Modulation of Aryl Hydrocarbon Receptor-Regulated Genes by Methylmercury

Environmental pollution poses a significant threat to public health, with various contaminants contributing to a wide range of adverse health effects. Among these contaminants, methylmercury (MeHg) and the aryl hydrocarbon receptor (AHR) ligand 2,3,7,8-tetrachlorodibenzodioxin (TCDD) are particularly concerning due to their persistence in the environment and potent biological activities. Both compounds have been extensively studied for their individual effects, but the potential health risks associated with their combined exposure are less understood. The primary objective of this work was to investigate the individual and combined effects of MeHg and TCDD on AHR-regulated enzymes. This investigation was conducted using the murine hepatoma Hepa-1c1c7 cell line and extended to mouse hepatic and extrahepatic tissues. The effects of MeHg on Ahr-regulated gene expression were examined in the absence and presence of TCDD, along with evaluations of protein expression and enzymatic catalytic activity. In hepatic tissue, both MeHg and Hg²⁺ inhibited the TCDD-mediated induction of Cyp1a1/1a2 mRNA levels. However, only Hg²⁺ inhibited the TCDD-mediated induction of CYP1A1/1A2 protein and catalytic activity at posttranscriptional levels, indicating differential modulation by Hg²⁺ and MeHg. Additionally, the inhibitory role of HO-1 (heme oxygenase-1) on CYP1A activity induced by TCDD was investigated in vitro using the HO-1 competitive inhibitor tin-mesoporphyrin, which partially restored the MeHg-mediated decrease in CYP1A1 activity. In extrahepatic tissues, MeHg exhibited mainly inhibitory effects, particularly decreasing the basal level of Cyp1a1 and Cyp1a2 mRNA and protein, which was more evident at the 24-hour time point in kidneys, followed by hearts. Similarly, when mice were co-exposed, MeHg reduced the TCDD-induced Cyp1a1 and Cyp1a2 expression. However, MeHg potentiated kidney Cyp1b1 mRNA expression, opposing the observed change in its protein level. Exposure to MeHg induces several antioxidant enzymes, including NAD(P)H:quinone oxidoreductase (NQO1), whose expression is regulated by both AHR and nuclear factor erythroid 2-related factor-2 (NRF2). This co-regulation prompted an investigation into which transcription factor primarily orchestrates NQO1 expression upon MeHg exposure. Our findings demonstrate that NQO1 induction by MeHg is, at least in part, mediated by NRF2. In conclusion, the findings of this work reveal an intricate interplay between MeHg and TCDD on AHR-regulated CYP1 enzymes, with notable inhibitory effects that might be significant for procarcinogen metabolism. Varied responses across tissues highlight the potential implications for environmental health.

Towards a better QA process

For web archivists, Quality Assurance (QA) is a lengthy manual process that involves inspecting hundreds or thousands of archived websites to see if they have been captured correctly, i.e., resemble the original. This paper describes how this process can be automated by using image comparison measures to detect quality problems in archived websites. To this end, we created a suite of Python tools to 1) create screenshots of live websites and their archived counterparts, and 2) calculate the image similarity between the screenshots. We tested our code on four web archive collections to test the efficacy and usefulness of six different image similarity measures. We compared their scores to human judgments of the quality of archived websites obtained from Amazon Mechanical Turk (AMT). Our results show that the Structural Similarity Index (SSIM) and the Normalized Root Mean Square (NRMSE) scores are able to distinguish between high and low-quality archived websites. Our research at every step was informed by the specific needs and challenges of web archivists. Having methods such as the one presented here can allow cultural heritage institutions or researchers to more quickly and effectively detect low-quality content and produce high-quality web archives

UNCONVENTIONAL COOPER PAIRING AND CONFINEMENT Studies of lattice superconductivity and superfluid helium-3 enclosed by surfaces

Superconductivity and superfluidity --- two related and quintessentially quantum properties of matter --- manifest in a variety of interacting many-particle systems at low temperatures. The conceptual breakthrough for understanding these properties in fermions was provided by Bardeen, Cooper and Schrieffer in 1957. Their theory demonstrated how a coherent macroscopic quantum state can arise from the microscopic pairing of two fermions into a bound state. Although most well-known for inviscid flow, these many-body systems can showcase a wide array of properties depending both on their internal microscopic states and externally imposed conditions. The internal state of the bound pairs sets a length scale known as the coherence length, and confining these systems to the order of the coherence length can give rise to phases which would otherwise be energetically unfavourable in the bulk. This thesis explores how superconductivity and superfluidity are affected by the presence of strongly confining surfaces. For the project on superconductivity, we use three different techniques --- the Bardeen-Cooper-Schrieffer (BCS), the Bogoliubov-de Gennes (BdG) and the Anderson methods --- to calculate the superconducting order parameters on a one-dimensional (1D) and two-dimensional (2D) lattice. For lattices with periodic boundary conditions (PBCs), these methods are means to the same end, producing identical ``bulk'' order parameters. However, using open boundary conditions (OBCs) exposes the underlying assumptions and limitations of each method; the BCS method is inapplicable to systems with OBCs, while the BdG and Anderson methods produce varying results for identical parameters. To contrast these methods, we first map out the bulk phase diagrams for 1D and 2D lattices using the BCS method, showing how these phase diagrams can change dramatically from the onset of superconductivity at T = Tc down to T = 0. We then explore the T = 0 superconducting phases with OBCs, using the results from the BdG method as a benchmark for comparison with the Anderson method. The BdG method allows us to calculate the OBC superconducting phases to a high degree of accuracy, while the Anderson method provides a trade-off of accuracy for a computationally simpler approach. However, the simplicity of the Anderson method stems from approximation, and we show that these approximations lead to its failure for some of the superconducting phases. On the superfluid side, we study superfluid helium-3 (3-He) when it is confined to a quasi-2D slab. Using Ginzburg-Landau (GL) theory, we construct a theory of a new spatially-modulated superfluid phase called the 2D pair density wave (PDW) phase. This phase demonstrates spontaneous symmetry breaking of the spatial translation and rotation symmetries of the superfluid. However, it still retains its zero-viscosity transport properties across the transition, and thus could be described as a superfluid crystal phase. This work was motivated by recent experiments which have found evidence of a new superfluid 3-He phase appearing under quasi-2D confinement. We hope that our theoretical work will spur further investigation of this confined phase and its predicted spatial structure

Transport and Accumulation of Blockage-Related Solids in Urban Sewers: Wet Wipes and FOG (Fat, Oil and Grease)

The accumulation of sewer solids significantly reduces the hydraulic capacity of urban sewer networks, ultimately leading to sanitary or combined sewer overflows. Recent studies and media coverage have identified wet wipes and FOG (fat, oil, and grease) deposits as two predominant solids contributing to sewer blockages; however, their transport and accumulation mechanisms remain poorly understood. This thesis aims to address this knowledge gap and propose mitigation strategies for blockages caused by wipes and FOG in sewers. First, the transport of wipes with different densities and sizes was systematically studied in a circular pipe (Chapter 2). Previous studies have primarily focused on quantifying wipe abundance in sewer networks, while their movement processes remain unexplored. The critical shear stress and flow velocity for the incipient motion of wipes were found to increase with increasing wipe density and with decreasing relative wipe size. Non-dimensional equations were developed to characterize the incipient motion using the critical Shields number and the particle Froude number. The mean wipe velocity and mean ambient flow velocity were accurately described by a power relationship. Wipe movement modes were classified based on the ambient cross-sectional average velocity. Next, wipe blockage due to a vertical obstruction was studied (Chapter 3). Blockages resulting from the interactions between instream solids and encountered obstacles have been extensively studied for other rigid materials; however, existing theories may not apply to flexible wipes in sewers. This study employed a vertical rod to simulate sewer obstructions. Stochastic interactions among wipes, turbulent flow, and the obstruction were studied in a circular pipe (diameter D = 25 cm), with systematic variations in flow Froude number (Fr), wipe length (L), flow depth (H), submerged rod length (hrod), and rod diameter (drod). The mean area ratio of wipes (ratio of projected area to original surface area) ranged from 0.14 to 0.30. The entrapment probability P (ratio of entrapped to released wipes) for a single wipe was strongly correlated with Fr, H/D, L/H, drod/H, and hrod/H. As more wipes were released, the influence of the obstruction on wipe accumulation processes became negligible. New equations were developed to characterize entrapment probability, blockage length, and backwater rise, which can be used to predict the development of wipe blockages and sewage levels. Afterwards, the influence of suspended solids on FOG deposit formation was studied (Chapter 4). The presence of suspended solids is a critical feature of wastewater, yet its effects have often been overlooked. This study examined the physicochemical properties of FOG deposits formed from oleic acid and palmitic acid in the presence and absence of suspended solids. Results show that palmitic acid solidified more rapidly and formed larger masses. Saponified FOG, metal silicates (calcium/magnesium silicates), and crushed concrete can trigger deposit formation by providing heterogeneous nuclei, facilitating adsorption, and leaching hydroxide/metal ions, respectively. Glass beads reduced deposit formation by 30% under a velocity gradient of 88.7 s-1 and 4-hour reaction time by forming a physical barrier. The asymmetric vibration of the carboxylate group was a suitable indicator for determining the percent saponification (PS). The saponification degree exhibited clear stratification, with PS reaching up to 69% in the inner layer of FOG deposits adjacent to the concrete surface and lower PS (7%–29%) in the outer layer. Last, the hydrodynamic effects on the FOG deposit formation were investigated (Chapter 5). Previous studies used constant flow conditions and did not correlate hydrodynamic parameters with FOG formation. This study analyzed the spatial distribution, growth behavior, and chemical composition of FOG deposits under varying flow conditions. Results show that the velocity magnitude (V), turbulent kinetic energy (TKE), and vorticity (|ω|) of the FFA-oil mixture were 15%, 22%, and 2% higher than those of water, respectively. Rather than accumulating in all low-velocity areas (V 20 s-1. Higher TKE (> 0.0037 m2/s2) near the concrete surface inhibits FOG accumulation. Increased TKE promoted outer layer growth and reduced inner layer thickness, indicating competitive formation processes. This thesis provides critical insights into sewer blockages caused by wipes and FOG. The findings can help municipalities and utility firms assess sewer blockage risks, optimize maintenance strategies, and implement targeted mitigation measures, ultimately enhancing sewer system efficiency and resilience

Online Conversion under Horizon Uncertainty: From Competitive Analysis to Learning-Augmented Algorithms

Online allocation problems involve making sequential decisions under incomplete information, where inputs are revealed incrementally over time. A prominent subclass of online allocation problems is the one-way online conversion problem (a.k.a. one-way trading), which focuses on selling (or buying) a single type of divisible resource under dynamically changing prices. Decision-making in online conversion requires balancing immediate reward against the potential for better future opportunities. A critical yet less-explored aspect of online conversion is the impact of time horizon uncertainty, which determines the duration over which decisions are made. The horizon may be predetermined, revealed partway, or entirely unknown, introducing layers of complexity that significantly influence conversion strategies. Additionally, practical constraints such as box constraints, which limit the maximum allowable trade per step, further complicate the decision-making process and demand more nuanced algorithmic approaches. Despite progress in addressing online conversion problems, significant research gaps remain. Existing studies often focus on unconstrained settings or assume complete knowledge of the horizon. Few works explore the combined effects of horizon uncertainty and practical constraints like box constraints on algorithm design and performance. Additionally, leveraging horizon predictions to enhance performance has been underexplored in this context. This thesis addresses these gaps by making two main contributions. First, we propose a unified algorithm to address three models of horizon uncertainty—known horizon, notification at a specific step, and unknown horizon—under both constrained and unconstrained settings. Through competitive analysis, the algorithm achieves tight guarantees, demonstrating optimal performance across all scenarios. Second, the thesis extends the unified algorithm to incorporate horizon predictions, introducing a learning-augmented algorithm that bridges the gap between worst-case and average-case performance. By balancing robustness under adversarial conditions with consistency when predictions are accurate, the algorithm exhibits adaptability in uncertain environments. Together, these contributions advance the theoretical foundation of online conversion and provide practical insights for applications where horizon uncertainty and constraints like box constraints play a critical role

Partial Element Equivalent Circuit Method for Electromagnetic Transient Simulation of Power System Apparatus

Electromagnetic (EM) equipment are ubiquitous in electrical power generation, transmission, and distribution systems, and they should be studied for reliable and continuous operation under switching operations, faults, and other transient conditions. Conventional lumped models lack the capability to consider EM field interactions, while distributed methods, such as the finite element method (FEM), are widely employed to address these interactions. The partial element equivalent circuit (PEEC) method effectively solves Maxwell's equations in integral form and the method has gained interest in EM modeling due to its equivalent circuit behavior and its potential for optimization using circuit solver techniques. Electromagnetic models can be classified into two categories based on geometry: 2D geometry-based models and 3D geometry-based models. This thesis presents two main contributions toward the efficient simulation of EM systems. It proposed a transmission line modeling (TLM) based PEEC approach for the parallel simulation of 2D power system apparatus. The method was later extended to perform 3D power system simulations, including electrodynamic and electrostatic scenarios. Additionally, model order reduction techniques were introduced to achieve higher performance. First, a novel TLM-based parallel PEEC time-domain solver is developed to solve nonlinear 2D EM problems. The method substitutes both linear and nonlinear components in the standard PEEC equivalent circuit with corresponding TLM models, leading to an electrical current based linear network and a magnetic current based nonlinear network. The proposed hybrid TLM-PEEC method effectively decouples the nonlinear elements from the linear network, enabling individual solutions for the nonlinearities and making it highly suitable for parallel processing. Each nonlinear element is solved using parallel Newton-Raphson (N-R) iterations, and the analytical calculation of the Jacobian is presented along with the solution process. The parallelization of the proposed hybrid TLM-PEEC method is explored and implemented on a many-core graphics processing unit (GPU) and a multi-core central processing unit (CPU) to provide detailed field-oriented information on electromagnetic transients (EMTs) in a single-phase 2D shell-type transformer. The proposed architecture was easily coupled with an external network, and the accuracy and computational efficiency of the TLM-PEEC method was verified through similar simulation results obtained from Comsol Multiphysics. Secondly, the hybrid TLM-PEEC technique is proposed for 3D EM transient simulations, providing comprehensive details on the matrix solver, time-domain algorithms, and the N-R solver for nonlinear magnetics. The 3D hybrid TLM-PEEC approach defines separate linear and nonlinear equivalent circuits, introducing parallel TLM iterations for the linear system, and individual solutions for the nonlinear network using the N-R method, thereby enabling parallel computing. The proper orthogonal decomposition (POD) method, a model order reduction (MOR) technique, was integrated into the hybrid TLM-PEEC method to improve performance by removing unnecessary features in the system. The parallelization of the methods has been fully explored and implemented on both many-core GPU and multi-core CPU, enabling field-oriented transient simulation for a 3-phase 3D core-type transformer coupled with external circuits, as well as quasi-static 3D simulation for a high-voltage insulator. The accuracy and computational efficiency of the proposed architectures were verified through simulation results obtained from similar case studies implemented in Comsol Multiphysics

Evolutionary, Biological and Physiological Characterization of Arabidopsis CTP:phosphocholine Cytidylyltransferase 1 (CCT1)

Phosphatidylcholine (PC) is the major phospholipid class in the non-plastidial membranes of plant cells. The de novo biosynthesis of PC via CDP-choline pathway involves three sequential steps. Among these reactions, CTP:phosphocholine cytidylyltransferase (CCT1) catalyzes the conversion of phosphocholine and CTP into CDP-choline and pyrophosphate, a reaction considered the key regulatory step in certain plant species. The genome of Arabidopsis thaliana encodes two CCT isoforms, known as AthCCT1 and AthCCT2. The overall objective of this doctoral thesis is to advance our understanding of AthCCT1 through a combination of evolutionary, biochemical, and physiological approaches. In the first study, a phylogenetic analysis of plant CCT genes was conducted to investigate the evolutionary history, genetic relationships, and structural variations among CCTs in the green lineage. To further explore the impact of selection pressure on the functional evolution of CCT genes, we conducted a selection pressure analysis on the representative gene AthCCT1 and investigated its biochemical properties through enzyme assays and protein structural analysis. The results revealed a widespread presence of CCT genes across green algae and land plants, with a notable expansion in eudicots. The phylogenetic division of the CCT gene family into eight primary clades was supported by the observed conservation and divergence in gene structures and motif patterns. The selection pressure analysis of AthCCT1, integrated with biochemical assays and three-dimensional structural investigation, has uncovered two amino acid sites under positive selection, emphasizing their important roles in modulating AthCCT1 enzyme activity and substrate affinity. In the second study, the physiological roles of AthCCT1 in lipid biosynthesis and root development under osmotic stress were examined. Due to the lack of lipid profiling data in the cct1 cct2 knockout mutant, the precise role of AthCCT1 in PC biosynthesis is yet to be fully understood. Moreover, AthCCT1 contains a key phosphorylation site, Serine-187 (S187), which is regulated by Sucrose-nonfermentation1-related protein kinase1 (SnRK1). This SnRK1-mediated phosphorylation leads to approximately a 67% reduction in AthCCT1 enzyme activity. However, the effects of the phosphorylation at the S187 site on the dynamic and in vivo functions of AthCCT1 remain unclear. Accordingly, we generated Arabidopsis cct1 knockdown cct2 knockout lines and revealed their reduced PC intensity under normal conditions and impaired root growth in response to osmotic stress compared to the wild type, which could both be rescued by AthCCT1 overexpression. The S187D phosphomimetic mutant, where S187 is substituted by aspartic acid (D) to mimic the negative charge phosphorylation, displayed reduced enzymatic activity and altered structural properties, including reduced lipid-induced conformational changes and a more compact state compared to the native AthCCT1. Moreover, overexpression of the S187D was unable to restore the root growth phenotype under osmotic stress in the cct1 knockdown cct2 knockout lines, indicating that the mimicked phosphorylation state at S187 may influence AthCCT1’s enzyme function. Taken together, these findings highlight the role of AthCCT1 in PC biosynthesis and suggest that its phosphorylation potentially regulates both enzymatic activity and its physiological functions. The third study aimed to further reveal the molecular mechanisms underlying the activity of AthCCT1, with an emphasis on its protein-protein interactions. The combination of yeast two-hybrid and bimolecular fluorescence complementation assays identified several interacting partners of AthCCT1, including AthCCT1 itself, AthCCT2, potential nuclear importin α and β subunits, and an Arabidopsis Sec14 family protein. These results shed light on the dimerization behavior of AthCCT1 and its role in forming potential protein complexes, which likely contribute to PC homeostasis. To summarize, this thesis investigates the roles of AthCCT1 in plant phospholipid metabolism, including its evolutionary history, structural dynamics, physiological functions, and protein-protein interactions. The research provides novel insights into AthCCT1’s involvement in PC biosynthesis, its important roles in plant development under stress conditions, and its participation in protein complexes, thereby contributing to a deeper understanding of its function in plant cellular processes

Uncovering Roles For Myristoylation in Cancer, and NMTs as a New Therapeutic Target in Acute Myeloid Leukemia

Protein myristoylation is a form of modification by the attachment of the fatty acid myristate to the N-terminus, helping to regulate protein localization, stability, and function. Myristoylation has been proposed as a therapeutic target in cancer for decades, but only recently have high-quality compounds targeting N-myristoyltransferase 1 and 2 (NMTs, the enzymes catalyzing protein myristoylation) been developed to enable the targeting of this process. Hematopoietic cancers such as Acute Myeloid Leukemia (AML) have been proposed as vulnerable to NMT inhibitors (NMTi) such as zelenirstat. AML is an aggressive cancer with poor clinical outcomes tied to disease relapse and resistance to therapy. Relapses are believed to be driven by leukemic stem cells (LSCs) which are highly resistant to conventional therapies and expand to re-establish the disease. Patient survival rates upon relapse are extremely low, highlighting a need for new therapies capable of both targeting LSCs, and overcoming common mechanisms of resistance. The primary goal of this study was to conduct a pre-clinical evaluation of zelenirstat as a novel therapeutic for AML, providing proof of concept and the necessary investigation to initiate clinical trials. Zelenirstat inhibits signaling through Src-family kinases necessary for oncogenic signaling through clinically relevant FLT3 and KIT receptors, in addition to inhibiting oxidative phosphorylation and AMPK activity necessary for LSC function. AML cell stress and apoptosis was induced by zelenirstat, and cell killing observed in vitro and in vivo, with an apparently selectivity for LSC-enriched populations of the OCI-AML-22 cell model. Zelenirstat also inhibited glycolysis in AML cells, presenting a potent multi-pathway inhibitor capable of targeting LSCs with high potential for synergy with venetoclax. Analysis of AML patient data revealed NMT2 expression functions as a prognostic marker in AML patients experiencing poor outcomes under current standards of care were associated with both low NMT2 expression and high MISS-54 score, predictive of positive response to zelenirstat. Following the broad metabolic impacts of zelenirstat in AML, we further explored the impacts upon mitochondria in HeLa cells. We confirmed inhibition of oxidative phosphorylation and glycolysis in this model, and demonstrated induction of cellular calcium leakage and suppression of glutathione metabolism as a consequence of zelenirstat treatment. Additionally, we provide the first evidence of NMTi disrupting mitochondrial structure, with loss of mitochondrial cristae organization and density upon zelenirstat treatment. Additional validation of the impacts of zelenirstat on AMPK show near-complete loss of activation, compromising the ability of the cell to respond to energetic stress. Next we attempted to contextualize the sensitivity of cancer cells to zelenirstat through pan-cancer analysis of NMT levels, response to zelenirstat, and differential analysis of multi-omics in the context of zelenirstat treatment or genetic NMT ablation. We find that genes related to oxidative phosphorylation are among the most responsive to disruption of protein myristoylation, and present myristoylation inhibition sensitivity signature MISS-54. Developed from differential genomic analysis of more than 1200 cell lines screened for sensitivity against NMTis, MISS-54 allows for prediction of tumor sensitivity to NMTi. MISS-54 is also demonstrated to be lower in cognate healthy tissues than in cancer, supporting the notion of increased sensitivity of cancer to NMTi. Collectively, this work identifies a critical role for myristoylation in oxidative phosphorylation and mitochondria as a significant, pan-cancer target of NMTi. This represents a key mechanism by which NMTi could target both LSCs and cancer stem cells at large, helping to improve and lengthen patient remissions. The large number of pathways in which myristoylated proteins participate give zelenirstat a pleiotropic function to tackle genetically and functionally diverse cancers, smothering resistance. In AML, zelenirstat is an exciting new therapeutic option starting clinical trials with predicted benefit to patients in desperate need of improved outcomes. This study identifies key mechanisms and provides rationale necessary for clinical trials and beyond

Conversion of barley straw and shrimp shell to value-added hydrogels and aerogels using environmentally friendly technologies: Pressurized fluid, high intensity ultrasound, and supercritical CO2 drying

Upcycling refers to the process of transforming low value biomass to new materials of higher quality, price, or functionality. Barley straw, an agricultural biomass mainly composed of cellulose (30-40%), hemicellulose (20-25%) and lignin (15-17%), and shrimp shell, an animal biomass composed of chitin (15-22%) and protein (41-49%), are underutilized by-products with low market value. The main objective of this thesis was to use pressurized fluids (PF) to fractionate barley straw and shrimp shell, and then bleach and nanofibrillate the obtained cellulose fiber via high-intensity ultrasound (HIUS) to produce self-assembled scaffolds. Specifically, barley straw and shrimp shell were first upcycled to obtain cellulose nanofiber (CNF) and chitosan (CS), respectively. In addition, CS, a natural cross-linker, was used to produce composite scaffolds with CNF, which were loaded with collagen peptide (COLP) that can be potentially used as scaffolds for tissue engineering. The first two studies investigated the catalytic effect of aqueous ethanol and carboxylic acid at subcritical water (sCW) conditions on the hydrolysis of barley straw (180-220°C, 50-200 bar, flow rate of 5 mL/min for 40 min, 0-100% v/v ethanol) and shrimp shell (140-260oC, 50 bar, 5 mL/min for 10-60 min, 0-10 wt.% citric and malic acid). The maximum amount of hemicellulose sugars was removed from barley straw after sCW treatment at 200°C/40 min, resulting in a cellulose-rich residue (purity 68.43%). Pressurized aqueous ethanol (PAE 60%) at 220oC removed more phenolic compounds (75.38 mg GAE/g straw) and lignin (63.77%). On the other hand, sCW treatment of shrimp shell at 260oC for 60 min resulted in the highest chitin yield of 26.39%, with deproteinization degree of 58.05%, and deacetylation degree of 66.29%. The sCW + malic acid (10 wt.%) treatment at 260oC/60 min improved amino acid removal to 140.11 mg/g shrimp shell. These results indicated that PAE and sCW + carboxylic acid can catalyze the delignification and deproteinization of barley straw and shrimp shell, respectively. The third and fourth studies investigated the effect of HIUS treatment on delignification and nanofibrillation of the obtained cellulose-rich residue. Three different bleaching processes (acidic sodium chlorite bleaching, alkaline hydrogen peroxide bleaching, and HIUS-assisted bleaching) at 75-80°C for 2-6 h were investigated, resulting in cellulose fiber with purity of 91%, and diameter of 3-5 μm. Then, cellulose fiber was nanofibrillated using the HIUS treatment (24-72 kJ/g) to obtain CNF hydrogels with a maximum fibrillation yield of 62 wt.% at 72 kJ/g. After, hydrogels were supercritical CO2 (SC-CO2) dried to form aerogels. The addition of shrimp shell CS improved aerogel stiffness to 3.2 bar, which is good for scaffolds. The last study loaded COLP (1-10 wt.%) in CNF + CS composite hydrogels using a HIUS treatment and freeze-dried to form aerogels. The cumulative release of COLP from CNF + CS aerogels followed a biphasic pattern, where 15.90 and 35.49% of COLP were released within 1 and 48 h, respectively. In summary, the results suggested that PF treatment followed by HIUS and SC-CO2 or freeze drying is a promising strategy for biorefining barley straw and shrimp shell towards nanofiber and potential tissue engineering scaffold production