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Adolescents with idiopathic scoliosis (AIS) often exhibit a slender body shape and reduced bone mass, even in the absence of evident vertebral deformities. Although prior studies have implicated microRNAs (miRNAs) in the development and progression of AIS, the precise mechanisms remain poorly understood. Therefore, primary osteoblasts and plasma samples from AIS patients and controls were isolated and associated mechanism was investigated in this study. We observed impaired osteogenic capacity of AIS-osteoblasts, and further identified a significant elevation of miRNA-130b-3p in AIS patients compared to controls through RNA sequencing of plasma samples. The expression levels of miR-130b-3p were validated in an independent cohort of 40 individuals using qPCR. Dual-energy X-ray absorptiometry showed reduced bone mineral density (BMD) in AIS patients. And the correlation analysis revealed a significant negative relationship between miR-130b-3p levels and BMD. Additionally, transcriptomic analysis and dual-luciferase assays confirmed that overexpression of miR-130b-3p in primary osteoblasts inhibited the activation of the ERK1/2 signaling pathway by targeting IGF1, thereby disrupting bone metabolism. Meanwhile, knockdown of miR-130b-3p in AIS-derived osteoblasts improved osteogenic function. In zebrafish, miR-130b-3p overexpression delayed vertebral development and induced spinal deformities. In summary, this study identifies a significant increase of miR-130b-3p in AIS patients and demonstrates its role in impairing osteogenic function through suppression of the IGF1/ERK signaling pathway.

Congenital scoliosis (CS) is a complex spinal malformation of unknown etiology with abnormal bone metabolism. Fibroblast growth factor 23 (FGF23), secreted by osteoblasts and osteocytes, can inhibit bone formation and mineralization. This research aims to investigate the relationship between CS and FGF23. We collected peripheral blood from two pairs of identical twins for methylation sequencing of the target region. FGF23 mRNA levels in the peripheral blood of CS patients and age-matched controls were measured. Receiver operator characteristic (ROC) curve analyses were conducted to evaluate the specificity and sensitivity of FGF23. The expression levels of FGF23 and its downstream factors fibroblast growth factor receptor 3 (FGFr3)/tissue non-specific alkaline phosphatase (TNAP)/osteopontin (OPN) in primary osteoblasts from CS patients (CS-Ob) and controls (CT-Ob) were detected. In addition, the osteogenic abilities of FGF23-knockdown or FGF23-overexpressing Ob were examined. DNA methylation of the FGF23 gene in CS patients was decreased compared to that of their identical twins, accompanied by increased mRNA levels. CS patients had increased peripheral blood FGF23 mRNA levels and decreased computed tomography (CT) values compared with controls. The FGF23 mRNA levels were negatively correlated with the CT value of the spine, and ROCs of FGF23 mRNA levels showed high sensitivity and specificity for CS. Additionally, significantly increased levels of FGF23, FGFr3, OPN, impaired osteogenic mineralization and lower TNAP levels were observed in CS-Ob. Moreover, FGF23 overexpression in CT-Ob increased FGFr3 and OPN levels and decreased TNAP levels, while FGF23 knockdown induced downregulation of FGFr3 and OPN but upregulation of TNAP in CS-Ob. Mineralization of CS-Ob was rescued after FGF23 knockdown. Our results suggested increased peripheral blood FGF23 levels, decreased bone mineral density in CS patients, and a good predictive ability of CS by peripheral blood FGF23 levels. FGF23 may contribute to osteopenia in CS patients through FGFr3/TNAP / OPN pathway.

Liposomes (Lip) are microstructures containing lipid and aqueous phases for encapsulation and delivery of bioactivators. In this study, Ginsenoside Rh2 liposomes (Rh2−Lip) were prepared by a thin-film hydrated ultrasonic binding method. But they are not stable during storage. In addition, Rh2−Lip was wrapped with Auricultural cornea polysaccharide (ACP) and Chitosan (CS) as coating materials to improve stability. CS coating was used as a positive control. The particle sizes determined by dynamic light scattering (DLS) showed 183 ± 5.52 nm for liposomes, 197 ± 6.7 nm for Auricultural cornea polysaccharide coated liposomes (ACP−Rh2−Lip), and 198 ± 3.5 nm for Chitosan coated liposomes (CS−Rh2−Lip). The polydispersity index (PDI) of all liposomes was less than 0.3. Transmission electron microscopy (TEM) showed that ACP and CS were successfully encapsulated on the liposome surface. In vitro simulations of digestive stability in the gastrointestinal tract showed that ACP−Rh2−Lip and CS−Rh2−Lip were more stable in gastrointestinal fluids compared to Lip. The antioxidant experiment revealed that ACP−Rh2−Lip has greater antioxidant activity than Lip. The purpose of this study was to look into the effects of ACP−Rh2−Lip and to offer a reference for Ginsenoside Rh2 (Rh2) delivery.

Introduction: Low molecular weight heparin (LMWH), a natural sulfated glycosaminoglycan with an affinity for proangiogenic factors, is produced by chemical or enzymatic depolymerization of unfractionated heparin (UFH). Known for its anticoagulant effects, LMWH has recently been reported to have a strong anti-inflammatory effect on colitis, myocarditis, and airway inflammation. However, as a newly-developed drug, its anti-inflammatory mechanism in upper respiratory tract inflammation has not been well-studied. Methods: SD rats were randomly divided into control and experimental groups. The experimental group was established by building an acute nasal sinusitis model with expansion sponges mixed with Streptococcus pneumoniae . Then the experimental group rats were subcutaneously injected with different concentrations of LMWH. After seven consecutive days of injection, some rats were sacrificed, and blood and nasal mucosa samples were taken to determine their inflammation status. The remaining acute sinusitis rats were randomly selected for a week of nasal irrigation with normal saline or saline mixed with different concentrations of LMWH. One week later, rats were sacrificed, and samples of blood and nasal mucosa were taken to determine the inflammation status. Results: Rat nasal mucosa in the model group had obvious inflammation. The degree of nasal mucosa inflammation damage in the experimental group was lower than in the experimental control group, proving that LMWH has a protective effect on the nasal mucosa and that the effect correlates with dosage. Irrigation of the nose with saline mixed with LMWH can improve the anti-inflammatory effect. Protein related to the TLR4-MyD88-NF-κB signaling pathway was activated in the acute sinusitis rat model, and LMWH can significantly inhibit its expression. Conclusion: This is the first report of the anti-inflammatory effect of LMWH in acute upper respiratory tract inflammation, together with an explanation of its anti-inflammatory mechanism. The findings contribute a theoretical basis for its potential anti-tumor effect.

Cobalt alloys have numerous applications, especially as critical components in orthopedic biomedical implants. However, recent investigations have revealed potential hazards associated with the release of nanoparticles from cobalt-based implants during implantation. This can lead to their accumulation and migration within the body, resulting in adverse reactions such as organ toxicity. Despite being a primary interface for cobalt nanoparticle (CoNP) exposure, skeletal muscle lacks comprehensive long-term impact studies. This study evaluated whether selenium nanoparticles (SeNPs) could mitigate CoNP toxicity in muscle cells and zebrafish models. CoNPs dose-dependently reduced C2C12 viability while elevating reactive oxygen species (ROS) and apoptosis. However, low-dose SeNPs attenuated these adverse effects. CoNPs downregulated myogenic genes and α-smooth muscle actin (α-SMA) expression in C2C12 cells; this effect was attenuated by SeNP cotreatment. Zebrafish studies confirmed CoNP toxicity, as it decreased locomotor performance while inducing muscle injury, ROS generation, malformations, and mortality. However, SeNPs alleviated these detrimental effects. Overall, SeNPs mitigated CoNP-mediated cytotoxicity in muscle cells and tissue through antioxidative and antiapoptotic mechanisms. This suggests that SeNP-coated implants could be developed to eliminate cobalt nanoparticle toxicity and enhance the safety of metallic implants.

Efficient and flexible responses are essential for successfully interacting with the environment. These interactions require an instantaneous integration of visual stimuli and responses, known as ‘stimulus–response binding’ (SR binding). SR binding is considered part of a holistic temporary representation, the event file, that integrates the stimulus, the response, and the action effect produced by this response. It is commonly assumed that an event file (or at least the SR binding) would end with the execution of the response or its action effect. This, however, has never been directly tested. Here, we tested whether the SR binding can be formed between another temporally close stimulus that people didn’t respond to by implementing a sequence of two stimuli where participants needed to respond only to the first or second stimulus. Our results indicate that a binding between the response and this temporally close stimulus can occur, but only when it’s placed after, and not before, the response execution. This finding suggests that the event file might operate a temporal binding window that is not decisively terminated by the response execution. Further, this insight into the temporal dynamics of the event file highlights the temporal flexibility of the SR binding and, thus, the need for careful consideration of its sub-structures and durability.

BackgroundAdolescent idiopathic scoliosis (AIS) is a scoliotic deformity of unknown etiology that occurs during adolescent development. Abnormal bone metabolism is closely related to AIS, but the cause is uncertain. Recent studies have shown that heat shock protein 27 (HSP27) and its phosphorylation (pHSP27) play important roles in bone metabolism. However, whether HSP27 and pHSP27 are involved in abnormal bone metabolism in AIS is unclear.MethodsOsteoblasts (OBs) and bone marrow stem cells (BMSCs) were extracted from the facet joints and bone marrow of AIS patients and controls who underwent posterior spinal fusion surgery. The expression levels of HSP27 and pHSP27, as well as the expression levels of bone formation markers in OBs from AIS patients and controls, were examined by quantitative real-time PCR (qRT–PCR) and Western blotting. The mineralization ability of OBs from AIS patients and controls was analyzed by alizarin red staining after osteogenic differentiation. Heat shock and thiolutin were used to increase the levels of pHSP27 in OBs, and the levels of bone formation markers were also investigated. In addition, the levels of pHSP27 and the bone formation ability of BMSCs from AIS patients and controls were investigated after heat shock treatment.ResultsLower pHSP27 levels and impaired osteogenic differentiation abilities were observed in the OBs of AIS patients than in those of controls. Thiolutin increased HSP27 phosphorylation and increased the mRNA levels of SPP1 and ALPL in OBs from AIS patients. Heat shock treatment increased SPP1 and HSP27 mRNA expression, pHSP27 levels, OCN expression, and mineralization ability of both OBs and BMSCs from AIS patients.ConclusionHeat shock treatment and thiolutin can increase the levels of pHSP27 and further promote the bone formation of OBs and BMSCs from AIS patients. Therefore, decreased pHSP27 levels may be associated with abnormal bone metabolism in AIS patients.

There is a much lively debate about whether new ventures should adopt employee stock ownership plans (ESOPs). The inconsistent findings may be due to the neglect of employees’ life quality. This paper analyzed the relationship between ESOPs and employee workplace-psychology-life well-being and the moderating effect of opportunity-enhancing human resource practices (OHRPs). It adopted a survey that was completed by 262 employees of new ventures in the Greater Bay Area of China. The results show that ESOPs had a positive effect on the workplace and psychological well-being, but a negative effect on life well-being, and that this effect was mediated by psychological ownership. OHRPs moderated the mediating effect of ESOPs on workplace and life well-being via psychological ownership. The results reveal a particular correlation pattern between new venture ESOPs and employee well-being, which helps address the debate about the effects of ESOPs by providing an explanation from the life aspect. These findings highlight the importance of considering employee life well-being in understanding new venture ESOPs.

When responding to the identity of a visual target, nearby stimuli ( flankers ) that are associated with the same response as the target cause faster and more accurate responding than flankers that are associated with different responses. Because this flanker-congruence effect (FCE) decreases with increasing target-flanker separation, it was thought to reflect limited precision of spatial selection mechanisms. Later studies, however, showed that FCEs are larger when the target and flankers are the same color compared to when they are different colors. This led to the group selection hypothesis , which states that flankers are perceptually grouped with the target and are obligatorily selected along with it, regardless of spatial separation. An alternative hypothesis, the image segmentation hypothesis , states that feature differences facilitate the segmentation of visual information into relevant and irrelevant parts, thereby mitigating the limitations of spatial precision of selection mechanisms. We test between these hypotheses using a design in which targets and flankers are grouped or not grouped, while holding feature differences in the stimulus constant. Contrary to earlier results, we found that same-colored flankers do not yield larger FCEs than different-colored flankers when feature differences are held constant. We conclude that similarity effects on the FCE reflect differential support for image segmentation, on which selection depends, rather than the obligatory selection of perceptually grouped flankers and targets.

Abstract Background: Congenital scoliosis (CS) is a complex spinal malformation of unknown etiology with abnormal bone metabolism. Fibroblast growth factor 23 (FGF23), secreted by osteoblasts and osteocytes, can inhibit bone formation and mineralization. This research aims to investigate the relationship between CS and FGF23. Methods: We collected peripheral blood from two pairs of identical twins for methylation sequencing of the target region. FGF23 mRNA levels in the peripheral blood of CS patients and age-matched controls were measured. Receiver operator characteristic (ROC) curve analyses were conducted to evaluate the specificity and sensitivity of FGF23. The expression levels of FGF23 and its downstream factors fibroblast growth factor receptor 3 (FGFr3)/tissue non-specific alkaline phosphatase (TNAP)/osteopontin (OPN) in primary osteoblasts from CS patients (CS-Ob) and controls (CT-Ob) were detected. In addition, the osteogenic abilities of FGF23-knockdown or FGF23-overexpressing Ob were examined. Results: DNA methylation of the FGF23 gene in CS patients was decreased compared to that of their identical twins, accompanied by increased mRNA levels. CS patients had increased peripheral blood FGF23 mRNA levels and decreased computed tomography (CT) values compared with controls. The FGF23 mRNA levels were negatively correlated with the CT value of the spine, and ROCs of FGF23 mRNA levels showed high sensitivity and specificity for CS. Additionally, significantly increased levels of FGF23, FGFr3, OPN, impaired osteogenic mineralization and lower TNAP levels were observed in CS-Ob. Moreover, FGF23 overexpression in CT-Ob increased FGFr3 and OPN levels and decreased TNAP levels, while FGF23 knockdown induced downregulation of FGFr3 and OPN but upregulation of TNAP in CS-Ob. Mineralization of CS-Ob was rescued after FGF23 knockdown. Conclusions: Our results suggested increased peripheral blood FGF23 levels, decreased bone mineral density in CS patients, and a good predictive ability of CS by peripheral blood FGF23 levels. FGF23 may contribute to osteopenia in CS patients through FGFr3/TNAP/OPN pathway.