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Bone defects cause significant socio-economic costs worldwide, while the clinical “gold standard” of bone repair, the autologous bone graft, has limitations including limited graft supply, secondary injury, chronic pain and infection. Therefore, to reduce surgical complexity and speed up bone healing, innovative therapies are needed. Bone tissue engineering (BTE), a new cross-disciplinary science arisen in the 21st century, creates artificial environments specially constructed to facilitate bone regeneration and growth. By combining stem cells, scaffolds and growth factors, BTE fabricates biological substitutes to restore the functions of injured bone. Although BTE has made many valuable achievements, there remain some unsolved challenges. In this review, the latest research and application of stem cells, scaffolds, and growth factors in BTE are summarized with the aim of providing references for the clinical application of BTE.

Critical-sized bone defects often lead to non-union and full-thickness defects of the calvarium specifically still present reconstructive challenges. In this study, we show that neurotrophic supplements induce robust in vitro expansion of mesenchymal stromal cells, and in situ transplantation of neurotrophic supplements-incorporated 3D-printed hydrogel grafts promote full-thickness regeneration of critical-sized bone defects. Single-cell RNA sequencing analysis reveals that a unique atlas of in situ stem/progenitor cells is generated during the calvarial bone healing in vivo. Notably, we find a local expansion of resident Msx1+ skeletal stem cells after transplantation of the in situ cell culture system. Moreover, the enhanced calvarial bone regeneration is accompanied by an increased endochondral ossification that closely correlates to the Msx1+ skeletal stem cells. Our findings illustrate the time-saving and regenerative efficacy of in situ cell culture systems targeting major cell subpopulations in vivo for rapid bone tissue regeneration. Critical-sized bone defects still present clinical challenges. Here the authors show that transplantation of neurotrophic supplement-incorporated hydrogel grafts promote full-thickness regeneration of the calvarium and perform scRNA-seq to reveal contributing stem/progenitor cells, notably a resident Msx1+ skeletal stem cell population.

Functional materials displaying tunable emission and long-lived luminescence have recently emerged as a powerful tool for applications in information encryption, organic electronics and bioelectronics. Herein, we present a design strategy to achieve color-tunable ultralong organic room temperature phosphorescence (UOP) in polymers through radical multicomponent cross-linked copolymerization. Our experiments reveal that by changing the excitation wavelength from 254 to 370 nm, these polymers display multicolor luminescence spanning from blue to yellow with a long-lived lifetime of 1.2 s and a maximum phosphorescence quantum yield of 37.5% under ambient conditions. Moreover, we explore the application of these polymers in multilevel information encryption based on the color-tunable UOP property. This strategy paves the way for the development of multicolor bio-labels and smart luminescent materials with long-lived emission at room temperature. Functional materials displaying tunable emission and long-lived luminescence are a powerful tool in information encryption, organic electronics and bioelectronics. Here the authors design a color-tunable ultralong organic room temperature phosphorescence polymer through radical multiple component cross-linked copolymerization.

Bone morphogenetic protein-2 (BMP-2) has been commercially approved by the Food and Drug Administration for use in bone defects and diseases. BMP-2 promotes osteogenic differentiation of mesenchymal stem cells. In bone tissue engineering, BMP-2 incorporated into scaffolds can be used for stimulating bone regeneration in organoid construction, drug testing platforms, and bone transplants. However, the high dosage and uncontrollable release rate of BMP-2 challenge its clinical application, mainly due to the short circulation half-life of BMP-2, microbial contamination in bone extracellular matrix hydrogel, and the delivery method. Moreover, in clinical translation, the requirement of high doses of BMP-2 for efficacy poses challenges in cost and safety. Based on these, novel strategies should ensure that BMP-2 is delivered precisely to the desired location within the body, regulating the timing of BMP-2 release to coincide with the bone healing process, as well as release BMP-2 in a controlled manner to optimize its therapeutic effect and minimize side effects. This review highlights improvements in bone tissue engineering applying spatiotemporal and controlled BMP-2 delivery, including molecular engineering, biomaterial modification, and synergistic therapy, aiming to provide references for future research and clinical trials. Graphical Abstract

This research is primarily focused on the issues of customer loyalty in the healthcare industry, particularly from the perspective of public hospitals in China. The research developed a theoretical model to test the relationship between patient satisfaction (PS), patient trust (PT), and patient loyalty (PL). The empirical data were collected from 1696 patients through the survey questionnaires from the public hospitals in Henan province. This research is an explanatory study, and adopts quantitative method. The measurement scales used in the survey were assessed and refined and the data analysis was performed using AMOS 19.0 to test the theoretical model and hypotheses developed. In addition, an exploratory factor analysis was used to identify the dimensions of PS, PT, and PL. Their reliability and validity were established through confirmatory factor analysis, and the structural equation modeling (SEM) was used in the related hypotheses. The findings indicate that PT is an important antecedent of PL, and PS has no direct relationship with PL. It is worth noting that PS can lead to PL with PT as the mediating variable. The survey results will help public hospital managers to formulate effective strategies and provide a basis for studying PL. The research will prompt hospital managers to pay attention to the factors which contribute to PS, PT, and PL, and maintain the loyalty of patients to medical institutions. This study is one of the few studies on the relationship between PS, PT, and PL in Chinese public hospitals, and it also explores the direct and indirect effects of PT on PL. The results have practical implications for the Chinese healthcare industry.

Rosmarinus officinalis leaves (ROLs) are widely used in the food and cosmetics industries due to their high antioxidant activity and fascinating flavor properties. Carnosic acid (CA) and rosmarinic acid (RA) are regarded as the characteristic antioxidant components of ROLs, and the selective separation of CA and RA remains a significant challenge. In this work, the feasibility of achieving the selective separation of CA and RA from ROLs by solid-phase extraction (SPE) and liquid–liquid extraction (LLE) was studied and compared. The experiments suggested that SPE with CAD-40 macroporous resin as the adsorbent was a good choice for selectively isolating CA from the extracts of ROLs and could produce raw CA with purity levels as high as 76.5%. The LLE with ethyl acetate (EA) as the extraction solvent was more suitable for extracting RA from the diluted extracts of ROLs and could produce raw RA with a purity level of 56.3%. Compared with the reported column chromatography and LLE techniques, the developed SPE–LLE method not only exhibited higher extraction efficiency for CA and RA, but can also produce CA and RA with higher purity.

Previous studies were mostly conducted based on two-dimensional feature space to monitor salinization, while studies on dense long-term salinization monitoring based on three-dimensional feature space have not been reported. Based on Landsat TM/ETM+/OLI images and three-dimensional feature space method, this study introduced six typical salinization surface parameters, including NDVI, salinity index, MSAVI, surface albedo, iron oxide index, wetness index to construct eight different feature space monitoring index. The optimal soil salinization monitoring index model was proposed base on field observed data and then the evolution process of salinization in Yellow River Delta (YRD) were analyzed and revealed during 1984-2022. The salinization monitoring index model of MSAVI-Albedo-I Fe2O3 feature space had the highest accuracy with R 2 = 0.93 and RMSE = 0.678g/kg. The spatial distribution of salinization in YRD showed an increasing trend from inland southwest to coastal northeast and the salinization intensity showed an increasing trend during 1984-2022 due to the implements of agricultural measures such as planting salt-tolerant crops, microbial remediation and fertility improvement. The rate of salinization deterioration in the northeast part was greater than others. Zones of salinization improvement were mainly located in cultivated land of the southwest parts.

Background This study aimed to systematically analyze the effect of a serine/threonine kinase (STK11) mutation (STK11 mut ) on therapeutic efficacy and prognosis in patients with non-small cell lung cancer (NSCLC). Methods Candidate articles were identified through a search of relevant literature published on or before April 1, 2023, in PubMed, Embase, Cochrane Library, CNKI and Wanfang databases. The extracted and analyzed data included the hazard ratios (HRs) of PFS and OS, the objective response rate (ORR) of immune checkpoint inhibitors (ICIs), and the positive rates of PD-L1 expression. The HR of PFS and OS and the merged ratios were calculated using a meta-analysis. The correlation between STK11 mut and clinical characteristics was further analyzed in NSCLC datasets from public databases. Results Fourteen retrospective studies including 4317 patients with NSCLC of whom 605 had STK11 mut were included. The meta-analysis revealed that the ORR of ICIs in patients with STK11 mut was 10.1% (95%CI 0.9–25.2), and the positive rate of PD-L1 expression was 41.1% (95%CI 25.3–57.0). STK11 mut was associated with poor PFS (HR = 1.49, 95%CI 1.28–1.74) and poor OS (HR = 1.44, 95%CI 1.24–1.67). In the bioinformatics analysis, PFS and OS in patients with STK11 alterations were worse than those in patients without alterations ( p  < 0.001, p  = 0.002). Nutlin-3a, 5-fluorouracil, and vinorelbine may have better sensitivity in patients with STK11 mut than in those with STK11 wt . Conclusions Patients with STK11-mutant NSCLC had low PD-L1 expression and ORR to ICIs, and their PFS and OS were worse than patients with STK11 wt after comprehensive treatment. In the future, more reasonable systematic treatments should be explored for this subgroup of patients with STK11-mutant NSCLC.

Background Identification of hot spots in protein–DNA binding interfaces is extremely important for understanding the underlying mechanisms of protein–DNA interactions and drug design. Since experimental methods for identifying hot spots are time-consuming and expensive, and most of the existing computational methods are based on traditional protein–DNA features to predict hot spots, unable to make full use of the effective information in the features. Results In this work, a method named WTL-PDH is proposed for hot spots prediction. To deal with the unbalanced dataset, we used the Synthetic Minority Over-sampling Technique to generate minority class samples to achieve the balance of dataset. First, we extracted the solvent accessible surface area features and structural features, and then processed the traditional features using discrete wavelet transform and wavelet packet transform to extract the wavelet energy information and wavelet entropy information, and obtained a total of 175 dimensional features. In order to obtain the best feature subset, we systematically evaluate these features in various feature selection strategies. Finally, light gradient boosting machine (LightGBM) was used to establish the model. Conclusions Our method achieved good results on independent test set with AUC, MCC and F1 scores of 0.838, 0.533 and 0.750, respectively. WTL-PDH can achieve generally better performance in predicting hot spots when compared with state-of-the-art methods. The dataset and source code are available at https://github.com/chase2555/WTL-PDH .

Implant-associated infections (IAIs) are severe complications following orthopedic procedures involving implanted materials. Previous researchers had created various antibacterial coatings to prevent early postoperative infections. Nevertheless, these coatings frequently lack the wear-resistant properties necessary for long-term effectiveness, and their production process is intricate. To overcome this challenge, we developed and employed a chemical technique, incorporating Ag or Cu 2 O nanoparticles uniformly into the surface of titanium alloys to confer antibacterial properties. The microstructure and elemental composition of the coating were characterized using scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS). Our results demonstrated that the coating exhibited potent antibacterial activity, eliminating nearly all adhered bacteria within the first 6 hours. Prolonged friction test results revealed that the coating retained notable antibacterial activity and excellent biocompatibility. Notably, the straightforward fabrication process of this coating could allow for its application on implants of various shapes and materials, underscoring its potential for broad clinical adoption. In summary, this simple chemical method for surface modification of titanium alloys could provide long-lasting antibacterial properties, offering a cost-efficient and transformative strategy for preventing implant-associated infections. Graphical Abstract A. Preparation and characterization of the Ag or Cu2O nanoparticle coatings based on titanium alloy. This simple chemical deposition method for surface modification of titanium alloys provides long-lasting antibacterial properties and wear resistance. B. In-vitro antibacterial activity assay. The number of bacteria on the Ag and Cu-coated samples was significantly reduced compared to the control group. The bacterial surfaces in the samples showed significant damage, such as rupture, collapse, and distortion. C-D. In-vivo antibacterial assay of the acute osteomyelitis models and subcutaneous infection models. These nanoparticle coatings exhibit excellent in vivo antibacterial properties and maintain favorable antibacterial efficacy even after prolonged wear. Created in BioRender. Fang, J. (2025) https://BioRender.com/v64b128