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Preserving and regulating cellular homeostasis in the light of changing environmental conditions or developmental processes is of pivotal importance for single cellular and multicellular organisms alike. To counteract an imbalance in cellular homeostasis transcriptional programs evolved, called the heat shock response, unfolded protein response, and integrated stress response, that act cell-autonomously in most cells but in multicellular organisms are subjected to cell-nonautonomous regulation. These transcriptional programs downregulate the expression of most genes but increase the expression of heat shock genes, including genes encoding molecular chaperones and proteases, proteins involved in the repair of stress-induced damage to macromolecules and cellular structures. Sixty-one years after the discovery of the heat shock response by Ferruccio Ritossa, many aspects of stress biology are still enigmatic. Recent progress in the understanding of stress responses and molecular chaperones was reported at the 12th International Symposium on Heat Shock Proteins in Biology, Medicine and the Environment in the Old Town Alexandria, VA, USA from 28th to 31st of October 2023.

The development of healthy peri-implant soft tissues is critical to achieving the esthetic and biological success of implant restorations throughout all stages of healing and tissue maturation, starting with provisionalization. The purpose of this study was to investigate the effects of eight different implant provisional materials on human gingival fibroblasts at various stages of cell settlement by examining initial cell attachment, growth, and function. Eight different specimens-bis-acrylic 1 and 2, flowable and bulk-fill composites, self-curing acrylic 1 and 2, milled acrylic, and titanium (Ti) alloy as a control-were fabricated in rectangular plates (n = 3). The condition of human gingival fibroblasts was divided into two groups: those in direct contact with test materials (contact experiment) and those in close proximity to test materials (proximity experiment). The proximity experiment was further divided into three phases: pre-settlement, early settlement, and late settlement. A cell culture insert containing each test plate was placed into a well where the cells were pre-cultured. The number of attached cells, cell proliferation, resistance to detachment, and collagen production were evaluated. In the contact experiment, bis-acrylics and composites showed detrimental effects on cells. The number of cells attached to milled acrylic and self-curing acrylic was relatively high, being approximately 70% and 20-30%, respectively, of that on Ti alloy. There was a significant difference between self-curing acrylic 1 and 2, even with the same curing modality. The cell retention ability also varied considerably among the materials. Although the detrimental effects were mitigated in the proximity experiment compared to the contact experiment, adverse effects on cell growth and collagen production remained significant during all phases of cell settlement for bis-acrylics and flowable composite. Specifically, the early settlement phase was not sufficient to significantly mitigate the material cytotoxicity. The flowable composite was consistently more cytotoxic than the bulk-fill composite. The harmful effects of the provisional materials on gingival fibroblasts vary considerably depending on the curing modality and compositions. Pre-settlement of cells mitigated the harmful effects, implying the susceptibility to material toxicity varies depending on the progress of wound healing and tissue condition. However, cell pre-settlement was not sufficient to fully restore the fibroblastic function to the normal level. Particularly, the adverse effects of bis-acrylics and flowable composite remained significant. Milled and self-curing acrylic exhibited excellent and acceptable biocompatibility, respectively, compared to other materials.

This is the first genome-wide transcriptional profiling study using RNA-sequencing to investigate osteoblast responses to different titanium surface topographies, specifically between machined, smooth and acid-etched, microrough surfaces. Rat femoral osteoblasts were cultured on machine-smooth and acid-etched microrough titanium disks. The culture system was validated through a series of assays confirming reduced osteoblast attachment, slower proliferation, and faster differentiation on microrough surfaces. RNA-sequencing analysis of osteoblasts at an early stage of culture revealed that gene expression was highly correlated (r = 0.975) between the two topographies, but 1.38 % genes were upregulated and 0.37 % were downregulated on microrough surfaces. Upregulated transcripts were enriched for immune system, plasma membrane, response to external stimulus, and positive regulation to stimulus processes. Structural mapping confirmed microrough surface-promoted gene sharing and networking in signaling pathways and immune system/responses. Target-specific pathway analysis revealed that Rho family G-protein signaling pathways and actin genes, responsible for the formation of stress fibers, cytoplasmic projections, and focal adhesion, were upregulated on microrough surfaces without upregulation of core genes triggered by cell-to-cell interactions. Furthermore, disulfide-linked or -targeted extracellular matrix (ECM) or membranous glycoproteins such as laminin, fibronectin, CD36, and thrombospondin were highly expressed on microrough surfaces. Finally, proliferating cell nuclear antigen (PCNA) and cyclin D1, whose co-expression reduces cell proliferation, were upregulated on microrough surfaces. Thus, osteoblasts on microrough surfaces were characterized by upregulation of genes related to a wide range of functions associated with the immune system, stress/stimulus responses, proliferation control, skeletal and cytoplasmic signaling, ECM-integrin receptor interactions, and ECM-membranous glycoprotein interactions, furthering our knowledge of the surface-dependent expression of osteoblastic biomarkers on titanium.

Abstract We investigate Krylov complexity of the fermion chain operator which consists of multiple Majorana fermions in the double-scaled SYK (DSSYK) model with finite temperature. Using the fact that Krylov complexity is computable from two-point functions, the analysis is performed in the limit where the two-point function becomes simple and we compare the results with those of other previous studies. We confirm the exponential growth of Krylov complexity in the very low temperature regime. In general, Krylov complexity grows at most linearly at very late times in any system with a bounded energy spectrum. Therefore, we have to focus on the initial growth to see differences in the behaviors of systems or operators. Since the DSSYK model is such a bounded system, its chaotic nature can be expected to appear as the initial exponential growth of the Krylov complexity. In particular, the time at which the initial exponential growth of Krylov complexity terminates is independent of the number of degrees of freedom. More generally, and not limited to the DSSYK model, we systematically and specifically study the Lanczos coefficients and Krylov complexity using a toy power spectrum and deepen our understanding of those initial behaviors. In particular, we confirm that the overall sech-like behavior of the power spectrum shows the initial linear growth of the Lanczos coefficient, even when the energy spectrum is bounded.

Abstract Background In patients with chronic obstructive pulmonary disease (COPD), the clinical use of the minute ventilation-carbon dioxide production ( $$\rm{\dot V}$$ E- $$\rm{\dot V}$$ CO2) slope has been reported as a measure of exercise efficiency, but the oxygen uptake efficiency slope (OUES), i.e., the slope of oxygen uptake ( $$\rm{\dot V}$$ O2) versus the logarithmically transformed $$\rm{\dot V}$$ E, has rarely been reported. Methods We hypothesized that the $$\rm{\dot V}$$ E- $$\rm{\dot V}$$ CO2 slope is more useful than OUES in clinical use for the pathophysiological evaluation of COPD. Then, we investigated the cardiopulmonary exercise testing parameters affecting each of these slopes in 122 patients with all Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPD grades selected from our database. Results Compared with the GOLD I-II group (n = 51), peak $$\rm{\dot V}$$ O2 (p

Abstract We study timelike and conventional entanglement entropy as potential probes of black hole singularities via the AdS/CFT correspondence. Using an analytically tractable example, we find characteristic behavior of holographic timelike entanglement entropy when the geometry involves a curvature singularity. We also observe interesting phenomena that, in some particular setups, holographic timelike and conventional entanglement entropy are determined from multiple complex saddle points, which fall outside the assumptions of the Lewkowycz-Maldacena type argument.

Abstract Background The characteristics of bronchiectasis (BE) in Asia, including Japan, remain largely unknown. We aimed to provide insights into the clinical characteristics and treatment outcomes of BE, especially regarding nontuberculous mycobacteria (NTM) infection and its poorly understood impact on prognosis. We also aimed to clarify the effect of long-term macrolide antibiotic use in patients with BE, who had no history of exacerbations. Methods In this single-center, retrospective study, the medical records of patients who satisfied the BE criteria between January 1, 2012, and August 31, 2023, were reviewed. Severe exacerbations and mortality during the observation period were recorded. Baseline characteristics and overall survival of patients with and without NTM infection, and factors influencing the time to the first exacerbation and death were analyzed. Additionally, the effects of long-term macrolide antibiotic use in patients without a history of severe exacerbations were estimated. Results In a cohort of 1044 patients with BE, the rate of severe exacerbation was 22.3%, with mortality rates of 3.2% over 3 years. Notably, the high prevalence of NTM infection (n = 410, 39.3%) in this cohort was distinctive. NTM infection was not associated with either the time to first severe exacerbation (p = 0.5676, adjusted hazard ratio = 1.11) or mortality (p = 0.4139, adjusted hazard ratio = 0.78). Compared with the NTM group, the non-NTM group had a higher proportion of elevated inflammatory markers, with significant differences in C-reactive protein levels (p = 0.0301) and blood neutrophil counts (p = 0.0273). Pseudomonas aeruginosa colonization was more frequent in the non-NTM group (p = 0.0003). Among patients with non-NTM infection and without a history of exacerbation in the past 2 years, 38.2% received long-term macrolide antibiotics that did not invariably prolong the time to first severe exacerbation (p = 0.4517, IPW p = 0.3555). Conclusions This study highlights BE epidemiology in Japan, noting that the presence of NTM infection may not necessarily worsen the prognostic outcomes and advising caution in the casual use of macrolides for milder cases without a history of exacerbations. Clinical trial registration UMIN Clinical Trials Registry Number: UMIN000054726 (Registered on 21 June 2024).

Abstract Type I spiral ganglion neurons are peripheral neurons essential for hearing perception. While they can be subdivided in mice based on characteristic gene expression patterns, detailed examinations of these subtypes in primates and humans are lacking. In this study, we investigated the developmental subtypes of spiral ganglion neurons in the common marmoset (Callithrix jacchus). We confirmed that Type I spiral ganglion can be divided based on the characteristic gene expression patterns of several marker genes. However, some combinations of these genes differ from those in rodents, suggesting common marmoset's suitability for advancing our understanding of human cochlear development. Additionally, identifying the essential time points for subtype specifications and subsequent maturation will aid in studying the primate-specific developmental biology of the inner ear. This could lead to new treatment strategies for hearing loss in humans and be valuable for studying age-related hearing loss, as well as designing regenerative therapies.

Abstract In this study, equine intestinal enteroids (EIEs) were generated from the duodenum, jejunum, and ileum and inoculated with equine coronavirus (ECoV) to investigate their suitability as in vitro models with which to study ECoV infection. Immunohistochemistry revealed that the EIEs were composed of various cell types expressed in vivo in the intestinal epithelium. Quantitative reverse-transcription PCR (qRT-PCR) and virus titration showed that ECoV had infected and replicated in the EIEs. These results were corroborated by electron microscopy. This study suggests that EIEs can be novel in vitro tools for studying the interaction between equine intestinal epithelium and ECoV.