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1.
BMC Surg ; 24(1): 136, 2024 May 06.
Article En | MEDLINE | ID: mdl-38711018

BACKGROUND: To explore the risk factors for postoperative abnormal coagulation (PAC) and establish a predictive model for patients with normal preoperative coagulation function who underwent hepatectomy. MATERIALS AND METHODS: A total of 661 patients with normal preoperative coagulation function who underwent hepatectomy between January 2015 and December 2021 at the First Affiliated Hospital of Sun Yat-sen University were divided into two groups: the postoperative abnormal coagulation group (PAC group, n = 362) and the normal coagulation group (non-PAC group, n = 299). Univariate and multivariate logistic analyses were used to identify the risk factors for PAC. RESULTS: The incidence of PAC in 661 patients who underwent hepatectomy was 54.8% (362/661). The least absolute shrinkage and selection operator (LASSO) method was used for multivariate logistic regression analysis. The preoperative international normalized ratio (INR), intraoperative succinyl gelatin infusion and major hepatectomy were found to be independent risk factors for PAC. A nomogram for predicting the PAC after hepatectomy was constructed. The model presented a receiver operating characteristic (ROC) curve of 0.742 (95% confidence interval (CI): 0.697-0.786) in the training cohort. The validation set demonstrated a promising ROC of 0.711 (95% CI: 0.639-0.783), and the calibration curve closely approximated the true incidence. Decision curve analysis (DCA) was performed to assess the clinical usefulness of the predictive model. The risk of PAC increased when the preoperative international normalized ratio (INR) was greater than 1.025 and the volume of intraoperative succinyl gelatin infusion was greater than 1500 ml. CONCLUSION: The PAC is closely related to the preoperative INR, intraoperative succinyl gelatin infusion and major hepatectomy. A three-factor prediction model was successfully established for predicting the PAC after hepatectomy.


Blood Coagulation Disorders , Hepatectomy , Postoperative Complications , Humans , Hepatectomy/adverse effects , Female , Male , Middle Aged , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Risk Factors , Blood Coagulation Disorders/etiology , Blood Coagulation Disorders/epidemiology , Blood Coagulation Disorders/diagnosis , Retrospective Studies , Adult , Aged , International Normalized Ratio , Nomograms , Incidence , Blood Coagulation/physiology , Preoperative Period
2.
Nat Commun ; 15(1): 1575, 2024 Feb 21.
Article En | MEDLINE | ID: mdl-38383478

The rise of touchless technology, driven by the recent pandemic, has transformed human-machine interaction (HMI). Projections indicate a substantial growth in the touchless technology market, nearly tripling from $13.6 billion in 2021 to an estimated $37.6 billion by 2026. In response to the pandemic-driven shift towards touchless technology, here we show an organic cage-based humidity sensor with remarkable humidity responsiveness, forming the basis for advanced touchless platforms in potential future HMI systems. This cage sensor boasts an ultrafast response/recovery time (1 s/3 s) and exceptional stability (over 800 cycles) across relative humidity (RH) changes from 11% to 95%. The crystal structure's 3D pore network and luxuriant water-absorbing functional groups both inside and outside of the cage contribute synergistically to superior humidity sensing. Demonstrating versatility, we showcase this cage in smart touchless control screens and touchless password managers, presenting cost-effective and easily processable applications of molecularly porous materials in touchless HMI.

3.
Angew Chem Int Ed Engl ; 62(46): e202311555, 2023 Nov 13.
Article En | MEDLINE | ID: mdl-37747113

Porous molecular sorbents have excellent selectivity towards hydrocarbon separation with energy saving techniques. However, to realize commercialization, molecular sieving processes should be faster and more efficient compared to extended frameworks. In this work, we show that utilizing fluorine to improve the hydrophobic profile of leaning pillararenes affords a substantial kinetic selective adsorption of benzene over cyclohexane (20 : 1 for benzene). The crystal structure shows a porous macrocycle that acts as a perfect match for benzene in both the intrinsic and extrinsic cavities with strong interactions in the solid state. The fluorinated leaning pillararene surpasses all reported organic molecular sieves and is comparable to the extended metal-organic frameworks that were previously employed for this separation such as UIO-66. Most importantly, this sieving system outperformed the well-known zeolitic imidazolate frameworks under low pressure, which opens the door to new generations of molecular sieves that can compete with extended frameworks for more sustainable hydrocarbon separation.

4.
J Am Chem Soc ; 145(35): 19143-19163, 2023 Sep 06.
Article En | MEDLINE | ID: mdl-37624708

The chemical industry and the chemical processes underscoring it are under intense scrutiny as the demands for the transition to more sustainable and environmentally friendly practices are increasing. Traditional industrial separation systems, such as thermally driven distillation for hydrocarbon purification, are energy intensive. The development of more energy efficient separation technologies is thus emerging as a critical need, as is the creation of new materials that may permit a transition away from classic distillation-based separations. In this Perspective, we focus on porous organic cages and macrocycles that can adsorb guest molecules selectively through various host-guest interactions and permit molecular sieving behavior at the molecular level. Specifically, we summarize the recent advances where receptor-based adsorbent materials have been shown to be effective for industrially relevant hydrocarbon separations, highlighting the underlying host-guest interactions that impart selectivity and permit the observed separations. This approach to sustainable separations is currently in its infancy. Nevertheless, several receptor-based adsorbent materials with extrinsic/intrinsic voids or special functional groups have been reported in recent years that can selectively capture various targeted guest molecules. We believe that the understanding of the interactions that drive selectivity at a molecular level accruing from these initial systems will permit an ever-more-effective "bottom-up" design of tailored molecular sieves that, in due course, will allow adsorbent material-based approaches to separations to transition from the laboratory into an industrial setting.

5.
Article En | MEDLINE | ID: mdl-37642924

As an important dietary supplement, S-adenosylmethionine (SAM) is currently synthesized by methionine adenosyltransferase (MAT) using ATP and methionine as substrates. However, the activity of MAT is severely inhibited by product inhibition, which limits the industrial production of SAM. Here, MAT from Bacteroides fragilis (BfMAT), exhibiting relatively low product inhibition and moderate specific activity, was identified by gene mining. Based on molecular docking, residues within 5 Å of ATP in BfMAT were subjected to mutagenesis for enhanced catalytic activity. Triple variants M3-1 (E42M/E55L/K290I), M3-2 (E42R/E55L/K290I), and M3-3 (E42C/E55L/K290I) with specific activities of 1.83, 1.81, and 1.94 U/mg were obtained, which were 110.5-125.6% higher than that of the wild type (WT). Furthermore, compared with WT, the Km values of M3-1 and M3-3 were decreased by 31.4% and 60.6%, leading to significant improvement in catalytic efficiency (kcat/Km) by 322.5% and 681.1%. All triple variants showed shifted optimal pH from 8.0 to 7.5. Moreover, interaction analysis suggests that the enhanced catalytic efficiency may be attributed to the decreased electrostatic interactions between ATP and the mutation sites (E42, E55, and K290). Based on MD simulation, coulomb energy and binding free energy analysis further reveal the importance of electrostatic interactions for catalytic activity of BfMAT, which could be an efficient strategy for improving catalytic performance of MATs.

6.
J Clin Anesth ; 90: 111211, 2023 11.
Article En | MEDLINE | ID: mdl-37480714

STUDY OBJECTIVE: The low central venous pressure (LCVP) technique is a key technique in hepatectomy, but its impact on acute kidney injury (AKI) is unclear. The purpose of this study was to explore risk factors (in particular LCVP time) for AKI following hepatectomy. DESIGN: A retrospective case-control study with propensity score matching. SETTING: Operating room. PATIENTS: A total of 1949 patients who underwent hepatectomy were studied. INTERVENTIONS: The patients were grouped with or without AKI within 7 days after surgery. Univariable and multivariable analyses were performed, including recognized intraoperative predictors. The final result is represented as a nomogram. MEASUREMENTS: Preoperative, intraoperative and postoperative data were collected. LCVP is monitored directly through a central venous catheter via the right internal jugular vein. MAIN RESULTS: AKI occurred in 148 patients (7.59%). Surgery time, minimum SBP, furosemide administration and norepinephrine were identified as independent risk factors. The area under the curve for the receiver operating characteristic curves was 0.726 (95% CI 0.668-0.783). CONCLUSION: Intraoperative parameters can be used to predict the probability of postoperative AKI. Although AKI increases the length of stay, it may not increase in-hospital mortality. LCVP time was not confirmed to be a risk factor for AKI.


Acute Kidney Injury , Hepatectomy , Humans , Propensity Score , Hepatectomy/adverse effects , Case-Control Studies , Nomograms , Retrospective Studies , Acute Kidney Injury/diagnosis , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology
7.
J Am Chem Soc ; 145(23): 12609-12616, 2023 06 14.
Article En | MEDLINE | ID: mdl-37277952

The effect of anions on the solubility and function of proteins was recognized in 1888 and is now termed the Hofmeister effect. Numerous synthetic receptors are known that overcome the associated anion recognition bias. However, we are unaware of a synthetic host being used to overcome Hofmeister effect perturbations to natural proteins. Here, we report a protonated small molecule cage complex that acts as an exo-receptor and displays non-Hofmeister solubility behavior, with only the chloride complex remaining soluble in aqueous media. This cage allows for the activity of lysozyme to be retained under conditions where anion-induced precipitation would otherwise cause it to be lost. To our knowledge, this is the first time a synthetic anion receptor is used to overcome the Hofmeister effect in a biological system.


Biomimetics , Proteins , Anions , Chlorides , Water
8.
Nat Commun ; 14(1): 3112, 2023 May 30.
Article En | MEDLINE | ID: mdl-37253741

The evolution of the chemical and pharmaceutical industry requires effective and less energy-intensive separation technologies. Engineering smart materials at a large scale with tunable properties for molecular separation is a challenging step to materialize this goal. Herein, we report thin film composite membranes prepared by the interfacial polymerization of porous organic cages (POCs) (RCC3 and tren cages). Ultrathin crosslinked polycage selective layers (thickness as low as 9.5 nm) are obtained with high permeance and strict molecular sieving for nanofiltration. A dual function is achieved by combining molecular separation and catalysis. This is demonstrated by impregnating the cages with highly catalytically active Pd nanoclusters ( ~ 0.7 nm). While the membrane promotes a precise molecular separation, its catalytic activity enables surface self-cleaning, by reacting with any potentially adsorbed dye and recovering the original performance. This strategy opens opportunities for the development of other smart membranes combining different functions and well-tailored abilities.

9.
Front Immunol ; 14: 1117310, 2023.
Article En | MEDLINE | ID: mdl-37063846

Mounting evidence indicates that inhibition of microglial activation and neuronal pyroptosis plays important roles in brain function recovery after subarachnoid hemorrhage (SAH). LDC7559 is a newly discovered gasdermin D (GSDMD) inhibitor. Previous studies have demonstrated that LDC7559 could inhibit microglial proliferation and pyroptosis. However, the beneficial effects of LDC7559 on SAH remain obscure. Based on this background, we investigated the potential role and the mechanism of LDC7559 on SAH-induced brain damage both in vivo and in vitro. The findings revealed that microglial activation and neuronal pyroptosis were evidently increased after SAH, which could be markedly suppressed by LDC7559 both in vivo and in vitro. Meanwhile, LDC7559 treatment reduced neuronal apoptosis and improved behavior function. Mechanistically, LDC7559 decreased the levels of GSDMD and cleaved GSDMD after SAH. In contrast, nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome activation by nigericin increased GSDMD-mediated pyroptosis and abated the beneficial effects of LDC7559 on SAH-induced brain damage. However, LDC7559 treatment did not significantly affect the expression of NLRP3 after SAH. Taken together, LDC7559 might suppress neuronal pyroptosis and microglial activation after SAH by inhibiting GSDMD, thereby promoting brain functional recovery.


Brain Injuries , Gasdermins , Subarachnoid Hemorrhage , Humans , Brain Injuries/metabolism , Inflammasomes/metabolism , Microglia/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Phosphate-Binding Proteins/metabolism , Pore Forming Cytotoxic Proteins/metabolism , Pyroptosis , Subarachnoid Hemorrhage/metabolism , Gasdermins/antagonists & inhibitors
10.
Front Immunol ; 14: 1105973, 2023.
Article En | MEDLINE | ID: mdl-36875102

Balancing microglia M1/M2 polarization is an effective therapeutic strategy for neuroinflammation after subarachnoid hemorrhage (SAH). Pleckstrin homology-like domain family A member 1 (PHLDA1) has been demonstrated to play a crucial role in immune response. However, the function roles of PHLDA1 in neuroinflammation and microglial polarization after SAH remain unclear. In this study, SAH mouse models were assigned to treat with scramble or PHLDA1 small interfering RNAs (siRNAs). We observed that PHLDA1 was significantly increased and mainly distributed in microglia after SAH. Concomitant with PHLDA1 activation, nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome expression in microglia was also evidently enhanced after SAH. In addition, PHLDA1 siRNA treatment significantly reduced microglia-mediated neuroinflammation by inhibiting M1 microglia and promoting M2 microglia polarization. Meanwhile, PHLDA1 deficiency reduced neuronal apoptosis and improved neurological outcomes after SAH. Further investigation revealed that PHLDA1 blockade suppressed the NLRP3 inflammasome signaling after SAH. In contrast, NLRP3 inflammasome activator nigericin abated the beneficial effects of PHLDA1 deficiency against SAH by promoting microglial polarization to M1 phenotype. In all, we proposed that PHLDA1 blockade might ameliorate SAH-induced brain injury by balancing microglia M1/M2 polarization via suppression of NLRP3 inflammasome signaling. Targeting PHLDA1 might be a feasible strategy for treating SAH.


Inflammasomes , Subarachnoid Hemorrhage , Animals , Mice , Microglia , NLR Family, Pyrin Domain-Containing 3 Protein , Neuroinflammatory Diseases , RNA, Small Interfering
11.
Oxid Med Cell Longev ; 2022: 2242833, 2022.
Article En | MEDLINE | ID: mdl-36439686

Subarachnoid hemorrhage (SAH) as a devastating neurological disorder is closely related to heightened oxidative insults and neuroinflammatory injury. Pinocembrin, a bioflavonoid, exhibits different biological functions, such as immunomodulatory, anti-inflammatory, antioxidative, and cerebroprotective activities. Herein, we examined the protective effects and molecular mechanisms of pinocembrin in a murine model of SAH. Using an endovascular perforation model in rats, pinocembrin significantly mitigated SAH-induced neuronal tissue damage, including inflammatory injury and free-radical insults. Meanwhile, pinocembrin improved behavior function and reduced neuronal apoptosis. We also revealed that sirtuin-1 (SIRT1) activation was significantly enhanced by pinocembrin. In addition, pinocembrin treatment evidently enhanced peroxisome proliferator-activated receptor-γ coactivator expression and suppressed ac-nuclear factor-kappa B levels. In contrast, EX-527, a selective SIRT1 inhibitor, blunted the protective effects of pinocembrin against SAH by suppressing SIRT1-mediated signaling. These results suggested that the cerebroprotective actions of pinocembrin after SAH were through SIRT1-dependent pathway, suggesting the potential application of pinocembrin for the treatment of SAH.


Brain Injuries , Subarachnoid Hemorrhage , Rats , Animals , Mice , Sirtuin 1/metabolism , Subarachnoid Hemorrhage/drug therapy , Subarachnoid Hemorrhage/metabolism , Rats, Sprague-Dawley , Brain Injuries/drug therapy , Brain Injuries/metabolism
12.
J Med Chem ; 65(22): 15140-15164, 2022 11 24.
Article En | MEDLINE | ID: mdl-36355693

MET alterations have been validated as a driven factor in NSCLC and gastric cancers. The c-Met inhibitors, capmatinib, tepotinib, and savolitinib, are only approved for the treatment of NSCLC harboring exon 14 skipping mutant MET. We used a molecular hybridization in conjunction with macrocyclization strategy for structural optimization to obtain a series of 2-(2-(quinolin-6-yl)ethyl)pyridazin-3(2H)-one derivatives as new c-Met inhibitors. One of the macrocyclic compounds, D6808, potently inhibited c-Met kinase and MET-amplified Hs746T gastric cancer cells with IC50 values of 2.9 and 0.7 nM, respectively. It also strongly suppressed Ba/F3-Tpr-Met cells harboring resistance-relevant mutations (F1200L/M1250T/H1094Y/F1200I/L1195V) with IC50 values of 4.2, 3.2, 1.0, 39.0, and 33.4 nM, respectively. Furthermore, D6808 exhibited extraordinary target specificity in a Kinome profiling against 373 wild-type kinases and served as a promising macrocycle-based compound for further anticancer drug development.


Lung Neoplasms , Macrocyclic Compounds , Proto-Oncogene Proteins c-met , Stomach Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Mutation , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins c-met/antagonists & inhibitors , Proto-Oncogene Proteins c-met/genetics , Stomach Neoplasms/drug therapy , Stomach Neoplasms/genetics , Macrocyclic Compounds/pharmacology , Macrocyclic Compounds/therapeutic use
13.
Genet Test Mol Biomarkers ; 26(7-8): 360-374, 2022.
Article En | MEDLINE | ID: mdl-35920832

Background: The importance of promoter methylation in non-small cell lung cancers (NSCLC) remains to be understood. Thus, we aimed to determine the diagnostic and prognostic value of the methylation of the endothelial PAS domain containing protein-1 (EPAS1) promoter in NSCLC. Methods: EPAS1 promoter methylation levels were quantitated by methylation-specific PCR. Further, we evaluated the expression, promoter methylation, prognostic value, and impact on immune cell infiltration of EPAS1 by analyzing the TCGA database using web-based bioinformatics tools including GEPIA, UALCAN and MethSurv. Results: Our results demonstrated that promoter methylation of EPAS1 downregulated its expression in NSCLC tissues. Additionally, an AUC value of 0.772 indicated that the methylation of the EPAS1 promoter is a potential diagnostic marker for NSCLC. A Kaplan-Meier analysis demonstrated that high methylation levels of CpG sites in the EPAS1 promoter were indicative of poorer overall survival. Further, EPAS1 expression levels were highly correlated with the infiltration of several types of immune cells, including γδ T cells, T follicular helper cells, CD8+ T cells, and CD4+ T-cells. Conclusion: Collectively, our findings suggest that methylation analyses of the EPAS1 promoter could be used as a prognostic biomarker for NSCLC and that EPAS1 potentially plays an important role in immune cell infiltration in NSCLC.


Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Biomarkers , DNA Methylation , Humans , Prognosis
14.
Entropy (Basel) ; 24(7)2022 Jul 07.
Article En | MEDLINE | ID: mdl-35885173

Based on the time series of articles obtained from the literature, we propose three analysis methods to deeply examine the characteristics of these articles. This method can be used to analyze the construction and development of various disciplines in institutions, and to explore the features of the publications in important periodicals in the disciplines. By defining the concepts and methods relevant to research and discipline innovation, we propose three methods for analyzing the characteristics of agency publications: numerical distribution, trend, and correlation network analyses. The time series of the issuance of articles in 30 important journals in the field of management sciences were taken, and the new analysis methods were used to discover some valuable results. The results showed that by using the proposed methods to analyze the characteristics of institution publications, not only did we find similar levels of discipline development or similar trends in institutions, achieving a more reasonable division of the academic levels, but we also determined the preferences of the journals selected by the institutions, which provides a reference for subject construction and development.

15.
Oxid Med Cell Longev ; 2022: 3099409, 2022.
Article En | MEDLINE | ID: mdl-35693703

Subarachnoid hemorrhage (SAH) is an acute cerebral vascular disease featured by oxidative insults and neuroinflammation. Cycloastragenol (CAG), the major active component of Astragalus radix, has a wide range of biological functions. However, the potential beneficial effects and the underlying molecular mechanisms of CAG on SAH remain obscure. In the current study, the cerebroprotective effects and mechanism of CAG on SAH were evaluated both in vivo and in vitro. Our results indicated that CAG significantly suppressed SAH-triggered oxidative insults, inflammatory mediators production, microglia activation, and the neutrophil infiltration in the brain. In addition, CAG improved neurological function and ameliorated neuronal apoptosis and degeneration after SAH. In vitro results also revealed the therapeutic effects of CAG on neurons and microglia co-culture system. Mechanistically, CAG treatment upregulated sirtuin 1 (SIRT1) expression, inhibited the levels of FoxO1, nuclear factor-kappa B, and p53 acetylation, and suppressed the subsequent oxidative, inflammatory, and apoptotic pathways. In contrast, inhibiting SIRT1 by pretreatment with Ex527 abrogated the protective actions of CAG both in vivo and in vitro models of SAH. Collectively, our findings indicated that CAG could be a promising and effective drug candidate for SAH.


Neuroprotective Agents , Subarachnoid Hemorrhage , Animals , Neuroinflammatory Diseases , Neuroprotective Agents/pharmacology , Oxidative Stress , Rats , Rats, Sprague-Dawley , Sapogenins , Signal Transduction , Sirtuin 1/metabolism , Subarachnoid Hemorrhage/drug therapy , Subarachnoid Hemorrhage/metabolism
16.
Sci Rep ; 12(1): 8230, 2022 05 17.
Article En | MEDLINE | ID: mdl-35581376

Lung adenocarcinoma is one of the most common malignant tumors worldwide. The purpose of this study was to construct a stable immune gene signature for prediction of prognosis (IGSPP) and response to immune checkpoint inhibitors (ICIs) therapy in LUAD patients. Five genes were screened by weighted gene coexpression network analysis, Cox regression and LASSO regression analyses and were used to construct the IGSPP. The survival rate of the IGSPP low-risk group was higher than that of the IGSPP high-risk group. Multivariate Cox regression analysis showed that IGSPP could be used as an independent prognostic factor for the overall survival of LUAD patients. IGSPP genes were enriched in cell cycle pathways. IGSPP gene mutation rates were higher in the high-risk group. CD4 memory-activated T cells, M0 and M1 macrophages had higher infiltration abundance in the high-risk group, which was associated with poor overall survival. In contrast, the abundance of resting CD4 memory T cells, monocytes, resting dendritic cells and resting mast cells associated with a better prognosis was higher in the low-risk group. TIDE scores and the expressions of different immune checkpoints showed that patients in the high-risk IGSPP group benefited more from ICIs treatment. In short, an IGSPP of LUAD was constructed and characterized. It could be used to predict the prognosis and benefits of ICIs treatment in LUAD patients.


Adenocarcinoma of Lung , Lung Neoplasms , Adenocarcinoma of Lung/drug therapy , Adenocarcinoma of Lung/genetics , Biomarkers, Tumor/genetics , Gene Expression Regulation, Neoplastic , Humans , Immunotherapy , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Prognosis
17.
Cell Tissue Res ; 385(3): 639-658, 2021 Sep.
Article En | MEDLINE | ID: mdl-33966092

In this study, effects of combining optimized tissue engineering bone (TEB) implantation with heel-strike like mechanical loading to repair segmental bone defect in New Zealand rabbits were investigated. Physiological characteristics of bone marrow mesenchymal stem cells (BMMSCs), compact bone cells (CBCs), and bone marrow and compact bone coculture cells (BMMSC-CBCs) were compared to select the optimal seed cells for optimized TEB construction. Rabbits with segmental bone defects were treated in different ways (cancellous bone scaffold for group A, cancellous bone scaffold and mechanical loading for group B, optimized TEB for group C, optimized TEB and mechanical loading for group D, n = 4), and the bone repair were compared. BMMSC-CBCs showed better proliferation capacity than CBCs (p < 0.01) and stronger osteogenic differentiation ability than BMMSCs (p < 0.05). Heel-strike like mechanical loading improved proliferation and osteogenic differentiation ability and expression levels of TGFß1 as well as BMP2 of seed cells in vitro (p < 0.05). At week 12 post-operation, group D showed the best bone repair, followed by groups B and C, while group A finished last (p < 0.05). During week 4 to 12 post-operation, group D peaked in terms of expression levels of TGFß1, BMP2, and OCN, followed by groups B and C, while group A finished last (p < 0.05). Thus, BMMSC-CBCs showed good proliferation and osteogenic differentiation ability, and they were thought to be better as seed cells than BMMSCs and CBCs. The optimized TEB implantation combined with heel-strike like mechanical loading had a synergistic effect on bone defect healing, and enhanced expression of TGFß1 and BMP2 played an important role in this process.


Bone and Bones/pathology , Tissue Engineering/methods , Animals , Rabbits
18.
J Orthop Surg Res ; 15(1): 240, 2020 Jul 01.
Article En | MEDLINE | ID: mdl-32611361

BACKGROUND: Alendronate (AL) is the most widely used bisphosphonate in the treatment of osteoporosis (OP). However, the role of circular RNAs (circRNAs) in the treatment of OP with AL remains unclear. METHODS: In this study, we showed that osteoclast (OC) precursors (OPCSs) could be induced into OCs with macrophage colony-stimulating factor (MCSF) and receptor activator of nuclear factor-κB ligand (RANKL) treatment. Subsequently, the OCs were treated with AL. OC differentiation-related biomarkers including RANK, tartrate-resistant acid phosphatase (TRAP), and cathepsin K (CTSK) were analyzed with TRAP staining, quantitative real-time (qPCR), and western blotting. Differentially expressed circRNAs (DECs) were identified among the OPCS, OC, and OC + AL groups. In addition, the expression levels of 10 DECs related to OC differentiation were verified by qPCR. RESULTS: TRAP staining showed that MCSF and RANKL treatment effectively induced OPCSs to differentiate into OCs. In addition, qPCR and western blot analysis revealed that the three biomarkers of OC (RANK, TRAP, and CTSK) were expressed significantly more in the OC group than those in the OPCS group. In contrast, the mRNA and protein expression levels of these three biomarkers decreased significantly in OCs treated with AL compared with those non-treated OCs. GO analysis of the DECs in the OPCS group vs. the OC group revealed that their functions were mainly related to cell, cell part, binding, and single-organism terms. KEGG analysis of the top 20 DECs in a comparison between the OPCS and OC groups showed that genes involved in mitogen-activated protein kinase signaling were the most common. Results of functional analyses of DECs in an OC vs. OC + AL comparison were similar to those in the OPCS vs. OC comparison. Finally, qPCR showed that, in the OC + AL vs. OC group comparison, the expression levels of seven and three DECs significantly decreased and increased, respectively. CONCLUSIONS: Having successfully induced OPCSs to differentiate into OCs, we showed that AL suppresses the differentiation of OPCS into OC and that 10 DECs were involved in the regulation of this process. This indicates that these DECs might be important to the treatment of OP.


Alendronate/pharmacology , Bone Density Conservation Agents/pharmacology , Cell Differentiation/drug effects , Cell Differentiation/genetics , Gene Expression , Osteoclasts/physiology , RNA, Circular/genetics , RNA, Circular/physiology , Depression, Chemical , Humans , Macrophage Colony-Stimulating Factor/pharmacology , RANK Ligand/pharmacology , RNA, Circular/metabolism , THP-1 Cells
19.
Sci Total Environ ; 739: 139899, 2020 Oct 15.
Article En | MEDLINE | ID: mdl-32540659

Preparing cities for sea-level rise is one of the critical challenges of the twenty-first century. Extreme weather events, natural hazards, and the failure of climate mitigation and adaptation are substantial risks. These risks are especially significant in fast-urbanizing deltas, such as the Pearl River Delta in China, because the conflict between urbanization and flooding caused by climate change will be more significant in the future. This paper elaborates on an approach that employs a future land-use simulation (FLUS) model for scenario-based 100-year coastal flood risk assessment. Storylines of future scenarios from the Intergovernmental Panel on Climate Change (IPCC), called the representative concentration pathways (RCPs) 2.6 and 8.5, are utilized in the present study. The Guangzhou Metropolitan Area (GMA) is used as a case study to explore the probable implications of future land-use changes due to the ongoing urbanization process in the region in relation to projected environmental changes (sea-level rise, storm surge, and land subsidence). The results indicate that there will be a significant increase in flooded urban areas in the future. The simulations show that, as compared to 2015, the built-up area in the GMA will increase by 246.57 km2 in 2030 and 513.03 km2 in 2050. As compared to 2015, the flooding of built-up areas in 2030 and 2050 will respectively increase by about 31.32 km2 and 48.49 km2 under the RCP 8.5 scenario. It is also found that, as the main driving factor, urbanization will increase the flooding of built-up areas in Guangzhou in 2030 and 2050 by about 1.9 km2 and 5.9 km2, respectively, under the RCP 2.6 scenario as compared to 2015. Additionally, due to environmental changes, the flooding of built-up areas in Guangzhou will increase by about 24.2 km2 and 26.8 km2, respectively, under the RCP 8.5 scenario by 2030 and 2050 as compared to 2015. This increasing flood risk information determined by the simulation provides insight into the spatial distribution of future flood-prone urban areas to facilitate the development and prioritization of flood mitigation measures at the most critical locations in the region.

20.
Chem Commun (Camb) ; 56(12): 1863-1866, 2020 Feb 11.
Article En | MEDLINE | ID: mdl-31950934

Sign inversions of circularly polarized luminescence (CPL) for the hydro[5]helicene and [5]helicene derivatives were discovered and studied experimentally and theoretically. The inverted CPL signs from the hydro[5]helicene to [5]helicene derivatives were realized by one-step oxidation. The introduction of triphenylamine (TPA) subunits into the helical skeletons also led to the sign inversion of CPL only when there existed an enhanced intramolecular charge-transfer state with a small enough Egap.

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