Development of Glucocorticoid Prodrug for the Treatment of Lupus Nephritis

Nephritis is one of the major complications of systemic lupus erythematosus (SLE). While glucocorticoids (GC) are frequently used as the first line treatment for lupus nephritis, long-term GC usage is often complicated by severe adverse effects. To address this challenge, we have developed a polyethylene glycol (PEG)-based macromolecular prodrug (ZSJ-0228) of dexamethasone, which self-assembles into micelles in aqueous media. When compared to the dose equivalent daily dexamethasone 21-phosphate disodium (Dex) treatment, monthly intravenous administration of ZSJ-0228 for two months significantly improved the survival of lupus-prone NZB/W F1 mice and was much more effective in normalizing proteinuria, with clear histological evidence of nephritis resolution. Different from the dose equivalent daily Dex treatment, monthly ZSJ-0228 administration has no impact on the serum anti-double-stranded DNA (anti-dsDNA) antibody level but can significantly reduce renal immune complex deposition. No significant systemic toxicities of GC (e.g. total IgG reduction, adrenal gland atrophy and osteopenia, etc.) were found to associate with ZSJ-0228 treatment. In vivo imaging, flow cytometry and pharmacokinetic studies reveal that the fluorescent or 125I-labeled ZSJ-0228 primarily distributes to the inflamed kidney after systemic administration, with renal myeloid cells and proximal tubular epithelial cells mainly responsible for its kidney retention. Collectively, these data suggest that the potent local anti-inflammatory/immunosuppressive effects and improved safety of ZSJ-0228 may be attributed to its tropism and cellular sequestration in the kidney. Pending further optimization, ZSJ-0228 may be developed into an effective and safe therapy for improved clinical management of lupus nephritis

Internet Finance: A Systematic Literature Review and Bibliometric Analysis

Internet finance has gained growing popularity in internet plus environment. While various problems have emerged, and hindered the sustainable growth of internet finance industry. Thus, a summary of existent research and directions for future study are expected. However, few comprehensive literature reviews has been published. This paper presents a thorough bibliometric and network analysis following a systematic literature review methodology. The analysis begins by identifying 331 published studies in Web of Science. Prolific authors, institutions and nations are identified by rigorous bibliometric tools. Based on citation and co-citation analysis, influential papers from different time periods are identified. Established and emergent research clusters are identified for topological analysis by coupling analysis. Future research opportunities are pointed out

Logistics service providers and value creation through collaboration: a case study

This is the accepted and refereed manuscript to the articleLogistics service provider (LSP) strategy and value creation is a cooperative endeavor. The study focuses on how LSPs create value by taking advantage of being connected and exploring the presence of various forms of interdependence. Using a single case study and a framework addressing network externalities and the concept of value logic interaction, we identify three types of collaborative value creation; distributive, functional and systemic. Whereas the fundamental logic of the LSP is mediation in terms of performing a distributive service, it is also subject to externalities in its functional and systemic value creation initiatives. LSPs are thereby portrayed as strategic entities dealing with a set of interdependencies in order to facilitate value creation in their networks. These firms need a rather advanced understanding of different types of economies and forms of collaboration to succeed. The study also associates different types of LSPs with the identified types of collaborative value creation.1. Forfatterversjo

Embeddable Advanced Sensors for Harsh Environment Sensing Applications

Research and development in advanced sensors with embedded monitoring capability have experienced significant growth in recent years, fueled by their broad applications in real-time measurement of a wide variety of physical, chemical, and biological quantities. Compared with conventional sensors with bulky assemblies, recent progress in 3D manufacturing technologies (e.g., ultrafast laser micromachining and additive manufacturing) has opened up a new avenue in one-step fabrication of assembly-freemicro devices in various materials as well as the development of compact, customized, and intricate smart structures/components. The merits of these advanced manufacturing techniques enable the integration of embeddable advanced sensors into smart structures and components for improved robustness, enriched functionality, enhanced intelligence, and unprecedented performance

SSL-Auth: An Authentication Framework by Fragile Watermarking for Pre-trained Encoders in Self-supervised Learning

Self-supervised learning (SSL), utilizing unlabeled datasets for training powerful encoders, has achieved significant success recently. These encoders serve as feature extractors for downstream tasks, requiring substantial resources. However, the challenge of protecting the intellectual property of encoder trainers and ensuring the trustworthiness of deployed encoders remains a significant gap in SSL. Moreover, recent researches highlight threats to pre-trained encoders, such as backdoor and adversarial attacks. To address these gaps, we propose SSL-Auth, the first authentication framework designed specifically for pre-trained encoders. In particular, SSL-Auth utilizes selected key samples as watermark information and trains a verification network to reconstruct the watermark information, thereby verifying the integrity of the encoder without compromising model performance. By comparing the reconstruction results of the key samples, malicious alterations can be detected, as modified encoders won't mimic the original reconstruction. Comprehensive evaluations on various encoders and diverse downstream tasks demonstrate the effectiveness and fragility of our proposed SSL-Auth.Comment: Submitted to AAAI2024. 9 pages, 7 figure

Examining a client network development framework for a logistics service provider: a longitudinal case study

Buyer-seller relationships represent a core theme in industrial marketing management. From the supplier’s perspective, extant marketing literature, however, focuses on client retention in preference to client recruitment. Within the context of logistics outsourcing, although numerous studies have taken the buyer’s perspective and shown how manufacturers/retailers select logistics service providers (LSPs), there is a shortage of studies and a lack of theoretical understanding from the supplier’s perspective on how LSPs recruit clients. This study contributes to rectifying this through a longitudinal case study conducted on a fourth-party logistics service provider appraising its recruitment of clients. A mid-range client recruitment framework is developed, built abductively on the case and through the theory of mediating firms value creation. Theoretically, the framework refines notions of the mediating firm theory. Managerially, this client recruitment framework is proposed as a guide to aid LSP managers in their organic growth strategies through client network development

A Highly Sensitive Intensity-Modulated Optical Fiber Magnetic Field Sensor Based on the Magnetic Fluid and Multimode Interference

Fiber-optic magnetic field sensing is an important method of magnetic field monitoring, which is essential for the safety of civil infrastructures, especially for power plant. We theoretically and experimentally demonstrated an optical fiber magnetic field sensor based on a single-mode-multimode-single-mode (SMS) structure immersed into the magnetic fluid (MF). The length of multimode section fiber is determined based on the self-image effect through the simulation. Due to variation characteristics of the refractive index and absorption coefficient of MF under different magnetic fields, an effective method to improve the sensitivity of SMS fiber structure is realized based on the intensity modulation method. This sensor shows a high sensitivity up to 0.097 dB/Oe and a high modulation depth up to 78% in a relatively linear range, for the no-core fiber (NCF) with the diameter of 125 μm and length of 59.8 mm as the multimode section. This optical fiber sensor possesses advantages of low cost, ease of fabrication, high sensitivity, simple structure, and compact size, with great potential applications in measuring the magnetic field

Advances in metabolic reprogramming of renal tubular epithelial cells in sepsis-associated acute kidney injury

Sepsis-associated acute kidney injury presents as a critical condition characterized by prolonged hospital stays, elevated mortality rates, and an increased likelihood of transition to chronic kidney disease. Sepsis-associated acute kidney injury suppresses fatty acid oxidation and oxidative phosphorylation in the mitochondria of renal tubular epithelial cells, thus favoring a metabolic shift towards glycolysis for energy production. This shift acts as a protective mechanism for the kidneys. However, an extended reliance on glycolysis may contribute to tubular atrophy, fibrosis, and subsequent chronic kidney disease progression. Metabolic reprogramming interventions have emerged as prospective strategies to counteract sepsis-associated acute kidney injury by restoring normal metabolic function, offering potential therapeutic and preventive modalities. This review delves into the metabolic alterations of tubular epithelial cells associated with sepsis-associated acute kidney injury, stressing the importance of metabolic reprogramming for the immune response and the urgency of metabolic normalization. We present various intervention targets that could facilitate the recovery of oxidative phosphorylation-centric metabolism. These novel insights and strategies aim to transform the clinical prevention and treatment landscape of sepsis-associated acute kidney injury, with a focus on metabolic mechanisms. This investigation could provide valuable insights for clinicians aiming to enhance patient outcomes in the context of sepsis-associated acute kidney injury

Biochemical and Morphological Mechanisms Underlying the Performance and Preference of Fall Armyworm (Spodoptera frugiperda) on Wheat and Faba Bean Plants

peer reviewedSpodoptera frugiperda (J. E. Smith), which attacked China in 2019, remains a significant threat to wheat production. Wheat–faba bean intercropping systems prevent damage caused by wheat aphids; however, the potential role in S. frugiperda control remains unclear. Here, the adaptability and preferences of S. frugiperda to wheat and its common intercropped plant, faba bean, were evaluated to implement an eco-friendly approach for S. frugiperda management. Their adaptability showed that both hosts could support S. frugiperda to complete their life cycle; however, the larvae performed worse on faba bean compared with on wheat. The biochemical analysis revealed that faba bean plants had lower contents of soluble sugars and total proteins but higher levels of phenolics and tannins than in wheat leaves. The gravid S. frugiperda preferred (during the preference assays) to oviposit on wheat rather than on faba bean plants in cage tests. The wheat odor was preferred over the faba bean odor in the Y-tube olfactometer bioassays. The morphological scanning electron microscopy (SEM) showed increased trichome density on wheat leaves. Therefore, the faba bean plants displayed antibiosis on larvae and were repellent to female moths, thus, suggesting that faba bean plants could serve as a push crop to be intercropped with wheat for S. frugiperda control for wheat fields

Transplanted adult human hepatic stem/progenitor cells prevent histogenesis of advanced hepatic fibrosis in mice induced by carbon tetrachloride

Transplantation of adult human hepatic stem/progenitor cells (hHSPCs) has been considered as an alternative therapy, replacing donor liver transplantation to treat liver cirrhosis. This study assessed the antifibrotic effects of hHSPCs in mice with fibrosis induced by carbon tetrachloride (CCl4) and examined the actions of hHSPCs on the fibrogenic activity of human hepatic stellate cells (HSCs) in a coculture system. Isolated hHSPCs expressed stem/progenitor cell phenotypic markers. Mice were given CCl4 (twice weekly for 7 weeks) and hHSPC transplantation weekly. CCl4 induced advanced fibrosis (bridging fibrosis and cirrhosis) in mice, which was prevented by hHSPC transplantation. The liver of hHSPC-transplanted mice showed only occasional short septa and focal parenchymal fibrosis, and a 50% reduction in hepatic collagen, assessed by Sirius red stain histomorphometry. Moreover, the proteins for α-smooth muscle actin (α-SMA) and collagen I were decreased. While α-SMA, collagen α1(I), and tissue inhibitor of metalloproproteinase-1 mRNAs were decreased, matrix metalloproteinase (MMP)-1 mRNA was increased, consistent with decreased fibrogenesis. MMP-2 and transforming growth factor-β were not affected. Alanine aminotransferase and aspartate aminotransferase were lower, suggesting improvement of liver function/damage. In coculture, hHSPCs elicited changes of α-SMA and fibrogenic molecules in HSCs similar to those observed in vivo, providing evidence for a functional link between hHSPCs and HSCs. A decreased HSC proliferation was noted. Thus, transplantation of hHSPCs prevents histogenesis of advanced liver fibrosis caused by CCl4. hHSPCs mediate downregulation of HSC activation coincident with modulation of fibrogenic molecule expression, leading to suppression of fibrogenesis both in vivo and in vitro