Optimization of a Decellularization/Recellularization Strategy for Transplantable Bioengineered Liver

The liver is a complex organ that requires constant perfusion for the delivery of nutrients and oxygen and the removal of waste in order to survive. Efforts to recreate or mimic the liver microstructure via a ground-up approach are essential for liver tissue engineering. A decellularization/recellularization strategy is one of the approaches aiming at the possibility of producing a fully functional organ with in vitro-developed construction for clinical applications to replace failed livers, such as end-stage liver disease (ESLD). However, the complexity of the liver microarchitecture along with the limited suitable hepatic component, such as the optimization of the extracellular matrix (ECM) of the biomaterials, the selection of the seed cells, and development of the liver-specific three-dimensional (3D) niche settings, pose numerous challenges. In this chapter, we have provided a comprehensive outlook on how the physiological, pathological, and spatiotemporal aspects of these drawbacks can be turned into the current challenges in the field, and put forward a few techniques with the potential to address these challenges, mainly focusing on a decellularization-based liver regeneration strategy. We hypothesize the primary concepts necessary for constructing tissue-engineered liver organs based on either an intact (from a naïve liver) or a partial (from a pretreated liver) structure via simulating the natural development and regenerative processes

Research on Comprehensive Evaluation of Electricity Market Risk Based on Subjective and Objective Weighting

[Introduction] With the emphasis and promotion of the electricity market system construction by the government, the electricity market is constantly growing towards a deeper and more unified direction. In order to promote the electricity market construction, the influence factors of the electricity market risk and its evaluation remain to be studied further. [Method] Based on the consideration of the whole cycle of electricity market trading, this paper took pre-trade risk, during-trade risk, and post-trade riskas the entry points, integrated the existing risks in each stage of electricity market, and established the risk evaluation index system for electricity market. Based on the thought of subjective and objective weighting, analytic hierarchy process (AHP) and entropy weight method were used to assign weights to the index system respectively, and fuzzy comprehensive evaluation (FCE) was adopted to evaluate the comprehensive risk level of the electricity market. [Result] The rationality, comprehensiveness and validity of the proposed model are verified through the analysis of the calculation examples of different electricity markets. [Conclusion] The model eatablished in this paper can conduct a comprehensive risk evaluation for the electricity market, and provide a theoretical reference for the construction of the risk system of the electricity market and its future development direction

Performance evaluation of heating tower heat pump systems over the world

Heating tower heat pumps (HTHPs) are proposed as an alternative to the conventional heat pumps. However, lacking performance evaluation of the HTHPs in different regions limits their applications worldwide. To address this issue, this paper carries out a large-scale comprehensive performance evaluation of the HTHPs in 869 typical locations. These locations are in the warm, mixed, and cool climate zones, where buildings need both cooling and heating supply. Seven performance indices are adopted, including the annual coefficient of performance (COP), COP in cooling season, COP in heating season, regeneration ratio, number of unsatisfactory hours, matching degree of heat pump, and matching degree of heating tower. The performance evaluation of the HTHPs is conducted by the processes of location selection, building load calculation, system sizing, simulation, and evaluation. The results show that the HTHPs have excellent performance in the warm and mixed climate zones, where the average annual COPs are 4.67 and 3.68, respectively. The HTHPs are also applicable in the cool climate zone with an average annual COP of 3.11. The distributions of all the performance indices are presented through color maps, and the results are analyzed considering the air temperature and relative humidity data of the locations.</p

Tenofovir alafenamide versus entecavir for treating hepatitis B virus-related acute-on-chronic liver failure: real-world study

Background and aimsReal-world data regarding hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients receiving tenofovir alafenamide (TAF) as an antiviral drug are limited. Hence, we evaluated the efficacy and kidney safety of TAF among this population.MethodsA total of 272 HBV-related ACLF patients hospitalized at Xiangya Hospital of Central South University were enrolled in this retrospective research. All patients received antiviral therapy with TAF (n = 100) or ETV (n = 172) and comprehensive medical treatments.ResultsThrough 1:1 propensity score matching, 100 patients were finally included in each group. At week 48, the survival rates without transplantation of the TAF group and ETV group were 76.00 and 58.00%, separately (P = 0.007). After 4 weeks of treatment, the TAF treatment group exhibited a significantly decline in HBV DNA viral load (P = 0.029). The mean estimated glomerular filtration rate was apparently improved in the TAF group compared with the ETV group (TAF 5.98 ± 14.46 vs. ETV 1.18 ± 18.07 ml/min/1.73 m2) (P &lt; 0.05). There were 6 patients in TAF group and 21 patients in ETV group with chronic kidney disease (CKD) stage progression ≥ 1. By contrast, the ETV treatment group has a greater risk of renal function progression in CKD 1 stage patients (P &lt; 0.05).ConclusionThis real-world clinical study showed that TAF is more effective than ETV in reducing viral load and improving survival rate in HBV-ACLF patients and the risk of renal function decline is lower.Clinical trial registrationhttps://ClinicalTrials.gov, identifier NCT05453448

Norepinephrine stimulates mobilization of endothelial progenitor cells after limb ischemia.

OBJECTIVE: During several pathological processes such as cancer progression, thermal injury, wound healing and hindlimb ischemia, the mobilization of endothelial progenitor cells (EPCs) mobilization was enhanced with an increase of sympathetic nerve activity and norepinephrine (NE) secretion, yet the cellular and molecular mechanisms involved in the effects of NE on EPCs has less been investigated. METHODS AND RESULTS: EPCs from BMs, peripheral circulation and spleens, the VEGF concentration in BM, skeletal muscle, peripheral circulation and spleen and angiogenesis in ischemic gastrocnemius were quantified in mice with hindlimbs ischemia. Systemic treatment of NE significantly increased EPCs number in BM, peripheral circulation and spleen, VEGF concentration in BM and skeletal muscle and angiogenesis in ischemic gastrocnemius in mice with hind limb ischemia, but did not affair VEGF concentration in peripheral circulation and spleen. EPCs isolated from healthy adults were cultured with NE in vitro to evaluate proliferation potential, migration capacity and phosphorylations of Akt and eNOS signal moleculars. Treatment of NE induced a significant increase in number of EPCs in the S-phase in a dose-dependent manner, as well as migrative activity of EPCs in vitro (p<0.05). The co-treatment of Phentolamine, I127, LY294002 and L-NAME with NE blocked the effects of NE on EPCs proliferation and migration. Treatment with NE significantly increased phosphorylation of Akt and eNOS of EPCs. Addition of phentolamine and I127 attenuated the activation of Akt/eNOS pathway, but metoprolol could not. Pretreatment of mice with either Phentolamine or I127 significantly attenuated the effects of NE on EPCs in vivo, VEGF concentration in BM, skeletal muscle and angiogenesis in ischemic gastrocnemius, but Metoprolol did not. CONCLUSION: These results unravel that sympathetic nervous system regulate EPCs mobilization and their pro-angiogenic capacity via α adrenoceptor, β 2 adrenoceptor and meanwhile Akt/eNOS signaling pathway

Effect of Vacancies on Dynamic Response and Spallation in Single-Crystal Magnesium by Molecular Dynamic Simulation

The effect of vacancies on dynamic response and spallation in single-crystal magnesium (Mg) is investigated by nonequilibrium molecular dynamics simulations. The initial vacancy concentration (Cv) ranges from 0% to 2.0%, and the shock loading is applied along [0001] and [10&ndash;10] directions. The simulation results show that the effects of vacancy defects are strongly dependent on the shock directions. For shock along the [0001] direction, vacancy defects have a negligible effect on compression-induced plasticity, but play a role in increasing spall damage. In contrast, for shock along the [10&ndash;10] orientation, vacancy defects not only provide the nucleation sites for compression-induced plasticity, which mainly involves crystallographic reorientation, phase transition, and stacking faults, but also significantly reduce spall damage. The degree of spall damage is probably determined by a competitive mechanism between energy absorption and stress attenuation induced by plastic deformation. Void evolution during spallation is mainly based on the emission mechanism of dislocations. The {11&ndash;22} &lt;11&ndash;23&gt; pyramidal dislocation facilitates the nucleation of void in the [0001] shock, as well as the {1&ndash;100} &lt;11&ndash;20&gt; prismatic dislocation in the [10&ndash;10] shock. We also investigated the variation of spall strength between perfect and defective Mg at different shock velocities. The relevant results can provide a reference for future investigations on spall damage

Characteristics of Klebsiella pneumoniae pyogenic liver abscess from 2010–2021 in a tertiary teaching hospital of South China

ABSTRACT: Objectives: Pyogenic liver abscess (PLA) is a severe and potentially fatal infectious disease. Klebsiella pneumoniae (K. pneumoniae) is the predominant pathogen responsible for PLA. This study aims to investigate the clinical characteristics and prognostic factors of K. pneumoniae–induced pyogenic liver abscess (KP-PLA), particularly those caused by carbapenem-resistant K. pneumoniae (CRKP). Methods: Analyses were performed on PLA patients from January 2010 to December 2021, to investigate the differences of K. pneumoniae from other etiologically infected PLA patients. Univariate and multivariate logistic regression analyses were used to compare prognostic factors between patients with carbapenem-resistant K. pneumoniae PLA (CRKP-PLA) and patients with carbapenem-sensitive K. pneumoniae PLA. Results: Univariate analysis demonstrated a significant association between KP-PLA and factors including diabetes mellitus (P < 0.001), cholecystitis and cholelithiasis (P = 0.032), single abscess (P = 0.016), and abscesses with a diameter over 50 mm (P = 0.004). The CRKP group exhibited a higher prevalence of therapeutic interventions before K. pneumoniae infection, including abdominal surgery, mechanical ventilation, sputum suction, tracheal cannula, routine drainage of the abdominal cavity, and peripherally inserted central venous catheters (P < 0.05). Multivariate logistic regression analysis revealed that admission to the intensive care unit was an independent risk factor associated with CRKP-PLA (odds ratio 36; 95% confidence interval 1.77–731.56; P = 0.020). Conclusion: The KP-PLA patients were significantly associated with diabetes and were more likely to have single abscesses larger than 50 mm. PLA patients with a history of admission to intensive care unit or invasive therapeutic procedures should be given special consideration if combined with CRKP infection

NE increased EPCs in spleen in mice bearing limb ischemia.

<p>Cells from splenic tissue homogenates were lysed and analyzed with flow cytometry. EPCs in spleen were defined as CD34+/KDR+ cells (B). Proportion of EPCs in spleen was increased from 1.94±0.39% to 4.89±0.36% after intraperitoneal injection of NE in mice with limb ischemia (A, * P<0.05 compared with model group). Representative flow cytometric analysis of EPCs (CD34+/Flk-1+cells) were showed in part B.</p