To determine the effects of linolenic acid (LNA, 18:3n‐3) in oriental river prawn (Macrobrachium nipponense), an 8‐week feeding experiment was conducted using six isonitrogenous and isoenergetic ...semi‐purified diets containing 0.07 g/kg (control), 7.3 g/kg, 16.6 g/kg, 20.2 g/kg, 27.3 g/kg and 36.3 g/kg LNA. The hepatopancreas lipid content decreased significantly when dietary LNA content was >20.2 g/kg. Fatty acid analysis revealed that the percentage of 18:3n‐3 in the hepatopancreas significantly increased with increasing dietary LNA levels, while 20:5n‐3, 22:5n‐3 and 22:6n‐3 levels in the hepatopancreas decreased in a curvilinear manner as dietary LNA increased. Additionally, qRT‐PCR results revealed that hepatopancreas mRNA expression of acetyl‐CoA carboxylase (ACC) decreased with increasing dietary LNA, while the greatest carnitine palmitoyl transferase‐1(CPT1) mRNA expression was observed in the 2.73 g/kg and 36.3 g/kg groups. Furthermore, hepatopancreas mRNA expression of acyl‐CoA delta‐9 desaturase (SCD) and fatty acyl elongase 6(elovl6) was downregulated when prawns fed the diets containing >20.2 g/kg LNA. These results indicate that dietary 18:3n‐3 could decrease lipid deposition through increased fatty acid β‐oxidation and modulated fatty acid synthesis, and alter fatty acid composition by regulating fatty acyl elongase and fatty acyl desaturase mRNA expression in the M. nipponense.
Pembrolizumab demonstrated clinically meaningful and durable antitumor activity with a manageable safety profile in recurrent/metastatic (R/M) cutaneous squamous cell carcinoma (cSCC).
KEYNOTE-629 ...was a global, open-label, nonrandomized, phase II trial of patients with locally advanced (LA) or R/M cSCC conducted at 59 centers. Eligible patients received intravenous pembrolizumab 200 mg every 3 weeks for up to 35 cycles. Primary endpoint was objective response rate (ORR), defined as the percentage of patients with a complete (CR) or partial response (PR), by blinded independent central review as per Response Evaluation Criteria in Solid Tumors 1.1. Secondary endpoints included duration of response (DOR), disease control rate, progression-free survival, overall survival, and safety and tolerability. Efficacy and safety were analyzed in patients who were treated with at least one dose of pembrolizumab.
Between 29 November 2017 and 25 September 2019, 159 patients were enrolled and treated with pembrolizumab (LA cohort, n = 54; R/M cohort, n = 105). The median time from the first dose to data cut-off date (29 July 2020) was 14.9 interquartile range (IQR), 12.6-17.2 months for the LA cohort and 27.2 (IQR, 25.6-29.2) months for the R/M cohort. In the LA cohort, ORR was 50.0% 95% confidence interval (CI), 36.1% to 63.9%, including 16.7% of patients with a CR and 33.3% with a PR. In the R/M cohort, ORR was 35.2% (95% CI, 26.2% to 45.2%), including 10.5% of patients with a CR and 24.8% with a PR. Median DOR was not reached in either cohort. Grade 3-5 treatment-related adverse events occurred in 11.9% of patients.
The robust antitumor activity of pembrolizumab in both LA and R/M cSCC was confirmed and demonstrated to be durable without unexpected safety signals. Our findings establish pembrolizumab as a promising treatment option for cSCC.
•The phase II KEYNOTE-629 study assessed the efficacy and safety of pembrolizumab in cSCC.•Pembrolizumab showed rapid, robust, and durable antitumor activity in both LA and R/M cSCC.•Adverse events were generally consistent with the established safety profile of pembrolizumab.•Our data establish pembrolizumab as a promising treatment option for cSCC.
A new alpha-emitting isotope U-214, produced by the fusion-evaporation reaction W-182(Ar-36,4n) U-214, was identified by employing the gas-filled recoil separator SHANS and the recoil-a correlation ...technique. More precise a-decay properties of even-even nuclei U-216,U-218 were also measured in the reactions of Ar-40, Ca-40 beams with W-180,W-182,W- 184 targets. By combining the experimental data, improved alpha-decay reduced widths delta(2) for the even-even Po-Pu nuclei in the vicinity of the magic neutron number N = 126 are deduced. Their systematic trends are discussed in terms of the N-p N-n scheme in order to study the influence of protonneutron interaction on a decay in this region of nuclei. It is strikingly found that the reduced widths of( 214,216)U are significantly enhanced by a factor of two as compared with the NpNn systematics for the 84 <= Z <= 90 and N < 126 even-even nuclei. The abnormal enhancement is interpreted by the strong monopole interaction between the valence protons and neutrons occupying the pi 1f (7/2) and nu 1f(5/2) spin-orbit partner orbits, which is supported by the large-scale shell model calculation.
To evaluate the effect of the different doses of antithymocyte globulin (ATG) on the incidence of acute GVHD among patients receiving hematopoietic SCT without ex vivo T-cell-depletion from ...haploidentical donors, 224 patients with standard-risk hematological malignancy were randomized in this study. One hundred and twelve patients received 6 mg/kg ATG, whereas the remaining patients received 10 mg/kg ATG. This study was registered at http://www.chictr.org as No. ChiCTR-TRC-11001761. The incidence of grade III-IV acute GVHD was higher in the ATG-6 group (16.1%, 95% confidence interval (CI), 9.1-23.1%) than in the ATG-10 group (4.5%, CI, 0.7-8.3%, P=0.005, 95% CI for the difference, -19.4% to -3.8%). EBV reactivation occurred more frequently in the ATG-10 group (25.3%, 17.1-33.5%) than in the ATG-6 group (9.6% (4.0-15.2%), P=0.001). The 1-year disease-free survival rates were 84.3% (77.3-91.3%) and 86.0% (79.2-92.8%) for the ATG-6 group and ATG-10 groups, respectively (P=0.88). In conclusion, although 6 mg/kg ATG applied in haploidentical transplantation decreased the risk of EBV reactivation compared with 10 mg/kg ATG, this treatment exposes patients to a higher risk for severe acute GVHD.
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.
The stability of the stacked two-dimensional (2D) transition metal carbides and their interlayered friction in different configurations are comparatively studied by means of density functional theory ...(DFT). At equilibrium, a larger interlayer distance corresponds to a smaller binding energy, suggesting an easier sliding between them. The oxygen-functionalized M 2 CO 2 possesses much lower sliding resistance than the bare ones due to the strong metallic interactions between the stacked M 2 C layers. Compared to the parallel stacking order of M 2 CO 2 -I, the mirror stacked M 2 CO 2 -II possesses better lubricant properties. At strained states, normal compression substantially enhances the sliding barrier owing to more charges transferring from the M to O atom. Furthermore, the in-plane biaxial strain may effectively hinder the interlayer sliding, while the uniaxial strain fundamentally modifies the preferred sliding pathway due to anisotropic expansion of surface electronic state. These results highlight that the functionalized MXenes with strain-controllable frictional properties are promising lubricating materials because of their low sliding energy barrier and excellent mechanical properties.
In a base solution containing 10g/L sodium hydroxide and 12g/L phytic acid, the influence of sodium silicate concentration on the formation and properties of anodic coatings obtained by micro arc ...oxidation (MAO) on magnesium alloys was systematically studied. The results demonstrate that sodium silicate can increase the solution conductivity, decrease the final voltage and change the coating color. Amorphous magnesium silicate is detected and the silicon content in the coatings continually increases with the increasing of sodium silicate concentration. Silicate ions can simultaneously combine with magnesium and aluminum ions to develop anodic coatings, while phytic acid radicals preferentially react with magnesium ions. Sodium silicate can further improve the corrosion resistance of MAO treated magnesium and the coating shows the best corrosion resistance in the base solution with 10g/L sodium silicate.
► Sodium silicate can change the coating color. ► Silicate ions combine with magnesium and aluminum ions to develop anodic coatings. ► Sodium silicate competes with phytic acid for taking part in coating formation. ► Sodium silicate improves the corrosion resistance of MAO treated magnesium alloys.
ABSTRACT This paper reports on the measurement of the large-scale anisotropy in the distribution of cosmic-ray arrival directions using the data collected by the air shower detector ARGO-YBJ from ...2008 January to 2009 December, during the minimum of solar activity between cycles 23 and 24. In this period, more than 2 × 1011 showers were recorded with energies between ∼1 and 30 TeV. The observed two-dimensional distribution of cosmic rays is characterized by two wide regions of excess and deficit, respectively, both of relative intensity ∼10−3 with respect to a uniform flux, superimposed on smaller size structures. The harmonic analysis shows that the large-scale cosmic-ray relative intensity as a function of R.A. can be described by the first and second terms of a Fouries series. The high event statistics allow the study of the energy dependence of the anistropy, showing that the amplitude increases with energy, with a maximum intensity at ∼10 TeV, and then decreases while the phase slowly shifts toward lower values of R.A. with increasing energy. The ARGO-YBJ data provide accurate observations over more than a decade of energy around this feature of the anisotropy spectrum.
Inositol polyphosphate 4-phosphatase type II (INPP4B) negatively regulates phosphatidylinositol 3-kinase signaling and is a tumor suppressor in some types of cancers. However, we have found that it ...is frequently upregulated in human colon cancer cells. Here we show that silencing of INPP4B blocks activation of Akt and serum- and glucocorticoid-regulated kinase 3 (SGK3), inhibits colon cancer cell proliferation and retards colon cancer xenograft growth. Conversely, overexpression of INPP4B increases proliferation and triggers anchorage-independent growth of normal colon epithelial cells. Moreover, we demonstrate that the effect of INPP4B on Akt and SGK3 is associated with inactivation of phosphate and tensin homolog through its protein phosphatase activity and that the increase in INPP4B is due to Ets-1-mediated transcriptional upregulation in colon cancer cells. Collectively, these results suggest that INPP4B may function as an oncogenic driver in colon cancer, with potential implications for targeting INPP4B as a novel approach to treat this disease.
PDF
