Enhanced therapeutic potential of Flotillins-modified MenSCs by improve the survival, proliferation and migration.

Menstrual blood-derived endometrial stem cells (MenSCs) have attracted increasing interest due to their excellent safety, and lack of ethical dilemma as well as their ability to be periodically obtained in a noninvasive manner. However, although preclinical research as shown the therapeutic potential of MenSCs in several diseases, their poor cell survival and low engraftment at disease sites reduce their clinical efficacy. Flotillins (including Flot1 and Flot2) are implicated in various cellular processes, such as vesicular trafficking, signal transduction, cell proliferation, migration and apoptosis. In this study, we aimed to determine the effects of Flotillins on MenSCs survival, proliferation and migration. Our experimental results show that MenSCs were modified to overexpress Flot1 and/or Flot2 without altering their intrinsic characteristics. Flot1 and Flot2 co-overexpression promoted MenSC viability and proliferation capacity. Moreover, Flot1 or Flot2 overexpression significantly promoted the migration and inhibited the apoptosis of MenSCs compared with the negative control group, and these effects were stronger in the Flot1 and Flot2 gene co-overexpression group. However, these effects were significantly reversed after Flot1 and/or Flot2 knockdown. In conclusion, our results indicate that Flot1 and Flot2 overexpression in MenSCs improved their proliferation and migration and inhibited their apoptosis, and this might be an effective approach to improve the efficiency of cell-based therapies.

Multi-omics analysis of kidney, bone and bone marrow explored potential mechanisms of Erzhi Wan against osteoporosis with kidney-Yin deficiency.

Osteoporosis (OP) is a metabolic bone disease that can lead to major health challenges. The theory of Traditional Chinese medicine believes that kidney-Yin deficiency (KYD) is the main cause of postmenopausal osteoporosis. This study was aimed to investigate the effect of EZW on anti-osteoporosis with KYD, and explore potential mechanisms from the perspective of the kidney, bone and bone marrow through analysis of metabolomics and proteomics. The model of OP with KYD was established by rats treated with bilateral ovariectomy (OVX), and then given intragastric administration of thyroid and reserpine to induce. Micro-CT was applied to determine the microstructures of bone. Serum levels associated with bone turnover markers and kidney-Yin deficiency were detected by enzyme-linked immunosorbent (ELISA) assay. The differential metabolites in the kidney, bone and bone marrow were analyzed by metabolomics. The differentially expressed proteins in these three tissues were detected via proteomics. The findings suggested that EZW could alleviate a variety of metabolites and proteins among the kidney, bone and bone marrow, primarily in amino acid metabolism, carbohydrate metabolism, nucleotide metabolism and lipid metabolism, thus leading to improvements of OP with KYD, which provided theoretical basis for clinical treatment of EZW on OP with KYD.

Integrated component identification, network pharmacology, and experimental verification revealed mechanism of Dendrobium officinale Kimura et Migo against lung cancer.

BACKGROUND: Dendrobium officinale Kimura et Migo (DO), a valuable Chinese herbal medicine, has been reported to exhibit potential effects in the prevention and treatment of lung cancer. However, its material basis and mechanism of action have not been comprehensively analyzed. PURPOSE: The objective of this study was to preliminarily elucidate the active components and pharmacological mechanisms of DO in treating lung cancer, according to UPLC-Q/TOF-MS, HPAEC-PAD, network pharmacology, molecular docking, and experimental verification. METHODS: The chemical components of DO were identified via UPLC-Q/TOF-MS, while the monosaccharide composition of Dendrobium officinale polysaccharide (DOP) was determined by HPAEC-PAD. The prospective active constituents of DO as well as their respective targets were predicted in the combined database of Swiss ADME and Swiss Target Prediction. Relevant disease targets for lung cancer were searched in OMIM, TTD, and Genecards databases. Further, the active compounds and potential core targets of DO against lung cancer were found by the C-T-D network and the PPI network, respectively. The core targets were then subjected to enrichment analysis in the Metascape database. The main active compounds were molecularly docked to the core targets and visualized. Finally, the viability of A549 cells and the relative quantity of associated proteins within the major signaling pathway were detected. RESULTS: 249 ingredients were identified from DO, including 39 flavonoids, 39 bibenzyls, 50 organic acids, 8 phenanthrenes, 27 phenylpropanoids, 17 alkaloids, 17 amino acids and their derivatives, 7 monosaccharides, and 45 others. Here, 50 main active compounds with high degree values were attained through the C-T-D network, mainly consisting of bibenzyls and monosaccharides. Based on the PPI network analysis, 10 core targets were further predicted, including HSP90AA1, SRC, ESR1, CREBBP, MAPK3, AKT1, PIK3R1, PIK3CA, HIF1A, and HDAC1. The results of the enrichment analysis and molecular docking indicated a close association between the therapeutic mechanism of DO and the PI3K-Akt signaling pathway. It was confirmed that the bibenzyl extract and erianin could inhibit the multiplication of A549 cells in vitro. Furthermore, erianin was found to down-regulate the relative expressions of p-AKT and p-PI3K proteins within the PI3K-Akt signaling pathway. CONCLUSIONS: This study predicted that DO could treat lung cancer through various components, multiple targets, and diverse pathways. Bibenzyls from DO might exert anti-lung cancer activity by inhibiting cancer cell proliferation and modulating the PI3K-Akt signaling pathway. A fundamental reference for further studies and clinical therapy was given by the above data.

Recent Advances in Topical Hemostatic Materials.

Untimely or improper treatment of traumatic bleeding may cause secondary injuries and even death. The traditional hemostatic modes can no longer meet requirements of coping with complicated bleeding emergencies. With scientific and technological advancements, a variety of topical hemostatic materials have been investigated involving inorganic, biological, polysaccharide, and carbon-based hemostatic materials. These materials have their respective merits and defects. In this work, the application and mechanism of the major hemostatic materials, especially some hemostatic nanomaterials with excellent adhesion, good biocompatibility, low toxicity, and high adsorption capacity, are summarized. In the future, it is the prospect to develop multifunctional hemostatic materials with hemostasis and antibacterial and anti-inflammatory properties for promoting wound healing.

Leech extract alleviates idiopathic pulmonary fibrosis by TGF-ß1/Smad3 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Leech, as a traditional Chinese medicine for the treatment of blood circulation and blood stasis, was also widely used to cure pulmonary fibrosis in China. In clinical practice, some traditional Chinese medicine preparation such as Shui Zhi Xuan Bi Hua Xian Tang and Shui Zhi Tong Luo Capsule composed of leech, could improve the clinical symptoms and pulmonary function in patients with idiopathic pulmonary fibrosis (IPF). However, the material basis of the leech in the treatment of IPF were not yet clear. AIM OF THE STUDY: Screen out the components of leech that have the anti-pulmonary fibrosis effects, and further explore the therapeutic mechanism of the active components. MATERIALS AND METHODS: In this study, the different molecular weight components of leech extract samples were prepared using the semi-permeable membranes with different pore sizes. The therapeutic effects of the leech extract groups with molecular weight greater than 10 KDa (>10 KDa group), between 3 KDa and 10 KDa (3-10 KDa group), and less than 3 KDa (<3 KDa group) on pulmonary fibrosis were firstly investigated by cell proliferation and cytotoxicity assay (MTT), cell wound healing assay, immunofluorescence staining (IF) and Western blot (WB) assay through the TGF-ß1-induced fibroblast cell model. Then bleomycin-induced pulmonary fibrosis (BML-induced PF) mouse model was constructed to investigate the pharmacological activities of the active component group of leech extract in vivo. Pathological changes of the mouse lung were observed by hematoxylin-eosin staining (H&E) and Masson's trichrome staining (Masson). The hydroxyproline (HYP) content of lung tissues was quantified by HYP detection kit. The levels of extracellular matrix-related fibronectin (FN) and collagen type Ⅰ (Collagen Ⅰ), pyruvate kinase M2 (PKM2) monomer and Smad7 protein were determined via WB method. PKM2 and Smad7 protein were further characterized by IF assays. RESULTS: Using TGF-ß1-induced HFL1 cell line as a PF cell model, the in vitro results demonstrated that the >10 KDa group could significantly inhibited the cell proliferation and migration, downregulated the expression level of cytoskeletal protein vimentin and α-smooth muscle actin (α-SMA), and reduced the deposition of FN and Collagen Ⅰ. In the BML-induced PF mouse model, the >10 KDa group significantly reduced the content of HYP, downregulated the expression levels of FN and Collagen Ⅰ in lung tissues, and delayed the pathological changes of lung tissue structure. The results of WB and IF assays further indicated that the >10 KDa group could up-regulate the expression level of PKM2 monomer and Smad7 protein in the cellular level, thereby delaying the progression of pulmonary fibrosis. CONCLUSIONS: Our study revealed that the >10 KDa group was the main material basis of the leech extract that inhibited pulmonary fibrosis through TGF-ß1/Smad3 signaling pathway.

Lightweight, flame retardant Janus carboxymethyl cellulose aerogel with fire-warning properties for smart sensor.

Lightweight, flame retardant biomass aerogels combining with multi-functionalities are promising for thermal insulation, noise absorption and smart sensors. However, high flammability hinders the application of these aerogels in extreme condition. Herein, lightweight, flame retardant aerogel with fire-warning properties fabricated from resource-abundant graphite and green carboxymethyl cellulose (CMC) is reported. During sonicating expandable graphite (EG) in CMC solution, CMC not only fabricates the downsizing process via hydrogen bonding effect but also forms stable dispersions. Then biomass aerogel is fabricated by freeze-drying strategy and enhanced by metal ionic cross-linking method. This aerogel demonstrates Janus properties for electrical conductivity and thermal conductivity. Due to the synergistic flame retardant effect of graphite nanocomposite and metal ions with a barrier effect and catalytic carbonization capacity, the flame retardancy of these aerogels are enhanced with fire-warning properties. Furthermore, these aerogels are used for monitoring physical deformations as smart sensors, which provides inspiration and a sustainable solution for developing low-cost biomass aerogel with multifunction.

Association between adult attachment style, communication patterns and caregiver burden in parents of children with solid tumors: A cross-sectional study.

PURPOSE: The primary purpose of this cross-sectional study was to delve into the connections among adult attachment styles, communication patterns, and caregiver burden within the sample of parents caring for children diagnosed with solid tumors. METHODS: A sample of 456 parents responsible for the care of children with solid tumors was conveniently recruited from a pediatric oncology ward at a tertiary hospital from September 2021 to September 2022. The data collection process included a questionnaire on general information, the Caregiver Burden Inventory, the Adult Attachment Questionnaire Short Form, and the Communication Pattern Questionnaire. RESULTS: The findings demonstrated a strong and positive connection between caregiver burden and attachment avoidance, whereas no considerable association was observed for attachment anxiety. Attachment avoidance exhibited a positive link with communication patterns and caregiver burden, and a noteworthy inverse correlation with attachment anxiety. Additionally, communication patterns were uncovered as a mediator in the association between attachment avoidance and caregiver burden. CONCLUSIONS: This study underscores the role of communication patterns as mediators between attachment avoidance and caregiver burden among parents of children with solid tumors. These outcomes emphasize the significance of considering attachment styles and communication patterns when comprehending caregiver burden, and can guide the development of targeted interventions to provide support for parents within this challenging context.

Conditioned medium of human menstrual blood-derived endometrial stem cells protects against cell inflammation and apoptosis of Npc1KO N2a cells.

Niemann-Pick disease type C1 (NPC1) is a hereditary neurodegenerative disorder caused by a mutation in the NPC1 gene. This gene encodes a transmembrane protein found in lysosomes. This disease characterized by hepatosplenomegaly, neurological impairments and premature death. Recent preclinical studies have shown promising results in using mesenchymal stem cells (MSCs) to alleviate the symptoms of NPC1. One type of MSCs, known as human menstrual blood-derived endometrial stem cells (MenSCs), has attracted attention due to its accessibility, abundant supply, and strong proliferation and regeneration capabilities. However, it remains uncertain whether the conditioned medium of MenSCs (MenSCs-CM) can effectively relieve the symptoms of NPC1. To investigate this further, we employed the CRISPR-Cas9 technique to successfully create a Npc1 gene knockout N2a cell line (Npc1KO N2a). Sanger sequencing confirmed the occurrence of Npc1 gene mutation in these cells, while western blotting revealed a lack of NPC1 protein expression. Filipin staining provided visual evidence of unesterified cholesterol accumulation in Npc1KO N2a cells. Moreover, Npc1KO N2a cells exhibited significantly decreased viability, increased inflammation, and heightened cell apoptosis. Notably, our study demonstrated that the viability of Npc1KO N2a cells was most significantly improved after being cultured by 36 h-collected MenSCs-CM for 0.5 days. Additionally, MenSCs-CM exhibited the ability to effectively reduce inflammation, counteract cell apoptosis, and ameliorate unesterified cholesterol accumulation in Npc1KO N2a cells. This groundbreaking finding establishes, for the first time, the protective effect of MenSCs-CM on N2a cells with Npc1 gene deletion. These findings suggest that the potential of MenSCs-CM as a beneficial therapeutic approach for NPC1 and other neurodegenerative diseases.

Development a prediction model for identifying bacterial meningitis in young infants aged 29-90 days: a retrospective analysis.

BACKGROUND: The early diagnosis and treatment of bacterial meningitis (BM) in young infants was very critical. But, it was difficult to make a definite diagnosis in the early stage due to nonspecific clinical symptoms. Our objectives were to find the risk factors associated with BM and develop a prediction model of BM especially for young infants. METHODS: We retrospectively reviewed the clinical data of young infants with meningitis between January 2011 and December 2020 in Children's Hospital of Soochow University. The independent risk factors of young infants with BM were screened using univariate and multivariate logistic regression analyses. The independent risk factors were used to construct a new scoring model and compared with Bacterial Meningitis Score (BMS) and Meningitis Score for Emergencies (MSE) models. RESULTS: Among the 102 young infants included, there were 44 cases of BM and 58 of aseptic meningitis. Group B Streptococcus (22, 50.0%) and Escherichia coli (14, 31.8%) were the main pathogens of BM in the young infants. Multivariate logistic regression analysis identified procalcitonin (PCT), cerebrospinal fluid (CSF) glucose, CSF protein as independent risk factors for young infants with BM. We assigned one point for CSF glucose ≤ 1.86 mmol/L, two points were assigned for PCT ≥ 3.80 ng/ml and CSF protein ≥ 1269 mg/L. Using the not low risk criterion (score ≥ 1) with our new prediction model, we identified the young infantile BM with 100% (95% CI 91.9%-100%) sensitivity and 60.3% (95% CI 46.4%-72.9%) specificity. Compared with BMS and MSE model, our prediction model had larger area under receiver operating characteristic curve and higher specificity, the differences were statistically significant. CONCLUSION: Our new scoring model for young infants can facilitate early identification of BM and has a better performance than BMS and MSE models.

Mechanism investigation of Shi-Xiao-San in treating blood stasis syndrome based on network pharmacology, molecular docking and in vitro/vivo pharmacological validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Shixiao San (SXS) is a traditional Chinese formula that has been widely used in clinical practice to treat blood stasis syndromes, such as hyperlipidemia, atherosclerotic, thrombosis and coronary heart disease. However, the effectiveness and mechanism of SXS have not been studied in detail yet. AIM OF THE STUDY: Current study aimed to identify the compounds in SXS, evaluate the formula efficacies using network pharmacology, molecular docking, and verify the pharmacological effects by in vivo and in vitro experiments. MATERIALS AND METHODS: The compounds in SXS were analyzed using UPLC-QTOF-MS. Potential target genes for identified compounds were obtained from three databases. DAVID database was used to perform GO and KEGG pathway enrichment analyses. PPI network was constructed to screen core targets. Molecular docking was used to examine interactions between active compounds and potential targets. The mechanism was also verified by model of acute blood stasis rats and human umbilical vein cells. RESULTS: In total, 45 compounds were identified from SXS. Among the detected phytochemicals, quercetin, isorhamnetin, kaempferol, D-catechin, naringenin and amentoflavone were identified as the active constituents. SXS is primarily involved in the modulation of hypoxic state, vascular regulation, and inflammation response, according to GO and KGG pathway enrichment analysis. A network of protein-protein interactions (PPIs) was constructed and five core targets were identified as VEGFA, AKT1, EGFR, PTGS2, and MMP9. Molecular docking simulation revealed good binding affinity of the five putative targets with the corresponding compounds. SXS reduced HIF-1α and COX-2 levels and increased the eNOS expression levels in hypoxic HUVECs. SXS can reduce the whole blood viscosity in adrenaline induced acute blood stasis rats and relieve blood stasis. CONCLUSIONS: SXS removes blood stasis might through VEGFA/AKT/eNOS/COX-2 pathway and flavonoids are the main active components in the formula.

Structural determination and pro-angiogenic effect of polysaccharide from the pollen of Typha angustifolia L.

Four fractions of polysaccharides (TPP-1, TPP-2, TPP-3, and TPP-4) were isolated and purified from the pollen of Typha angustifolia L., and the structure of TPP-3 was furtherly determined by HPGPC (High Performance Gel Permeation Chromatography), monosaccharide composition analysis, methylation analysis and NMR (Nuclear Magnetic Resonance). TPP-3 was found to be a homogeneous heteropolysaccharide with an average molecular weight of 5.5 × 104 Da and composed of eight types of monosaccharides. The pro-angiogenic activities of TPP-3 were verified on HUVECs and VEGFR tyrosine kinase inhibitor II (VRI)-induced vascular defect zebrafish model. Furthermore, the underlying mechanism investigation showed that its pro-angiogenic activities were closely related with the activation of VEGF/PI3K/Akt signaling pathway.

Clinical characteristics of 68 children with atypical hand, foot, and mouth disease caused by coxsackievirus A6: a single-center retrospective analysis.

Background: Hand, foot, and mouth disease (HFMD) caused by coxsackievirus A6 (CV-A6) has become prevalent in many parts of the world. It is commonly referred to as atypical HFMD which more likely to present as bullous lesions. Compared with traditional HFMD, its misdiagnosis rate is relatively high, which brings difficulties to clinical diagnosis. We retrospectively analyze the clinical characteristics of children with HFMD with bullous lesions caused by CV-A6. Methods: The study included 68 children with atypical HFMD caused by CV-A6 who were hospitalized from 2018 to 2020. Data of the children including age, sex, month of HFMD onset, the morphologies and distribution of rashes, the details of fever, the presence or absence of onychomadesis, and laboratory test results were analyzed and compared between an infant group (<1 year), a toddler group (1-<3 years), and a preschool group (3-<6 years). Results: Of the 68 children, 67 were younger than 5 years old, with a male to female ratio of 1.62:1. The disease peaked in the period from June to September. With 75.0% of the infant group had more than three kinds of rashes; 95.0% of the preschool group had rashes in more than five locations. These differences were statistically significant (P<0.05). All children had fever. The peak fever in the toddler group was lower (P=0.033). No critical cases were observed in any of the groups. Of the 61 children who were successfully followed up, 68.9% developed onychomadesis within 2-3 weeks. The proportion of cases with abnormal liver function was 83.3%, 41.7%, and 10.0% in the infant, toddler, and preschool groups (P<0.001). The proportion of cases with increased serum creatine kinase MB isoenzyme (CK-MB) were significantly higher in the toddler group (P<0.05). Conclusions: Atypical HFMD caused by CV-A6 infection usually occurred in children under 5 years old. The morphologies of the rashes in the infant group changed more, while the rashes in the preschool group was more widely distributed. The incidence of critical cases was low. More than half of the cases can develop onychomadesis in the recovery period. Organ damage was relatively mild in the preschool group.

A Phenomenological Study of Nurses' Experiences in a Pediatric Fever Clinic During the COVID-19 Epidemic.

BACKGROUND AND PURPOSE: In the initial COVID-19 outbreak, nursing staff reportedly experienced high levels of psychological stress. The purpose of this study was to explore the real experience of the first cohort of pediatric fever clinic nurses during the COVID-19 epidemic. METHODS: Semi-structured interviews were conducted with eight nurses who worked in a fever clinic at a children's hospital in China. The interviews were conducted by an experienced and trained interviewer. Qualitative content analysis was used to describe the experiences of the nurses. RESULTS: Three themes were distilled from the interviews: 1) complex psychological experiences including positive experiences (increased sense of responsibility and honor, gaining the respect and recognition of parents, having a sense of achievement in personal growth) and negative experiences (panic and compulsion, guilt towards their family, antipathy, and dissatisfaction); 2) extreme physical discomfort; and 3) a lack of relevant knowledge. IMPLICATIONS FOR PRACTICE: The nurses in the pediatric fever clinic experienced various psychological impacts and physiological discomfort. Nursing managers should improve the management of hospital emergency nursing, strengthen the psychological guidance and logistics support of frontline nurses, and provide nurses with the relevant knowledge and skills training. These improvements would support frontline nurses in their work to provide effective patient treatment during the COVID-19 epidemic.

Metformin's Mechanisms in Attenuating Hallmarks of Aging and Age-Related Disease.

Aging is a major global challenge, and there is growing demand for new strategies to address the burden of aging. The intensive search for antiaging agents has led to the discovery of a variety of drugs that promote the extension of healthspan and/or life. Metformin is a safe, effective, and globally affordable antihyperglycemic agent that has gained much attention in recent years as a potential antiaging treatment. Metformin has been shown to significantly delay the onset of age-related diseases and increase lifespan in several model organisms. In this paper, we reviewed aging hallmarks and the role of metformin in countering these hallmarks. We examined the beneficial effects of metformin on several age-related diseases and the feasibility of metformin as an agent to extend lifespan and healthspan. Finally, we discussed new research directions to better understand the translational potential of metformin in humans.

A Comprehensive Review of Rosmarinic Acid: From Phytochemistry to Pharmacology and Its New Insight.

Polyphenolic acids are the widely occurring natural products in almost each herbal plant, among which rosmarinic acid (RA, C18H16O8) is well-known, and is present in over 160 species belonging to many families, especially the Lamiaceae. Aside from this herbal ingredient, dozens of its natural derivatives have also been isolated and characterized from many natural plants. In recent years, with the increasing focus on the natural products as alternative treatments, a large number of pharmacological studies have been carried out to demonstrate the various biological activities of RA such as anti-inflammation, anti-oxidation, anti-diabetes, anti-virus, anti-tumor, neuroprotection, hepatoprotection, etc. In addition, investigations concerning its biosynthesis, extraction, analysis, clinical applications, and pharmacokinetics have also been performed. Although many achievements have been made in various research aspects, there still exist some problems or issues to be answered, especially its toxicity and bioavailability. Thus, we hope that in the case of natural products, the present review can not only provide a comprehensive understanding on RA covering its miscellaneous research fields, but also highlight some of the present issues and future perspectives worth investigating later, in order to help us utilize this polyphenolic acid more efficiently, widely, and safely.

Discovery of processing-associated Q-marker of carbonized traditional Chinese medicine: An integrated strategy of metabolomics, systems pharmacology and in vivo high-throughput screening model.

BACKGROUND: Carbonized traditional Chinese medicine (TCM) is a kind of distinctive traditional medicine, which has been widely used to cure various bleeding syndromes in clinic for over 2000 years. However, there are no effective quality control methods developed on carbonized TCM so far. PURPOSE: This study aimed at developing a processing-associated quality marker (Q-marker) discovery strategy, which would enable to promote the quality control study of carbonized TCM. METHODS: Carbonized Typhae Pollen (CTP), a typical carbonized TCM with fantastic efficacy of stanching bleeding and removing blood stasis, was used as an example. First, a ultraperformance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) method was established to characterize four types of CTP in different processing degrees. Second, chemometric method was applied to screen candidate Q-markers. Third, peak area changes and Aratio changes of each candidate markers in 57 batches samples were described (Traceability and Transitivity). Fourth, systems pharmacology and two high-throughput zebrafish models: cerebral hemorrhage model and thrombus model were used to furtherly screen Q-markers (Effectiveness). Finally, a ultraperformance liquid chromatographic coupled with triple quadrupole tandem mass spectrometry (UPLC-TQ-MS) method was established and applied to quantify Q-markers in additional 10 batches of CTP samples (Measurability). RESULTS: The chemical profiles of Typhae Pollen during the carbonized process were investigated. Then, 12 candidate compounds were screened in chemometric part. Six Q-markers (isorhamnetin-3-O-neohesperidoside, isorhamnetin-3-O-rutinoside, kaempferol-3-O-neohesperidoside, naringenin, quercetin and isorhamnetin) were subsequently screened out using three principles of Q-markers combined with content changes and two in vivo zebrafish models. Their average contents in additional 10 batches of CTP were 316.8 µg/g, 13.7 µg/g, 6.1 µg/g, 197.8 µg/g, 12.9 µg/g and 199.3 µg/g, respectively. Their content proportion was about 25: 1: 0.5: 15: 1: 15. CONCLUSION: A processing-associated Q-marker discovery strategy was developed for carbonized TCM. It might provide a novel insight to solve the problem of 'Chao Tan Cun Xing' in carbonized process.

Metabolomics-driven of relationships among kidney, bone marrow and bone of rats with postmenopausal osteoporosis.

As a global public health problem, postmenopausal osteoporosis (PMOP) poses a great threat to old women's health. Bone is the target organ of PMOP, and the dynamic changes of bone marrow could affect the bone status. Kidney is the main organ regulating calcium and phosphorus homeostasis. Kidney, bone marrow and bone play crucial roles in PMOP, but the relationships of the three tissues in the disease have not been completely described. Here, metabolomics was employed to investigate the disease mechanism of PMOP from the perspectives of kidney, bone marrow and bone, and the relationships among the three tissues were also discussed. Six-month-old female Sprague-Dawley (SD) rats were randomly divided into ovariectomized (OVX) group (with bilateral ovariectomy) and sham group (with sham surgery). 13 weeks after surgery, gas chromatography-mass spectrometry (GC-MS) was performed to analyze the metabolic profiling of two groups. Multivariate statistical analysis revealed that the number of differential metabolites in kidney, bone marrow and bone between the two groups were 37, 16 and 17, respectively. The common differential metabolites of the three tissues were N-methyl-L-alanine. Kidney and bone marrow had common differential metabolites, including N-methyl-L-alanine, 2-hydroxybutyric acid, (R)-3-hydroxybutyric acid (ß-hydroxybutyric acid, ßHBA), urea and dodecanoic acid. There were three common differential metabolites between kidney and bone, including N-methyl-L-alanine, α-tocopherol and isofucostanol. The common differential metabolite of bone marrow and bone was N-methyl-L-alanine. Some common metabolic pathways were disturbed in multiple tissues of OVX rats, such as glycine, serine and threonine metabolism, purine metabolism, tryptophan metabolism, ubiquinone and other terpenoid-quinone biosynthesis and fatty acid biosynthesis. In conclusion, our study demonstrated that profound metabolic changes have taken place in the kidney, bone marrow and bone, involving common differential metabolites and metabolic pathways. The evaluation of differential metabolites strengthened the understanding of the kidney-bone axis and the metabolic relationships among the three tissues of OVX rats.

Effective Enrichment of Low-Concentration Rare-Earth Ions by Three-Dimensional Thiostannate K2Sn2S5.

Rare-earth elements (REEs) in industrial wastewaters have great value for recycling and reuse, but their characteristic of low concentration poses a challenge to an efficient enrichment from wastewaters. In recent years, thiometallates featuring two-dimensional layers have shown great potential in the enrichment of REEs via the ion-exchange process. However, investigations on thiometallates featuring three-dimensional anionic frameworks for the recovery of REEs have not been reported. Herein, K2Sn2S5 (KTS-2), a thiostannate possessing a three-dimensional porous framework, was chosen as an ion-exchange material for capturing REEs from an aqueous solution. Indeed, KTS-2 exhibited excellent ion-exchange performance for all 16 REEs (except Pm). Specifically, KTS-2 displayed a high capture capacity (232.7 ± 7.8 mg/g) and a short equilibrium time (within 10 min) for Yb3+ ions. In addition, KTS-2 had a high distribution coefficient for Yb3+ ions (Kd > 105 mL/g) in the presence of excessive interfering ions. Impressively, KTS-2 could reach removal rates of above 95% for all 16 REEs in a large quantity of wastewater with low initial concentration (∼7 mg/L). Moreover, KTS-2 could be used as an eco-friendly material for ion exchange of REEs, since the released K+ cations would not cause secondary pollution to the water solution.

"Don't eat me/eat me"-combined apoptotic body analogues for efficient targeted therapy of triple-negative breast cancer.

For the purpose of efficient targeted therapies, suppressing phagocytosis by a mononuclear phagocyte system (MPS), enhancing the "active" targeted delivery, and meeting clinical production criteria are extremely critical for engineering strategies of novel drug delivery systems. Herein, we used a chemically-induced membrane blebbing and extrusion combined method to induce triple-negative breast cancer (TNBC) cell apoptosis to secrete apoptotic body analogue (ABA) vesicles on a large scale for therapeutic drug delivery. After optimization, the ABAs have a desirable size, good biocompatibility, and long-term colloidal stability. Furthermore, ABAs present anti-phagocytosis ("don't eat me") and specific homologous targeting ("eat me") capacities because of their inheritance of membrane proteins such as CD47 and cellular adhesion molecules from parent cells. After loading with toxic protein saporin and anti-twist siRNA, ABAs can significantly inhibit the growth and lung metastasis of TNBC in an orthotopic metastasis model due to their reduced clearance of immune organs, long circulation time, and enhanced targeted accumulation at the tumor sites. These results suggest the great potential of ABAs for targeted drug delivery therapy, in particular efficient TNBC treatment.