Exome-Wide Sequencing Study Identified Genetic Variants Associated With Sarcopenic Obesity.

Sarcopenic obesity (SO) is an age-related disease characterized by the coexistence of excessive adiposity and low muscle mass or function. Although obesity and sarcopenia are heritable conditions, the genetic determinants of SO have not been fully understood. We conducted a large-scale exome-wide association analysis of SO in a sequenced sample of 2 887 cases and 113 284 controls and an imputed sample of 4 003 cases and 161 990 controls in the UK Biobank cohort. Single-variant association analysis identified one locus 1q41 (lead SNP rs1417066, LYPLAL1-AS1, odds ratio [OR] = 1.15, 95% confidence interval [CI] = [1.11-1.19], p = 1.75 × 10-14) that was significantly associated with SO at the exome-wide significance level (p < 1 × 10-8). Colocalization analysis in the Genotype-Tissue Expression expression quantitative trait locus database showed that LYPLAL1-AS1 was colocalized with SO in multiple musculoskeletal-related tissues. Gene-based burden test of rare loss-of-function variants identified 5 genes at the gene-wise significance level (p < 4.3 × 10-6): PDE3B (OR = 2.48, p = 1.10 × 10-6), MYOZ3 (OR = 25.49, p = 1.41 × 10-7), SLC15A3 (OR = 4.75, p = 6.82 × 10-7), RNF130 (OR = 25.83, p = 4.07 × 10-6), and TNK2 (OR = 4.25, p = 8.75 × 10-8). Overall, our study uncovered the genetic effects of both common and rare variants on SO susceptibility, expanded existing knowledge of the genetic architecture of SO, and improved understanding of the genetic mechanisms underlying SO.

Curcumin suppressed the proliferation and apoptosis of HPV-positive cervical cancer cells by directly targeting the E6 protein.

Most human papillomavirus (HPV) types, including HPV16 and HPV18, are closely related to the occurrence of cervical cancer, predominantly through the action of viral oncoproteins E6 and E7. Curcumin, the active ingredient of the turmeric plant, has been gaining attention over the past two decades as an antioxidant, anti-inflammatory, and anticancer agent. In the present study, the HPV-positive cervical cancer cells HeLa and CaSki were treated with curcumin, and the results showed that curcumin has a dose-dependent and time-dependent inhibitory effect on cell viability. In addition, apoptosis induction was further quantitatively confirmed through flow cytometric analysis. Furthermore, the influence of different concentrations of curcumin on the mitochondrial membrane potential was evaluated through JC-1 staining and found to dramatically decrease the membrane potential in treated HeLa and CaSki cells, suggesting the critical role of the mitochondrial pathway in their apoptosis-inducing effect. This study also demonstrated the wound-healing potential of curcumin, and the results of transwell assays showed that curcumin treatment inhibited HeLa and CaSki cell invasion and migration in a dose-dependent manner compared with the control treatment. Curcumin also downregulated the expression of Bcl-2, N-cadherin, and Vimentin and upregulated the expression of Bax, C-caspase-3, and E-cadherin in both cell lines. Further research showed that curcumin also selectively inhibited the expression of the viral oncoproteins E6 and E7, as demonstrated by western blot analysis; moreover, the downregulation of E6 was more significant than that of E7. Our research also showed that coculture with cells infected with siE6 lentivirus (siE6 cells) can inhibit the proliferation, invasion, and metastasis of HPV-positive cells. While the siE6 cells were also treated with curcumin, the effect of curcumin monotherapy was offset. In summary, our research shows that curcumin regulates the apoptosis, migration, and invasion of cervical cancer cells, and the mechanism may be related to its ability to downregulate E6. This study provides a foundation for future research on the prevention and treatment of cervical cancer.

Ligand Torsion Engineering in Three Flexible Metal-Organic-Frameworks Exhibiting Distinct Breathing Behavior for Enhancing C2H2 Capture.

Acetylene is an important industrial gas for the production of vinyl chloride and 1,4-butynediol, but its storage remains a major challenge because it is highly explosive. Flexible metal-organic frameworks (FMOFs) are always at the forefront of porous materials due to the transformation of the structure under the external stimuli. In this work, divalent metal ions and multifunctional aromatic N,O-donor ligands were chosen, and three FMOFs [M(DTTA)2]·guest [M = Mn (1), Cd (2), and Cu (3)] (H2DTTA = 2,5-bis(1H-1,2,4-trazol-1-yl) terephthalic acid) have been successfully constructed. Single-crystal X-ray diffractions show that these compounds are isostructural and feature a three-dimensional framework. Topological analysis shows a (4, 6)-connected network with a Schläfli symbol of {44.610.8}{44.62}. All three compounds exhibit breathing behavior on N2 adsorption at 77 K, and due to the difference of ligand torsion angles, compounds 2 and 3 exhibit extraordinary adsorptions for C2H2 of 101 and 122 cm3 g-1 at 273 K under 1 bar, respectively. Compared with previous work, successfully obtaining compound 3 with an innovative structure can be attributed to the solvent-induced effect in the process of crystal synthesis, leading to the structure transformation promoting the significantly increased C2H2 adsorption performance. This study provides a platform for improvement of synthetic structures, which can effectively boost gas adsorption performance.

Recovering three-dimensional shape through a small hole using three laser scatterings.

An approach was proposed and developed to recover the 3D shape concealed in a shelter with a small hole only using three laser scatterings. This approach extends reconstruction of concealed 3D shape from "around a corner" to "through a small hole". Based on principle of rectilinear propagation of light, a simple geometric mapping tentative theoretical frame independent of scene was proposed to extract 3D information of concealed objects. Experimental setup mainly consists of a nanosecond laser and a single-photon APD, both of which are commercially available. The 3D reconstructions of three hidden objects were acquired with a resolution of centimeters.