RESUMO
Particle dispersions have been widely studied inside rooms, but few databases have examined the transmission risk of respiratory droplets outdoors. This study investigated the wind effect on the dispersion of coughed droplets and the influence of social distancing on the infection risk in different susceptible persons using computational fluid dynamics simulations. Infection risk was evaluated based on direct depositions and exposure fractions. The results indicated that a reverse and upward flow formed in front of an infected man, and it enhanced as the wind strengthened, which transported more medium particles higher and increased the deposition on both infected and susceptible persons. Small particles moved above the neck, and they rarely deposited on the body. Medium particles larger than 60 µm were more likely to deposit and could reach the head of a healthy person under stronger winds. The exposure fraction achieved peak values when numerous particles passed the breathing zone. Although longer social distancing could alleviate the particle deposition on the face and delay the most dangerous time, its effect on infection risk was ambiguous. The infection risk was larger for a shorter susceptible person because more particles were deposited on the face, and the exposure fraction contributed by particles above the neck was larger.
RESUMO
Neuroinflammation plays an important role in the pathogenesis of Parkinson's disease (PD). Genistein is an estrogen-like phytoestrogen that can exert biological effects via the crosstalk of estrogen receptor and insulin-like growth factor 1 receptor (IGF-1R). The present study aimed to evaluate the involvement of G protein-coupled estrogen receptor (GPER) and IGF-1R in the anti-inflammatory effects of genistein against lipopolysaccharide (LPS)-induced nigrostriatal injury in ovariectomized rats. Our results showed that genistein treatment could ameliorate the apomorphine-induced rotational behavior in LPS-induced inflammatory PD rat model. Genistein attenuated LPS-induced decrease of the contents of dopamine (DA) and its metabolites in striatum as well as the loss of tyrosine hydroxylase-immunoreactive (TH-IR) neurons in the substantia nigra (SN) of the lesioned side, which could be blocked by GPER antagonist G15 or IGF-1R antagonist JB1. Meanwhile, G15 or JB1 could attenuate the anti-inflammatory effects of genistein in LPS-induced microglial activation and production of tumor necrosis factor-α (TNF-α), interleukin 1ß (IL-1ß), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, genistein could inhibit the LPS-induced phosphorylation of p38, JNK, ERK and IκB in the lesioned side of SN and these effects could also be blocked by G15 or JB1. Taken together, our data provide the first evidence that genistein can inhibit the increase of microglia and protect dopaminergic neurons at least in part via GPER and IGF-1R signaling pathways in ovariectomized PD rat model.
Assuntos
Genisteína/farmacologia , Lipopolissacarídeos/metabolismo , Microglia/efeitos dos fármacos , Receptor IGF Tipo 1/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Substância Negra/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Neurônios Dopaminérgicos/metabolismo , Feminino , Sistema de Sinalização das MAP Quinases , NF-kappa B/metabolismo , Doença de Parkinson/metabolismo , Ratos , Ratos Wistar , Transdução de SinaisRESUMO
Forkhead box M1(FoxM1) played an important role in the pathogenesis of ovarian cancer, but its downstream molecular network is mysterious. Here, we combined ChIP-seq with RNA-seq analysis and identified 687 FoxM1-binding regions and 182 genes regulated by FoxM1. The above data pointed out that KRT5 and KRT7 were downstream target genes of FoxM1. Next, we used qPCR and Western blot to verify that FoxM1 knockdown inhibited the expression levels of KRT5 and KRT7. We also demonstrated that FoxM1 regulated KRT5 and KRT7 genes expression through binding a consensus AP-2 cis element, and showed that KRT5 and KRT7 deficiency could prevent the migration but not proliferation of SK-OV-3 cells. Finally, tissue microarray results indicated that KRT5 and KRT7 were highly expressed in ovarian cancer and positively correlated with FoxM1 expression. TCGA database showed that high expression of KRT5 and KRT7 could significantly reduce the survival rate of patients with ovarian cancer. The above results clarify the specific downstream molecular network of FoxM1 to promote the pathogenesis of ovarian cancer, and provide a basis experiment for the judgment of ovarian cancer prognosis and the design of drug targets.
Assuntos
Movimento Celular , Proteína Forkhead Box M1/metabolismo , Queratina-5/metabolismo , Queratina-7/metabolismo , Neoplasias Ovarianas/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Feminino , Proteína Forkhead Box M1/genética , Humanos , Queratina-5/genética , Queratina-7/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologiaRESUMO
Based on magnetic field directed self-assembly (MDSA) of the ternary Fe3O4@PANI/rGO nanocomposites, a facile and controllable molecularly imprinted electrochemical sensor (MIES) was fabricated through a one-step approach for detection of glutathione (GSH). The ternary Fe3O4@PANI/rGO nanocomposites were obtained by chemical oxidative polymerization and intercalation of Fe3O4@PANI into the graphene oxide layers via π-π stacking interaction, followed by reduction of graphene oxide in the presence of hydrazine hydrate. In molecular imprinting process, the pre-polymers, including GSH as template molecule, Fe3O4@PANI/rGO nanocomposites as functional monomers and pyrrole as both cross-linker and co-monomer, was assembled through N-H hydrogen bonds and the electrostatic interaction, and then was rapidly oriented onto the surface of MGCE under the magnetic field induction. Subsequently, the electrochemical GSH sensor was formed by electropolymerization. In this work, the ternary Fe3O4@PANI/rGO nanocomposites could not only provide available functionalized sites in the matrix to form hydrogen bond and electrostatic interaction with GSH, but also afford a promoting network for electron transfer. Moreover, the biomimetic sensing membrane could be controlled more conveniently and effectively by adjusting the magnetic field strength. The as-prepared controllable sensor showed good stability and reproducibility for the determination of GSH with the detection limit reaching 3 nmol L(-1) (S/N = 3). In addition, the highly sensitive and selective biomimetic sensor has been successfully used for the clinical determination of GSH in biological samples.