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If you would like to write for this, or any other Emerald publication, then please use our Emerald for Authors service information about how to choose which publication to write for and submission guidelines are available for all. Please visit www.emeraldinsight.com/authors for more information. About Emerald www.emeraldinsight.comEmerald is a global publisher linking research and practice to the benefit of society. The company manages a portfolio of more than 290 journals and over 2,350 books and book series volumes, as well as providing an extensive range of online products and additional customer resources and services.Emerald is both COUNTER 4 and TRANSFER compliant. The organization is a partner of the Committee on Publication Ethics (COPE) and also works with Portico and the LOCKSS initiative for digital archive preservation. AbstractPurpose -Construction is a competitive, ever-changing, and challenging industry. Therefore, it is not surprising that the majority of construction professionals suffer from stress, especially construction project managers (C-PMs), who are often driven by the time pressures, uncertainties, crisis-ridden environment, and dynamic social structures that are intrinsic to every construction project. Extensive literature has indicated that stress can be categorized into: job stress, burnout, and physiological stress. This study aims to investigate the impact of stress on the performance of C-PMs. Design/methodology/approach -To investigate the relationships between stress and performance among C-PMs, a questionnaire was designed based on the extensive literature, and was sent to 500 C-PMs who had amassed at least five years' direct working experience in the construction industry. A total of 108 completed questionnaires were returned, representing a response rate of 21.6 percent. Based on the data collected, an integrated structural equation model of the stresses and performances of C-PMs was developed using Lisrel 8.0. Findings -The results of structural equation modelling reveal the following: job stress is the antecedent of burnout, while burnout can further predict physiological stress for C-PMs; job stress is negatively related only to their task performance; both burnout and physiological stress are negatively related to their organizational performance; and task performance leads positively to their interpersonal performance. Recommendations are given based on the findings to enhance their stress and performance levels.Originality/value -This study provides a comprehensive investigation into the impact of various types of stress on the performances of C-PMs. The result constitutes a significant step towards the stress management of C-PMs in the dynamic and stressful construction industry.

Although a variety of nanoparticles (NPs) have been used for drug delivery applications, their surfaces are immediately covered by plasma protein corona upon systemic administration. As a result, the adsorbed proteins create a unique biological identity of the NPs that lead to unpredictable performance. The protein corona on NPs could also impede active targeting, induce off-target effects, trigger particle clearance and even provoke toxicity. This article reviews the fundamentals of NP-plasma protein interaction, the consequences of the interactions, and provides insights into the correlations of protein corona with biodistribution and cellular delivery. We hope that this review will trigger additional questions and possible solutions that lead to more favorable developments in NP-based targeted delivery systems.

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive, metabolic disorder caused by mutations of alanine-glyoxylate aminotransferase (AGT), a key hepatic enzyme in the detoxification of glyoxylate arising from multiple normal metabolic pathways to glycine. Accumulation of glyoxylate, a precursor of oxalate, leads to the overproduction of oxalate in the liver, which accumulates to high levels in kidneys and urine. Crystalization of calcium oxalate (CaOx) in the kidney ultimately results in renal failure. Currently, the only treatment effective in reduction of oxalate production in patients who do not respond to high-dose vitamin B6 therapy is a combined liver/kidney transplant. We explored an alternative approach to prevent glyoxylate production using Dicer-substrate small interfering RNAs (DsiRNAs) targeting hydroxyacid oxidase 1 (HAO1) mRNA which encodes glycolate oxidase (GO), to reduce the hepatic conversion of glycolate to glyoxylate. This approach efficiently reduces GO mRNA and protein in the livers of mice and nonhuman primates. Reduction of hepatic GO leads to normalization of urine oxalate levels and reduces CaOx deposition in a preclinical mouse model of PH1. Our results support the use of DsiRNA to reduce liver GO levels as a potential therapeutic approach to treat PH1.

The Wnt/β-catenin pathway is among the most frequently altered signaling networks in human cancers. Despite decades of preclinical and clinical research, efficient therapeutic targeting of Wnt/β-catenin has been elusive. RNA interference (RNAi) technology silences genes at the mRNA level, and therefore can be applied to previously-undruggable targets. Lipid nanoparticles (LNPs) represent an elegant solution for delivery of RNAi-triggering oligonucleotides to disease-relevant tissues, but have been mostly restricted to applications in the liver. In this study, we systematically tuned the composition of a prototype LNP to enable tumor-selective delivery of a Dicer-substrate siRNA (DsiRNA) targeting CTNNB1, the gene encoding β-catenin. This formulation, termed EnCore-R, demonstrated pharmacodynamic activity in subcutaneous human tumor xenografts, orthotopic patient-derived xenograft (PDx) tumors, disseminated hematopoietic tumors, genetically induced primary liver tumors, metastatic colorectal tumors, murine metastatic melanoma. DsiRNA delivery was homogeneous in tumor sections, selective over normal liver and independent of apolipoprotein-E binding. Significant tumor growth inhibition was achieved in Wnt-dependent colorectal and hepatocellular carcinoma models, but not in Wnt-independent tumors. Finally, no evidence of accelerated blood clearance or sustained liver transaminase elevation was observed after repeated dosing in nonhuman primates. These data support further investigation to gain mechanistic insight, optimize dose regimens and identify efficacious combinations with standard-of-care therapeutics.

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The experimental realization of a Kerr frequency comb represented the convergence of research in materials, physics, and engineering, and this symbiotic relationship continues to underpin efforts in comb innovation today. While the initial focus developing cavity-based frequency combs relied on existing microresonator architectures and classic optical materials, in recent years, this trend has been disrupted. This paper reviews the latest achievements in frequency comb generation using resonant cavities, placing them within the broader historical context of the field. After presenting well-established material systems and device designs, the emerging materials and device architectures are examined. Specifically, the unconventional material systems as well as atypical device designs that have enabled tailored dispersion profiles and improved comb performance are compared to the current state of art. The remaining challenges and future outlook for the field of cavity-based frequency combs is evaluated.