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Natural bone is a material with a hierarchical porous structure; therefore, the pore size of bone tissue at the micro-scale is crucial for osteoblast function and osteogenesis. However, the physiological mechanisms behind pore size-regulated osteogenesis remain unclear. Trabecular separation is one of the main parameters of bone trabeculae structure, which is the gap between the trabeculae and can be understood as porosity. This study uses a bioinspired bone chip made from polydimethylsiloxane (PDMS) to mimic the multiscale microstructures of healthy and osteoporotic bone tissue based on data on trabecular separation from healthy and osteoporotic mice. Microchannels in the chip were made in the same topology and substrate but at different micro-scales. The result showed that osteoblasts seeded into the smaller microchannel (200 μm in diameter, mimicking healthy bone) demonstrate greater osteogenic capability and autophagy than in the larger one (350 μm in diameter, mimicking osteoporotic bone). In addition, changes in osteogenesis between each microchannel after using the autophagy inhibitor chloroquine (CQ) indicated that osteogenesis was accelerated by autophagy in the 200 μm microchannel. Finally, we found stronger osteogenesis in the 200 μm microchannel, which depends on the activation of Hippo/YAP signaling. This bioinspired bone chip, which mimics the cellular behavioral changes in the osteoporotic microenvironment at the tissue level during the transition from healthy to osteoporotic bone, is expected to be the ideal in vitro platform for studying osteoporosis (OP).

Regular prophylaxis with exogenous Factor VIII (FVIII) is recommended for individuals with severe haemophilia A (HA), but standardised data on bleeding, FVIII use, and quality of life (QoL) for this population in routine clinical practice are scarce. In a prospective, multinational, noninterventional study, male participants age ≥18 years with severe HA (FVIII ≤1 IU/dL) receiving prophylactic FVIII were followed for at least 6 months. Bleeding and FVIII use were reported weekly. Annualised bleeding rate (ABR) and FVIII infusion rate were calculated for participants with ≥6 months follow-up and combined with retrospective data from 6 months prior to baseline. Adverse events (AEs) were collected monthly. Participants completed the haemophilia-specific health-related QoL questionnaire for adults (Haemo-QoL-A) at baseline. This abstract presents a sub analysis of the study's Brazilian population. For all 54 Brazilian participants, median (range) age was 27 (18–47) years. For the 41 (76%) Brazilian participants with ≥6 months follow-up, mean (standard deviation [SD]; median) ABR for treated bleeds was 2.42 (4.05; 0.80) bleeds per year and mean (SD; median) annualised FVIII infusion rate was 167.87 (60.22; 155.17) infusions per year. Mean (SD; median) ABRs of treated traumatic, spontaneous, and joint bleeds were 0.90 (1.6; 0.0), 1.52 (3.3; 0.0), and 1.91 (3.29; 0.0) bleeds per year, respectively. Median (range) percentage of follow-up time adherent with prescribed prophylaxis frequency in Brazilian participants was 94.7%(49%-100%). Mean (SD) Haemo-QoL-A total transformed score (0–100) score was 70.3 (15.1) The lowest mean (SD) domain scores (representing lower QoL) in all Brazilian participants were for treatment concern 45.7 (30.85), physical functioning 66.9 (21.33), and consequences of bleeding 68.1 (22.92). AEs were reported in 22 (40.7%) participants, with the most common AEs being haemophilic arthropathy, nasopharyngitis, and synovitis, each reported in 2 (3.7%) Brazilian participants. Two serious AEs (oesophageal haemorrhage and haematoma) were reported, each by single participant (1.9%). Despite high prophylaxis adherence, participants reported breakthrough spontaneous and joint bleeding and impaired physical functioning. Additional haemostatic options for severe HA are needed.

In this paper, pre-extrusion treatment was applied to AZ80 alloy prior to caliber rolling, and microstructural evolution as well as mechanical properties of groove-rolled AZ80 alloy were studied. The results shown that the pre-deformation treatment can enhance the formability of AZ80 alloy and the cracking can be avoided. In addition, the pre-extrusion also resulted in fine grain structure after rolling process. Especially, 8-pass caliber rolling following by pre-extrusion of AZ80 alloy shown uniform and fine dynamic recrystallized (DRX) structure. Besides, the introduction of pre-deformation also promotes more second phases during caliber rolling. Therefore, the mechanical properties shown that the yield strength (TYS), tensile strength (UTS) and elongation after fracture (El.) of pre-extruded AZ80 caliber-rolled bars are 250 MPa, 440 MPa and 15%, respectively, which increased by 72%, 37%, and 88% compared with their as-cast counterparts. The improvement of mechanical properties is attributed to synergy effects of grain refinement, second precipitates strengthening and texture optimization.

The application of artificial intelligence (AI) in academic writing has raised concerns regarding accuracy, ethics, and scientific rigour. Some AI content detectors may not accurately identify AI-generated texts, especially those that have undergone paraphrasing. Therefore, there is a pressing need for efficacious approaches or guidelines to govern AI usage in specific disciplines. Our study aims to compare the accuracy of mainstream AI content detectors and human reviewers in detecting AI-generated rehabilitation-related articles with or without paraphrasing. This cross-sectional study purposively chose 50 rehabilitation-related articles from four peer-reviewed journals, and then fabricated another 50 articles using ChatGPT. Specifically, ChatGPT was used to generate the introduction, discussion, and conclusion sections based on the original titles, methods, and results. Wordtune was then used to rephrase the ChatGPT-generated articles. Six common AI content detectors (Originality.ai, Turnitin, ZeroGPT, GPTZero, Content at Scale, and GPT-2 Output Detector) were employed to identify AI content for the original, ChatGPT-generated and AI-rephrased articles. Four human reviewers (two student reviewers and two professorial reviewers) were recruited to differentiate between the original articles and AI-rephrased articles, which were expected to be more difficult to detect. They were instructed to give reasons for their judgements.Originality.ai correctly detected 100% of ChatGPT-generated and AI-rephrased texts. ZeroGPT accurately detected 96% of ChatGPT-generated and 88% of AI-rephrased articles. The areas under the receiver operating characteristic curve (AUROC) of ZeroGPT were 0.98 for identifying human-written and AI articles. Turnitin showed a 0% misclassification rate for human-written articles, although it only identified 30% of AI-rephrased articles. Professorial reviewers accurately discriminated at least 96% of AI-rephrased articles, but they misclassified 12% of human-written articles as AI-generated. On average, students only identified 76% of AI-rephrased articles. Reviewers identified AI-rephrased articles based on 'incoherent content' (34.36%), followed by 'grammatical errors' (20.26%), and 'insufficient evidence' (16.15%).This study directly compared the accuracy of advanced AI detectors and human reviewers in detecting AI-generated medical writing after paraphrasing. Our findings demonstrate that specific detectors and experienced reviewers can accurately identify articles generated by Large Language Models, even after paraphrasing. The rationale employed by our reviewers in their assessments can inform future evaluation strategies for monitoring AI usage in medical education or publications. AI content detectors may be incorporated as an additional screening tool in the peer-review process of academic journals.

Science teacher leaders have been identified as an important lever for the implementation of science education reform. However, science reform implementation is locally controlled and not uniform across districts; therefore, the work of STLs within a reform context can vary. In this descriptive case study, we explore the work of 11 science teacher leaders who support science education reform in a variety of organizational contexts. Through the analysis of multiple data sources, we describe the roles that these science teacher leaders take up in their work and identified how variation in these roles related to localized contexts and priorities for science education. We identified seven roles that science teacher leaders enacted in their work: activist, ambassador, collaborator, innovator, networker, organizer, and translator. We found that each science teacher leader prioritized one or two of these roles in their work, with other roles supporting these primary roles. While most science teacher leaders named some aspect of collaborator, networker, and ambassador as part of their work, only the district-level science leaders named translator. Furthermore, there were important differences across the science teacher leaders in our sample, which related to their district and/or school contexts. We end with suggestions for leveraging the existing variation in the work of science teacher leaders for designing professional development including opportunities for science teacher leaders to surface the various roles they occupy in their work and to provide choice in professional learning based on those roles.

Morphometric parameters and productivity of Arnica foliosa and Arnica Chamissonis in a comparative perspective were studied. The identification of their materials by external features and qualitative reactions was established.

Marine bivalves have a set of unique capabilities to adapt to the complicated conditions owing to their habitats, living habits and feeding ways. Meanwhile, marine bivalves can be the biosensors to monitor the quality of the intertidal zones or other habitats. It is interesting for every biologist to find out the mechanisms by which organisms adapt to environmental challenges and the factors limiting their adaptive capacities. The development of biotechnology over the past few decades has provided biologists with a vast repertoire of biosensors that allow testing mRNA expression in response to environmental factors. This minireview is focused on the transcriptomic responses to abiotic and biotic stressors in bivalves and the relative methods to provide new perspectives as well as improve applications for bivalve biomonitoring studies.

[This corrects the article DOI: 10.1371/journal.pone.0152310.].

Although in vivo studies have shown that low-magnitude, high-frequency (LMHF) vibration (LM: < 1 ×g; HF: 20-90 Hz) exhibits anabolic effects on skeletal homeostasis, the underlying cellular/molecular regulation involved in bone adaptation to LMHF vibration is little known. In this report, we tested the effects of microvibration (magnitude: 0.3 ×g, frequency: 40 Hz, amplitude: ± 50 μm, 30 min/12 h) on proliferation and osteodifferentiation of bone marrow-derived mesenchymal stromal cells (BMSCs) seeded on human bone-derived scaffolds. The scaffolds were prepared by partial demineralisation and deproteinisation. BMSCs were allowed to attach to the scaffolds for 3 days. Morphological study showed that spindle-shaped BMSCs almost completely covered the surface of bone-derived scaffold and these cells expressed higher ALP activity than those cultured on plates. After microvibration treatment, BMSC proliferation was decreased on day 7 and 10; however, numbers of genes and proteins expressed during osteogenesis, including Cbfa1, ALP, collagen I and osteocalcin were greatly increased. ERK1/2 activation was involved in microvibration-induced BMSC osteogenesis. Taken together, this study suggests that bone-derived scaffolds have good biocompatibility and show osteoinductive properties. By increasing the osteogenic lineage commitment of BMSCs and enhancing osteogenic gene expressions, microvibration promotes BMSC differentiation and increase bone formation of BMSCs seeded on bone-derived scaffolds. Moreover, ERK1/2 pathway plays an important role in microvibration-induced osteogenesis in BMSC cellular scaffolds.

DENV envelope glycoprotein (E) is responsible for interacting with host cell receptors and is the main target for the development of a dengue vaccine based on an induction of neutralizing antibodies. It is well known that DENV E glycoprotein has two potential N-linked glycosylation sites at Asn67 and Asn153. The N-glycans of E glycoprotein have been shown to influence the proper folding of the protein, its cellular localization, its interactions with receptors and its immunogenicity. However, the precise structures of the N-glycans that are attached to E glycoprotein remain elusive, although the crystal structure of DENV E has been determined. This study characterized the structures of envelope protein N-linked glycans on mature DENV-2 particles derived from insect cells via an integrated method that used both lectin microarray and MALDI-TOF-MS. By combining these methods, a high heterogeneity of DENV N-glycans was found. Five types of N-glycan were identified on DENV-2, including mannose, GalNAc, GlcNAc, fucose and sialic acid; high mannose-type N-linked oligosaccharides and the galactosylation of N-glycans were the major structures that were found. Furthermore, a complex between a glycan on DENV and the carbohydrate recognition domain (CRD) of DC-SIGN was mimicked with computational docking experiments. For the first time, this study provides a comprehensive understanding of the N-linked glycan profile of whole DENV-2 particles derived from insect cells.

Oxidized low density lipoprotein (LDL) is thought to mediate the transformation of macrophages to cholesterol-rich foam cells. Yet convincing evidence for this process is lacking in vitro. We suggest that oxidized LDL-mediated foam cell formation is not seen in vitro because the cholesteryl ester content of LDL particles (oxidized in the presence of transition metals) is dramatically reduced. Thus, if oxidized LDL could be cholesterol-enriched prior to its addition to macrophages, this lipoprotein would be made more capable of inducing the cellular deposition of cholesteryl esters. When we enriched cupric sulfate-oxidized LDL with cholesterol by incubation of this lipoprotein with unesterified cholesterol/phosphatidylcholine liposomes and added it to mouse peritoneal macrophage cultures, we found that: a) the enrichment of oxidized LDL with cholesterol did not alter the extent of oxidized LDL degradation; b) the cells accumulated massive amounts of cholesteryl ester (148 microg/mg cell protein) and unesterified cholesterol (260 microg/mg cell protein) after 24 h of incubation; and c) Sephacryl S-1000 chromatography of the cholesterol-enriched oxidized LDL verified the formation of large oxidized LDL-unesterified cholesterol/phosphatidylcholine complexes. These results demonstrate that oxidized LDL, when cholesterol-enriched, can mediate the formation of macrophage foam cells in culture

The alloys of the Ti-Zr-Mn system based on the C14-type Laves phase are considered as ones of the most promising materials for safe storage and transportation of hydrogen. These alloys have appropriate parameters for activating the processes of absorption and release of hydrogen, a low cost, and a fairly high cyclic stability. In this work, the microstructure and phase composition of the starting alloys and the crystal structure of the hydrides synthesized from them are studied. Possible ways to reduce the cost of the final products are shown. The fact that changing the method of the alloy fabrication does not significantly affect its hydrogen absorption properties is shown. On the example of the considered alloys, it is shown that, as expected, alloying with an element with a larger atomic radius that forms a stable chemical compound with hydrogen results in an increase in the hydrogen capacity. This is explained by both the increased radius of the tetrahedral interstitial sites, where hydrogen atoms are located after dissolution, and the higher total amount of the element interacting with hydrogen. [ABSTRACT FROM AUTHOR]

Planaria offer practical substitutes to chemicals for controlling mosquites and chironomid midges in some aquatic pest management systems. Unlike chemical larvicides, planaria produce a sustained high level of control that endures through the entire season without pest quests.