Cinobufagin, a bufadienolide from traditional Chinese medicine Bufo bufo gargarizans CANTOR, inhibits PC3 cell growth in vitro and in vivo

Objective:To explore the effects of cinobufagin (CBF),an active component of toad venom (Bufo bufo gargarizans CANTOR),on the proliferation and apoptosis of PC3 human prostate cancer cells in vitro and preliminarily investigate the mechanism of CBF in suppressing tumor cell growth in vivo.Methods:The effect of CBF on PC3 cells proliferation was detected using MTT assay.The morphological changes of PC3 cells were observed under an optical microscope.Colony formation assays were used to observe the CBF effect on colony formation by PC3 cells.PC3 cell apoptosis after treatment with CBF for 48 hours was monitored using flow cytometry.Furthermore,the effect of CBF on the expression of myeloid cell leukemia-1 (MCL-1) and related apoptotic proteins was examined using western blotting.A xenograft model was established in BALB/c nude mice to evaluate the effect of CBF on prostate cancer in vivo.Results:The MT-T assay results illustrated that PC3 cell proliferation was inhibited in vitro by CBF in a concentration-and time-dependent manner.Compared with the control group findings,CBF significantly inhibited the formation of PC3 cells (P =.005).Flow cytometry revealed that after treatment with 50 nM CBF for 48 hours,the apoptotic rate of PC3 cells was 41.97 (5.16)%,indicating that CBF could significantly induce its apoptosis (P =.003).In addition,optical and fluorescence microscopy uncovered remarkable inhibition of cell proliferation accompanied by morphologic changes.The western blotting result indicated that CBF obviously downregulated the expression of the anti-apoptotic protein MCL-1.Most importantly,ClBF reduced the carcinogenicity of PC3 xenografts in nude mice.Conclusion:CBF can inhibit the growth of PC3 cells both in vitro and in vivo and induce apoptosis of tumor cells.The corresponding mechanism may be correlated with the activation of caspase family proteins via MCL-1.

Single-domain antibodies as therapeutics for solid tumor treatment

Single-domain antibodies(sdAbs),initially identified in camelids or sharks and commonly referred to as nanobodies or VNARs,have emerged as a promising alternative to conventional therapeutic antibodies.These sdAbs have many superior physicochemical and pharmacological properties,including small size,good solubility and thermostability,easier accessible epitopes,and strong tissue penetration.However,the inherent challenges associated with the animal origin of sdAbs limit their clinical use.In recent years,various innovative humanization technologies,including complementarity-determining region(CDR)grafting or complete engineering of fully human sdAbs,have been developed to mitigate potential immunogenicity issues and enhance their compatibility.This review provides a comprehensive exploration of sdAbs,emphasizing their distinctive features and the progress in humanization methodologies.In addition,we provide an overview of the recent progress in developing drugs and therapeutic strategies based on sdAbs and their potential in solid tumor treatment,such as sdAbedrug conjugates,multispecific sdAbs,sdAb-based delivery systems,and sdAb-based cell therapy.

Abundance and sources of particulate polycyclic aromatic hydrocarbons and aromatic acids at an urban site in central China

We conducted a simultaneous field study of PM_(2.5)-bound particulate polycyclic aromatic hydrocarbons(PAHs)and aromatic acids(AAs)in a polluted city Zhengzhou to explore the concentration,sources and potential conversion pathways between PAHs and AAs in different seasons.The average concentrations of PM_(2.5),28PAHs and 8AAs during the sampling period were 77μg/m^(3),75 ng/m^(3),and 283 ng/m^(3),respectively.The concentration of both28PAHs and 8AAs were highest in winter and lowest in summer with ratios of 6.3 and 2.3,respectively.PAHs with 5-7 rings were the main components of PAHs(52%),followed by 4rings PAHs(30%)and 2-3 rings PAHs(18%).According to the source appointment results obtained by positive matrix factorization,the main sources of PAHs were combustion and vehicle emissions,which account for 37%and 34%,respectively.8AAs were divided into three groups,including four benzene dicarboxylic acids(B2CAs),three benzene tricarboxylic acids(B3CAs)and one benzene tetracarboxylic acid(B4CA).And interspecies correlation analysis with PM_(2.5)source markers were used to investigate potential sources.Phthalic acid(o-Ph)was the most abundant specie of 8AAs(157 ng/m^(3),55%of 8AAs),which was well correlated with sulfate.Meanwhile,B3CAs and B4CA were highly correlated with sulfate and weakly correlated with levoglucosan,suggesting that secondary formation was their main source.As logical oxidation products of PAHs,o-Ph and B3CAs showed good correlations with a number of PAHs,indicating possible photochemical oxidation pathway by PAHs.In addition,O_(3),NO_(2),temperature and relative humidity have positive effects on the secondary formation of B3CAs.

Early Activation of Astrocytes does not Affect Amyloid Plaque Load in an Animal Model of Alzheimer's Disease

Astrocytes are closely associated with Alzheimer’s disease(AD). However, their precise roles in AD pathogenesis remain controversial. One of the reasons behind the different results reported by different groups might be that astrocytes were targeted at different stages of disease progression. In this study, by crossing h APP(human amyloid precursor protein)-J20 mice with a line of GFAP-TK mice, we found that astrocytes were activated specifically at an early stage of AD before the occurrence of amyloid plaques, while microglia were not affected by this crossing. Activation of astrocytes at the age of 3–5 months did not affect the proteolytic processing of hAPP and amyloid plaque loads in the brains of hAPP-J20 mice. Our data suggest that early activation of astrocytes does not affect the deposition of amyloid b in an animal model of AD.

Battery package design optimization for small electric aircraft

The increasing gross weight of electric Unmanned Aerial Vehicle(UAV) poses a challenge in practical applications. The range and endurance of the electric UAV are limited by the fixed mass of the battery package. In this work, a design optimization method for the battery package topology of small electric UAV is proposed to enhance the performance. To improve the accuracy of the method, the dynamic battery model and simplified electric component models are presented.These models are utilized by the trajectory optimization method, which takes the dynamic characteristic into consideration to calculate the aircraft performance. The direct optimal control method is used for solving the trajectory optimization problem, and this method is tested on a small blended-wing-body electric aircraft. The test result shows that the range and energy-consumption are mainly influenced by the parallel topology of the battery package, while the flight time in climb phase is more sensitive to the series topology. It is deduced that the range-and energy-optimal design points can be considered concurrently in design optimization. The work proves the feasibility of integrating the trajectory optimization and battery package design.

Assessment of piloting behavior impact on landing risk of transport aircraft

The human factors and their interaction with other factors play an important role in the flight safety of transport aircraft.In this paper,a paradigm of risk assessment for transport aircraft interacting with piloting behaviors is proposed,with focus on landing which is the most accident-prone flight stage in aviation safety statistics.Model-based flight simulation serves as our data source for landing risk analysis under uncertainties.A digital pilot in the loop that reflects the human piloting behaviors is employed to facilitate simulation efficiency.Eight types of unsafe events in landing are identified from statistics.On this basis,the landing safety boundary is extracted via stochastic simulation to divide safety and hazardous flight status domains,which con-tributes to flight status management and risk warning.The simulation results indicate that appro-priate piloting behavior,which is active response and fast target acquisition with minimum overshoot and fluctuation,shows benefit to landing safety.The subset simulation technique is employed to further refine the boundary with less computational workload.Furthermore,the effect of airspeed,windspeed,and other factors on landing risk is also discussed.The proposed risk assess-ment method would help optimize operation procedure and develop targeted pilot training program.