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Aim: This study aimed to reveal the unique microenvironment of peri‐implantitis through single‐cell analysis. Materials and Methods: Herein, we performed single‐cell RNA sequencing (scRNA‐seq) of biopsies from patients with peri‐implantitis (PI) and compared the results with healthy individuals (H) and patients with periodontitis (PD). Results: Decreased numbers of stromal cells and increased immune cells were found in the PI group, which implies a severe inflammatory infiltration. The fibroblasts were found to be heterogeneous and the specific pro‐inflammatory CXCL13+ sub‐cluster was more represented in the PI group, in contrast to the PD and H groups. Furthermore, more neutrophil infiltration was detected in the PI group than in the PD group, and cell–cell communication and ligand–receptor pairs revealed most neutrophils were recruited by CXCL13+ fibroblasts through CXCL8/CXCL6‐CXCR2/CXCR1. Notably, our study demonstrated that the unique microenvironment of the PI group promoted the differentiation of monocyte/macrophage lineage cells into osteoclasts, which might explain the faster and more severe bone resorption in the progression of PI than PD. Conclusions: Collectively, this study suggests a unique immune microenvironment of PI, which may explain the differences between PI and PD in the clinic. These outcomes will aid in finding new specific and effective treatments for PI. [ABSTRACT FROM AUTHOR]

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A near-isothermal thermomechanical processing scheme was put forward to obtain bi-modal microstructure for near β-Ti alloys. To this end, this paper focuses on the microstructure evolution and deformation behavior under non-equilibrium forging conditions. Two types of experiments were performed for the Ti-55531 alloy with an original equiaxed structure: (1) static cooling and (2) concurrent deformation/cooling. In static cooling, the formation mode of αs phase is via αp/β phase interface instability or sympathetic nucleation, which is determined by the deviation degree of Burgers orientation relationship (BOR) of αp and β phases. In the near-isothermal deformation, formed low-angle boundaries and high-angle boundaries increase the available nucleation locations and cause the loss of BOR, which contribute to the morphology change for αs phase and accelerated phase transformation kinetics of β to αs. The bi-modal microstructure, including αp phase and fine-equiaxed or rodlike αs phase, respectively, is produced by a cooperation between dynamic precipitation of αs phase and DRX and DRV of β phase. Moreover, the texture intensity of α phase is weakened, and flow stress is reduced by 30% compared to that in the isothermal deformation, due to a delay in α phase precipitation, and grain-boundary sliding at αs–β interfaces. This finding provides a novel method to achieve bi-modal microstructure with weak material anisotropy and load-saving forming. [ABSTRACT FROM AUTHOR]

Aim: Rev‐erbα has been reported to regulate the healing of inflammatory lesions through its effect on the immune system in a variety of inflammatory disease. Moreover, the balance of macrophages polarization plays a crucial role in immune response and inflammatory progression. However, in refractory periapical periodontitis (RAP), the role of Rev‐erbα in inflammatory response and bone resorption by regulating macrophage polarization remains unclarified. The aims of the present study were to investigate the expression of Rev‐erbα in experimental RAP and to explore the relationship between Rev‐erbα and macrophage polarization through the application of its pharmacological agonist SR9009 into the in vivo and in vitro experiments. Methodology: Enterococcus faecalis‐induced RAP models were established in SD rats. Histological staining and micro‐computed tomography scanning were used to evaluate osteoclastogenesis and alveolar bone resorption. The expression of Rev‐erbα and macrophage polarization were detected in the periapical tissues from rats by immunofluorescence, flow cytometry, and western blots. Furthermore, immunohistochemical staining and enzyme‐linked immunosorbent assay were performed to explore the relationship between Rev‐erbα and inflammatory cytokines related to macrophage polarization. Result: Compared to healthy periapical tissue, the expression of Rev‐erbα was significantly down‐regulated in macrophages from inflammatory periapical area, especially in Enterococcus faecalis‐induced periapical lesions, with obvious type‐1 macrophage (M1)‐like dominance and the production of pro‐inflammatory cytokines. In addition, Rev‐erbα activation by SR9009 could induce type‐2 macrophage (M2)‐like polarization in periapical tissue and THP1 cell line, followed by increased secretion of anti‐inflammatory cytokines IL‐10 and TGF‐β. Furthermore, intracanal application of SR9009 reduced the lesion size and promoted the repair of RAP by decreasing the number of osteoclasts and enhancing the formation of mineralized tissue in periapical inflammatory lesions. Conclusions: Rev‐erbα played an essential role in the pathogenesis of RAP through its effect on macrophage polarization. Targeting Rev‐erbα might be a promising and prospective therapy method for the prevention and management of RAP. [ABSTRACT FROM AUTHOR]

The multi-markers combined detection can make up for the deficiency of single marker detection and significantly increase the positive detection rates of tumors. This study aimed to assess the performance of serum HER-2 extracellular domain (HER-2/neu ECD), carcinoembryonic antigen (CEA), and cancer antigen 15-3 (CA15-3) in early screening and auxiliary diagnosis of breast cancer. The HER-2, CEA, and CA15-3 serum levels were measured in 164 healthy volunteers, 111 patients with benign nodules (BN), 123 with early breast cancer (EBC), and 25 with advanced breast cancer. In distinguishing health and EBC, the sensitivity and specificity of joint detection of HER-2, CEA, and CA15-3 were 96.75% and 96.95%, respectively; the accuracy was up to 96.19%, and the AUC was 0.994. In the cohort for distinguishing BN from EBC, serum HER-2, CEA, and CA15-3 sensitivities were 77.03%, 75.27%, and 48.65%, respectively. Combined with three markers, the sensitivity was increased to 84.46%, the AUC was 0.834. All in all, through the combined detection of serum HER-2, CEA and CA15-3 levels in healthy volunteers, BN and EBC, our study found that this method can significantly improve the diagnosis level of breast cancer, suggesting that the three markers panel can be used as an effective tool to improve the early screening level, early diagnosis, and clinical intervention of breast cancer. [ABSTRACT FROM AUTHOR]

As a crucial source of mesenchymal stromal cells, CD51+/PDGFR-α+ human dental pulp stromal cells (hDPSCs) are promising seeding cells for regenerative medicine. Cellular senescence hinders the translational application of hDPSCs. However, it remains unclear whether chronological and replicative senescence results in distinct outcomes for hDPSCs. To investigate the influence of senescence on DPSCs, we used transgenic lineage tracking, immunofluorescence, flow cytometry, and various molecular experiments to depict the dynamic pattern of hDPSCs in mice and humans during chronological and replicative senescence. The data demonstrated that CD51+/PDGFR-α+ cells were decreased in chronological senescence. Impaired self-renewal and higher ossificatory differentiation were observed in chronologically senescent hDPSCs. Regarding replicative senescence, a decreased CD51+ but upregulated PDGFR-α+ population was observed in culture. Furthermore, weakened self-renewal and osteogenic differentiation were observed in replicatively senescent hDPSCs. In summary, CD51+/PDGFR-α+ hDPSCs decrease in chronologically aged pulp, with self-renewal that is impaired without impaired osteogenic differentiation. However, replicative senescence has a different impact: self-renewal and ossific differentiation are impaired and CD51 expression is reduced, but PDGFR-α expression remains. These findings demonstrate the different outcomes of chronological and replicative senescence in CD51+/PDGFR-α+ hDPSCs. Furthermore, we revealed that impaired self-renewal is the core dysfunction for both types of cellular aging and that osteogenic differentiation capability differs between them. This study provides insights into the influence of chronological and replicative senescence on the characteristics and capabilities of hDPSCs. These advances provide fundamental knowledge to alleviate cellular aging of CD51+/PDGFR-α+ hDPSCs and promote their translational applications. [ABSTRACT FROM AUTHOR]

A mathematical model is developed that makes it possible, within the framework of a single phenomenological approach, to investigate the stability of a planar phase boundary during directional solidification of binary alloy, taking into account the effect of a density change and heat transfer in the solid phase. The study reveals a complex picture of alternating areas of stability and instability, which is sensitive to changes in parameters of growth and temperature gradient at the interface. Areas of instability are formed by the development of a set of disturbances of different frequencies and rates of propagations. As shown, the irreducible liquid-phase flow caused by density change plays a major role in the loss of stability of the solidification front and is realized for perturbations with any wave number k > 0. [ABSTRACT FROM AUTHOR]

Background: Circular RNA (circRNA) has been reported to regulate respiratory diseases. In the study, we aimed to elucidate the role of circ_0000157 in smoke-related chronic obstructive pulmonary disease (COPD) and the inner mechanism. Methods: COPD-like cell injury was induced by treating human bronchial epithelioid cells (16HBE) with cigarette smoke extract (CSE). The expression of circ_0000157, miR-149-5p, bromodomain containing 4 (BRD4), BCL2-associated x protein (Bax) and B-cell lymphoma-2 (Bcl-2) was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) or Western blotting. Enzyme-linked immunosorbent assay was performed to detect interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels. Malondialdehyde (MDA) production was detected by a lipid peroxidation MDA assay kit. Superoxide dismutase (SOD) activity was analyzed by a SOD activity assay kit. Results: Circ_0000157 and BRD4 expression were upregulated, while miR-149-5p expression was downregulated in the blood of smokers with COPD and CSE-induced 16HBE cells compared with control groups. CSE treatment inhibited 16HBE cell proliferation and induced cell apoptosis, inflammation, and oxidative stress; however, these effects were remitted when circ_0000157 expression was decreased. In addition, circ_0000157 acted as a miR-149-5p sponge and regulated CSE-caused 16HBE cell damage by targeting miR-149-5p. The overexpression of BRD4, a target gene of miR-149-5p, attenuated the inhibitory effects of miR-149-5p introduction on CSE-induced cell damage. Further, circ_0000157 modulated BRD4 expression by associating with miR-149-5p in CSE-treated 16HBE cells. Conclusion: Circ_0000157 knockdown ameliorated CSE-caused 16HBE cell damage by targeting the miR-149-5p/BRD4 pathway, providing a potential therapeutic strategy for clinic intervention in COPD. [ABSTRACT FROM AUTHOR]

The creep characteristics of soft soil from the Luogang District of Guangzhou (China) were analyzed using a laboratory-based direct shear creep apparatus. Normal stress was applied to the samples, and the corresponding displacement was monitored under constant horizontal shear stress. The results show that at lower shear stress levels, Luogang soft soil shows the characteristics of attenuated stable creep. At higher shear stress levels, the creep curve enters a phase of constant creep. The constant creep rate increases with increasing shear stress. We developed a nonlinear creep constitutive model by combining the nonlinear creep stress-strain isochronous curve of the soft soil with theoretical and empirical models. This model will be useful for devising strategies to prevent landslides during sudden natural disasters. [ABSTRACT FROM AUTHOR]

To assess feasibility of a novel video directly observed therapy (DOT)-based digital asthma program intended to support correct inhaled corticosteroid (ICS) use among children. We conducted a 60-day pilot study among patients 2–18 years attending a primary care clinic with prescribed ICS and sub-optimally controlled asthma (recent hospitalization, ICS nonadherence, frequent rescue inhaler use, therapy escalation, or Asthma Control Test <20). Participants used a mobile application to receive reminders, submit videos of ICS doses (video DOT), and receive asynchronous feedback on adherence and inhaler technique. We assessed enrollment, engagement, program metrics, and user experience; adherence and inhaler errors were secondary outcomes. Of 26 eligible patients, 21 (81%) enrolled and submitted ≥1 video; median age was 11 years (8–15), 71% were male, 90% had Medicaid, and 62% experienced ≥1 exacerbation in the previous 6 months. Retention was 57% and 52% at week 5 and 8, respectively. Participants submitted 810 videos. Missed doses, inhaler errors (n = 247) and adherence issues (n = 107) prompted 543 communications; inadequate inspiration or holding breath were most common. Among 16 patients with engagement >7 days and >4 videos, median inhaler error rate (proportion of videos with ≥1 error) decreased from week 1 to week 2 (73% vs 8%, p ≤ 0.05) with median adherence >80%. Participants experienced the program as long, but easy to use; benefits included building routines, skill, and independence. This pilot study suggests high program acceptability among our cohort. High engagement with improved inhaler technique over the first 14 days suggests shorter implementation. Supplemental data for this article is available online at at [ABSTRACT FROM AUTHOR]

Background: Non-Hodgkin lymphoma (NHL) represents a heterogenous group of malignant lymphoproliferative neoplasms originating from lymphoid tissue cells and having distinct clinical, cytomorphological, immunological and molecular and genetic features. Primary orbital lymphomas are rare and account for approximately 1% of all NHL. Lymphomas are, however, the most common primary orbital tumor in adults 60 years of age and older. Purpose: To present a rare case of primary B-cell MALT lymphoma of marginal zone of the upper eyelid, to highlight its clinical features, and to demonstrate the importance of a multidisciplinary approach to its treatment. Results: A male patient presented to the eye clinic complaining of bilateral pterygium and periodic nasal congestion. Within the course of examination and prolonged observation, the ophthalmologist suspected the symptoms of massive orbital disease, and the patient was referred for magnetic resonance imaging (MRI) of the brain. On the basis of imaging assessment and the oncologist's opinion, the patient was hospitalized at the Podillia Regional Oncology Center with a preliminary diagnosis of orbital lymphoma. Thereat, a final diagnosis of "extranodal, non-Hodgkin's B-cell lymphoma of the marginal zone (MALT lymphoma) of Stage 3a, with metastases in the lungs, pleura and lymph nodes of the mediastinum" was established. At the moment, he is under observation by an oncologist and on the way to stabilization of his major disease. Conclusion: Management of orbital non-Hodgkin's lymphomas remains a challenge requiring a multidisciplinary approach involving ophthalmologists and oncologists. [ABSTRACT FROM AUTHOR]

Background: Older people receive care from multiple providers which often results in a lack of coordination. The Information and Communication Technology (ICT) enabled value-based methodology for integrated care (ValueCare) project aims to develop and implement efficient outcome-based, integrated health and social care for older people with multimorbidity, and/or frailty, and/or mild to moderate cognitive impairment in seven sites (Athens, Greece; Coimbra, Portugal; Cork/Kerry, Ireland; Rijeka, Croatia; Rotterdam, the Netherlands; Treviso, Italy; and Valencia, Spain). We will evaluate the implementation and the outcomes of the ValueCare approach. This paper presents the study protocol of the ValueCare project; a protocol for a pre-post controlled study in seven large-scale sites in Europe over the period between 2021 and 2023.Methods: A pre-post controlled study design including three time points (baseline, post-intervention after 12 months, and follow-up after 18 months) and two groups (intervention and control group) will be utilised. In each site, (net) 240 older people (120 in the intervention group and 120 in the control group), 50-70 informal caregivers (e.g. relatives, friends), and 30-40 health and social care practitioners will be invited to participate and provide informed consent. Self-reported outcomes will be measured in multiple domains; for older people: health, wellbeing, quality of life, lifestyle behaviour, and health and social care use; for informal caregivers and health and social care practitioners: wellbeing, perceived burden and (job) satisfaction. In addition, implementation outcomes will be measured in terms of acceptability, appropriateness, feasibility, fidelity, and costs. To evaluate differences in outcomes between the intervention and control group (multilevel) logistic and linear regression analyses will be used. Qualitative analysis will be performed on the focus group data.Discussion: This study will provide new insights into the feasibility and effectiveness of a value-based methodology for integrated care supported by ICT for older people, their informal caregivers, and health and social care practitioners in seven different European settings.Trial Registration: ISRCTN registry number is 25089186 . Date of trial registration is 16/11/2021. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment is common in the elderly. Prior studies suggest a link between chronic inflammation and cognitive dysfunction, while aging‐associated epidermal dysfunction has been connected to elevations in circulating cytokines. Objective: We assessed here whether improvements in epidermal function can mitigate the progression of cognitive impairment. Methods: This randomized, open‐label pilot trial was carried out in two cities in northern China. A total of 200 participants aged ≥65 years were randomly assigned to the emollient‐treated and untreated groups at 1:1 ratio. Participants in the treated group were treated topically with Atopalm cream® twice‐daily from November to the following May each year for three consecutive years, while the untreated subjects served as controls. The Global Deterioration Scale (GDS) was used to assess the severity of cognitive impairment, while epidermal biophysical properties were measured on the forearms and the shins in parallel. Results: Over the three‐year trial, GDS significantly increased from baseline (P < 0.0001) in the controls, while in the treated group, GDS stabilized. While stratum corneum hydration on the forearms did not change significantly in the controls, transepidermal water loss rates (TEWL), significantly increased by the end of the trial compared to baselines in the controls (P < 0.0001). On the forearms of the treated group, stratum corneum hydration increased (P < 0.0001) while skin surface pH decreased from baseline (P < 0.0001). Conclusions: These results suggest that improvements in epidermal function with topical emollient can mitigate the progression of cognitive impairment. However, the sample size was relatively small, and trials in a larger cohort are needed to validate the present results. [ABSTRACT FROM AUTHOR]

New optical coordinated complexes CuxNi1 – x(C2H6N2O)6SO4 (x = 0.31, 0.49, 0.66) were synthesized and the single crystal Cu0.66Ni0.34(C2H6N2O)6SO4 (I) was selected for characterization. FT-IR and Raman spectroscopic studies were carried out to identify the various functional groups present in crystal. The crystal structure I was established by single crystal X-ray diffraction (XRD) technique (CIF file CCDC no. 2068488) and the complex belongs to trigonal system, space group. TGA–DTA measurements showed complex I remains stable until about 180°C. UV−Vis spectrum of complex I exhibited three absorption bands in ultraviolet, visible and near-infrared region, respectively, which was attributed to d–d, L–M and π–π* transitions absorption. Moreover, the absorption peaks of I have a distinct bathochromic shift (20 nm) compared with M(H2O units (M = Ni, Cu). The photophysical properties allow it to selectively filter yellow-green and blue-violet light. [ABSTRACT FROM AUTHOR]

Artificial sweeteners can bind to the sweet taste receptors T1R2/T1R3 on the cell membrane of taste receptor cells, including intestinal enteroendocrine cells, and induce an increase in intracellular Ca2+ concentration ([Ca2+]i). Acute adaptation or a reduction in receptor signalling was observed after prolonged exposure to a taste stimulus in an animal model. However, at the cell level, it remains unclear whether the expression level of T1R2/T1R3 will be changed by pre-exposure to sweetener molecules, and whether the corresponding change in [Ca2+]i induced by the altered expression of sweet taste receptors varies. In the present work, western blotting and qPCR analysis showed that the expression level of T1R2/T1R3 in NCI-H716 cells was upregulated by sucralose stimulation. In the sucralose-treated cells, the accumulation of intracellular Ca2+ in the sweetener pre-treated cells was significantly enhanced as compared to that in cells without sweetener pre-treatment, although the sweet response differed between acesulfame K and sucralose with the same sweetness. Collectively, the increased expression of T1Rs in sweetener pre-incubated cells enhanced the sweet taste signal response, which implies that long-term administration of artificial sweeteners in beverages or foods could alter the sensitivity of taste receptor cells to sweetener molecules. [ABSTRACT FROM AUTHOR]

This article discusses a case of plasma cell dactylitis, a rare disease that can mimic bacterial and fungal infections. The case involves a 56-year-old woman who presented with ulceration on both toes that did not respond to previous treatments. Histopathological analysis confirmed the diagnosis of plasma cell dactylitis. The patient was treated with a combination of oral medications and showed improvement after one month. The article also provides information on the etiology, clinical presentation, and treatment options for plasma cell dactylitis. [Extracted from the article]

Aim: To explore the mechanism of secreted frizzled‐related protein I (sFRP1) involvement in the osteogenic differentiation of human periodontal ligament cells (hPDLCs) under inflammatory conditions. Methodology: hPDLCs were cultured in an osteogenic differentiation‐inducing medium (odi) and subjected to the stimulation of Porphyromonas gingivalis lipopolysaccharide (P. gingivalis LPS) with or without the inhibition of sFRP1. Quantitative real‐time polymerase chain reaction, Western blot and enzyme‐linked immunosorbent assay were carried out to evaluate the expression of osteogenic markers as well as the classic Wnt signalling pathway. Periapical periodontitis was induced in Wistar rats to further confirm the effect of sFRP1 inhibitor on bone loss in vivo. After the Shapiro–Wilk normality test, data were analysed by Student's paired t‐test or one‐way Anova test with a P value less than 0.05 as the level of statistical significance. Results: Significantly decreased mRNA and protein expression of osteogenic markers were detected in hPDLCs treated with P. gingivalis LPS during osteogenic induction (P < 0.001). Increased expression of sFRP1 was observed (P < 0.01), whilst Wnt/β‐catenin signalling pathway was inhibited by the addition of P. gingivalis LPS (P < 0.01). After the addition of the sFRP1 inhibitor, the decrease of osteogenic markers (P < 0.05) and the inhibition of Wnt/β‐catenin signalling pathway (P < 0.05) were reversed significantly. The animal experiment further confirmed that the sFRP1 inhibitor significantly reduced bone loss of periapical lesions in vivo (P < 0.0001). Conclusions: Wnt antagonist sFRP1 was involved in the osteogenic differentiation of hPDLCs under inflammation. Modulation of the Wnt/β‐catenin signalling pathway through the inhibition of sFRP1 may offer a new perspective on the treatment of chronic apical periodontitis. [ABSTRACT FROM AUTHOR]

This study focuses on the interactions between sediment stability and biological and physical variables that influence the erodibility across different habitats. Sampling at short‐term temporal scales illustrated the persistence of the microphytobenthos (MPB) biomass even during periods of frequent, high physical disturbance. The role of MPB in biological stabilization along the changing sedimentary habitat was also assessed. Key biological and physical properties, such as the MPB biomass, composition, and extracellular polymeric substances, were used to predict the sediment stability (erosion threshold) of muddy and sandy habitats within close proximity to one another over multiple days, and within emersion periods. The effects of dewatering, MPB growth, and productivity were examined as well as the resilience and recovery of the MPB community after disturbance from tidal currents and waves. Canonical analysis of principal components (CAP) ordinations were used to visualize and assess the trends observed in biophysical properties between the sites, and marginal and sequential distance‐based linear models were used to identify the key properties influencing erodibility. While the particle size of the bed was important for differences between sites in the CAP analysis, it contributed less to the variability in sediment erodibility than key biological parameters. Among the biological predictors, MPB diversity explained very little variation in marginal tests but was a significant predictor in sequential tests when MPB biomass was also considered. MPB diversity and biomass were both key predictors of sediment stability, contributing 9% and 10%, respectively, to the final model compared to 2% explained by grain size. [ABSTRACT FROM AUTHOR]

Most of the lunar surface area has been observed from different viewing conditions thanks to the on-orbit work of lunar orbiters, a large amount of images are available for photogrammetric three-dimensional mapping, which is an important issue for lunar exploration. Theoretically, multi-view images contain more information than a single stereo pair and can get better 3D mapping results. In this paper, the semi-global matching method is applied to the object space, and the steps of cost calculation, cost aggregation, and elevation calculation are performed to obtain the three-dimensional coordinates directly. Compared with the traditional image-based semi-global matching method, the object-based semi-global method is more easily extended to multi-view images, which is beneficial for applying multi-view image information. In addition, it does not require steps such as stereo rectification and forward intersection, that is, the overall pipeline is more elegant. Using the LRO NAC images covering Apollo 11 landing area as the experimental data, the result shows that the object-based semi-global matching is competent for the multi-view image matching and the multi-view image result achieves higher accuracy and more details than the single stereo pair. Furthermore, the experimental results of Zhinyu crater data show that this method can also alleviate the uncertainty of the lunar orbiter's positioning to some extent. [ABSTRACT FROM AUTHOR]

A bimetallic coordination polymer is prepared via a hydrothermal reaction of H2DDBA and In(NO3) water with NaOH as a pH regulator. Its chemical formula is [In2Na(H2O)6(ddba)3](NO3)(H2O)7 (1, H2ddba = 4,4′-dithiodibenzoic acid). The composition and atomic arrangement of the prepared complexes are studied by the elemental analysis (EA) and the thermogravimetric analysis (TGA), powder and single crystal X-ray diffraction measurements. Moreover, a process of sonochemistry with oleic acid treatment at 453 K is used to produce nanostructure the biological function detection, a miRNA relative expression is detected via RT-PCR and Bcl-2 expression level is determined with the Western blot. The Annexin V-FITC/PI staining is performed to detect retinoblastoma cell apoptosis after treatment with nano-1. [ABSTRACT FROM AUTHOR]

This paper establishes a numerical model for simulating submarine surfacing through the ice. The numerical model is simplified to be the interaction between a submarine and an ice sheet. The ice sheet is discretized into a number of ice material particles, and the motion and the failure of them are calculated by the peridynamic method. A contact detection method is used to determine the interpenetration between ice material particles and the submarine. To verify the feasibility of peridynamics in modelling ice failure, the two cases of three-point bending of columnar ice and vertical penetration of ice sheet for a cylinder are simulated. Convergence studies are taken with respect to the particle spacing size for submarine surfacing through ice. The surfacing process of the submarine has been simulated, and the calculation results are discussed. The calculated ice failure feature is similar to the full-scale observation. [ABSTRACT FROM AUTHOR]

This study verifi ed the applicability of Raman spectroscopy for the detection and classifi cation of disease in citrus leaves. The Raman spectra of citrus leaves were collected using a SENTERRA confocal microprobe Raman spectrometer and divided into fi ve types, Huanglongbing (HLB), moderate HLB, serious HLB, nutrient defi ciency, and normal. The backgrounds of the spectra were deducted by different methods, and partial least squares discrimination analysis (PLS-DA) and extreme learning machine (ELM) were used to build the mathematical model. At the same time, the data dimension was reduced using principal component analysis (PCA) and successive projection algorithm (SPA) in order to optimize and improve the classifi cation accuracy of the model. The experiments showed that the predictive ability of the PLS-DA model with 1850 input variables by 2 times polynomial fi tting deducted backgrounds was better, the recognition correct rate being 100%. The results show that Raman spectroscopy has potential for rapid diagnosis of citrus HLB. [ABSTRACT FROM AUTHOR]

Summary: Neopterin is primarily synthesized and released by activated macrophages/monocytes upon stimulation with interferon‐γ and is considered as a marker for macrophage activation. This study aimed to analyze the serum levels of neopterin in patients with dermatomyositis (DM) in association with clinical manifestations, laboratory data and patient prognosis. One hundred and eighty‐two consecutive DM patients and 30 healthy controls were retrospectively enrolled into the study. Serum levels of neopterin were significantly increased in DM patients compared to healthy controls (P < 0·001). High serum neopterin levels were associated with anti‐melanoma differentiation‐associated gene (MDA5) antibody, rapidly progressive interstitial lung disease (RP‐ILD) and characteristic DM cutaneous involvement. Longitudinal assessment of serum samples revealed that the serum neopterin levels were closely correlated with disease severity (β = 30·24, P < 0·001). In addition, a significant increase in serum neopterin concentration of non‐survivors was observed when compared to that of survivors (P < 0·001). Receiver operator characteristic curves showed that serum neopterin could distinguish non‐survivors and survivors at an optimal cut‐off level of 22·1 nmol/l with a sensitivity and specificity of 0·804 and 0·625, respectively (P < 0·001). Kaplan–Meier survival curves revealed that DM patients with serum neopterin > 22·1 nmol/l had a significantly higher mortality compared to the patient group with serum neopterin < 22·1 nmol/l (log‐rank P < 0·001). Multivariate regression analysis identified high serum neopterin concentration to be an independent risk factor for poor prognosis in DM (adjusted hazard ratio = 4·619, 95% confidence interval = 2·092–10·195, P < 0·001). In conclusion, increased serum levels of neopterin were significantly associated with RP‐ILD and reduced survival in DM patients, suggesting it as a promising biomarker in disease evaluation of DM. [ABSTRACT FROM AUTHOR]

A Zr47.7Cu31Ni9Al12.3 bulk metallic glass was irradiated directly by KrF excimer laser pulses with wavelength 248 nm and duration 10 ns. Scanning electronic microscope photographs indicated that many ripples in micro-nano scale would be generated on the edge of the irradiated area under the action of the higher intensity laser pulse. Detailed observation demonstrated that the ripples exhibited fluidity and became closer and closer out from interior. Theoretical analysis revealed the formation mechanism of the ripples, including melting, subsequent propagation of capillary waves and final solidification. [ABSTRACT FROM AUTHOR]

The atomic and electronic structures of the Si(001)2×2-Pb and Si(001)2×1-Pb surfaces are investigated using the first-principles total energy calculations. The atomic structures consist of rows of Pb ad-dimers, which are buckled on Si(001)2×2-Pb but symmetric on Si(001)2×1-Pb, verifying previous experimental results. The calculated electronic densities of states and band structures of the optimized Si(001)2×2-Pb and Si(001)2×1-Pb surfaces coincide qualitatively with the previous experimental observations. [ABSTRACT FROM AUTHOR]

A survey of seasonal variations in the distribution of nutrients along a standard section of the East China Sea was carried out between 1991 and 2015. Here, interannual variations of five key nutrients are analyzed and discussed in the context of possible controlling factors, with special attention given to seasonal variations recorded over the year 2015. Results indicate that concentrations of dissolved inorganic nitrogen (DIN), phosphate (DIP) and silicate (DSi) exhibit gradual increases over this period. Measured concentrations of DIN, DIP and DSi were 5.34-11.87 µmol/L, 0.31-0.53 µmol/L and 11.12-23.15 µmol/L, respectively. Since 1996, concentrations of DIN, DIP and DSi have increased significantly. The annual average concentration of DIN, DIP and DSi in the East China Sea were ~2 times greater in 2015 than in 1991, respectively. The N/P ratio exhibits an increasing trend followed by steady-state asymmetric M-type fluctuations. Conversely, the Si/N ratio is generally stable and exhibits an asymmetric W-type fluctuation. The distribution of nutrients in the East China Sea exhibits clear seasonal variations, with phosphate and inorganic nitrogen contents generally higher in autumn and winter than in spring and summer. Silicate content is higher in summer and winter than in autumn and spring. The main source of nutrients into the East China Sea is the Yangtze River plume, with the Taiwan Warm Current providing an additional, secondary source. The combined effects of the Yangtze River plume and the Taiwan Warm Current enforce a decreasing trend in nutrient concentrations from west to east. [ABSTRACT FROM AUTHOR]

Aims: Lynch syndrome (LS) is associated with an increased risk of developing endometrial carcinoma (EC) and ovarian carcinoma (OC). There is considerable variability in current practices and opinions related to screening of newly diagnosed patients with EC/OC for LS. An online survey was undertaken to explore the extent of these differences. Methods and results: An online questionnaire was developed by a panel of experts and sent to all members of the British Association of Gynaecological Pathologists (BAGP) and the International Society of Gynecological Pathologists (ISGyP). Anonymised results were received and analysed. Thirty‐six BAGP and 44 ISGyP members completed the survey. More than 90% of respondents were aware of the association of LS with both EC and OC, but 34% were not aware of specific guidelines for LS screening. Seventy‐one per cent of respondents agreed that universal screening for LS should be carried out in all newly diagnosed EC cases, with immunohistochemistry (IHC) alone as the preferred approach. Only 36% of respondents currently performed IHC or microsatellite instability testing on all newly diagnosed EC cases, with most of the remaining respondents practising selective screening, based on clinical or pathological features or both. A significant minority of respondents (35%) believed that patient consent was required before performance of mismatch repair (MMR) protein IHC. Almost all respondents favoured the use of standardised terminology for reporting MMR protein staining results, and this is proposed herein. Conclusion: There is wide support for universal LS screening in patients with EC, but this survey highlights areas of considerable variation in practice. [ABSTRACT FROM AUTHOR]

SUMMARY Aims/Objectives: We aimed to analyse the molecular backgrounds and red blood cell (RBC) antigen expression of a male blood donor with Rhmod phenotype and his family members. Background: Rh deficiency phenotypes are rarely found worldwide and are characterised by the lack of Rh antigen expression on RBCs. During routine screening, we found a blood donor who seemingly lacked Rh antigens. Therefore, we recruited the donor and his family for further investigation. Methods: RBC serotyping and antibody screening/identification were performed for each sample. A routine blood examination was also conducted. RHD, RHCE and RHAG were sequenced at the genomic DNA or RNA level. Eleven antigens or proteins associated with Rh complex were tested using flow cytometry analysis. Results: The proband and one of his brothers showed extremely weak D antigen and Rh expression levels but did not manifest anaemia. Most of the expressed RBC antigens of the two Rh‐deficient individuals were similar to the previously reported cases but with some exceptions. Molecular analyses demonstrated homozygous expression of a novel RHAG allele, namely, c.[572G>A;707A>C], both in the proband and one of his brothers. Conclusions: To our knowledge, we identified the second double‐variant RHAG allele and the first one related to Rhmod phenotype. The novel allele was also confirmed to be heritable by family analyses. [ABSTRACT FROM AUTHOR]

In vitro produced β-like cells can provide promising cell therapy for curing the epidemic of diabetes. In this context, we aimed to investigate the effects of different concentrations of γ-aminobutyric acid (GABA) on the differentiation of rat pancreatic ductal epithelial-like stem cells (PDESCs) into β-like cells. The PDESC line cells were cultured in the basal media (DMEM/F12 + 10% FBS + 1% penicillinstreptomycin) supplemented with 0 μM, 5 μM, 50 μM, 500 μM, and 5 mM of GABA for 28 days to induce their differentiation. The differentiated cells were detected by cell morphology, dithizone (DTZ) staining, immunofluorescence staining, real-time polymerase chain reaction (qPCR), and glucose-stimulated insulin secretion (GSIS) assay to validate their identity. At the end of 28 days, compared with the control group, enrichment of induced cells was high among the 5 μM, 50 μM, 500 μM, and 5 mM GABA induction groups. The formation of islet-like cell clusters (ICCs) began at 14 days, and the cell clusters showed a growth trend with the culture time. The induced ICCs were positive for DTZ staining, while the control group showed negative results for DTZ staining and the differentiated cells were also positive for β-cell-specific markers (Ins1 and Pdx1). GSIS assay of 50 μM induction group cells at 28 days showed significantly higher levels of C-peptide and insulin secretion than the control, 5 μM, 500 μM, and 5 mM GABA-treated groups (P < 0.01). At the same time, the 50 μM induction group cells also showed significantly higher levels of Ins1, Pdx1 and Nkx6.1 mRNA as compared to the 5 μM, 500 μM and 5 mM GABA groups (P < 0.01). Thus, the addition of GABA to the basal medium effectively induced differentiation of adult rat PDESCs into insulin-secreting β-like cells, and 50 μM was the most effective concentration for the induction. [ABSTRACT FROM AUTHOR]

Elastic electron–proton scattering (e–p) and the spectroscopy of hydrogen atoms are the two methods traditionally used to determine the proton charge radius, rp. In 2010, a new method using muonic hydrogen atoms1 found a substantial discrepancy compared with previous results2, which became known as the 'proton radius puzzle'. Despite experimental and theoretical efforts, the puzzle remains unresolved. In fact, there is a discrepancy between the two most recent spectroscopic measurements conducted on ordinary hydrogen3,4. Here we report on the proton charge radius experiment at Jefferson Laboratory (PRad), a high-precision e–p experiment that was established after the discrepancy was identified. We used a magnetic-spectrometer-free method along with a windowless hydrogen gas target, which overcame several limitations of previous e–p experiments and enabled measurements at very small forward-scattering angles. Our result, rp = 0.831 ± 0.007stat ± 0.012syst femtometres, is smaller than the most recent high-precision e–p measurement5 and 2.7 standard deviations smaller than the average of all e–p experimental results6. The smaller rp we have now measured supports the value found by two previous muonic hydrogen experiments1,7. In addition, our finding agrees with the revised value (announced in 2019) for the Rydberg constant8—one of the most accurately evaluated fundamental constants in physics. A magnetic-spectrometer-free method for electron–proton scattering data reveals a proton charge radius 2.7 standard deviations smaller than the currently accepted value from electron–proton scattering, yet consistent with other recent experiments. [ABSTRACT FROM AUTHOR]

Background: While increased levels of circulating inflammatory cytokines in chronologically aged humans have been linked to the development of ageing‐associated chronic disorders (e.g., cardiovascular disease, type II diabetes, osteoporosis and Alzheimer's disease), approaches that reduce circulating cytokines are not yet available. In chronologically aged mice, we recently demonstrated that epidermal dysfunction largely accounts for age‐associated elevations in circulating cytokine levels, and that improving epidermal function reduced circulating cytokine levels. Objective: We performed a pilot study to determine whether improving epidermal function reduces circulating pro‐inflammatory cytokine levels in aged humans. Methods: Thirty‐three aged humans were topically treated twice‐daily for 30 days, with ≈ 3 mL of an emollient, previously shown to improve epidermal function, while untreated, aged humans and a cohort of young volunteers served as controls. Changes in epidermal function and levels of three key, age‐related, plasma cytokines (IL‐1β, IL‐6 and TNFα) were measured at baseline and after treatment, using Luminex 200™ system. Results: We also found significantly higher baseline levels of IL‐1β, IL‐6 and TNFα in aged vs. young humans (P < 0.001), as previously reported. Topical applications of the barrier repair emollient significantly enhanced epidermal permeability barrier function (P < 0.01) and stratum corneum hydration (P < 0.05). In parallel, circulating levels of IL‐1β and IL‐6 normalized, while TNFα levels declined substantially. Conclusion: The results of this preliminary study suggest that a larger clinical trial should be performed to confirm whether improving epidermal function also can reduce circulating pro‐inflammatory cytokine levels in aged humans, while also possibly attenuating the downstream development of chronic inflammatory disorders in the aged humans. [ABSTRACT FROM AUTHOR]

During peroral endoscopic myotomy (POEM), creation of the tunnel is highly technically demanding and mucosal injury is one of the most common potential complications. We explored a method without a submucosal tunnel, which we call open peroral endoscopic myotomy (O-POEM). This study aimed to assess the feasibility and safety of O-POEM. O-POEM was performed on 82 patients with achalasia. Treatment success was defined as an Eckardt score of less than or equal to 3 after the myotomy. Adverse events including operative and postoperative adverse events were recorded. Treatment success and procedure-related adverse events were analyzed. After a median follow-up of 18 months (range: 6–26 months), the treatment success (Eckhart score ≤3) was achieved in 96.3% of cases (mean score pre- vs. post-treatment (7.4 vs. 1.8); P < 0.001) with a recurrence of 3 cases. Ten patients (12.2%) had adverse events consisting of 2 cases of mediastinitis, 1 case of post-O-POEM bleeding, 1 case of subcutaneous emphysema, 6 cases of pleural effusion. Two cases of mediastinitis required intraprocedural drainage, and other patients were managed by endoscopy and conservative medical treatment. There were no deaths. No patients required surgical conversion. Clinical reflux occurred in 15.9% of patients (13/82). O-POEM was reliable and effective for the treatment of achalasia. In addition, O-POEM might be a better option for patients with severe submucosal fibrosis. [ABSTRACT FROM AUTHOR]

Background Recent studies have demonstrated the possibility of negative associations between prior influenza vaccines and subsequent influenza vaccine effectiveness (VE), depending on season and strain. We investigated this association over 4 consecutive influenza seasons (2011–2012 through 2014–2015) in Canada. Methods Using a matched test-negative design, laboratory-confirmed influenza cases and matched test-negative controls admitted to hospitals were enrolled. Patients were stratified into 4 groups according to influenza vaccine history (not vaccinated current and prior season [referent], vaccinated prior season only, vaccinated current season only, and vaccinated both current and prior season). Conditional logistic regression was used to estimate VE; prior vaccine impact was assessed each season for overall effect and effect stratified by age (<65 years, ≥65 years) and type/subtype (A/H1N1, A/H3N2, influenza B). Results Overall, mainly nonsignificant associations were observed. Trends of nonsignificant decreased VE among patients repeatedly vaccinated in both prior and current season relative to the current season only were observed in the A/H3N2-dominant seasons of 2012–2013 and 2014–2015. Conversely, in 2011–2012, during which B viruses circulated, and in 2013–2014, when A/H1N1 circulated, being vaccinated in both seasons tended to result in a high VE in the current season against the dominant circulating subtype. Conclusions Prior vaccine impact on subsequent VE among Canadian inpatients was mainly nonsignificant. Even in circumstances where we observed a trend of negative impact, being repeatedly vaccinated was still more effective than not receiving the current season's vaccine. These findings favor continuation of annual influenza vaccination recommendations, particularly in older adults. Clinical Trials Registration NCT01517191. [ABSTRACT FROM AUTHOR]

Summary: While therapeutic approaches for psoriasis are widely available, preventive regimens are lacking. We aimed to determine whether improvements in epidermal function could prevent psoriasis relapse. Two self‐controlled cohort studies were designed, enrolling two cohorts of patients with psoriasis (n = 30 and n = 60) to be treated topically with an in‐house‐prepared emollient or ATOPALM® cream applied twice daily to one forearm for 20 and 30 days, respectively, while the same sites on the contralateral arm served as the untreated control. Epidermal function on both arms was assessed prior to and at the end of the trials. Delayed relapse on the treated arm was seen in 54.5% and 71% of patients in the first and second cohort, respectively. The time of psoriatic relapse correlated with the extent of abnormalities in baseline epidermal function. These results suggest that improvements in epidermal function with topical emollients can prevent/attenuate the development of psoriasis. [ABSTRACT FROM AUTHOR]

In organizations, green creativity of the employees is an essential part of implementing sustainable development. Our research proposed that workplace status has a significant impact on green creativity. Through an empirical study, we came to the conclusion that an increase in workplace status can lead to green creativity and prosocial motivation mediates the process. Since workplace status promotes the attention for group interests, employees will evaluate their self-worth considering the sustainable development of the environment. Based on the analysis framework of moderated mediation model, this study indicated that organization identification had a positive moderating effect on the relationship between workplace status and green creativity, and it is the boundary condition for workplace status to be effective. [ABSTRACT FROM AUTHOR]

Aim: To explore the function and mechanisms of NLRP6 (NOD‐, LRR‐ and pyrin domain‐containing 6) in the inflammatory response of human periodontal ligament cells (HPDLCs). Methodology: Tissues associated with apical periodontitis were obtained from three patients who underwent endodontic microsurgery. The expression of NLRP6 in 3 human apical periodontitis tissues and HPDLCs was examined by immunohistochemistry and immunofluorescence, respectively. The expressions of NLRP6, Phospho(p)‐ p65, p65, IκB‐α, p‐ IκB‐α, ERK, p‐ ERK, NLRP3, Pro interleukin (IL)‐1β, Pro caspase‐1 and apoptosis‐associated speck‐like protein containing a CARD (ASC) were examined by western blot. The gene expression and secretion of proinflammatory cytokines were detected using quantitative real‐time polymerase chain reaction and enzyme‐linked immunosorbent assay. Data were analysed statistically with independent sample t‐tests. Results: NLRP6 was expressed in inflammatory periapical tissues and HPDLCs. Lipopolysaccharide (LPS) from Escherichia coli induced NLRP6 in HPDLCs (P < 0.05). After silencing NLRP6, E. coli LPS‐induced activation of NF‐κB and ERK signalling was enhanced, which was also accompanied by elevated levels of IL‐6 and tumour necrosis factor‐α (TNF‐α) (P < 0.05). Moreover, knockdown of NLRP6 led to up‐regulation of NLRP3, Pro IL‐1β and Pro caspase‐1 (P < 0.05), whereas down‐regulation of ASC (P < 0.05), which may contribute to unchanged levels of IL‐1β in HPDLCs inflammation. Conclusion: NLRP6 was functionally expressed in inflamed periapical tissues and HPDLCs. NLRP6 negatively regulated the production of IL‐6 and TNF‐α in HPDLCs inflammation by inhibiting NF‐κB and ERK signal pathways. [ABSTRACT FROM AUTHOR]

We present the quasi-static and dynamic switching characteristics of orthogonal spin-transfer devices incorporating an out-of-plane magnetized polarizing layer and an in-plane magnetized spin valve device at cryogenic temperatures. Switching at 12K between parallel and anti-parallel spinvalve states is investigated for slowly varied current as well as for current pulses with durations as short as 200 ps. We demonstrate 100% switching probability with current pulses 0.6 ns in duration. We also present a switching probability diagram that summarizes device switching operation under a variety of pulse durations, amplitudes, and polarities. [ABSTRACT FROM AUTHOR]

Nanoparticle self-assembly dynamics are monitored in real-time by detecting optical diffraction from an all-nanoparticle grating as it self-assembles on a grating pattern recorded on a magnetic medium. The diffraction efficiency strongly depends on concentration, pH, and colloidal stability of nanoparticle suspensions, demonstrating the nanoparticle self-assembly process is highly tunable. This metrology could provide an alternative for detecting nanoparticle properties such as colloidal stability. [ABSTRACT FROM AUTHOR]