Immunoglobin G Sero-Dynamics Aided Host Specific Linear Epitope Identification and Differentiation of Infected from Vaccinated Hosts.

Differentiation of infected from vaccinated hosts (DIVH) is a critical step in virus eradication programs. DIVH-compatible vaccines, however, take years to develop, and are therefore unavailable for fighting the sudden outbreaks that typically drive pandemics. Here, we establish a protocol for the swift and efficient development of DIVH assays, and show that this approach is compatible with any type of vaccines. Using porcine circovirus 2 (PCV2) as the experimental model, the first step is to use Immunoglobin G (IgG) sero-dynamics (IsD) curves to aid epitope discovery (IsDAED): PCV2 Cap peptides were categorized into three types: null interaction, nonspecific interaction (NSI), and specific interaction (SI). We subsequently compared IsDAED approach and traditional approach, and demonstrated identifying SI peptides and excluding NSI peptides supports efficient diagnostic kit development, specifically using a protein-peptide hybrid microarray (PPHM). IsDAED directed the design of a DIVH protocol for three types of PCV2 vaccines (while using a single PPHM). Finally, the DIVH protocol successfully differentiated infected pigs from vaccinated pigs at five farms. This IsDAED approach is almost certainly extendable to other viruses and host species. IMPORTANCE Sudden outbreaks of pandemics caused by virus, such as SARS-CoV-2, has been determined as a public health emergency of international concern. However, the development of a DIVH-compatible vaccine is time-consuming and full of uncertainty, which is unsuitable for an emergent situation like the ongoing COVID-19 pandemic. Along with the development and public health implementation of new vaccines to prevent human diseases, e.g., human papillomavirus vaccines for cervical cancer; enterovirus 71 vaccines for hand, foot, and mouth disease; and most recently SARS-CoV-2, there is an increasing demand for DIVH. Here, we use the IsDAED approach to confirm SI peptides and to exclude NSI peptides, finally to direct the design of a DIVH protocol. It is plausible that our IsDAED approach is applicable for other infectious disease.

Genetic polymorphism of nonsyndromic cleft lip with or without cleft palate is associated with developmental dyslexia in Chinese school-aged populations.

Developmental dyslexia (DD) is a neurodevelopment disorder characterized by reading disabilities without apparent etiologies. Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a structural craniofacial malformation featured by isolated orofacial abnormalities. Despite substantial phenotypic differences, potential linkage between these two disorders has been suggested as prevalence of DD among NSCL/P patients was much higher than that in general populations. Previous neuroimaging studies observed impaired short-term memory in patients with DD and NSCL/P, respectively. Genetic factors have a fundamental role during neurodevelopment and craniofacial morphogenesis but there lacks of evidence to support the linkage between DD and NSCL/P at genetic level. A recent genome-wide association study in Chinese populations identified a number of genetic polymorphisms associated with NSCL/P. Herein, we selected three risk variants of NSCL/P namely rs8049367, rs4791774 and rs2235371, and performed association analysis with DD in a Chinese population consisting 631 elementary school-aged children with 288 dyslexic cases without NSCL/P and 343 healthy controls. After Bonferroni correction for multiple comparisons, the T allele of rs8049367 showed significant association with DD (OR=1.41, P=0.0085). It is an intergenic variant between CREBBP and ADCY9 located at 16p13.3. The CREBBP gene was reported to have an essential role during memory formation, although ADCY9 was involved in dental development. In future studies, understanding functional effects of rs8049367 on CERBBP and ADCY9 might contribute to explain underlying etiologies shared by DD and NSCL/P.

Metal-organic framework-based advanced therapeutic tools for antimicrobial applications.

The escalating concern over conventional antibiotic resistance has emphasized the urgency in developing innovative antimicrobial agents. In recent times, metal-organic frameworks (MOFs) have garnered significant attention within the realm of antimicrobial research due to their multifaceted antimicrobial attributes, including the sustained release of intrinsic or exogenous antimicrobial components, chemodynamically catalyzed generation of reactive oxygen species (ROS), and formation of photogenerated ROS. This comprehensive review provides a thorough overview of the synthetic approaches employed in the production of MOF-based materials, elucidating their underlying antimicrobial mechanisms in depth. The focal point lies in elucidating the research advancements across various antimicrobial modalities, encompassing intrinsic component release system, extraneous component release system, auto-catalytical system, and energy conversion system. Additionally, the progress of MOF-based antimicrobial materials in addressing wound infections, osteomyelitis, and periodontitis is meticulously elucidated, culminating in a summary of the challenges and potential opportunities inherent within the realm of antimicrobial applications for MOF-based materials. STATEMENT OF SIGNIFICANCE: Growing concerns about conventional antibiotic resistance emphasized the need for alternative antimicrobial solutions. Metal-organic frameworks (MOFs) have gained significant attention in antimicrobial research due to their diverse attributes like sustained antimicrobial components release, catalytic generation of reactive oxygen species (ROS), and photogenerated ROS. This review covers MOF synthesis and their antimicrobial mechanisms. It explores advancements in intrinsic and extraneous component release, auto-catalysis, and energy conversion systems. The paper also discusses MOF-based materials' progress in addressing wound infections, osteomyelitis, and periodontitis, along with existing challenges and opportunities. Given the lack of related reviews, our findings hold promise for future MOF applications in antibacterial research, making it relevant to your journal's readership.

Design and fabrication of intracellular therapeutic cargo delivery systems based on nanomaterials: current status and future perspectives.

Intracellular cargo delivery, the introduction of small molecules, proteins, and nucleic acids into a specific targeted site in a biological system, is an important strategy for deciphering cell function, directing cell fate, and reprogramming cell behavior. With the advancement of nanotechnology, many researchers use nanoparticles (NPs) to break through biological barriers to achieving efficient targeted delivery in biological systems, bringing a new way to realize efficient targeted drug delivery in biological systems. With a similar size to many biomolecules, NPs possess excellent physical and chemical properties and a certain targeting ability after functional modification on the surface of NPs. Currently, intracellular cargo delivery based on NPs has emerged as an important strategy for genome editing regimens and cell therapy. Although researchers can successfully deliver NPs into biological systems, many of them are delivered very inefficiently and are not specifically targeted. Hence, the development of efficient, target-capable, and safe nanoscale drug delivery systems to deliver therapeutic substances to cells or organs is a major challenge today. In this review, on the basis of describing the research overview and classification of NPs, we focused on the current research status of intracellular cargo delivery based on NPs in biological systems, and discuss the current problems and challenges in the delivery process of NPs in biological systems.

Integrated osteoimmunomodulatory strategies based on designing scaffold surface properties in bone regeneration.

Those who have used traditional biomaterials as bone substitutes have always regarded the immune response as an obstacle leading to implant failure. However, cumulative evidence revealed that blindly minimizing host immune reactions cannot induce successful bone regeneration. With the emergence of the new concept of osteoimmunology, the intimate mutual effects between the skeletal system and the immune system have been gradually recognized, promoting the innovation of biomaterials with osteoimmunomodulatory properties. By tuning the surface properties, biomaterials can precisely manipulate the osteoimmune environment favoring bone regeneration. In this review, we first reviewed the mutual effects between the skeletal system and the immune system to show the importance of immunomodulation on bone regeneration. Subsequently, we summarize the recent developments in surface modification strategies in terms of the surface physicochemical properties and surface coatings and explain how these modification strategies work.

Pathogenic Mechanisms of Fusobacterium nucleatum on Oral Epithelial Cells.

Periodontitis is an oral chronic inflammatory disease and may cause tooth loss in adults. Oral epithelial cells provide a barrier for bacteria and participate in the immune response. Fusobacterium nucleatum (F. nucleatum) is one of the common inhabitants of the oral cavity and has been identified as a potential etiologic bacterial agent of oral diseases, such as periodontitis and oral carcinomas. F. nucleatum has been shown to be of importance in the development of diverse human cancers. In the dental biofilm, it exhibits a structural role as a bridging organism, connecting primary colonizers to the largely anaerobic secondary colonizers. It expresses adhesins and is able to induce host cell responses, including the upregulation of defensins and the release of chemokines and interleukins. Like other microorganisms, its detection is achieved through germline-encoded pattern-recognition receptors (PRRs) and pathogen-associated molecular patterns (PAMPs). By identification of the pathogenic mechanisms of F. nucleatum it will be possible to develop effective methods for the diagnosis, prevention, and treatment of diseases in which a F. nucleatum infection is involved. This review summarizes the recent progress in research targeting F. nucleatum and its impact on oral epithelial cells.

The presence of a side population and its marker ABCG2 in human deciduous dental pulp cells.

Stem cells have been identified using the DNA-binding dye Hoechst 33342 and flow cytometry (FCM) in various tissues known as the side population (SP). The present study shows, for the first time, the presence of side population cells in human deciduous dental pulp cells (DPCs). Flow cytometric identification revealed that 2% of human deciduous DPCs were SP cells and that this SP profile disappeared in the presence of verapamil. The SP marker ABCG2 protein was localized to DPCs in the cell membrane by immunofluorescence staining, and flow cytometric analysis demonstrated that 3.6% of DPCs were ABCG2-positive. Furthermore, quantitative real-time PCR proved that ABCG2 mRNA expression in DPCs isolated from human exfoliated deciduous teeth was higher than in DPCs from permanent teeth. Our findings demonstrate that DPCs from human exfoliated deciduous teeth contain a higher proportion of the SP phenotype than permanent teeth and that they may constitute a stem cell population.