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Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 loaded by vectors could induce high rates of specific site genome editing and correct disease-causing mutations. However, most monogenic genetic diseases such as hemophilia are caused by different mutations dispersed in one gene, instead of an accordant mutation. Vectors developed for correcting specific mutations may not be suited to different mutations at other positions. Site-specific gene addition provides an ideal solution for long-term, stable gene therapy. We have demonstrated SaCas9-mediated homology-directed factor IX (FIX) in situ targeting for sustained treatment of hemophilia B. In this study, we tested a more efficient dual adeno-associated virus (AAV) strategy with lower vector dose for liver-directed genome editing that enables CRISPR-Cas9-mediated site-specific integration of therapeutic transgene within the albumin gene, and we aimed to develop a more universal gene-targeting approach. We successfully achieved coagulation function in newborn and adult hemophilia B mice by a single injection of dual AAV vectors. FIX levels in treated mice persisted even after a two-thirds partial hepatectomy, indicating stable gene integration. Our results suggest that this CRISPR-Cas9-mediated site-specific gene integration in hepatocytes could transform into a common clinical therapeutic method for hemophilia B and other genetic diseases.

Engineering, procurement, and construction (EPC) contracting does not promote collaboration and thus, may not be suitable for building information modeling (BIM) projects. Joint-contract functions that combine contractual control, coordination, and contingency adaptability may positively influence the performance of these BIM-enabled projects. This study hypothesized that perceived fairness, calculative trust, relational trust, and positive outcomes of distrust influence the relationship between joint contract functions and BIMenabled project performance. It collected 252 observations from industry practitioners in EPC oil and gas projects and analyzed them using partial least squares structural equation modelling (PLS-SEM). The results show no direct effect of joint-contract functions on BIM-enabled EPC project performance but do show significant total and indirect relationship effects that are influenced by perceived fairness and relational trust. The findings contribute to construction contracting research by empirically showing how formal contracts focusing on joint-contract functions can influence BIM-enabled EPC project performance. The current findings also shed light on appropriate contract framing for BIM-enabled EPC project stakeholders, an area not explored in the previous literature.

Highly interconnected porous polymer scaffolds were prepared by gas foaming.Poly(ε-caprolactone)/poly(lactic acid) blends were melt mixed and batch foamed using CO 2 as a physical blowing agent. The effects of the foaming temperature, pressure, and CO 2 saturation time on the foam morphology were related to the mechanical properties of the scaffolds. The cell size in cross section of scaffolds decreased and became more homogeneous until CO 2 saturation time reached 1.5 hours. With an increase in temperature, the cell size increased markedly and the cell size uniformity decreased gradually, whereas the reverse happened when the foaming pressure was increased. Meanwhile, many open cells can also be detected on the surface of scaffolds. High porosity and an open-cell content of greater than 90% were obtained. The compressive strength of scaffolds was regulated by controlling the foam architecture. The information gathered in this study may provide a theoretical basis for research into porous tissue engineering scaffolds. KEYWORDS batch foaming, mechanical properties, poly(ε-caprolactone)/poly(lactic acid), pore morphology, scaffold

A concise synthesis of phenanthridine derivatives is achieved by an iridium-catalyzed direct fusion of oxime ethers and heteroarenes, which is a successful example of a cascade C–H/C–H cross-coupling/cyclization strategy for polycyclic heteroaromatic synthesis. By subtle tuning of the reaction conditions, both benzo- and simple five-membered heteroarenes are suitable substrates under similar but different conditions. The key is the right choice of a silver salt. The detailed mechanistic study discloses that the first C–H/C–H cross-coupling step involves an [IrII]–[IrIV] catalytic cycle, which needs Ag2O as the oxidant. For the second cyclization step, a radical process takes control in the reactions of benzoheteroarenes and Ag2O is required; however, a C–H cyclization functions in the reactions of simple five-membered heteroarenes involving an [IrI]–[IrIII] catalytic cycle, and AgTFA is necessary.

Generating promising materials for the conversion of CO2 to valuable industrial products under mild conditions is important for both ameliorating the greenhouse effect and sustainable development. Pillar[5]arene-incorporated materials have recently emerged as building frameworks to construct versatile functional polymeric materials. Herein, we demonstrate that highly efficient fixation of CO2 to cyclic carbonates can be achieved by employing a novel pillar[5]arene-based Co(III)-loaded covalent organic polymer (COP) as a heterogeneous catalyst (Co(III)–P5COP). The catalyst was created first by condensation of bromo-functionalized pillar[5]arene and a Schiff-base derivative (BHPD–OH) to afford the pillar[5]arene-based COP (P5COP), followed by loading Co(III) to prepare the target material bearing abundant salen–Co(III) sites. Results of catalysis with various substrates reveal excellent catalytic performance for CO2 cycloaddition with the conversion and selectivity of cyclic carbonate reaching up to 96 and 99%, respectively, under mild conditions of 30 °C and 1 atm CO2. Moreover, Co(III)–P5COP exhibits general applicability to other bulky epoxides. The polymeric pillar[5]arene-based catalysts could be easily recovered and reused without marked loss in their activity. Therefore, the marriage of Co(III)–salen and the pillar[5]arene platform constitutes a feasible approach to offering easily accessible and macrocycle-based new materials for the conversion of CO2 to valuable products.

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Drawing on the theory of relational governance, this study determines the nexus of inter-organizational trust, principled negotiation, and joint action in cost performance. To this end, it formulates five hypotheses based on established management theories or principles of organizational studies. The study uses partial least squares structural equation modeling to analyze the 248 valid questionnaires collected from the analyzed organizations involved in megaprojects. The results show that interorganizational trust has a direct and indirect positive effect on improving cost performance. Principled negotiation and joint action can serve as multiple mediating roles between inter-organizational trust and cost performance. Contractual governance also has different moderation effects on principled negotiation and joint action toward cost performance. In conclusion, this study contributes to the knowledge on inter-organizational trust and its mediating effects on cost performance from the perspective of megaprojects. The results are generalizable to other projects with complicated organizational and working relationships.