Summary Background The frequent recurrence of early-stage non-small-cell lung cancer (NSCLC) is generally attributable to metastatic disease undetected at complete resection. Management of such ...patients depends on prognostic staging to identify the individuals most likely to have occult disease. We aimed to develop and validate a practical, reliable assay that improves risk stratification compared with conventional staging. Methods A 14-gene expression assay that uses quantitative PCR, runs on formalin-fixed paraffin-embedded tissue samples, and differentiates patients with heterogeneous statistical prognoses was developed in a cohort of 361 patients with non-squamous NSCLC resected at the University of California, San Francisco. The assay was then independently validated by the Kaiser Permanente Division of Research in a masked cohort of 433 patients with stage I non-squamous NSCLC resected at Kaiser Permanente Northern California hospitals, and on a cohort of 1006 patients with stage I–III non-squamous NSCLC resected in several leading Chinese cancer centres that are part of the China Clinical Trials Consortium (CCTC). Findings Kaplan-Meier analysis of the Kaiser validation cohort showed 5 year overall survival of 71·4% (95% CI 60·5–80·0) in low-risk, 58·3% (48·9–66·6) in intermediate-risk, and 49·2% (42·2–55·8) in high-risk patients (ptrend =0·0003). Similar analysis of the CCTC cohort indicated 5 year overall survivals of 74·1% (66·0–80·6) in low-risk, 57·4% (48·3–65·5) in intermediate-risk, and 44·6% (40·2–48·9) in high-risk patients (ptrend <0·0001). Multivariate analysis in both cohorts indicated that no standard clinical risk factors could account for, or provide, the prognostic information derived from tumour gene expression. The assay improved prognostic accuracy beyond National Comprehensive Cancer Network criteria for stage I high-risk tumours (p<0·0001), and differentiated low-risk, intermediate-risk, and high-risk patients within all disease stages. Interpretation Our practical, quantitative-PCR-based assay reliably identified patients with early-stage non-squamous NSCLC at high risk for mortality after surgical resection. Funding UCSF Thoracic Oncology Laboratory and Pinpoint Genomics.
Total mercury (THg) and methylmercury (MMHg) were investigated in 259 wild plants belonging to 49 species in 29 families that grew in heavily Hg-contaminated wastelands composed of cinnabar ore mine ...tailings (calcines) in the Wanshan region, southwestern China, the world's third largest Hg mining district. The bioconcentration factors (BCFs) of THg and MMHg from soil to roots (THgroot/THgsoil, MMHgroot/MMHgsoil) were evaluated. The results showed that THg and MMHg in both plants and soils varied widely, with ranges of 0.076–140 μg/g THg and 0.19–87 ng/g MMHg in roots, 0.19–106 μg/g THg and 0.06–31 ng/g MMHg in shoots, and 0.74–1440 μg/g THg and 0.41–820 ng/g MMHg in soil. Among all investigated species, Arthraxon hispidus, Eremochloa ciliaris, Clerodendrum bunge, and Ixeris sonchifolia had significantly elevated concentrations of THg in shoots and/or roots that reached 100 μg/g, whereas Chenopodium glaucum, Corydalisedulis maxim, and Rumex acetosa contained low values below 0.5 μg/g. In addition to the high THg concentrations, the fern E. ciliaris also showed high BCF values for both THg and MMHg exceeding 1.0, suggesting its capability to extract Hg from soils. Considering its dominance and the tolerance identified in the present study, E. ciliaris is suggested to be a practical candidate for phytoextraction, whereas A. hispidus is identified as a potential candidate for phytostabilization of Hg mining-contaminated soils.
Display omitted
•Total and methylmercury in wild plants grown at wastelands were characterized.•As high as 100 mg/kg total mercury was observed in A. hispidus and E. ciliaris.•Species of E. ciliaris was defined as a hyperaccumulator for Hg phytoremediation.
The species Eremochloa ciliaris and Arthraxon hispidus exhibited elevated Hg concentrations in shoots and roots, respectively, and can be considered candidates for phytoremediation of contaminated soils.
Barium (Ba) is a non-essential and toxic element. In China, intensive Ba mining and Ba salt manufacturing have led to sharp increases in Ba in the environment, but little information is available ...regarding Ba concentrations in paddy soil and rice. The total concentrations and phytoavailability of Ba in paddy soils and paired rice samples collected from the world's largest Ba mine in Dahebian, Tianzhu, Guizhou Province, southwestern China, were investigated. Risk assessments of Ba exposure via rice consumption were also evaluated. The results indicated that extremely high Ba concentrations existed in paddy soils, ranging between 518 mg/kg and 65,760 mg/kg, which demonstrated severe Ba contamination, as expected. The concentrations of rice Ba varied from 0.10 to 3.5 mg/kg, and a significantly positive correlation (r = 0.51, p < 0.05) between rice Ba and water-extractable Ba was observed, suggesting that water, rather than weak acid (0.43 M CH3COOH), chelating agents (DTPA) or neutral salts (0.1 M NaNO3, 0.01 M CaCl2 or 1 M NH4OAc), is a suitable extractant for predicting the phytoavailable Ba in the studied soils. Risk assessments showed that residents experienced low Ba exposure via rice consumption when considered in isolation of other sources in this study area.
•Elevated Ba concentrations existed in paddy soils adjacent to the Ba mine and Ba salt plant.•Water-extractable Ba was a good indicator of the phytoavailability of Ba in paddy soils.•Ba in rice represented low risks to human health when considered in isolation of other sources.
Mercury contamination is a serious problem in the Hg mining area of Xiushan County, Chongqing, southwestern China. The concentrations of total mercury (THg) and methylmercury (MeHg) in paddy soil, ...surface water, and rice (grain) samples were determined to investigate the regional distribution of Hg contamination. Simultaneously, gaseous elemental Hg (GEM) in ambient air near the sampling sites was measured. The total Hg concentrations in surface water were highly elevated, ranging from 13 to 2390 ng/L, and the total MeHg concentrations varied between 0.17 and 1.1 ng/L. The dissolved Hg and MeHg concentrations in surface water ranged from 4.7 to 470 ng/L and 0.14–0.35 ng/L, respectively. High THg and MeHg concentrations were also obtained in paddy soils from mining areas, ranging from 0.45 to 68 μg/g and 0.13–4.8 ng/g, respectively. Similar to the high concentrations in water and soil, the THg concentration in rice (grain) ranged from 4.7 to 550 ng/g and MeHg from 2.9 to 26 ng/g. Elevated Hg concentrations in rice, as a staple food of local residents, confirmed that rice consumption could be a vital pathway for MeHg exposure to native people. Humic acid and fulvic acid had significant correlations with soil MeHg, implying that they have important roles that influence MeHg production in soil. The spatial distribution characteristics of Hg and MeHg pollution in the local environment indicated their origins from historic Hg mining sites in the Xiushan area.
•Mercury spatial distribution was investigated in the study area.•The upstream residues and calcines were origins of both THg and MeHg in water, soil, and rice.•GEM in the atmosphere was elevated.•In soil, humic and fulvic acids had significant correlations with MeHg indicating the vital roles in MeHg production.
The fertilization rate is adjusted through the regulation of opening length and the rotational speed for bivariate fertilizer applicators. It is essential to optimally determine the control ...combination according to the target fertilization rate and further improve the control performance of fertilization operation in precision agriculture. In this study, a novel decision-making capability optimization scheme of control combination and PID controller parameters is proposed to improve the feasibility and practicability of variable fertilizer applicators. Firstly, EDEM is adopted to acquire the minimum allowable opening length and the proper gap between the spiral blades and the discharge cavity wall, and then calibration experiments are implemented to establish the fitting model of fertilization rate using polynomial fitting. Secondly, the modified sparrow search algorithm (SSA) with chaotic operator and mutation section of the DE algorithm is used to optimize the control combination utilizing the accuracy, uniformity, and adjustment time as the evaluation criteria. Moreover, the tent mapping bat algorithm (TBA) is applied to tune the PID controller parameters for enhancing the accuracy and response speed of the fertilization-rate control system. Compared to the PID controller based on the bat algorithm (BA), traditional PID controller, and fuzzy PID controller, the rise time of the PID controller improved by TBA decreases by 0.018 s, 0.09 s, and 0.038 s, respectively, and the average steady-state deviation of that drops by 0.02 kg ha−1, 1.45 kg ha−1, and 0.19 kg ha−1, respectively. In addition, under the condition of the same controller, compared with SSA, GA, and MOEA/D-DE, the average accuracy of the proposed decision-making algorithm decreases from 1.9%, 2.5%, and 3.5% to 1.8%, the average uniformity drops from 0.52% and 0.48% to 0.47%, and the average adjustment time declines from 0.99 s, 1.48 s, and 1.34 s to 0.5 s. It can be concluded that the method proposed in this study performs better in terms of accuracy and adjustment time but exhibits no apparent effect on the improvement of uniformity.
Methylmercury (MeHg) in rice has attracted growing health concern over the past decade, due to the accumulation of high MeHg levels, which may pose potential health risk to humans. Rice is the staple ...food in Sri Lanka; nevertheless, the presence of micro pollutants, such as MeHg has been not investigated. Therefore, commercial rice samples from the Sri Lankan market (n = 163) were measured to reveal the total mercury (THg) and MeHg levels. THg (mean: 1.73 ± 0.89 ng/g, range: 0.21–6.13 ng/g) and MeHg concentrations (mean: 0.51 ± 0.37 ng/g; range: 0.03–3.81 ng/g) were low. Compared to the fish MeHg exposure, the rice MeHg exposure was generally lower in different consumption groups, suggesting that rice plays a less role than fish in MeHg exposure in Sri Lanka. Babies (infants and toddlers) at one year old may face fish MeHg exposure (0.17 μg/kg bw/day) higher than the reference dose for MeHg (RfD)-0.1 μg/kg bw/day, which was more than 5 times that of rice MeHg exposure (0.031 μg/kg bw/day). Future studies in Sri Lanka should focus on health impacts under long-term overexposure of MeHg, especially in vulnerable populations. Some diet changes should be made to mitigate MeHg exposure levels in Sri Lankans.
•We firstly carried a nationwide investigation of Hg in Sri Lankan commercial rice.•THg and MeHg exposures in different rice and fish eating populations were assessed.•Rice consumption plays less important role in MeHg exposure in Sri Lanka.
Alterations of the EGFR/ERK and Hippo/YAP pathway have been found in non-small cell lung cancer (NSCLC). Herein, we show that ERK1 and ERK2 have an effect on the Hippo/YAP pathway in human NSCLC ...cells. Firstly, inhibition of ERK1/2 by siRNA or small-molecular inhibitors decreased the YAP protein level, the reporter activity of the Hippo pathway, and the mRNA levels of the Hippo downstream genes, CTGF, Gli2, and BIRC5. Secondly, degradation of YAP protein was accelerated after ERK1/2 depletion in NSCLC cell lines, in which YAP mRNA level was not decreased. Thirdly, forced over-expression of the ERK2 gene rescued the YAP protein level and Hippo reporter activity after siRNA knockdown targeting 3'UTR of the ERK2 gene in NSCLC cells. Fourthly, depletion of ERK1/2 reduced the migration and invasion of NSCLC cells. Combined depletion of ERK1/2 had a greater effect on cell migration than depletion of either one separately. Finally, the MEK1/2 inhibitor Trametinib decreased YAP protein level and transcriptional activity of the Hippo pathway in NSCLC cell lines. Our results suggest that ERK1/2 inhibition participates in reducing YAP protein level, which in turn down-regulates expression of the downstream genes of the Hippo pathway to suppress migration and invasion of NSCLC cells.
Display omitted
The reference standard (4-((5-chloro-4-(methylamino)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (HG-10-102-01) and its precursor ...(4-((5-chloro-4-(methylamino)pyrimidin-2-yl)amino)-3-hydroxyphenyl)(morpholino)methanone (desmethyl-HG-10-102-01) were synthesized from 2,4,5-trichloropyrimide and 3-methoxy-4-nitrobenzoic acid with overall chemical yield 49% in four steps and 14% in five steps, respectively. The target tracer (4-((5-chloro-4-(methylamino)pyrimidin-2-yl)amino)-3-11Cmethoxyphenyl)(morpholino)methanone (11CHG-10-102-01) was prepared from the precursor desmethyl-HG-10-102-01 with 11CCH3OTf through O-11Cmethylation and isolated by HPLC combined with SPE in 45–55% radiochemical yield, based on 11CCO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the specific activity (SA) at EOB was 370–1110GBq/μmol with a total synthesis time of ∼40-min from EOB.
Display omitted
The authentic standard PBB3 and its precursor N-desmethyl-PBB3 as well as TBS-protected N-desmethyl-PBB3 precursor for radiolabeling were synthesized from 5-bromo-2-nitropyridine, ...acrolein diethyl acetal, 6-methoxy-2-methylbenzothiazole, and diethylchlorophosphate with overall chemical yield 1% in six steps, 2% in five steps, and 1% in six steps, respectively. 11CPBB3 was prepared from either desmethyl-PBB3 or TBS-protected desmethyl-PBB3 with 11CCH3OTf through N-11Cmethylation and isolated by HPLC combined with SPE in 20–25% and 15–20% radiochemical yield, respectively, based on 11CCO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the specific activity at EOB was 370–1110GBq/μmol with a total synthesis time of ∼40-min from EOB.
PDF
![Synthesis of [11C]HG-10-102...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0960-894X/small "Synthesis of [11C]HG-10-102-01 as a new potential PET agent for imaging of LRRK2 enzyme in Parkinson’s disease")