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Can preoperative or perioperative intervention reduce the risk of recurrence of endometriosis caused by either incomplete excision or spillage and dissemination? A mouse model of endometriosis recurrence caused by spillage and dissemination was first established using 24 female Balb/c mice. The spillage and dissemination model was used to test the efficacy of preoperative use of ketorolac, perioperative use of aprepitant and combined use of propranolol and andrographolide in a prospective, randomized mouse experiment involving 75 mice. The efficacy of these preoperative and perioperative interventions in a mouse recurrence model caused by incomplete excision was also tested using 72 mice. In all experiments, the baseline body weight and hotplate latency of all mice were measured and recorded before the induction of endometriosis, before the primary surgery and before sacrifice. In addition, all lesions were excised, weighed and processed for quantification and immunohistochemistry analysis of E-cadherin, α-SMA, VEGF, ADRB2 and putative markers of recurrence PR-B, p-p65, as well as Masson trichrome staining. All interventions substantially and significantly suppressed the outgrowth of endometriotic lesions and reduced the risk of recurrence caused by either spillage and dissemination or incomplete excision (P = 0.0007 to 0.042). These interventions also significantly attenuated the generalized hyperalgesia, inhibited the staining of α-SMA, p-p65, VEGF and ADRB2 but increased staining of E-cadherin and PR-B, resulting in reduced fibrosis. Given the excellent safety profiles of these drugs, these data strongly suggest that preoperative and perioperative intervention may potentially reduce the risk of endometriosis recurrence effectively. [ABSTRACT FROM AUTHOR]

[Display omitted] • The various hydrogen-bonded complexes involving the imidazol-2‑ylidene and its heavier congeners are investigated and compared. • Two types of hydrogen-bonded geometries can be located on the basis of the molecular electrostatic potential surfaces. • The relaxed potential energy surface scans were performed for some selected complexes. The hydrogen-bonded complexes formed between the imidazol-2‑ylidene and its heavier congeners C 2 H 4 N 2 T: (T = C, Si, Ge, Sn, Pb) and the three selected electron acceptors (HF, HCN and C 2 H 2) have been optimized at the aug-cc-pVTZ level, and the nature of these complexes has been investigated by natural bond orbital (NBO), atoms in molecules (AIM) and energy decomposition analyses. The complexes can be classified into type-A structure and type-B structure according to the location of the electron acceptors. The electron acceptors are around T atoms of C 2 H 4 N 2 T: for the type-A complexes, and the electron acceptors are above the five-membered ring (π-system) of C 2 H 4 N 2 T: for the type-B complexes. The electron-donating ability of T atoms becomes weaker, and that of π-systems becomes stronger when T atoms become heavier for C 2 H 4 N 2 T:, which is consistent with the molecular electrostatic potentials (MEP) maps of C 2 H 4 N 2 T:. For a given C 2 H 4 N 2 T:, the E int values of the type-A complexes go in the order HF > HCN > C 2 H 2 , and the E int values of the type-B complexes go in the order HF ≈ HCN > C 2 H 2. The contribution of electrostatic energy to the interaction energy of complexes becomes smaller for the type-A complexes when the T atoms become heavier. The interaction energies are dominated by the electrostatic energies for all the type-B complexes involving HF, and the interaction energies are dominated by the dispersion energies for most type-B complexes involving HCN and C 2 H 2. The relaxed potential energy surface scans were performed for some selected complexes involving HF and HCN to examine the difference in binding behavior between HF and HCN. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic highlighted the need for decision-support tools to help cities become more resilient to infectious diseases. Through urban design and planning, non-pharmaceutical interventions can be enabled, impelling behaviour change and facilitating the construction of lower risk buildings and public spaces. Computational tools, including computer simulation, statistical models, and artificial intelligence, have been used to support responses to the current pandemic as well as to the spread of previous infectious diseases. Our multidisciplinary research group systematically reviewed state-of-the-art literature to propose a toolkit that employs computational modelling for various interventions and urban design processes. We selected 109 out of 8,737 studies retrieved from databases and analysed them based on the pathogen type, transmission mode and phase, design intervention and process, as well as modelling methodology (method, goal, motivation, focus, and indication to urban design). We also explored the relationship between infectious disease and urban design, as well as computational modelling support, including specific models and parameters. The proposed toolkit will help designers, planners, and computer modellers to select relevant approaches for evaluating design decisions depending on the target disease, geographic context, design stages, and spatial and temporal scales. The findings herein can be regarded as stand-alone tools, particularly for fighting against COVID-19, or be incorporated into broader frameworks to help cities become more resilient to future disasters. • We propose a toolkit for designers to select design interventions and modelling tools to improve resilience against COVID or future pandemics. • For a systemic literature review, this study analyses 109 papers using computational models. • We figure out the pathogen types, transmission modes and phases, and map the design interventions as well as modelling methodologies used. • The relationship between different types of infectious diseases, design interventions, and the supports of computer models is examined. • The toolkit can help cities become more resilient to future uncertain disasters in pursuit of creating healthy and resilient cities. [ABSTRACT FROM AUTHOR]

Poly (lactic-co-glycolic acid) (PLGA) and poly- l -lactate acid (PLLA) are biodegradable polymers widely utilized as scaffold materials for cartilage tissue engineering. Their acid degradation products have been widely recognized as being detrimental to cell function. However, the biological effects of lactate, rather than lactic acid, on chondrocytes have never been investigated. This is the major focus of this study. The amounts of lactate and the pH value (acid) of the PLGA and PLLA degradation medium were measured. The effects of PLGA and PLLA degradation medium, as well as different lactate concentrations and timing of exposure on chondrocytes proliferation and cartilage-specific matrix synthesis were investigated by various techniques including global gene expression profiling and gene knockdown experiments. It was shown that PLGA and PLLA degradation medium differentially regulated chondrocyte proliferation and matrix synthesis. Acidic pH caused by lactate inhibited chondrocyte proliferation and matrix synthesis. The effect of lactate on chondrocyte matrix synthesis was both time and dose dependent. A lactate concentration of 100 mM and exposure duration of 8 h significantly enhanced matrix synthesis. Lactate could also inhibit expression of cartilage matrix degradation genes in osteoarthritic chondrocytes, such as the major aggrecanase ADAMTS5, whilst promoting matrix synthesis simultaneously. Pulsed addition of lactate was shown to be more efficient in promoting COL2A1 expression. Global gene expression data and gene knock down experiments demonstrated that lactate promote matrix synthesis through up-regulation of HIF1A. These observed differential biological effects of lactate on chondrocytes would have implications for the future design of polymeric cartilage scaffolds. Statement of Significance Lactic acid is a widely used substrate for polymers synthesis, PLGA and PLLA in particular. Although physical and biological modifications have been made on these polymers to make them be better cartilage scaffolds, little concern has been given on the biological effect of lactic acid, the main degradation product of these polymers, on chondrocytes. Our finding illustrates the differential biological function of lactate and acid on chondrocytes matrix synthesis. These results can facilitate future design of lactate polymers-based cartilage scaffolds [ABSTRACT FROM AUTHOR]

Highlights: [•] The anion-binding ability of FH2As is stronger than that of FH2P. [•] The binding strength is in the sequence of SO4 2− >F− >Cl− >NO3 − >Br− >I−. [•] The anion-binding strength of pnicogen bonding is comparable to that of hydrogen and halogen bonding. [•] The anion-binding ability of pnicogen bonding can be strengthened through multiple receptor–anion interactions. [Copyright &y& Elsevier]

Abstract: Background: Paeonia lactiflora root (baishao in Chinese) is a commonly used herb in TCM. Research has shown baishao to have positive pharmacological actions, including, particularly, anti-inflammatory properties. In this paper we studied the influence of baishao extract on cAMP-phosphodiesterase (PDE) activity and related anti-inflammatory action to identify new pharmacologic action for its clinically widespread use. Methods: PDE activity was calculated by cAMP change examined with HPLC, respiratory burst of neutrophils was detected with method of cytochrome C reduction, elastase release was indicated with the substrate reduction, rat arthritis model was caused by complete Freund''s adjuvant, mouse capillary permeability model was made by acetic acid, and chemical constituents of baishao extract was identified by HPLC, mass spectroscopy and NMR spectrum. Results: Baishao extract had significant inhibition on cAMP-PDE activity (p <0.01), had dose dependent restraint on neutrophils respiratory burst (p <0.001), had inhibition at low concentration and promotion at high concentration on elastase release (p <0.05), and had obvious restraint on local inflammation of animal model (p <0.01). Analysis of HPLC, mass spectroscopy and NMR spectrum showed baishao extract mainly had five components (identified as gallic acid, paeoniflorin sulfonate, albiflorin, paeoniflorin and benzoic acid), among which gallic acid had the largest inhibition on cAMP-PDE activity. Conclusion: The anti-inflammatory effects of baishao may be mediated, at least in part, through its gallic acid content, and this effect may be regulated in part by an inhibition on cAMP-PDE. [Copyright &y& Elsevier]

Abstract Nanoparticles are widely developed and utilized in the pharmaceutical and medicine industry, as they can be easily distributed and infiltrated throughout the whole body once administered; however, the body wide effect of nanoparticles infiltration is still unclear. In this study, we developed a new strategy of Nano Genome Altas (NGA) of multi-tissues to study the acute Body-wide-Organ-Transcriptomic response to nanomaterials. Hydroxyapatite(HA)-Nanoparticles (HANPs) was applied in this study as an example both in vitro and in vivo. Results showed that the effect of HANPs is organ specific and mainly related to immune responses in spleen and muscle, proliferation in spleen and bone, stress and apoptosis in spleen and PBMC, ion transport in spleen, kidney, and liver tissues, metabolism in heart, spleen, and muscle, as well as tissue specific epigenetic and signal pathways. In vitro experiments also confirmed that the effects of HANPs on different tissue stem cells were tissue specific. Thus, Nano Genome Altas can provide a body-wide view of the transcriptomic response of multiple organs and tissue specific stem cells to HANPs; it could also be useful for optimizing HANPs and other nano-delivery systems. [ABSTRACT FROM AUTHOR]

The mobility of phosphorus (P) induced by sediment resuspension have been examined in a circulated flume. During the flume run, the water level and velocity were monitored, and water samples were taken for measurement of sediment and P concentrations. Peak values of both the P and sediment concentrations existed at x = 4 m, and then decreased slightly along the flume due to deposition. A faster P release was observed for coarser sediment, while a more sustained P release for finer sediment. Combining with the measured data from Yangtze River and sorption experiment, the relation between the load of total P ( L TP ) and sediment load ( Q s ) was estimated, and the expressions of distribution coefficient K d and the concentration of particulate P (PP) were obtained. This study established a bridge between the small-scale sorption experiment and the field observation of natural scale, providing references for the management of contaminated sediment in natural rivers. [ABSTRACT FROM AUTHOR]

Abstract: This work aims to develop curcumin (Cur) loaded biodegradable self-assembled polymeric micelles (Cur-M) to overcome poor water solubility of Cur and to meet the requirement of intravenous administration. Cur-M were prepared by solid dispersion method, which was simple and easy to scale up. Cur-M had a small particle size of 28.2±1.8nm and polydisperse index (PDI) of 0.136±0.050, and drug loading and encapsulation efficiency of Cur-M were 14.84±0.11% and 98.91±0.70%, respectively. Besides, in vitro release profile showed a significant difference between rapid release of free Cur and much slower and sustained release of Cur-M. Cytotoxicity study showed that the encapsulated Cur remained its potent anti-tumor effect. Furthermore, Cur-M were more effective in inhibiting tumor growth and spontaneous pulmonary metastasis in subcutaneous 4T1 breast tumor model, and prolonged survival of tumor-bearing mice. In addition, immunofluorescent and immunohistochemical studies also showed that tumors of Cur-M-treated mice had more apoptosis cells, fewer microvessels, and fewer proliferation-positive cells. In conclusion, polymeric micelles encapsulating Cur were developed with enhanced anti-tumor and anti-metastasis activity on breast tumor, and Cur-M is excellent water-based formulation of Cur which may serve as a candidate for breast cancer therapy. [Copyright &y& Elsevier]

Abstract: For developing aqueous formulation and improving anti-tumor activity of curcumin (Cur), we prepared Cur encapsulated MPEG-PCL micelles by solid dispersion method without using any surfactants or toxic organic solvent. Cur micelles could be lyophilized into powder form without any cryoprotector or excipient, and the re-dissolved Cur micelles are homogenous and stable. Molecular modeling study suggested that Cur tended to interact with PCL serving as a core embraced by PEG as a shell. After Cur was encapsulated into polymeric micelles, cytotoxicity and cellular uptake were both increased. Cur micelles had a stronger inhibitory effect on proliferation, migration, invasion, and tube formation of HUVECs than free Cur. Besides, Cur micelles showed a sustained in vitro release behavior and slow extravasation from blood vessels in transgenic zebrafish model. Embryonic angiogenesis and tumor-induced angiogenesis were both dramatically inhibited by Cur micelles in transgenic zebrafish model. Furthermore, Cur micelles were more effective in inhibiting tumor growth and prolonged survival in both subcutaneous and pulmonary metastatic LL/2 tumor models. In pharmacokinetic and tissue distribution studies, Cur micelles showed higher concentration and longer retention time in plasma and tumors. Our findings suggested that Cur micelles may have promising applications in pulmonary carcinoma therapy. [Copyright &y& Elsevier]

Changes in the stiffness of chondrocyte extracellular matrix (ECM) are involved in the pathological progression of osteoarthritis (OA). However, the downstream responses of cartilage ECM stiffness are still unclear. YAP (Yes-associated protein) has been extensively studied as a mechanotransducer, we thus hypothesized that by targeting the downstream molecule activity of ECM stiffness could maintain chondrocyte phenotype and prevent cartilage degeneration in OA. Here, we showed that human cartilage matrix stiffened during pathological progression of OA, and the chondrocyte YAP activity was associated with ECM stiffness. We then mimicked the physiological and pathological stiffness of human cartilage by using PDMS-based substrates, and found that YAP was activated in chondrocytes seeded on stiff substrate, gradually losing their phenotype. In addition, it was observed that YAP was also significantly activated in mice OA development, and conditional knockout (cKO) of YAP in mice preserved collagen II expression and protected cartilage from degeneration in the OA model. Furthermore, intra-articular injection of YAP-selective inhibitor, Verteporfin, significantly maintained cartilage homeostasis in mice OA model. This study indicates that the application of mechanotransducer-targeted drugs could be a potential therapeutic approach for cartilage repair in OA. [ABSTRACT FROM AUTHOR]