Genome-wide identification of WRKY transcription factors in Casuarina equisetifolia and the function analysis of CeqWRKY11 in response to NaCl/NaHCO3 stresses.

BACKGROUND: Casuarina equisetifolia (C. equisetifolia) is a woody species with many excellent features. It has natural resistance against drought, salt and saline-alkali stresses. WRKY transcription factors (TFs) play significant roles in plant response to abiotic stresses, therefore, molecular characterization of WRKY gene family under abiotic stresses holds great significance for improvement of forest trees through molecular biological tools. At present, WRKY TFs from C. equisetifolia have not been thoroughly studied with respect to their role in salt and saline-alkali stresses response. The current study was conducted to bridge the same knowledge gap. RESULTS: A total of 64 WRKYs were identified in C. equisetifolia and divided into three major groups i.e. group I, II and III, consisting of 10, 42 and 12 WRKY members, respectively. The WRKY members in group II were further divided into 5 subgroups according to their homology with Arabidopsis counterparts. WRKYs belonging to the same group exhibited higher similarities in gene structure and the presence of conserved motifs. Promoter analysis data showed the presence of various response elements, especially those related to hormone signaling and abiotic stresses, such as ABRE (ABA), TGACG (MeJA), W-box ((C/T) TGAC (T/C)) and TC-rich motif. Tissue specific expression data showed that CeqWRKYs were mainly expressed in root under normal growth conditions. Furthermore, most of the CeqWRKYs were up-regulated by NaCl and NaHCO3 stresses with few of WRKYs showing early responsiveness to both stresses while few others exhibiting late response. Although the expressions of CeqWRKYs were also induced by cold stress, the response was delayed compared with other stresses. Transgenic C. equisetifolia plants overexpressing CeqWRKY11 displayed lower electrolyte leakage, higher chlorophyll content, and enhanced tolerance to both stresses. The higher expression of abiotic stress related genes, especially CeqHKT1 and CeqPOD7, in overexpression lines points to the maintenance of optimum Na+/K+ ratio, and ROS scavenging as possible key molecular mechanisms underlying salt stress tolerance. CONCLUSIONS: Our results show that CeqWRKYs might be key regulators of NaCl and NaHCO3 stresses response in C. equisetifolia. In addition, positive correlation of CeqWRKY11 expression with increased stress tolerance in C. equisetifolia encourages further research on other WRKY family members through functional genomic tools. The best candidates could be incorporated in other woody plant species for improving stress tolerance.

Molecular characterization of Golgi apparatus-related genes indicates prognosis and immune infiltration in osteosarcoma.

BACKGROUND: The Golgi apparatus (GA) is crucial for protein synthesis and modification, and regulates various cellular processes. Dysregulation of GA can lead to pathological conditions like neoplastic growth. GA-related genes (GARGs) mutations are commonly found in cancer, contributing to tumor metastasis. However, the expression and prognostic significance of GARGs in osteosarcoma are yet to be understood. METHODS: Gene expression and clinical data of osteosarcoma patients were obtained from the TARGET and GEO databases. A consensus clustering analysis identified distinct molecular subtypes based on GARGs. Discrepancies in biological processes and immunological features among the subtypes were explored using GSVA, ssGSEA, and Metascape analysis. A GARGs signature was constructed using Cox regression. The prognostic value of the GARGs signature in osteosarcoma was evaluated using Kaplan-Meier curves and a nomogram. RESULTS: Two GARG subtypes were identified, with Cluster A showing better prognosis, immunogenicity, and immune cell infiltration than Cluster B. A novel risk model of 3 GARGs was established using the TARGET dataset and validated with independent datasets. High-risk patients had poorer overall survival, and the GARGs signature independently predicted osteosarcoma prognosis. Combining risk scores and clinical characteristics in a nomogram improved prediction performance. Additionally, we discovered Stanniocalcin-2 (STC2) as a significant prognostic gene highly expressed in osteosarcoma and potential disease biomarker. CONCLUSIONS: Our study revealed that patients with osteosarcoma can be divided into two GARGs subgroups. Furthermore, we have developed a GARGs prognostic signature that can accurately forecast the prognosis of osteosarcoma patients.

Reorganization of structural brain networks in Parkinson's disease with postural instability/gait difficulty.

The Postural Instability/Gait Difficulty (PIGD) subtype of Parkinson's disease (PD) has a faster disease progression, a higher risk of cognitive and motor decline, yet the alterations of structural topological organization remain unknown. Diffusion Tensor Imaging (DTI) and 3D-TI scanning were conducted on 31 PD patients with PIGD (PD-PIGD), 30 PD patients without PIGD (PD-non-PIGD) and 35 Healthy Controls (HCs). Structural networks were constructed using DTI brain white matter fiber tractography. A graph theory approach was applied to characterize the topological properties of complex structural networks, and the relationships between significantly different network metrics and motor deficits were analyzed within the PD-PIGD group. PD-PIGD patients exhibited increased shortest path length compared with PD-non-PIGD and HCs (P < 0.05, respectively). Additionally, PD-PIGD patients exhibited decreased nodal properties, mainly in the cerebellar vermis, prefrontal cortex, paracentral lobule, and visual regions. Notably, the degree centrality of the cerebellar vermis was negatively correlated with the PIGD score (r = -0.390; P = 0.030) and Unified Parkinson's Disease Rating Scale Part III score (r = -0.436; P = 0.014) in PD-PIGD patients. Furthermore, network-based statistical analysis revealed decreased structural connectivity between the prefrontal lobe, putamen, supplementary motor area, insula, and cingulate gyrus in PD-PIGD patients. Our findings demonstrated that PD-PIGD patients existed abnormal structural connectomes in the cerebellar vermis, frontal-parietal cortex and visual regions. These topological differences can provide a topological perspective for understanding the potential pathophysiological mechanisms of PIGD in PD.

Modified Percutaneous Endoscopic Interlaminar Discectomy through the Near-spinous Process Approach for L4/5 Disc Herniation: A Retrospective Clinical Study.

OBJECTIVE: Compared with traditional open surgery, percutaneous endoscopic lumbar discectomy (PELD) has the advantages of less trauma, faster recovery, and less postoperative pain, so it has been widely used in the field of spinal surgery. However, it still has the defect of intraoperative fluoroscopy occurrences, complications, and even the risk of damage to the spinal cord and nerve. This study aims to compare the clinical efficacy of modified percutaneous endoscopic interlaminar discectomy (MPEID) with percutaneous endoscopic transforaminal discectomy (PETD) in treating L4/5 lumbar disc herniation (LDH) and to evaluate the effectiveness and safety of MPEID. METHODS: Thirty-four L4/5 LDH patients treated at the Second Affiliated Hospital of Nanchang University from June 2020 to June 2021 were studied retrospectively. Seventeen underwent MPEID and seventeen PETD. Variables analyzed included demographics, operative duration, intraoperative fluoroscopy occurrences, and surgical outcomes. Effectiveness was evaluated using the visual analogue scale (VAS), Oswestry disability index (ODI), and modified MacNab criteria. Lumbar Magnetic Resonance Imaging (MRI) was used to assess radiological outcomes. A paired t-test was performed to compare intragroup pre- and postoperative clinical data, VAS, and ODI scores. RESULTS: The average operative time in PETD group was 91.65 ± 14.04 min, and the average operative time in MPEID group was 65.41 ± 12.61 min (p < 0.001). In PETD group, the fluoroscopy occurrences averaged 9.71 ± 1.05 times, with fluoroscopy occurrences averaging 6.47 ± 1.00 times (p < 0.001) in MPEID group. At 12 months follow-up, the clinical effect showed significant improvement in both two groups. The MPEID group showed a decrease in average VAS-back score from 5.41 ± 2.18 to 1.76 ± 1.09 (p < 0.001) and VAS-leg score from 6.53 ± 1.66 to 0.82 ± 0.64 (p < 0.001). The ODI scores decreased from 51.35 ± 10.65 to 11.71 ± 2.91 (p < 0.001). In the PETD group, the VAS-back score decreased from 4.94 ± 1.98 to 2.06 ± 1.25 (p < 0.001), VAS-leg score from 7.12 ± 1.73 to 1.12 ± 0.60 (p < 0.001), and ODI scores from 48.00 ± 11.62 to 12.24 ± 2.56 (p < 0.001). According to the modified MacNab criteria, MPEID had 15 excellent and two good results; PETD had 12 excellent and 5 good (p = 0.23). No nerve root injuries, dural tears, or significant complications were reported. CONCLUSION: MPEID and PETD effectively treat L4/5 LDH, with MPEID showing shorter operative times and fewer fluoroscopies. Furthermore, the MPEID group can provide excellent clinical efficacy as the PETD group in the short term.

Spectrum-effect relationship study between ultra-high-performance liquid chromatography fingerprints and anti-hepatoma effect in vitro of Cnidii Fructus.

Cnidii Fructus, derived from the dried ripe fruit of Cnidium monnieri (L.) Cuss, has the effect of warming kidneys and invigorating Yang. This study established the spectrum-effect relationships between ultra-high-performance liquid chromatography (UHPLC) fingerprints and the antitumor activities of Cnidii Fructus on human hepatocellular carcinoma (HepG2) cells. In UHPLC fingerprints, 19 common peaks were obtained, and 17 batches of herbs had similarity >0.948. In Cell Counting Kit-8 (CCK-8) test, 17 batches of Cnidii Fructus extract significantly inhibited the proliferation of HepG2 cells to different degrees, showing different half-maximal inhibitory concentration (IC50) values. Furthermore, gray correlation analysis, Pearson's analysis, and orthogonal partial least squares discriminant analysis were performed to screen out eight components. The analysis of mass spectrum data and a comparison with standards revealed that the eight components were methoxsalen, isopimpinellin, osthenol, imperatorin, osthole, ricinoleic acid, linoleic acid, and oleic acid. The verification experiments by testing single compounds indicated that these eight compounds were the major anti-hepatoma compounds in Cnidii Fructus. This work provides a model combining UHPLC fingerprints and antitumor activities to study the spectrum-effect relationships of Cnidii Fructus, which can be used to determine the principal components responsible for the bioactivity.

Fenton-like Reaction Inspired "·OH Catalyzed" Osteogenic Process for the Treatment of Osteoporosis.

Inspired by the Fenton-like reaction, this work combines copper peroxide (CP) nanoparticles with black phosphorus (BP) nanosheets to form a hydroxyl radical (·OH)-centered "catalytic" osteogenic system. CP-produced ·OH interacts with BP to rapidly produce a large amount of phosphate ions, thus accelerating self-mineralization and promoting bone formation. In turn, BP not only exerts anti-inflammatory effects, thereby providing a favorable microenvironment for bone formation, but also offsets the potential toxicity of CP induced by reactive oxygen species (ROS). Together with copper ions (Cu2+ ), phosphate ions are also released as a byproduct of this process, which can contribute to the comprehensive promotion of osteogenesis.

Delivery of paclitaxel by carboxymethyl chitosan-functionalized dendritic fibrous nano-silica: Fabrication, characterization, controlled release performance and pharmacokinetics.

In this study, carboxymethyl chitosan (CMCS) with excellent biocompatibility was used as the "gatekeeper" to design and fabricate a pH-responsive drug delivery system (CMCS-DFNS) as paclitaxel carriers. Characterization results showed that CMCS-DFNS was successfully prepared and the nanocarriers displayed excellent drug loading efficiency of 19.8 %, and the results of the adsorption mechanism revealed that the adsorption of PTX was consistent with the Freundlich isotherm and pseudo-second-order kinetic model. Furthermore, the pH-responsive controlled release behavior at different pH (pH = 7.4, 6.5, and 5.0) was evaluated, and the results demonstrated that the cumulative release at pH 5.0 was 58.8 %, which was 2.7 times higher than that at pH 7.4, suggesting that the carrier exhibited a good pH sensitivity. The results of in vitro cellular experiments further indicated that CMCS-DFNS significantly improved the drug uptake efficiency in breast cancer MCF-7 cells. Importantly, the results of in vivo and cellular pharmacokinetic revealed that CMCS-DFNS can improve the circulation time and enhance the relative bioavailability of paclitaxel. Therefore, the fabricated pH-responsive drug delivery system has potential applications in the delivery of anti-tumor drugs, and provides a new delivery pathway for other compounds with low bioavailability.

Identification of CXCL16 as a diagnostic biomarker for obesity and intervertebral disc degeneration based on machine learning.

Intervertebral disc degeneration (IDD) is the primary cause of neck and back pain. Obesity has been established as a significant risk factor for IDD. The objective of this study was to explore the molecular mechanisms affecting obesity and IDD by identifying the overlapping crosstalk genes associated with both conditions. The identification of specific diagnostic biomarkers for obesity and IDD would have crucial clinical implications. We obtained gene expression profiles of GSE70362 and GSE152991 from the Gene Expression Omnibus, followed by their analysis using two machine learning algorithms, least absolute shrinkage and selection operator and support vector machine-recursive feature elimination, which enabled the identification of C-X-C motif chemokine ligand 16 (CXCL16) as a shared diagnostic biomarker for obesity and IDD. Additionally, gene set variant analysis was used to explore the potential mechanism of CXCL16 in these diseases, and CXCL16 was found to affect IDD through its effect on fatty acid metabolism. Furthermore, correlation analysis between CXCL16 and immune cells demonstrated that CXCL16 negatively regulated T helper 17 cells to promote IDD. Finally, independent external datasets (GSE124272 and GSE59034) were used to verify the diagnostic efficacy of CXCL16. In conclusion, a common diagnostic biomarker for obesity and IDD, CXCL16, was identified using a machine learning algorithm. This study provides a new perspective for exploring the possible mechanisms by which obesity impacts the development of IDD.

Evaluation of Safety and Efficacy of Preoperative Coronal MRI-Guided Minimally Invasive Surgery for Cervical Spondylotic Radiculopathy.

BACKGROUND Key-hole surgery is a minimally invasive technique that has shown promise in various surgical procedures. This study aimed to assess the clinical effectiveness of preoperative coronal MRI-assisted key-hole surgery for the treatment of patients with cervical spondylotic radiculopathy (CSR). MATERIAL AND METHODS A total of 30 patients diagnosed with CSR and undergoing key-hole surgery with CMRI assistance were included in the study. Various parameters, including surgical segments, incision length, disease duration, operative time, intraoperative fluoroscopy times, intraoperative blood loss, complications, and length of hospitalization, were recorded. Precise measurements of Cobb angles and intervertebral space height were taken before and after the surgical procedure. Surgical outcomes were evaluated using modified Macnab criteria, visual analogue scale (VAS), Japanese Orthopaedic Association Scores (JOA), and neck disability index (NDI). RESULTS The average duration of disease was 6.47±3.29 months, with an average incision length of 1.94±0.15 cm and operative time of 57.83±4.34 minutes. The average intraoperative blood loss was 33.70±9.28 ml, with an average of 3.50±0.73 intraoperative fluoroscopies. The average duration of hospitalization was 4.10±1.27 days. Preoperative and postoperative measurements showed no statistically significant difference in C2-C7 Cobb angles and intervertebral space height. However, there were significant improvements in postoperative VAS, NDI, and JOA scores compared to preoperative scores. The surgical effectiveness rate was 100%, with a high rate of good and excellent outcomes. CONCLUSIONS The findings of this study suggest that preoperative CMRI-assisted key-hole surgery for single-segment CSR is a safe and effective treatment option with low complication rates. The clinical benefits include high security and good outcomes. Further research and larger studies are warranted to validate these findings.

Identification of mitochondrial-related signature and molecular subtype for the prognosis of osteosarcoma.

Mitochondria play a vital role in osteosarcoma. Therefore, the purpose of this study was to investigate the potential role of mitochondrial-related genes (MRGs) in osteosarcoma. Based on 92 differentially expressed MRGs, osteosarcoma samples were divided into two subtypes using the nonnegative matrix factorization (NMF). Ultimately, a univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox analysis were performed to construct a prognostic risk model. The single-sample gene set enrichment analysis assessed the immune infiltration characteristics of osteosarcoma patients. Finally, we identified an osteosarcoma biomarker, malonyl-CoA decarboxylase (MLYCD), which showed downregulation. Osteosarcoma cells proliferation, migration, and invasion were effectively inhibited by the overexpression of MLYCD. Our findings will help us to further understand the molecular mechanisms of osteosarcoma and contribute to the discovery of new diagnostic biomarkers and therapeutic targets.

Molecular characterization of cancer-intrinsic immune evasion genes indicates prognosis and tumour microenvironment infiltration in osteosarcoma.

Cancer-intrinsic immune evasion (IE) to cells is a critical factor in tumour growth and progression, yet the molecular characterization of IE genes (IEGs) in osteosarcoma remains underexplored. In this study, 85 osteosarcoma patients were comprehensively analyzed based on 182 IEGs, leading to the identification of two IE clusters linked to distinct biological processes and clinical outcomes. In addition, two IE clusters demonstrated diverse immune cell infiltration patterns, with IEGcluster A displaying increased levels compared to IEGcluster B. Moreover, an IE score was identified as an independent prognostic factor and nomogram may serve as a practical tool for the individual prognostic evaluation of patients with osteosarcoma. Finally, GBP1, a potential biomarker with high expression in osteosarcoma was identified. The findings of this study highlight the presence of two IE clusters, each associated with differing patient outcomes and immune infiltration properties. The IE score may serve to assess individual patient IE characteristics, enhance comprehension of immune features, and guide more efficacious treatment approaches.

Comparative analysis of chemical components in fruits of Chebulae Fructus and its pulp based on chromatographic technology coupled with multivariate chemometric methods.

Chebulae Fructus, was extensively used as a food supplement and medicinal herb, which contained two medicinal forms corresponding to the mature fruit of Chebulae Fructus (CF) and CF pulp. They were widely used in the Chinese clinical medicine and it played a significant role in the Mongolian and Tibetan medicine for the treatment of sore throat, asthma, diarrhea and other diseases. Both of them were recorded in the 2020 Edition (Volume I) of the Chinese Pharmacopoeia. However, the chemical components of CF and CF pulp have not been holistically explored, which seriously hindered its quality evaluation. This study investigated the overall chemical profile of the CF and CF pulp using ultra high-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UHPLC-Q-TOF/MS) and ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Sixty-four chemical components were tentatively identified, and 13 components were quantified in Chebulae Fructus. Furthermore, multivariate chemometric methods were applied to compare the differences among CF samples, and all samples were classified by orthogonal partial least squares-discriminant analysis (OPLS-DA) based on the 13 quantified compounds. The results showed that CF and CF pulp were clustered in two different areas. Ellagic acid, chebulagic acid, chebulinic acid, corilagin and pentagalloyl glucose were selected as the significant constituents to different of CF and CF pulp. LC-MS coupled with chemometrics strategy analysis could comprehensively evaluate the holistic quality of CF, which provided a necessary information for the rational development and utilization of CF and CF pulp resource.

QTG-Miner aids rapid dissection of the genetic base of tassel branch number in maize.

Genetic dissection of agronomic traits is important for crop improvement and global food security. Phenotypic variation of tassel branch number (TBN), a major breeding target, is controlled by many quantitative trait loci (QTLs). The lack of large-scale QTL cloning methodology constrains the systematic dissection of TBN, which hinders modern maize breeding. Here, we devise QTG-Miner, a multi-omics data-based technique for large-scale and rapid cloning of quantitative trait genes (QTGs) in maize. Using QTG-Miner, we clone and verify seven genes underlying seven TBN QTLs. Compared to conventional methods, QTG-Miner performs well for both major- and minor-effect TBN QTLs. Selection analysis indicates that a substantial number of genes and network modules have been subjected to selection during maize improvement. Selection signatures are significantly enriched in multiple biological pathways between female heterotic groups and male heterotic groups. In summary, QTG-Miner provides a large-scale approach for rapid cloning of QTGs in crops and dissects the genetic base of TBN for further maize breeding.

Genetic mapping and functional analysis of a classical tassel branch number mutant Tp2 in maize.

Tassel branch number is a key trait that contributes greatly to grain yield in maize (Zea mays). We obtained a classical mutant from maize genetics cooperation stock center, Teopod2 (Tp2), which exhibits severely decreased tassel branch. We conducted a comprehensive study, including phenotypic investigation, genetic mapping, transcriptome analysis, overexpression and CRISPR knock-out, and tsCUT&Tag of Tp2 gene for the molecular dissection of Tp2 mutant. Phenotypic investigation showed that it is a pleiotropic dominant mutant, which is mapped to an interval of approximately 139-kb on Chromosome 10 harboring two genes Zm00001d025786 and zma-miR156h. Transcriptome analysis showed that the relative expression level of zma-miR156h was significantly increased in mutants. Meanwhile, overexpression of zma-miR156h and knockout materials of ZmSBP13 exhibited significantly decreased tassel branch number, a similar phenotype with Tp2 mutant, suggesting that zma-miR156h is the causal gene of Tp2 and targets ZmSBP13 gene. Besides, the potential downstream genes of ZmSBP13 were uncovered and showed that it may target multiple proteins to regulate inflorescence structure. Overall, we characterized and cloned Tp2 mutant, and proposed a zma-miR156h-ZmSBP13 model functioning in regulating tassel branch development in maize, which is an essential measure to satisfy the increasing demands of cereals.

Role of non­coding RNAs in cartilage endplate (Review).

Cartilage endplate (CEP) degeneration is considered one of the major causes of intervertebral disc degeneration (IDD), which causes non-specific neck and lower back pain. In addition, several non-coding RNAs (ncRNAs), including long ncRNAs, microRNAs and circular RNAs have been shown to be involved in the regulation of various diseases. However, the particular role of ncRNAs in CEP remains unclear. Identifying these ncRNAs and their interactions may prove to be is useful for the understanding of CEP health and disease. These RNA molecules regulate signaling pathways and biological processes that are critical for a healthy CEP. When dysregulated, they can contribute to the development disease. Herein, studies related to ncRNAs interactions and regulatory functions in CEP are reviewed. In addition, a summary of the current knowledge regarding the deregulation of ncRNAs in IDD in relation to their actions on CEP cell functions, including cell proliferation, apoptosis and extracellular matrix synthesis/degradation is presented. The present review provides novel insight into the pathogenesis of IDD and may shed light on future therapeutic approaches.

ZmHOX32 is related to photosynthesis and likely functions in plant architecture of maize.

HOX32, a member of the HD-ZIP III family, functions in the leaf morphogenesis and plant photosynthesis. However, the regulatory mechanism of HOX32 in maize has not been studied and the regulatory relationship in photosynthesis is unclear. We conducted a comprehensive study, including phylogenetic analysis, expression profiling at both transcriptome and translatome levels, subcellular localization, tsCUT&Tag, co-expression analysis, and association analysis with agronomic traits on HOX32 for the dissection of the functional roles of HOX32. ZmHOX32 shows conservation in plants. As expected, maize HOX32 protein is specifically expressed in the nucleus. ZmHOX32 showed constitutively expression at both transcriptome and translatome levels. We uncovered the downstream target genes of ZmHOX32 by tsCUT&Tag and constructed a cascaded regulatory network combining the co-expression networks. Both direct and indirect targets of ZmHOX32 showed significant gene ontology enrichment in terms of photosynthesis in maize. The association study suggested that ZmHOX32 plays an important role in regulation of plant architecture. Our results illustrate a complex regulatory network of HOX32 involving in photosynthesis and plant architecture, which deepens our understanding of the phenotypic variation in plants.

A translatome-transcriptome multi-omics gene regulatory network reveals the complicated functional landscape of maize.

BACKGROUND: Maize (Zea mays L.) is one of the most important crops worldwide. Although sophisticated maize gene regulatory networks (GRNs) have been constructed for functional genomics and phenotypic dissection, a multi-omics GRN connecting the translatome and transcriptome is lacking, hampering our understanding and exploration of the maize regulatome. RESULTS: We collect spatio-temporal translatome and transcriptome data and systematically explore the landscape of gene transcription and translation across 33 tissues or developmental stages of maize. Using this comprehensive transcriptome and translatome atlas, we construct a multi-omics GRN integrating mRNAs and translated mRNAs, demonstrating that translatome-related GRNs outperform GRNs solely using transcriptomic data and inter-omics GRNs outperform intra-omics GRNs in most cases. With the aid of the multi-omics GRN, we reconcile some known regulatory networks. We identify a novel transcription factor, ZmGRF6, which is associated with growth. Furthermore, we characterize a function related to drought response for the classic transcription factor ZmMYB31. CONCLUSIONS: Our findings provide insights into spatio-temporal changes across maize development at both the transcriptome and translatome levels. Multi-omics GRNs represent a useful resource for dissection of the regulatory mechanisms underlying phenotypic variation.

Pharmacokinetics of active compounds of a Terminalia chebula Retz. Ethanolic extract after oral administration rats using UPLC-MS/MS.

Terminalia chebula Retz. (TC) is a well-known Chinese herbal medicine and rich in chemical components with multiple pharmacological effects. In this study, an ultra-performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) method was developed and used to determine the blood concentrations of nine active compounds (chebulic acid, gallic acid, protocatechuic acid, corilagin, chebulagic acid, chebulinic acid, 1,2,3,4,6-O-pentagalloylglucose, ellagic acid and ethyl gallate) after oral administration of TC extracts in rats. Pretreatment of plasma samples with protein precipitate with methanol was carried out, and caffeic acid was used as the internal standard (IS). Compounds precisions of intra- and inter-day were less than 14.6%, and the accuracy ranged from -11.7% to 13.5%. The extraction recoveries of compounds were between 84.9% and 108.4%, while matrix effects occurred between 86.4% and 115.9%. Stability tests showed that all nine analytes had been stable under four storage conditions, and statistically significant the relative standard deviations were under 13.7%. The validated UPLC-MS/MS method was applied with great success to plasma pharmacokinetics analysis of the TC extracts, and the pharmacokinetic results showed that among the nine components, the area under the concentration-time curve (AUC(0-tn), 231112.38 ± 64555.20 h ng/mL) and maximum concentration (Cmax, 4,983.57 ± 1721.53 ng/mL) of chebulagic acid were relatively large, which indicated that it had a higher level of plasma exposure. The half-life of elimination (T1/2) of chebulinic acid, corilagin and chebulagic acid were 43.30, 26.39 and 19.98 h, respectively, suggesting that these analytes showed prolonged retention and metabolize more slowly in vivo. This study would deliver a theoretical foundation for the further application of TC in clinical practice.

Bimetallic Metal-Organic Framework for Mitigating Aseptic Osteolysis.

The disability rate of joint diseases can be reduced by the use of artificial joints, but joint loosening at a late state limits the lifespan and surgical efficacy of the joints. Wear particles can be recognized by macrophages and induce cells to produce reactive oxygen species (ROS) and inflammatory factors, causing persistent inflammation and decreased osteogenic activity, which ultimately leads to loosening of joint prostheses. Here, the platinum (Pt) nanozymes with excellent ROS scavenging and anti-inflammatory capabilities were encapsulated in zinc imidazolium zeolite framework-8 (ZIF-8), and then the osteogenic active element lanthanum (La) was introduced through ion exchange to finally construct a bimetallic metal-organic framework (Pt@ZIF-8@La). In vitro and in vivo experiments demonstrated that this multifunctional nanoplatform possessed the functions of efficient scavenging of ROS, immune regulation, and promotion of osteogenic differentiation. Meanwhile, the mechanism is explored that Pt@ZIF-8@La can also promote osteogenic mineralization by upregulating the ratio of the osteoprotegerin (OPG)/receptor activator of the NF-κB ligand (RANKL), which can achieve a synergistic therapeutic effect of immunomodulation and osteogenesis, thereby realizing the purpose of relieving aseptic osteolysis.