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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.

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

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.

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.

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.

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.

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.

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.

Regenerative repair of the brain after traumatic brain injury (TBI) remains an extensive clinical challenge, inspiring intensified interest in therapeutic approaches to explore superior repair strategies. Exosome therapy is another research hotspot following stem cell alternative therapy. Prior research verified that exosomes produced by neural stem cells can participate in the physiological and pathological changes associated with TBI and have potential neuroregulatory and repair functions. In comparison with their parental stem cells, exosomes have superior stability and immune tolerance and lower tumorigenic risk. In addition, they can readily penetrate the blood‒brain barrier, which makes their treatment efficiency superior to that of transplanted stem cells. Exosomes secreted by neural stem cells present a promising strategy for the development of novel regenerative therapies. Their tissue regeneration and immunomodulatory potential have made them encouraging candidates for TBI repair. The present review addresses the challenges, applications and potential mechanisms of neural stem cell exosomes in regenerating damaged brains.

Encapsulation of polymer chains into nanochannels of metal-organic frameworks (MOFs) to construct polymer-MOF hybrid materials can retain the desired properties of two disparate materials. However, the facile fabrication of such hybrids remains challenging, given the difficulty in unraveling entanglement of polymer chains and constraining them into ordered conformations. Herein, we introduce an in situ molecular weaving strategy to construct ionic polymer-MOF hybrid materials, employing shear forces and coordination interactions to untangle cationic polymer chains and guide their realignment within MOF nanochannels during framework formation. Notably, this realignment promotes uniform polymer distribution and exposes more anion-exchange sites. The resulting hybrids capture ReO 4 ¯ (a nonradioactive surrogate of 99 TcO 4 ¯ ) with a capacity of 438 mg g -1 and reach adsorption equilibrium within 20 min. Characterization and theoretical calculations reveal that the hydrophobic pores in the hybrid materials confer strong affinity toward less hydrated 99 TcO 4 ¯ anions, thereby enhancing their selectivity over competing anions. The combination of crystallinity, porosity and processability make polymer- metal-organic frameworks interesting materials but their fabrication is challenging. Here, the authors fabricate these materials via an in situ molecular weaving strategy in which the alignment of cationic polymer chains within the metal-organic frameworks is guided by shear forces and coordination interactions.