Visible light-induced C(sp3)-H azolation of ethers via radical-polar crossover.

Reported herein is a photochemical strategy for C(sp3)-H azolation of ethers via a hydrogen-atom transfer and radical-polar crossover process, offering efficient access to valuable N-alkylated azoles under visible-light irradiation. The protocol is metal-free and photocatalyst-free, and exhibits good to excellent yields and broad substrate scope with regard to azoles. EPR experiments provide evidence for the formation of intermediates formed in situ.

Trophoblast Differentiation: Mechanisms and Implications for Pregnancy Complications.

Placental development is a tightly controlled event, in which cell expansion from the trophectoderm occurs in a spatiotemporal manner. Proper trophoblast differentiation is crucial to the vitality of this gestational organ. Obstructions to its development can lead to pregnancy complications, such as preeclampsia, fetal growth restriction, and preterm birth, posing severe health risks to both the mother and offspring. Currently, the only known treatment strategy for these complications is delivery, making it an important area of research. The aim of this review was to summarize the known information on the development and mechanistic regulation of trophoblast differentiation and highlight the similarities in these processes between the human and mouse placenta. Additionally, the known biomarkers for each cell type were compiled to aid in the analysis of sequencing technologies.

Nutrition and Supplements during Pregnancy: A Vital Component in Building the Health and Well-Being of Both the Mother and the Developing Baby.

Maternal health is of the utmost importance during pregnancy, not just for the mother but also for the developing fetus [...].

Understanding PPARγ and Its Agonists on Trophoblast Differentiation and Invasion: Potential Therapeutic Targets for Gestational Diabetes Mellitus and Preeclampsia.

The increasing incidence of pregnancy complications, particularly gestational diabetes mellitus (GDM) and preeclampsia (PE), is a cause for concern, as they can result in serious health consequences for both mothers and infants. The pathogenesis of these complications is still not fully understood, although it is known that the pathologic placenta plays a crucial role. Studies have shown that PPARγ, a transcription factor involved in glucose and lipid metabolism, may have a critical role in the etiology of these complications. While PPARγ agonists are FDA-approved drugs for Type 2 Diabetes Mellitus, their safety during pregnancy is not yet established. Nevertheless, there is growing evidence for the therapeutic potential of PPARγ in the treatment of PE using mouse models and in cell cultures. This review aims to summarize the current understanding of the mechanism of PPARγ in placental pathophysiology and to explore the possibility of using PPARγ ligands as a treatment option for pregnancy complications. Overall, this topic is of great significance for improving maternal and fetal health outcomes and warrants further investigation.

FoxO1 Deficiency Enhances Cell Proliferation and Survival Under Normoglycemia and Promotes Angiogenesis Under Hyperglycemia in the Placenta.

FoxO1 is an important transcriptional factor that regulates cell survival and metabolism in many tissues. Deleting FoxO1 results in embryonic death due to failure of chorioallantoic fusion at E8.5; however, its role in placental development during mid-late gestation is unclear. In both human patients with gestational diabetes and pregnant mice with hyperglycemia, placental FoxO1 expression was significantly increased. Using FoxO1+/- mice, the effects of FoxO1 haploinsufficiency on placental development under normoglycemia and hyperglycemia were investigated. With FoxO1 haploinsufficiency, the term placental weight increased under both normal and hyperglycemic conditions. Under normoglycemia, this weight change was associated with a general enlargement of the labyrinth, along with increased cell proliferation, decreased cell apoptosis, and decreased expression of p21, p27, Casp3, Casp8, and Rip3. However, under hyperglycemia, the placental weight change was associated with increased fetal blood space, VEGFA overexpression, and expression changes of the angiogenic markers, Eng and Tsp1. In conclusion, FoxO1 plays a role in regulating cell proliferation, cell survival, or angiogenesis, depending on blood glucose levels, during placenta development.

Search for exotic parity-violation interactions with quantum spin amplifiers.

Quantum sensing provides sensitive tabletop tools to search for exotic spin-dependent interactions beyond the standard model, which have attracted great attention in theories and experiments. Here, we develop a technique based on Spin Amplifier for Particle PHysIcs REsearch (SAPPHIRE) to resonantly search for exotic interactions, specifically parity-odd spin-spin interactions. The present technique effectively amplifies exotic interaction fields by a factor of about 200 while being insensitive to spurious magnetic fields. Our studies, using such a quantum amplification technique, explore the parity-violation interactions mediated by a new vector boson in the challenging parameter space (force range between 3 mm and 1 km) and set the most stringent constraints on axial-vector electron-neutron couplings, substantially improving previous limits by five orders of magnitude. Moreover, our constraints on axial-vector couplings between nucleons reach into a hitherto unexplored parameter space. The present constraints complement the existing astrophysical and laboratory studies on potential standard model extensions.

Limits on Axions and Axionlike Particles within the Axion Window Using a Spin-Based Amplifier.

Searches for the axion and axionlike particles may hold the key to unlocking some of the deepest puzzles about our Universe, such as dark matter and dark energy. Here, we use the recently demonstrated spin-based amplifier to constrain such hypothetical particles within the well-motivated "axion window" (10 µeV-1 meV) through searching for an exotic dipole-dipole interaction between polarized electron and neutron spins. The key ingredient is the use of hyperpolarized long-lived ^{129}Xe nuclear spins as an amplifier for the pseudomagnetic field generated by the exotic interaction. Using such a spin sensor, we obtain a direct upper bound on the product of coupling constants g_{p}^{e}g_{p}^{n}. The spin-based amplifier technique can be extended to searches for a wide variety of hypothetical particles beyond the standard model.

Floquet Spin Amplification.

Detection of weak electromagnetic waves and hypothetical particles aided by quantum amplification is important for fundamental physics and applications. However, demonstrations of quantum amplification are still limited; in particular, the physics of quantum amplification is not fully explored in periodically driven (Floquet) systems, which are generally defined by time-periodic Hamiltonians and enable observation of many exotic quantum phenomena such as time crystals. Here we investigate the magnetic-field signal amplification by periodically driven ^{129}Xe spins and observe signal amplification at frequencies of transitions between Floquet spin states. This "Floquet amplification" allows us to simultaneously enhance and measure multiple magnetic fields with at least one order of magnitude improvement, offering the capability of femtotesla-level measurements. Our findings extend the physics of quantum amplification to Floquet spin systems and can be generalized to a wide variety of existing amplifiers, enabling a previously unexplored class of "Floquet spin amplifiers".

Hyperglycemia results in significant pathophysiological changes of placental spiral artery remodeling and angiogenesis, further contributing to congenital defects.

Introduction: Hyperglycemic conditions achieved during pregnancy have been shown to have detrimental effects to fetal development and increase the prevalence of childhood comorbidities. However, the mechanisms in which diabetic pregnancies affect placental development and subsequently contribute to adverse health effects on the mother and offspring remain unclear. Research design and methods: Streptozotocin was used to induce gestational diabetes in mice. In this model, hyperglycemia was established at embryonic day 3.5 (E3.5). Pregnancy mass was collected at E10.5, E12.5, E14.5, and E16.5 for different assessments. Results: Both placental and embryonic weights were found to be significantly elevated at E16.5. At E14.5, a significantly larger junctional zone with increased number of glycogen trophoblasts was found in the placentas from hyperglycemic pregnancies (HG group) compared to the placentas from normoglycemic pregnancies (NG group). Importantly, the HG placenta exhibited decreased trophoblast giant cell (TGC) association and TUNEL+ cells, and increased expression of α-SMA on the spiral artery, suggesting arterial remodeling was impacted. Moreover, the interhemal membrane of the labyrinth layer, was found to be thicker in the HG placentas. Furthermore, hyperglycemia resulted in more offspring congenital defects, which were associated with a thicker interhemal membrane. Conclusions: Together, these results suggest that gestational diabetes perturbs proper placental development and function, specifically spiral artery remodeling and angiogenesis, thereby negatively impacting embryonic development.

Tbx5 inhibits hedgehog signaling in determination of digit identity.

Dominant TBX5 mutation causes Holt-Oram syndrome (HOS), which is characterized by limb defects in humans, but the underlying mechanistic basis is unclear. We used a mouse model with Tbx5 conditional knockdown in Hh-receiving cells (marked by Gli1+) during E8 to E10.5, a previously established model to study atrial septum defects, which displayed polydactyly or hypodactyly. The results suggested that Tbx5 is required for digit identity in a subset of limb mesenchymal cells. Specifically, Tbx5 deletion in this cell population decreased cell apoptosis and increased the proliferation of handplate mesenchymal cells. Furthermore, Tbx5 was found to negatively regulate the Hh-signaling activity through transcriptional regulation of Ptch1, a known Hh-signaling repressor. Repression of Hh-signaling through Smo co-mutation in Tbx5 heterozygotes rescued the limb defects, thus placing Tbx5 upstream of Hh-signaling in limb defects. This work reveals an important missing component necessary for understanding not only limb development but also the molecular and genetic mechanisms underlying HOS.