Investigating the stability of chimeric murine polyomavirus VP1 Capsomeres via molecular dynamics simulations and experimental analysis.

The development of modular virus-like particle (VLP) vaccine platforms with genetically inserted antigens in viral structural proteins shows great promise for advancing vaccine technology. However, the instability of many constructs leads to trial-and-error approaches, and the challenge of predicting stability based solely on amino acid sequences remains unresolved, yet highly appealing. This study evaluates the stability of wild-type murine polyomavirus (MPV) VP1 capsomeres and three engineered chimeric variants using molecular dynamics (MD) simulations and laboratory experiments.

The variation of resistome, mobilome and pathogen in domestic and industrial wastewater treatment systems.

Wastewater treatment plants (WWTPs), including both domestic and industrial facilities, are key contributors to antibiotic resistance genes (ARGs) and human pathogens in the environment. However, the characteristics and dissemination mechanisms of ARGs in domestic (SD) and industrial (SI) wastewater treatment systems remain unclear, leading to uncertainties in risk assessment. Based on metagenomic analysis, we observed significant differences in the compositions of resistome (ARGs and metal resistance genes, MRGs), mobilome (mobile genetic elements, MGEs), and bacterial community between SD and SI.

Metagenomic insights into resistome, mobilome and virulome in different fecal waste.

Fecal waste is a significant source of antimicrobial resistance (AMR) pollution and provides valuable insights into the AMR development in animal and human populations within the "One health" framework. Various genetic elements, including antibiotic resistance genes (ARGs), biocide and metal resistance genes (BMGs), mobile genetic elements (MGEs), and virulence factor genes (VFGs), are crucial AMR risk determinants (ARDs). However, few studies focused on compositional characteristics of ARDs in different feces.

Experimental and molecular dynamics simulation studies on the physical properties of three HBc-VLP derivatives as nanoparticle protein vaccine candidates.

Self-assembling virus-like particles (VLPs) are promising platforms for vaccine development. However, the unpredictability of the physical properties, such as self-assembly capability, hydrophobicity, and overall stability in engineered protein particles fused with antigens, presents substantial challenges in their downstream processing. We envision that these challenges can be addressed by combining more precise computer-aided molecular dynamics (MD) simulations with experimental studies on the modified products, with more to-date forcefield descriptions and larger models closely resembling real assemblies, realized by rapid advancement in computing technology.

Pore-blocking steric mass-action model for adsorption of bioparticles.

The steric mass-action (SMA) model has been widely reported to describe the adsorption of proteins in different types of chromatographic adsorbents. Here in the present work, a pore-blocking steric mass-action model (PB-SMA) was developed for the adsorption of large-size bioparticles, which usually exhibit the unique pore-blocking characteristic on the adsorbent and thus lead to a fraction of ligands in the deep channels physically inaccessible to bioparticles adsorption, instead of being shielded due to steric hindrance by adsorbed bioparticles. This unique phenomenon was taken into account by introducing an additional parameter, L, which is defined as the inaccessible ligand densities in the physically blocked pore area, into the PB-SMA model.

Integration of Zn, ATP, and bFGF to Nanodressing with Core-Shell Structure Fabricated by Emulsion Electrospinning for Wound Healing.

Basic fibroblast growth factor (bFGF) plays an important role in active wound repair. However, the existing dosage forms in clinical applications are mainly sprays and freeze-dried powders, which are prone to inactivation and cannot achieve a controlled release. In this study, a bioactive wound dressing named bFGF-ATP-Zn/polycaprolactone (PCL) nanodressing with a "core-shell" structure was fabricated by emulsion electrospinning, enabling the sustained release of bFGF.

In situ bio-mineralized Mn nanoadjuvant enhances anti-influenza immunity of recombinant virus-like particle vaccines.

Virus like particles (VLPs) have been well recognized as one of the most important vaccine platforms due to their structural similarity to natural viruses to induce effective humoral and cellular immune responses. Nevertheless, lack of viral nucleic acids in VLPs usually leads the vaccine candidates less efficient in provoking innate immune against viral infection. Here, we constructed a biomimetic dual antigen hybrid influenza nanovaccines THM-HA@Mn with robust immunogenicity via in situ synthesizing a stimulator of interferon genes (STING) agonist MnO inside the cavity of a recombinant Hepatitis B core antigen VLP (HBc VLP) having fused SpyTag and influenza M2e antigen peptides (Tag-HBc-M2e, THM for short), followed by conjugating a recombinant hemagglutinin (rHA) antigen on the surface of the nanoparticles through SpyTag/SpyCatcher ligating.

Global WWTP Microbiome-based Integrative Information Platform: From experience to intelligence.

Domestic and industrial wastewater treatment plants (WWTPs) are facing formidable challenges in effectively eliminating emerging pollutants and conventional nutrients. In microbiome engineering, two approaches have been developed: a top-down method focusing on domesticating seed microbiomes into engineered ones, and a bottom-up strategy that synthesizes engineered microbiomes from microbial isolates. However, these approaches face substantial hurdles that limit their real-world applicability in wastewater treatment engineering.

Metagenomics reveals the influence of small microplastics on microbial communities in coastal sediments.

The ecological impact of microplastics (MPs) in coastal environments has been widely studied. However, the influence of small microplastics in the actual environment is often overlooked due to measurement challenges. In this study, Hangzhou Bay (HZB), China, was selected as our study area.

[Quantification of complete viral particles in inactivated avian influenza virus antigen by high performance size exclusion chromatography coupled with multi-angle laser light scattering].

We developed a method for accurate quantification of the intact virus particles in inactivated avian influenza virus feedstocks. To address the problem of impurities interference in the detection of inactivated avian influenza virus feedstocks by direct high performance size exclusion chromatography (HPSEC), we firstly investigated polyethylene glycol (PEG) precipitation and ion exchange chromatography (IEC) for H5N8 antigen purification. Under the optimized conditions, the removal rate of impurity was 86.

On-column capping of poly dT media-tethered mRNA accomplishes high capping efficiency, enhanced mRNA recovery, and improved stability against RNase.

The messenger RNA (mRNA) 5'-cap structure is indispensable for mRNA translation initiation and stability. Despite its importance, large-scale production of capped mRNA through in vitro transcription (IVT) synthesis using vaccinia capping enzyme (VCE) is challenging, due to the requirement of tedious and multiple pre-and-post separation steps causing mRNA loss and degradation. Here in the present study, we found that the VCE together with 2'-O-methyltransferase can efficiently catalyze the capping of poly dT media-tethered mRNA to produce mRNA with cap-1 structure under an optimized condition.

Moderate anthropogenic disturbance stimulates versatile microbial taxa contributing to denitrification and aromatic compound degradation.

Wastewater treatment plants (WWTPs) effluent often contains a significant amount of residual organic pollutants and nutrients, causing disturbance to the coastal effluent receiving areas (ERA). Microbial communities in coastal ERA sediments may benefit from the coexistence of organic pollutants and nutrients, promoting the emergence of versatile taxa that are capable of eliminating these substances simultaneously. However, the identification and exploration of versatile taxa in natural environments under anthropogenic disturbances remain largely uncharted territory.

Messenger RNA chromatographic purification: advances and challenges.

Messenger RNA (mRNA) technologies have shown great potential in prophylactic vaccines and therapeutic medicines due to their adaptability, rapidity, efficacy, and safety. The purity of mRNA determines the efficacy and safety of mRNA drugs. Though chromatographic technologies are currently employed in mRNA purification, they are facing challenges, mainly arising from the large size, relatively simple chemical composition, instability, and high resemblance of by-products to the target mRNA.

Screening of priority antibiotics in Chinese seawater based on the persistence, bioaccumulation, toxicity and resistance.

Antibiotics are emerging pollutants that have detrimental effects on both target and non-target organisms in the environment. However, current methods for environmental risk assessment primarily focus on the risk to non-target organisms in ecosystems, overlooking a crucial risk of antibiotics - the induction of resistance in targeted bacteria. To address this oversight, we have incorporated resistance (R) risk with persistence, bioaccumulation and toxicity (PBT) to establish a more comprehensive PBTR (persistence, bioaccumulation, toxicity, and resistance) framework for antibiotic-specific risk assessment.

The position of Spy Tag/Catcher system in hepatitis B core protein particles affects the immunogenicity and stability of the synthetic vaccine.

Presenting exogenous antigens on virus-like particles (VLPs) through "plug-and-display" decoration strategies based on SpyTag/SpyCatcher isopeptide bonding have emerged as attractive technology for vaccine synthesis. However, whether the position of ligation site in VLPs will impose effects on immunogenicity and physiochemical properties of the synthetic vaccine remains rarely investigated. Here in the present work, the well-established hepatitis B core (HBc) protein was used as chassis to construct dual-antigen influenza nanovaccines, with the conserved epitope peptides derived from extracellular domain of matrix protein M2 (M2e) and hemagglutinin (HA) as target antigens.

Thermal-triggered loading and GSH-responsive releasing property of HBc particles for drug delivery.

Hepatitis B core protein virus-like particles (HBc VLPs) have attracted wide attentions using as drug delivery vehicles, due to its excellent stability and easy in large scale production. Here in the present work, we report unique thermal-triggered loading and glutathione-responsive releasing property of the HBc particles for anticancer drug delivery. Through reversible temperature-dependent hole gating of the HBc particle capsid, about 4248 doxorubicin (DOX) were successfully encapsulated inside nanocage of a single nanoparticle at high HBc recovery of 83.

PTB Regulates the Metabolic Pathways and Cell Function of Keloid Fibroblasts through Alternative Splicing of PKM.

Keloids, benign fibroproliferative cutaneous lesions, are characterized by abnormal growth and reprogramming of the metabolism of keloid fibroblasts (KFb). However, the underlying mechanisms of this kind of metabolic abnormality have not been identified. Our study aimed to investigate the molecules involved in aerobic glycolysis and its exact regulatory mechanisms in KFb.

Synthesis of a crystalline zeolitic imidazole framework-8 nano-coating on single environment-sensitive viral particles for enhanced immune responses.

Encapsulating antigens with zeolitic imidazole framework-8 (ZIF-8) exhibits many advantages in vaccine development. However, most viral antigens with complex particulate structures are sensitive to pH or ionic strength, which cannot tolerate harsh synthesis conditions of ZIF-8. Balancing the viral integrity and the growth of ZIF-8 crystals is crucial for the successful encapsulation of these environment-sensitive antigens in ZIF-8.

Wastewater treatment plant effluent discharge decreases bacterial community diversity and network complexity in urbanized coastal sediment.

The wastewater treatment plant (WWTP) effluent discharge affects the microorganisms in the receiving water bodies. Despite the ecological significance of microbial communities in pollutant degradation and element cycling, how the community diversity is affected by effluent remains obscure. Here, we compared the sediment bacterial communities exposed to different intensities of WWTP effluent discharge in Hangzhou Bay, China: i) a severely polluted area that receives effluent from an industrial WWTP, ii) a moderately polluted area that receives effluent from a municipal WWTP, and iii) less affected area that inner the bay.

Industrial effluents boosted antibiotic resistome risk in coastal environments.

Wastewater treatment plants (WWTPs) have been regarded as an important source of antibiotic resistance genes (ARGs) in environment, but out of municipal domestic WWTPs, few evidences show how environment is affected by industrial WWTPs. Here we chose Hangzhou Bay (HZB), China as our study area, where land-based municipal and industrial WWTPs discharged their effluent into the bay for decades. We adopted high-throughput metagenomic sequencing to examine the antibiotic resistome of the WWTP effluent and coastal sediment samples.

A New Technique for Chondrolaryngoplasty in Patients Assigned Female at Birth.

Background: Chondrolaryngoplasty is a classical facial feminization surgery for transgender women. In recent years, however, an increasing number of patients assigned female at birth are seeking chondrolaryngoplasty for esthetic purposes. Traditional chondrolaryngoplasty can no longer cope with problems of the growing group whose leading cause of laryngeal prominence differs from the transgender population.

Mechanism and inhibition of abnormal chromatographic behavior of serotype type a inactivated foot and mouth disease virus in high-performance size-exclusion chromatography.

High-performance size-exclusion chromatography (HPSEC) has been developed for the rapid and quantitative analysis of inactivated foot and mouth disease virus (FMDV) and adopted by regulatory agencies and vaccine manufacturers. However, strong non-specific adsorption of type A/AKT III FMDV was found on some batches of TSK G4000 SW column, which significantly affected the analysis accuracy. The adsorption mechanism was studied by investigating the charge and hydrophobicity of A/AKT III FMDV and another serotype O/Mya 98, as well as several model proteins, by zeta potential and hydrophobic interaction chromatography analysis.

Temperature affects variations of class 1 integron during sludge anaerobic digestion.

Revealing class 1 integron characteristics under different operating conditions is of great importance to control antibiotic resistance genes (ARGs) during sludge anaerobic digestion (AD). This study investigated the variations of class 1 integrons and the ARGs carried by class 1 integrons in anaerobic sludge digesters under 25 °C, 35 °C, and 55 °C. The results showed lower intI1 abundance and fewer class I integrons with long gene cassette arrays at 55 °C than at 25 °C and 35 °C.

[Effects of Wastewater Discharge on Antibiotic Resistance Genes and Microbial Community in a Coastal Area].

Wastewater treatment plants (WWTPs) are important sources of antibiotic resistance genes (ARGs) in aquatic environments. Mobile genetic elements (MGEs) and microbial communities are key factors that affect the proliferation of ARGs. To reveal the effects of WWTPs effluent discharge on the ARGs and microbial community in a coastal area, the structure and distribution of ARGs, MGEs, and microbial community in Shangyu (SY) and Jiaxing (JX) effluent receiving areas (ERAs) and the offshore area of Hangzhou Bay (HB) were investigated via high-throughput quantitative PCR and 16S rRNA high-throughput sequencing.