RS retrogradation by WPH was studied by TPA, XRD, ATR-FTIR and LF-NMR.•Avrami model was utilized to the retrogradation kinetics of RS-WPH mixtures.•Formation of hydrogen bonds among polymer chains was weakened by WPH.•WPH could effectively inhibit the recrystallization of RS upon storage.
Pancreatic ductal adenocarcinoma (PDAC) is the most malignant tumor. Zinc finger and SCAN domain-containing protein 23 (
) is a new member of the SCAN domain family. The expression regulation and ...biological function remain to be elucidated. In this study, we explored the epigenetic regulation and the function of
in PDAC.
was methylated in 60.21% (171/284) of PDAC and its expression was regulated by promoter region methylation. The expression of
inhibited cell proliferation, colony formation, migration, invasion, and induced apoptosis and G1/S phase arrest.
suppressed Panc10.05 cell xenograft growth in mice. Mechanistically,
inhibited Wnt signaling by interacting with myosin heavy chain 9 (MYH9) in pancreatic cancer cells.
is frequently methylated in PDAC and may serve as a detective marker.
suppresses PDAC cell growth both
and
.
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