Effects of artificial light with different spectral compositions on refractive development and matrix metalloproteinase 2 and tissue inhibitor of metalloproteinases 2 expression in the sclerae of juvenile guinea pigs.

Artificial light can affect eyeball development and increase myopia rate. Matrix metalloproteinase 2 (MMP-2) degrades the extracellular matrix, and induces its remodeling, while tissue inhibitor of matrix MMP-2 (TIMP-2) inhibits active MMP-2. The present study aimed to look into how refractive development and the expression of MMP-2 and TIMP-2 in the guinea pigs' remodeled sclerae are affected by artificial light with varying spectral compositions. Three weeks old guinea pigs were randomly assigned to groups exposed to five different types of light: natural light, LED light with a low color temperature, three full spectrum artificial lights, i.e. E light (continuous spectrum in the range of ~390-780 nm), G light (a blue peak at 450 nm and a small valley 480 nm) and F light (continuous spectrum and wavelength of 400 nm below filtered). A-scan ultrasonography was used to measure the axial lengths of their eyes, every two weeks throughout the experiment. Following twelve weeks of exposure to light, the sclerae were observed by optical and transmission electron microscopy. Immunohistochemistry, Western blot and RT-qPCR were used to detect the MMP-2 and TIMP-2 protein and mRNA expression levels in the sclerae. After four, six, eight, ten, and twelve weeks of illumination, the guinea pigs in the LED and G light groups had axial lengths that were considerably longer than the animals in the natural light group while the guinea pigs in the E and F light groups had considerably shorter axial lengths than those in the LED group. Following twelve weeks of exposure to light, the expression of the scleral MMP-2 protein and mRNA were, from low to high, N group, E group, F group, G group, LED group; however, the expression of the scleral TIMP-2 protein and mRNA were, from high to low, N group, E group, F group, G group, LED group. The comparison between groups was statistically significant (p<0.01). Continuous, peaks-free or valleys-free artificial light with full-spectrum preserves remodeling of scleral extracellular matrix in guinea pigs by downregulating MMP-2 and upregulating TIMP-2, controlling eye axis elongation, and inhibiting the onset and progression of myopia.

Factors influencing the job embeddedness of new graduate nurses: A multicentre cross-sectional study.

AIM: To identify factors associated with job embeddedness from the perspective of retaining new graduate nurses. DESIGN: The study was cross-sectional in design. METHODS: Convenience and stratified sampling were used to recruit 415 newly graduated nurses from 12 tertiary hospitals in China. Anonymized data were collected through self-designed sociodemographic questionnaires, job embeddedness scale, feedback-seeking behaviour scale, authentic leadership perception scale and decent work scale. Appropriate indicators were used for descriptive statistics and t-tests, ANOVA, Pearson correlation analysis and multiple linear regression to examine the influencing factors. RESULTS: The study showed that monthly income level, decent labour, authentic leadership and feedback-seeking behaviour were significant predictors of job embeddedness among new graduate nurses. CONCLUSION: The job embeddedness of new graduate nurses is moderate. Nursing managers need to construct reasonable and fair compensation incentives, adopt positive leadership styles and encourage proactive feedback-seeking behaviours to improve the job embeddedness of new graduate nurses and alleviate the nursing talent shortage. IMPACT: Exploring the factors influencing the job embeddedness of new graduate nurses provides a reference for establishing new graduate nurse retention strategies to help promote the career development of new graduate nurses and alleviate the nursing brain drain. REPORTING METHOD: We adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Size-Dependent Effect of Titania Nanotubes on Endoplasmic Reticulum Stress to Re-establish Diabetic Macrophages Homeostasis.

In patients with diabetes, endoplasmic reticulum stress (ERS) is a crucial disrupting factor of macrophage homeostasis surrounding implants, which remains an obstacle to oral implantation success. Notably, the ERS might be modulated by the implant surface morphology. Titania nanotubes (TNTs) may enhance diabetic osseointegration. However, a consensus has not been achieved regarding the tube-size-dependent effect and the underlying mechanism of TNTs on diabetic macrophage ERS. We manufactured TNTs with small (30 nm) and large diameters (100 nm). Next, we assessed how the different titanium surfaces affected diabetic macrophages and regulated ERS and Ca2+ homeostasis. TNTs alleviated the inflammatory response, oxidative stress, and ERS in diabetic macrophages. Furthermore, TNT30 was superior to TNT100. Inhibiting ERS abolished the positive effect of TNT30. Mechanistically, topography-induced extracellular Ca2+ influx might mitigate excessive ERS in macrophages by alleviating ER Ca2+ depletion and IP3R activation. Furthermore, TNT30 attenuated the peri-implant inflammatory response and promoted osseointegration in diabetic rats. TNTs with small nanodiameters attenuated ERS and re-established diabetic macrophage hemostasis by inhibiting IP3R-induced ER Ca2+ depletion.

Hierarchical online contrastive anomaly detection for fetal arrhythmia diagnosis in ultrasound.

Arrhythmia is a major cardiac abnormality in fetuses. Therefore, early diagnosis of arrhythmia is clinically crucial. Pulsed-wave Doppler ultrasound is a commonly used diagnostic tool for fetal arrhythmia. Its key step for diagnosis involves identifying adjacent measurable cardiac cycles (MCCs). As cardiac activity is complex and the experience of sonographers is often varied, automation can improve user-independence and diagnostic-validity. However, arrhythmias pose several challenges for automation because of complex waveform variations, which can cause major localization bias and missed or false detection of MCCs. Filtering out non-MCC anomalies is difficult because of large intra-class and small inter-class variations between MCCs and non-MCCs caused by agnostic morphological waveform variations. Moreover, rare arrhythmia cases are insufficient for classification algorithms to adequately learn discriminative features. Using only normal cases for training, we propose a novel hierarchical online contrastive anomaly detection (HOCAD) framework for arrhythmia diagnosis during test time. The contribution of this study is three-fold. First, we develop a coarse-to-fine framework inspired by hierarchical diagnostic logic, which can refine localization and avoid missed detection of MCCs. Second, we propose an online learning-based contrastive anomaly detection with two new anomaly scores, which can adaptively filter out non-MCC anomalies on a single image during testing. With these complementary efforts, we precisely determine MCCs for correct measurements and diagnosis. Third, to the best of our knowledge, this is the first reported study investigating intelligent diagnosis of fetal arrhythmia on a large-scale and multi-center ultrasound dataset. Extensive experiments on 3850 cases, including 266 cases covering three typical types of arrhythmias, demonstrate the effectiveness of the proposed framework.

Anticancer activity of 8-hydroxyquinoline-triphenylphosphine rhodium(III) complexes targeting mitophagy pathways.

Metallodrugs exhibiting distinct mechanisms of action compared with cisplatin hold promise for overcoming cisplatin resistance and improving the efficacy of anticancer drugs. In this study, a new series of rhodium (Rh)(III) complexes containing tris(triphenylphosphine)rhodium(I) chloride [(TPP)3RhCl] (TPP = triphenylphosphine, TPP=O = triphenylphosphine oxide) and 8-hydroxyquinoline derivatives (H-XR1-H-XR4), namely [Rh(XR1)2(TPP)Cl]·(TPP=O) (Yulin Normal University-1a [YNU-1a]), [Rh(XR2)2(TPP)Cl] (YNU-1b), [Rh(XR3)2(TPP)Cl] (YNU-1c), and [Rh(XR4)2(TPP)Cl] (YNU-1d), was synthesized and characterized via X-ray diffraction, mass spectrometry and IR. The cytotoxicity of the compounds YNU-1a-YNU-1d in Hep-G2 and HCC1806 human cancer cell lines and normal HL-7702 cell line was evaluated. YNU-1c exhibited cytotoxicity and selectivity in HCC1806 cells (IC50 = 0.13 ± 0.06 µM, selectivity factor (SF) = 384.6). The compounds YNU-1b and YNU-1c, which were selected for mechanistic studies, induced the activation of apoptotic pathways and mitophagy. In addition, these compounds released cytochrome c, cleaved caspase-3/pro-caspase-3 and downregulated the levels of mitochondrial respiratory chain complexes I/IV (M1 and M4) and ATP. The compound YNU-1c, which was selected for in vivo experiments, exhibited tumor growth inhibition (58.9 %). Importantly, hematoxylin and eosin staining and TUNEL revealed that HCC1806 tumor tissues exhibited significant apoptotic characteristics. YNU-1a-YNU-1d compounds are promising drug candidates that can be used to overcome cisplatin resistance.

Work-family conflict categories and support strategies for married female nurses: a latent profile analysis.

Objective: To clarify subgroups of married female nurses experiencing work-family conflict (WFC), explore the factors associated with the subgroups, and determine how desired support strategies differ among the subgroups. Methods: Data was collected from a sample of 646 married female nurses from public hospitals in Zhejiang Province, China, in December 2021. Latent profile analysis was used to group the participants, and multiple logistic regression was used to identify factors associated with higher WFC. The STROBE criteria were used to report results. Results: According to latent profile analysis, there were three distinct profiles of WFC among married female nurses: "low-conflict type," "work-dominant-conflict type," and "high-conflict type." These profiles differed in the number of children, night shifts, family economic burden, childcare during working hours, family harmony, colleague support, and nurse-patient relationships. Nurses with multiple children, higher pressures in childcare during working hours, heavier family economic burdens, lower family harmony, lower colleague support, and poorer nurse-patient relationships are more likely to be classified as "high-conflict type" nurses. Conclusion: This study found that married female nurses experience different types of WFCs. The structure of these WFCs and their associated factors suggests that customized intervention strategies can be developed to address the specific needs of married female nurses.

Synthesis and anticancer mechanisms of four novel platinum(II) 4'-substituted-2,2':6',2''-terpyridine complexes.

Mitophagy, a selective autophagic process, has emerged as a pathway involved in degrading dysfunctional mitochondria. Herein, new platinum(II)-based chemotherapeutics with mitophagy-targeting properties are proposed. Four novel binuclear anticancer Pt(II) complexes with 4'-substituted-2,2':6',2''-terpyridine derivatives (tpy1-tpy4), i.e., [Pt2(tpy1)(DMSO)2Cl4]·CH3OH (tpy1Pt), [Pt(tpy2)Cl][Pt(DMSO)Cl3]·CH3COCH3 (tpy2Pt), [Pt(tpy3)Cl][Pt(DMSO)Cl3] (tpy3Pt), and [Pt(tpy4)Cl]Cl·CH3OH (tpy4Pt), were designed and prepared. Moreover, their potential antitumor mechanism was studied. Tpy1Pt-tpy4Pt exhibited more selective cytotoxicity against cisplatin-resistant SK-OV-3/DDP (SKO3cisR) cancer cells compared with those against ovarian SK-OV-3 (SKO3) cancer cells and normal HL-7702 liver (H702) cells. This selective cytotoxicity of Tpy1Pt-tpy4Pt was better than that of its ligands (i.e., tpy1-tpy4), the clinical drug cisplatin, and cis-Pt(DMSO)2Cl2. The results of various experiments indicated that tpy1Pt and tpy2Pt kill SKO3cisR cancer cells via a mitophagy pathway, which involves the disruption of the mitophagy-related protein expression, dissipation of the mitochondrial membrane potential, elevation of the [Ca2+] and reactive oxygen species levels, promotion of mitochondrial DNA damage, and reduction in the adenosine triphosphate and mitochondrial respiratory chain levels. Furthermore, in vivo experiments indicated that the dinuclear anticancer Pt(II) coordination compound (tpy1Pt) has remarkable therapeutic efficiency (ca. 52.4%) and almost no toxicity. Therefore, the new 4'-substituted-2,2':6',2''-terpyridine Pt(II) coordination compound (tpy1Pt) is a potential candidate for next-generation mitophagy-targeting dinuclear Pt(II)-based anticancer drugs.

"Discovering shine through feedback seeking"---feedback seeking among new graduate nurses: a qualitative study.

BACKGROUND: Feedback is critical to improving practitioners' clinical practice and professional growth. Although they are still considered junior practitioners, their feedback-seeking experiences have yet to be investigated. This study aimed to understand the fundamental thoughts and experiences of new graduate nurses regarding feedback-seeking and to identify the main factors that influence their feedback-seeking behaviors. METHODS: Conducting a descriptive phenomenological study, semi-structured in-depth interviews with newly graduated nurses from four hospitals in Zhejiang Province, China, face-to-face or via video call in the hospital conference room through purposive and snowball sampling. Interview data were evaluated using Colaizzi's 7-step phenomenological data analysis. The COREQ checklist was followed. RESULTS: A total of 15 new graduate nurses were interviewed as a sample, and 13 categories emerged from our data. They were categorized into four central elements: (1) perceptions and attitudes, (2) drivers, (3) dilemmas and needs, and (4) transformation and growth. CONCLUSIONS: This study found that new graduate nurses have various needs but face dilemmas in the feedback-seeking process. Nursing managers should be proficient at providing positive leadership, collaborating with clinical mentors to foster an atmosphere where new graduate nurses may obtain honest, transparent, and fair feedback, and exercising caution when providing negative feedback.

An intelligent quantification system for fetal heart rhythm assessment: A multicenter prospective study.

BACKGROUND: The motion relationship and time intervals of the pulsed-wave Doppler (PWD) spectrum are essential for diagnosing fetal arrhythmia. However, few technologies currently are available to automatically calculate fetal cardiac time intervals (CTIs). OBJECTIVE: The purpose of this study was to develop a fetal heart rhythm intelligent quantification system (HR-IQS) for the automatic extraction of CTIs and establish the normal reference range for fetal CTIs. METHODS: A total of 6498 PWD spectrums of 2630 fetuses over the junction between the left ventricular inflow and outflow tracts were recorded across 14 centers. E, A, and V waves were manually labeled by 3 experienced fetal cardiologists, with 17 CTIs extracted. Five-fold cross-validation was performed for training and testing of the deep learning model. Agreement between the manual and HR-IQS-based values was evaluated using the intraclass correlation coefficient and Spearman's rank correlation coefficient. The Jarque-Bera test was applied to evaluate the normality of CTIs' distributions, and the normal reference range of 17 CTIs was established with quantile regression. Arrhythmia subset was compared with the non-arrhythmia subset using the Mann-Whitney U test. RESULTS: Significant positive correlation (P <.001) and moderate-to-excellent consistency (P <.001) between the manual and HR-IQS automated measurements of CTIs was found. The distribution of CTIs was non-normal (P <.001). The normal range (2.5th to 97.5th percentiles) was successfully established for the 17 CTIs. CONCLUSIONS: Using our HR-IQS is feasible for the automated calculation of CTIs in practice and thus could provide a promising tool for the assessment of fetal rhythm and function.

Effect of artificial landmarks of the prefabricated auxiliary devices located at different arch positions on the accuracy of complete-arch edentulous digital implant scanning: An in-vitro study.

OBJECTIVES: To examine the effect of artificial landmarks of prefabricated auxiliary devices (PAD) located at different arch positions on the accuracy of complete-arch edentulous digital implant scanning. METHODS: A reference model containing four analogs and PAD were fabricated by a 3D printer (AccuFab-C1s, 3DShining). 10 digital scans were performed using an intraoral scanner (Aoralscan 3, 3DShining), sv 1.0.0.3115, with artificial landmarks located at different arch positions: group I, without any artificial landmarks; group II, with artificial landmarks at the anterior region; group III, with artificial landmarks at the posterior region. group IV: with artificial landmarks at both anterior and posterior regions. For group V: Conventional open-tray splinted impressions. The reference file and conventional stone casts were digitalized by using a dental laboratory scanner. The related files were imported into inspection software for trueness and precision assessment. Statistical analysis was performed with One-way ANOVA and Kruskal-Wallis test. The level of significance was set at α=0.05. RESULTS: For the global accuracy assessment, significantly higher global trueness was seen in group II (p < 0.01), III (p < 0.001), IV (p < 0.001) and V (p < 0.001) than group I. Significantly higher global precision was seen in group III (p < 0.001), IV (p < 0.001) and V (p < 0.001) than group I. For the local accuracy assessment, the PAD primarily improved accuracy on the linear deviations. CONCLUSIONS: Artificial landmarks of PAD at different arch positions significantly influenced the scanning accuracy. Applying the PAD in group IV could achieve comparable outcomes to conventional open-tray splinted impressions. Artificial landmarks on the posterior region may be more pivotal than those on the anterior region. CLINICAL SIGNIFICANCE: Group IV could achieve comparable accuracy to conventional open-tray splinted impressions.

Effect of prefabricated auxiliary devices and scanning patterns on the accuracy of complete-arch implant digital impressions.

OBJECTIVES: This study aimed to evaluate the impact of prefabricated auxiliary devices (PAD) and scanning patterns on the accuracy of complete-arch implant digital impressions. METHODS: An edentulous maxillary model was inserted with four parallel implant analogs and four PAD. The model was scanned with D2000 dental laboratory scanner as the reference scans. Test scans were obtained by 8 different scanning patterns (SP), which including SPA, SPB, SPC, SPD, SPE, SPF, SPG and SPH, with (test group) or without (control group) using the PAD by an intraoral scanner (Aoralscan 3, 3DShining). SPA was the scanning pattern recommended by the manufacturer. Each scanning time was recorded. The related files were imported into inspection software for assessment. Aligned Ranks Transformation ANOVA, Kruskal-Wallis and Mann-Whitney tests were used to evaluate the values. The level of significance was set at α = 0.05. RESULTS: The scanning patterns significantly influenced the linear accuracy in the test group and the scanning time for both groups. Lower linear trueness in the test group was found in SPF (p<0.05) and SPG (p<0.05). Longer scanning time was found in SPB and SPG for both groups. The test group demonstrated linear accuracy enhancement in all the scanning patterns; angular trueness enhancement was seen in SPA (p<0.05), SPC (p<0.01) and SPH (p<0.01). Significant longer scanning time was found in SPB (p<0.05), SPF (p<0.05), SPG (p<0.05) and SPH (p<0.05) when using PAD. CONCLUSION: The scanning patterns impact the accuracy differently depending on the PAD's existence. The scanning time can be significantly influenced by the scanning patterns and the PAD. CLINICAL SIGNIFICANCE: In daily clinical practice, selecting a suitable scanning pattern is significant in achieving accurate digital impressions. The PAD demonstrated effective linear accuracy enhancement in all the scanning patterns tested.

Antitumor studies evaluation of triphenylphosphine ruthenium complexes with 5,7-dihalo-substituted-8-quinolinoline targeting mitophagy pathways.

Both ruthenium-containing complexes and 8-quinolinoline compounds have emerged as a potential novel agent for malignant tumor therapy. Here, three triphenylphosphine ruthenium complexes, [Ru(ZW1)(PPh3)2Cl2] (PPh3 = triphenylphosphine) (RuZ1), [Ru(ZW2)(PPh3)2Cl2] (RuZ2) and [Ru(ZW2)2(PPh3)Cl2]·CH2Cl2 (RuZ3) bearing 5,7-dichloro-8-quinolinol (H-ZW1) and 5,7-dichloro-8-hydroxyquinaldine (H-ZW2), have been synthesized, characterized and tested for their anticancer potential. We showed that triphenylphosphine ruthenium complexes RuZ1-RuZ3 impaired the cell viability of ovarian adenocarcinoma cisplatin-resistant SK-OV-3/DDP (SKO3CR) and SK-OV-3 (SKO3) cancer cells with greater selectivity and specificity than cisplatin. In addition, RuZ1-RuZ3 show higher excellent cytotoxicity than cisplatin towards SKO3CR cells, with IC50 values of 9.66 ± 1.08, 4.05 ± 0.67 and 7.18 ± 0.40 µM, respectively, in which the SKO3CR cells was the most sensitive to RuZ1-RuZ3. Depending on the substituent type, the antiproliferative ability of RuZ1-RuZ3 followed the trend: -CH3 > -H. However, RuZ1-RuZ3 have no obvious toxicity to normal cell HL-7702. Besides, RuZ1 and RuZ2 could induce mitophagy related-apoptosis pathways through suppression of mitochondrial membrane potential (ΔΨm), accumulation of [Ca2+] and reactive oxygen species (ROS), and regulation of LC3 II/LC3 I, Beclin-1, P62, FUNDC1, PINK1, Parkin, cleaved-caspase-3, caspase-9 and cytochrome c signaling pathway, and hindering the preparation of mitochondrial respiration complexes I and IV and ATP levels. Mechanistic study revealed that RuZ1 and RuZ2 induce apoptosis in SKO3CR cells via mitophagy related-apoptosis pathways induction and energy (ATP) generation disturbance. Taken together, the studied triphenylphosphine ruthenium complexes RuZ1-RuZ3 are promising chemotherapeutic agents with high effectiveness and low toxicity.

Effect of novel prefabricated auxiliary devices attaching to scan bodies on the accuracy of intraoral scanning of complete-arch with multiple implants: An in-vitro study.

OBJECTIVES: To examine the effect of novel prefabricated auxiliary devices with different geometric features called Scan Body Clasp (SBC) at different levels on the accuracy of intraoral scanning of complete-arch with multiple implants. METHODS: An edentulous maxilla 4-implant model and SBCs with different geometric features (flat or curved) were fabricated by a 3D printer (AccuFab-C1s, 3DShining, Hangzhou, China). Test scans were performed using an intraoral scanner (Aoralscan 3, 3DShining, Hangzhou, China) software version 1.0.0.3104 under different scenarios: group A (CO), without any SBCs; group B&C (LC&HC), with curved SBCs adjacent to and away from the mucosa; group D&E (LF&HF), with flat SBCs adjacent to and away from the mucosa. 20 scans were done for each group (CO, LC, HC, LF and HF). Reference Scans were obtained by digitizing the model in group A using a dental laboratory scanner (D2000, 3Shape, Copenhagen, Denmark). The related files were imported into inspection software for trueness and precision assessment. Statistical analysis was performed with One-way ANOVA, Independent-Sample T test for trueness values. Kruskal-Wallis test and Mann-Whitney test were used to assess the precision values. The level of significance was set at α=0.05. RESULTS: Groups with SBCs demonstrated trueness enhancement, among which LF revealed the best trueness. Significant differences were also found between LF and HC (p < .01), LF and HF (p < .001), LC and HF (p < .01). LF and HF showed precision enhancement. The best precision was LF, which was found to be more precise than LC (p < .001) and HC (p < .001). HF was more precise than LC (p < .001) and HC (p < .001). CONCLUSIONS: Attaching the scan bodies with SBCs at different levels significantly influenced the scanning accuracy. The SBCs near the mucosa result in superior trueness, while the flat morphology benefits the precision. CLINICAL SIGNIFICANCE: The results demonstrated the feasibility of the SBCs in enhancing intraoral complete-arch implant scanning accuracy. Among the configurations tested in the present study, low-level and flat surfaces of the artificial landmarks may be the potential pivotal elements to optimizing long-span scanning accuracy.

Accuracy of single-implant digital impression with various scanbody exposure levels at anterior and posterior regions.

OBJECTIVES: This in vitro study aimed to evaluate the effect of the exposure heights of the scanbody on the accuracy of digital implant impressions at different positions. METHODS: Four maxillary master models with one analog at the anterior and posterior region were fabricated by a 3-dimensional (3D) printer. The analogs were submerged from the gingival margin to ensure four exposure heights of the scanbody: 10, 8, 6, and 4 mm. . The master models were then scanned with D2000 dental laboratory scanner as the reference models. An intraoral scanner obtained ten test models for each group. After aligning the scanbody library file, the related files were imported into inspection software for superimposition by a local fit algorithm based on the adjacent teeth. RESULTS: 3D trueness was significantly decreased at 6 and 4 mm scanbody exposure at the anterior region. In comparison, a significant decrease was only seen at 4 mm scanbody exposure at the posterior region. 3D precision was significantly decreased at 4 mm scanbody exposure at both anterior and posterior regions. CONCLUSION: The exposure height of the scanbody influenced the accuracy of the digital implant impression, according to the implant positions. Scanbody exposure of less than 6 mm at the anterior region and 4 mm scanbody exposure at the posterior region could lead to increased deviations, but still in the tolerance range. CLINICAL SIGNIFICANCE: The scanbody exposure height less than 6 mm at the anterior region and 4 mm scanbody exposure height at the posterior region could lead to significantly increased deviations. Though these deviations may be still in the clinically acceptable range, caution should be taken.

Ebselen restores peri-implantitis-induced osteogenic inhibition via suppressing BMSCs ferroptosis.

It is hard to reconstruct bone defects in peri-implantitis due to osteogenesis inhibited by excessive reactive oxygen species (ROS). Ferroptosis, a recently identified regulated cell death characterized by iron- and ROS- dependent lipid peroxidation, provides us with a new explanation. Our study aims to explore whether ferroptosis is involved in peri-implantitis-inhibited osteogenesis and confirm ebselen, an antioxidant with glutathione peroxidase (GPx)-like activity, could inhibit ferroptosis and promote osteogenesis in peri-implantitis. In this study, we used LPS to mimic the microenvironment of peri-implantitis. The osteogenic differentiation of bone-marrow-derived mesenchymal stem cells (BMSCs) was assessed by alkaline phosphatase (ALP), Alizarin Red S, and mRNA and protein expression of osteogenic-related markers. Ferroptosis index analysis included iron metabolism, ROS production, lipid peroxidation and mitochondrial morphological changes. Iron overload, reduced antioxidant capability, excessive ROS, lipid peroxidation and the characteristic mitochondrial morphological changes of ferroptosis were observed in LPS-treated BMSCs, and adding Ferrostatin-1 (Fer-1) restored the inhibitory effect of ferroptosis on osteogenic differentiation of BMSCs. Furthermore, ebselen ameliorated LPS-induced ferroptosis and osteogenic inhibition, which were reversed by erastin. Our results demonstrated that ferroptosis is involved in osteogenic inhibition in peri-implantitis and ebselen could attenuate osteogenic dysfunction of BMSCs via inhibiting ferroptosis.

Test-time bi-directional adaptation between image and model for robust segmentation.

BACKGROUND AND OBJECTIVE: Deep learning models often suffer from performance degradations when deployed in real clinical environments due to appearance shifts between training and testing images. Most extant methods use training-time adaptation, which almost require target domain samples in the training phase. However, these solutions are limited by the training process and cannot guarantee the accurate prediction of test samples with unforeseen appearance shifts. Further, it is impractical to collect target samples in advance. In this paper, we provide a general method of making existing segmentation models robust to samples with unknown appearance shifts when deployed in daily clinical practice. METHODS: Our proposed test-time bi-directional adaptation framework combines two complementary strategies. First, our image-to-model (I2M) adaptation strategy adapts appearance-agnostic test images to the learned segmentation model using a novel plug-and-play statistical alignment style transfer module during testing. Second, our model-to-image (M2I) adaptation strategy adapts the learned segmentation model to test images with unknown appearance shifts. This strategy applies an augmented self-supervised learning module to fine-tune the learned model with proxy labels that it generates. This innovative procedure can be adaptively constrained using our novel proxy consistency criterion. This complementary I2M and M2I framework demonstrably achieves robust segmentation against unknown appearance shifts using existing deep-learning models. RESULTS: Extensive experiments on 10 datasets containing fetal ultrasound, chest X-ray, and retinal fundus images demonstrate that our proposed method achieves promising robustness and efficiency in segmenting images with unknown appearance shifts. CONCLUSIONS: To address the appearance shift problem in clinically acquired medical images, we provide robust segmentation by using two complementary strategies. Our solution is general and amenable for deployment in clinical settings.

Optimizing the combined soft tissue repair and osteogenesis using double surfaces of crosslinked collagen scaffolds.

Excessive tissue damage or loss has been solved by guided tissue regeneration and guided bone regeneration theories. However, the unfavorable degradation property of the resorbable collagen scaffold brings a big challenge to support soft tissue stabilization and time-consuming osteogenesis. The combined effect for soft tissue and bone of the collagen scaffold with better degradation pattern has not been clearly proven. This study determined whether the double surfaces of crosslinked collagen scaffolds could optimize the combined soft tissue repair and osteogenesis. In this study, we applied the chemically crosslinking treatment to the commercially available collagen scaffolds. Surface characterization, mechanical property and cell proliferation in vitro were evaluated. Combined bilateral skin and bone defects were established with the smooth surface of scaffold facing the skin defect and the rough surface facing the bone defect on the calvaria of rat. Micro-CT and histological evaluation were applied to determine the scaffold degradation pattern, soft tissue repair and osteogenesis. The crosslinked collagen scaffolds showed comparably favorable surface porosity, structure intactness, superhydrophilicity and mechanical properties. Compared to the native scaffolds, the crosslinked scaffolds could optimize the combined soft tissue repair and osteogenesis by preferably prolonged degradation time. Early pro-angiogenesis facilitated soft tissue repair and osteogenesis by upregulated soft tissue matrix degradation and balanced pro-osteogenesis with limited osteoclast-mediated bone resorption. Taken together, this study offers a promising repair strategy for the combined soft tissue and bone defects. Further, the possible mechanism of controllable scaffold degradation should be conducted.

The influences of PEG-functionalized graphdiyne on cell growth and osteogenic differentiation of bone marrow mesenchymal stem cells.

Guided bone regeneration (GBR) is a frequently used technique for patients with insufficient alveolar bone. The discovery of bone substitutes that can enhance osteogenesis is critical for GBR. Graphdiyne (GDY), a newly discovered carbon-based nanomaterial, has been recognized as the most stable allotrope of acetylene carbon and is anticipated to be able to promote osteogenesis. Whereas it still remains unknown whether it could enhance osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). In this study, GDY was modified with polyethylene glycol (PEG) and the influences of GDY-PEG at different concentrations on BMSCs cell growth and osteogenic differentiation were researched for the first time. In this study, we found that GDY-PEG at low concentration possessed premium bio-compatibility and revealed evident facilitation of BMSCs osteogenic differentiation. The cell growth and osteogenic differentiation of BMSCs treated with GDY-PEG were dose-dependent. GDY-PEG at 1 µg/mL demonstrated the optimal promoting effects of BMSCs osteogenic differentiation. Moreover, the regulating effect of BMSCs osteogenic differentiation by GDY-PEG might be associated with the Wnt/ß-catenin signaling pathway. In all, the present study indicated a novel application of GDY in promoting bone tissue regeneration, providing a novel biomaterial for bone augmentation in clinics.

Near-infrared light-responsive multifunctional hydrogel releasing peptide-functionalized gold nanorods sequentially for diabetic wound healing.

Treatment for chronic diabetic wounds remains a clinical challenge. Wound healing process occurs in three phases: inflammation, proliferation and remodeling. Several factors including bacterial infection, decreased local angiogenesis and diminished blood supply delay wound healing. There is an urgent need to develop wound dressings with multiple biological effects for different stages of diabetic wound healing. Here, we develop a multifunctional hydrogel with two-stage sequential release upon near-infrared (NIR) stimulation, antibacterial activity and pro-angiogenic efficacy. This hydrogel consists of covalently crosslinked bilayer structure, with the lower thermoresponsive poly(N-isopropylacrylamide)/gelatin methacrylate (NG) layer and the upper highly stretchable alginate/polyacrylamide (AP) layer embedding different peptide-functionalized gold nanorods (AuNRs) in each layer. Antimicrobial peptide-functionalized AuNRs released from NG layer exert antibacterial effects. After NIR irradiation, the photothermal transition efficacy of AuNRs synergistically enhances bactericidal efficacy. The contraction of thermoresponsive layer also promotes the release of embedded cargos during early stage. The pro-angiogenic peptide-functionalized AuNRs released from AP layer promote angiogenesis and collagen deposition by accelerating fibroblast and endothelial cell proliferation, migration and tube formation during the subsequent healing phases. Therefore, the multifunctional hydrogel with effective antibacterial activity, pro-angiogenic efficacy and sequential release behaviors is a potential biomaterial for diabetic chronic wound healing.

Interactions between genetic variants and near-work activities in incident myopia in schoolchildren: a 4-year prospective longitudinal study.

CLINICAL RELEVANCE: Knowledge of interactions between genetic variants and near-work activities at the onset of myopia can facilitate health education regarding myopia. BACKGROUND: To investigate the interactions between genetic variants (PDE10A, AREG and GABRR1) and near-work activities in the onset of myopia in southeastern Chinese school children. METHODS: A total of 458 non-myopic, grade 1 children aged 6-7 years were included in a 4-year follow-up examination; 409 children were assessed further. Manifest (non-cycloplegic) refraction and axial length (AL) were measured every year, and questionnaires were administered annually to assess information regarding the demographic characteristics of children, near-work activities, outdoor exposure and parental myopia. Oral mucosa was collected in the last year of follow-up, and Sanger sequencing was used to genotype single nucleotide polymorphisms (SNPs) in DNA. RESULTS: The cumulative change in the spherical equivalent refraction (SER) over 4 years was -1.20 ± 1.00 D, and the proportion of children with incident myopia was 42.9%. Multivariate logistic regression analysis showed that an increased amount of time spent doing homework (>2 h/d) was an independent risk factor for incident myopia. The PDE10A rs12206610CT genotype and spending > 5 h/d on near-work activities showed an interaction for incident myopia (OR = 4.29, 95% CI: 1.27-14.53; Pinteraction = 0.02); moreover, the rs12206610CT genotype carriers who used electronic devices for > 1 h/d displayed an increased risk of incident myopia (OR = 3.43, 95% CI: 1.07-11.01; Pinteraction = 0.043). CONCLUSIONS: The rs2206610CT genotype carriers with near-work activities of >5 h/d were more likely to show incident myopia, especially those who used electronic devices >1 h/d. However, interactions between the rs12206610 SNP and near-work activities require further verification in animal models and larger sample cohorts.