Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme that generates NADPH to maintain reduced glutathione (GSH), which scavenges reactive oxygen species (ROS) to protect cancer cell from ...oxidative damage. In this study, we mainly investigate the potential roles of G6PD in colorectal cancer (CRC) development and chemoresistance. We discover that G6PD is overexpressed in CRC cells and patient specimens. High expression of G6PD predicts poor prognosis and correlated with poor outcome of oxaliplatin-based first-line chemotherapy in patients with CRC. Suppressing G6PD decreases NADPH production, lowers GSH levels, impairs the ability to scavenge ROS levels, and enhances oxaliplatin-induced apoptosis in CRC via ROS-mediated damage in vitro. In vivo experiments further shows that silencing G6PD with lentivirus or non-viral gene delivery vector enhances oxaliplatin anti-tumor effects in cell based xenografts and PDX models. In summary, our finding indicated that disrupting G6PD-mediated NADPH homeostasis enhances oxaliplatin-induced apoptosis in CRC through redox modulation. Thus, this study indicates that G6PD is a potential prognostic biomarker and a promising target for CRC therapy.
This study evaluated maintenance treatment with niraparib, a potent inhibitor of poly(ADP-ribose) polymerase 1/2, in patients with platinum-sensitive recurrent ovarian cancer.
In this phase III, ...double-blind, placebo-controlled study conducted at 30 centers in China, adults with platinum-sensitive recurrent ovarian cancer who had responded to their most recent platinum-containing chemotherapy were randomized 2 : 1 to receive oral niraparib (300 mg/day) or matched placebo until disease progression or unacceptable toxicity (NCT03705156). Following a protocol amendment, patients with a bodyweight <77 kg or a platelet count <150 × 103/μl received 200 mg/day, and all other patients 300 mg/day, as an individualized starting dose (ISD). Randomization was carried out by an interactive web response system and stratified by BRCA mutation, time to recurrence following penultimate chemotherapy, and response to most recent chemotherapy. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review.
Between 26 September 2017 and 2 February 2019, 265 patients were randomized to receive niraparib (n = 177) or placebo (n = 88); 249 patients received an ISD (300 mg, n = 14; 200 mg, n = 235) as per protocol. In the intention-to-treat population, median PFS was significantly longer for patients receiving niraparib versus placebo: 18.3 95% confidence interval (CI), 10.9-not evaluable versus 5.4 (95% CI, 3.7-5.7) months hazard ratio (HR) = 0.32; 95% CI, 0.23-0.45; P < 0.0001, and a similar PFS benefit was observed in patients receiving an ISD, regardless of BRCA mutation status. Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively; the most common events were neutrophil count decreased (20.3% versus 8.0%) and anemia (14.7% versus 2.3%).
Niraparib maintenance treatment reduced the risk of disease progression or death by 68% and prolonged PFS compared to placebo in patients with platinum-sensitive recurrent ovarian cancer. Individualized niraparib dosing is effective and safe and should be considered standard practice in this setting.
•Chinese patients with platinum-sensitive recurrent ovarian cancer received maintenance niraparib (n = 177) or placebo (n = 88).•Median PFS was longer for niraparib versus placebo: 18.3 versus 5.4 months (HR = 0.32; 95% CI, 0.23-0.45; P < 0.0001).•Niraparib had a similar PFS benefit for 249 patients receiving individualized dosing based on bodyweight and platelet count.•Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively.•In the niraparib group, Grade ≥3 platelet count decreased/thrombocytopenia occurred in 11.3% of patients.
Towards super-clean graphene Lin, Li; Zhang, Jincan; Su, Haisheng ...
Nature communications,
04/2019, Letnik:
10, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Impurities produced during the synthesis process of a material pose detrimental impacts upon the intrinsic properties and device performances of the as-obtained product. This effect is especially ...pronounced in graphene, where surface contamination has long been a critical, unresolved issue, given graphene's two-dimensionality. Here we report the origins of surface contamination of graphene, which is primarily rooted in chemical vapour deposition production at elevated temperatures, rather than during transfer and storage. In turn, we demonstrate a design of Cu substrate architecture towards the scalable production of super-clean graphene (>99% clean regions). The readily available, super-clean graphene sheets contribute to an enhancement in the optical transparency and thermal conductivity, an exceptionally lower-level of electrical contact resistance and intrinsically hydrophilic nature. This work not only opens up frontiers for graphene growth but also provides exciting opportunities for the utilization of as-obtained super-clean graphene films for advanced applications.
Through molecular engineering, single diarylethenes were covalently sandwiched between graphene electrodes to form stable molecular conduction junctions. Our experimental and theoretical studies of ...these junctions consistently show and interpret reversible conductance photoswitching at room temperature and stochastic switching between different conductive states at low temperature at a single-molecule level. We demonstrate a fully reversible, two-mode, single-molecule electrical switch with unprecedented levels of accuracy (on/off ratio of ~100), stability (over a year), and reproducibility (46 devices with more than 100 cycles for photoswitching and ~10⁵ to 10⁶ cycles for stochastic switching).
Percutaneous sacroplasty is a variation of percutaneous vertebroplasty that has gained attention as a therapeutic option for patients with painful sacral insufficiency fractures due to osteoporosis ...or metastases. Additionally, percutaneous sacroplasty can also be used to treat painful sacral metastases without a pathologic fracture. The purpose of this retrospective study was to compare the efficacy and safety of fluoroscopy-guided percutaneous sacroplasty alone versus percutaneous sacroplasty plus radiofrequency ablation for the treatment of painful sacral metastases.
For this retrospective study, 126 patients (with a total of 162 painful sacral metastases) were enrolled from October 2012 to February 2021 and assigned to receive either percutaneous sacroplasty plus radiofrequency ablation (
= 51, group A) or percutaneous sacroplasty alone (
= 75, group B). Four different approaches were used for percutaneous sacroplasty: transiliac, interpedicular, anterior-oblique, and posterior. The Visual Analog Scale, Oswestry Disability Index, and Karnofsky Performance Scale were used to evaluate outcomes.
The Visual Analog Scale, Oswestry Disability Index, and Karnofsky Performance Scale scores showed significant improvement in both groups after treatment (
< .05). The overall pain relief rate was significantly better in group A than in group B (90% versus 76%,
= .032). There were no significant differences in the incidence of polymethylmethacrylate leakage between the 2 groups or among the 4 different approaches (
> .05).
Both percutaneous sacroplasty alone and the combination of percutaneous sacroplasty and radiofrequency ablation are safe and effective for treatment of painful sacral metastases. The combination of percutaneous sacroplasty and radiofrequency ablation appears to be more effective than percutaneous sacroplasty alone.
Patterning of high-quality two-dimensional chalcogenide crystals with unique planar structures and various fascinating electronic properties offers great potential for batch fabrication and ...integration of electronic and optoelectronic devices. However, it remains a challenge that requires accurate control of the crystallization, thickness, position, orientation and layout. Here we develop a method that combines microintaglio printing with van der Waals epitaxy to efficiently pattern various single-crystal two-dimensional chalcogenides onto transparent insulating mica substrates. Using this approach, we have patterned large-area arrays of two-dimensional single-crystal Bi2Se3 topological insulator with a record high Hall mobility of ∼1,750 cm(2) V(-1) s(-1) at room temperature. Furthermore, our patterned two-dimensional In2Se3 crystal arrays have been integrated and packaged to flexible photodetectors, yielding an ultrahigh external photoresponsivity of ∼1,650 A W(-1) at 633 nm. The facile patterning, integration and packaging of high-quality two-dimensional chalcogenide crystals hold promise for innovations of next-generation photodetector arrays, wearable electronics and integrated optoelectronic circuits.
Our previous study demonstrated that extracellular adenosine 5'-triphosphate (ATP) stimulated prostate cancer cell invasion via P2Y receptors. However, the purinergic receptor subtype(s) involved in ...this process remains unclear. Here we aimed to determine whether P2Y2, one subtype of P2Y receptors, was involved in the invasion and metastasis of prostate cancer cells, and elucidated the underlying mechanism.
RNAi was introduced to silence the expression of P2Y2. In vitro invasion and migration assays and in vivo experiments were carried out to examine the role of P2Y2 receptor in cell invasion and metastasis. cDNA microarray was performed to identify the differentially expressed genes downstream of ATP treatment.
P2Y2 was significantly expressed in the prostate cancer cells. Knockdown of P2Y2 receptor suppressed cell invasion and metastasis in vitro and in vivo. Further experiments identified that ATP could promote IL-8 and Snail expression and inhibit E-cadherin and Claudin-1 expression. Knockdown of P2Y2 receptor affected the expression of these EMT/invasion-related genes in vitro and in vivo.
P2Y2 receptor promotes cell invasion and metastasis in prostate cancer cells via some EMT/invasion-related genes. Thereby, P2Y2 receptor could be a potential therapeutic target for the treatment of prostate cancer.
Recent developments on laser surface modification of titanium and its alloys are reviewed. Due to the intrinsic properties of high coherence and directionality, laser beam can be focus onto metallic ...surface to perform a broad range of treatments such as remelting, alloying and cladding, which are used to improve the wear and corrosion resistance of titanium alloys. In addition, the fabrication of bioactive films on the surface of titanium alloys to improve their biocompatibility can be performed by the method of laser ablation deposition. The effect of some laser processing parameters on the resulting surface properties of titanium alloys is discussed. The problems to be solved and the prospects in the field of laser modification of titanium and its alloys are elucidated.
The magnetosheath is inherently complex and rich, exhibiting various kinds of structures and perturbations. It is important to understand how these structures propagate and evolve and how they relate ...to the perturbations. Here we investigate a kind of magnetosheath structure known as a magnetic dip (MD). As far as we are aware, there have been no previous studies concerning the evolution (contracting or expanding) of these types of structures, and their propagation properties cannot be unambiguously determined. In this study, using Magnetospheric MultiScale (MMS) high‐temporal resolution data and multispacecraft analysis methods, we obtain the propagation and dynamic features of a set of MDs. Four different types of MDs are identified: “frozen‐in,” “expanding,” “contracting,” and “stable‐propagating.” Significantly, a stable‐propagation event is observed with a sunward propagation component. This indicates that the source of the structure in this case is closely associated with the magnetopause, which provides strong support to the contention in earlier research. We further reveal the mechanism leading to the MD contraction or expansion. The motion of the MDs boundary is found closely related with the dynamic pressure. The scale of the contracting and expanding events are typically ~5–20 ρi (ion gyroradius), significantly smaller than that of frozen‐in events (~40 ρi). The observations could relate large‐scale (more than several tens of ρi) and kinetic‐scale (less than ρi) MDs, by revealing an evolution that spans these different scales, and help us better understand the variation and dynamics of magnetosheath structures and plasmas.
Key Points
Four different propagation properties of magnetosheath magnetic dips are identified by using several multispacecraft analysis methods
Pressure imbalance plays an important role in the evolution (contracting and expanding) of sub‐MHD scale magnetic dips
A sunward propagating magnetic dip indicates that the structure source is closely associated with the magnetopause
The small-scale mirror mode excited by electron dynamics is a fundamental physical process, attracting research interest in space, laboratory, and astrophysical plasma physics over the past half ...century. However, the investigations of this process were mostly limited to theories and numerical simulations, with no direct observational evidence for their existence. In this study we present clear observations of electron mirror-mode using Magnetospheric Multiscale data at unprecedented high temporal cadence. These structures are train-like, compressible, nonpropagating, and satisfy the theoretical excitation and electron trapping conditions. They were observed near the Earth's foreshock and its downstream turbulence during the corotating interaction region events, which could be involved with the interaction between solar wind and Earth.
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