Notes

Curcumin: May This particular Compound Be Useful while pregnant and also Pregnancy-Related Problems?
Polycyclic aromatic hydrocarbons (PAHs) are fundamental molecular building blocks of fullerenes and carbonaceous nanostructures in the interstellar medium and in combustion systems. However, an understanding of the formation of aromatic molecules carrying five-membered rings-the essential building block of nonplanar PAHs-is still in its infancy. Exploiting crossed molecular beam experiments augmented by electronic structure calculations and astrochemical modeling, we reveal an unusual pathway leading to the formation of indene (C9H8)-the prototype aromatic molecule with a five-membered ring-via a barrierless bimolecular reaction involving the simplest organic radical-methylidyne (CH)-and styrene (C6H5C2H3) through the hitherto elusive methylidyne addition-cyclization-aromatization (MACA) mechanism. Through extensive structural reorganization of the carbon backbone, the incorporation of a five-membered ring may eventually lead to three-dimensional PAHs such as corannulene (C20H10) along with fullerenes (C60, C70), thus offering a new concept on the low-temperature chemistry of carbon in our galaxy.Here, we report the topology-matched design of heteromultivalent nanostructures as potent and broad-spectrum virus entry inhibitors based on the host cell membrane. Initially, we investigate the virus binding dynamics to validate the better binding performance of the heteromultivalent moieties as compared to homomultivalent ones. The heteromultivalent binding moieties are transferred to nanostructures with a bowl-like shape matching the viral spherical surface. Unlike the conventional homomultivalent inhibitors, the heteromultivalent ones exhibit a half maximal inhibitory concentration of 32.4 ± 13.7 μg/ml due to the synergistic multivalent effects and the topology-matched shape. At a dose without causing cellular toxicity, >99.99% reduction of virus propagation has been achieved. Since multiple binding sites have also been identified on the S protein of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), we envision that the use of heteromultivalent nanostructures may also be applied to develop a potent inhibitor to prevent coronavirus infection.Understanding dynamics across phase transformations and the spatial distribution of minerals in the lower mantle is crucial for a comprehensive model of the evolution of the Earth's interior. Using the multigrain crystallography technique (MGC) with synchrotron x-rays at pressures of 30 GPa in a laser-heated diamond anvil cell to study the formation of bridgmanite [(Mg,Fe)SiO3] and ferropericlase [(Mg,Fe)O], we report an interconnected network of a smaller grained ferropericlase, a configuration that has been implicated in slab stagnation and plume deflection in the upper part of the lower mantle. Furthermore, we isolated individual crystal orientations with grain-scale resolution, provide estimates on stress evolutions on the grain scale, and report 110 twinning in an iron-depleted bridgmanite, a mechanism that appears to aid stress relaxation during grain growth and likely contributes to the lack of any appreciable seismic anisotropy in the upper portion of the lower mantle.Light-inducible gene switches represent a key strategy for the precise manipulation of cellular events in fundamental and applied research. However, the performance of widely used gene switches is limited due to low tissue penetrance and possible phototoxicity of the light stimulus. To overcome these limitations, we engineer optogenetic synthetic transcription factors to undergo liquid-liquid phase separation in close spatial proximity to promoters. Phase separation of constitutive and optogenetic synthetic transcription factors was achieved by incorporation of intrinsically disordered regions. Supported by a quantitative mathematical model, we demonstrate that engineered transcription factor droplets form at target promoters and increase gene expression up to fivefold. This increase in performance was observed in multiple mammalian cells lines as well as in mice following in situ transfection. The results of this work suggest that the introduction of intrinsically disordered domains is a simple yet effective means to boost synthetic transcription factor activity.Quantum estimation of a single parameter has been studied extensively. Practical applications, however, typically involve multiple parameters, for which the ultimate precision is much less understood. Here, by relating the precision limit directly to the Heisenberg uncertainty relation, we show that to achieve the highest precisions for multiple parameters at the same time requires the saturation of multiple Heisenberg uncertainty relations simultaneously. Guided by this insight, we experimentally demonstrate an optimally controlled multipass scheme, which saturates three Heisenberg uncertainty relations simultaneously and achieves the highest precisions for the estimation of all three parameters in SU(2) operators. With eight controls, we achieve a 13.27-dB improvement in terms of the variance (6.63 dB for the SD) over the classical scheme with the same loss. As an experiment demonstrating the simultaneous achievement of the ultimate precisions for multiple parameters, our work marks an important step in multiparameter quantum metrology with wide implications.Fluorescence lifetime imaging microscopy (FLIM) is a powerful tool for quantitative fluorescence imaging because fluorescence lifetime is independent of concentration of fluorescent molecules or excitation/detection efficiency and is robust to photobleaching. However, since most FLIMs are based on point-to-point measurements, mechanical scanning of a focal spot is needed for forming an image, which hampers rapid imaging. Here, we demonstrate scan-less full-field FLIM based on a one-to-one correspondence between two-dimensional (2D) image pixels and frequency-multiplexed radio frequency (RF) signals. A vast number of dual-comb optical beats between dual optical frequency combs are effectively adopted for 2D spectral mapping and high-density frequency multiplexing in the RF region. Bimodal images of fluorescence amplitude and lifetime are obtained with high quantitativeness from amplitude and phase spectra of fluorescence RF comb modes without the need for mechanical scanning. The parallelized FLIM will be useful for rapid quantitative fluorescence imaging in life science.Inflammation is a hallmark of aging and is negatively affecting female fertility. In this study, we evaluate the role of the NLRP3 inflammasome in ovarian aging and female fertility. Age-dependent increased expression of NLRP3 in the ovary was observed in WT mice during reproductive aging. High expression of NLRP3, caspase-1, and IL-1β was also observed in granulosa cells from patients with ovarian insufficiency. Ablation of NLRP3 improved the survival and pregnancy rates and increased anti-Müllerian hormone levels and autophagy rates in ovaries. Deficiency of NLRP3 also reduced serum FSH and estradiol levels. Consistent with these results, pharmacological inhibition of NLRP3 using a direct NLRP3 inhibitor, MCC950, improved fertility in female mice to levels comparable to those of Nlrp3-/- mice. These results suggest that the NLRP3 inflammasome is implicated in the age-dependent loss of female fertility and position this inflammasome as a potential new therapeutic target for the treatment of infertility.We present results from a study in the Democratic Republic of the Congo that uses mobile money networks to run rotating savings and credit associations (ROSCAs), peer-to-peer finance groups ubiquitous across the developing world. We find high rates of contribution and ROSCA success. The unexpected success of such e-ROSCAs and their potential to extend banking to the bankless poor necessitate further exploration.The high mechanical strength and long-term resistance to the fibrous capsule formation are two major challenges for implantable materials. Unfortunately, these two distinct properties do not come together and instead compromise each other. Here, we report a unique class of materials by integrating two weak zwitterionic hydrogels into an elastomer-like high-strength pure zwitterionic hydrogel via a "swelling" and "locking" mechanism. These zwitterionic-elastomeric-networked (ZEN) hydrogels are further shown to efficaciously resist the fibrous capsule formation upon implantation in mice for up to 1 year. Such materials with both high mechanical properties and long-term fibrous capsule resistance have never been achieved before. This work not only demonstrates a class of durable and fibrous capsule-resistant materials but also provides design principles for zwitterionic elastomeric hydrogels.Environmental stress can induce survival advantages that are passed down to multiple generations, representing an evolutionarily advantageous adaptation at the species level. Using the nematode worm Caenorhabditis elegans as a model, we found that heat shock experienced in either parent could increase the longevity of themselves and up to the fifth generation of descendants. Mechanistic analyses revealed that transcription factor DAF-16/FOXO, heat shock factor HSF-1, and nuclear receptor DAF-12/FXR functioned transgenerationally to implement the hormetic stress response. Histone H3K9me3 methyltransferases SET-25 and SET-32 and DNA N6-methyl methyltransferase DAMT-1 participated in transmitting high-temperature memory across generations. H3K9me3 and N6-methyladenine could mark heat stress response genes and promote their transcription in progeny to extend life span. We dissected the mechanisms responsible for implementing and transmitting environmental memories in descendants from heat-shocked parents and demonstrated that hormetic stress caused survival benefits could be transmitted to multiple generations through H3K9me3 and N6-mA modifications.Various characteristics of cancers exhibit tissue specificity, including lifetime cancer risk, onset age, and cancer driver genes. Previously, the large variation in cancer risk across human tissues was found to strongly correlate with the number of stem cell divisions and abnormal DNA methylation levels. Here, we study the role of synthetic lethality in cancer risk. Analyzing normal tissue transcriptomics data in the Genotype-Tissue Expression project, we quantify the extent of co-inactivation of cancer synthetic lethal (cSL) gene pairs and find that normal tissues with more down-regulated cSL gene pairs have lower and delayed cancer risk. Consistently, more cSL gene pairs become up-regulated in cells treated by carcinogens and throughout premalignant stages in vivo. We also show that the tissue specificity of numerous tumor suppressor genes is associated with the expression of their cSL partner genes across normal tissues. Overall, our findings support the possible role of synthetic lethality in tumorigenesis.Liquid droplets have been studied for decades and have recently experienced renewed attention as a simplified model for numerous fascinating physical phenomena occurring on size scales from the cell nucleus to stellar black holes. Here, we present an acoustofluidic centrifugation technique that leverages an entanglement of acoustic wave actuation and the spin of a fluidic droplet to enable nanoparticle enrichment and separation. By combining acoustic streaming and droplet spinning, rapid ( less then 1 min) nanoparticle concentration and size-based separation are achieved with a resolution sufficient to identify and isolate exosome subpopulations. The underlying physical mechanisms have been characterized both numerically and experimentally, and the ability to process biological samples (including DNA segments and exosome subpopulations) has been successfully demonstrated. Together, this acoustofluidic centrifuge overcomes existing limitations in the manipulation of nanoscale ( less then 100 nm) bioparticles and can be valuable for various applications in the fields of biology, chemistry, engineering, material science, and medicine.
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