Stability engineering

Monoclonal antibodies (mAbs) require a high level of purity for regulatory approval and safe administration. High-molecular weight (HMW) species are a common impurity associated with mAb therapies. Hydrophobic interaction chromatography (HIC) resins are often used to remove these HMW impurities. Determination of a suitable HIC resin can be a time and resource-intensive process. In this study, we modeled the chromatographic behavior of seven mAbs across 13 HIC resins using measurements of surface hydrophobicity, surface charge, and thermal stability for mAbs, and hydrophobicity and zeta-potential for HIC resins with high fit quality (adjusted R2  > 0...

The Thermomyces lanuginosus lipase (TLLs) was successfully immobilized within a novel hydrogel matrix through a two-step crosslinking method. TLLs were initially crosslinked through the Schiff base reaction by oxidized carboxymethyl cellulose (OCMC). The water-soluble OCMC@TLLs complex was subsequently crosslinked by carboxymethyl chitosan (CMCSH) in a microfluidic apparatus to form the CMCHS/OCMC@TLLs microspheres. The CD (Circular Dichroism, CD) and FT-IR (Fourier Transform infrared spectroscopy, FT-IR) spectra demonstrated that the crosslinking of TLLs with OCMC resulted in a less significant impact on their structure compared to that with glutaraldehyde...

Enzymatic degradation of synthetic dyes holds an immense promise for addressing the environmental concerns associated with the textile and dye industries. This study aimed to isolate bacteria capable of producing laccase enzymes from an anthropogenic environment. Subsequently, viability of utilizing cost-effective agricultural residues as substrates for laccase production was assessed. Response Surface Methodology (RSM) and the One Variable at a Time (OVAT) approach was pursued for the optimization of laccase production, followed by pH and temperature stability, dye degradation and decolorization experiments, toxicological studies on the degraded dye metabolites...

Ultrasonic manufacturing has emerged as a promising eco-friendly approach to synthesize lipid-based nanocarriers for targeted drug delivery. This study presents the novel ultrasonic preparation of lipid nanocarriers loaded with Scutellaria barbata extract, repurposed for anticancer and antibacterial use. High-frequency ultrasonic waves enabled the precise self-assembly of DSPE-PEG, Span 40, and cholesterol to form nanocarriers encapsulating the therapeutic extract without the use of toxic solvents, exemplifying green nanotechnology...

5-Hydroxymethylfurfural (HMF) is a versatile platform chemical derived from the dehydration of renewable carbohydrates (typically glucose/fructose-based monosaccharides, oligosaccharides, and polysaccharides). Some useful compounds, such as 2,5-furandimethanol (FDM), 2,5-dimethylfuran (DMF) and 2,5-dimethyltetrahydrofuran (DMTHF), have been synthesized by reduction of HMF. Among these, FDM is a promising diol and can be further converted towards fine chemicals, liquid fuels and polymer materials. In this review, some typical catalytic systems for the synthesis of FDM from both HMF and carbohydrates were summarized...

Fermentation is the key process required for developing the characteristic properties of cigar tobacco leaves, complex microorganisms are involved in this process. However, the microbial fermentation mechanisms during the fermentation process have not been well-characterized. This study investigated the dynamic changes in conventional chemical composition, flavor compounds, and bacterial community during the fermentation of cigar tobacco leaves from Hainan and Sichuan provinces in China, as well as the potential roles of bacteria...

Biocopolymers based on vanillin/fufurylamine-biobenzoxazine (V-fa) and epoxide castor oil (ECO), a bioepoxy, were prepared for application as dental fiber-reinforced composite post. The mechanical and thermal properties of the V-fa/ECO biocopolymers were assessed with regard to the influence of ECO content. The addition of the ECO at an amount of 20% by weight into the poly(V-fa) preserved the stiffness, glass transition temperature and thermal stability nearly to the poly(V-fa). Differential scanning calorimetry (DSC) was used to examine the curing kinetics of the V-fa/ECO monomer system with different heating rates...

There is increasing attention to the production of cellulose nanocrystals (CNCs) from lignocellulosic biomass by enzymatic hydrolysis with cellulase. In this study, the feasibility of the application of a cellulase system from engineered strain Penicillium oxalicum cEES in the production of CNCs was assessed. Using commercial eucalyptus dissolving pulp (EDP) as substrate, the CNCs were successfully obtained by enzymatic hydrolysis with the cellulase cEES, and the total yields of CNCs reached 15.7% through three-step enzymatic hydrolysis of total 72 h (24 h for each step)...

A critical measure of the quality of pharmaceutical proteins is the preservation of native conformations of the active pharmaceutical ingredients. Denaturation of the active proteins in any step before administration into patients could lead to loss of potency and/or aggregation, which is associated with an increased risk of immunogenicity of the products. Interfacial stress enhances protein instability as their adsorption to the air-liquid and liquid-solid interfaces are implicated in the formation of denatured proteins and aggregates...

Patients with brain cancers including medulloblastoma lack treatments that are effective long-term and without side effects. In this study, a multifunctional fluoropolymer-engineered iron oxide nanoparticle gene-therapeutic platform is presented to overcome these challenges. The fluoropolymers are designed and synthesized to incorporate various properties including robust anchoring moieties for efficient surface coating, cationic components to facilitate short interference RNA (siRNA) binding, and a fluorinated tail to ensure stability in serum...

Ligand engineering is crucial for tuning the structural and optoelectronic properties of perovskite nanocrystals (NCs), which also improves their stability. In contrast to the typically used long-chain alkylamine ligands, we successfully introduced an aromatic 1-( p -tolyl)ethylamine (PTEA) ligand to synthesize the CsPbX3 (X = Br or I) NCs. The CsPbI3 and CsPbBr3 NCs demonstrated long carrier lifetimes of ∼877 and 49 ns, respectively, as well as high photoluminescence quantum yields (PLQYs) of ∼99% and 95%, respectively...

As living standards rise, more and more people are paying attention to their own health, especially issues such as cerebral thrombosis, cerebral infarction, and other cerebral blood flow problems. An accurate simulation of blood flow within cerebral vessels has emerged as a crucial area of research. In this study, we focus on microcirculatory blood flow in ischemic brain tissue and employ a 0D-1D geometric multi-scale coupled model to characterize this process. Given the intricate nature of human cerebral vessels, we apply a numerical method combining the finite element method and the third-order Runge-Kutta method to resolve the coupled model...

Successful engineering of functional salivary glands necessitates the creation of cell-instructive environments for ex vivo expansion and lineage specification of primary human salivary gland stem cells (hS/PCs). Herein, basement membrane mimetic hydrogels were prepared using hyaluronic acid, cell adhesive peptides, and hyperbranched polyglycerol (HPG), with or without sulfate groups, to produce "hyperGel+" or "hyperGel", respectively. Differential scanning fluorescence experiments confirmed the ability of the sulphated HPG precursor to stabilize fibroblast growth factor 10...

Despite recent studies indicating a significant correlation between somatosensory deficits and rehabilitation outcomes, how prevailing somatosensory deficits affect stroke survivors' ability to correct their movements and recover overall remains unclear. To explore how major deficits in somatosensory systems impede stroke survivors' motor correction to various external loads, we conducted a study with 13 chronic stroke survivors who had hemiparesis. An inertial, elastic, or viscous load, which was designed to impose perturbing forces with various force profiles, was introduced unexpectedly during the reaching task using a programmable haptic robot...

This study focuses on modifying the porous structure of acid-treated rice husk ash (ARHA) to enhance the thermal energy storage capacity of poly(ethylene glycol) (PEG) confined within shape-stabilized phase change materials. The modification process involved a cost-effective sol-gel method in which ARHA was initially dissolved in an alkaline solution and subsequently precipitated in an acidic environment. ARHA, being a mesoporous SiO2 -based material with a high surface area but low pore volume, had limited capacity to adsorb PEG (50%)...

Transparent microelectrodes have received much attention from the biomedical community due to their unique advantages in concurrent crosstalk-free electrical and optical interrogation of cell/tissue activity. Despite recent progress in constructing transparent microelectrodes, a major challenge is to simultaneously achieve desirable mechanical stretchability, optical transparency, electrochemical performance, and chemical stability for high-fidelity, conformal, and stable interfacing with soft tissue/organ systems...

Bismuth-based materials have been recognized as the appealing anodes for potassium-ion batteries (PIBs) due to their high theoretical capacity. However, the kinetics sluggishness and capacity decline induced by the structure distortion predominately retard their further development. Here, a heterostructure of polyaniline intercalated Bi2 O2 CO3 /MXene (BOC-PA/MXene) hybrids is reported via simple self-assembly strategy. The ingenious design of heterointerface-rich architecture motivates significantly the interior self-built-in electric field (IEF) and high-density electron flow, thus accelerating the charge transfer and boosting ion diffusion...

Single-atom enzymes (SAzymes) exhibit great potential for chemodynamic therapy (CDT); while, general application is still challenged by their instability and unavoidable side effects during delivery. Herein, a manganese-based polyoxometalate single-atom enzyme (Mn-POM SAE) is first introduced into tumor-specific CDT, which exhibits tumor microenvironment (TME)-activated transition of nontoxicity-to-toxicity. Different from traditional POM materials, the aggregates of low-toxic Mn-POM SAE nanospheres are obtained at neutral conditions, facilitating efficient delivery and avoiding toxicity problems in normal tissues...

Lipid-polymer nanoparticles offer a promising strategy for improving gene nanomedicines by combining the benefits of biocompatibility and stability associated with the individual systems. However, research to date has focused on poly-lactic-co-glycolic acid (PLGA) and resulted in inefficient transfection. In this study, biocompatible Eudragit constructs E100 and RS100 were formulated as lipid-polymer nanoparticles loaded with pDNA expressing red fluorescent protein (RFP) as a model therapeutic. Using a facile nanoprecipitation technique, a core-shell structure stabilised by lipid-polyethylene glycol (PEG) surfactant was produced and displayed resistance to ultracentrifugation...

Non-equilibrium (NEQ) alchemical free energy calculations are an emerging tool for accurately predicting changes in protein folding free energy resulting from amino acid mutations. In this study, this method in combination with the Rosetta ddg monomer tool was applied to predict more thermostable variants of the polyethylene terephthalate (PET) degrading enzyme DuraPETase. The Rosetta ddg monomer tool efficiently enriched promising mutations prior to more accurate prediction by NEQ alchemical free energy calculations...