Effects of foliar application of Zn combined with organic matters on Cd accumulation and its chemical forms in rice.

Rice consumption is a key Cd exposure pathway, which poses a health risk to humans. Reducing cadmium (Cd) concentrations in rice remains challenging. In this study, a pot experiment was conducted to examine the effects of foliar spray of Zn combined with organic matters (including Zn-lysine (Zn-Lys), Zn-fulvic acid (Zn-FA), Zn-amino acid (Zn-AA), and Zn combined with glutathione (Zn + GSH)) on Cd accumulation in rice grains. Compared with the control group, all treatment groups exhibited reduced Cd concentration in rice grains, while improving plant growth, and reducing Cd transport from other tissues to the grains. Zn-FA was found to be the most effective fertilizer, which considerably reduced Cd concentrations in grains from 0.77 ± 0.068 to 0.14 ± 0.021 mg/kg and yielded reductions of up to 81%, which is within the Chinese food maximum tolerable limit of 0.2 mg/kg. Furthermore, the analysis of the chemical forms of Cd of rice tissues indicated that the treatment groups had increased proportions of integrated with pectates and protein in the stems. Except for the group treated with Zn-Lys spray, the percentages of undissolved Cd phosphate in the leaves were increased in all treatment groups, which reduced Cd toxicity to rice plants. The foliar application of Zn combined with organic matters may be a promising strategy to decrease Cd concentration in rice grains cultivated in severely Cd-contaminated agricultural soil, particularly in the karst area in southwest China with limited available cultivable agricultural land.

Significant biomagnification of methylmercury in songbird nestlings through a rice-based food web: Insights from stable mercury isotopes.

To elucidate the sources and transfer of mercury (Hg) in terrestrial food chains, particularly in heavily Hg-contaminated rice paddy ecosystems, we collected rice leaves, invertebrates, and Russet Sparrow nestlings from a clear food chain and analyzed the dietary compositions and potential Hg sources using stable Hg isotopes coupled with a Bayesian isotope mixing model (BIMM). Our findings indicated that MeHg exposure is dominant through the dietary route, with caterpillars, grasshoppers, and katydids being the main prey items, while the less provisioned spiders, dragonflies, and mantises contributed the most of the Hg to nestlings. We found minimal MIF but certain MDF in this terrestrial food chain and identified two distinct MeHg sources of dietary exposure and maternal transfer. We firstly found that the dietary route contributed substantially (almost tenfold) more MeHg to the nestlings than maternal transfer. These findings offer new insights into the integration of Hg from the dietary route and maternal transfers, enhancing our understanding of fluctuating Hg exposure risk during the nestling stage. Our study suggested that Hg isotopes combined with BIMM is an effective approach for tracing Hg sources in birds and for gaining in-depth insight into the trophic transfers and biomagnification of MeHg in food chains.

Using live videography observation and Bayesian isotope mixing model to identify food composition and dietary contribution to inorganic mercury and methylmercury intake by songbird nestlings.

Mercury (Hg) exposure is increasing in terrestrial birds; however, studies on its sources are scarce. In the present study, we elucidated the food composition of green-backed tit nestlings from three urban forest parks (CPL, AHL, and LCG) using live videography observation (LVO). Furthermore, the daily dietary intakes of inorganic Hg (IHg) (MDIIHg) and methylmercury (MeHg) (MDIMeHg) were determined using the Bayesian isotope mixing model (BIMM) to uncover the nestlings' specific dietary Hg contribution. Both LVO and BIMM indicated that Lepidoptera (primarily caterpillar) constituted the primary food source for the nestlings in the three forests, accounting for approximately 60% of their diet in all three forest parks. The estimated MDI of Hg revealed that lepidopterans and spiders primarily contributed to IHg exposure, with a co-contribution ratio of 71.8%-97.7%. Unexpectedly, dietary MeHg was mostly derived from spiders; the highest contribution ratio of 93.6% was recorded at CPL, followed by another peak ratio of 92.9% at LCG. However, the dietary exposure was primarily IHg, accounting for 69.8% (AHL), 62.0% (LCG), and 61.3% (CPL) of the nestlings. Our study findings highlight the importance of dietary IHg transfer in evaluating the effects of Hg in nestlings. LVO, coupled with BIMM, is an effective tool for determining the food compositions of songbird nestlings and estimating the contribution of specific diets.

Home-produced eggs: An important pathway of methylmercury exposure for residents in mercury mining areas, southwest China.

In light of the documented elevated concentrations of total mercury (Hg) and methylmercury (MeHg) in poultry originating from Hg-contaminated sites, a knowledge gap persists regarding the levels of Hg found in home-produced eggs (HPEs) and the associated dietary exposure risks in regions affected by Hg mining. To address this knowledge gap, a comprehensive investigation was undertaken with the primary objectives of ascertaining the concentrations of THg and MeHg in HPEs and evaluating the potential hazards associated with the consumption of eggs from the Wanshan Hg mining area in Southwest China. The results showed that THg concentrations in HPEs varied within a range of 10.5-809 ng/g (with a geometric mean (GM) of 64.1 ± 2.7 ng/g), whereas MeHg levels spanned from 1.3 to 291 ng/g (GM, 23.1 ± 3.4 ng/g). Remarkably, in half of all eggs, as well as those collected from regions significantly impacted by mining activities, THg concentrations exceeded the permissible maximum allowable value for fresh eggs (50 ng/g). Consumption of these eggs resulted in increased exposure risks associated with THg and MeHg, with GM values ranging from 0.024 to 0.17 µg/kg BW/day and 0.0089-0.066 µg/kg BW/day, respectively. Notably, the most substantial daily dosage was observed among children aged 2-3 years. The study found that consuming HPEs could result in a significant IQ reduction of 34.0 points for the whole mining area in a year. These findings highlight the potential exposure risk, particularly concerning MeHg, stemming from the consumption of local HPEs by residents in mining areas, thereby warranting serious consideration within the framework of Hg exposure risk assessment in mining locales.

Downregulation of CLDN6 inhibits cell migration and invasion and promotes apoptosis by regulation of the JAK2/STAT3 signaling pathway in hepatocellular carcinoma.

Background: High expression of CLDN6 in hepatocellular carcinoma (HCC) has been widely reported. During this research, CLDN6's effect on the infiltration, migration, and apoptosis of HCC cells was investigated. Methods: Initially, the knockdown and overexpression of CLDN6 in HCC cells were carried out by short interfering RNA (siRNA) and plasmid transfection. The transfection efficiency was detected by means of a quantitative real-time polymerase chain reaction (qRT-PCR) assay, immunofluorescence staining, and Western blot analysis. Transwell and wound-healing assays were employed for the detection of invasion and migration ability. CCK-8 assay and flow cytometry were utilized for the detection of apoptosis. Finally, analysis of the expression of pathway-related proteins (JAK2, STAT3, p-JAK2, and p-STAT3) and the regulation of apoptotic responses (by measurement of cleaved caspase-3, Bax, and Bcl-2 levels) was carried out. Results: When CLDN6 was knocked down, the cellular invasion and migration ability decreased, and apoptosis increased, which decreased p-JAK2, p-STAT3, and anti-apoptotic protein bcl-2 expression. Furthermore, an elevation was observed in cleaved caspase-3 and Bax expression levels. Contrarily, upon overexpression of CDLN6, the aforementioned experimental results were reversed. Conclusions: CLDN6 knockdown results in the inhibition of HCC cells' infiltration and migration and promotes apoptosis via downregulation of the JAK2/STAT3 signaling pathway.

The mercury flow through a terrestrial songbird food chain in subtropical pine forest: Elucidated by Bayesian isotope mixing model and stable mercury isotopes.

In order to comprehend the transfer of inorganic mercury (IHg) and methylmercury (MeHg) within food chains in terrestrial pine forests, we collected samples of Great Tit nestlings, common invertebrates, plants, and soil in a subtropical pine forest and used Bayesian isotope mixing model analysis, Hg daily intake, and stable Hg isotopes to elucidate the flow of MeHg and IHg in these food chains. Results indicate that caterpillars and cockroaches are the predominant prey items for nestlings, accounting for a combined contribution of 81.5%. Furthermore, caterpillars, cockroaches, and spiders were found to contribute the most (∼80%) of both IHg and MeHg that dietary accumulated in nestlings. The provisoned invertebrates tend to supply more IHg and diluting the proportion of MeHg as total Hg (MeHg%). Notably, nestling feathers displayed the highest Δ199Hg values but a relatively lower MeHg%, suggesting an imbalanced incorporation of Hg from maternal transfer and dietary accumulation during the nestling stage. This study highlights the efficacy of nestlings as indicators for identifying Hg sources and transfers in avian species and food chains. However, caution must be exercised when using Hg isotope compositions in growing feathers, and the contribution of maternally transferred Hg should not be ignored.

A carbon-11 labeled imidazo[1,2-a]pyridine derivative as a new potential PET probe targeting PI3K/mTOR in cancer.

The PI3K/Akt/mTOR pathway is frequently dysregulated in cancer due to its central role in cell growth, survival, and proliferation. Overactivation of the PI3K/Akt/mTOR pathway may occur through varying mechanisms including mutations, gene amplification, and upstream signaling events, ultimately resulting in cancer. Therefore, PI3K/Akt/mTOR pathway has emerged as an attractive target for cancer therapy and imaging. A promising approach to inhibit this pathway involves a simultaneous inhibition of both PI3K and mTOR using a dual inhibitor. Recently, a potent dual PI3K/mTOR inhibitor, 2,4-difluoro-N-(2-methoxy-5-(3-(5-(2-(4-methylpiperazin-1-yl)ethyl)-1,3,4-oxadiazol-2-yl)imidazo[1,2-a]pyridin-6-yl)pyridin-3-yl)benzenesulfonamide (7), was discovered and demonstrated excellent kinase selectivity IC50 (PI3K/mTOR) = 0.20/21 nM; good cellular growth inhibition IC50 (HCT-116 cell) = 10 nM, modest plasma clearance, and acceptable oral bioavailability. Expanding on this discovery, here we present the synthesis of the carbon-11 labeled imidazo[1,2-a]pyridine derivative 2,4-difluoro-N-(2-methoxy-5-(3-(5-(2-(4-[11C]methylpiperazin-1-yl)ethyl)-1,3,4-oxadiazol-2-yl)imidazo[1,2-a]pyridin-6-yl)pyridin-3-yl)benzenesulfonamide (N-[11C]7) as a new potential radiotracer for the biomedical imaging technique positron emission tomography (PET) imaging of PI3K/mTOR in cancer. The reference standard 7 and its N-demethylated precursor, 2,4-difluoro-N-(2-methoxy-5-(3-(5-(2-(piperazin-1-yl)ethyl)-1,3,4-oxadiazol-2-yl)imidazo[1,2-a]pyridin-6-yl)pyridin-3-yl)benzenesulfonamide (11), were synthesized in 7 and 8 steps with 10% and 7% overall chemical yield, respectively. N-[11C]7 was prepared from 11 using [11C]methyl triflate ([11C]CH3OTf) through N-11C-methylation and isolated by high-performance liquid chromatography (HPLC) and solid-phase extraction (SPE) formulation in 40-50% radiochemical yield decay corrected to end of bombardment (EOB) based on [11C]CO2. The radiochemical purity was > 99% and the molar activity (Am) at EOB was in the range of 296-555 GBq/µmol (n = 5).

Enhanced Mercury Accumulation in Riparian Spiders: An Evidence of Insects' Emergence Effect in Aquatic and Upland Terrestrial Crossed Habitat.

Many studies have focused on mercury (Hg) accumulation in both aquatic and terrestrial organisms, but the effects of aquatic Hg on terrestrial organisms have rarely been documented. Here we report the accumulation of Hg in two species of spiders, Argiope bruennichi, inhabiting paddy fields, and Nephila clavata, inhabiting small forests in the riparian zones of two hydroelectric reservoirs in Guiyang, southwest China. The mean concentration of total mercury (THg) was higher in N. clavata (0.38 mg kg-1) than in A. bruennichi (0.20 mg kg-1). The monthly average THg in N. clavata, collected consecutively from May to October, and the highest values for THg in June (1.2 mg kg-1) could be related to the emergence of aquatic insects during early summer, suggesting that emerging insects play a crucial role in the accumulation of Hg in riparian spiders. The high values could also be attributable to the different times of spider sampling or individual differences.

Aquatic methylmercury is a significant subsidy for terrestrial songbirds: Evidence from the odd mass-independent fractionation of mercury isotopes.

In contrast to aquatic food chains, knowledge of the origins and transfer of mercury (Hg) and methylmercury (MeHg) in terrestrial food chains is relatively limited, especially in songbirds. We collected soil, rice plants, aquatic and terrestrial invertebrates, small wild fish, and resident songbird feathers from an Hg-contaminated rice paddy ecosystem for an analysis of stable Hg isotopes to clarify the sources of Hg and its transfer in songbirds and their prey. Significant mass-dependent fractionation (MDF, δ202Hg), but no mass-independent fractionation (MIF, ∆199Hg) occurred in the trophic transfers in terrestrial food chains. Piscivorous, granivorous, and frugivorous songbirds and aquatic invertebrates were all characterized by elevated Δ199Hg values. The estimated MeHg isotopic compositions obtained using linear fitting and a binary mixing model explained both the terrestrial and aquatic origins of MeHg in the terrestrial food chains. We found that MeHg from aquatic habitats is an important subsidy for terrestrial songbirds, even those that feed mainly on seeds, fruits, or cereals. The results show that MIF of the MeHg isotope is a reliable tool to reveal MeHg sources in songbirds. Because the MeHg isotopic compositions was calculated with a binary mixing model or directly estimated from the high proportions of MeHg, compound-specific isotope analysis of Hg would be more useful for the interpretation of the Hg sources, and is highly recommended for future studies.

Total and methylmercury concentrations in nocturnal migratory birds passing through Mount Ailao, Southwest China.

Despite growing concerns over mercury (Hg) accumulation in birds in recent decades, little is known about Hg exposure in nocturnal migratory birds. Here, total mercury (THg) and methylmercury (MeHg) were detected in the feathers of nocturnal migratory birds (n = 286, belonging to 46 species) passing through Mount Ailao in Southwest China. The stable isotope ratios of carbon (δ13C) and nitrogen (δ15N) were also determined to clarify the effects of trophic position, foraging guild, and foraging behavior on Hg bioaccumulation. Our results show that the THg and MeHg concentrations varied by two orders of magnitude among all nocturnal migratory birds investigated, with the lowest values (THg: 0.056 mg kg-1; MeHg: 0.038 mg kg-1) in the Asian koel (Eudynamys scolopaceus) and the highest (THg: 12 mg kg-1; MeHg: 7.8 mg kg-1) in the hair-crested drongo (Dicrurus hottentottus). Waterbirds showed higher δ15N values and higher THg and MeHg concentrations than songbirds, and the Hg concentrations in piscivorous species were significantly higher than those in herbivores, omnivores, and insectivores. Significant effects of foraging guilds (Kruskal-Wallis one-way ANOVA, p < 0.001) and foraging behaviors (Kruskal-Wallis one-way ANOVA, p < 0.001) on the Hg concentrations in migratory bird feathers were detected. A risk assessment indicated that approximately 7.0% of individuals were at moderate (2.4-5.0 mg kg-1) to high (>5.0 mg kg-1) risk of Hg exposure, and were therefore vulnerable to adverse physiological and behavioral effects. A long-term monitoring campaign during the migratory period is highly recommended to better understand the bioaccumulation of Hg in these nocturnal migratory bird populations over time.

Microstructure and Wear of W-Particle-Reinforced Al Alloys Prepared by Laser Melt Injection.

W-particle-reinforced Al alloys were prepared on a 7075 aluminum alloy surface via laser melt injection to improve their wear resistance, and the microstructure, microhardness, and wear resistance of the W/Al layers were studied. Scanning electron microscopy (SEM) results confirmed that a W/Al laser melting layer of about 1.5 mm thickness contained W particles, and Al4W was formed on the surface of the Al alloys. Due to the reinforcement of the W particles and good bonding of the W and Al matrix, the melting layer showed excellent wear resistance compared to that of Al alloys.

Terrestrial mercury and methylmercury bioaccumulation and trophic transfer in subtropical urban forest food webs.

As the "lungs of the city", urban forests can improve air quality by absorbing air pollutants, becoming hotspots for mercury (Hg) pollution from anthropogenic activities. However, the bioaccumulation and transfer of Hg in the urban forest food web are unclear. In this study, total mercury (THg) and methylmercury (MeHg) concentrations, as well as the stable isotopes of carbon (δ13C) and nitrogen (δ15N) in organisms with different trophic levels (TLs) were investigated in a mid-subtropical urban forest of the Changpoling Forest Park (CFP) in Guiyang City, Guizhou Province, southwestern China. The results showed that THg and MeHg among all taxa ranged from 5.6 to 1267 ng g-1 and 0.046-692 ng g-1, respectively. MeHg% (% of Hg present as MeHg) at different TLs exhibited a wide range of 5.0-69% on average. Both THg and MeHg increased with the TLs from plants to nestling birds, indicating distinct biomagnification through the food web of grasses/pine needles - grasshoppers/caterpillars/katydids/mantis - spiders/songbird nestlings. The trophic magnification slope (TMS) of THg and MeHg were 0.18 ± 0.05 and 0.37 ± 0.08, respectively, suggesting both of them significantly increase along food webs. These findings improve the understanding of biogeochemical Hg cycles in terrestrial food webs and highlight the impacts of terrestrial MeHg on nestling birds.

Phytochemical profile and anti-oxidation activity changes during ginger (Zingiber officinale) harvest: Baby ginger attenuates lipid accumulation and ameliorates glucose uptake in HepG2 cells.

We determined the phenolic content and anti-oxidation properties of ginger at different harvesting time and tested its effects on lipid droplet formation and glucose uptake in HepG2 cells. Ginger samples at different stages of maturity were harvested every two weeks starting from mid-October for 16 weeks. Our data indicate that ginger has the highest phenolic contents and superior anti-oxidation activity when harvested early (immature baby ginger); however, the concentration of phenolic contents and its anti-oxidation activity were progressively reduced up to 50% as ginger matures. Furthermore, the data indicate that baby ginger extract inhibits lipid accumulation and triglyceride content in oleic acid-induced HepG2 cells up to 20% in a dose-dependent manner. Baby ginger exhibited significant inhibition of α-amylase enzyme activity by 29.5% and ameliorated glucose uptake in HepG2 cell at similar level. Our results suggest that harvesting ginger at an appropriate (early) time may be beneficial for optimizing its biological active contents and qualitative properties. The data also suggest that a regular use of ginger can potentially lower incidences of obesity and diabetes.

A Human-Inspired Soft Finger with Dual-Mode Morphing Enabled by Variable Stiffness Mechanism.

Elevating stiffness without compromising compliance and agility is a key problem for soft finger applications, especially for articulate ones. Inspired by human finger, a multijoint soft finger with dual morphing through active/passive variable rigidity is proposed. The fabricated soft finger weighs 27.4 g. Conductive thermoplastic starch polymers (CTPSs) are embedded in a U-shape-joint pneumatic soft actuator segmentally like biological phalanges. Their stiffness can be independently adjusted utilizing customized thermomechanical property. Yoshimura origami imitating ligaments can passively match deformation and stiffness of the joints. Through electrothemal activation of CTPSs, the finger can realize dual independent articulate morphing: stiffened phalanges (mode 1) for dexterous manipulation and heavy load, softened phalanges (mode 2) for large deformation contact and light load. Comparative experiments of bending angle, output force, and stiffness are carried out between the active and passive stiffness adjustment of mode 1 and mode 2. The results show that the output force and stiffness of the finger adopting mode 1 can be improved more than two times and five times, and its compliance using mode 2 is almost similar, compared with the pure soft one. To further demonstrate performances of dual-mode morphing, a three-fingered gripper is assembled for grasping and manipulating targets with different shapes, sizes, rigidity, and weight, including playing card, unshelled raw egg, grapes, and unscrewing the bottle cap. It can successfully lift a dumbbell weighing 1460 g with a 7.6 load/weight ratio through a two-mode switch.

A Wide-Range Stiffness-Tunable Soft Actuator Inspired by Deep-Sea Glass Sponges.

Achieving both high compliance and stiffness is a key issue in stiffness-tunable soft robots. A wide-range variable-stiffness method keeping pure soft characteristic is proposed by bioinspired design of deep-sea glass sponges adopting thermoplastic starch. The stiffness-tunable mechanism is designed through force analysis and optimization of its bionic cellular structure. It is fabricated with load-weight ratio exceeding 470. Then, a wide-range stiffness-tunable omnidirectional-bending soft actuator (WOSA) is realized, and the bending stiffness model is established. Comparative experiments of stiffness and deformation are conducted on WOSA and a pure soft actuator (PSA) with the same size. Results show that the WOSA can get 92.3 times initial bending and 70.8 times torsional stiffness variation range, of which the flexibility is even better than PSA. A gripper assembled by three WOSAs is verified through stiffness adjustment that it can grasp different weight fragile, soft items from the unshelled fresh egg, boiled egg yolk to grapes. It can even lift a dumbbell weighting 3.32 kg. Finally, a manipulator demonstrated its potential in future minimally invasive surgical applications due to its wide stiffness range and large deformation capacity.

Biomagnification and trophic transfer of total mercury and methylmercury in a sub-tropical montane forest food web, southwest China.

Little is known about the bioaccumulation and trophic transfer of total mercury (THg) and methylmercury (MeHg) via food webs in terrestrial ecosystems, especially in subtropical forest ecosystems. In the present study, THg and MeHg were determined as well as the carbon (δ13C) and nitrogen (δ15N) isotope composition in samples of soils, plants, invertebrates, and songbird feathers to construct food webs in a remote subtropical montane forest in Mt. Ailao, southwest China and assess the bioaccumulation, biomagnification, and trophic transfer of Hg. Results showed that the trophic levels (TLs) of all consumers ranged from 0.8 to 3.3 and followed the order of songbirds > spiders > omnivorous insects > herbivorous insects > plants, and THg and MeHg exhibited a clear biomagnification up the food chain from plants-herbivorous/omnivorous insects-spiders-songbirds. The lowest MeHg concentration was observed in pine needles ranged from 0.104 to 0.949 ng g-1 with only a 1.6% ratio of MeHg to THg (MeHg%), while the highest MeHg concentrations ranged from 425 to 5272 ng g-1 in songbirds with MeHg% values of up to 96%. High values of trophic magnification slope (TMS) for THg (0.22) and MeHg (0.38) were observed in plant-invertebrate-songbird food chain, verifying the significant bioaccumulation of Hg, particularly MeHg, in the remote subtropical forest ecosystem. This study confirmed the production and efficient biomagnification of MeHg in remote subtropical montane forest and the significant bioaccumulation of MeHg in terrestrial top predators.

Passerine bird reproduction does not decline in a highly-contaminated mercury mining district of China.

Mercury (Hg) is a neurotoxic element with severe effects on humans and wildlife. Widely distributed by atmospheric deposition, it can also be localized near point sources such as mines. Mercury has been shown to reduce the reproduction of bird populations in field observations in North America and Europe, but studies are needed in Asia, where the majority of emissions now occur. We investigated the reproduction of two passerines, Japanese Tit (Parus minor) and Russet Sparrow (Passer rutilans), in a large-scale Hg mining district, and a non-mining district, both in Guizhou, southwest China. Concentrations of Hg were elevated in the mining district (blood levels of 2.54 ± 2.21 [SD] and 0.71 ± 0.40 µg/g, in adult tits and sparrows, respectively). However, we saw no evidence of decreased breeding there: metrics such as egg volume, nestling weight, hatching and fledgling success, were all similar between the different districts across two breeding seasons. Nor were there correlations at the mining district between Hg levels of adults or juveniles, and hatching or fledgling success, or nestling weight. Nest success was high even in the mining district (tit, 64.0%; sparrow: 83.1%). This lack of reproductive decline may be related to lower blood levels in nestlings (means < 0.15 µg/g for both species). Concentrations of selenium (Se), and Se-to-Hg molar ratio, were also not correlated to breeding success. Although blood levels of 3.0 µg/g have been considered as a threshold of adverse effects in birds, even leading to severe effects, we detected no population-level reproductive effects, despite ~25% of the adult tits being above this level. Future work should investigate different locations in the mining district, different life-stages of the birds, and a wider variety of species. The hypothesis that bird populations can evolve resistance to Hg in contaminated areas should also be examined further.

Distributions of Total Mercury and Methylmercury in Dragonflies from a Large, Abandoned Mercury Mining Region in China.

Dragonflies (Order Odonata) often are considered to be biosentinels of environmental contamination, e.g., heavy metals and/or persistent organic pollutants (POPs). Dragonflies (n = 439) belonging to 15 species of 8 genera were collected from an abandoned mercury (Hg) mining region in China to investigate the bioaccumulation of total Hg (THg) and methylmercury (MeHg). THg and MeHg concentrations in dragonflies varied widely within ranges of 0.06-19 mg/kg (average: 1.5 ± 2.2 mg/kg) and 0.02-5.7 mg/kg (average: 0.75 ± 0.65 mg/kg), respectively. THg and MeHg were positively correlated with bodyweight (THg: r2 = 0.10, P = 0.000; MeHg: r2 = 0.09, P = 0.000). Significant variations were observed among species, with the highest MeHg value (in Orthetrum triangulare) was fivefold higher than the lowest (in Pantala flavescens). These variations were consistent with those of nitrogen isotope (δ15N) values, indicating that increased δ15N, i.e., trophic levels, may reflect increased exposure and uptake of biomagnifying MeHg in dragonflies. A toxicological risk assessment found hazard quotients for specialist dragonfly-consuming birds of up to 7.2, which is 2.4 times greater than the permissible limit of 3, suggesting a potential toxicological risk of exposure.

Extremely Elevated Total Mercury and Methylmercury in Forage Plants in a Large-Scale Abandoned Hg Mining Site: A Potential Risk of Exposure to Grazing Animals.

Ninety-five wild forage plants (belonging to 22 species of 18 families) and their corresponding rhizosphere soil samples were collected from wastelands of a large-scale abandoned Hg mining region for total Hg (THg) and methylmercury (MeHg) analysis. The forage plant communities on the wastelands were dominated by the Asteraceae, Crassulaceae, and Polygonaceae families. The THg and MeHg concentrations in the forage plants varied widely and were in the range of 0.10 to 13 mg/kg and 0.19 to 23 µg/kg, respectively. Shoots of Aster ageratoides showed the highest average THg concentration of 12 ± 1.1 mg/kg, while those of Aster subulatus had the highest average MeHg concentrations of 7.4 ± 6.1 µg/kg. Both the THg and MeHg concentrations in the aboveground plant parts exhibited positive correlations with the THg (r = 0.70, P < 0.01) and MeHg (r = 0.68, P < 0.01) concentrations in the roots; however, these were not correlated with the THg and MeHg concentrations in their rhizosphere soils. The species A. ageratoides, A. subulatus, and S. brachyotus showed strong accumulation of Hg and are of concern for herbivorous/omnivorous wildlife and feeding livestock. Taking the provisional tolerable weekly intake (PTWI) values for IHg recommended by the Joint FAO/WHO Expert Committee on Food Additives (JECFA in Summary and conclusions of the seventy-second meeting of the joint FAO/WHO expert committee on food additives Rome, Italy, 2010) for human dietary exposure of 4 ng/g into account, the daily intake of IHg by a 65 kg animal grazing on 1.0 kg of forage (dry weight) would be between 190 and 13,200 µg, three to five orders of magnitude higher than the permitted limit, suggesting a potential risk of exposure.

A novel isoform of Homeodomain-interacting protein kinase-2 promotes YAP/TEAD transcriptional activity in NSCLC cells.

Homeodomain-interacting protein kinase-2 (HIPK2) can either promote or inhibit transcription depending on cellular context. In this study, we show that a new HIPK2 isoform increases TEAD reporter activity in NSCLC cells. We detected HIPK2 copy number gain in 5/6 (83.3%) NSCLC cell lines. In NSCLC patients with high HIPK2 mRNA expression in the Human Protein Atlas, the five-year survival rate is significantly lower than in patients with low expression (38% vs 47%; p = 0.047). We also found that 70/78 (89.7%) of NSCLC tissues have moderate to strong expression of the N-terminal HIPK2 protein. We detected and cloned a novel HIPK2 isoform 3 and found that its forced overexpression promotes TEAD reporter activity in NSCLC cells. Expressing HIPK2 isoform 3_K228A kinase-dead plasmid failed to increase TEAD reporter activity in NSCLC cells. Next, we showed that two siRNAs targeting HIPK2 decreased HIPK2 isoform 3 and YAP protein levels in NSCLC cells. Degradation of the YAP protein was accelerated after HIPK2 knockdown in NSCLC cells. Inhibition of HIPK2 isoform 3 decreased the mRNA expression of YAP downstream gene CTGF. The specific HIPK2 kinase inhibitor TBID decreased TEAD reporter activity, reduced cancer side populations, and inhibited tumorsphere formation of NSCLC cells. In summary, this study indicates that HIPK2 isoform 3, the main HIPK2 isoform expressed in NSCLC, promotes YAP/TEAD transcriptional activity in NSCLC cells. Our results suggest that HIPK2 isoform 3 may be a potential therapeutic target for NSCLC.