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The compressive creep deformation behavior of a Co-base single-crystalline superalloy is studied in the high temperature / low stress regime at 950°C/150 MPa. Emphasis is placed on the mechanisms causing the double minimum creep behavior consisting of a local and a global creep rate minimum. The local minimum occurs at ∼0.2% strain with dislocation accumulation at γ/γ′ interfaces after bowing out of dislocations in horizontal matrix channels. Plate-like rafting occurring normal to the applied stress axis in the early creep stages is regarded as the primary reason for the decreasing creep rate until the global minimum takes place at ∼0.8% strain. In the final creep stage following the global minimum the creep rate accelerates due to coarsening and extensive precipitate shearing. The shearing by partial dislocations leads to the formation of numerous stacking faults, nano/microtwins, and occasionally to the formation of small amounts of ordered D019-Co3W precipitates. The reasons for twinning and second phase formation as well as differences of the deformation mechanisms between Co- and Ni-base superalloys during double minimum creep are discussed in detail in this work. [ABSTRACT FROM AUTHOR]

Selective neck dissection (SND) is the treatment of choice in patients with oral squamous cell carcinomas (OSCCs) and clinically node-negative necks (cN0). The treatment of patients with positive-staged necks (cN+) includes SND as well as comprehensive neck dissection (CND). The clear benefit of one or the other remains under debate. We aim to address this lack of clarity by analysing patients with OSCC staged with clinically node-positive necks, treated with either CND or SND using a level-by-level approach. This retrospective study included patients diagnosed with OSCC with clinically (cN+) and pathologically (pN+) positive cervical lymph nodes (LNs) with clear neck level categorization during the years 2010-2019. In total, 74 patients were analysed. Cox regression analysis found no significance for the type of ND being an independent risk factor, neither for overall survival (OS) nor for disease-free survival (DFS). Regional recurrence of CND cases (5.77%) was comparable to SND cases (9.09%). For OS, extracapsular spread (ECS) and male sex were identified as independent risk factors with poorer outcome. pT-stage and ECS were found to be independent risk factors for DFS. The results of this study suggest that both CND and SND may be viable treatment options for certain patients with OSCC pN+., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Jan Oliver Voss et al.)

Snow-farming is one of the adaptive strategies used to face the snow deficit in ski resorts. We studied the impact of a shifting snow-farming technique on a pasture slope in Adelboden, Switzerland. Specifically, we compared plots covered by a compressed snow pile for 1.5, 2.5 or 3.5 years, which then recovered from the snow cover for three, two or one vegetation seasons, respectively, with control plots situated around the snow pile. In plots with >1.5 years of compressed snow pile, plant mortality was high, recovery of vegetation was very slow, and few plant species recolonized the bare surface. Soil biological activity decreased persistently under prolonged snow cover, as indicated by reduced soil respiration. The prolonged absence of fresh plant litter and root exudates led to carbon (C) limitation for soil microbial respiration, which resulted in a significant decrease in the ratio of total organic carbon to total nitrogen (TOC/TN) under the snow pile. Microbial C, nitrogen (N) and phosphorus (P) immobilization decreased, while dissolved N concentration increased with compressed snow cover. Longer snow cover and a subsequent shorter recovery period led to higher microbial C/P and N/P but lower microbial C/N. Nitrate and ammonium were released massively once the biological activity resumed after snow clearance and soil aeration. The soil microbial community composition persistently shifted towards oxygen-limited microbes with prolonged compressed snow cover. This shift reflected declines in the abundance of sensitive microorganisms, such as plant-associated symbionts, due to plant mortality or root die-off. In parallel, resistant taxa that benefit from environmental changes increased, including facultative anaerobic bacteria (Bacteroidota, Chloroflexota), obligate anaerobes (Euryarchaeota), and saprophytic plant degraders. We recommend keeping snow piles in the same spot year after year to minimize the area of the impacted soil surface and plan from the beginning soil and ecosystem restoration measures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Epidermal keratinocytes form the first-line cellular barrier of the skin for protection against external injuries and maintenance of local tissue homeostasis. Expression of ZBP1 was shown to cause necroptotic keratinocyte cell death and skin inflammation in mice. We sought to characterize the relevance of ZBP1 and necroptosis in human keratinocytes and type 1-driven cutaneous acute graft-versus-host disease. in this study, we identify ZBP1 expression, necroptosis, and interface dermatitis as being the hallmarks of acute graft-versus-host disease. ZBP1 expression was dependent on leukocyte-derived IFNγ, and interference with IFNγ signaling by Jak inhibition prevented cell death. In predominantly IL-17-driven psoriasis, both ZBP1 expression and necroptosis could not be detected. Of note, in contrast to the signaling in mice, ZBP1 signaling in human keratinocytes was not affected by RIPK1's presence. These findings show that ZBP1 drives inflammation in IFNγ-dominant type 1 immune responses in human skin and may further point to a general role of ZBP1-mediated necroptosis., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: In lateralized oral squamous cell carcinoma (OSCC) with ipsilateral cervical lymph node metastasis (CLNM), the surgical management of the unsuspicious contralateral neck remains a matter of debate. The aim of this study was to analyze this cohort and to compare the outcomes of patients with and without contralateral elective neck dissection (END)., Material and Methods: A retrospective analysis of patients with lateralized OSCC, ipsilateral CLNM (pN+) and contralateral cN0-stage was performed. Patients were divided into two groups according to the surgical management of the contralateral neck: I: END; and II: no END performed. Adjuvant radiotherapy was applied bilaterally in both groups according to individual risk., Results: A total of 65 patients (group I: 16 (24.6%); group II: 49 (75.4%)) with a median follow-up of 28 months were included. Initially, there was no case of contralateral CLNM after surgery. During follow-up, 6 (9.2%) patients presented with recurrent CLNM. In 5 of these cases (7.7%), the contralateral neck (group I: 3/16 (18.8%); group II: 2/49 (4.1%)) was affected. Increased ipsilateral lymph node ratio was associated with contralateral CLNM ( p = 0.07). END of the contralateral side showed no significant benefit regarding OS ( p = 0.59) and RFS ( p = 0.19)., Conclusions: Overall, the risk for occult contralateral CLNM in patients with lateralized OSCC ipsilateral CLNM is low. Our data suggest that END should not be performed routinely in this cohort. Risk-adapted radiotherapy of the contralateral neck alone seems to be sufficient from the oncological point of view.

Objectives: Different parameters have been identified in patients with oral squamous cell carcinomas (OSCC) that have a serious impact on survival, including residual tumour and extracapsular spread. Moreover, other factors, including the lymph node ratio (LNR) and lymph node yield (LNY), have been suggested as prognostic markers., Material and Methods: This retrospective study included patients diagnosed with OSCC and cervical lymph node metastases during the years 2010-2020. Patients' records were evaluated regarding lymph node status, final therapy regime, tumour recurrence, time to death, tumour association with death, disease-free survival (DSF), and overall survival (OS)., Results: In 242 patients with a mean age of 63.57 ± 11.24 years, treated either by selective neck dissection (SND; n = 70) or by modified radical neck dissection (MRND; n = 172), 5772 lymph nodes were detected. The LNR and LNY were identified as independent risk factors in OS and DFS. The optimal cut-off point for the LNY was ≥ 17 lymph nodes in the SND and ≥ 27 lymph nodes in the MRND group. The metastatic lymph node clearance (MLNC) was established as a score to relate the LNR and LNY to the extent of lymph node removal. Survival analysis showed statistically significant differences among score levels., Conclusions: As information about the extent of nodal dissection is excluded from LNR and LNY, we propose the use of a new scoring system comprising individual cut-off values for LNY and LNR with regard to the extent of neck dissection., Clinical Relevance: MLNC might help to identify high-risk OSCC patients with metastatic lymph nodes., (© 2022. The Author(s).)

Fertility drugs have not definitively been linked to malignant melanoma. By the use of data from a large nationwide cohort of women aged 20.0-45.0 years and living in Denmark between January 1, 1995 and December 31, 2011, we assessed the association between the use of fertility drugs and the risk of malignant melanoma. Information on fertility status and the use of fertility drugs was obtained from the population-based Danish Infertility Cohort. Cox proportional hazard regression models were applied to estimate hazard ratios and 95% confidence intervals with adjustment for potential confounders. The study population comprised 1,330,954 women, of whom 86,231 (6.5%) were treated with fertility drugs. During a median follow-up of 21.0 years, 6,139 women were diagnosed with malignant melanoma. Compared with fertile women, women with fertility challenges who had used any fertility drugs had an increased risk of malignant melanoma (hazard ratio = 1.14; 95% confidence interval = 1.02-1.27). Furthermore, the use of specific types of fertility drugs (clomiphene, gonadotropins, human chorionic gonadotropin, gonadotropin-releasing hormone preparations, and progesterone) was also associated with an increased risk of malignant melanoma, with hazard ratios ranging between 1.09 and 1.13; however, the association did not reach statistical significance. Our findings indicate that the use of fertility drugs was associated with a modestly increased risk of malignant melanoma., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The additive-free tetrazine/enol ether click reaction was performed in ultra-high vacuum (UHV) with an enol ether group covalently linked to a silicon surface: Dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate molecules were coupled to the enol ether group of a functionalized cyclooctyne which was adsorbed on the silicon (001) surface via the strained triple bond of cyclooctyne. The reaction was observed at a substrate temperature of 380 K by means of X-ray photoelectron spectroscopy (XPS). A moderate energy barrier was deduced for this click reaction in vacuum by means of density functional theory based calculations, in good agreement with the experimental results. This UHV-compatible click reaction thus opens a new, flexible route for synthesizing covalently bound organic architectures., (© 2021 The Authors. Published by Wiley-VCH GmbH.)

Evolutionary diversification can occur in allopatry or sympatry, can be driven by selection or unselected, and can be phenotypically manifested immediately or remain latent until manifested in a newly encountered environment. Diversification of host-parasite interactions is frequently studied in the context of intrinsically selective coevolution, but the potential for host-parasite interaction phenotypes to diversify latently during parasite-blind host evolution is rarely considered. Here, we use a social bacterium experimentally adapted to several environments in the absence of phage to analyse allopatric diversification of host quality-the degree to which a host population supports a viral epidemic. Phage-blind evolution reduced host quality overall, with some bacteria becoming completely resistant to growth suppression by phage. Selective-environment differences generated only mild divergence in host quality. However, selective environments nonetheless played a major role in shaping evolution by determining the degree of stochastic diversification among replicate populations within treatments. Ancestral motility genotype was also found to strongly shape patterns of latent host-quality evolution and diversification. These outcomes show that (i) adaptive landscapes can differ in how they constrain stochastic diversification of a latent phenotype and (ii) major effects of selection on biological diversification can be missed by focusing on trait means. Collectively, our findings suggest that latent-phenotype evolution should inform host-parasite evolution theory and that diversification should be conceived broadly to include latent phenotypes.

Antibody-modified gold nanomaterials are central to many novel biosensing technologies for example the lateral flow assays technology. The combination of the specificity, provided by antibody-antigen interactions, and the unique optical properties of nanomaterials provide excellent properties for biosensors. Here, we present the use of gold nanorods (GNR) with the localized Surface Plasmon Resonance (LSPR) peak in the visible range for biomarker detection. The colour of the GNR can be tuned by the reaction conditions to provide multi-coloured gold nanorod conjugates. These antibody functionalized GNR have the potential to provide significant improvements in multiplexed analysis and sensitivity compared to conventional gold nanoparticle based lateral flow assays. However, a major challenge is the synthesis of stable conjugates that resist aggregation in samples with high ionic strength, (e.g. salt solutions) and allow highly sensitive detection of proteins. A detailed investigation of different reagents for the functionalization of gold nanorod materials are reported. An antibody modified GNR based lateral flow assay is validated for the determination of C-reactive Protein (CRP)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Mononuclear phagocytes and NK cells constitute the first line of innate immune defense. How these cells interact and join forces against cancer is incompletely understood. Here, we observed an early accumulation of slan + (6-sulfo LacNAc) non-classical monocytes (slanMo) in stage I melanoma, which was followed by an increase in NK cell numbers in stage III. Accordingly, culture supernatants of slanMo induced migration of primary human NK cells in vitro via the chemotactic cytokine IL-8 (CXCL8), suggesting a role for slanMo in NK cell recruitment into cancer tissues. High levels of TNF-α and IFN-γ were produced in co-cultures of TLR-ligand stimulated slanMo and NK cells, whereas much lower levels were contained in cultures of slanMo and NK cells alone. Moreover, TNF-α and IFN-γ concentrations in slanMo/NK cell co-cultures exceeded those in CD14 + monocyte/NK cell and slanMo/T cell co-cultures. Importantly, TNF-α and IFN-γ that was produced in TLR-ligand stimulated slanMo/NK cell co-cultures induced senescence in different melanoma cell lines, as indicated by reduced melanoma cell proliferation, increased senescence-associated β-galactosidase expression, p21 upregulation, and induction of a senescence-associated secretory phenotype (SASP). Taken together, we identified a role for slanMo and NK cells in a collaborative innate immune defense against melanoma by generating a tumor senescence-inducing microenvironment. We conclude that enhancing the synergistic innate immune crosstalk of slanMo and NK cells could improve current immunotherapeutic approaches in melanoma., (© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Psoriasis is an inflammatory skin disease with strong neutrophil (PMN) infiltration and high levels of the antimicrobial peptide, LL37. LL37 in complex with DNA and RNA is thought to initiate disease exacerbation via plasmacytoid dendritic cells. However, the source of nucleic acids supposed to start this initial inflammatory event remains unknown. We show here that primary murine and human PMNs mount a fulminant and self-propagating neutrophil extracellular trap (NET) and cytokine response, but independently of the canonical NET component, DNA. Unexpectedly, RNA, which is abundant in NETs and psoriatic but not healthy skin, in complex with LL37 triggered TLR8/TLR13-mediated cytokine and NET release by PMNs in vitro and in vivo. Transfer of NETs to naive human PMNs prompts additional NET release, promoting further inflammation. Our study thus uncovers a self-propagating vicious cycle contributing to chronic inflammation in psoriasis, and NET-associated RNA (naRNA) as a physiologically relevant NET component.

With cellular products being on the front run there is a rising demand for non-animal-based test platforms to predict, study and treat undesired immunity. Here, we generated human organotypic skin models from human biopsies isolating and expanding keratinocytes, fibroblasts and microvascular endothelial cells finally allowing to seed these components on a collagen matrix or a biological vascularized scaffold matrix in a bioreactor. Afterwards, we were able to induce inflammation-based tissue damage by pre-stimulated mismatched allogeneic lymphocytes and/or inflammatory cytokine containing supernatants histomorphologically mimicking severe graft versus host disease (GvHD) of the skin. The effects could be prevented by the addition of immunosuppressants to the models. Consequently, these models would harbor a promising potential to serve as a test platform for the prediction, prevention and treatment of GvHD. This would also allow functional studies of immune effectors and suppressors including but not limited to allodepleted lymphocytes, gamma-delta T cells, regulatory T cells and mesenchymal stromal cells which would otherwise be limited to animal models. Thus, the current test platform developed with the limitation given that no professional APC are in place could highly reduce animal testing for investigation of novel immune therapies.

Bacteria frequently exchange metabolites by diffusion through the extracellular environment, yet it remains generally unclear whether bacteria can also use cell-cell connections to directly exchange nutrients. Here we address this question by engineering cross-feeding interactions within and between Acinetobacter baylyi and Escherichia coli, in which two distant bacterial species reciprocally exchange essential amino acids. We establish that in a well-mixed environment E. coli, but likely not A. baylyi, can connect to other bacterial cells via membrane-derived nanotubes and use these to exchange cytoplasmic constituents. Intercellular connections are induced by auxotrophy-causing mutations and cease to establish when amino acids are externally supplied. Electron and fluorescence microscopy reveal a network of nanotubular structures that connects bacterial cells and enables an intercellular transfer of cytoplasmic materials. Together, our results demonstrate that bacteria can use nanotubes to exchange nutrients among connected cells and thus help to distribute metabolic functions within microbial communities.