Synergistic treatment of osteosarcoma with biomimetic nanoparticles transporting doxorubicin and siRNA

IntroductionOsteosarcoma tumors are the most common malignant bone tumors in children and adolescents. Their treatment usually requires surgical removal of all detectable cancerous tissue and multidrug chemotherapy; however, the prognosis for patients with unresectable or recurrent osteosarcoma is unfavorable. To make chemotherapy safer and more effective for osteosarcoma patients, biomimetic nanoparticles (NPs) camouflaged by mesenchymal stem cell membranes (MSCMs) were synthesized to induce osteosarcoma cell apoptosis by co-delivering the anticancer drug doxorubicin hydrochloride(DOX) and a small interfering RNA (siRNA). Importantly, these NPs have high biocompatibility and tumor-homing ability. This study aimed to improve the efficacy of osteosarcoma therapy by using the synergistic combination of DOX and an siRNA targeting the apoptosis suppressor gene survivin.MethodsBiomimetic NPs (DOX/siSUR-PLGA@MSCM NPs) were synthesized by coloading DOX and survivin siRNA (siSUR) into poly (lactide-co-glycolide acid) (PLGA) via a double-emulsion solvent evaporation method. The NPs were camouflaged by MSCMs to deliver both DOX and survivin-targeting siRNA and characterized and evaluated in terms of cellular uptake, in vitro release, in vitro and in vivo antitumor effects, and biosafety.ResultsDOX/siSUR-PLGA@MSCM NPs had good tumor-homing ability due to the MSCMs modification. The drug-laden biomimetic NPs had good antitumor effects in homozygous MG63 tumor-bearing mice due to the synergistic effect of the drug combination.ConclusionDOX/siSUR-PLGA@MSCM NPs can show improved therapeutic effects in osteosarcoma patients due to the combination of a chemotherapeutic drug and gene therapy based on their good tumor targeting and biosafety

Clinical research on RSV prevention in children and pregnant women: progress and perspectives

Respiratory syncytial virus (RSV) is a significant causative agent of bronchitis and pneumonia in infants and children. The identification and structural analysis of the surface fusion glycoprotein of RSV represents a pivotal advancement in the development of RSV prevention. This review provides a comprehensive summary of RSV monoclonal antibody (mAb) and vaccine clinical trials registered on ClinicalTrials.gov, emphasizing on the classification, name, target, phase, clinical outcomes, and safety data of RSV vaccination in newborns, infants and children. We also discuss the characteristics of the types of RSV vaccines for maternal immunity and summarize the current clinical research progress of RSV vaccination in pregnant women and their protective efficacy in infants. This review will provide new ideas for the development of RSV prevention for children in the future

Effects of Veratrilla baillonii Extract on Hepatic Gene Expression Profiles in Response to Aconitum brachypodum-Induced Liver Toxicity in Mice

This manuscript was aimed to explore the hepato-protective effect of water extract of Veratrilla baillonii Franch. (Gentianaceae) (WVBF) on serious hepatic toxicity induced in mice treated with Aconitum brachypodum Diels (Ranunculaceae) at transcriptome level. The physiological and pathological symptoms were evaluated as the markers for hepato toxicity induced by A. brachypodum Diels (CFA) extracted compounds. Moreover, gene chip method was used to compare and investigate the gene expression level of WVBF on CFA induced-liver toxicity to identify the potential target of WVBF and CFA on liver. The results showed that WVBF had a significant detoxification effect on CFA-induced acute hepatic toxicity. There were 130 genes with lower expression and 124 genes expressed at higher rate in CFA treated group as compared with normal control group, while there are 67 genes down-regulated and 74 genes up-regulated in WVBF treated group in comparison with CFA treated group. WVBF could attenuate CFA-induced liver damage in mice through regulating oxidative stress, inflammatory injury and cell apoptosis/necrosis pathways. On the other hand, WVBF and CFA may have potential synergetic effects on the target genes of certain diseases such as inflammation, cancer and diabetes

Characteristics of Biohydrogen Production and Performance of Hydrogen-Producing Acetogen by Increasing Normal Molasses Wastewater Proportion in Anaerobic Baffled Reactor

The biohydrogen production efficiency and performance of hydrogen-producing acetogen in a four-compartment anaerobic baffled reactor (ABR) were studied by gradually increasing the influent normal molasses wastewater (NMWW) proportion. When the influent NMWW proportion increased to 55%, ABR could develop microbial community with methanogenic function in 63 days and reach a stable operation. When the influent NMWW proportion increased to 80% and reached a stable state, ethanol fermentation was established from butyric acid fermentation in the first three compartments, whereas butyric acid fermentation in the fourth compartment was strengthened. The average biohydrogen production yield and biohydrogen production capacity by COD removal increased to as high as 12.85 L/day and 360.22 L/kg COD when the influent NMWW proportion increased from 55% to 80%, respectively. Although the biogas yield and the specific biogas production rate reached 61.54 L/day and 232 L/kg MLVSS·day, the biohydrogen production yield and specific biohydrogen production rate were only 12.85 L/day and 48 L/kg MLVSS·day, which results in hydrogen consumption by homoacetogenesis and methanogenesis

Aberrant Amplitude of Low-Frequency Fluctuation and Degree Centrality within the Default Mode Network in Patients with Vascular Mild Cognitive Impairment

This study aimed to investigate whole-brain spontaneous activities changes in patients with vascular mild cognitive impairment (VaMCI), and to evaluate the relationships between these brain alterations and their neuropsychological assessments. Thirty-one patients with VaMCI and thirty-one healthy controls (HCs) underwent structural MRI and resting-state functional MRI (rs-fMRI) and neuropsychological assessments. The functional alterations were determined by the amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC). The gray matter volume (GMV) changes were analyzed using voxel-based morphometry (VBM). Linear regression analysis was used to evaluate the relationships between the structural and functional changes of brain regions and neuropsychological assessments. The VaMCI group had significantly lower scores in the Montreal Cognitive Assessment (MoCA), and higher scores on the Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD). Compared to the HCs, the VaMCI group exhibited GM atrophy in the right precentral gyrus (PreCG) and right inferior temporal gyrus (ITG). VaMCI patients further exhibited significantly decreased brain activity within the default mode network (DMN), including the bilateral precuneus (PCu), angular gyrus (AG), and medial frontal gyrus (medFG). Linear regression analysis revealed that the decreased ALFF was independently associated with lower MoCA scores, and the GM atrophy was independently associated with higher HAMD scores. The current finding suggested that aberrant spontaneous brain activity in the DMN might subserve as a potential biomarker of VaMCI, which may highlight the underlying mechanism of cognitive decline in cerebral small vessel disease

Improved Adaptive Federated Kalman Filtering for INS/GNSS/VNS Integrated Navigation Algorithm

To address the issue of low positioning accuracy in unmanned vehicles navigating in obstructed spaces due to easily contaminated navigation measurement information, an improved adaptive federated Kalman filtering INS/GNSS/VNS integrated navigation algorithm is proposed. In this algorithm, an inertial navigation system (INS) serves as the common reference system, and, together with the global navigation satellite system (GNSS) and visual navigation system (VNS), they form the subsystems that together make up the main system. In the event of faulty measurement values in the subsystems, a combination of the residual chi-square and sliding-window averaging methods are used for fault detection to improve the fault tolerance of the integrated navigation algorithm. Additionally, an adaptive sharing factor is proposed to adjust the accuracy of the integrated navigation algorithm based on the accuracy of the sub-filters. Simulation experiments demonstrated that, compared with classic federated Kalman filtering, the proposed algorithm reduced the root mean square errors (RMSEs) of the three-dimensional position by 56.4%, 54.8%, and 43.4% and the root mean square errors of the three-dimensional velocity by 71.0%, 72.1%, and 28.4% in the event of sub-filter faults, effectively solving the problem of low positioning accuracy for unmanned vehicles in obstructed spaces while ensuring the real-time performance of the system