Unleashing the Potential: Designing Antibody-Targeted Lipid Nanoparticles for Industrial Applications with CMC Considerations and Clinical Outlook.

Antibody-targeted lipid nanoparticles (Ab-LNPs) are rapidly gaining traction as multifaceted platforms in precision medicine, adept at delivering a diverse array of therapeutic agents, including nucleic acids and small molecules. This review provides an incisive overview of the latest developments in the field of Ab-LNP technology, with a special emphasis on pivotal design aspects such as antibody engineering, bioconjugation strategies, and advanced formulation techniques. Furthermore, it addresses critical chemistry, manufacturing, and controls (CMC) considerations and thoroughly examines the in vivo dynamics of Ab-LNPs, underscoring their promising potential for clinical application. By seamlessly blending scientific advancements with practical industrial perspectives, this review casts a spotlight on the burgeoning role of Ab-LNPs as an innovative and potent tool in the realm of targeted drug delivery.

Oral P. gingivalis impairs gut permeability and mediates immune responses associated with neurodegeneration in LRRK2 R1441G mice.

BACKGROUND: The R1441G mutation in the leucine-rich repeat kinase 2 (LRRK2) gene results in late-onset Parkinson's disease (PD). Peripheral inflammation and gut microbiota are closely associated with the pathogenesis of PD. Chronic periodontitis is a common type of peripheral inflammation, which is associated with PD. Porphyromonas gingivalis (Pg), the most common bacterium causing chronic periodontitis, can cause alteration of gut microbiota. It is not known whether Pg-induced dysbiosis plays a role in the pathophysiology of PD. METHODS: In this study, live Pg were orally administrated to animals, three times a week for 1 month. Pg-derived lipopolysaccharide (LPS) was used to stimulate mononuclear cells in vitro. The effects of oral Pg administration on the gut and brain were evaluated through behaviors, morphology, and cytokine expression. RESULTS: Dopaminergic neurons in the substantia nigra were reduced, and activated microglial cells were increased in R1441G mice given oral Pg. In addition, an increase in mRNA expression of tumor necrosis factor (TNF-α) and interleukin-1ß (IL-1ß) as well as protein level of α-synuclein together with a decrease in zonula occludens-1 (Zo-1) was detected in the colon in Pg-treated R1441G mice. Furthermore, serum interleukin-17A (IL-17A) and brain IL-17 receptor A (IL-17RA) were increased in Pg-treated R1441G mice. CONCLUSIONS: These findings suggest that oral Pg-induced inflammation may play an important role in the pathophysiology of LRRK2-associated PD.

Amphiphilic DNA Organic Hybrids: Functional Materials in Nanoscience and Potential Application in Biomedicine.

Due to the addressability and programmability, DNA has been applied not merely in constructing static elegant nanostructures such as two dimensional and three dimensional DNA nanostructures but also in designing dynamic nanodevices. Moreover, DNA could combine with hydrophobic organic molecules to be a new amphiphilic building block and then self-assemble into nanomaterials. Of particular note, a recent state-of-the-art research has turned our attention to the amphiphilic DNA organic hybrids including small molecule modified DNA (lipid-DNA, fluorescent molecule-DNA, etc.), DNA block copolymers, and DNA-dendron hybrids. This review focuses mainly on the development of their self-assembly behavior and their potential application in nanomaterial and biomedicine. The potential challenges regarding of the amphiphilic DNA organic hybrids are also briefly discussed, aiming to advance their practical applications in nanoscience and biomedicine.

Digging More Missing Proteins Using an Enrichment Approach with ProteoMiner.

Human Proteome Project (HPP) aims at mapping entire human proteins with a systematic effort upon all the emerging techniques, which would enhance understanding of human biology and lay a foundation for development of medical applications. Until now, 2563 missing proteins (MPs, PE2-4) are still undetected even using the most sensitive approach of protein detection. Herein, we propose that enrichment of low-abundance proteins benefits MPs finding. ProteoMiner is an equalizing technique by reducing high-abundance proteins and enriching low-abundance proteins in biological liquids. With triton X-100/TBS buffer extraction, ProteoMiner enrichment, and peptide fractionation, 20 MPs (at least two non-nested unique peptides with more than eight a.a. length) with 60 unique peptides were identified from four human tissues including eight membrane/secreted proteins and five nucleus proteins. Then 15 of them were confirmed with two non-nested unique peptides (≥9 a.a.) identified by matching well with their chemically synthetic peptides in PRM assay. Hence, these results demonstrated ProteoMiner as a powerful means in discovery of MPs.

[Comparison of soft and hard tissue stability between immediate implant and delayed implant in maxillary anterior region after loading 2 years].

OBJECTIVE: To compare the peri-implant tissue stability between immediate implant and delayed implant in maxillary anterior region after loading 2 years. METHODS: In the study, 38 patients with single anterior tooth loss in the Second Clinical Division of Peking University School and Hospital of Stomatology from October 2010 to December 2011 were enrolled, and 43 implants were inserted. The gingival contour was induced using implant-supported temporary crowns prior to restoration till permanent prostheses delivered. The gingival papilla height, labial gingival margin level and peri-implant bone level were measured immediately after the permanent restoration and 2 years later. RESULTS: In the study, 16 patients were treated by immediate implant for 17 implants; 22 patients were treated by delayed implant for 26 implants. The implant stability quotient (ISQ) value of the 2 groups showed no significant difference before permanent restoration (P>0.05). In all the cases after loading 2 years, the average mesial gingival papilla height in the implant area of the immediate group and delayed group increased by (0.15 ± 0.42) mm and (0.06 ± 0.65) mm, respectively; the distal gingival papilla height increased by (0.06 ± 0.50) mm and (0.02 ± 0.57) mm respectively; while the labial gingival margin level shrinkages were (0.15 ± 0.23) mm and (0.15 ± 0.46) mm, respectively. The peri-implant bone losses in the mesial side were (0.67 ± 0.35) mm and (0.6 9 ± 0.49) mm, respectively, while in the distal side were (0.73 ± 0.31) mm and (0.75 ± 0.48) mm, respectively. All these indicators showed no significant difference between the 2 groups (P>0.05). CONCLUSION: Both the cases obtained optimizer results after loading 2 years, and the soft and hard tissues around the implant were very stable, which means that both the protocols can achieve reliable therapeutic effects. If we can handle the indications, immediate implant for anterior teeth shows similar efficacy with delayed implant in the short term. But immediate implant in terms of shortening the course of treatment is clearly superior to delayed implant.

The influence of impaction to the third molar mineralization in northwestern Chinese population.

Age estimation by third molar mineralization has been developed for a period of time. Recent studies showed that impaction status has an influence on the rate of the third molar mineralization in Europids and male Black African populations. In this regard, the present study was conducted to determine whether the impaction status could delay the chronological process of third molar mineralization in northwestern Chinese population too. A total of 3,512 digital orthopantomograms of 1,255 male and 2,257 female northwestern Chinese subjects aged from 11 to 26 years were assessed based on the formation stages described by Demirjian et al. with two modifications. Mineralization stage and impaction status were determined for all third molars. Statistical measures were calculated at stages C-H in the male and female gender for both impacted and non-impacted third molars. It was ascertained that the mean ages with impacted third molars at stages C-H were 0.02-1.42 years higher in males and 0.04-1.52 years higher in females than those with non-impacted third molars, but statistical differences were only found at stages C, D, and E in males and stages D and E in females. The probabilities of being under 14, 16, or 18 years of age with non-impacted third molars were all higher than those with impacted third molars. The results prove that impacted third molars show significant slower mineralization than non-impacted ones at stages D and E in both males and females of northwestern Chinese population. It is recommended to consider the influence of impaction on the rate of third molar mineralization for dental age estimation.

Preparation of novel polyvinyl alcohol-carbon nanotubes containing imidazolyl ionic liquid/chitosan hydrogel for highly efficient uranium extraction from seawater.

A novel polyvinyl alcohol-carbon nanotube containing an imidazolyl ionic liquid/chitosan composite hydrogel (termed CBCS) was prepared for highly selective uranium adsorption from seawater. The results show that CBCS has good adsorption properties for uranium within the pH range of 5.0-8.0. Kinetics and thermodynamics experiments show that the theoretical maximum adsorption capacity of CBCS to U(VI) is 496.049 mg/g (288 K, pH = 6.0), indicating a spontaneous exothermic reaction. Mechanism analysis shows that the hydroxyl group, amino group, and CN bond on the surface of CBCS directly participate in uranium adsorption and that the dense pores on the surface of CBCS play an important role in uranium adsorption. The competitive adsorption experiment shows that CBCS has excellent uranium adsorption selectivity. In addition, CBCS exhibits good reusability. After five adsorption-desorption cycles, the uranium adsorption rate of CBCS can still reach >98 %. Hence, CBCS has excellent potential for uranium extraction from seawater.

Diffusion-based culture and real-time impedance monitoring of tumor spheroids in hydrogel microwells of a suspended membrane under microfluidic conditions.

Tumor spheroids are widely studied for in vitro modeling of tumor growth and responses to anticancer drugs. However, current methods are mostly limited to static and perfusion-based cultures, which can be improved by more accurately mimicking pathological conditions. Here, we developed a diffusion-based dynamic culture system for tumor spheroids studies using a thin membrane of hydrogel microwells and a microfluidic device. This allows for effective exchange of nutrients and metabolites between the tumors and the culture medium flowing underneath, resulting in uniform tumor spheroids. To monitor the growth and drug response of the spheroids in real-time, we performed spectroscopic analyses of the system's impedance, demonstrating a close correlation between the tumor size and the resistance and capacitance of the system. Our results also indicate an enhanced drug effect on the tumor spheroids in the presence of a low AC electric field, suggesting a weakening mechanism of the spheroids induced by external perturbation.

Abundance, characteristics and ecological risks of microplastics from South Yellow Sea Mudflat.

Microplastic (MP) pollution in global marine environments has been extensively reported and attracted significant concerns, but MP distribution in mudflat has rarely been studied. In this paper, the abundance, features and ecological risk of MP in South Yellow Sea Mudflat were investigated comprehensively. MP were both detected in waters (5.4 ± 0.38-11.3 ± 0.78 items/L) and sediments (5.1 ± 0.36-10.1 ± 0.69 items/g) from South Yellow Sea Mudflat. There existed different MP abundance tendencies from sampling Group I (coastal estuary or port) and II (purely coastal mudflat), while MP abundance in water from Group II was lower than that from Group I generally, but MP abundance in sediment from Group I was lower than that from Group II generally. This suggested that MP abundance in mudflat water could be associated with frequent human activities significantly, and disturbance might not be beneficial to MP accumulation in sediments. Fragments, transparent, polyethylene (PE), polypropylene (PP) and polystyrene (PS) were major MP features in mudflat water and sediment, and maximum proportion of size of MP was 0.001-0.25 mm in both water and sediment. Furthermore, the primary risk assessment indicated that MP pollution load for mudflat was low level. However, potential MP ecological risk for mudflat could reach dangerous level to very dangerous level by calculating and evaluating polymer risk index (PRI) and potential ecological risk index (PERI), which could be caused by high proportions of polyvinyl chloride (PVC) and polyacrylonitrile (PAN) with high hazard score. For the first time, reference data about MP pollution from South Yellow Sea Mudflat were supplied in this paper, which would be helpful for management and control of MP in mudflat.

Toward the Development of Simplified Lateral Flow Assays Using Hydrogels as the Universal Control Line.

Lateral flow assays (LFA) have been widely utilized as point-of-care testing devices in diverse fields. However, it is imperative to preprint costly bioreceptors onto the lateral flow nitrocellulose membrane at the control line. The complex manufacturing process and relatively limited detection capabilities of LFA have impeded their utilization in more challenging fields. Here, we propose a novel and simple strategy to simplify the manufacture of LFA while simultaneously improving the sensitivity by modifying the hydrogel line (HL). In our study, it was observed that the sensitivity of commercial LFA strips could be enhanced by 2-5-fold by incorporating an extra HL. Particularly, a universal control line was developed to accommodate multiple LFA detection modes by substituting the conventional antibody control line with a hydrogel control line (HCL). As a proof of concept, the HCL performance could be associated with the slowdown and interception effect toward fluid, which are dependent on the permeation and hydrophilicity of the hydrogel with varying concentrations in the nitrocellulose membrane. This new design builds the foundation to enhance the sensitivity and develop the simplified LFA sensing platform without additional complicated processes.

High salinity effects on the depletion attraction in colloid-polymer mixtures.

HYPOTHESIS: Depletion attraction induced by polymers can be employed across multiple disciplines. Previous studies implied that besides screening the electrostatic repulsion between colloids, adding salt may also affect the polymers even in a nonpolar solvent. Here, we study the depletion-induced gelation of a colloid-polymer model system, focusing on the salt effects on the depletion attraction. EXPERIMENTS: Confocal microscopy was used to quantitatively characterize the colloidal gels formed by the polymethylmethacrylate (PMMA)/polystyrene (PS) model system. The attraction experienced by colloids was estimated by correlating the colloidal dynamics with the local structure. Correspondingly, static light scattering was employed to systematically investigate the polymers. The resulting radius of gyration Rg and osmotic pressure were used to evaluate the depletion attraction offered by polymers. FINDINGS: Salt was discovered to lower the strength of inter-particle attraction, which can be attributed to the salt-induced decrease in Rg. The depletion attraction grew sublinearly with c, owing to the considerable decrease in Rg in the good solvent as c increased. We demonstrated how the close form equations in the framework of renormalization group theory can be employed to predict the depletion interaction using the properly determined zero-concentration radius of gyration.

Characteristics and potential human health risks of microplastics identified in typical clams from South Yellow Sea Mudflat.

The ingestion of clams (Meretrix) with microplastics (MP) contamination could pose potential risk to human health. The characteristics and potential risks of MP identified in wild-clam and farm-clam from South Yellow Sea Mudflat were studied comprehensively in this paper. The results indicated that MP were identified in both wild-clam (3.4-21.3 items/individual, 2.11-10.65 items/g) and farm-clam (1.3-20.8 items/individual, 0.62-8.67 items/g) among 21 sampling sites along South Yellow Sea Mudflat. The MP abundance of clams from marine estuarine or coast ports were significantly higher than those from purely marine coast mudflat, implying that environmental habitats played an important role on MP characteristics. MP abundance were significantly and positively related to shell length, shell height, shell width and soft tissue wet weight by Pearson test, suggesting the bigger the shell, there existed more MP abundance. Among MP in wild-clams and farm-clams, fragment, fiber were most abundant MP shapes, most MP's sizes were lower than 0.25 mm, the predominant colors were black, red, blue and transparent, chlorinated polyethylene (CPE) was the major polymer. Additionally, estimated dietary intake (EDI) of MP for adults via consumption of wild-clam and farm-clam were 1123.33 ± 399.97 and 795.07 ± 326.72 items/kg/year, respectively, suggesting EDI values of wild-clams were higher than those of farm-clams, and MP intake via wild-clam consumption were more than that via farm-clam consumption. The polymer risk indexes (PRI) of MP in total tissue and digestive system for wild-clam were 1297.8 ± 92.15 (hazard level: IV ~ V), 1038 ± 69.55 (IV ~ V), respectively, while PRI of MP in total tissue and digestive system for farm-clam were 979.92 ± 75.45 (III ~ IV), 735 ± 47.78 (III ~ IV), respectively, implying that PRI and hazard level of MP from wild-clam were higher than those from farm-clam, and the potential risks would decrease greatly when digestive systems of clams are removed during ingestion.

Recent advances in chiral discrimination on host-guest functionalized interfaces.

Chiral discrimination has gained much focus in supramolecular chemistry, since it is one of the fundamental processes in biological systems, enantiomeric separation and biochemical sensors. Though most of the biochemical processes can routinely recognize biological enantiomers, enantioselective identification of chiral molecules in artificial systems is currently one of the challenging topics in the field of chiral discrimination. Inaccuracy, low separation efficiency and expensive instrumentation were considered typical problems in artificial systems. Recently, chiral recognition on the interfaces has been widely used in the fields of electrochemical detection and biochemical sensing. For the moment, a series of macrocyclic host functionalized interfaces have been developed for use as chiral catalysts or for enantiomeric separation. Here, we have briefly exposited the most recent advances in the fabrication of supramolecular functionalized interfaces and their application for chiral recognition.

Temperature/near-infrared light-responsive conductive hydrogels for controlled drug release and real-time monitoring.

Stimuli-responsive hydrogels with adaptable physical properties show great potential in the biomedical field. In particular, the collection of electrical signals is essential for precision medicine. Here, a simple strategy is demonstrated for achieving controlled drug release and real-time monitoring using an interpenetrating binary network consisting of a graphene aerogel and a poly(N-isopropylacrylamide) hydrogel with incorporated polydopamine nanoparticles (PDA-NPs). Owing to the good physical properties of graphene and the embedded PDA-NPs, the hybrid hydrogel shows enhanced mechanical properties and good electrical conductivity. In addition, the hybrid hydrogel also shows dual thermo- and near-infrared light responsiveness, as revealed by the controlled release of a model drug. In addition, as the hydrogel exhibits detectable changes in resistance during drug release, the drug-release behavior of the hydrogel can be monitored in real time using electrical signals. Moreover, owing to the abundance of catechol groups on the PDA-NPs, the hybrid hydrogel shows good tissue adhesiveness, as demonstrated using in vivo experiments. Thus, the developed hybrid hydrogel exhibits considerable practical applicability for drug delivery and precision medicine.

Melt electrohydrodynamic 3D printed poly (ε-caprolactone)/polyethylene glycol/roxithromycin scaffold as a potential anti-infective implant in bone repair.

Implanted scaffold or bone substitute is a common method to treat bone defects. However, the possible bone infection caused by orthopaedic surgery has created a challenging clinical problem and generally invalidate bone repair and regeneration. In this study, a poly (ε-caprolactone) (PCL)/polyethylene glycol (PEG)/roxithromycin (ROX) composite scaffold was prepared via melt electrohydrodynamic (EHD) 3D printing. Fourier transform infrared spectroscopy (FTIR) spectroscopy was performed to verify the existence of PEG and ROX in the scaffolds. By water contact angle measurement, the addition of both PEG and ROX was found to improve the hydrophilicity of the scaffolds. By in vitro drug release assay, the PCL/PEG/ROX scaffolds showed an initial burst drug release and subsequent long-term sustained release behaviour, which is favourable for the prevention and treatment of bone infections. The antibacterial assays against E. coli and S. aureus demonstrated that the composite scaffold with ROX possessed effective antibacterial activity, especially for S. aureus, the main cause of bone infection. The immunostaining and MTT assay with human osteoblast-like cells (MG63) indicated that cells showed good viability and growth on the scaffolds. Therefore, the melt EHD 3D printed PCL/PEG/ROX scaffold could be a promising anti-infective implant for bone tissue engineering.

Sensitive Deep Ultraviolet Photodetector and Image Sensor Composed of Inorganic Lead-Free Cs3Cu2I5 Perovskite with Wide Bandgap.

In this work, a sensitive deep ultraviolet (DUV) light photodetector based on inorganic and lead-free Cs3Cu2I5 crystalline film derived by a solution method was reported. Optoelectronic characterization revealed that the perovskite device exhibited nearly no sensitivity to visible illumination with wavelength of 405 nm but exhibited pronounced sensitivity to both DUV and UV light illumination with response speeds of 26.2/49.9 ms for rise/fall time. The Ilight/Idark ratio could reach 127. What is more, the responsivity and specific detectivity were calculated to be 64.9 mA W-1 and 6.9 × 1011 Jones, respectively. In addition, the device could keep its photoresponsivity after storage in air environment for a month. It is also found that the capability of Cs3Cu2I5 crystalline film device can readily record still DUV image with acceptable resolution. The above results confirm that the DUV photodetector may hold great potential for future DUV optoelectronic device and systems.

A simple polymer electrolyte membrane system for enrichment of low-level tritium (3H) in environmental water samples.

Tritium (3H) is an essential tracer of the Earth's water cycle; yet widespread adoption of tritium in hydrologic studies remains a challenge because of analytical barriers to quantification and detection of 3H by electrolytic pre-concentration. Here, we propose a simple tritium electrolytic enrichment system based on the use of solid polymer electrolyte membranes (PEMs) that can be used to enrich 3H in 250-3000 mL environmental water samples to a 10-mL final volume. The IAEA PEM-3H system reported here can produce high enrichment factors (>70-fold) and, importantly, removes some of the deterrents to conventional 3H enrichments methods, including the use of toxic electrolysis and neutralization chemicals, spike standards, a complex electrolysis apparatus that requires extensive cooling and temperature controls, and improves precision by eliminating the need for tracking recovery gravimetrics. Preliminary results with varying operating conditions show 3H enrichments to 70-fold and higher are feasible, spanning a wide range of tritium activities from 5 to 150 TU with a precision of ∼4.5 %. Further work is needed to quantify inter-sample memory and to establish lower 3H detection limits. The IAEA PEM-3H system is open source, with 3-D CAD and design files made freely available for adoption and improvement by others.

Fabrication of porous ultra-short single-walled carbon nanotube nanocomposite scaffolds for bone tissue engineering.

We investigated the fabrication of highly porous scaffolds made of three different materials [poly(propylene fumarate) (PPF) polymer, an ultra-short single-walled carbon nanotube (US-tube) nanocomposite, and a dodecylated US-tube (F-US-tube) nanocomposite] in order to evaluate the effects of material composition and porosity on scaffold pore structure, mechanical properties, and marrow stromal cell culture. All scaffolds were produced by a thermal-crosslinking particulate-leaching technique at specific porogen contents of 75, 80, 85, and 90 vol%. Scanning electron microcopy, microcomputed tomography, and mercury intrusion porosimetry were used to analyze the pore structures of scaffolds. The porogen content was found to dictate the porosity of scaffolds. There was no significant difference in porosity, pore size, and interconnectivity among the different materials for the same porogen fraction. Nearly 100% of the pore volume was interconnected through 20microm or larger connections for all scaffolds. While interconnectivity through larger connections improved with higher porosity, compressive mechanical properties of scaffolds declined at the same time. However, the compressive modulus, offset yield strength, and compressive strength of F-US-tube nanocomposites were higher than or similar to the corresponding properties for the PPF polymer and US-tube nanocomposites for all the porosities examined. As for in vitro osteoconductivity, marrow stromal cells demonstrated equally good cell attachment and proliferation on all scaffolds made of different materials at each porosity. These results indicate that functionalized ultra-short single-walled carbon nanotube nanocomposite scaffolds with tunable porosity and mechanical properties hold great promise for bone tissue engineering applications.

Preparation of a novel antibacterial chitosan-poly(ethylene glycol) cryogel/silver nanoparticles composites.

Cryogel was synthesized through cryogelation of methacrylated carboxymethyl chitosan (mCMC) and poly(ethylene glycol) diacrylate (PEGDA) precursors by photopolymerization. Due to its excellent properties, such as fast swelling behavior, inter-connective porous structure, high water absorbing capacity, especially the presence of abundant carboxylmethyl groups on its backbone, the cryogel not only favored the absorption of silver ions but also was proved to be a good matrix for the incorporation of silver nanoparticles (AgNPs) by in situ chemical reduction. The structure, morphology, and swelling behavior of the cryogel and cryogel/AgNPs composite were characterized. And the results of inhibition zone test and antibacterial inhibition ratio indicated the cryogel/AgNPs composite exhibited prominent and durable antibacterial activity against Gram-negative E. coli and could be utilized as potential antibacterial materials.

Strong Antibacterial Polydopamine Coatings Prepared by a Shaking-assisted Method.

Strong antibacterial polydopamine (PDA) coatings prepared by a facile shaking-assisted method is reported for the first time. It was found that a minor modification made to the conventional synthesis procedure of PDA coatings, viz. replacing the static solution condition with a shaking solution condition by using a mechanical shaker, can produce the roughened polydopamine (rPDA) coatings at different substrates, e.g., glass, stainless steel, plastic, and gauze. The resulting rPDA coatings were characterized with Raman spectrum, zeta-potential analysis and contact angle measurement. The antibacterial activity of the rPDA coatings was evaluated by a shake flask test with gram-positive Staphylococcus aureus, and gram-negative Escherichia coli and Pseudomonas aeruginosa as bacteria models. Testing results revealed that, in the absence of any other antibacterial agents, the rPDA coatings exhibited remarkably enhanced antibacterial activities. In addition, such enhanced antibacterial activities of the rPDA coatings were found to be unimpaired by steam sterilization treatments.