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ObjectivesThe poor safety profile of sunitinib capsules has encouraged the identification of targeted drug delivery systems against renal cell carcinoma. This study aimed to explore the effect of sunitinib‐loaded microbubbles along with ultrasound (US) treatment on proliferation and apoptosis of human GRC‐1 granulocyte renal carcinoma cells in vitro and in vivo (xenograft tumor growth in nude mice).MethodsLiposomes containing sunitinib were prepared by using the transmembrane ammonium sulfate gradient method and then absorbed into polymer microbubbles to generate sunitinib‐loaded microbubbles. Entrapment of sunitinib was verified by 25‐25‐[N‐[(7‐nitro‐2‐1,3‐benzoxadiazol‐4‐yl)methyl]amino]‐27‐norcholesterol staining. GRC‐1 cells were treated with microbubbles alone, liposomes alone, sunitinib alone, sunitinib‐loaded microbubbles without and with US, and no treatment (control). Cell survival and apoptosis were assessed at 12, 24, and 48 hours after treatment. Xenograft tumors were induced by implantation of GRC‐1 cells in nude mice. The animals with tumors were then randomly assigned to sunitinib alone, sunitinib‐loaded microbubbles − US, sunitinib‐loaded microbubbles + US, and no treatment (control; n = 10 per group). The tumor volumes were analyzed on the 7th, 15th, and 21st days.ResultsThe sunitinib entrapment efficiency in the liposomes was approximately 78%. The effective sunitinib concentration in each group was 0.1 μg/mL. The sunitinib‐loaded microbubble + US group showed a lower in vitro cell survival rate (P < .001) compared with the other groups. Greater in vivo inhibition of xenograft tumor growth was also observed in the sunitinib‐loaded microbubble + US group compared with the other groups.ConclusionsCombined sunitinib‐loaded microbubbles and US treatment significantly inhibits growth of renal carcinoma cells both in vitro and in vivo.

Artificial intelligence has great potential for use in smart grids. Power system image recognition based on artificial intelligence is an important research direction. The insulator is essential equipment for the power grid and is related to operational safety. Online operating insulator location identification and fault diagnosis technologies based on unmanned aerial vehicle (UAV) patrol the images, and deep learning algorithms have been continuously suggested and developed. These technologies have achieved good results in practical application. By compiling the recent literature on insulator detection technology, three common application scenarios and research difficulties are uncovered: The need for increased detection accuracy and real-time speed; faulty image recognition of complex backgrounds and target occlusion; and multiscale object and small object detection improvements. At the same time, the improved algorithms in the literature are comprehensively summarized, and the performance evaluation indices of various algorithms are compared.

Abstract Toosendanin has been suggested as a potential agent for controlling zooplankton contamination in microalgal cultivation. Growth inhibitory and antifeedant influences of toosendanin on the rotifer Brachionus plicatilis were investigated. Sublethal concentrations of toosendanin (1.76–2.59 mg m −3 ) reduced population abundance of rotifers, decreased the lorica length and width, and shrank the body size of survivors notably. No changes were observed in the amictic egg sizes, although the egg production per female rotifer was decreased by toosendanin. Exposure to toosendanin for 4 h significantly decreased the rotifer chlorophyll consumption per individual, indicating the antifeedant effect on rotifers. Analysis on the digestive enzymes showed that exposure to toosendanin had no effect on cellulose activity, but reduced the activities of diastase, pepsase and tryptase in rotifer homogenate. In addition, the half-saturation constant (K m ) of tryptase was increased and the maximum velocity (V max ) of pepsase was decreased by toosendanin, suggesting the direct inhibition of these two proteases by toosendanin in B. plicatilis. This may contribute to the feeding deterrent property of toosendanin on rotifers. The present study heralds the very beginning of studies regarding the toxic mechanism of toosendanin on rotifers, and will accelerate its potential uses for zooplankton extermination in microalgal cultivation.

AbstractActivation of potassium (K+) currents plays a critical role in the control of programmed cell death. Because pituitary adenylate cyclase‐activating polypeptide (PACAP) has been shown to inhibit the apoptotic cascade in the cerebellar cortex during development, we have investigated the effect of PACAP on K+ currents in cultured cerebellar granule cells using the patch‐clamp technique in the whole‐cell configuration. Two types of outward K+ currents, a transient K+ current (IA) and a delayed rectifier K+ current (IK) were characterized using two different voltage protocols and specific inhibitors of K+ channels. Application of PACAP induced a reversible reduction of the IK amplitude, but did not affect IA, while the PACAP‐related peptide vasoactive intestinal polypeptide had no effect on either types of K+ currents. Repeated applications of PACAP induced gradual attenuation of the electrophysiological response. In the presence of guanosine 5′‐[γthio]triphosphate (GTPγS), PACAP provoked a marked and irreversible IK depression, whereas cell dialysis with guanosine 5′‐[βthio]diphosphate GDPβS totally abolished the effect of PACAP. Pre‐treatment of the cells with pertussis toxin did not modify the effect of PACAP on IK. In contrast, cholera toxin suppressed the PACAP‐induced inhibition of IK. Exposure of granule cells to dibutyryl cyclic adenosine monophosphate (dbcAMP) mimicked the inhibitory effect of PACAP on IK. Addition of the specific protein kinase A inhibitor H89 in the patch pipette solution prevented the reduction of IK induced by both PACAP and dbcAMP. PACAP provoked a sustained increase of the resting membrane potential in cerebellar granule cells cultured either in high or low KCl‐containing medium, and this long‐term depolarizing effect of PACAP was mimicked by the IK specific blocker tetraethylammonium chloride (TEA). In addition, pre‐incubation of granule cells with TEA suppressed the effect of PACAP on resting membrane potential. TEA mimicked the neuroprotective effect of PACAP against ethanol‐induced apoptotic cell death, and the increase of caspase‐3 activity observed after exposure of granule cells to ethanol was also significantly inhibited by TEA. Taken together, the present results demonstrate that, in rat cerebellar granule cells, PACAP reduces the delayed outward rectifier K+ current by activating a type 1 PACAP (PAC1) receptor coupled to the adenylyl cyclase/protein kinase A pathway through a cholera toxin‐sensitive Gs protein. Our data also show that PACAP and TEA induce long‐term depolarization of the resting membrane potential, promote cell survival and inhibit caspase‐3 activity, suggesting that PACAP‐evoked inhibition of IK contributes to the anti‐apoptotic effect of the peptide on cerebellar granule cells.

The macroalgal industry is expanding, and the quest for novel ingredients to improve and develop innovative products is crucial. Consumers are increasingly looking for natural-derived ingredients in cosmetic products that have been proven to be effective and safe. Macroalgae-derived compounds have growing popularity in skincare products as they are natural, abundant, biocompatible, and renewable. Due to their high biomass yields, rapid growth rates, and cultivation process, they are gaining widespread recognition as potentially sustainable resources better suited for biorefinery processes. This review demonstrates macroalgae metabolites and their industrial applications in moisturizers, anti-aging, skin whitening, hair, and oral care products. These chemicals can be obtained in combination with energy products to increase the value of macroalgae from an industrial perspective with a zero-waste approach by linking multiple refineries. The key challenges, bottlenecks, and future perspectives in the operation and outlook of macroalgal biorefineries were also discussed.

The aim of this study is to provide an overview of deaths caused by poisoning (especially illicit drugs) in Estonia from 2000 to 2009. The data on poisoning deaths (N = 4132) were collected from the autopsy reports of the Estonian Forensic Science Institute. Ethanol poisoning was the most frequent cause of death (N = 1449, 35.1%), followed by carbon monoxide (N = 1151, 27.9%) and poisoning from illicit drugs (N = 888, 21.5%). The study included 3267 male (79.1%) and 865 female fatalities, with the prevalent age group being 35-64 years. Since 2002, deaths from fentanyles have increased sharply and remained at a high level - from 63 cases in 2002 to 138 cases in 2009. This high number indicates that in spite of the state's drug policies, illegal drugs remain easily available and that this area requires more attention. Alcohol abuse prevention policies - restrictions on alcohol advertisements in the media, limitations on sale times and anti-alcohol campaigns concerning traffic - have not brought about a significant decrease in ethanol poisoning.

Thirty-two pregnant Long-Evans rats were divided into 10 groups of 3 or 4 pregnant rats, and each rat was given a single dose of 4 ml ethanol/kg (20 ml/kg of a 20% solution) between d 6 and 15 of gestation. An 11th group of 50 pregnant rats received distilled water and served as controls. Offspring body weights were decreased in groups of rats given ethanol as compared to controls (3.0-3.6 g, versus 3.9 g for controls). Total litter weight was decreased in dams given ethanol on d 6. Skeletal variants were seen in 13-78% of the offspring given ethanol, compared to 0.6% of the controls. Variations may be considered as additional signs of embryotoxicity. Malformations such as hydronephrosis, pelvic kidney, microcephalus, cranioschisis, and microphthalmia occurred in 72-100% of the ethanol treated offspring, as compared to 12% of controls. Hydronephrosis was most frequent on d 9 or 14, pelvic kidney on d 8 and 11, and microphthalmia from d 10-12. Cranioschisis was maximal on d 7, 11, and 15, and microcephalic offspring were most frequently born to dams given ethanol on d 7 or 14. Skeletal defects were usually single entities, while soft-tissue anomalies occurred in a consistent pattern. These results suggest that ethanol is a stage-specific teratogen in the rat at comparable exposure levels attained by many humans.

Environmental pollution damages public health and affects economic development. Environmental regulation is the main way for the government to solve environmental pollution. So what type of environmental regulation works better for public health and economic development? Can environmental regulation have an influence on economic development through public health? To solve these problems, this research uses China’s provincial panel data from 2013 to 2017 to divide environmental regulation into command-control policy tools and economic incentive policy tools and uses the mediating effect model to examine the relationship among environmental regulation, public health and economic development. The results show that: (1) There is a positive correlation between economic incentive policy tools and economic development; while no significant relationship between command-control policy tools and economic development is founded; (2) The relationship between command-control policy tools and public health is not significant, while the relationship between economic incentive policy tools and public health is positive; (3) Public health does not play a mediating role between command-control policy tools and economic development but plays a partial mediating role between economic incentive policy tools and economic development. Therefore, the government should strengthen the use of economic incentive policy tools to promote public health and sustainable economic development.

AbstractAlthough the process of microbial degradation of coal to produce biomethane has got much attention from many research works, the products profiles of coal at the initial stage of methanogenic bioconversion are not clear yet. In this study, five coal‐degrading bacterial strains (CD1, CD10, CD20, CD24, and CD25) from a methanogenic community were isolated and identified. Among them, CD1 and CD24 belong to Paenibacillus sp., CD10 and CD20 belong to Bacillus sp., and CD25 belongs to Stenotrophomonas sp. After biotreatment of lignite and bituminous coal, the kinds of newly produced compounds were 33 and 45, respectively. Metabolomics analysis showed that a large number of alkane compounds and heterocyclic aromatic compounds were produced after degradation of bituminous coal and lignite by isolated bacteria, and most of the compounds had been produced in a hydroxylated or acylated manner, indicating that the initial microbial treatment enhanced the bioavailability of coal. Some alkaloids and biosurfactants were also detected in the aforementioned products, such as glycerophosphocholine, proveratrol A, proveratrol B, surfactin, etc. These microbial metabolites may play an important role in solubilization during the degradation of coal. This study added to the understanding of the complicated metabolic process of methanogenic coal bioconversion and enabled effective production of biomethane with appropriate metabolic strategies.