The early developmental period is a critical window during which brain cells mature and contribute to both brain development and later life functions.Gamma-aminobutyric acid(GABA),recognized as a major neurotransmitte...The early developmental period is a critical window during which brain cells mature and contribute to both brain development and later life functions.Gamma-aminobutyric acid(GABA),recognized as a major neurotransmitter,plays a crucial role in coordinating synapse formation,neuronal proliferation,and migration during this time.展开更多
Objective: Hereditary breast and ovarian cancer syndrome (HBOC) increases the risk of developing breast, ovarian, prostate, and pancreatic cancers. With the insurance coverage for BRCA genetic testing, the number of i...Objective: Hereditary breast and ovarian cancer syndrome (HBOC) increases the risk of developing breast, ovarian, prostate, and pancreatic cancers. With the insurance coverage for BRCA genetic testing, the number of individuals diagnosed with HBOC has increased. To use these test results effectively, cascade genetic testing (CGT) is recommended for at-risk relatives;however, it is not yet widely available. The purpose of this study was to investigate the willingness of the general population to share genetic test results and undergo CGT, as well as to analyze the factors influencing these decisions. Based on these findings, the study aimed to identify the types of support needed to support the sharing of genetic test results and promote the use of CGT. Methods: An online survey was conducted with 500 participants (50 men and women from each of the five generations, ranging from 20 to 69 years). Results: Among the HBOC blood relatives, 51.2% wanted to share the genetic results and 71.9% expressed a willingness to undergo CGT. “Matters to be shared with relatives” and “Helpful for my cancer prevention” were identified as key factors promoting the willingness to share the BRCA genetic test results and undergo CGT. The motivation for “Helpful for my cancer prevention” had a particularly strong influence on the decision to undergo CGT. Conclusion: In the general population, there is an emerging understanding that the genetic information impacts not only the individuals but also their entire families and can be valuable for cancer prevention. To promote the sharing of BRCA genetic test results and CGT uptake, the healthcare providers should offer support tailored to each family’s circumstances and establish cancer prevention measures recommended for HBOC.展开更多
While spray-drying has been widely utilized to improve the bioavailability of poorly water-soluble drugs,the outcomes often exhibit suboptimal particle size distribution and large particle sizes,limiting their effecti...While spray-drying has been widely utilized to improve the bioavailability of poorly water-soluble drugs,the outcomes often exhibit suboptimal particle size distribution and large particle sizes,limiting their effectiveness.In this study,we introduce electrostatic spraying as an advanced technology tailored for poorly water-soluble drugs,enabling the fabrication of nanoparticles with fine and uniform particle size distribution.Regorafenib(1 g),as a model drug,copovidone(5 g),and sodium dodecyl sulfate(0.1 g)were dissolved in 200 ml ethanol and subjected to conventional-spray-dryer and electrostatic spray dryer.The electrostatic spray-dried nanoparticles(ESDN)showed smaller particle sizes with better uniformity compared to conventional spray-dried nanoparticles(CSDN).ESDN demonstrated significantly enhanced solubility and rapid release in water.In vitro studies revealed that ESDN induced apoptosis in HCT-116 cells to a greater extent,exhibiting superior cytotoxicity compared to CSDN.Furthermore,ESDN substantially improved oral bioavailability and antitumor efficacy compared to CSDN.These findings suggest that ESD shows potential in developing enhanced drug delivery systems for poorly water-soluble drugs,effectively addressing the limitations associated with CSD methods.展开更多
To unlock the full potential of PSCs,machine learning(ML)was implemented in this research to predict the optimal combination of mesoporous-titanium dioxide(mp-TiO_(2))and weight percentage(wt%)of phenyl-C_(61)-butyric...To unlock the full potential of PSCs,machine learning(ML)was implemented in this research to predict the optimal combination of mesoporous-titanium dioxide(mp-TiO_(2))and weight percentage(wt%)of phenyl-C_(61)-butyric acid methyl ester(PCBM),along with the current density(J_(sc)),open-circuit voltage(V_(oc)),fill factor(ff),and energy conversion efficiency(ECE).Then,the combination that yielded the highest predicted ECE was selected as a reference to fabricate PCBM-PSCs with nanopatterned TiO_(2)layer.Subsequently,the PCBM-PSCs with nanopatterned TiO_(2)layers were fabricated and characterized to further understand the effects of nanopatterning depth and wt%of PCBM on PSCs.Experimentally,the highest ECE of 17.338%is achieved at 127 nm nanopatterning depth and 0.10 wt%of PCBM,where the J_(sc),V_(oc),and ff are 22.877 mA cm^(-2),0.963 V,and 0.787,respectively.The measured J_(sc),V_(oc),ff,and ECE values show consistencies with the ML prediction.Hence,these findings not only revealed the potential of ML to be used as a preliminary investigation to navigate the research of PSCs but also highlighted that nanopatterning depth has a significant impact on J_(sc),and the incorporation of PCBM on perovskite layer influenced the V_(oc)and ff,which further boosted the performance of PSCs.展开更多
Humans have relied on biomass for survival and development since the Stone Age. All aspects of human needs for materials are covered by tools, fuel, and buildings. Nowadays, metals and petroleum-based materials are wi...Humans have relied on biomass for survival and development since the Stone Age. All aspects of human needs for materials are covered by tools, fuel, and buildings. Nowadays, metals and petroleum-based materials are widely used in highly developed industries. Unfortunately, environmental contamination and the loss of natural resources have led to the reemergence of biomass resources as efficient and sustainable energy sources. Notably, simple and direct applications can no longer meet the demand for functionalization, high performance of materials and construction materials. Therefore, it is imperative to modify biomass and combine its utilisation to produce functionalization and high performance materials. For example, construction materials with superior mechanical properties and water resistance can be produced by reinforcing fibres to facilitate crosslinking. Water-oil separation or adsorption effects of hydrogels and aerogels are determined by the porosity and lightness of biomass, biocomposite conductor is prepared by chimaeric conductive material. Here, we review the approaches that have been taken to devise an environmentally friendly yet fully recyclable and sustainable functionalised biocomposites from biomass and its potential directions for future research.展开更多
The objective of this study was to carry out a review of the literature covering the topic of the association between sleep, insomnia and the medicinal use of cannabis. The guiding question for carrying out this study...The objective of this study was to carry out a review of the literature covering the topic of the association between sleep, insomnia and the medicinal use of cannabis. The guiding question for carrying out this study was whether the medicinal use of cannabis could have a significant positive impact on reducing insomnia. To this end, a review of the literature on the topic was prepared, both in English and Portuguese, from 2005 to 2023, in the PubMed, Scielo and LILACS databases. To search the databases, the keywords “cannabis”, “cannabidiol”, “tetrahydrocannabinol”, “insomnia” and “endocannabinoid” were used. In total, the initial search resulted in 17 articles. After a more careful analysis, only 6 of these articles met the inclusion criteria established for this study. Thus, it was concluded that, although some studies link the use of medicinal cannabis with an improvement in sleep quality, the current literature still lacks more studies on the topic.展开更多
The monoclonal antibodies consist of an innovative form of immunotherapy,capable of defeating several diseases,such as cancer.It is an emergent and important theme,that advances evaluation,challenges,and future perspe...The monoclonal antibodies consist of an innovative form of immunotherapy,capable of defeating several diseases,such as cancer.It is an emergent and important theme,that advances evaluation,challenges,and future perspectives with high relevance to identify gaps in recent studies and to consolidate this general theme in only one research.Its action in Chronic and Acute Lymphoid Leukemia has been evaluated in several clinical trials,which were selected between 2022 and 2023,in order to understand better the monoclonal antibodies that were most studied.The biopharmaceutical compounds Ibrutinib,Obinutuzumab,Rituximab,Venetoclax,and Inotuzumab Ozogamicin were the ones that most appeared in the most recent publications,indicating the importance of amplifying the studies.The action mechanisms that are used imply that their combined use has more success in the disease remission,showing a lower recurrence,adverse effects,and toxicity.Besides the adverse effects and overwhelming prices of the treatment,these immunotherapies results are promising,amplifying the survival rates,improving the patient’s life quality,and resulting in a precision medicine,aiming a custom treatment.The future perspectives on this therapy consist of its application in the public health system,with patients being able to be submitted to this treatment without any costs and receive a better life quality.展开更多
Objective:To investigate the anti-melanogenic potential of ligustroside isolated from Ligustrum japonicum.Methods:The cytotoxicity of ligustroside was tested via MTT assay.Furthermore,the effects of ligustroside on th...Objective:To investigate the anti-melanogenic potential of ligustroside isolated from Ligustrum japonicum.Methods:The cytotoxicity of ligustroside was tested via MTT assay.Furthermore,the effects of ligustroside on the expression of critical melanogenic markers such as tyrosinase,tyrosinase related proteins(TRPs),and microphthalmia-associated transcription factor(MITF)were analyzed at both mRNA and protein levels via RT-qPCR and Western blot,respectively,inα-melanocyte stimulating hormoneinduced B16F10 cells.In addition,phosphorylation of p38,ERK and JNK proteins was investigated.Immunofluorescence analysis of MITF was also conducted.Results:Ligustroside significantly reduced intracellular tyrosinase activity and melanin content by 37.11%and 29.12%,respectively,compared to untreated cells.Moreover,it downregulated the expression of MITF,tyrosinase,TRP-1,and TRP-2 at the mRNA and protein levels by regulating both the mitogen-activated protein kinase(MAPK)and protein kinase A(PKA)/cAMP response element-binding protein(CREB)signaling pathways.Ligustroside also suppressed the nuclear protein expression of MITF,β-catenin,and p-CREB,and decreased immunofluorescence intensity of nuclear MITF.Conclusions:Ligustroside derived from Ligustrum japonicum shows a significant anti-melanogenesis effect via suppression of the MAPK and PKA/CREB signaling pathways.展开更多
Objectives:Bladder Cancer(BC)is one of the most commonly diagnosed malignancies worldwide,with high rates of mortality and morbidity.It can be classified as non-muscle invasive bladder cancer(NMIBC)or muscle-invasive ...Objectives:Bladder Cancer(BC)is one of the most commonly diagnosed malignancies worldwide,with high rates of mortality and morbidity.It can be classified as non-muscle invasive bladder cancer(NMIBC)or muscle-invasive bladder cancer(MIBC),with radical cystectomy being the treatment for MIBC,which significantly reduces quality of life.MicroRNAs(miRs)act as critical genetic regulators,with both oncogenic and tumor-suppressive roles.MiR-10a is described as a tumor suppressor in various neoplasms,but its role in BC is controversial.This study aims to assess the activity of miR-10a in cellular invasion and proliferation in two distinct BC cell lines.Methods:The study used high-grade T24 and low-grade RT4 bladder cell lines.Cells were transfected with miR-10a mimic or a non-targeting control.Transfection efficiency was validated by qPCR.Cell proliferation was cultured for 10–14 days.Cell migration and invasion were evaluated using Matrigel.All assays were conducted in triplicate.Results:The T24 cells transfected with miR-10a presented decreased cellular proliferation and invasion compared to the Scramble(p=0.0481 and p<0.0001,respectively).In the RT4 cell line,there was only a significant reduction in cellular proliferation after miR-10a transfection(p=0.0029).Conclusions:Our findings suggest that miR-10a has a tumoral suppressor role in BC,demonstrating higher efficacy in high-grade cells.展开更多
An iterative optimization strategy is proposed and applied to the steady state optimizing control of the bio-dissimilation process of glycerol to 1,3-propanediol in the presence of model-plant mismatch and input const...An iterative optimization strategy is proposed and applied to the steady state optimizing control of the bio-dissimilation process of glycerol to 1,3-propanediol in the presence of model-plant mismatch and input constraints. The scheme is based on the Augmented Integrated System Optimization and Parameter Estimation (AI- SOPE) technique, but a linearization of some performance function in the modified model-based optimization problem of AISOPE is introduced to overcome the difficulty of determining an appropriate penalty parameter. When carrying out the iterative optimization, the penalty coefficient is set to a larger value at the current iteration than at the previous iteration, which can promote the evolution rate of the iterative optimization. Simulation studies illustrate the potential ofthe approach presented for the optimizing control of the bioTdissimilation process of glycerol to 1,3-propanediol. The effects of measurement noise, measured and unmeasured disturbances on the proposed algorithm are also investigated.展开更多
Hirudin is the most anticoagulant drug found in nature, but its short serum half-life significantly inhibits its clinical anpplication. The PEGvlation of hirudin, the most promising anticoagulant drug, was performed i...Hirudin is the most anticoagulant drug found in nature, but its short serum half-life significantly inhibits its clinical anpplication. The PEGvlation of hirudin, the most promising anticoagulant drug, was performed in this paper. The optimal reaction conditions for PEG ylated hirudin were investigated, wh.en the PEGylation react, on.wasconducted under 4℃ after 10h, in the borate buffer at pH 8.5 .with the molar ratio 230 : 1 of PEG to hirudin, a higher modification extent was achieved. Finally, the bioactivity of PEGylated hirudin was measured in vitro.Compared with unmodified hirudin, 26% of anti-thrombin activity was retained.展开更多
Objective To further investigate the neuroprotective effects of five isoflavonoids from Astragalus mongholicus on xanthine (XA)/xanthine oxidase (XO)-induced injury to PC12 cells. Methods PC12 cells were damaged b...Objective To further investigate the neuroprotective effects of five isoflavonoids from Astragalus mongholicus on xanthine (XA)/xanthine oxidase (XO)-induced injury to PC12 cells. Methods PC12 cells were damaged by XA/XO. The activities of antioxidant enzymes, MTT, LDH, and GSH assays were used to evaluate the protection of these five isofavonoids. Contents of Bcl-2 family proteins were determined with flow cytometry. Results Among the five isoflavonoids including formononetin, ononin, 9, 10-dimethoxypterocarpan-3-O-β-D-glucoside, calycosin and calycosin-7-O-glucoside, calycosin and calycosin-7-O-glucoside were found to inhibit XA/XO-induced injury to PC12 cells. Their ECs0values of formononetin and calycosin were 0.05 μg/mL. Moreover, treatment with these three isoflavonoids prevented a decrease in the activities of antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), while formononetin and calycosin could prevent a significant deletion of GSH. In addition, only calycosin and calycosin-7-O-glucoside were shown to inhibit XO activity in cell-free system, with an approximate IC50 value of 10 μg/mL and 50 μg/mL. Formononetin and calycosin had no significant infuence on Bcl-2 or Bax protein contents. Conclusion Neuroprotection of formononetin, calycosin and calycosin-7-O-glucoside may be mediated by increasing endogenous antioxidants, rather by inhibiting XO activities or by scavenging free radicals.展开更多
Objective:To isolate and identify the anticancer compound against proliferation of human colon cancer cells from ethyl acetate(EtOAc)extract ol Phellinus linteus grown on germinated brown rice(PB).Methods:EtOAc extrac...Objective:To isolate and identify the anticancer compound against proliferation of human colon cancer cells from ethyl acetate(EtOAc)extract ol Phellinus linteus grown on germinated brown rice(PB).Methods:EtOAc extract of PB was partitioned with n-hexane,EtOAc,and water-saturated n-butanol.Anticancer compound of n-hexane layer was isolated and identified by HPLC and NMR,respectively.Cytotoxicity against HT-29 cells was tested by SRB assay.Results:The n-hexane layer obtained after solvent fractionation of PB EtOAc extracts showed a potent anticancer activity against the HT-29 cell line.Atractylenolide I,a eudesmane-type sesquiterpene lactone,a major anticancer substance of PB,was isolated from the n-hexane layer by silica gel column chromatography and preparative-HPLC.This structure was elucidated by one-and two-dimensional NMR spectroscopic data.Atractylenolide I has not been reported in mushrooms or rice as of yet.The isolated compound dose-dependently inhibited the growth of HT-29 human colon cancer cells.Conclusions:Atractylenolide I might contribute to the anticancer effect of PB.展开更多
A robust controller is designed by using the bilinear transformation and H∞ mixed sensitivity method for bio-dissimilation process of glycerol to 1,3-propanediol. Under the controller the system works near an optimal...A robust controller is designed by using the bilinear transformation and H∞ mixed sensitivity method for bio-dissimilation process of glycerol to 1,3-propanediol. Under the controller the system works near an optimal steady-state for the volumetric productivity of 1,3-propanediol attaining its maximization. The design procedure is carried out by tuning the transformation parameter and DC gain of the performance weighted function, which is an iterative and optimal search process. Simulation results are presented which show that the designed robust controller not only ensures the robust stability of the system in face of the parametric variations in the model, but also makes the system have a favourable robust tracking performance. The validity of the proposed H∞ controller has been tested.展开更多
Antimicrobial peptides(AMPs) are a group of gene-encoded small peptides that play pivotal roles in the host immune system of multicellular organisms.Cathelicidins are an important family of AMPs that exclusively exist...Antimicrobial peptides(AMPs) are a group of gene-encoded small peptides that play pivotal roles in the host immune system of multicellular organisms.Cathelicidins are an important family of AMPs that exclusively exist in vertebrates. Many cathelicidins have been identified from mammals, birds, reptiles and fish. To date, however, cathelicidins from amphibians are poorly understood. In the present study, two novel cathelicidins(OL-CATH1 and 2) were identified and studied from the odorous frog Odorrana livida.Firstly, the cDNAs encoding the OL-CATHs(780 and735 bp in length, respectively) were successfully cloned from a lung cDNA library constructed for the frog. Multi-sequence alignment was carried out to analyze differences between the precursors of the OL-CATHs and other representative cathelicidins.Mature peptide sequences of OL-CATH1 and 2 were predicted(33 amino acid residues) and their secondary structures were determined(OL-CATH1 showed a random-coil conformation and OL-CATH2 demonstrated α-helical conformation). Furthermore,OL-CATH1 and 2 were chemically synthesized and their in vitro functions were determined. Antimicrobial and bacterial killing kinetic analyses indicated that OL-CATH2 demonstrated relatively moderate and rapid antimicrobial potency and exhibited strong anti-inflammatory activity. At very low concentrations(10 μg/mL), OL-CATH2 significantly inhibited the lipopolysaccharide(LPS)-induced transcription and production of pro-inflammatory cytokines TNF-α, IL-1βand IL-6 in mouse peritoneal macrophages. In contrast, OL-CATH1 did not exhibit any detectableantimicrobial or anti-inflammatory activities. Overall,identification of these OL-CATHs from O. livida enriches our understanding of the functions of cathelicidins in the amphibian immune system. The potent antimicrobial and anti-inflammatory activities of OL-CATH2 highlight its potential as a novel candidate in anti-infective drug development.展开更多
The plant cellulose powder was activated by two different methods using 1,4-butanediol diglycidyl ether(BTDE)and 1,1′-Carbonyldiimidazole(CDI) as the chemical coupling agents.Organophosphorus hydrolase(OPH) from Flav...The plant cellulose powder was activated by two different methods using 1,4-butanediol diglycidyl ether(BTDE)and 1,1′-Carbonyldiimidazole(CDI) as the chemical coupling agents.Organophosphorus hydrolase(OPH) from Flavobacterium ATCC 27551 was immobilized on any of activated support through covalent bonding.The optimal conditions of affecting parameters on enzyme immobilization in both methods were found, and it was demonstrated that the highest activity yields of immobilized OPH onto epoxy and CDI treated cellulose were 68.32%and 73.51%, respectively.The surface treatment of cellulose via covalent coupling with BTDE and CDI agents was proved by FTIR analysis.The kinetic constants of the free and immobilized enzymes were determined, and it was showed that both immobilization techniques moderately increased the Kmvalue of the free OPH.The improvements in storage and thermal stability were investigated and depicted that the half-life of immobilized OPH over the surface of epoxy modified cellulose had a better growth compared to the free and immobilized enzymes onto CDI treated support.Also, the pH stability of the immobilized preparations was enhanced relative to the free counterpart and revealed that all enzyme samples would have the same optimum pH value for stability at 9.0.Additionally, the immobilized OPH onto epoxy and CDI activated cellulose retained about 59% and 68% of their initial activity after ten turns of batch operation, respectively.The results demonstrated the high performance of OPH enzyme in immobilized state onto an inexpensive support with the potential of industrial applications.展开更多
Complex topography buffers forests against deforestation in mountainous regions. However, it is unknown if terrain also shapes forest distribution in lowlands where human impacts are likely to be less constrained by t...Complex topography buffers forests against deforestation in mountainous regions. However, it is unknown if terrain also shapes forest distribution in lowlands where human impacts are likely to be less constrained by terrain. In such regions, if important at all, to- pographic effects will depend on cultural-historical factors and thus be human-driven (an- thropogenic) rather than natural, except in regions where the general climate or extreme soils limit the occurrence of forests. We used spatial regression modeling to assess the extent to which topographic factors explain forest distribution (presence-absence at a 48x48 m resolu- tion) in a lowland agricultural region (Denmark, 43,075 km2) at regional and landscape scales (whole study area and 10x10 km grid cells, respectively), how landscape-scale for- est-topography relationships vary geographically, and which potential drivers (topographic heterogeneity, forest cover, clay content, coastal/inland location) determine this geographic heterogeneity. Given a moist temperate climate and non-extreme soils all landscapes in Denmark would naturally be largely forest covered, and any topographic relationships will be totally or primarily human-driven. At regional scale, topographic predictors explained only 5% of the distribution of forest. In contrast, the explanatory power of topography varied from 0%-61% at landscape scale, with clear geographic patterning. Explanatory power of topog- raphy at landscape scale was moderately dependent on the potential drivers, with topog- raphic control being strongest in areas with high topographic heterogeneity and little forest cover. However, these conditioning effects were themselves geographically variable. Our findings show that topography by shaping human land-use can affect forest distribution even in flat, lowland regions, but especially via localized, geographically variable effects.展开更多
Light climate is of key importance for the growth, community composition of submerged macrophytes in lakes and, they, in turn, are affected by lake depth and the degree of eutrophication. To test the relationships bet...Light climate is of key importance for the growth, community composition of submerged macrophytes in lakes and, they, in turn, are affected by lake depth and the degree of eutrophication. To test the relationships between submerged macrophyte presence and the ratio of Secchi disk depth(SDD) to water depth, i.e. SDD/depth, nutrients and wind, we conducted an extensive sampling campaign in a macrophyte-dominated area of the eastern region( n = 36) in 2016 in Lake Taihu, China, and combined the data gathered with results from extensive physico-chemical monitoring data from the entire lake. We confirmed that SDD/Depth is the primary factor controlling the community composition of macrophytes and showed that plant abundance increased with increasing SDD/Depth ratio( p < 0.01), but that only SDD/Depth > 0.4 ensured growth of submerged macrophytes. Total phosphorus and total nitrogen also influenced the growth and community composition of macrophytes( p < 0.01), while Chl a was an indirectly affecting factor by reducing underwater light penetration. Wave height significantly influenced plant abundance( p < 0.01), whereas it had little effect on the biomass( p > 0.05). The key to restore the macrophyte beds in the lake is to reduce the nutrient loading. A decrease of the water level may contribute as well in the shallow bays but will not bring plants back in the main part of the lake. As the tolerance of shade and nutrients varied among the species studied, this should be taken into account in the restoration of lakes by addition of plants.展开更多
A new bacterial strain DMT-7 capable of selectively desulfurizing dibenzothiophene(DBT) was isolated from diesel contaminated soil.The DMT-7 was characterized and identified as Lysinibacillus sphaericus DMT-7(NCBI ...A new bacterial strain DMT-7 capable of selectively desulfurizing dibenzothiophene(DBT) was isolated from diesel contaminated soil.The DMT-7 was characterized and identified as Lysinibacillus sphaericus DMT-7(NCBI GenBank Accession No.GQ496620) using 16S rDNA gene sequence analysis.The desulfurized product of DBT,2-hydroxybiphenyl(2HBP),was identified and confirmed by high performance liquid chromatography analysis and gas chromatography-mass spectroscopy analysis respectively.The desulfurization kinetics revealed that DMT-7 started desulfurization of DBT into 2HBP after the lag phase of 24 hr,exponentially increasing the accumulation of 2HBP up to 15 days leading to approximately 60% desulfurization of the DBT.However,further growth resulted into DBT degradation.The induced culture of DMT-7 showed shorter lag phase of 6 hr and early onset of stationary phase within 10 days for desulfurization as compared to that of non-induced culture clearly indicating the inducibility of the desulfurization pathway of DMT-7.In addition,Lysinibacillus sphaericus DMT-7 also possess the ability to utilize broad range of substrates as sole source of sulfur such as benzothiophene,3,4-benzo DBT,4,6-dimethyl DBT,and 4,6-dibutyl DBT.Therefore,Lysinibacillus sphaericus DMT-7 could serve as model system for efficient biodesulfurization of diesel and petrol.展开更多
From Juglans mandshurica leaves, a new quinone compound was isolated through bioassay-guided fractionation. The structure elucidation of the compound was established based on spectroscopic studies, notably of the 2D N...From Juglans mandshurica leaves, a new quinone compound was isolated through bioassay-guided fractionation. The structure elucidation of the compound was established based on spectroscopic studies, notably of the 2D NMR spectra. The compound exhibited moderate cytotoxic activities against Hela, MCF-7, BGC823 and 3T3-Llcell lines with IC50 ranges from 7.5 to 26.8 μmol/L.展开更多
基金supported by the Center for Cognition and Sociality,Institute for Basic Science(IBS)(IBS-R001-D2)(to WK).
文摘The early developmental period is a critical window during which brain cells mature and contribute to both brain development and later life functions.Gamma-aminobutyric acid(GABA),recognized as a major neurotransmitter,plays a crucial role in coordinating synapse formation,neuronal proliferation,and migration during this time.
文摘Objective: Hereditary breast and ovarian cancer syndrome (HBOC) increases the risk of developing breast, ovarian, prostate, and pancreatic cancers. With the insurance coverage for BRCA genetic testing, the number of individuals diagnosed with HBOC has increased. To use these test results effectively, cascade genetic testing (CGT) is recommended for at-risk relatives;however, it is not yet widely available. The purpose of this study was to investigate the willingness of the general population to share genetic test results and undergo CGT, as well as to analyze the factors influencing these decisions. Based on these findings, the study aimed to identify the types of support needed to support the sharing of genetic test results and promote the use of CGT. Methods: An online survey was conducted with 500 participants (50 men and women from each of the five generations, ranging from 20 to 69 years). Results: Among the HBOC blood relatives, 51.2% wanted to share the genetic results and 71.9% expressed a willingness to undergo CGT. “Matters to be shared with relatives” and “Helpful for my cancer prevention” were identified as key factors promoting the willingness to share the BRCA genetic test results and undergo CGT. The motivation for “Helpful for my cancer prevention” had a particularly strong influence on the decision to undergo CGT. Conclusion: In the general population, there is an emerging understanding that the genetic information impacts not only the individuals but also their entire families and can be valuable for cancer prevention. To promote the sharing of BRCA genetic test results and CGT uptake, the healthcare providers should offer support tailored to each family’s circumstances and establish cancer prevention measures recommended for HBOC.
基金This work was supported by the National Research Foundation of South Korea(NRF)grants funded by the South Korean government(MEST)(No.2022R1A2C2004197,RS-2024-00407053 and RS-2023-00208448).
文摘While spray-drying has been widely utilized to improve the bioavailability of poorly water-soluble drugs,the outcomes often exhibit suboptimal particle size distribution and large particle sizes,limiting their effectiveness.In this study,we introduce electrostatic spraying as an advanced technology tailored for poorly water-soluble drugs,enabling the fabrication of nanoparticles with fine and uniform particle size distribution.Regorafenib(1 g),as a model drug,copovidone(5 g),and sodium dodecyl sulfate(0.1 g)were dissolved in 200 ml ethanol and subjected to conventional-spray-dryer and electrostatic spray dryer.The electrostatic spray-dried nanoparticles(ESDN)showed smaller particle sizes with better uniformity compared to conventional spray-dried nanoparticles(CSDN).ESDN demonstrated significantly enhanced solubility and rapid release in water.In vitro studies revealed that ESDN induced apoptosis in HCT-116 cells to a greater extent,exhibiting superior cytotoxicity compared to CSDN.Furthermore,ESDN substantially improved oral bioavailability and antitumor efficacy compared to CSDN.These findings suggest that ESD shows potential in developing enhanced drug delivery systems for poorly water-soluble drugs,effectively addressing the limitations associated with CSD methods.
基金supported by the“Human Resources Program in Energy Technology”of the Korea Institute of Energy Technology Evaluation and Planning(KETEP),which received financial resources from the Ministry of Trade,Industry&Energy,Republic of Korea(No.20204010600470)the Korea Evaluation Institute of Industrial Technology(KEIT)and the Ministry of Trade,Industry&Energy(MOTIE)of the Republic of Korea(No.20018608)Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(No.2022R1I1A1A01064236)
文摘To unlock the full potential of PSCs,machine learning(ML)was implemented in this research to predict the optimal combination of mesoporous-titanium dioxide(mp-TiO_(2))and weight percentage(wt%)of phenyl-C_(61)-butyric acid methyl ester(PCBM),along with the current density(J_(sc)),open-circuit voltage(V_(oc)),fill factor(ff),and energy conversion efficiency(ECE).Then,the combination that yielded the highest predicted ECE was selected as a reference to fabricate PCBM-PSCs with nanopatterned TiO_(2)layer.Subsequently,the PCBM-PSCs with nanopatterned TiO_(2)layers were fabricated and characterized to further understand the effects of nanopatterning depth and wt%of PCBM on PSCs.Experimentally,the highest ECE of 17.338%is achieved at 127 nm nanopatterning depth and 0.10 wt%of PCBM,where the J_(sc),V_(oc),and ff are 22.877 mA cm^(-2),0.963 V,and 0.787,respectively.The measured J_(sc),V_(oc),ff,and ECE values show consistencies with the ML prediction.Hence,these findings not only revealed the potential of ML to be used as a preliminary investigation to navigate the research of PSCs but also highlighted that nanopatterning depth has a significant impact on J_(sc),and the incorporation of PCBM on perovskite layer influenced the V_(oc)and ff,which further boosted the performance of PSCs.
基金the National Natural Science Foundation of China (No.32201491)China Postdoctoral Science Foundation (No.2021M690847)+5 种基金Natural Science Foundation of Jiangsu Province (No.BK20200775)Natural Science Foundation of the Jiangsu Higher Education Institutions of China (No.21KJB220011)Science and Technology Innovation Program of Hunan Province (No.2021RC2106)Deputy General Project of Science and Technology of Jiangsu Province (No.FZ20211507)Hunan Province Biomass-based Materials Green and Low-carbon Intelligent Manufacturing Engineering Technology Research centre (No.2022TP2033)Technology centre of Hunan Hongsen Novel Material Technology Co., Ltd. (No.HNJSZX2022290)。
文摘Humans have relied on biomass for survival and development since the Stone Age. All aspects of human needs for materials are covered by tools, fuel, and buildings. Nowadays, metals and petroleum-based materials are widely used in highly developed industries. Unfortunately, environmental contamination and the loss of natural resources have led to the reemergence of biomass resources as efficient and sustainable energy sources. Notably, simple and direct applications can no longer meet the demand for functionalization, high performance of materials and construction materials. Therefore, it is imperative to modify biomass and combine its utilisation to produce functionalization and high performance materials. For example, construction materials with superior mechanical properties and water resistance can be produced by reinforcing fibres to facilitate crosslinking. Water-oil separation or adsorption effects of hydrogels and aerogels are determined by the porosity and lightness of biomass, biocomposite conductor is prepared by chimaeric conductive material. Here, we review the approaches that have been taken to devise an environmentally friendly yet fully recyclable and sustainable functionalised biocomposites from biomass and its potential directions for future research.
文摘The objective of this study was to carry out a review of the literature covering the topic of the association between sleep, insomnia and the medicinal use of cannabis. The guiding question for carrying out this study was whether the medicinal use of cannabis could have a significant positive impact on reducing insomnia. To this end, a review of the literature on the topic was prepared, both in English and Portuguese, from 2005 to 2023, in the PubMed, Scielo and LILACS databases. To search the databases, the keywords “cannabis”, “cannabidiol”, “tetrahydrocannabinol”, “insomnia” and “endocannabinoid” were used. In total, the initial search resulted in 17 articles. After a more careful analysis, only 6 of these articles met the inclusion criteria established for this study. Thus, it was concluded that, although some studies link the use of medicinal cannabis with an improvement in sleep quality, the current literature still lacks more studies on the topic.
文摘The monoclonal antibodies consist of an innovative form of immunotherapy,capable of defeating several diseases,such as cancer.It is an emergent and important theme,that advances evaluation,challenges,and future perspectives with high relevance to identify gaps in recent studies and to consolidate this general theme in only one research.Its action in Chronic and Acute Lymphoid Leukemia has been evaluated in several clinical trials,which were selected between 2022 and 2023,in order to understand better the monoclonal antibodies that were most studied.The biopharmaceutical compounds Ibrutinib,Obinutuzumab,Rituximab,Venetoclax,and Inotuzumab Ozogamicin were the ones that most appeared in the most recent publications,indicating the importance of amplifying the studies.The action mechanisms that are used imply that their combined use has more success in the disease remission,showing a lower recurrence,adverse effects,and toxicity.Besides the adverse effects and overwhelming prices of the treatment,these immunotherapies results are promising,amplifying the survival rates,improving the patient’s life quality,and resulting in a precision medicine,aiming a custom treatment.The future perspectives on this therapy consist of its application in the public health system,with patients being able to be submitted to this treatment without any costs and receive a better life quality.
基金supported by the BB21plus funded by Busan Metropolitan City and Busan Techno Park,and the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(No.NRF-2023R1A2C1006268 and RS-2023-00212560).
文摘Objective:To investigate the anti-melanogenic potential of ligustroside isolated from Ligustrum japonicum.Methods:The cytotoxicity of ligustroside was tested via MTT assay.Furthermore,the effects of ligustroside on the expression of critical melanogenic markers such as tyrosinase,tyrosinase related proteins(TRPs),and microphthalmia-associated transcription factor(MITF)were analyzed at both mRNA and protein levels via RT-qPCR and Western blot,respectively,inα-melanocyte stimulating hormoneinduced B16F10 cells.In addition,phosphorylation of p38,ERK and JNK proteins was investigated.Immunofluorescence analysis of MITF was also conducted.Results:Ligustroside significantly reduced intracellular tyrosinase activity and melanin content by 37.11%and 29.12%,respectively,compared to untreated cells.Moreover,it downregulated the expression of MITF,tyrosinase,TRP-1,and TRP-2 at the mRNA and protein levels by regulating both the mitogen-activated protein kinase(MAPK)and protein kinase A(PKA)/cAMP response element-binding protein(CREB)signaling pathways.Ligustroside also suppressed the nuclear protein expression of MITF,β-catenin,and p-CREB,and decreased immunofluorescence intensity of nuclear MITF.Conclusions:Ligustroside derived from Ligustrum japonicum shows a significant anti-melanogenesis effect via suppression of the MAPK and PKA/CREB signaling pathways.
基金supported by grants from the São Paulo Research Foundation(FAPESP)to ThaináRodrigues(2021/04603-8).
文摘Objectives:Bladder Cancer(BC)is one of the most commonly diagnosed malignancies worldwide,with high rates of mortality and morbidity.It can be classified as non-muscle invasive bladder cancer(NMIBC)or muscle-invasive bladder cancer(MIBC),with radical cystectomy being the treatment for MIBC,which significantly reduces quality of life.MicroRNAs(miRs)act as critical genetic regulators,with both oncogenic and tumor-suppressive roles.MiR-10a is described as a tumor suppressor in various neoplasms,but its role in BC is controversial.This study aims to assess the activity of miR-10a in cellular invasion and proliferation in two distinct BC cell lines.Methods:The study used high-grade T24 and low-grade RT4 bladder cell lines.Cells were transfected with miR-10a mimic or a non-targeting control.Transfection efficiency was validated by qPCR.Cell proliferation was cultured for 10–14 days.Cell migration and invasion were evaluated using Matrigel.All assays were conducted in triplicate.Results:The T24 cells transfected with miR-10a presented decreased cellular proliferation and invasion compared to the Scramble(p=0.0481 and p<0.0001,respectively).In the RT4 cell line,there was only a significant reduction in cellular proliferation after miR-10a transfection(p=0.0029).Conclusions:Our findings suggest that miR-10a has a tumoral suppressor role in BC,demonstrating higher efficacy in high-grade cells.
基金the State Science and Technology Project of China (No.2001BA204B01).
文摘An iterative optimization strategy is proposed and applied to the steady state optimizing control of the bio-dissimilation process of glycerol to 1,3-propanediol in the presence of model-plant mismatch and input constraints. The scheme is based on the Augmented Integrated System Optimization and Parameter Estimation (AI- SOPE) technique, but a linearization of some performance function in the modified model-based optimization problem of AISOPE is introduced to overcome the difficulty of determining an appropriate penalty parameter. When carrying out the iterative optimization, the penalty coefficient is set to a larger value at the current iteration than at the previous iteration, which can promote the evolution rate of the iterative optimization. Simulation studies illustrate the potential ofthe approach presented for the optimizing control of the bioTdissimilation process of glycerol to 1,3-propanediol. The effects of measurement noise, measured and unmeasured disturbances on the proposed algorithm are also investigated.
文摘Hirudin is the most anticoagulant drug found in nature, but its short serum half-life significantly inhibits its clinical anpplication. The PEGvlation of hirudin, the most promising anticoagulant drug, was performed in this paper. The optimal reaction conditions for PEG ylated hirudin were investigated, wh.en the PEGylation react, on.wasconducted under 4℃ after 10h, in the borate buffer at pH 8.5 .with the molar ratio 230 : 1 of PEG to hirudin, a higher modification extent was achieved. Finally, the bioactivity of PEGylated hirudin was measured in vitro.Compared with unmodified hirudin, 26% of anti-thrombin activity was retained.
基金supported by the Natural Science Foundation of China(No.NSFC.30670415).
文摘Objective To further investigate the neuroprotective effects of five isoflavonoids from Astragalus mongholicus on xanthine (XA)/xanthine oxidase (XO)-induced injury to PC12 cells. Methods PC12 cells were damaged by XA/XO. The activities of antioxidant enzymes, MTT, LDH, and GSH assays were used to evaluate the protection of these five isofavonoids. Contents of Bcl-2 family proteins were determined with flow cytometry. Results Among the five isoflavonoids including formononetin, ononin, 9, 10-dimethoxypterocarpan-3-O-β-D-glucoside, calycosin and calycosin-7-O-glucoside, calycosin and calycosin-7-O-glucoside were found to inhibit XA/XO-induced injury to PC12 cells. Their ECs0values of formononetin and calycosin were 0.05 μg/mL. Moreover, treatment with these three isoflavonoids prevented a decrease in the activities of antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), while formononetin and calycosin could prevent a significant deletion of GSH. In addition, only calycosin and calycosin-7-O-glucoside were shown to inhibit XO activity in cell-free system, with an approximate IC50 value of 10 μg/mL and 50 μg/mL. Formononetin and calycosin had no significant infuence on Bcl-2 or Bax protein contents. Conclusion Neuroprotection of formononetin, calycosin and calycosin-7-O-glucoside may be mediated by increasing endogenous antioxidants, rather by inhibiting XO activities or by scavenging free radicals.
基金Supported by a grant from the Korea Food Research Institute(Grant number:E0131601)
文摘Objective:To isolate and identify the anticancer compound against proliferation of human colon cancer cells from ethyl acetate(EtOAc)extract ol Phellinus linteus grown on germinated brown rice(PB).Methods:EtOAc extract of PB was partitioned with n-hexane,EtOAc,and water-saturated n-butanol.Anticancer compound of n-hexane layer was isolated and identified by HPLC and NMR,respectively.Cytotoxicity against HT-29 cells was tested by SRB assay.Results:The n-hexane layer obtained after solvent fractionation of PB EtOAc extracts showed a potent anticancer activity against the HT-29 cell line.Atractylenolide I,a eudesmane-type sesquiterpene lactone,a major anticancer substance of PB,was isolated from the n-hexane layer by silica gel column chromatography and preparative-HPLC.This structure was elucidated by one-and two-dimensional NMR spectroscopic data.Atractylenolide I has not been reported in mushrooms or rice as of yet.The isolated compound dose-dependently inhibited the growth of HT-29 human colon cancer cells.Conclusions:Atractylenolide I might contribute to the anticancer effect of PB.
基金Supported by National Science and Technology Pursuit Project (2001BA204B01)
文摘A robust controller is designed by using the bilinear transformation and H∞ mixed sensitivity method for bio-dissimilation process of glycerol to 1,3-propanediol. Under the controller the system works near an optimal steady-state for the volumetric productivity of 1,3-propanediol attaining its maximization. The design procedure is carried out by tuning the transformation parameter and DC gain of the performance weighted function, which is an iterative and optimal search process. Simulation results are presented which show that the designed robust controller not only ensures the robust stability of the system in face of the parametric variations in the model, but also makes the system have a favourable robust tracking performance. The validity of the proposed H∞ controller has been tested.
基金supported by grants from the Jiangsu Students' Innovation and Entrepreneurship Training Program(2017suda098)the National Natural Science Foundation of China(31772455)+2 种基金Natural Science Foundation of Jiangsu Province(BK20160336 and BK20171214)Natural Science Foundation of College in Jiangsu Province(16KJB350004)Suzhou Science and Technology Development Project(SYN201504 and SNG2017045)
文摘Antimicrobial peptides(AMPs) are a group of gene-encoded small peptides that play pivotal roles in the host immune system of multicellular organisms.Cathelicidins are an important family of AMPs that exclusively exist in vertebrates. Many cathelicidins have been identified from mammals, birds, reptiles and fish. To date, however, cathelicidins from amphibians are poorly understood. In the present study, two novel cathelicidins(OL-CATH1 and 2) were identified and studied from the odorous frog Odorrana livida.Firstly, the cDNAs encoding the OL-CATHs(780 and735 bp in length, respectively) were successfully cloned from a lung cDNA library constructed for the frog. Multi-sequence alignment was carried out to analyze differences between the precursors of the OL-CATHs and other representative cathelicidins.Mature peptide sequences of OL-CATH1 and 2 were predicted(33 amino acid residues) and their secondary structures were determined(OL-CATH1 showed a random-coil conformation and OL-CATH2 demonstrated α-helical conformation). Furthermore,OL-CATH1 and 2 were chemically synthesized and their in vitro functions were determined. Antimicrobial and bacterial killing kinetic analyses indicated that OL-CATH2 demonstrated relatively moderate and rapid antimicrobial potency and exhibited strong anti-inflammatory activity. At very low concentrations(10 μg/mL), OL-CATH2 significantly inhibited the lipopolysaccharide(LPS)-induced transcription and production of pro-inflammatory cytokines TNF-α, IL-1βand IL-6 in mouse peritoneal macrophages. In contrast, OL-CATH1 did not exhibit any detectableantimicrobial or anti-inflammatory activities. Overall,identification of these OL-CATHs from O. livida enriches our understanding of the functions of cathelicidins in the amphibian immune system. The potent antimicrobial and anti-inflammatory activities of OL-CATH2 highlight its potential as a novel candidate in anti-infective drug development.
基金Supported by the Malek-Ashtar University of Technology(925826018,2015)
文摘The plant cellulose powder was activated by two different methods using 1,4-butanediol diglycidyl ether(BTDE)and 1,1′-Carbonyldiimidazole(CDI) as the chemical coupling agents.Organophosphorus hydrolase(OPH) from Flavobacterium ATCC 27551 was immobilized on any of activated support through covalent bonding.The optimal conditions of affecting parameters on enzyme immobilization in both methods were found, and it was demonstrated that the highest activity yields of immobilized OPH onto epoxy and CDI treated cellulose were 68.32%and 73.51%, respectively.The surface treatment of cellulose via covalent coupling with BTDE and CDI agents was proved by FTIR analysis.The kinetic constants of the free and immobilized enzymes were determined, and it was showed that both immobilization techniques moderately increased the Kmvalue of the free OPH.The improvements in storage and thermal stability were investigated and depicted that the half-life of immobilized OPH over the surface of epoxy modified cellulose had a better growth compared to the free and immobilized enzymes onto CDI treated support.Also, the pH stability of the immobilized preparations was enhanced relative to the free counterpart and revealed that all enzyme samples would have the same optimum pH value for stability at 9.0.Additionally, the immobilized OPH onto epoxy and CDI activated cellulose retained about 59% and 68% of their initial activity after ten turns of batch operation, respectively.The results demonstrated the high performance of OPH enzyme in immobilized state onto an inexpensive support with the potential of industrial applications.
基金economic support from Aarhus University Research Foundationa Center of the Danish National Research Foundation
文摘Complex topography buffers forests against deforestation in mountainous regions. However, it is unknown if terrain also shapes forest distribution in lowlands where human impacts are likely to be less constrained by terrain. In such regions, if important at all, to- pographic effects will depend on cultural-historical factors and thus be human-driven (an- thropogenic) rather than natural, except in regions where the general climate or extreme soils limit the occurrence of forests. We used spatial regression modeling to assess the extent to which topographic factors explain forest distribution (presence-absence at a 48x48 m resolu- tion) in a lowland agricultural region (Denmark, 43,075 km2) at regional and landscape scales (whole study area and 10x10 km grid cells, respectively), how landscape-scale for- est-topography relationships vary geographically, and which potential drivers (topographic heterogeneity, forest cover, clay content, coastal/inland location) determine this geographic heterogeneity. Given a moist temperate climate and non-extreme soils all landscapes in Denmark would naturally be largely forest covered, and any topographic relationships will be totally or primarily human-driven. At regional scale, topographic predictors explained only 5% of the distribution of forest. In contrast, the explanatory power of topography varied from 0%-61% at landscape scale, with clear geographic patterning. Explanatory power of topog- raphy at landscape scale was moderately dependent on the potential drivers, with topog- raphic control being strongest in areas with high topographic heterogeneity and little forest cover. However, these conditioning effects were themselves geographically variable. Our findings show that topography by shaping human land-use can affect forest distribution even in flat, lowland regions, but especially via localized, geographically variable effects.
基金jointly funded by the National Key R&D Program of China(No.2017YFC0405205)the Major Projects on Control and Rectification of Water Body Pollution(No.2017ZX07203–004)+1 种基金the National Natural Science Foundation of China(Nos.42071118 and 41621002)supported by the TüBITAK,BIDEB program 2232.
文摘Light climate is of key importance for the growth, community composition of submerged macrophytes in lakes and, they, in turn, are affected by lake depth and the degree of eutrophication. To test the relationships between submerged macrophyte presence and the ratio of Secchi disk depth(SDD) to water depth, i.e. SDD/depth, nutrients and wind, we conducted an extensive sampling campaign in a macrophyte-dominated area of the eastern region( n = 36) in 2016 in Lake Taihu, China, and combined the data gathered with results from extensive physico-chemical monitoring data from the entire lake. We confirmed that SDD/Depth is the primary factor controlling the community composition of macrophytes and showed that plant abundance increased with increasing SDD/Depth ratio( p < 0.01), but that only SDD/Depth > 0.4 ensured growth of submerged macrophytes. Total phosphorus and total nitrogen also influenced the growth and community composition of macrophytes( p < 0.01), while Chl a was an indirectly affecting factor by reducing underwater light penetration. Wave height significantly influenced plant abundance( p < 0.01), whereas it had little effect on the biomass( p > 0.05). The key to restore the macrophyte beds in the lake is to reduce the nutrient loading. A decrease of the water level may contribute as well in the shallow bays but will not bring plants back in the main part of the lake. As the tolerance of shade and nutrients varied among the species studied, this should be taken into account in the restoration of lakes by addition of plants.
文摘A new bacterial strain DMT-7 capable of selectively desulfurizing dibenzothiophene(DBT) was isolated from diesel contaminated soil.The DMT-7 was characterized and identified as Lysinibacillus sphaericus DMT-7(NCBI GenBank Accession No.GQ496620) using 16S rDNA gene sequence analysis.The desulfurized product of DBT,2-hydroxybiphenyl(2HBP),was identified and confirmed by high performance liquid chromatography analysis and gas chromatography-mass spectroscopy analysis respectively.The desulfurization kinetics revealed that DMT-7 started desulfurization of DBT into 2HBP after the lag phase of 24 hr,exponentially increasing the accumulation of 2HBP up to 15 days leading to approximately 60% desulfurization of the DBT.However,further growth resulted into DBT degradation.The induced culture of DMT-7 showed shorter lag phase of 6 hr and early onset of stationary phase within 10 days for desulfurization as compared to that of non-induced culture clearly indicating the inducibility of the desulfurization pathway of DMT-7.In addition,Lysinibacillus sphaericus DMT-7 also possess the ability to utilize broad range of substrates as sole source of sulfur such as benzothiophene,3,4-benzo DBT,4,6-dimethyl DBT,and 4,6-dibutyl DBT.Therefore,Lysinibacillus sphaericus DMT-7 could serve as model system for efficient biodesulfurization of diesel and petrol.
文摘From Juglans mandshurica leaves, a new quinone compound was isolated through bioassay-guided fractionation. The structure elucidation of the compound was established based on spectroscopic studies, notably of the 2D NMR spectra. The compound exhibited moderate cytotoxic activities against Hela, MCF-7, BGC823 and 3T3-Llcell lines with IC50 ranges from 7.5 to 26.8 μmol/L.