Cell fusing agent virus (CFAV) was the first insect-specific virus to be characterized, and has been reported to negatively influence the growth of arboviruses such as dengue, Zika, and La Cross, ...making it a promising biocontrol agent for mosquito-borne disease prevention. Aedes aegypti Aag2 cells were naturally infected with CFAV. However, the ability of this virus to stably colonize an Ae. aegypti population via artificial infection and how it influences the vector competence of this mosquito have yet to be demonstrated. CFAV used in this study was harvested from Aag2 cells and its complete genome sequence was obtained by polymerase chain reaction and rapid amplification of complementary DNA ends, followed by Sanger sequencing. Phylogenetic analysis of newly identified CFAV sequences and other sequences retrieved from GenBank was performed. CFAV stock was inoculated into Ae. aegypti by intrathoracic injection, the survival of parental mosquitoes was monitored and CFAV copies in the whole bodies, ovaries, and carcasses of the injected F0 generation and in the whole bodies of the F1 generation on different days were examined by reverse transcription-quantitative polymerase chain reaction. The virus harvested from Aag2 cells comprised a mixture of three CFAV strains. All genome sequences of CFAV derived from Aag2 cells clustered into one clade but were far from those isolated or identified from Ae. aegypti. Aag2-derived CFAV efficiently replicated in the mosquito body and did not attenuate the survival of Ae. aegypti. However, the viral load in the ovarian tissues was much lower than that in other tissues and the virus could not passage to the offspring by vertical transmission. The results of this study demonstrate that Aag2-derived CFAV was not vertically transmitted in Ae. aegypti and provide valuable information on the colonization of mosquitoes by this virus.
Brucea javanica oil emulsion (BJOE) is a compound Chinese medicine used for treating various cancers, such as lung cancer. However, the exact mechanism of its antilung cancer active ingredient ...remains unclear. This study aims to explore and validate the effective active ingredients and mechanism of action of BJOE in the treatment of lung cancer through network pharmacology, molecular docking technology, and cell experiments. The results showed that there were 13 active ingredients, 136 target genes, and 42 disease target-coexpressed genes in BJOE. The molecular docking results indicated that the main active components of the oil emulsion, YD1 (β-sitosterol), YD2 (luteolin), and YD3 (bruceitol), could stably bind to TP53 and MAPK1. Furthermore, the commercially available β-sitosterol luteolin was used as a representative compound to conduct cell experiments to verify its anticancer activity and mechanism. It was found that luteolin can inhibit the proliferation better than β-sitosterol and the activity of lung cancer cells by regulating the expression of related proteins through the P53/MAPK1 signaling pathway. This study combines network pharmacology prediction with experiments to demonstrate the “multicomponent, multitarget, multipathway” approach of B. javanica oil emulsion in treating lung cancer.
Mannan-binding lectin (MBL) is a pattern-recognition molecule that plays a crucial role in innate immunity. MBL deficiency correlates with an increased risk of chronic kidney disease (CKD). However, ...the molecular mechanisms are not fully defined. Here, we established a CKD model in wild-type (WT) and MBL-deficient (MBL−/−) mice via unilateral ureteral obstruction (UUO). The result showed that MBL deficiency aggravated the pathogenesis of renal fibrosis in CKD mice. Strikingly, the in vivo macrophage depletion investigation revealed that macrophages play an essential role in the MBL-mediated suppression of renal fibrosis. We found that MBL limited the progression of macrophage-to-myofibroblast transition (MMT) in kidney tissues of UUO mice. Further in vitro study showed that MBL−/− macrophages exhibited significantly increased levels of fibrotic-related molecules compared with WT cells upon transforming growth factor beta (TGF-β) stimulation. We demonstrated that MBL inhibited the MMT process by suppressing the production of matrix metalloproteinase 9 (MMP-9) and activation of Akt signaling. In summary, our study revealed an expected role of MBL on macrophage transition during renal fibrosis, thus offering new insight into the potential of MBL as a therapeutic target for CKD.
The problem of radar constant-modulus (CM) waveform design for the detection of multiple targets is considered in this paper. The CM constraint is imposed from the perspective of hardware realization ...and full utilization of the transmitter's power. Two types of CM waveforms — the arbitrary-phase waveform and the quadrature phase shift keying waveform — are obtained by maximizing the minimum of the signal-to-clutter-plus-noise ratios of the various targets. Numerical results show that the designed CM waveforms perform satisfactorily, even when compared with their counterparts without constraints on the peak-to-average ratio.
Mannan-binding lectin (MBL) is a vital element in the host innate immune system, which is primarily produced by the liver and secreted into the circulation. Low serum level of MBL is reported to be ...associated with an increased risk of arthritis. However, the underlying mechanism by which MBL contributes to the pathogenesis of arthritis is poorly understood. In this study, we investigated the precise role of MBL on the course of experimental murine adjuvant-induced arthritis (AIA). MBL-deficient (MBL
) AIA mice showed significantly increased inflammatory responses compared with wild-type C57BL/6 AIA mice, including exacerbated cartilage damage, enhanced histopathological features and high level of tartrate-resistant acid phosphatase (TRAP)-positive cells. MBL protein markedly inhibited the osteoclast formation from human blood monocytes induced by receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF)
. Mechanistic studies established that MBL inhibited osteoclast differentiation
down-regulation of p38 signaling pathway and subsequent nuclear translocation of c-fos as well as activation of nuclear factor of activated T-cells c1 (NFATc1) pathway. Importantly, we have provided the evidence that concentrations of MBL correlated negatively with the serum levels of amino-terminal propeptide of type I procollagen (PINP) and C-terminal telopeptide of type I collagen (β-CTX), serum markers of bone turnover, in patients with arthritis. Our study revealed an unexpected function of MBL in osteoclastogenesis, thus providing new insight into inflammatory arthritis and other bone-related diseases in patients with MBL deficiency.
Aberrant fibroblast growth factor receptor-1 (FGFR1), a key driver promoting gastric cancer (GC) progression and chemo-resistance, has been increasingly recognized as a potential therapeutic target ...in GC. Hereon, we designed and synthesized a series of asymmetric analogues using
Af23
and NDGA as lead compounds by retaining the basic structural framework (bisaryl-1,4-dien-3-one) and the unilateral active functional groups (3,4-dihydroxyl). Thereinto,
Y14
showed considerable inhibitory activity against FGFR1. Next, pharmacological experiments showed that
Y14
could significantly inhibit the phosphorylation of FGFR1 and its downstream kinase AKT and ERK, thus inhibiting the growth, survival, and migration of gastric cancer cells. Furthermore, compared with 5-FU treatment alone, the combination of
Y14
and 5-FU significantly reduced the phosphorylation level of FGFR1, and enhanced the anti-cancer effect by inhibiting the viability and colony formation in two gastric cancer cell lines. These results confirmed that
Y14
exerted anti-gastric activity and chemosensitizing effect by inhibiting FGFR1 phosphorylation and its downstream signaling pathway
in vitro
. This work also provides evidence that
Y14
, an effective FGFR1 inhibitor, could be used alone or in combination with chemotherapy to treat gastric cancer in the future.
There is an ongoing trend to design new kinds of food packaging materials with excellent properties which are environmentally friendly enough. The aim of this study was to prepare and characterize ...egg white protein (EWP)-based composite films with and without ε-polylysine (Lys), as well as to compare their physical-chemical properties, structural properties, degradation and antibacterial properties. The results showed that with the addition of Lys, the composite films showed a decreasing tendency of the water permeability due to the enhanced interaction between proteins and water molecules. As indicated by the structural properties, stronger cross-linking and intermolecular interactions happened with increasing concentration of Lys. In addition, the composite films presented excellent antibacterial activities against
and
on chilled pork in the presence of Lys. Therefore, our prepared films might be used as a freshness-keeping material with an application in meat preservation. The biodegradation evaluation demonstrated that the composite films were environmental-friendly and have potential applications in the field of food packaging.
Drug-related problems (DRPs) are common among surgical patients, especially older patients with polypharmacy and underlying diseases. DRPs can potentially lead to morbidity, mortality, and increased ...treatment costs. The enhanced recovery after surgery (ERAS) system has shown great advantages in managing surgical patients. Medication therapy management for surgical patients (established as "surgical pharmacy" by Guangdong Province Pharmaceutical Association (GDPA)) is an important part of the ERAS system. Improper medication therapy management can lead to serious consequences and even death. In order to reduce DRPs further, and promote the rapid recovery of surgical patients, the need for pharmacists in the ERAS program is even more pressing. However, the medication therapy management services of surgical pharmacy and how surgical pharmacists should participate in ERAS programs are still unclear worldwide. Therefore, this article reviews the main perioperative medical management strategies and precautions from several aspects, including antimicrobial agents, antithrombotic agents, pain medication, nutritional therapy, blood glucose monitoring, blood pressure treatment, fluid management, treatment of nausea and vomiting, and management of postoperative delirium. Additionally, the way surgical pharmacists participate in perioperative medication management, and the relevant medication pathways are explored for optimizing medication therapy management services within the ERAS programs. This study will greatly assist surgical pharmacists' work, contributing to surgeons accepting that pharmacists have an important role in the multidisciplinary team, benefitting medical workers in treating, counseling, and advocating for their patients, and further improving the effectiveness, safety and economy of medication therapy for patients and promoting patient recovery.
AKT2 is one of the key molecules that involves in the insulin-induced signaling and the development of cancer. In B cells, the function of AKT2 is unclear.
In this study, we used AKT2 knockout mice ...model to study the role of AKT2 in BCR signaling and B cell differentiation.
AKT2 promotes the early activation of B cells by enhancing the BCR signaling and actin remodeling. B cells from AKT2 KO mice exhibited defective spreading and BCR clustering upon stimulation in vitro. Disruption of Btk-mediated signaling caused the impaired differentiation of germinal center B cells, and the serum levels of both sepecific IgM and IgG were decreased in the immunized AKT2 KO mice. In addition, the actin remodeling was affected due to the decreased level of the activation of WASP, the actin polymerization regulator, in AKT2 KO mice as well. As a crucial regulator of both BCR signaling and actin remodeling during early activation of B cells, the phosphorylation of CD19 was decreased in the AKT2 absent B cells, while the transcription level was normal.
AKT2 involves in the humoral responses, and promotes the BCR signaling and actin remodeling to enhance the activation of B cells via regulating CD19 phosphorylation. Video Abstract.
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