The re-emergence of Zika virus (ZIKV) in the Western Hemisphere has resulted in global public health crisis since 2015. ZIKV preferentially infects and targets human neural progenitor cells (hNPCs) ...and causes fetal microcephaly upon maternal infection. hNPCs not only play critical roles during fetal brain development, but also persist in adult brain throughout life. Yet the mechanism of innate antiviral immunity in hNPCs remains largely unknown. Here, we show that ZIKV infection triggers the abundant production of virus-derived small interfering RNAs in hNPCs, but not in the more differentiated progenies or somatic cells. Ablation of key RNAi machinery components significantly enhances ZIKV replication in hNPCs. Furthermore, enoxacin, a broad-spectrum antibiotic that is known as an RNAi enhancer, exerts potent anti-ZIKV activity in hNPCs and other RNAi-competent cells. Strikingly, enoxacin treatment completely prevents ZIKV infection and circumvents ZIKV-induced microcephalic phenotypes in brain organoid models that recapitulate human fetal brain development. Our findings highlight the physiological importance of RNAi-mediated antiviral immunity during the early stage of human brain development, uncovering a novel strategy to combat human congenital viral infections through enhancing RNAi.
Development of fluoroquinolone resistance can involve several mechanisms that include chromosomal mutations in genes (
gyrAB
and
parCE
) encoding the target bacterial topoisomerase enzymes, increased ...expression of the AcrAB-TolC efflux system, and acquisition of transmissible quinolone-resistance genes. In this study, 176
Salmonella
isolates from animals with a broad range of ciprofloxacin MICs were collected to analyze the contribution of these different mechanisms to different phenotypes. All isolates were classified according to their ciprofloxacin susceptibility pattern into five groups as follows: highly resistant (HR), resistant (R), intermediate (I), reduced susceptibility (RS), and susceptible (S). We found that the ParC T57S substitution was common in strains exhibiting lowest MICs of ciprofloxacin while increased MICs depended on the type of GyrA mutation. The ParC T57S substitution appeared to incur little cost to bacterial fitness on its own. The presence of PMQR genes represented an route for resistance development in the absence of target-site mutations. Switching of the plasmid-mediated quinolone resistance (PMQR) gene location from a plasmid to the chromosome was observed and resulted in decreased ciprofloxacin susceptibility; this also correlated with increased fitness and a stable resistance phenotype. The overexpression of AcrAB-TolC played an important role in isolates with small decreases in susceptibility and expression was upregulated by MarA more often than by RamA. This study increases our understanding of the relative importance of several resistance mechanisms in the development of fluoroquinolone resistance in
Salmonella
from the food chain.
Treadmill exercise and mesenchymal stem cell transplantation are both practical and effective methods for the treatment of cerebral ischemia. However, whether there is a synergistic effect between ...the two remains unclear. In this study, we established rat models of ischemia/reperfusion injury by occlusion of the middle cerebral artery for 2 hours and reperfusion for 24 hours. Rat models were perfused with bone marrow mesenchymal stem cell-derived exosomes (MSC-exos) via the tail vein and underwent 14 successive days of treadmill exercise. Neurological assessment, histopathology, and immunohistochemistry results revealed decreased neuronal apoptosis and cerebral infarct volume, evident synaptic formation and axonal regeneration, and remarkably recovered neurological function in rats subjected to treadmill exercise and MSC-exos treatment. These effects were superior to those in rats subjected to treadmill exercise or MSC-exos treatment alone. Mechanistically, further investigation revealed that the activation of JNK1/c-Jun signaling pathways regulated neuronal apoptosis and synaptic-axonal remodeling. These findings suggest that treadmill exercise may exhibit a synergistic effect with MSC-exos treatment, which may be related to activation of the JNK1/c-Jun signaling pathway. This study provides novel theoretical evidence for the clinical application of treadmill exercise combined with MSC-exos treatment for ischemic cerebrovascular disease.
Wind erosion is the main form of soil erosion in arid and semiarid areas. It leads to soil loss and land degradation, which aggravates ecosystem vulnerability and threatens regional sustainable ...development. Exploring wind erosion and associating driving factors can provide useful information to reduce soil wind erosion and solve corresponding environmental problems. Southern Africa is characterized with severe soil wind erosion, which has brought a series of socioeconomic issues, such as food crises and poverty. This study used meteorological and remote sensing data, and the revised wind erosion equation (RWEQ) model to explore the spatio‐temporal dynamics of soil erosion in Southern Africa from 1991 to 2015. The impact of climate change on soil wind erosion was also analyzed. The results showed that wind erosion fluctuated during the study period, which first showed a downward trend and then stabilized at a relatively low level after 2010. Soil wind erosion across 66.65% of the study area significantly decreased (p < .05) and near‐surface wind speed was the most important influencing factor. The decrease of wind speed can significantly reduce the soil wind erosion across 39.89% of the study area. Temperature and precipitation were significantly related to soil wind erosion over 18.96% and 24.63% of the study area, respectively. Both can indirectly affect soil wind erosion through their impacts on vegetation cover. This study will help decision‐makers to identify high‐risk areas for soil erosion in Southern Africa and to take countermeasures effectively.
Endocrine resistance is a major obstacle to hormonal therapy for breast cancers. Although reduced expression of estrogen receptor-α (ER-α) is a known contributing factor to endocrine resistance, the ...mechanism of ER-α downregulation in endocrine resistance is still not fully understood. Here we report that CUE domain-containing protein-2 (CUEDC2), a ubiquitin-binding motif-containing protein, is a key factor in endocrine resistance in breast cancer. We show that CUEDC2 modulates ER-α protein stability through the ubiquitin-proteasome pathway. Through the study of specimens from a large cohort of subjects with breast cancer, we found a strong inverse correlation between CUEDC2 and ER-α protein expression. Notably, subjects with tumors that highly expressed CUEDC2 had poor responsiveness to tamoxifen treatment and high potential for relapse. We further show that ectopic CUEDC2 expression impaired the responsiveness of breast cancer cells to tamoxifen. Therefore, our findings suggest that CUEDC2 is a crucial determinant of resistance to endocrine therapies in breast cancer.
Motivated by quantum statistical mechanics, we propose an accurate analytical solution to the problem of Bose–Einstein condensation (BEC) of ideal bosons in a two-dimensional anisotropic harmonic ...trap. The study reveals that the number of noncondensed bosons is characterized by an analytical function, which relates to a series expansion of q-digamma functions in mathematics. The q-digamma function is a function of temperature, boson number, and anisotropic parameter. The analytical solution describes fully the experimental results of the BEC of ideal bosons in a two-dimensional anisotropic harmonic trap. We derive the analytical expressions of the critical temperature and the condensate fraction in the thermodynamic limit. The first main conclusion is that for a fixed temperature and boson number, there is a critical anisotropic parameter, which is the precise onset of BEC in this harmonically trapped two-dimensional system. The second main conclusion is that the critical temperature in a two-dimensional anisotropic harmonic trap is larger than that in a two-dimensional isotropic harmonic trap.
Our experimental scheme is based on a barrel optical microcavity filled with a dye solution. It is found that the number of non-condensed photons is characterized by an analytical function, which ...involves a
q
-digamma function in mathematics. We employ the
q
-digamma function to calculate the spatial and momentum distributions of ideal photons in a one-dimensional barrel cavity. The first main finding in this paper is that the spatial and momentum distributions possess a similar profile. The second main finding is that when photons are in the normal state, the density profile exhibits Friedel oscillations. The third main finding is that when photons are in the BEC state, the density profile exhibits a sharp peak with extremely narrow width. The fourth main finding is that the central peak of the density distribution is a monotonically increasing function of the photon number
N
but is a monotonically decreasing function of the temperature
T
.
Driver modeling is important for both automobile industry and intelligent transportation. One of its key topics has been studied in this paper, i.e., the style-oriented driver modeling for speed ...control, and a modeling scheme based on distal learning control and real-world vehicle test data (VTD) is proposed to make this possible. The driver model adapts to be an inverse model of the vehicle at run, which is accomplished under the distal guidance of the discrepancy between the actual and the desired vehicle speed. To tackle the divergence and local mutability of real-world vehicle data, the partly connected multilayered perceptron (PCMLP), which is a locally designed neural network, is utilized to fulfill the imitating of human operations on gas or brake pedals during real-world driving. The FTP-75 driving cycles are borrowed to test the established driver models, and driving styles of the original human drivers are retained and reproduced while accomplishing the speed following task. Simulations are conducted to verify the effectiveness of the proposed scheme.
The aim of this study was to elucidate the prevalence of blaCTX-M-27-producing Escherichia coli and transmission mechanisms of blaCTX-M-27 from swine farms in China. A total of 333 E. coli isolates ...were collected from two farms from 2013 to 2016. Thirty-two CTX-M-27-positive E. coli were obtained, and all were multidrug-resistant. Pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) profiles indicated a wide range of strain types that carried blaCTX-M-27, and the sequence type ST10 predominated. Conjugation, replicon typing, S1-PFGE and hybridization experiments confirmed that 28 out of 32 CTX-M-27 positive isolates carried blaCTX-M-27 genes on plasmids F18:A-:B10 (16) and F24:A-:B1 (12).The blaCTX-M-27 genes for 24 isolates were transmitted by plasmids with sizes ranging from 40 to 155 kb. A comparative analysis with blaCTX-M-27-plasmids indicated that the tra-trb region of F24:A-:B1 plasmids was destroyed by insertion of a complex region (eight isolates) and a novel structure containing blaCTX-M-27 in the F18:A-:B10 plasmids (12 isolates). The novel structure increased the stability of the blaCTX-M-27 gene in E. coli. This study indicated that the predominant vehicle for blaCTX-M-27 transmission has diversified over time and that control strategies to limit blaCTX-M-27 transmission in farm animals are necessary.
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