Aim: Liver fibrosis is mainly characterized by the formation of fibrous scars. Galactosylated chitosan (GC) has gained increasing attention as a liver-targeted drug carrier in recent years. The ...present study aimed to investigate the availability of betulinic acid-loaded GC nanoparticles (BA-GC-NPs) for liver protection. Covalently-conjugated galactose, recognized by asialoglycoprotein receptors exclusively expressed in hepatocytes, was employed to target the liver. Materials and Methods: Galactose was coupled to chitosan by chemical covalent binding. BA-GC-NPs were synthesized by wrapping BA into NPs via ion-crosslinking method. The potential advantage of BA- GC-NP as a liver-targeting agent in the treatment of liver fibrosis has been demonstrated in vivo and in vitro. Results: BA-GC-NPs with diameters <200 nm were manufactured in a virtually spherical core-shell arrangement, and BA was released consistently and continuously for 96 h, as assessed by an in vitro release assay. According to the safety evaluation, BA-GCNPs demonstrated good biocompatibility at the cellular level and did not generate any inflammatory reaction in mice. Importantly, BAGC-NPs showed an inherent liver-targeting potential in the uptake behavioral studies in cells and bioimaging tests in vivo. Efficacy tests revealed that administering BA-GC-NPs in a mouse model of liver fibrosis reduced the degree of liver injury in mice. Conclusion: The findings showed that BA-GC-NPs form a safe and effective anti- hepatic fibrosis medication delivery strategy. Keywords: nanoparticles, lactobionic acid, chitosan, liver fibrosis, betulinic acid
Land models, which have been developed by the modeling community in the past few decades to predict future states of ecosystems and climate, have to be critically evaluated for their performance ...skills of simulating ecosystem responses and feedback to climate change. Benchmarking is an emerging procedure to measure performance of models against a set of defined standards. This paper proposes a benchmarking framework for evaluation of land model performances and, meanwhile, highlights major challenges at this infant stage of benchmark analysis. The framework includes (1) targeted aspects of model performance to be evaluated, (2) a set of benchmarks as defined references to test model performance, (3) metrics to measure and compare performance skills among models so as to identify model strengths and deficiencies, and (4) model improvement. Land models are required to simulate exchange of water, energy, carbon and sometimes other trace gases between the atmosphere and land surface, and should be evaluated for their simulations of biophysical processes, biogeochemical cycles, and vegetation dynamics in response to climate change across broad temporal and spatial scales. Thus, one major challenge is to select and define a limited number of benchmarks to effectively evaluate land model performance. The second challenge is to develop metrics of measuring mismatches between models and benchmarks. The metrics may include (1) a priori thresholds of acceptable model performance and (2) a scoring system to combine data-model mismatches for various processes at different temporal and spatial scales. The benchmark analyses should identify clues of weak model performance to guide future development, thus enabling improved predictions of future states of ecosystems and climate. The near-future research effort should be on development of a set of widely acceptable benchmarks that can be used to objectively, effectively, and reliably evaluate fundamental properties of land models to improve their prediction performance skills.
Fe, N and C tri-doped polymorphic TiO2 nano-materials show good photocatalytic activity for Cr(VI) reduction under visible light irradiation.
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•Fe, N and C atoms were successfully ...tri-doped into the nanostructures of Fe-N-C-TiO2.•The band gap energy of Fe-N-C-TiO2 reduced after (Fe, N and C) tri-doping.•Fe, N and C tri-doping in polymorphic TiO2 were effective for the photocatalytic reduction of Cr(VI).
The (Fe, N and C) tri-coped polymorphic TiO2 (Fe-N-C-TiO2), containing anatase, rutile and brookite phase, were synthesized by a hydrothermal method. The tri-coped polymorphic TiO2 were characterized in detail by several techniques in terms of their structure, composition, optics, morphology, surface area, and so on. The photocatalytic activities of Fe-N-C-TiO2 nano-materials were examined under visible light illumination using Cr(VI) as target pollutant. The results showed that Fe/Ti weight ratio crucially determines the photocatalytic activity of Fe-N-C-TiO2 nano-materials. Fe-N-C-TiO2 nano-materials with Fe/Ti weight ratio of 0.30% exhibits highest photocatalytic activity than that of the other nano-materials under visible light irradiation, which can be attributed to the synergic effect of the higher BET surface area, separation rate of electron-hole pairs, more number of surface absorbed hydroxyl groups (OH), stronger absorption in the visible-light region and optimum Fe/Ti weight ratio.
5-Fluorouracil (5-FU) is a widely used anticancer drug for the treatment of colorectal cancer (CRC). However, resistance to 5-FU often prevents the success of chemotherapy. Nuclear factor-erythroid ...2-related factor 2 (Nrf2) is a transcriptional regulator and a possible target to overcome 5-FU resistance. The present study examined epigenetic changes associated with Nrf2 induction in a human CRC cell line (SNUC5) resistant to 5-FU (SNUC5/5-FUR). Nrf2 expression, nuclear translocation, and binding to promoter were higher in SNUC5/5-FUR cells than in SNUC5 cells. The activated Nrf2 in SNUC5/5-FUR cells led to an increase in the protein expression and activity of heme oxygenase-1 (HO-1), an Nrf2-regulated gene. SNUC5/5-FUR cells produced a larger amount of reactive oxygen species (ROS) than SNUC5 cells. The siRNA- or shRNA-mediated knockdown of Nrf2 or HO-1 significantly suppressed cancer cell viability and tumor growth in vitro and in vivo, resulting in enhanced 5-FU sensitivity. Methylation-specific (MS) or real-time quantitative MS-PCR data showed hypomethylation of the Nrf2 promoter CpG islands in SNUC5/5-FUR cells compared with SNUC5 cells. Expression of the DNA demethylase ten-eleven translocation (TET) was upregulated in SNUC5/5-FUR cells. ROS generated by 5-FU upregulated TET1 expression and function, whereas antioxidant had the opposite effect. These results suggested that the mechanism underlying the acquisition of 5-FU resistance in CRC involves the upregulation of Nrf2 and HO-1 expression via epigenetic modifications of DNA demethylation.
Clubroot disease, caused by Plasmodiophora brassicae Wor., is highly damaging for Chinese cabbage. The CR (clubroot resistant) Shinki DH (doubled haploid) line of Chinese cabbage carries a single ...dominant gene, CRb, which confers resistance to the P. brassicae races 2, 4, and 8. An F2 population derived from a cross between the CR Shinki DH line and a susceptible line, 94SK, was used to map the CRb gene. Inoculation of F3 families with SSI (single-spore isolate) resulted in a 1:2:1 segregation ratio. Use of the AFLP technique combined with bulked segregant analysis allowed five co-dominant AFLP markers, and four and seven dominant AFLP markers linked in coupling and repulsion, respectively, to be identified. Six of the 16 AFLP markers showing low frequencies of recombination with the CRb locus among 138 F2 lines were cloned. A reliable conversion procedure allowed five AFLP markers to be successfully converted into CAPS and SCAR markers. An F2 population (143 plants) was analyzed with these markers and a previously identified SCAR marker, and a genetic map around CRb covering a total distance of 6.75 cM was constructed. One dominant marker, TCR09, was located 0.78 cM from CRb. The remaining markers (TCR05, TCR01, TCR10, TCR08, and TCR03) were located on the other side of CRb, and the nearest of these was TCR05, at a distance of 1.92 cM.
With rapid development of genetic testing techniques, neuroimaging and neuroelectrophysiological technologies, our understanding of malformations of cortical development continues to be deepened and ...updated. In particular, mutations in genes related to the mammalian target of rapamycin (mTOR) signaling pathway have been successively discovered in focal cortical dysplasia (FCD). At the same time, the classification consensus on FCD issued by the International League Against Epilepsy (ILAE) in 2011 has encountered problems and challenges in diagnostic practice. Therefore, in 2022, ILAE proposed an updated version of the FCD classification based on the progress in molecular genetics over the past decade. The main addition to the classification system is "white matter lesions, " and it is also suggested to integrate histopathological, neuroimaging, and molecular testing results for multi-level integrated diagnosis to achieve reliable, clinically relevant, and therapeutic targeted final diagnosis.
Two experiments were conducted to evaluate the effect of supplementing a corn-soybean meal-based diet with an enzyme complex containing amylase, protease and xylanase on the performance, intestinal ...health, apparent ileal digestibility of amino acids and nutrient digestibility of weaned pigs. In Exp. 1, 108 piglets weaned at 28 d of age were fed one of three diets containing 0 (control), 100, or 150 ppm enzyme complex for 4 wks, based on a two-phase feeding program namely 1 to 7 d (phase 1) and 8 to 28 d (phase 2). At the end of the experiment, six pigs from the control group and the group supplemented with 150 ppm enzyme complex were chosen to collect digesta samples from intestine to measure viscosity and pH in the stomach, ileum, and cecum, as well as volatile fatty acid concentrations and composition of the microflora in the cecum and colon. There were linear increases (p<0.01) in weight gain, gain: feed ratio and digestibility of gross energy with the increasing dose rate of enzyme supplementation during the whole experiment. Supplementation with enzyme complex increased the digesta viscosity in the stomach (p<0.05) and significantly increased (p<0.01) the concentrations of acetic, propionic and butyric acid in the cecum and colon. Enzyme supplementation also significantly increased the population of Lactobacilli (p<0.01) in the cecum and decreased the population of E. coli (p<0.05) in the colon. In Exp. 2, six crossbred barrows (initial body weight: 18.26±1.21 kg), fitted with a simple T-cannula at the distal ileum, were assigned to three dietary treatments according to a replicated 3×3 Latin Square design. The experimental diets were the same as the diets used in phase 2 in Exp. 1. Apparent ileal digestibility of isoleucine (p<0.01), valine (p<0.05) and aspartic acid (p<0.05) linearly increased with the increasing dose rate of enzyme supplementation. In conclusion, supplementation of the diet with an enzyme complex containing amylase, protease and xylanase improved piglet performance. This is likely a result of improvement in nutrient digestibility, volatile fatty acid concentrations and bacteria ratio in the large intestine.
Oplopanax elatus
Nakai is a high-value medicinal plant, but the availability of this resource is rare under natural conditions. To provide a novel source of
O. elatus
products, we used balloon-type ...airlift bioreactor systems to investigate a culture method. This method was developed to obtain adventitious roots (ARs), which contain a high yield of bioactive compounds. Antioxidant and anticancer properties were also investigated to evaluate the bioactivity of AR extracts. The bioreactor culture more efficiently promoted AR growth and bioactive compound accumulation (polysaccharides, phenolics, and flavonoids) than the agitated flask and solid cultures. During bioreactor culture, the maximum AR fresh (114.6 g L
−1
) and dry (12.7 g L
−1
) weights were found in the medium supplemented with 50 g L
−1
sucrose and 3 mg L
−1
IBA. The highest bioactive compound content was also found in the same medium; the productivities of polysaccharides, phenolics, and flavonoids reached 1913.9, 459.7, and 713.7 g L
−1
, respectively. The polysaccharide, phenolic, and flavonoid content of ARs from the bioreactor culture were compared with those of roots from field-grown plants. The polysaccharide content reached the maximum levels in ARs (152.5 mg g
−1
DW) and in roots of 3-year-old plants (147.5 mg g
−1
DW), with no evident difference. The phenolic (32.1 mg g
−1
DW) and flavonoid (50.5 mg g
−1
DW) contents in ARs were higher than those in the roots of plants grown in the field for 2 and 3 years. The kinetic study showed that the highest AR biomass and bioactive compound productivity were found at 40 days. Therefore, 40 days of culture is appropriate for the mass production of bioactive compounds from
O. elatus
by AR culture in bioreactor systems. Polysaccharide, phenolic, and flavonoid contents were higher in bioreactor-cultured ARs than in the roots of 2-and 3-year-old field-grown plants. ARs exhibited an effective antioxidant activity; the rate of DPPH radical scavenging in the AR extract was higher than that in the root extracts of field-grown plants (2 and 3 years); IC
50
of AR extract was only 33.5 μg mL
−1
. The AR extract also elicited anticancer effect on human cancer cell lines, particularly the gastric cancer cell line AGS. AGS cell proliferation was reduced by 50 % after 24 h of these cells were exposed to 78.3 μg mL
−1
AR extracts. Our results suggested that the bioreactor culture of
O. elatus
AR can be used to produce bioactive compounds (polysaccharides, phenolics, and flavonoids). ARs are also a potential resource to develop
O. elatus
products.
Rapid, large-scale generation of a Ds transposant population was achieved using a regeneration procedure involving tissue culture of seed-derived calli carrying Ac and inactive Ds elements. In the F2 ...progeny from genetic crosses between the same Ds and Ac starter lines, most of the crosses produced an independent germinal transposition frequency of 10-20%. Also, many Ds elements underwent immobilization even though Ac was expressed. By comparison, in a callus-derived regenerated population, over 70% of plants carried independent Ds insertions, indicating transposition early in callus formation. In the remaining population, the majority of plants carried only Ac. Most of the new Ds insertions were stably transmitted to a subsequent generation. An exceptionally high proportion of independent transposants in the regenerated population means that selection markers for transposed Ds and continual monitoring of Ac/Ds activities may not necessarily be required. By analyzing 1297 Ds-flanking DNA sequences, a genetic map of 1072 Ds insertion sites was developed. The map showed that Ds elements were transposed onto all of the rice chromosomes, with preference not only near donor sites (36%) but also on certain physically unlinked arms. Populations from both genetic crossing and tissue culture showed the same distribution patterns of Ds insertion sites. The information of these mapped Ds insertion sites was deposited in GenBank. Among them, 55% of Ds elements were on predicted open-reading frame (ORF) regions. Thus, we propose an optimal strategy for the rapid generation of a large population of Ds transposants in rice.
This REgional Carbon Cycle Assessment and Processes regional study provides a synthesis of the carbon balance of terrestrial ecosystems in East Asia, a region comprised of China, Japan, North and ...South Korea, and Mongolia. We estimate the current terrestrial carbon balance of East Asia and its driving mechanisms during 1990–2009 using three different approaches: inventories combined with satellite greenness measurements, terrestrial ecosystem carbon cycle models and atmospheric inversion models. The magnitudes of East Asia's terrestrial carbon sink from these three approaches are comparable: −0.293±0.033 PgC yr−1 from inventory–remote sensing model–data fusion approach, −0.413±0.141 PgC yr−1 (not considering biofuel emissions) or −0.224±0.141 PgC yr−1 (considering biofuel emissions) for carbon cycle models, and −0.270±0.507 PgC yr−1 for atmospheric inverse models. Here and in the following, the numbers behind ± signs are standard deviations. The ensemble of ecosystem modeling based analyses further suggests that at the regional scale, climate change and rising atmospheric CO2 together resulted in a carbon sink of −0.289±0.135 PgC yr−1, while land-use change and nitrogen deposition had a contribution of −0.013±0.029 PgC yr−1 and −0.107±0.025 PgC yr−1, respectively. Although the magnitude of climate change effects on the carbon balance varies among different models, all models agree that in response to climate change alone, southern China experienced an increase in carbon storage from 1990 to 2009, while northern East Asia including Mongolia and north China showed a decrease in carbon storage. Overall, our results suggest that about 13–27% of East Asia's CO2 emissions from fossil fuel burning have been offset by carbon accumulation in its terrestrial territory over the period from 1990 to 2009. The underlying mechanisms of carbon sink over East Asia still remain largely uncertain, given the diversity and intensity of land management processes, and the regional conjunction of many drivers such as nutrient deposition, climate, atmospheric pollution and CO2 changes, which cannot be considered as independent for their effects on carbon storage.
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