Inflammatory microenvironment regulation and osteogenesis promotion by bone-targeting calcium and magnesium repletion nanoplatform for osteoporosis therapy.

Osteoporosis is the most common bone metabolic disease that affects the health of middle-aged and elderly people, which is hallmarked by imbalanced bone remodeling and a deteriorating immune microenvironment. Magnesium and calcium are pivotal matrix components that participate in the bone formation process, especially in the immune microenvironment regulation and bone remodeling stages. Nevertheless, how to potently deliver magnesium and calcium to bone tissue remains a challenge. Here, we have constructed a multifunctional nanoplatform composed of calcium-based upconversion nanoparticles and magnesium organic frameworks (CM-NH2-PAA-Ald, denoted as CMPA), which features bone-targeting and pH-responsive properties, effectively regulating the inflammatory microenvironment and promoting the coordination of osteogenic functions for treating osteoporosis. The nanoplatform can efficaciously target bone tissue and gradually degrade in response to the acidic microenvironment of osteoporosis to release magnesium and calcium ions. This study validates that CMPA possessing favorable biocompatibility can suppress inflammation and facilitate osteogenesis to treat osteoporosis. Importantly, high-throughput sequencing results demonstrate that the nanoplatform exerts a good inflammatory regulation effect through inhibition of the nuclear factor kappa-B signaling pathway, thereby normalizing the osteoporotic microenvironment. This collaborative therapeutic strategy that focuses on improving bone microenvironment and promoting osteogenesis provides new insight for the treatment of metabolic diseases such as osteoporosis.

Thickened Perirenal Fat Predicts Poor Renal Outcome in Patients with Immunoglobulin A Nephropathy: A Population-Based Retrospective Cohort Study.

Introduction: Perirenal fat is a pad that fills the retroperitoneal space outside the kidney, which affects kidney function in various ways. However, the association between perirenal fat and IgA nephropathy (IgAN) has not yet been elucidated. This study aimed to investigate the role of perirenal fat in predicting IgAN progression. Methods: A total of 473 patients with biopsy-proven IgAN and follow-up information were recruited, and perirenal fat thickness (PFT) was measured using color Doppler ultrasonography at renal biopsy. Patients were divided into two groups according to the median PFT: the low-PFT group (PFT ≤1.34 cm, n = 239) and the high PFT group (PFT >1.35 cm, n = 234). A total of 473 healthy participants were included in the control group. Basic clinical characteristics were assessed at the time of renal biopsy, and the relationship between PFT and combined endpoints was analyzed. The renal composite endpoints were defined as a two-fold increase in blood creatinine level, end-stage renal disease (dialysis over 3 months). Kaplan-Meier survival analysis was used to explore the role of PFT in the progression of IgAN. Three clinicopathological models of multivariate Cox regression analysis were established to evaluate the association between PFT and renal prognosis in patients with IgAN. Results: Compared to healthy subjects, patients with IgAN showed significantly higher PFT. After a median follow-up of 50 months, 75 of 473 patients (15.9%) with IgAN reached renal composite endpoints. Among those, 13 of 239 patients (5.4%) were in the low PFT group, and 62 of 234 patients (26.5%) were in the high PFT group (p < 0.001). The results of three Cox regression models (including demographics, pathological and clinical indicators, and PFT) demonstrated that a higher PFT was significantly associated with a higher risk of reaching renal composite endpoints in patients with IgAN. Conclusion: This study indicated a positive relationship between PFT at renal biopsy and renal progression in patients with IgAN, suggesting that perirenal fat might act as a marker of poor prognosis in patients with IgAN.

Traditional Scraping (Gua Sha) Combined with Copper-Curcumin Nanoparticle Oleogel for Accurate and Multi-Effective Therapy of Androgenic Alopecia.

Androgenetic alopecia (AGA) is a prevalent systemic disease caused by diverse factors, for which effective treatments are currently limited. Herein, the oleogel (OG) containing copper-curcumin (CuR) nanoparticles is developed, designated as CuRG, which is also combined with traditional naturopathic scraping (Gua Sha, SCR) as a multifunctional therapy for AGA. With the assistance of lipophilic OG and SCR, CuR can efficaciously penetrate the epidermal and dermal regions where most hair follicles (HFs) reside, thereby releasing curcumin (CR) and copper ions (Cu2+) subcutaneously to facilitate hair regeneration. Concomitantly, the mechanical stimulation induced by SCR promotes the formation of new blood vessels, which is conducive to reshaping the microenvironment of HFs. This study validates that the combination of CuRG and SCR is capable of systematically interfering with different pathological processes, ranging from improvement of perifollicular microenvironment (oxidative stress and insufficient vascularization), regulation of inflammatory responses to degradation of androgen receptor, thus potentiating hair growth. Compared with minoxidil, a widely used clinical drug for AGA therapy, the designed synergistic system displays augmented hair regeneration in the AGA mouse model.

A smartphone-intergrated dual-emission fluorescent nanoprobe for visual and ratiometric detection of anthrax biomarkers.

A novel dual-emission fluorescent nanoprobe based on rare-earth nanosheets was fabricated to detect 2,6-pyridine dicarboxylic acid (DPA), which is the biomarker of Bacillus anthracis. 2-amino terephthalic acid (BDC-NH2) and surfactant sodium dodecyl sulfate (SDS) were co-intercalated into layered europium hydroxide (LEuH) to prepare the organic/inorganic composite, which was delaminated to obtain the rare-earth nanosheets. The ratio detection of DPA is possible due to the antenna effect between DPA and Eu3+. The nanoprobe shows high accuracy and sensitivity due to the large specific surface area of the rare-earth nanosheets. The limit of detection (LOD) is 4.4 nM for DPA in the range of 0-20 µM. In addition, a more convenient and faster smartphone-based visual detection platform was established based on the obvious color change. This work offers an effective way for developing visual sensing platforms, which opens a new path for designing fluorescent probes with superior sensing capabilities.

The Utility of Perirenal Fat in Determining the Risk of Onset and Progression of Diabetic Kidney Disease.

Background: Perirenal fat (PRF) has multiple effects on the kidney through its physical structure and adipocytokine-secreting ability. The present study explored the relationship between PRF thickness and the onset and progression of albuminuria in patients with diabetes. Methods: In the cross-sectional analysis, we screened 959 patients from 8764 subjects with type 2 diabetes mellitus (T2DM) who met the inclusion criteria and measured their perirenal fat thickness (PFT) using color Doppler ultrasound. A group of laboratory indexes were included in the analysis models. In a longitudinal study, a total of 218 patients with a baseline UACR <30 mg/g were included in the follow-up study. Results: In a cross-sectional analysis, patients with diabetes and higher PFT presented with higher albuminuria. Multiple logistic regression analysis indicated that PFT was an independent risk factor for the degree of albuminuria in patients with T2DM (odds ratio = 4.186, 95%CI: 2.290-7.653, P < 0.001). In a longitudinal study, 218 albuminuria-free patients with T2DM at the baseline were followed up for a mean of 12.3 months. Based on the cutoff value from the ROC diagnostic test in the cross-sectional study, patients were divided into two groups: higher PFT (H-PFT) and lower PFT (L-PFT). Kaplan-Meier survival curve analysis showed that H-PFT was associated with a higher incidence of albuminuria than L-PFT (log-rank test, χ2 = 4.522, P = 0.033). Cox regression analysis showed that PFT was a risk factor for the earlier onset of albuminuria (hazard ratio 2.83, 95% CI: 1.34-4.88, P < 0.001). Conclusions: PRF evaluated by color Doppler ultrasound is an easy and reliable tool for predicting the onset and progression of albuminuria in patients with T2DM.

BA-GCA Net: Boundary-Aware Grid Contextual Attention Net in Osteosarcoma MRI Image Segmentation.

Osteosarcoma is one of the most common bone tumors that occurs in adolescents. Doctors often use magnetic resonance imaging (MRI) through biosensors to diagnose and predict osteosarcoma. However, a number of osteosarcoma MRI images have the problem of the tumor shape boundary being vague, complex, or irregular, which causes doctors to encounter difficulties in diagnosis and also makes some deep learning methods lose segmentation details as well as fail to locate the region of the osteosarcoma. In this article, we propose a novel boundary-aware grid contextual attention net (BA-GCA Net) to solve the problem of insufficient accuracy in osteosarcoma MRI image segmentation. First, a novel grid contextual attention (GCA) is designed to better capture the texture details of the tumor area. Then the statistical texture learning block (STLB) and the spatial transformer block (STB) are integrated into the network to improve its ability to extract statistical texture features and locate tumor areas. Over 80,000 MRI images of osteosarcoma from the Second Xiangya Hospital are adopted as a dataset for training, testing, and ablation studies. Results show that our proposed method achieves higher segmentation accuracy than existing methods with only a slight increase in the number of parameters and computational complexity.

[Human mesenchymal stem cells modified by hepatocyte growth factor gene promote chicken embryonic angiogenesis].

This study was purposed to investigate the angiogenesis-promoting activities of human mesenchymal stem cells (hMSCs) modified by hepatocyte growth factor (HGF) and the underlying mechanisms. The hMSCs were transfected by recombinant adenoviral vector carrying human HGF gene and seeded onto the chicken chorioallantoic membrane. Three days later, the number of blood vessels was counted and their angiogenic response was compared with those of hMSCs of same generation, recombinant basic fibroblast growth factor (bFGF) and alpha-MEM as control. The expression levels of bFGF, VEGF, angiopoietin-1 and angiopoietin-2 were evaluated by RT-PCR assay. The results showed that gene-modified hMSCs exhibited greatest activity to promote angiogenesis while the angiogenic response was nearly same between groups treated by hMSCs and bFGF, all of which were significantly higher than that observed in control (p < 0.01). RT-PCR analysis revealed that hMSCs constitutively expressed multiple angiogenesis-associated growth factors and their levels seemed up-regulated by HGF gene transfer. It is concluded that HGF gene-modified hMSCs show a potent angiogenesis-promoting function and may be useful in the treatment of ischemic disorders.