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Fe3O4nanoparticles are the most widely used magnetic nanoparticles in the biomedicine field. The biodistribution of most nanoparticles in vivo is determined by the capture of macrophages; however, the effects of nanoparticles on macrophages remain poorly understood. Here, we demonstrated that Fe3O4nanoparticles could reduce macrophage viability after 48 h of treatment and induce a shift in macrophage polarization toward the M1 phenotype; RNA sequencing revealed the activation of the ferroptosis pathway and p53upregulation compared to the control group. The expression in p53, xCT, glutathione peroxidase 4 (GPX4), and transferrin receptor (TFR) in macrophages was similar to that in erastin-induced ferroptosis in macrophages, and the ultrastructural morphology of mitochondria was consistent with that of erastin-treated cells. We used DCFH-DA to estimate the intracellular reactive oxygen species content in Fe3O4nanoparticles treated with Ana-1 and JC-1 fluorescent probes to detect the mitochondrial membrane potential change; both showed to be time-dependent. Fer-1 inhibited the reduction of the glutathione/oxidized glutathione (GSH/GSSG) ratio and inhibited intracellular oxidative stress states; therefore, Fe3O4nanoparticles induced ferroptosis in macrophages. Finally, we used pifithrin-α hydrobromide (PFT) as a p53 inhibitor to verify whether the high expression of p53 is involved in mediating this process. After PFT treatment, the live/dead cell rate, TFR, p53 expression, and GPX4 consumption were inhibited and mitigated the GSH/GSSG ratio reduction as well. This indicates that p53 may contribute to Fe3O4nanoparticle-induced ferroptosis of macrophages. We provide a theoretical basis for the molecular mechanisms of ferroptosis in macrophages and the biotoxicity in vivo induced by Fe3O4nanoparticles.

Wilms’ tumor 1 (Wt1) encodes a zinc finger nuclear transcription factor which is mutated in 15–20% of Wilms’ tumor, a pediatric kidney tumor. Wt1has been found to be involved in the development of many organs. In gonads, Wt1is expressed in genital ridge somatic cells before sex determination, and its expression is maintained in Sertoli cells and granulosa cells after sex determination. It has been demonstrated that Wt1is required for the survival of the genital ridge cells. Homozygous mutation of Wt1causes gonad agenesis. Recent studies find that Wt1plays important roles in lineage specification and maintenance of gonad somatic cells. In this review, we will summarize the recent research works about Wt1in gonadal somatic cell differentiation.Wt1is indispensable for somatic cell differentiation and gonad development at different developmental stages.

The limited electronic applications of magnetorheological elastomers (MREs), polymer composites with carbonyl iron powder (CIP), are addressed in this study with a groundbreaking methodology. By utilizing a noncontact AC electric field, CIP manipulation at low concentrations (0.5–5 vol%) leads to the formation of conductive pathways within MREs. The resulting H-shaped structure exhibits columnar conductive pathways along the film’s thickness and interconnected pathways throughout the matrix, effectively reducing both volume and surface resistivity. Insights into the formation process are gained through real-time observations and numerical simulations. Experimental measurements reveal a remarkable reduction in volume and surface resistivity, achieving three and two orders of magnitude reduction, respectively, in 5 vol% H-shaped structure MREs. Remarkably, the H-shaped structure MREs display exceptional magneto-resistive and magneto-rheological behavior. Variations in surface resistance and resonant frequency occur with changing magnetic fields, with surface resistance decreasing by up to 89.6% (510 mT) and resonant frequency decreasing by up to 49.05% (300 mT). The efficacy of electric field-treated H-shaped structure MRE films is confirmed for practical applications in self-sensing tunable vibration absorbers. This research presents an innovative approach to enhance MRE conductivity, introducing a significant advancement in electronic functionality that opens doors to cutting-edge applications.

Just like we have small dedicated networks in houses, cars, factories, etc., we will have small clouds in all these places. We need a way to glue all these clouds together into a single worldwide infrastructure. The Cloud Abstraction Layer could provide such glue.

Multiple morphological abnormalities of the sperm flagella (MMAF) are one of the major causes of male infertility and are characterized by multiple defects. In this study, we found that the coiled-coil domain-containing 189 (Ccdc189) gene was predominantly expressed in mouse testes and that inactivation of the Ccdc189gene caused male infertility. Histological studies revealed that most sperm from Ccdc189-deficientmice carried coiled, curved or short flagella, which are typical MMAF phenotypes. Immunoelectron microscopy showed that the CCDC189 protein was located at the radial spoke of the first peripheral microtubule doublet in the sperm axoneme. A CCDC189-interacting protein, CABCOCO1 (ciliary-associated calcium-binding coiled-coil protein 1), was discovered via co-immunoprecipitation and mass spectrometry, and inactivation of Cabcoco1caused malformation of sperm flagella, which was consistent with findings obtained with Ccdc189-deficientmice. Further studies revealed that inactivation of CCDC189 caused downregulation of CABCOCO1 protein expression and that both CCDC189 and CABCOCO1 interacted with the radial-spoke-specific protein RSPH1 and intraflagellar transport proteins. This study demonstrated that Ccdc189is a radial-spoke-associated protein and is involved in sperm flagellum formation through its interactions with CABCOCO1 and intraflagellar transport proteins.Discovering a novel candidate gene for MMAF disease and unraveling the roles of CCDC189 and CABCOCO1 in sperm flagellar development.

Neural activation increases blood flow locally. This vascular signal is used by functional imaging techniques to infer the location and strength of neural activity. However, the precise spatial scale over which neural and vascular signals are correlated is unknown. Furthermore, the relative role of synaptic and spiking activity in driving haemodynamic signals is controversial. Previous studies recorded local field potentials as a measure of synaptic activity together with spiking activity and low-resolution haemodynamic imaging. Here we used two-photon microscopy to measure sensory-evoked responses of individual blood vessels (dilation, blood velocity) while imaging synaptic and spiking activity in the surrounding tissue using fluorescent glutamate and calcium sensors. In cat primary visual cortex, where neurons are clustered by their preference for stimulus orientation, we discovered new maps for excitatory synaptic activity, which were organized similarly to those for spiking activity but were less selective for stimulus orientation and direction. We generated tuning curves for individual vessel responses for the first time and found that parenchymal vessels in cortical layer 2/3 were orientation selective. Neighbouring penetrating arterioles had different orientation preferences. Pial surface arteries in cats, as well as surface arteries and penetrating arterioles in rat visual cortex (where orientation maps do not exist), responded to visual stimuli but had no orientation selectivity. We integrated synaptic or spiking responses around individual parenchymal vessels in cats and established that the vascular and neural responses had the same orientation preference. However, synaptic and spiking responses were more selective than vascular responses—vessels frequently responded robustly to stimuli that evoked little to no neural activity in the surrounding tissue. Thus, local neural and haemodynamic signals were partly decoupled. Together, these results indicate that intrinsic cortical properties, such as propagation of vascular dilation between neighbouring columns, need to be accounted for when decoding haemodynamic signals.

To establish a collagen type II-induced rat model of rheumatoid arthritis (RA) presenting characteristics of the human form of the traditional Chinese syndrome pattern of toxic heat-stasis painful obstruction (bi zheng; arthromyodynia) as well as pathologic features of active RA. The Chinese herbal medicine Tengmei decoction was used to validate the animal model.

Marmosets are highly social non-human primates that live in families. They exhibit rich vocalization, but the neural basis underlying this complex vocal communication is largely unknown. Here we report the existence of specific neuron populations in marmoset A1 that respond selectively to distinct simple or compound calls made by conspecific marmosets. These neurons were spatially dispersed within A1 but distinct from those responsive to pure tones. Call-selective responses were markedly diminished when individual domains of the call were deleted or the domain sequence was altered, indicating the importance of the global rather than local spectral-temporal properties of the sound. Compound call-selective responses also disappeared when the sequence of the two simple-call components was reversed or their interval was extended beyond 1 s. Light anesthesia largely abolished call-selective responses. Our findings demonstrate extensive inhibitory and facilitatory interactions among call-evoked responses, and provide the basis for further study of circuit mechanisms underlying vocal communication in awake non-human primates.