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Background: Rod fracture (RF) is the most common cause of revision in adult spinal deformity (ASD) surgery, and various treatment strategies for preventing RF are reported in the literature. This retrospective study, involving 139 ASD patients (aged ≥65 years and a minimum 2-year follow-up) who underwent long-segment fixation from T10 to sacrum with pedicle subtraction osteotomy (PSO), analyzed long-term results, including radiographical parameters and the incidence of recurrent RF (re-RF), to determine the most effective revision method for preventing RF. Methods: Patients were classified into three groups according to the revision method performed for RF: simple rod replacement (RR group, n = 17), lateral lumbar interbody fusion around the PSO site (RR + LLIF group, n = 8), and accessory rod insertion (RR + AR group, n = 22). Baseline characteristics and radiographical and clinical parameters were analyzed. Results: RF occurred in 47 patients (34%) at an average of 28 months following primary deformity correction. Re-RF occurred in six patients (13%) at an average of 37 months. Re-RF occurred most commonly in the RR group (p = 0.048). Every re-RF in the RR group occurred at the PSO site; none occurred in the RR + LLIF group, and one in the RR + AR group occurred near the L4–5. After both primary deformity correction and revision surgery, spinopelvic parameters had shown favorable results, and clinical outcomes had improved in all three groups without significant intergroup differences. Conclusions: Accessory rod insertion or an additional LLIF around the PSO site seems to provide greater strength and stability to the previously fused segments than a simple rod replacement, which demonstrates the need for additional support in revision surgery for RF after a PSO. [ABSTRACT FROM AUTHOR]

RAS proteins are peripheral membrane GTPases that activate multiple downstream effectors for cell proliferation and differentiation. The formation of a signaling RAS–RAF complex at the plasma membrane is implicated in a quarter of all human cancers; however, the underlying mechanism remains unclear. In this work, nanodisc platforms and paramagnetic relaxation enhancement (PRE) analyses to determine the structure of a hetero‐tetrameric complex comprising KRAS and the RAS‐binding domain (RBD) and cysteine‐rich domain (CRD) of activated RAF1 are employed. The binding of the RBD or RBD–CRD differentially alters the dimerization modes of KRAS on both anionic and neutral membranes, validated by interface‐specific mutagenesis. Notably, the RBD binding allosterically generated two distinct KRAS dimer interfaces in equilibrium, favored by KRAS free and in complex with the RBD–CRD, respectively. Additional interactions of the CRD with both KRAS protomers are mutually cooperative to stabilize a new dimer configuration of KRAS bound to the RBD–CRD. The RAF binding sequentially alters KRAS dimerization, providing new insights into RAF activation, including a configurational transition of the KRAS dimer to provide an interaction site for the CRD and release the autoinhibited RAF complex. These methods are applicable to many other signaling protein complexes on the membrane. [ABSTRACT FROM AUTHOR]

The topological properties of photonic microstructures are of great interest because of their experimental feasibility for fundamental study and potential applications. Here, we show that robust guided-mode-resonance states exist in photonic domain-wall structures whenever the complex photonic band structures involve certain topological correlations in general. Using the non-Hermitian photonic analogy of the one-dimensional Dirac equation, we derive essential conditions for photonic Jackiw-Rebbi-state resonances taking advantage of unique spatial confinement and spot-like spectral features which are remarkably robust against random parametric errors. Therefore, the proposed resonance configuration potentially provides a powerful method to create compact and stable photonic resonators for various applications in practice.

Self‐assemblies (i.e. nanoclusters) of the RAS GTPase on the membrane act as scaffolds that activate downstream RAF kinases and drive MAPK signaling for cell proliferation and tumorigenesis. However, the mechanistic details of nanoclustering remain largely unknown. Here, size‐tunable nanodisc platforms and paramagnetic relaxation enhancement (PRE) analyses revealed the structural basis of the cooperative assembly processes of fully processed KRAS, mutated in a quarter of human cancers. The cooperativity is modulated by the mutation and nucleotide states of KRAS and the lipid composition of the membrane. Notably, the oncogenic mutants assemble in nonsequential pathways with two mutually cooperative 'α/α' and 'α/β' interfaces, while α/α dimerization of wild‐type KRAS promotes the secondary α/β interaction sequentially. Mutation‐based interface engineering was used to selectively trap the oligomeric intermediates of KRAS and probe their favorable interface interactions. Transiently exposed interfaces were available for the assembly. Real‐time NMR demonstrated that higher‐order oligomers retain higher numbers of active GTP‐bound protomers in KRAS GTPase cycling. These data provide a deeper understanding of the nanocluster‐enhanced signaling in response to the environment. Furthermore, our methodology is applicable to assemblies of many other membrane GTPases and lipid nanoparticle‐based formulations of stable protein oligomers with enhanced cooperativity. [ABSTRACT FROM AUTHOR]