Miracle-dz/UniFAR-FTUs huggingface dataset:
Injectable hydrogel with immobilized BMP-2 mimetic peptide for local bone regeneration

Osteoporosis is a disease characterized by a decrease in bone mineral density, thereby increasing the risk of sustaining a fragility fracture. Most medical therapies are systemic and do not restore bone in areas of need, leading to undesirable side effects. Injectable hydrogels can locally deliver therapeutics with spatial precision, and this study reports the development of an injectable hydrogel containing a peptide mimic of bone morphogenetic protein-2 (BMP-2). To create injectable hydrogels, hyaluronic acid was modified with norbornene (HANor) or tetrazine (HATet) which upon mixing click into covalently crosslinked Nor-Tet hydrogels. By modifying HANor macromers with methacrylates (Me), thiolated BMP-2 mimetic peptides were immobilized to HANor via a Michael addition reaction, and coupling was confirmed with 1H NMR spectroscopy. BMP-2 peptides presented in soluble and immobilized form increased alkaline phosphatase (ALP) expression in MSCs cultured on 2D and encapsulated in 3D Nor-Tet hydrogels. Injection of bioactive Nor-Tet hydrogels into hollow intramedullary canals of Lewis rat femurs showed a local increase in trabecular bone density as determined by micro-CT imaging. The presented work shows that injectable hydrogels with immobilized BMP-2 peptides are a promising biomaterial for the local regeneration of bone tissue and for the potential local treatment of osteoporosis.
Adaptation and Validation of a Scale for Measuring the Curriculum-Based Professional Learning Community in Early Childhood Education in China

Teachers' professional learning community, as an effective path to promote teachers' professional development and elevate teaching quality, has been widely used in school contexts. In preschools, the practice of teachers' professional learning community mainly focuses on the curriculum in early childhood education. The revision and adaptation of the scale of the professional learning community for preschool teachers in the Chinese cultural context are of great significance for understanding the current situation of the professional learning community for preschool teachers and improving the quality of collaboration within the community. Teachers' Professional Learning Community scale was revised into the Curriculum-Based Professional Learning Community scale according to the characteristics of the curriculum in early childhood education in the Chinese context. Based on the data from a sample of 2,823 teachers, the study conducted an item analysis and exploratory factor analysis (EFA) on participants from sample A (N = 1,410) and confirmatory factor analyses (CFAs) on participants from sample B (N = 1, 413). Short-form Teacher Self-Efficacy scale was used as the criteria-related validity instrument. Sample A and sample B were used to explore the relationship between various dimensions of teachers' professional learning community and teachers' teaching efficacy. The results showed that instead of the five-factor structure of the original PLC scale, the Chinese version of the CBPLC scale consists of four factors: Shared Sense of Purpose, Collective Focus on Children Learning and Development, Collaborative and Reflective Activity, and Deprivatized Practice. The revised scale has high reliability and validity and can be used as an effective tool to measure the curriculum-based professional learning community of preschool teachers in China. The results of CFA indicated that the four-factor CFA model fit the data well, and the CBPLC significantly and positively predicted teachers' self-efficacy including instructional strategies, students' engagement, and classroom management.
Energy, Exergy, and Economic Performances of Combined CO2 Power and Cooling Systems: Comparison and Multi-Objective Optimization

As a natural working fluid, carbon dioxide (CO2) has been extensively applied to produce power and cooling in thermodynamic cycles. So far, various combined CO2 power and cooling systems have been proposed to enhance the energy conversion efficiency and reduce the cost further. However, how to evaluate the performance of different combined systems for a practical application scenario is still an open question. Thus, in this work, four representative systems are considered to investigate and compare the energy, exergy, and economic performances under design conditions. The corresponding models are established, and various performance parameters are calculated. According to the obtained results, the total products of four systems are 6831.36 kW, 4421.73 kW, 6252.81 kW, and 6978.69 kW, respectively. The minimum total cost is obtained by System 2. Thereafter, in order to maximize the total product (the sum of net work and refrigerating capacity), and simultaneously minimize the total cost, key system parameters are optimized by a multi-objective optimization algorithm, namely, NSGA-Ⅱ. The optimization results show that System 1 provides the highest total product (7345.4 kW), while System 2 has the lowest cost (27.51 $/h). After comprehensive comparisons for the net work, cooling capacity, efficiencies, and total cost, System 1 is regarded as the best among the considered four systems.
Glycyl-L-histidyl-L-lysine-Cu2+ attenuates cigarette smoke-induced pulmonary emphysema and inflammation by reducing oxidative stress pathway

Background: Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder manifested as chronic airway inflammation and persistent airflow limitation with the essential mechanism as inflammatory response and oxidative stress induced by toxic exposures such as cigarette smoke (CS). Glycyl-L-histidyl-L-lysine (GHK) is a nontoxic tripeptide involved in the process of healing and regeneration as a natural product. With the combination of Cu(II), glycyl-L-histidyl-L-lysine-Cu2+ (GHK-Cu) improves antioxidative and anti-inflammatory bioavailability, and they might offer potential therapeutic properties for COPD. Thus, the present study aimed to identify the potential effects of GHK-Cu on emphysema induced by cigarette smoke. Methods: In the in vivo experiment, C57BL/6J mice were exposed to CS for 12 weeks to induce pulmonary emphysema. GHK-Cu was injected intraperitoneally at doses of 0.2, 2 and 20 μg/g/day in 100 µl of saline on alternative days from the 1st day after CS exposure. The effects of GHK-Cu on the morphology of CS-induced emphysema, the inflammatory response and oxidative stress were evaluated. The antioxidative effect of GHK-Cu on human alveolar epithelial A549 cells was assessed in vitro. Results: GHK-Cu treatment attenuated the CS-induced emphysematous changes and partially reversed the matrix metalloprotein -9 (MMP-9)/tissue inhibitor of metalloproteinases-1 (TIMP-1) imbalance in the lung tissue. GHK-Cu reduced the inflammation and oxidation by decreasing the expression of inflammatory cytokines (IL-1β and TNF-α) in the bronchoalveolar lavage and the enzymatic activity of MPO and MDA in the lung homogenate while restoring the T-AOC and GSH content. Furthermore, administration of GHK-Cu reversed the increase in NF-κB expression induced by CS and increased the Nrf2 level, as an antioxidant defense component, in mice with chronic CS exposure. In CSE-exposed human alveolar epithelial A549 cells, GHK-Cu also inhibited oxidative stress by suppressing MDA levels and restoring T-AOC and GSH levels, which were modulated by upregulating Nrf2 expression. Conclusion: GHK-Cu treatment attenuated CS-induced emphysema by anti-inflammation by downregulating NF-κB and antioxidation via upregulation of the Nrf2/Keap1 in lung tissues.
Regulation of metabolic and transcriptional responses by the thyroid hormone in cellular models of murine macrophages

Oncogene-immortalized bone marrow-derived macrophages are considered to be a good model for the study of immune cell functions, but the factors required for their survival and proliferation are still unknown. Although the effect of the thyroid hormones on global metabolic and transcriptional responses in macrophages has not yet been examined, there is increasing evidence that they could modulate macrophage functions. We show here that the thyroid hormone T3 is an absolute requirement for the growth of immortal macrophages. The hormone regulates the activity of the main signaling pathways required for proliferation and anabolic processes, including the phosphorylation of ERK and p38 MAPKs, AKT, ribosomal S6 protein, AMPK and Sirtuin-1. T3 also alters the levels of metabolites controlling transcriptional and post-transcriptional actions in macrophages, and causes widespread transcriptomic changes, up-regulating genes needed for protein synthesis and cell proliferation, while down-regulating genes involved in immune responses and endocytosis, among others. This is not observed in primary bone marrow-derived macrophages, where only p38 and AMPK activation is regulated by T3 and in which the metabolic and transcriptomic effects of the hormone are much weaker. However, the response to IFN-γ is reduced by T3 similarly in immortalized macrophages and in the primary cells, confirming previous results showing that the thyroid hormones can antagonize JAK/STAT-mediated signaling. These results provide new perspectives on the relevant pathways involved in proliferation and survival of macrophage cell culture models and on the crosstalk between the thyroid hormones and the immune system.
Effects of Dietary Lipid Sources on the Growth, Gonad Development, Fatty Acid Composition and Spawning Performance of Broodstock, and Early Larvae Quality of Sea Urchin (Strongylocentrotus intermedius)

This study was carried out to investigate the effects of five formulated feeds with different lipid sources (colza oil (CO), fish oil (FO), linseed oil (LO), soybean oil (SO), or palm oil (PO)) and kelp (Laminaria japonica) on the growth, reproductive performance of broodstock, and early larvae quality of sea urchin (Strongylocentrotus intermedius). The experimental diets were randomly allocated to a total of 48 (eight urchins per experimental group) individually cultured S. intermedius(initial weight 90.51 ± 0.82g) and the feeding period lasted for 12 weeks. The results showed that the weight gain rate of female sea urchins fed kelp was significantly higher than those fed formulated feeds while the gonadosomatic index of spawned female sea urchins fed kelp was significantly lower than those fed formulated feeds.S. intermedius broodstock fed FO showed the largest egg diameter and fecundity, which could be due to the abundant n-3 LC-PUFA deposited in the gonads of this group. Sea urchins fed SO showed the lowest fecundity and hatching rate, and the highest inflammation level. Sea urchins fed CO showed the highest content of oleic acid in the gonads and eggs, but the lowest fertilization rate. The highest hatching rate was observed in the kelp treatment, which was comparable to that in the LO and PO but was significantly higher than that in CO, FO, and SO. Before mouth opening, all prismatic larvae showed no significant differences in survival during the first 2 days post hatchery (DPH). At the 3 DPH, the survival of S. intermedius larvae was highest in the FO group, followed by those in the PO group, with the lowest survival observed in the kelp group. Thus, FO was accepted as the most ideal lipid source based on growth, reproductive performance, and early larval quality. These results could contribute to adopting an efficient feeding strategy to promote the reproductive performance and offspring quality by choosing the optimal lipid source for S. intermedius broodstock.
Cost-effectiveness of nivolumab plus ipilimumab as first-line treatment for American patients with unresectable malignant pleural mesothelioma

Background The treatment paradigm of unresectable malignant pleural mesothelioma (MPM) has changed in recent years. Checkmate 743 demonstrate that nivolumab plus ipilimumab showed good clinical benefits compared with chemotherapy in the treatment of MPM. The study is aim to evaluate the cost-effectiveness of Nivolumab plus ipilimumab vs. platinum plus chemotherapy for the first-line treatment of unresectable MPM. Methods A Markov model was developed to compare the cost and quality-adjusted life-year (QALY) of nivolumab plus ipilimumab and chemotherapy over a 10-year time horizon. Clinical efficacy and safety data were extracted from the CheckMate 743 trials. Health state utilities were obtained from published literature. Costs were collected from an US payer perspective. One-way and probabilistic sensitivity analyses were conducted to explore the impact of uncertainties on the cost-effectiveness's results. Results In the base case analysis, the incremental healthcare costs and QALYs for Nivolumab plus Ipilimumab vs. chemotherapy are $196,604.22 and 0.53, respectively, resulting an incremental cost-effectiveness ratio (ICER) of $372,414.28/QALYs for the model cohort of patients with locally advanced or metastatic MPM. However, Probabilistic sensitivity analysis showed that there was no probability that Nivolumab plus ipilimumab was cost-effective within the fluctuation range of other model parameters in first-line in unresectable MPM. The results of one-way sensitivity analysis showed that the cost of Nivolumab was the most sensitive parameter. Conclusions The ICER of Nivolumab plus ipilimumab is above the theoretical willingness-to-pay threshold in the U.S, which suggests that first-line nivolumab plus ipilimumab for unresectable MPM may be not a cost-effective choice.
Soil properties, rhizosphere bacterial community, and plant performance respond differently to fumigation and bioagent treatment in continuous cropping fields

Continuous cropping barriers lead to huge agriculture production losses, and fumigation and biological agents are developed to alleviate the barriers. However, there is a lack of literature on the differences between strong chemical fumigant treatment and moderate biological agent treatment. In this study, we investigated those differences and attempted to establish the links between soil properties, rhizosphere microbial community, and plant performance in both fumigation- and bioagent-treated fields. The results showed that the fumigation had a stronger effect on both soil functional microbes, i.e., ammonia oxidizers and soil-borne bacterial pathogens, and therefore, led to a significant change in soil properties, higher fertilizer efficiency, lower disease infections, and improved plant growth, compared with untreated control fields. Biological treatment caused less changes to soil properties, rhizosphere bacterial community, and plant physiology. Correlation and modeling analyses revealed that the bioagent effect was mainly direct, whereas fumigation resulted in indirect effects on alleviating cropping barriers. A possible explanation would be the reconstruction of the soil microbial community by the fumigation process, which would subsequently lead to changes in soil characteristics and plant performance, resulting in the effective alleviation of continuous cropping barriers.
Impact of digital manufacturing on health care industry

Healthcare industry is one of the most important sectors that had made substantial progress over the past few decades and is continuing to evolve in many different areas. The applications of digital manufacturing technologies such as three dimensional (3D) printing are rapidly increasing and likely to transform the healthcare industry. Moreover, 3D printing capabilities align well with the needs of medical applications and are feasible for specialized pre-surgical planning, prosthetic applications, tissue engineering and organ printing, regenerative medicine etc. Furthermore, 3D printing technology has significant potential for development in various aspects of the modern healthcare industry, due to its capability of printing customized, complex, multi-material geometries.Therefore, in the next few years, 3D printing is expected to transform the healthcare industry. However, the limitations due to initial equipment cost, lack of expertise, and lack of suitable materials and stability of the printed materials need to be addressed to take full advantage of the technology.
Targeted Deletion of the Claudin12 Gene in Mice Increases Articular Cartilage and Inhibits Chondrocyte Differentiation

To study the role of Claudin (CLDN)12 in bone, we developed mice with a targeted deletion of exon2 in the Cldn12 gene for skeletal phenotype analysis. Micro-CT analysis of the secondary spongiosa of distal femurs of mice with targeted disruption of the Cldn12 gene and control littermates showed no significant genotype-specific differences in either cortical or trabecular bone parameters for either gender in 13-week-old mice. Immunohistochemistry revealed that while CLDN12 was expressed in both differentiating chondrocytes and osteoblasts of the secondary spongiosa of 3-week-old wild-type mice, its expression was restricted to differentiating chondrocytes in the articular cartilage and growth plate in adult mice. Articular cartilage area at the knee were increased by 47% in Cldn12 knockout (KO) mice compared to control littermates. Micro-CT analyses found that while the trabecular number was increased by 9% and the trabecular spacing was reduced by 9% in the femoral epiphysis of Cldn12 KO mice, neither bone volume nor bone volume adjusted for tissue volume was different between the two genotypes. The expression levels of Clusterin, Lubricin and Mmp13 were increased by 56%, 46%, and 129%, respectively, in primary articular chondrocytes derived from KO compared to control mice. Our data indicate that targeted deletion of the Cldn12 gene in mice increases articular cartilage, in part, by promoting articular chondrocyte phenotype.
Knowledge Mapping of Exosomes in Autoimmune Diseases: A Bibliometric Analysis (2002–2021)

Background Autoimmune diseases (AIDs) are a class of chronic disabling diseases characterized by inflammation and damage to muscles, joints, bones, and internal organs. Recent studies have shown that much progress has been made in the research of exosomes in AIDs. However, there is no bibliometric analysis in this research field. This study aims to provide a comprehensive overview of the knowledge structure and research hotspots of exosomes in AIDs through bibliometrics. Method Publications related to exosomes in AIDs from 2002 to 2021 were searched on the web of science core collection (WoSCC) database. VOSviewers, CiteSpace and R package “bibliometrix” were used to conduct this bibliometric analysis. Results 312 articles from 48 countries led by China and the United States were included. The number of publications related to exosomes in AIDs is increasing year by year. Central South University, Sun Yat Sen University, Tianjin Medical University and University of Pennsylvania are the main research institutions. Frontiers in immunology is the most popular journal in this field, and Journal of Immunology is the most co-cited journal. These publications come from 473 authors among which Ilias Alevizos, Qianjin Lu, Wei Wei, Jim Xiang and Ming Zhao had published the most papers and Clotilde Théry was co-cited most often. Studying the mechanism of endogenous exosomes in the occurrence and development of AIDs and the therapeutic strategy of exogenous exosomes in AIDs are the main topics in this research field. “Mesenchymal stem cells”, “microRNA”, “biomarkers”, “immunomodulation”, and “therapy” are the primary keywords of emerging research hotspots. Conclusion This is the first bibliometric study that comprehensively summarizes the research trends and developments of exosomes in AIDs. This information identifies recent research frontiers and hot directions, which will provide a reference for scholars studying exosomes.
Oxidation and Reduction Dual-Responsive Polymeric Prodrug Micelles Co-delivery Precisely Prescribed Paclitaxel and Honokiol for Laryngeal Carcinoma Combination Therapy

Laryngeal carcinoma is the most common head and neck malignancy globally, and chemotherapy is still the most common treatment for this type of carcinoma. Monotherapy has become powerless because of the lack of drugs in the anticancer agent library, the difficult process of new drug discovery, and the widespread drug resistance. Combination therapy with two agents, in particular Chinese herbal medicines with chemotherapy drugs, is a potential alternative to chemotherapy alone. However, combination therapy faces difficulties in delivering multiple drugs to tumor tissue in a precise ratio. Here, a cocktail polymeric prodrug micelle (PHPPM) was developed using an oxidation and reduction dual-responsive polymeric paclitaxel (PTX) and polymeric honokiol (HK) prodrugs. Both of them were obtained by covalently conjugating the drug to dextran via diselenium bonds. Following optimization and characterization, the PHPPM with the precise mass ratio of PTX and HK was obtained, enabling ratiometric drug loading, synchronized drug release in response to tumor high-level reactive oxygen species and glutathione environment, long blood circulation, and high tumor accumulation. This co-delivery system can effectively inhibit laryngeal carcinoma growth in vitro and in vivo. Codelivery of chemotherapy agents and Chinese herbal medicine with a precise ratio and controlled release of the two drugs at the tumor site provides an effective approach to clinical therapy for other laryngeal carcinomas.
Elevated monocyte-to-HDL cholesterol ratio predicts post-stroke depression

Objectives Inflammation plays an important role in the development of depression after stroke. Monocyte-to-HDL Cholesterol Ratio (MHR) recently emerged as a novel comprehensive inflammatory indicator in recent years. This study aimed to investigate whether there is a relationship between MHR levels and post-stroke depression (PSD). Methods From February 2019 to September 2021, patients with acute ischemic stroke (AIS) were recruited within 7 days post-stroke from the two centers and blood samples were collected after admission. The 17-item Hamilton Depression Scale (HAMD-17) was used to measure depressive symptoms at 3 months after stroke. Patients were given the DSM-V criteria for diagnosis of PSD. Results Of the 411 enrolled patients, 92 (22.38%) patients were diagnosed with PSD at 3-months follow-up. The results also showed significantly higher level of MHR in patients with depression [0.81 (IQR 0.67–0.87) vs. 0.61 (IQR 0.44–0.82), P < 0.001] at admission than patients without depression. Multivariate logistic regression revealed that MHR (OR 6.568, 95% CI: 2.123–14.565, P = 0.015) was an independent risk factor for the depression at 3 months after stroke. After adjustment for potential confounding factors, the odds ratio of PSD was 5.018 (95% CI: 1.694–14.867, P = 0.004) for the highest tertile of MHR compared with the lowest tertile. Based on the ROC curve, the optimal cut-off value of MHR as an indicator for prediction of PSD was projected to be 0.55, which yielded a sensitivity of 87% and a specificity of 68.3%, with the area under the curve at 0.660 (95% CI: 0.683–0.781; P = 0.003). Conclusion Elevated level of MHR was associated with PSD at 3 months, suggesting that MHR might be a useful Inflammatory markers to predict depression after stroke.