Leptin, IL-6, and suPAR reflect distinct inflammatory changes associated with adiposity, lipodystrophy and low muscle mass in HIV-infected patients and controls

BACKGROUND: HIV-infected patients could exhibit accelerated ageing, since age-associated complications like sarcopenia; increased inflammation; lipodystrophy with loss of subcutaneous adipose tissue and/or gain of visceral adipose tissue (VAT); and cardiovascular disease occur at an earlier age. Inflammation is involved in age-associated complications. However, it is not understood whether it is the same inflammatory changes that are involved in the various ageing-associated complications. Our objective was to study whether leptin, interleukin 6 (IL-6), and soluble urokinase plasminogen activator receptor (suPAR) were associated distinctively with adiposity, lipodystrophy and sarcopenia, in HIV-infected patients and healthy Controls. RESULTS: Systemic leptin levels were significantly higher in patients with lipodystrophy than without, whereas there was no difference in IL-6 or suPAR levels. Leptin was significantly positively associated with fat mass index (FMI) and abdominal VAT, but not with lean mass index (LMI). IL-6 was significantly associated with both FMI and VAT, and low LMI. High suPAR was associated with low LMI, and weakly with high FMI and VAT. CONCLUSIONS: Leptin reflected adiposity- and lipodystrophy-related inflammation, but not sarcopenia. IL-6 reflected both adiposity-, but also sarcopenia-related inflammation; and suPAR was a marker of sarcopenia-related inflammation. Our results indicate that different inflammatory processes can be active simultaneously contributing to the systemic low grade inflammatory state. Identifying major contributors to circulating leptin, IL-6, and suPAR levels could levels could therefore improve our understanding of which inflammatory processes are involved in the various age-related complications

The seventh blind test of crystal structure prediction: structure ranking methods

\ua9 2024 International Union of Crystallography. All rights reserved. A seventh blind test of crystal structure prediction has been organized by the Cambridge Crystallographic Data Centre. The results are presented in two parts, with this second part focusing on methods for ranking crystal structures in order of stability. The exercise involved standardized sets of structures seeded from a range of structure generation methods. Participants from 22 groups applied several periodic DFT-D methods, machine learned potentials, force fields derived from empirical data or quantum chemical calculations, and various combinations of the above. In addition, one non-energy-based scoring function was used. Results showed that periodic DFT-D methods overall agreed with experimental data within expected error margins, while one machine learned model, applying system-specific AIMnet potentials, agreed with experiment in many cases demonstrating promise as an efficient alternative to DFT-based methods. For target XXXII, a consensus was reached across periodic DFT methods, with consistently high predicted energies of experimental forms relative to the global minimum (above 4 kJ mol- 1 at both low and ambient temperatures) suggesting a more stable polymorph is likely not yet observed. The calculation of free energies at ambient temperatures offered improvement of predictions only in some cases (for targets XXVII and XXXI). Several avenues for future research have been suggested, highlighting the need for greater efficiency considering the vast amounts of resources utilized in many cases

The seventh blind test of crystal structure prediction: structure generation methods

\ua9 2024 International Union of Crystallography. All rights reserved. A seventh blind test of crystal structure prediction was organized by the Cambridge Crystallographic Data Centre featuring seven target systems of varying complexity: a silicon and iodine-containing molecule, a copper coordination complex, a near-rigid molecule, a cocrystal, a polymorphic small agrochemical, a highly flexible polymorphic drug candidate, and a polymorphic morpholine salt. In this first of two parts focusing on structure generation methods, many crystal structure prediction (CSP) methods performed well for the small but flexible agrochemical compound, successfully reproducing the experimentally observed crystal structures, while few groups were successful for the systems of higher complexity. A powder X-ray diffraction (PXRD) assisted exercise demonstrated the use of CSP in successfully determining a crystal structure from a low-quality PXRD pattern. The use of CSP in the prediction of likely cocrystal stoichiometry was also explored, demonstrating multiple possible approaches. Crystallographic disorder emerged as an important theme throughout the test as both a challenge for analysis and a major achievement where two groups blindly predicted the existence of disorder for the first time. Additionally, large-scale comparisons of the sets of predicted crystal structures also showed that some methods yield sets that largely contain the same crystal structures