Graph Convolutional Network-Enhanced Model for Screening Persistent, Mobile, and Toxic and Very Persistent and Very Mobile Substances.

The global management for persistent, mobile, and toxic (PMT) and very persistent and very mobile (vPvM) substances has been further strengthened with the rapid increase of emerging contaminants. The development of a ready-to-use and publicly available tool for the high-throughput screening of PMT/vPvM substances is thus urgently needed. However, the current model building with the coupling of conventional algorithms, small-scale data set, and simplistic features hinders the development of a robust model for screening PMT/vPvM with wide application domains. Here, we construct a graph convolutional network (GCN)-enhanced model with feature fusion of a molecular graph and molecular descriptors to effectively utilize the significant correlation between critical descriptors and PMT/vPvM substances. The model is built with 213,084 substances following the latest PMT classification criteria. The application domains of the GCN-enhanced model assessed by kernel density estimation demonstrate the high suitability for high-throughput screening PMT/vPvM substances with both a high accuracy rate (86.6%) and a low false-negative rate (6.8%). An online server named PMT/vPvM profiler is further developed with a user-friendly web interface (http://www.pmt.zj.cn/). Our study facilitates a more efficient evaluation of PMT/vPvM substances with a globally accessible screening platform.

Realizing high-efficiency third harmonic generation via accidental bound states in the continuum.

The bound states in the continuum (BICs) have attracted much attention in designing metasurface due to their high Q-factor and effectiveness in suppressing radiational loss. Here we report on the realization of the third harmonic generation (THG) at a near-ultraviolet wavelength (343 nm) via accidental BICs in a metasurface. The absolute conversion efficiency of the THG reaches 1.13 × 10-5 at a lower peak pump intensity of 0.7 GW/cm2. This approach allows the generation of an unprecedentedly high nonlinear conversion efficiency with simple structures.

[UPLC-Q-TOF-MS-based metabolomics reveals mechanism of Morinda officinalis iridoid glycosides in treating rheumatoid arthritis and bone loss].

This study aimed to investigate the therapeutic effects of Morinda officinalis iridoid glycosides(MOIG) on paw edema and bone loss of rheumatoid arthritis(RA) rats, and analyze its potential mechanism based on ultra-high performance liguid chromatography-guadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS) serum metabolomics. RA rats were established by injecting bovin type Ⅱ collagen. The collagen-induced arthritis(CIA) rats were administered drug by gavage for 8 weeks, the arthritic score were used to evaluate the severity of paw edem, serum bone metabolism biochemical parameters were measured by ELISA kits, Masson staining was used to observe the bone microstructure of the femur in CIA rats. UPLC-Q-TOF-MS was used to analyze the alteration of serum metabolite of CIA rats, principal component analysis(PCA) and partial least squares-discriminant analysis(PLS-DA) were used to screen the potential biomarkers, KEGG database analysis were used to construct related metabolic pathways. The results demonstrated that the arthritic score, serum levels of IL-6 and parameters related with bone metabolism including OCN, CTX-Ⅰ, DPD and TRAP were significantly increased, and the ratio of OPG and RANKL was significantly decreased, the microstructure of bone tissue and cartilage were destructed in CIA rats, while MOIG treatments could significantly reduce arthritis score, mitigate the paw edema, reverse the changes of serum biochemical indicators related with bone metabolism, and improve the microstructure of bone tissue and cartilage of CIA rats. The non-targeted metabolomics results showed that 24 altered metabolites were identified in serum of CIA rats; compared with normal group, 13 significantly altered metabolites related to RA were identified in serum of CIA rats, mainly involving alanine, aspartate and glutamate metabolism; compared with CIA model group, MOIG treatment reversed the alteration of 15 differential metabolites, mainly involving into alanine, aspartate and glutamate metabolism, D-glutamine and D-glutamate metabolism, taurine and hypotaurine metabolism, valine, leucine and isoleucine biosynthesis. Therefore, MOIG significantly alleviated paw edema, improved the destruction of microstructure of bone and cartilage in CIA rats maybe through involving into the regulation of amino acid metabolism.

Angular Engineering Strategy for Enhanced Surface Nonlinear Frequency Conversion in Centrosymmetric Topological Semimetal HfGe0.92Te.

Surface nonlinear optics are essential for developments in integrated photonics and micro/nano optoelectronics. However, the nonlinear optical conversion efficiency on a surface is restricted by the finite nonlinear susceptibility of matter and the intrinsic atomic-layered interaction length between light and matter. In this work, based on an angular engineering strategy, it is demonstrated that the centrosymmetric topological semimetal HfGe0.92Te crystal has a giant and anisotropic surface second-order nonlinear susceptibility up to 5535 ± 308 pm V-1 and exhibits efficient and unprecedented second-harmonic generation (SHG). The maximum optical conversion efficiency is found to be up to 3.75‰, which is 104 times higher than that obtained from a silicon surface. Because of the linear dispersion over a wide range of energies around the Dirac points, this high conversion efficiency can be maintained with SHG wavelengths ranging from the visible region (779 nm) to the deep-UV region (257.5 nm). This study can facilitate the development of topological photonics and integrated nonlinear photonics based on topological semimetals.

A green, efficient and stable platform based on hyperbranched quaternized hydrothermal magnetic chitosan nanospheres integrated cytomembranes for screening drug candidates from natural products.

Compared with traditional tedious organic solvent-assisted separation process in natural medicinal chemistry, cytomembrane (CM) fishing technique became a more appealing and greener choice for screening bioactive components from natural products. However, its large-scale practical value was greatly weakened by the easy fall-off of CMs from magnetic supports, rooted in the instability of common Fe3O4 particles and their insufficient interaction with CMs. In this research, a new green biostable platform was developed for drug screening through the integration of hyperbranched quaternized hydrothermal magnetic carbon spheres (HQ-HMCSs) and CMs. The positive-charged HQ-HMCSs were constructed by chitosan-based hydrothermal carbonization onto Fe3O4 nanospheres and subsequent aqueous hyperbranching quaternization with 1,4-butanediol diglycidyl ether and methylamine. The strong interaction between HQ-HMCSs and CMs was formed via electrostatic attraction of HQ-HMCSs to negative-charged CMs and covalent linkage derived from the epoxy-amine addition reactions. The chemically stable HMCSs and its integration with CMs contributed to dramatically higher stability and recyclability of bionic nanocomposites. With the fishing of osteoblast CMs integrated HQ-HMCSs, two novel potential anti-osteoporosis compounds, narcissoside and beta-ionone, were discovered from Hippophae rhamnoides L. Enhanced osteoblast proliferation, alkaline phosphatase, and mineralization levels proved their positive osteogenesis effects. Preliminary pharmacological investigation demonstrated their potential action on membrane proteins of estrogen receptor alpha and insulin-like growth factor 1. Furthermore, beta-ionone showed apparent therapeutic effects on osteogenic lesions in zebrafish. These results provide a green, stable, cost-efficient, and reliable access to rapid discovery of drug leads, which verifiably benefits the design of nanocarbon-based biocomposites with increasingly advanced functionality.

Preliminary study of a new macro-micro robot system for dental implant surgery: Design, development and control.

BACKGROUND: This study aims to develop a new dental implant robotic system (DIRS) to relieve the burden and enhance the quality of dental implant surgery. METHODS: The implanting actuator and system controller are two parts. The implanting actuator is designed on the basis of the RCM mechanism, with its kinematics modelled. Besides, a multi-DOF admittance control strategy and a hybrid position-admittance control strategy were designed, endowing the actuator with environmental compliance. RESULTS: In force sensing, about 97% of mixed force/torque are eliminated. Then, 30 groups of implantation are done, of which 15 groups are simple implantation, while another 15 groups are force-based implantation. The results show that the average contact force/torque can be reduced by 73.03% and 62.66%, and the peak contact force/torque can be reduced by 68.26% and 50.46%. CONCLUSIONS: The results of preliminary experiments validate the effectiveness of DIRS, which has great potential to assist dentists with higher efficiency, better quality, and lower burden.

Preoperative Planning Framework for Robot-Assisted Dental Implant Surgery: Finite-Parameter Surrogate Model and Optimization of Instrument Placement.

For robot-assisted dental implant surgery, it is necessary to feed the instrument into a specified position to perform surgery. To improve safety and efficiency, a preoperative planning framework, including a finite-parameter surrogate model (FPSM) and an automatic instrument-placement method, is proposed in this paper. This framework is implemented via two-stage optimization. In the first stage, a group of closed curves in polar coordinates is used to represent the oral cavity. By optimizing a finite number of parameters for these curves, the oral structure is simplified to form the FPSM. In the second stage, the FPSM serves as a fast safety estimator with which the target position/orientation of the instrument for the feeding motion is automatically determined through particle swarm optimization (PSO). The optimized feeding target can be used to generate a virtual fixture (VF) to avoid undesired operations and to lower the risk of collision. This proposed framework has the advantages of being safe, fast, and accurate, overcoming the computational burden and insufficient real-time performance of complex 3D models. The framework has been developed and tested, preliminarily verifying its feasibility, efficiency, and effectiveness.

Advances and applications of machine learning and deep learning in environmental ecology and health.

Machine learning (ML) and deep learning (DL) possess excellent advantages in data analysis (e.g., feature extraction, clustering, classification, regression, image recognition and prediction) and risk assessment and management in environmental ecology and health (EEH). Considering the rapid growth and increasing complexity of data in EEH, it is of significance to summarize recent advances and applications of ML and DL in EEH. This review summarized the basic processes and fundamental algorithms of the ML and DL modeling, and indicated the urgent needs of ML and DL in EEH. Recent research hotspots such as environmental ecology and restoration, environmental fate of new pollutants, chemical exposures and risks, chemical hazard identification and control were highlighted. Various applications of ML and DL in EEH demonstrate their versatility and technological revolution, and present some challenges. The perspective of ML and DL in EEH were further outlined to promote the innovative analysis and cultivation of the ML-driven research paradigm.

Percutaneous Closure vs. Surgical Repair for Postinfarction Ventricular Septal Rupture: A Systematic Review and Meta-Analysis.

INTRODUCTION: Ventricular septal rupture is an important high-mortality complication in the scope of myocardial infarctions. The effectiveness of different treatment modalities is still controversial. This meta-analysis compares the efficacy of percutaneous closure vs. surgical repair for the treatment of postinfarction ventricular septal rupture (PI-VSR). METHODS: A meta-analysis was performed on relevant studies found through PubMed®, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (or CNKI), Wanfang Data, and VIP databases searching. The primary outcome was a comparison of in-hospital mortality between the two treatments, and the secondary outcome was documentation of one-year mortality, postoperative residual shunts, and postoperative cardiac function. Differences were expressed as odds ratios (ORs) with 95% confidence intervals (CIs) to assess the relationships between predefined surgical variables and clinical outcomes. RESULTS: Qualified studies (742 patients from 12 trials) were found and investigated for this meta-analysis (459 patients in the surgical repair group, 283 patients in the percutaneous closure group). When comparing surgical repair to percutaneous closure, it was found that the former significantly reduced in-hospital mortality (OR: 0.67, 95% CI 0.48-0.96, P=0.03) and postoperative residual shunts (OR: 0.03, 95% CI 0.01-0.10, P<0.00001). Surgical repair also improved postoperative cardiac function overall (OR: 3.89, 95% CI 1.10-13.74, P=0.04). However, there was no statistically significant difference in one-year mortality between the two surgical strategies (OR: 0.58, 95% CI 0.24-1.39, P=0.23). CONCLUSION: We found that surgical repair appears to be a more effective therapeutic option than percutaneous closure for PI-VSR.

Embryonic Exposure to UV-328 Impairs the Cell Cycle in Zebrafish (Danio rerio) by Inhibiting the p38 MAPK/p53/Gadd45a Signaling Pathway.

The benzotriazole UV stabilizer UV-328 is well known for its potent antioxidative properties; however, there are concerns about how it may affect signaling nodes and lead to negative consequences. This study identified the key signaling cascades involved in oxidative stress in zebrafish (Danio rerio) larvae and evaluated the cell cycle arrests and associated developmental alternations. Exposure to UV-328 at 0.25, 0.50, 1.00, 2.00, and 4.00 µg/L downregulated gene expression associated with oxidative stress (cat, gpx, gst, and sod) and apoptosis (caspase-3, caspase-6, caspase-8, and caspase-9) at 3 days postfertilization (dpf). The transcriptome aberration in zebrafish with disrupted p38 mitogen-activated protein kinase (MAPK) cascades was validated based on decreased mRNA expressions of p38 MAPK (0.36-fold), p53 (0.33-fold), and growth arrest and DNA damage-inducible protein 45 α (Gadd45a) (0.52-fold) after a 3- and 14-day exposure alongside a correspondingly decreased protein expression. The percentage of cells in the Gap 1 (G1) phase increased from 69.60% to a maximum of 77.07% (p < 0.05) in the 3 dpf embryos. UV-328 inhibited the p38 MAPK/p53/Gadd45a regulatory circuit but promoted G1 phase cell cycle arrest, abnormally accelerating the embryo hatching and heart rate. This study provided mechanistic insights that enrich the risk profiles of UV-328.

Jintiange proteins promote osteogenesis and inhibit apoptosis of osteoblasts by enhancing autophagy via PI3K/AKT and ER stress pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Tiger bone, which had long been used in traditional Chinese medicine, had the action of removing wind and alleviating pain, strengthening the sinews and bones, and often used to treat bone impediment, and atrophic debility of bones in TCM clinical practice. As a substitute of natural bone tiger, artificial tiger bone Jintiange (JTG), has been approved by the State Food and Drug Administration of China for relief the symptom of osteoporosis, such as lumbago and back pain, lassitude in loin and legs, flaccidity and weakness legs, and walk with difficulty based on TCM theory. JTG has similar chemical profile to natural tiger bone, and contains mineral substance, peptides and proteins, and has been shown to protect bone loss in ovariectomized mice and exert the regulatory effects on osteoblast and osteoclast activities. But how the peptides and proteins in JTG modulate bone formation remains unclear. AIM: To investigate the stimulating effects of JTG proteins on osteogenesis and explore the possible underlying mechanisms. MATERIALS AND METHODS: JTG proteins were prepared from JTG Capsules by extracting calcium, phosphorus and other inorganic elements using SEP-PaktC18 desalting column. MC3T3-E1 cells were treated with JTG proteins to evaluate their effects and explore the underlying mechanisms. Osteoblast proliferation was detected by CCK-8 method. ALP activity was detected using a relevant assay kit, and bone mineralized nodules were stained with alizarin red-Tris-HCl solution. Cell apoptosis was analyzed by flow cytometry. Autophagy was observed by MDC staining, and autophagosomes were observed by TEM. Nuclear translocations of LC3 and CHOP were detected by immunofluorescence and observed under a laser confocal microscope. The expression of key proteins related to osteogenesis, apoptosis, autophagy and PI3K/AKT and ER stress pathways was analyzed by Western Blot analysis. RESULTS: JTG proteins improved osteogenesis as evidenced by the alteration of proliferation, differentiation and mineralization of MC3T3-E1 osteoblasts, inhibited their apoptosis, and enhanced autophagosome formation and autophagy. They also regulated the expression of key proteins of PI3K/AKT and ER stress pathways. In addition, PI3K/AKT and ER stress pathway inhibitors could reverse the regulatory effects of JTG proteins on osteogenesis, apoptosis, autophagy and PI3K/AKT and ER stress pathways. CONCLUSION: JTG proteins increased the osteogenesis and inhibited osteoblast apoptosis by enhancing autophagy via PI3K/AKT and ER stress signaling pathways.

Patient-Specific Implants for Correction of Midfacial Aging.

The nasolabial folds (NLFs) may be shallowed with the use of nostril base augmentation. This study aimed to design and customize patient-specific implants (PSIs) with computer-aided design/computer-aided manufacturing (CAD/CAM) to correct NLF deepening caused by midfacial aging. The patient's head computed tomography data obtained and were used for reconstruction. The PSIs were customized by CAD/CAM techniques, which were implanted into a nasal base for shallow NLFs caused by midfacial aging. Preoperative and postoperative photos and a wrinkle severity rating scale were used to evaluate the changes in NLFs. Also, the global esthetic improvement scale was used to investigate the surgical satisfaction of patients. Eleven patients (22 NLFs) received PSIs in the nasal base (22 implants). The customized PSI matched well with premaxilla, reducing the difficulty of operation. After 3 to 12 months of follow-up, PSI was stable without foreign body reaction or inflammatory reaction. Postoperative wrinkle severity rating scale scores showed that NLF severity was reduced in all patients, with a significant esthetic improvement compared with preoperatively ( P < 0.01). The global esthetic improvement scale showed an extremely satisfied improved NLF in 27.27% of patients, much improved in 63.63%, and improved in 9.90% (2/22), and none reported change or poor NLF. Patient satisfaction with their midface appearance differed significantly before and after surgery ( P < 0.01). Individualized PSI designed with high precision and matching degree by CAD and prepared using CAM could be applied to overcome the limitations of noncustomized implants.

Percutaneous Closure vs. Surgical Repair for Postinfarction Ventricular Septal Rupture: A Systematic Review and Meta-Analysis

ABSTRACT Introduction: Ventricular septal rupture is an important high-mortality complication in the scope of myocardial infarctions. The effectiveness of different treatment modalities is still controversial. This meta-analysis compares the efficacy of percutaneous closure vs. surgical repair for the treatment of postinfarction ventricular septal rupture (PI-VSR). Methods: A meta-analysis was performed on relevant studies found through PubMed®, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (or CNKI), Wanfang Data, and VIP databases searching. The primary outcome was a comparison of in-hospital mortality between the two treatments, and the secondary outcome was documentation of one-year mortality, postoperative residual shunts, and postoperative cardiac function. Differences were expressed as odds ratios (ORs) with 95% confidence intervals (CIs) to assess the relationships between predefined surgical variables and clinical outcomes. Results: Qualified studies (742 patients from 12 trials) were found and investigated for this meta-analysis (459 patients in the surgical repair group, 283 patients in the percutaneous closure group). When comparing surgical repair to percutaneous closure, it was found that the former significantly reduced in-hospital mortality (OR: 0.67, 95% CI 0.48-0.96, P=0.03) and postoperative residual shunts (OR: 0.03, 95% CI 0.01-0.10, P<0.00001). Surgical repair also improved postoperative cardiac function overall (OR: 3.89, 95% CI 1.10-13.74, P=0.04). However, there was no statistically significant difference in one-year mortality between the two surgical strategies (OR: 0.58, 95% CI 0.24-1.39, P=0.23). Conclusion: We found that surgical repair appears to be a more effective therapeutic option than percutaneous closure for PI-VSR.

[Research progress on anti-inflammatory effects of plant-derived cannabinoid type 2 receptor modulators].

Excessive and persistent inflammatory responses are a potential pathological condition that can lead to diseases of various systems, including nervous, respiratory, digestive, circulatory, and endocrine systems. Cannabinoid type 2 receptor(CB2R) belongs to the G protein-coupled receptor family and is widely distributed in immune cells, peripheral tissues, and the central nervous system. It plays a role in inflammatory responses under various pathological conditions. The down-regulation of CB2R activity is an important marker of inflammation and and CB2R modulators have been shown to have anti-inflammatory effects. This study explored the relationship between CB2R and inflammatory responses, delved into its regulatory mechanisms in inflammatory diseases, and summarized the research progress on CB2R modulators from plants other than cannabis, including plant extracts and monomeric compounds, in exerting anti-inflammatory effects. The aim is to provide new insights into the prevention and treatment of inflammatory diseases.

Machine Learning-Based Models with High Accuracy and Broad Applicability Domains for Screening PMT/vPvM Substances.

Persistent, mobile, and toxic (PMT) substances and very persistent and very mobile (vPvM) substances can transport over long distances from various sources, increasing the public health risk. A rapid and high-throughput screening of PMT/vPvM substances is thus warranted to the risk prevention and mitigation measures. Herein, we construct a machine learning-based screening system integrated with five models for high-throughput classification of PMT/vPvM substances. The models are constructed with 44 971 substances by conventional learning, deep learning, and ensemble learning algorithms, among which, LightGBM and XGBoost outperform other algorithms with metrics exceeding 0.900. Good model interpretability is achieved through the number of free halogen atoms (fr_halogen) and the logarithm of partition coefficient (MolLogP) as the two most critical molecular descriptors representing the persistence and mobility of substances, respectively. Our screening system exhibits a great generalization capability with area under the receiver operating characteristic curve (AUROC) above 0.951 and is successfully applied to the persistent organic pollutants (POPs), prioritized PMT/vPvM substances, and pesticides. The screening system constructed in this study can serve as an efficient and reliable tool for high-throughput risk assessment and the prioritization of managing emerging contaminants.

Solvent-Type Passivation Strategy Controls Solid-State Self-Quenching-Resistant Behavior in Sulfur Dots.

Treatment of sulfur dots with polyethylene glycol (PEG) has been an efficient way to achieve a high luminescence quantum yield, and such a PEG-related quantum dot (QD)-synthesis strategy has been well documented. However, the polymeric insulating capping layer acting as the "thick shell" will significantly slow down the electron-transfer efficiency and severely hamper its practical application in an optoelectric field. Especially, the employment of synthetic polymers with long alkyl chains or large molecular weights may lead to structural complexity or even unexpected changes of physical characteristics for QDs. Therefore, in sulfur dot preparation, it is a breakthrough to use short-chain molecular species to replace PEG for better control and reproducibility. In this article, a solvent-type passivation (STP) strategy has been reported, and no PEG or any other capping agent is required. The main role of the solvent, ethanol, is to directly react with NaOH, and the generated sodium ethoxide passivates the surface defects. The afforded STP-enhanced emission sulfur dots (STPEE-SDs) possess not only the self-quenching-resistant feature in the solid state but also the extension of fluorescence band toward the wavelength as long as 645 nm. The realization of sulfur dot emission in the deep-red region with a decent yield (8.7%) has never been reported. Moreover, a super large Stokes shift (300 nm, λex = 345 nm, λem = 645 nm) and a much longer decay lifetime (109 µs) have been found, and such values can facilitate to suppress the negative influence from background signals. Density functional theory demonstrates that the surface passivation via sodium ethoxide is dynamically favorable, and the spectroscopic insights into emission behavior could be derived from the passivation effect of the sulfur vacancy as well as the charge-transfer process dominated by the highly electronegative ethoxide layer.

Use of liquid concentrated growth factor in the management of necrotic tissue after facial vascular complications induced by hyaluronic acid injection.

INTRODUCTION: HA fillers may induce facial vascular embolism. The resulting tissue ischemia and necrosis are severe iatrogenic complications for which no effective treatments are available. OBJECTIVE: This single-center case series studied the use of liquid CGF in the management of facial tissue necrosis due to HA injection. METHODS: All 12 patients with facial tissue necrosis (2 mild, 3 moderate, 7 severe) were previously treated with hyaluronidase injection in outside hospitals. They received a routine injection of hyaluronidase (dose of 400-1500 U) at the site of ischemia immediately after admission to the authors' hospital, but CGF was also injected. CGF injection was repeated once weekly until wound healing. Efficacy was assessed at 4 weeks (mean, 24.08 days). RESULTS: No patient experienced wound expansion or aggravation or infection at the sites of necrosis. A complete healing rate of 91.67% was noted at the 4-week follow-up. No scarring was evident in patients with mild to moderate necrosis. Those with moderate necrosis exhibited varied degrees of scarring after recovery, and scarring was evident in those with severe necrosis. No severe adverse effects occurred. CONCLUSION: CGF promoted the healing of ischemic and necrotic tissue wounds induced by facial vascular embolism following injection of HA fillers. CGF should be considered as a nonsurgical treatment method for vascular embolism following HA filler injection.

Jin-Tian-Ge ameliorates ovariectomy-induced bone loss in rats and modulates osteoblastogenesis and osteoclastogenesis in vitro.

BACKGROUND: Tiger bone, which had been one of the most famous traditional Chinese medicine for 2000 years, was originate from the skeleton of Panthera tigris L., and had the actions of anti-inflammatory, analgesic, immune-regulatory and promoting healing of bone fracture, and was used for the treatment of osteoporosis and rheumatoid arthritis. Jin-Tian-Ge (JTG), the artificial tiger bone powder, were prepared from skeletons of several farmed animals to substitute the natural tiger bone, and has been used for the treatment of osteoporosis in clinical practice. However, the characteristic and mechanism of action of JTG for the therapy of osteoporosis need to be further evidenced by using modern pharmacological methods. The aim of this work is to investigate the bone-protective effects of JTG, and explore the possible underlying mechanism. METHODS: Ovariectomy (OVX) rats were orally administrated JTG or estradiol valerate (EV) for 12 weeks. We investigated the pharmacodynamic effects of JTG on anti-bone loss in OVX rats, and also investigated the role of JTG in promoting osteogenesis and inhibiting osteoclast differentiation. RESULTS: JTG increased the bone mineral density (BMD), improved the bone microarchitecture and biomechanical properties in ovariectomized rast, whereas reversed the bone high turnover in OVX rats as evidenced by serum biochemical markers in OVX rats. JTG increased osteogenic differentiation of BMSCs in vitro, and up-regulated the expression of the key proteins of BMP and Wnt/ß-catenin pathways. JTG also inhibited the osteoclastogenesis of BMM as evidenced by the alteration of the TRAP activity, F-actin construction and the expression of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), c-Fos, Cathepsin K (Ctsk) and matrix metallopeptidase 9 (MMP9) of OCs induced with RANKL and LPS, reduced the expression and phosphorylation of NF-κB in OCs. CONCLUSIONS: JTG prevented bone loss in OVX rats and increased osteogenic differentiation of BMSCs through regulation of the BMP and Wnt/ß-catenin pathway, inhibited osteoclastogenesis by suppressing the NF-κB pathway, suggesting that JTG had the potentials for prevention and treatment of osteoporosis by modulating formation and differentiation of osteoblast and osteoclast.

Evaluating the effect of tanning response to sun exposure on the risk of skin diseases through Mendelian randomization.

Background: Until now, the relevance of the tanning response to sun exposure and skin diseases has incomplete and inconsistent epidemiological observations. In this case, it is valuable to find out the causality of tanning response to sun exposure and skin diseases, and take a step further toward developing effective therapies as well as prevention methods. Methods: We investigated the causal effect of tanning response to sun exposure on 10 major skin diseases that have been studied in recent large-scale genome-wide association studies (GWASs). Significant independent genetic variants from large-scale GWAS on ease of skin tanning (N = 453,065) are selected as the effective instrumental variables (IVs). For each skin disease, we extracted the summary statistics of those IVs (or their proxies) from the corresponding skin disease-GWAS as the valid IVs. Mendelian randomization (MR) was further performed to evaluate the causal association of ease of skin tanning with each of the skin diseases using different statistical methods, including inverse-variance weighted (IVW), the weighted median, and MR-Egger. Sensitivity analysis was also conducted to evaluate the effect of horizontal pleiotropy and heterogeneity. Results: We observe significant associations between six skin diseases with tanning response to sun exposure with adjusted p-value derived by IVW less than 0.05 and with nominal p value less than 0.05 at the same time derived by either MR-Egger or weighted median. The six skin diseases include actinic keratosis (IVW FDR = 1.71E-40, MR Egger p-value = 3.46E-22), seborrhoeic keratosis (IVW FDR = 2.97E-4, MR Egger p-value = 1.06E-3), blepharochalasis (IVW FDR = 1.30E-3, MR Egger p-value = 2.91E-4), seborrhoeic dermatitis (IVW FDR = 1.29E-2, MR Egger p-value = 1.23E-2), malignant melanoma of skin (IVW FDR = 2.95E-2, MR Egger p-value = 1.91E-2), and freckles (IVW FDR = 2.95E-2, weighted median p-value = 1.02E-3). Interestingly, we find increased trends of developing all of the six skin diseases with increased tanning response to sun exposure (beta values are positive using IVW, MR-egger, and weighted median methods). We also replicate the association on three skin diseases using an independent outcome GWAS cohort, including malignant melanoma of the skin (replication IVW p-value = 2.13E-39), actinic keratosis (replication IVW p-value = 4.64E-32), and seborrhoeic keratosis (replication IVW p-value = 1.79E-3). Conclusion: Our observation shows that the tanning response to sun exposure is positively correlated with the development of skin diseases in people of European descent by Mendelian randomization studies. But randomized controlled trials are still needed to add proof to our observations.

Application progress of immobilized biomembrane in the discovery of active compounds of natural products.

Natural products (NP) are an important source of bioactive compounds. Considering their complex matrix effects, the development of suitable methodologies for the quick identification and analysis of active substances in NPs played a significant role in controlling their quality and discovering new drugs. In recent years, the technology of immobilized biomembrane has attracted increasing attention, due to its advantages such as multitarget efficiency, accuracy, and/or time-saving compared with traditional activity-guided separation and ligand fishing methods. This article provides a systematic review of the latest advances in screening technologies based on biomembrane in the field of NPs. It includes detailed discussions on these technologies, including cell membrane chromatography, artificial membrane chromatography, cell membrane fishing, living cell fishing methods, and their applications in screening various active molecules from NPs. Their limitations and future development prospects are further discussed.