The morphological mapping of lateral compression type 1 pelvic fracture and pelvic ring stability classification: a finite element analysis

Purpose This finite element analysis assessed lateral compression (LC-1) fracture stability using machine learning for morphological mapping and classification of pelvic ring stability. Methods Computed tomography (CT) files of LC-1 pelvic fractures were collected. After morphological mapping and producing matrix data, we used K-means clustering in unsupervised machine learning to classify the fractures. Based on these subtypes, we manually added fracture lines in ANSYS software. Finally, we performed a finite element analysis of a normal pelvis and eight fracture subtypes based on von Mises stress and total deformation changes. Results A total of 218 consecutive cases were analyzed. According to the three main factors—zone of sacral injury and completion, pubic ramus injury side, and the sagittal rotation of the injured hemipelvis—the LC-1 injuries were classified into eight subtypes (I–VIII). No significant differences in stress or deformation were observed between unilateral and bilateral public ramus fractures. Subtypes VI and VIII showed the maximum stress while subtypes V–VIII showed the maximum deformation in the total pelvis and sacrum. The subtypes did not differ in superior public ramus deformation. Conclusions Complete fracture of sacrum zones 2/3 may be a feature of unstable LC-1 fractures. Surgeons should give surgical strategies for subtypes V–VIII.

Elucidating the Dynamics and Selective Mechanistic Mode of Inhibition of a Novel Poly ADP-Ribose Polymerase-1 Inhibitor

: Poly ADP-ribose polymerase-1 (PARP-1), due to its role in DNA damage and repair, has been identified as a crucial therapeutic target to attenuate cancer development and progression. More so, selective inhibition has remained a focal point in PARP-1 targeting and has led to the development of numerous compounds, including the recently identified Cpd10n, a novel homoerythrina alkaloid derivative. To expound on the selective PARP-1 inhibition mechanisms by Cpd10n, we employed computational simulation methods in this study. Findings revealed that the inhibitor stabilized the characteristic motion of activated PARP-1 as evidenced by reductions in residual deviations and structural flexibility. Findings further revealed that Cpd10n was favorably bound at the active site PARP-1 as supported by the occurrence of strong hydrogen and halogen bonds based on complementarity. These were in addition to aromatic bonds with an enhanced ring to ring stability. Steady and high-affinity interactions between the fluorine atom of Cpd10n and Glu988 could potentiate the selective activity of the compound. Interaction analyses also revealed that inhibitor binding was strongly dependent on electrostatic effects over van der Waal contributions, which were relatively minimal. We believe findings from this study will further contribute to the rational structure-based design of highly selective PARP-1 inhibitors.

Bacterial division FtsZ forms liquid condensates with nucleoid-associated Z-ring inhibitor SlmA

Macromolecular condensation resulting from biologically regulated liquid-liquid phase transitions is emerging as a mechanism to organize the intracellular space in eukaryotic systems, with broad implications in cell physiology and pathology. Here we show that FtsZ, central element of the division ring in most bacteria, forms condensates when in complex with SlmA, the protein preventing septal ring assembly nearby the chromosome in E. coli. The formation of condensates is promoted by crowding and enhanced by sequence-specific binding of SlmA to DNA. These structures are dynamic and FtsZ within them remains active for GTP-triggered fiber formation. Their location is sensitive to compartmentalization and to the presence of a membrane boundary in microfluidics-based cell mimetic systems, likely affecting their reactivity. We propose that reversible condensation may play a role in the modulation of FtsZ assembly and/or location by SlmA and, hence, in the regulation of ring stability, constituting a singular example of a prokaryotic nucleoprotein complex exhibiting this kind of phase transition.