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Prostaglandin E2 (PGE2) plays a crucial role in inflammation. Non-steroidal anti-inflammatory medications are commonly utilized to alleviate pain and address inflammation by blocking the production of PGE2 and cyclooxygenase (COX). However, selective inhibition of COX can easily lead to a series of risks for cardiovascular diseases. Hence, it is imperative to discover safer and more efficient targets for reducing inflammation. Research has demonstrated that mPGES-1 serves as the final enzyme that controls the rate of prostaglandin E2 synthesis. Moreover, it is only triggered by inflammation and could serve as a possible treatment target instead of COX in cases of inflammation. 2,5-dimethylcelecoxib (DMC) can effectively inhibit mPGES-1 expression, maintain the overall balance of prostaglandins, reduce the secretion of PGE2, and, most importantly, avoid the side effects of COX inhibitors. DMC has the ability to address illnesses through the stimulation of autophagy and apoptosis, as well as the regulation of the immune microenvironment and intestinal flora. This study provides a comprehensive overview of the advancements in DMC within experimental research and offers suggestions for potential avenues of future investigation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Secure multi-party computation of Chebyshev distance represents a crucial method for confidential distance measurement, holding significant theoretical and practical implications. Especially within electronic archival management systems, secure computation of Chebyshev distance is employed for similarity measurement, classification, and clustering of sensitive archival information, thereby enhancing the security of sensitive archival queries and sharing. This paper proposes a secure protocol for computing Chebyshev distance under a semi-honest model, leveraging the additive homomorphic properties of the NTRU cryptosystem and a vector encoding method. This protocol transforms the confidential computation of Chebyshev distance into the inner product of confidential computation vectors, as demonstrated through the model paradigm validating its security under the semi-honest model. Addressing potential malicious participant scenarios, a secure protocol for computing Chebyshev distance under a malicious model is introduced, utilizing cryptographic tools such as digital commitments and mutual decryption methods. The security of this protocol under the malicious model is affirmed using the real/ideal model paradigm. Theoretical analysis and experimental simulations demonstrate the efficiency and practical applicability of the proposed schemes., (© 2024. The Author(s).)

Geopolymer solidification/stabilization technology has developed rapidly in the remediation field of heavy metal-contaminated soil. However, geopolymers exhibit low anionic heavy metal immobilization efficiency due to their electronegativity and alkali activation characteristics. This study constructed a one-part blast furnace slag-based geopolymer system using landfill leachate concentrate (LLC) as chlorine and humic acid sources and achieved the solidification/stabilization of cations (Cd, Cu, Hg, and Pb) and anions (Sb and As) in the antimony mine soils (AMS). The LLC addition increased the Sb and As fixation rates from 92%∼94% and 82∼86%, respectively, to over 99%, reducing the leaching concentration of all heavy metal ions to the ppb level. LLC improved the chemical stability and physical encapsulation of Sb/As in three ways: inducing a Friedel's salt (FS) formation, enhancing humic acid complexation/chelation, and promoting geopolymerization. Wet curing was more conducive to FS formation in the geopolymer than dry curing and increased the 28-day compressive strength by 38.5%. Due to the SiO 2 skeleton support effect in AMS, a 30 wt% AMS addition was beneficial for geopolymer strength development. Our study provided a harmless method for the codisposal of LLC and AMS and improved the efficiency of geopolymer fixation of complex heavy metal cations and anions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Adeno-associated virus (AAV) is a promising gene therapy vector, but questions remain regarding mechanisms of basic viral functions. We previously showed that a serine/threonine (S/T) triplet motif and its flanking residues, located in the overlapping N-terminus of VP1/VP2 and highly conserved across most AAV serotypes, are critical for viral transcript production in vitro. Here we generate a panel of S/T triplet mutants in AAV serotypes 2, 4, and 9 and characterize their behaviors in vitro and in vivo using next generation sequencing. We show that S/T triplet mutations can significantly hinder some stages of transduction in a serotype-dependent manner in vitro. Interestingly, these defects are largely overcome in C57BL/6 mice, with only one mutant displaying altered behavior in vivo. Taken together, our results identify a short N-terminal capsid motif with diverse roles across several AAV serotypes which better informs engineering efforts to improve AAV as a vector for gene therapy., (Copyright © 2021. Published by Elsevier Inc.)

This paper proposes a joint encryption and screen-cam robust watermarking scheme. This method combines the advantages of smartphone, encryption and watermarking technologies, thereby achieving watermark extraction with a smartphone, partial decryption and tracking leakage from sneak shots. We design a dual watermarking algorithm to achieve watermark detection from both encrypted and decrypted images. First, a watermark is embedded in the discrete Fourier transform (DFT) domain to enable leakage tracking. Then, a second watermark is generated based on QR (Quick response) code encoding and inverse DFT to achieve high watermark capacity and error correction ability, where the secret key for decryption is included in the watermark message. By hiding this message carrying the watermark for the encrypted image in the changes caused by embedding the first watermark, we can improve imperceptibility and will not affect the effectiveness of the proposed scheme. Finally, to enhance the robustness of watermark after encryption, a chaotic mapping-based segment encryption algorithm is proposed. In the process of watermark detection, to cope with perspective correction, a frame locating based algorithm is employed to achieve watermark synchronization from a recaptured picture of the encrypted image. Considering the severe quality degradation, we use a noise component and local statistic feature-based method to extract the message bits. The experimental results show that the proposed scheme is secure, and highly robust, to screen-cam the process for both before and after decryption. Additionally, after decryption, the proposed scheme also has high robustness against common image processing attacks.

Autografting is currently the gold standard for treatment of bone defects, but has shown disadvantages in the limited volume of and donor site morbidity associated with harvested bone. Customized bone scaffolds that mimic the mechanical and biological properties of native bone are needed to augment the currently limited bone regeneration strategies. To achieve this goal, a repeated cross-hatch structure with uniform cubic pores was designed and 3D printed using polylactic acid (PLA) via fused deposition modeling (FDM). PLA surfaces were modified by wet chemical (alkali) treatment for either 1 h (1hAT) or 6 h (6hAT), followed by coating with nano-hydroxyapatite (nHA). Our hypotheses were that: (i) 6-hour (but not 1-hour) alkali treatment would enhance nHA coating, (ii) the nHA coating on the 6-hour alkali-treated surface would increase hydrophilicity and cell attachment/proliferation, and (iii) stiffness, but not effective Young's modulus, would be reduced by 6-hour alkali treatment. The effects of AT and nHA coating on scaffold morphology was observed by scanning electron microscopy and quantified using a custom MATLAB script. Chemical composition and hydrophilicity were evaluated via energy dispersive X-ray spectroscopy and Fourier transform infrared spectroscopy, and water contact angle analyses, respectively. Mechanical testing and in vitro cell culture were further employed to analyze compressive properties, and cell attachment and proliferation, respectively. As expected, 6hAT led to reduced strut width and stiffness, while improving the nHA coating and hydrophilicity. Interestingly, PLA/6hAT but not PLA/6hAT/nHA demonstrated a reduction in effective modulus compared to PLA and PLA/nHA scaffolds. From in vitro experiments, the combined PLA/6hAT/nHA modification resulted in the greatest extent of cell attachment but not proliferation. These results collectively demonstrate that the PLA/6hAT/nHA scaffold exhibits properties that may prove beneficial for cancellous bone regeneration., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Adeno-associated virus (AAV) is a promising vector for gene therapy, but its broad tropism can be detrimental if the transgene being delivered is harmful when expressed ubiquitously in the body, i.e. in non-target tissues. Delivering the transgene of interest to target cells at levels high enough to be therapeutically effective while maintaining safety by minimizing delivery to off-target cells is a prevalent challenge in the field of gene therapy. We have developed a protease activatable vector (provector) platform based on AAV9 that can be injected systemically to deliver therapeutic transgenes site-specifically to diseased cells by responding to extracellular proteases present at the disease site. The provector platform consists of a peptide insertion into the virus capsid which disrupts the virus' ability to bind to cell surface receptors. This peptide contains a blocking motif (aspartic acid residues) flanked on either side by cleavage sequences that are recognized by certain proteases. Exposure to proteases cleaves the peptides off the capsid, activating or "switching ON" the provector. In response to the activation, the provectors regain their ability to bind and transduce cells. Here, we have designed a provector that is activated by cysteine aspartic proteases (caspases), which have roles in inflammation and apoptosis and thus are elevated at sites of diseases such as heart failure, neurodegenerative diseases, and ischemic stroke. This provector demonstrates a 200-fold reduction in transduction ability in the OFF state compared to AAV9, reducing the virus' ability to transduce off-target healthy tissue. Following exposure to and proteolysis by caspase-3, the provector shows a 95-fold increase in transduction compared to the OFF state. The switchable transduction behavior was found to be a direct result of the peptide insertion ablating the ability of the virus to bind to cells. In vivo studies were conducted to characterize the biodistribution, blood circulation time, neutralizing antibody formation, and targeted delivery ability of the caspase-activatable provector in a model of heart failure., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Adeno-associated virus (AAV) is one of the most researched, clinically utilized gene therapy vectors. Though clinical success has been achieved, transgene delivery and expression may be hindered by cellular and tissue barriers. Understanding the role of receptor binding, entry, endosomal escape, cytoplasmic and nuclear trafficking, capsid uncoating, and viral transcription in therapeutic efficacy is paramount. Previous studies have shown that N-terminal regions of the AAV capsid proteins are responsible for endosomal escape and nuclear trafficking, however the mechanisms remain unknown. We identified a highly-conserved three-residue serine/threonine (S/T) motif in the capsid N-terminus, previously uncharacterized in its role in intracellular trafficking and transduction. Using alanine scanning mutagenesis, we found S155 and the flanking residues, D154 and G158, are essential for AAV2 transduction efficiency. Remarkably, specific capsid mutants show a 5 to 9-fold decrease in viral mRNA transcripts, highlighting a potential role of the S/T motif in transcription of the viral genome., Competing Interests: Declaration of competing interest Junghae Suh is an employee of Biogen as of August 2019. All other authors declare that they have no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The fields of physical, chemical, and synthetic virology work in partnership to reprogram viruses as controllable nanodevices. Physical virology provides the fundamental biophysical understanding of how virus capsids assemble, disassemble, display metastability, and assume various configurations. Chemical virology considers the virus capsid as a chemically addressable structure, providing chemical pathways to modify the capsid exterior, interior, and subunit interfaces. Synthetic virology takes an engineering approach, modifying the virus capsid through rational, combinatorial, and bioinformatics-driven design strategies. Advances in these three subfields of virology aim to develop virus-based materials and tools that can be applied to solve critical problems in biomedicine and biotechnology, including applications in gene therapy and drug delivery, diagnostics, and immunotherapy. Examples discussed include mammalian viruses, such as adeno-associated virus (AAV), plant viruses, such as cowpea mosaic virus (CPMV), and bacterial viruses, such as Qβ bacteriophage. Importantly, research efforts in physical, chemical, and synthetic virology have further unraveled the design principles foundational to the form and function of viruses. This article is categorized under: Diagnostic Tools > Diagnostic Nanodevices Biology-Inspired Nanomaterials > Protein and Virus-Based Structures., (© 2018 Wiley Periodicals, Inc.)

Adeno-associated virus (AAV) has emerged as a promising gene delivery vector because of its non-pathogenicity, simple structure and genome, and low immunogenicity compared to other viruses. However, its adoption as a safe and effective delivery vector for certain diseases relies on altering its tropism to deliver transgenes to desired cell populations. To this end, we have developed a protease-activatable AAV vector, named provector, that responds to elevated extracellular protease activity commonly found in diseased tissue microenvironments. The AAV9-based provector is initially inactive, but then it can be switched on by matrix metalloproteinases (MMP)-2 and -9. Cryo-electron microscopy and image reconstruction reveal that the provector capsid is structurally similar to that of AAV9, with a flexible peptide insertion at the top of the 3-fold protrusions. In an in vivo model of myocardial infarction (MI), the provector is able to deliver transgenes site specifically to high-MMP-activity regions of the damaged heart, with concomitant decreased delivery to many off-target organs, including the liver. The AAV provector may be useful in the future for enhanced delivery of transgenes to sites of cardiac damage., (Copyright © 2019 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

The study of how mammalian cell division is regulated in a 3D environment remains largely unexplored despite its physiological relevance and therapeutic significance. Possible reasons for the lack of exploration are the experimental limitations and technical challenges that render the study of cell division in 3D culture inefficient. Here, we describe an imaging-based method to efficiently study mammalian cell division and cell-matrix interactions in 3D collagen matrices. Cells labeled with fluorescent H2B are synchronized using the combination of thymidine blocking and nocodazole treatment, followed by a mechanical shake-off technique. Synchronized cells are then embedded into a 3D collagen matrix. Cell division is monitored using live-cell microscopy. The deformation of collagen fibers during and after cell division, which is an indicator of cell-matrix interaction, can be monitored and quantified using quantitative confocal reflection microscopy. The method provides an efficient and general approach to study mammalian cell division and cell-matrix interactions in a physiologically relevant 3D environment. This approach not only provides novel insights into the molecular basis of the development of normal tissue and diseases, but also allows for the design of novel diagnostic and therapeutic approaches.

Image-based assays, such as alkaline phosphatase staining or immunocytochemistry for pluripotent markers, are common methods used in the stem cell field to assess pluripotency. Although an increased number of image-analysis approaches have been described, there is still a lack of software availability to automatically quantify pluripotency in large images after pluripotency staining. To address this need, we developed a robust and rapid image processing software, Pluri-IQ, which allows the automatic evaluation of pluripotency in large low-magnification images. Using mouse embryonic stem cells (mESC) as a model, we combined an automated segmentation algorithm with a supervised machine-learning platform to classify colonies as pluripotent, mixed, or differentiated. In addition, Pluri-IQ allows the automatic comparison between different culture conditions. This efficient user-friendly open-source software can be easily implemented in images derived from pluripotent cells or cells that express pluripotent markers (e.g., OCT4-GFP) and can be routinely used, decreasing image assessment bias., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

How the division axis is determined in mammalian cells embedded in three-dimensional (3D) matrices remains elusive, despite that many types of cells divide in 3D environments. Cells on two-dimensional (2D) substrates typically round up completely to divide. Here, we show that in 3D collagen matrices, mammalian cells such as HT1080 human fibrosarcoma and MDA-MB-231 breast cancer cells exhibit division modes distinct from their Counterparts on 2D substrates, with a markedly higher fraction of cells remaining highly elongated through mitosis in 3D matrices. The long axis of elongated mitotic cells accurately predicts the division axis, independently of matrix density and cell-matrix interactions. This 3D-specific elongated division mode is determined by the local confinement produced by the matrix and the ability of cells to protrude and locally remodel the matrix via β1 integrin. Elongated division is readily recapitulated using collagen-coated microfabricated channels. Cells depleted of β1 integrin still divide in the elongated mode in microchannels, suggesting that 3D confinement is sufficient to induce the elongated cell-division phenotype.