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C18H22N5O2·C7H4ClO2, orthorhombic, P212121 (no. 19), a = 8.9188(2) Å, b = 10.8391(2) Å, c = 25.9295(5) Å, V = 2506.65(9) Å3, Z = 4, Rgt (F) = 0.0357, wRref (F 2) = 0.1085, T = 293(2) K.

C18H15ClN2O2S·C8H6O4, triclinic, P 1‾ $\overline{1}$ (no. 2), a = 8.4340(17) Å, b = 12.172(2) Å, c = 12.816(3) Å, α = 89.98(3)° $89.98(3){}^{\circ}$ , β = 77.41(3)° $77.41(3){}^{\circ}$ , γ = 72.52(3)° $72.52(3){}^{\circ}$ , V = 1221.7(5) Å3, Z = 2, R gt(F) = 0.0482, wR ref(F 2) = 0.1344, T = 293 K.

C17H14N2O6S·C3H7NO, triclinic, P1‾ $P\overline{1}$ (no. 2), a = 5.4146(4) Å, b = 11.7925(8) Å, c = 16.9527(12) Å, α = 85.238(2)°, β = 86.674(4)°, γ = 78.959(2)°, V = 1057.77(13) Å3, Z = 2, R gt(F) = 0.0418, wR ref(F 2) = 0.1175, T = 296(2) K.

Radioactive iodine from nuclear waste poses a major threat to public safety due to its toxicity and long half-life. The capture and storage of radioactive iodine remains a major challenge. The incorporation of electron-rich heterocycles into the adsorbents could increase the adsorption capacity for iodine due to their strong interaction. In this study, three novel spiro-thioketal-based porous organic polymers, POPSP-1–3, were synthesized in excellent yields by a thiol-aldehyde polycondensation reaction. The polymers of POPSPs were thoroughly characterized using FT-IR, 13C-NMR, BET, and PXRD techniques. These analyses revealed that the polymers are amorphous in nature and have a low surface area. The iodine uptake capacities of POPSP-1, POPSP-2, and POPSP-3 were measured to be 4.13, 5.25, and 5.65 g g−1, respectively, at a temperature of 75 °C due to the increased density of the adsorption sites. Furthermore, the POPSPs exhibit exceptional adsorption performance in iodine/n-hexane solution and their effectiveness in removing iodine is excellent. This work provides a novel approach for the development of sulfur-rich porous organic polymers (POPs) as effective adsorbents for iodine capture. [ABSTRACT FROM AUTHOR]

The structures of three 1:1 cocrystal forms of etoricoxib {ETR; systematic name: 5‐chloro‐2‐(6‐methylpyridin‐3‐yl)‐3‐[4‐(methylsulfonyl)phenyl]pyridine, C18H15ClN2O2S} have been synthesized and characterized by single‐crystal X‐ray diffraction; these are etoricoxib–benzoic acid (1/1), C18H15ClN2O2S·C7H6O2 (ETR–Bz), etoricoxib–4‐fluorobenzoic acid (1/1), C18H15ClN2O2S·C7H5FO2 (ETR–PFB), and etoricoxib–4‐nitrobenzoic acid (1/1), C18H15ClN2O2S·C7H5NO4 (ETR–PNB). Powder X‐ray diffraction and thermal differential scanning calorimetry–thermogravimetry (DSC–TG) techniques were also used to characterize these multicomponent systems. Due to the influence of the corresponding acids, ETR shows different conformations. Furthermore, the energetic contributions of the supramolecular motifs have been established by energy framework studies of the stabilizing interaction forces and are consistent with the thermal stability of the cocrystals. [ABSTRACT FROM AUTHOR]

ContextOsteocyte activity is crucial to the maintenance of bone quality. Sclerostin, an osteocyte product, inhibits bone formation, yet higher circulating sclerostin is associated with higher bone density. Bone marrow fat (MF) is associated with osteoporosis, but little is known about the relationship between osteocyte activity and MF.ObjectiveOur objective was to assess the relationships between circulating sclerostin, vertebral MF, volumetric bone mineral density (vBMD), and other fat depots in older adults.Design, setting, and participantsWe conducted a cross-sectional study in the Age Gene/Environment Susceptibility-Reykjavik cohort.Main outcome measuresOutcome measures included vertebral MF (L1-L4) measured with magnetic resonance spectroscopy and vBMD (spine and hip) and abdominal fat measured with quantitative computed tomography.ResultsAfter excluding subjects with bone-active medication use (n = 50), inadequate serum (n = 2), or inadequate magnetic resonance spectroscopy (n = 1), analyses included 115 men and 134 women (mean age 79 y, mean body mass index 27.7 kg/m(2)). In men, but not women, vertebral MF was greater in those with higher serum sclerostin levels. MF was 52.2 % in the lowest tertile of serum sclerostin and 56.3% in the highest tertile in men (P for trend

C18H15ClN2O2S·C8H6O4, triclinic, P 1 ‾ (no. 2), a = 8.4340(17) Å, b = 12.172(2) Å, c = 12.816(3) Å, α = 89.98 (3) ° , β = 77.41 (3) ° , γ = 72.52 (3) ° , V = 1221.7(5) Å3, Z = 2, Rgt(F) = 0.0482, wRref(F2) = 0.1344, T = 293 K. [ABSTRACT FROM AUTHOR]

C18H15ClN2O2S·C8H6O4, triclinic, P 1 ‾ (no. 2), a = 8.4340(17) Å, b = 12.172(2) Å, c = 12.816(3) Å, α = 89.98 (3) ° , β = 77.41 (3) ° , γ = 72.52 (3) ° , V = 1221.7(5) Å3, Z = 2, Rgt(F) = 0.0482, wRref(F2) = 0.1344, T = 293 K. [ABSTRACT FROM AUTHOR]

C17H14N2O6S·C3H7NO, triclinic, P 1 ‾ (no. 2), a = 5.4146(4) Å, b = 11.7925(8) Å, c = 16.9527(12) Å, α = 85.238(2)°, β = 86.674(4)°, γ = 78.959(2)°, V = 1057.77(13) Å3, Z = 2, Rgt(F) = 0.0418, wRref(F2) = 0.1175, T = 296(2) K. [ABSTRACT FROM AUTHOR]

Osteocytes' mechano-regulation of bone formation and resorption is key to maintaining appropriate bone health. Although extensive in vitro studies have explored osteocyte mechanobiology using the well-established MLO-Y4 cell model, the low amount of sclerostin secreted by this cell line renders it inadequate for studying cross-talk between osteocytes and osteoblasts under mechanical loading. Here, we investigated the potential of the sclerostin-expressing OCY454 osteocyte cell model in fulfilling this role. Fully differentiated OCY454 cells were tested for mechano-sensitivity by measuring changes in protein secretion, total adenosine triphosphate (ATP) content, and intracellular calcium in response to oscillatory fluid flow. Increases in sclerostin expression and total ATP content were observed. However, very low levels of receptor activator of the nuclear factor κ-B ligand were detected, and there was a great inconsistency in calcium response. Conditioned medium (CM) from OCY454 cells was then used to culture osteoblast and osteoclast precursors. Osteoblast activity was quantified with alkaline phosphatase (ALP) and Alizarin Red S stain, while osteoclast differentiation was quantified with tartrate-resistant acid phosphatase (TRAP) staining. We demonstrated that mechanically stimulated OCY454 cells released soluble factors that increased osteoblasts' ALP activity (p < 0.05) and calcium deposition (p < 0.05). There was also a significant decrease of large-sized TRAP-positive osteoclasts when osteoclast precursors were treated with CM from flow-stimulated OCY454 cells (p < 0.05). Results from this study suggest that OCY454 cells respond to mechanical loading with the release of key factors such as sclerostin to regulate downstream bone cells, thus demonstrating its potential as a novel cell model for in vitro osteocyte mechanobiology studies. [ABSTRACT FROM AUTHOR]

The recent expansion of human genomics repositories has facilitated the discovery of novel TP53 variants in populations of different ethnic origins. Interpreting TP53 variants is a major clinical challenge because they are functionally diverse, confer highly variable predisposition to cancer (including elusive low-penetrance alleles), and interact with genetic modifiers that alter tumor susceptibility. Here, we discuss how a cancer risk continuum may relate to germline TP53 mutations on the basis of our current review of genotype-phenotype studies and an integrative analysis combining functional and sequencing datasets. Our study reveals that each ancestry contains a distinct TP53 variant landscape defined by enriched ethnic-specific alleles. In particular, the discovery and characterization of suspected low-penetrance ethnic-specific variants with unique functional consequences, including P47S (African), G334R (Ashkenazi Jewish), and rs78378222 (Icelandic), may provide new insights in terms of managing cancer risk and the efficacy of therapy. Additionally, our analysis highlights infrequent variants linked to milder cancer phenotypes in various published reports that may be underdiagnosed and require further investigation, including D49H in East Asians and R181H in Europeans. Overall, the sequencing and projected functions of TP53 variants arising within ethnic populations and their interplay with modifiers, as well as the emergence of CRISPR screens and AI tools, are now rapidly improving our understanding of the cancer susceptibility spectrum, leading toward more accurate and personalized cancer risk assessments., (© The Author(s) 2023. Published by Oxford University Press.)

Objective: We investigated whether Piezo1 could regulate oxygen-glucose deprivation/reoxygenation injury of neurons through Ca 2+ /calpain signaling., Methods: Piezo1 expression in rat brain cortex and PC12 cells were confirmed by immunohistochemistry, immunofluorescence and Western blotting. The effects of Yoda1 and GsMTx4 on OGD/R-induced decrease in cell viability, increase in cell apoptosis and activation of downstreaming Ca 2+ /calpain signaling were investigated. Furthermore, calpain signaling was inhibited by PD151746 to see whether Ca 2+ /calpain signaling participated in the neurotoxic effects of Piezo1 activation., Results: Piezo1 expression was increased in rat cerebral cortex after ischemia/reperfusion and in PC12 cells after OGD/R. Activation of Piezo1 by Yoda1 enhanced OGD/R-induced cell viability inhibition, apoptosis, increase intracellular calcium levels and enhanced calpain activity while GsMTx4 showed the opposite effects. The effects of Piezo1 activation on cell viability and apoptosis were reversed by PD151746., Conclusion: Piezo1 could regulate neuron oxygen-glucose deprivation/reoxygenation injury via activation of Ca 2+ /calpain signaling., (Copyright © 2019. Published by Elsevier Inc.)

Agonists of peroxisome proliferator-activated receptor gamma (PPARgamma) are of interest as a treatment of type II diabetes, and indenone derivatives are a new class of non-TZD PPARgamma agonists. Based on existing indenone derivatives, a series of novel ones have been designed and synthesized. Meanwhile the structures have been comfirmed with 1H NMR and MS. Among them, 17b and 19 showed higher agonistic activities than rosiglitazone.

Ubiquitin-proteasome pathway (UPP) is one of the ways utilized for selective degradation of many proteins in cells, and the 20S proteasome takes the functional machinery where hydrolysis of targeted proteins takes place. Based on existing peptide inhibitors, a series of novel tripeptidic tetrazoles have been designed, synthesized, and the structures have been confirmed with 1H NMR, MS and elemental analysis. Among them, three compounds (6b, 6d and 6h) showed inhibitory activities of ChT-L of 20S proteasome.