Alterations in the microenvironment and the effects produced of TRPV5 in osteoporosis.

The pathogenesis of osteoporosis involves multiple factors, among which alterations in the bone microenvironment play a crucial role in disrupting normal bone metabolic balance. Transient receptor potential vanilloid 5 (TRPV5), a member of the TRPV family, is an essential determinant of the bone microenvironment, acting at multiple levels to influence its properties. TRPV5 exerts a pivotal influence on bone through the regulation of calcium reabsorption and transportation while also responding to steroid hormones and agonists. Although the metabolic consequences of osteoporosis, such as loss of bone calcium, reduced mineralization capacity, and active osteoclasts, have received significant attention, this review focuses on the changes in the osteoporotic microenvironment and the specific effects of TRPV5 at various levels.

Genetic Dissection of Phosphorus Use Efficiency and Genotype-by-Environment Interaction in Maize.

Genotype-by-environment interaction (G-by-E) is a common but potentially problematic phenomenon in plant breeding. In this study, we investigated the genotypic performance and two measures of plasticity on a phenotypic and genetic level by assessing 234 maize doubled haploid lines from six populations for 15 traits in seven macro-environments with a focus on varying soil phosphorus levels. It was found intergenic regions contributed the most to the variation of phenotypic linear plasticity. For 15 traits, 124 and 31 quantitative trait loci (QTL) were identified for genotypic performance and phenotypic plasticity, respectively. Further, some genes associated with phosphorus use efficiency, such as Zm00001eb117170, Zm00001eb258520, and Zm00001eb265410, encode small ubiquitin-like modifier E3 ligase were identified. By significantly testing the main effect and G-by-E effect, 38 main QTL and 17 interaction QTL were identified, respectively, in which MQTL38 contained the gene Zm00001eb374120, and its effect was related to phosphorus concentration in the soil, the lower the concentration, the greater the effect. Differences in the size and sign of the QTL effect in multiple environments could account for G-by-E. At last, the superiority of G-by-E in genomic selection was observed. In summary, our findings will provide theoretical guidance for breeding P-efficient and broadly adaptable varieties.

Single Side-Chain-Modulatory of Hemicyanine for Optimized Fluorescence and Photoacoustic Dual-Modality Imaging of H2S In Vivo.

Near-infrared fluorescence (NIRF)/photoacoustic (PA) dual-modality imaging integrated high-sensitivity fluorescence imaging with deep-penetration PA imaging has been recognized as a reliable tool for disease detection and diagnosis. However, it remains an immense challenge for a molecule probe to achieve the optimal NIRF and PA imaging by adjusting the energy allocation between radiative transition and nonradiative transition. Herein, a simple but effective strategy is reported to engineer a NIRF/PA dual-modality probe (Cl-HDN3) based on the near-infrared hemicyanine scaffold to optimize the energy allocation between radiative and nonradiative transition. Upon activation by H2S, the Cl-HDN3 shows a 3.6-fold enhancement in the PA signal and a 4.3-fold enhancement in the fluorescence signal. To achieve the sensitive and selective detection of H2S in vivo, the Cl-HDN3 is encapsulated within an amphiphilic lipid (DSPE-PEG2000) to form the Cl-HDN3-LP, which can successfully map the changes of H2S in a tumor-bearing mouse model with the NIRF/PA dual-modality imaging. This work presents a promising strategy for optimizing fluorescence and PA effects in a molecule probe, which may be extended to the NIRF/PA dual-modality imaging of other disease-relevant biomarkers.

Application of Mg-MOF-loaded gelatin microspheres with osteogenic, angiogenic, and ROS scavenging capabilities in bone defect repair.

The management of bone defects, particularly those with irregular geometries resulting from osteoporotic fractures, remains fraught with challenges. Microspheres have emerged as a promising vehicle for tissue engineering, distinguished by their controlled release, safety, and ease of application. Various bioactive components are integrated into microspheres to improve their performance. Metal-organic frameworks, formed from metal ions interconnected by organic ligands, are increasingly utilized in tissue engineering. Specifically, magnesium-based MOFs are notable for their broad applicability; Mg2+ ions are instrumental in bone reconstruction and repair, facilitating osteogenesis, angiogenesis, antibacterial effects, and anti-inflammatory properties. Mg-MOF was synthesized using magnesium chloride and gallic acid, and it was incorporated into gelatin microspheres to create Gel@Mg-MOF composite microspheres. Leveraging gelatin's biocompatibility, controlled release, and biodegradability, the composites' biocompatibility was evaluated through toxicity and adhesion assays. Moreover, the osteogenic and angiogenic potentials of the Gel@Mg-MOF microspheres were assessed, alongside their capacity for ROS scavenging. Results suggest that controlled Mg2+ release from Gel@Mg-MOF microspheres promotes osteogenic activity in RBMSCs and enhances angiogenic potential in HUVECs. Additionally, the gallic acid-containing composite microspheres exhibited antioxidative properties. Collectively, the findings suggest that Gel@Mg-MOF microspheres could provide effective support for bone defect repair, with potential for clinical deployment.

Formation of Twin Boundaries in Rapidly Solidified Metals through Deformation Twinning.

The rapid solidification process is relevant to many emerging metallurgical technologies. Compared with conventional solidification processes, high-density microstructure defects and residual thermal stress are commonly seen in rapidly solidified metals. Among the various defects, potentially beneficial twin boundaries have been observed in the rapidly solidified nanocrystalline microstructures of many alloy systems. In this work, a pathway for forming twin boundaries in rapid solidification processes is proposed. A detailed derivation of strain inhomogeneities upon thermal shrinkage and the deformation twinning phase field method is given. By calculating cooling-induced thermal strain inhomogeneity in nanocrystalline metals and growth thresholds for deformation twinning using the phase field method, it is shown that residual thermal strain hotspots in the microstructure can reach the threshold for deformation twinning when the shear elastic property of grain boundaries is significantly different from the bulk.

Effects and mechanisms of microenvironmental acidosis on osteoclast biology.

Due to continuous bone remodeling, the bone tissue is dynamic and constantly being updated. Bone remodeling is precisely regulated by the balance between osteoblast-induced bone formation and osteoclast-induced bone resorption. As a giant multinucleated cell, formation and activities of osteoclasts are regulated by macrophage colony-stimulating factor (M-CSF), receptor activator of nuclear factor-kappaB ligand (RANKL), and by pathological destabilization of the extracellular microenvironment. Microenvironmental acidosis, as the prime candidate, is a driving force of multiple biological activities of osteoclast precursor and osteoclasts. The mechanisms involved in these processes, especially acid-sensitive receptors/channels, are of great precision and complicated. Recently, remarkable progress has been achieved in the field of acid-sensitive mechanisms of osteoclasts. It is important to elucidate the relationship between microenvironmental acidosis and excessive osteoclasts activity, which will help in understanding the pathophysiology of diseases that are associated with excess bone resorption. This review summarizes physiological consequences and in particular, potential mechanisms of osteoclast precursor or osteoclasts in the context of acidosis microenvironments.

Decellularized liver as a translucent ex vivo model for vascular embolization evaluation.

Transarterial chemoembolization (TACE) is the preferred treatment for patients with unresectable intermediate stage hepatocellular carcinoma, however currently the development of embolic agents for TACE lacks in vitro models that closely represent the sophisticated features of the organ and the vascular systems therein. In this study, we presented a new strategy using an ex vivo liver model to provide a translucent template for evaluating embolic agents of TACE. The ex vivo liver model was developed through decellularizion of rat liver organs with preserved liver-specific vasculatures and improved transmittance of the whole liver up to 23% at 550 nm. Using this model, we investigated the embolization performances of both liquid and particle-based embolic agents, including penetration depth, embolization end-points, injection pressure and spatial distribution dynamics. We found that the embolization endpoint of liquid embolic agent such as ethiodised oil was strongly dependent on the injection pressure, and the pressure quickly built up when reaching the capillary endings, which could cause embolic agent leaking and potential tissue damages. In contrast, for particle-based embolic agents such as poly-dl-lactide microparticles and CalliSpheres® beads, their embolization endpoints were mainly determined by the particle size, whereas the particle densities close to the endpoints dramatically dropped down, which with the penetration depth represented two critical factors determining the embolic distribution. Such a decellularized organ model may open a new route to visually and quantitatively characterize embolization effects of various embolotherapies.

Concentrations of VEGF and PlGF Decrease in Eyes After Intravitreal Conbercept Injection.

INTRODUCTION: Conbercept is a new anti-vascular endothelial growth factor drug approved for the treatment of age-related macular degeneration by the China Food and Drug Administration (CFDA) in 2013. In this study, we for the first time evaluated the concentrations of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) after patients with proliferative diabetic retinopathy were treated with intravitreal conbercept (IVC) injection. METHODS: Sixteen patients with proliferative diabetic retinopathy were randomly divided into two equal groups (A and B). Nine patients with rhegmatogenous retinal detachment were used as the control group. The patients in group A received 0.5 mg IVC and their aqueous humor was collected. After 7 days, all patients underwent vitrectomy, and their aqueous and vitreous humor were collected. RESULTS: In the aqueous humor, the concentrations of VEGF and PlGF were higher pre- than post-IVC injection in group A. Similarly, the concentrations of VEGF and PlGF in group A (pre-IVC) and group B were higher than those in the control group. In vitreous humor, the concentrations of VEGF and PlGF were higher in group B than those in the control group, and the concentrations of VEGF were lower in group A (post-IVC) than those in group B. CONCLUSIONS: Our study proved that the concentration of VEGF and PlGF reduced after IVC injection in aqueous humor. However, the concentration of PlGF did not reduce after IVC injection in vitreous humor.

Atomic-level insights in optimizing reaction paths for hydroformylation reaction over Rh/CoO single-atom catalyst.

Rh-based heterogeneous catalysts generally have limited selectivity relative to their homogeneous counterparts in hydroformylation reactions despite of the convenience of catalyst separation in heterogeneous catalysis. Here, we develop CoO-supported Rh single-atom catalysts (Rh/CoO) with remarkable activity and selectivity towards propene hydroformylation. By increasing Rh mass loading, isolated Rh atoms switch to aggregated clusters of different atomicity. During the hydroformylation, Rh/CoO achieves the optimal selectivity of 94.4% for butyraldehyde and the highest turnover frequency number of 2,065 h-1 among the obtained atomic-scale Rh-based catalysts. Mechanistic studies reveal that a structural reconstruction of Rh single atoms in Rh/CoO occurs during the catalytic process, facilitating the adsorption and activation of reactants. In kinetic view, linear products are determined as the dominating products by analysing reaction paths deriving from the two most stable co-adsorbed configurations. As a bridge of homogeneous and heterogeneous catalysis, single-atom catalysts can be potentially applied in other industrial reactions.