The ability to control the instantaneous state of light, from high-energy pulses down to the single-photon level, is an indispensable requirement in photonics. This has, for example, facilitated ...spatiotemporal probing and coherent control of ultrafast light-matter interactions, and enabled capabilities such as generation of exotic states of light with complexity, or at wavelengths, that are not easily accessible. Here, by leveraging the multifunctional control of light at the nanoscale offered by metasurfaces embedded in a Fourier transform setup, we present a versatile approach to synthesize ultrafast optical transients with arbitrary control over its complete spatiotemporal evolution. Our approach, supporting an ultrawide bandwidth with simultaneously high spectral and spatial resolution, enables ready synthesis of complex states of structured space-time wave packets. We expect our results to offer unique capabilities in coherent ultrafast light-matter interactions and facilitate applications in microscopy, communications, and nonlinear optics.
Arbitrary space-time wave packets over an ultrawide bandwidth are synthesized using metasurface optics.
Liquid nitrogen has been proposed to promote fracture networks generated by hydraulic fracturing in geothermal reservoirs. To compare the deterioration in mechanical properties due to water and ...liquid nitrogen cooling under conditions of high temperatures and confining pressures, three stress thresholds (crack initiation stress, crack damage stress, and peak stress) of granite were studied by performing triaxial compression tests (under 0, 20, 40, 50, and 60 MPa) after heating and rapid cooling. The relationships between the three stress thresholds and the confining pressures were analyzed. The effects of different cooling treatments on the stress thresholds were analyzed under different confining pressures. The thermal damage mechanism and confining pressure effect were revealed. For both rapid cooling treatments, the three stress thresholds showed convex nonlinear relationships with the confining pressure. The temperature sensitivity on the stress thresholds can be weakened by confining pressure. Under low confining pressures (< 40 MPa), the three stress thresholds of samples cooled by liquid nitrogen were higher than those by water, and the differences were suppressed at higher confining pressures. The higher mechanical properties observed under liquid nitrogen were due to the heat transfer restriction by the Leidenfrost effect and the crack closure induced by volumetric contraction. A higher thermal expansion heterogeneity contributed to the complexity of cracks induced by liquid nitrogen. Under high confining pressures (> 40 MPa), there was a trend that the stress thresholds of samples cooled by liquid nitrogen were lower than those by water, which was related to cohesion.
3D concrete printing technology has enabled the construction of full-scale bridges. However, structural carbon emissions due to higher cement content and limitations of embedded reinforcement have ...limited its widespread adoption. This paper presents a non-reinforced 3D printed concrete box arch bridge and describes its design, construction, dismantlement, and reconstruction, as well as evaluation of the carrying capacity of reconstructed primary arch ring. The bridge adheres to current technical principles and bridge engineering specifications. By taking into account the mechanical anisotropy and primary stress characteristics of the arch, the design negates the need for reinforcement. The study showcases the reusability and potential carbon emission reduction through block printing, on-site assembly, block removal, and secondary usage. The safety of the reconstructed arch bridge was confirmed through an in-situ load test.
Highly virulent Streptococcus suis (S. suis) infections can cause Streptococcal toxic shock-like syndrome (STSLS) in pigs and humans, in which an excessive inflammatory response causes severe damage. ...Hemolysin (SLY) is a major virulence factor of S. suis serotype 2 that produces pores in the target cell membrane, leading to cytoplasmic Ksup.+ efflux and activation of the NLRP3 inflammasome, ultimately causing STSLS. The critical aspect of hemolysin in the pathogenesis of S. suis type 2 makes it an attractive target for the development of innovative anti-virulence drugs. Here, we use the S. suis toxin protein (SLY) as a target for virtual screening. A compound called canagliflozin, a hypoglycemic agent, was identified through screening. Canagliflozin significantly inhibits the hemolytic activity of hemolysin. The results combined with molecular dynamics simulation, surface plasmon resonance, and nano differential scanning fluorimetry show that canagliflozin inhibits the hemolytic activity of SLY by binding to SLY. In addition, canagliflozin markedly reduced the release of SC19-induced inflammatory factors at the cellular level and in mice. Importantly, the combination of canagliflozin and ampicillin had a 90% success rate in mice, significantly greater than the therapeutic effect of ampicillin. The findings suggest that canagliflozin may be a promising new drug candidate for S. suis infections.
Upon publication of the original article 1, the authors noticed that they omitted Additional file 16: Table S10 from the Additional file list. Additional file 16: Table S10 can be found attached to ...this Correction and the caption of this Additional file can be found below.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Type VI secretion system (T6SS) functions as a protein transport nanoweapon in several stages of bacterial life. Even though bacterial competition is the primary function of T6SS, different ...bacteria exhibit significant variations. Particularly in Extraintestinal pathogenic Escherichia coli (ExPEC), research into T6SS remains relatively limited. This study identified the uncharacterized gene evfG within the T6SS cluster of ExPEC RS218. Through our experiments, we showed that evfG is involved in T6SS expression in ExPEC RS218. We also found evfG can modulate T6SS activity by competitively binding to c-di-GMP, leading to a reduction in the inhibitory effect. Furthermore, we found that evfG can recruit sodA to alleviate oxidative stress. The research shown evfG controls an array of traits, both directly and indirectly, through transcriptome and additional tests. These traits include cell adhesion, invasion, motility, drug resistance, and pathogenicity of microorganisms. Overall, we contend that evfG serves as a multi-functional regulator for the T6SS and several crucial activities. This forms the basis for the advancement of T6SS function research, as well as new opportunities for vaccine and medication development.
Male infertility, age-related changes, and tumors have been increasingly studied in the field of male reproductive health due to the emergence of environmental stressors, declining fertility rates, ...and aging populations. Numerous studies have demonstrated that the ERK1/2 signaling pathway plays a significant role in male reproduction. The ERK1/2 pathway is associated with several signaling pathways and has a complex interplay that influences the spermatogenic microenvironment, sperm viability, gonadal axis regulation, as well as resistance to testicular aging and tumors. Moreover, the ERK1/2 pathway directly or indirectly regulates testicular somatic cells, which are crucial for maintaining spermatogenesis and microenvironment regulation. Given the critical role of the ERK1/2 signaling pathway in male reproductive health, comprehensive exploration of its multifaceted effects on male reproduction and underlying mechanisms is necessary. This study aims to provide a solid foundation for in-depth research in the field of male reproduction and further enhance the reproductive health of males.
Influenza activity is subject to environmental factors. Accurate forecasting of influenza epidemics would permit timely and effective implementation of public health interventions, but it remains ...challenging. In this study, we aimed to develop random forest (RF) regression models including meterological factors to predict seasonal influenza activity in Jiangsu provine, China. Coefficient of determination (R2) and mean absolute percentage error (MAPE) were employed to evaluate the models' performance. Three RF models with optimum parameters were constructed to predict influenza like illness (ILI) activity, influenza A and B (Flu-A and Flu-B) positive rates in Jiangsu. The models for Flu-B and ILI presented excellent performance with MAPEs <10%. The predicted values of the Flu-A model also matched the real trend very well, although its MAPE reached to 19.49% in the test set. The lagged dependent variables were vital predictors in each model. Seasonality was more pronounced in the models for ILI and Flu-A. The modification effects of the meteorological factors and their lagged terms on the prediction accuracy differed across the three models, while temperature always played an important role. Notably, atmospheric pressure made a major contribution to ILI and Flu-B forecasting. In brief, RF models performed well in influenza activity prediction. Impacts of meteorological factors on the predictive models for influenza activity are type-specific.
Aims
This study aimed to illuminate the neuropathological landscape of attention deficit hyperactivity disorder (ADHD) by a multiscale macro–micro‐molecular perspective from in vivo neuroimaging ...data.
Methods
The “ADHD‐200 initiative” repository provided multi‐site high‐quality resting‐state functional connectivity (rsfc‐) neuroimaging for ADHD children and matched typically developing (TD) cohort. Diffusion mapping embedding model to derive the functional connectome gradient detecting biologically plausible neural pattern was built, and the multivariate partial least square method to uncover the enrichment of neurotransmitomic, cellular and chromosomal gradient‐transcriptional signatures of AHBA enrichment and meta‐analytic decoding.
Results
Compared to TD, ADHD children presented connectopic cortical gradient perturbations in almost all the cognition‐involved brain macroscale networks (all pBH <0.001), but not in the brain global topology. As an intermediate phenotypic variant, such gradient perturbation was spatially enriched into distributions of GABAA/BZ and 5‐HT2A receptors (all pBH <0.01) and co‐varied with genetic transcriptional expressions (e.g. DYDC2, ATOH7, all pBH <0.01), associated with phenotypic variants in episodic memory and emotional regulations. Enrichment models demonstrated such gradient‐transcriptional variants indicated the risk of both cell‐specific and chromosome‐ dysfunctions, especially in enriched expression of oligodendrocyte precursors and endothelial cells (all pperm <0.05) as well enrichment into chromosome 18, 19 and X (pperm <0.05).
Conclusions
Our findings bridged brain macroscale neuropathological patterns to microscale/cellular biological architectures for ADHD children, demonstrating the neurobiologically pathological mechanism of ADHD into the genetic and molecular variants in GABA and 5‐HT systems as well brain‐derived enrichment of specific cellular/chromosomal expressions.
Exploring novel antimicrobial drugs and strategies has become essential to the fight MRSA-associated infections. Herein, we found that membrane-disrupted repurposed antibiotic salifungin had ...excellent bactericidal activity against MRSA, with limited development of drug resistance. Furthermore, adding salifungin effectively decreased the minimum inhibitory concentrations of clinical antibiotics against Staphylococcus aureus. Evaluations of the mechanism demonstrated that salifungin disrupted the level of H+ and K+ ions using hydrophilic and lipophilic groups to interact with bacterial membranes, causing the disruption of bacterial proton motive force followed by impacting on bacterial the function of the respiratory chain and adenosine 5′-triphosphate, thereby inhibiting phosphatidic acid biosynthesis. Moreover, salifungin also significantly inhibited the formation of bacterial biofilms and eliminated established bacterial biofilms by interfering with bacterial membrane potential and inhibiting biofilm-associated gene expression, which was even better than clinical antibiotics. Finally, salifungin exhibited efficacy comparable to or even better than that of vancomycin in the MRSA-infected animal models. In conclusion, these results indicate that salifungin can be a potential drug for treating MRSA-associated infections.
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