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Plant‐derived extracellular vesicles (EVs) are promising therapeutic agents owing to their natural abundance, accessibility, and unique biological properties. This review provides a comprehensive exploration of the therapeutic potential of plant‐derived EVs and emphasizes their anti‐inflammatory, antimicrobial, and tumor‐inhibitory effects. Here, we discussed the advancements in isolation and purification techniques, such as ultracentrifugation and size‐exclusion chromatography, which are critical for maintaining the functional integrity of these nanovesicles. Next, we investigated the diverse administration routes of EVs and carefully weighed their respective advantages and challenges related to bioavailability and patient compliance. Moreover, we elucidated the multifaceted mechanisms of action of plant‐derived EVs, including their roles in anti‐inflammation, antioxidation, antitumor activity, and modulation of gut microbiota. We also discussed the impact of EVs on specific diseases such as cancer and inflammatory bowel disease, highlighting the importance of addressing current challenges related to production scalability, regulatory compliance, and immunogenicity. Finally, we proposed future research directions for optimizing EV extraction and developing targeted delivery systems. Through these efforts, we envision the seamless integration of plant‐derived EVs into mainstream medicine, offering safe and potent therapeutic alternatives across various medical disciplines. [ABSTRACT FROM AUTHOR]

Biosensors are valuable tools in accelerating the test phase of the design‐build‐test‐learn cycle of cell factory development, as well as in bioprocess monitoring and control. G protein‐coupled receptor (GPCR)‐based biosensors enable cells to sense a wide array of molecules and environmental conditions in a specific manner. Due to the extracellular nature of their sensing, GPCR‐based biosensors require compartmentalization of distinct genotypes when screening production levels of a strain library to ensure that detected levels originate exclusively from the strain under assessment. Here, we explore the integration of production and sensing modalities into a single Saccharomyces cerevisiae strain and compartmentalization using three different methods: (1) cultivation in microtiter plates, (2) spatial separation on agar plates, and (3) encapsulation in water‐in‐oil‐in‐water double emulsion droplets, combined with analysis and sorting via a fluorescence‐activated cell sorting machine. Employing tryptamine and serotonin as proof‐of‐concept target molecules, we optimize biosensing conditions and demonstrate the ability of the autocrine screening method to enrich for high producers, showing the enrichment of a serotonin‐producing strain over a nonproducing strain. These findings illustrate a workflow that can be adapted to screening for a wide range of complex chemistry at high throughput using commercially available microfluidic systems. [ABSTRACT FROM AUTHOR]

Bioartificial livers have showcased significant value in the treatment of acute liver failure (ALF). Current efforts are directed toward overcoming challenges in the development of microcarriers, with a specific emphasis on integrating higher‐density liver cells to enhance detoxification capabilities. Here, inspired by the radial filtration model in hepatic lobules, ion‐specific silk fibroin microcarriers are proposed with biomimetic niches for cultivating functional liver cells at high density. These biomimetic microcarriers are generated by capillary microfluidic device with controllable adjustments of ion type or concentration within the aqueous phase. When cultivating human induced pluripotent stem cell ‐differentiated mature liver cells on these recrystallized microcarriers, notably enhanced cell proliferation activity, as well as increased metabolic and secretory functionality is observed. Based on these features, the microcarrier‐integrated bioreactor can effectively reduce hepatic transaminase levels and significantly improve urea, albumin production, and survival rate in rabbit ALF models is demonstrated. Thus, it is believed that the biomimetic microcarriers and their derived bioreactor may hold potential for clinical applications in managing ALF and other liver diseases. [ABSTRACT FROM AUTHOR]

The main vectors of Zika virus (ZIKV) and dengue virus (DENV) are Aedes aegypti and Ae. albopictus, with Ae. aegypti being more competent. However, the underlying mechanisms remain unclear. Here, we find Ae. albopictus shows comparable vector competence to ZIKV/DENV with Ae. aegypti by blood-feeding after antibiotic treatment or intrathoracic injection. This suggests that midgut microbiota can influence vector competence. Enterobacter hormaechei_B17 (Eh_B17) is isolated from field-collected Ae. albopictus and conferred resistance to ZIKV/DENV infection in Ae. aegypti after gut-transplantation. Sphingosine, a metabolite secreted by Eh_B17, effectively suppresses ZIKV infection in both Ae. aegypti and cell cultures by blocking viral entry during the fusion step, with an IC50 of approximately 10 μM. A field survey reveals that Eh_B17 preferentially colonizes Ae. albopictus compared to Ae. aegypti. And field Ae. albopictus positive for Eh_B17 are more resistant to ZIKV infection. These findings underscore the potential of gut symbiotic bacteria, such as Eh_B17, to modulate the arbovirus vector competence of Aedes mosquitoes. As a natural antiviral agent, Eh_B17 holds promise as a potential candidate for blocking ZIKV/DENV transmission. Here the authors show that arbovirus vector competence of Aedes mosquitoes is modulated by the midgut microbiota and identify the metabolite sphingosine from the gut symbiotic bacterium Enterobacter hormaechei_B17 (Eh_B17) as a factor mediating resistance to ZIKV and DENV infection. [ABSTRACT FROM AUTHOR]

The excessive discharge of antibiotics into aquatic systems is a major issue in many countries worldwide and poses a threat to human health and the sustainable development of society. Hence, developing efficient treatment methods and purification technologies to degrade antibiotics is essential. Herein, we present the synthesis of low-cost, self-propelled tubular Fe3+-incorporated graphitic carbon nitride (g-C3N4-Fe@KF) micromotors using kapok fibers (KFs) as templates and their application as photo-catalysts for the photo-Fenton degradation of tetracycline (TC) under visible-light irradiation. The g-C3N4-Fe@KF micromotors moved rapidly when being propelled by oxygen bubbles generated in a hydrogen peroxide (H2O2) solution as a result of a photo-assisted Fenton reaction. The motion behavior of the g-C3N4-Fe@KF micromotors was dependent on the concentration of H2O2 and the length of the micromotors. The propulsion mechanism was discussed in detail. The micromotors efficiently degraded antibiotics via the photo-Fenton process. Photo-Fenton degradation efficiency was attributed to the synergistic effects of the doped Fe3+ and g-C3N4 under visible-light irradiation and self-propulsion of the micromotors. In addition, the micromotors possessed good reusability, thereby efficiently realizing multiple cycles of degradation. The current work offers an avenue for the design of micromotors, using inexpensive approaches, for various potential environmental applications. [ABSTRACT FROM AUTHOR]

Epsilon toxin (ETX), a potential agent of biological and toxic warfare, causes the death of many ruminants and threatens human health. It is crucial to understand the toxic mechanism of such a highly lethal and rapid course toxin. In this study, we detected the effects of ETX on the proteome and phosphoproteome of MDCK cells after 10 min and 30 min. A total of 44 differentially expressed proteins (DEPs) and 588 differentially phosphorylated proteins (DPPs) were screened in the 10 min group, while 73 DEPs and 489 DPPs were screened in the 30 min group. ETX-induced proteins and phosphorylated proteins were mainly located in the nucleus, cytoplasm, and mitochondria, and their enrichment pathways were related to transcription and translation, virus infection, and intercellular junction. Meanwhile, the protein–protein interaction network screened out several hub proteins, including SRSF1/2/6/7/11, SF3B1/2, NOP14/56, ANLN, GTPBP4, THOC2, and RRP1B. Almost all of these proteins were present in the spliceosome pathway, indicating that the spliceosome pathway is involved in ETX-induced cell death. Next, we used RNAi lentiviruses and inhibitors of several key proteins to verify whether these proteins play a critical role. The results confirmed that SRSF1, SF3B2, and THOC2 were the key proteins involved in the cytotoxic effect of ETX. In addition, we found that the common upstream kinase of these key proteins was SRPK1, and a reduction in the level of SRPK1 could also reduce ETX-induced cell death. This result was consistent with the phosphorylated proteomics analysis. In summary, our study demonstrated that ETX induces phosphorylation of SRSF1, SF3B2, THOC2, and SRPK1 proteins on the spliceosome pathway, which inhibits normal splicing of mRNA and leads to cell death. [ABSTRACT FROM AUTHOR]

Nano‐delivery systems hold great promise for the treatment of rheumatoid arthritis (RA). Current research efforts are primarily focused on enhancing their targeting capabilities and efficacy. Here, this study proposes a novel viral‐mimicking ternary polyplexes system for the controlled delivery of the anti‐inflammatory drug Cyclosporin A (CsA) to effectively treat RA. The ternary polyplexes consist of a nanogel core loaded with CsA and a hyaluronic acid shell, which facilitates CD44‐mediated targeting. By mimicking the Trojan Horse strategy employed by viruses, these polyplexes undergo a stepwise process of deshielding and disintegration within the inflamed joints. This process leads to the release of CsA within the cells and the scavenging of pathogenic factors. This study demonstrates that these viral‐mimicking ternary polyplexes exhibit rapid targeting, high accumulation, and prolonged persistence in the joints of RA mice. As a result, they effectively reduce inflammation and alleviate symptoms. These results highlight the potential of viral‐mimicking ternary polyplexes as a promising therapeutic approach for the targeted and programmed delivery of drugs to treat not only RA but also other autoimmune diseases. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) have certain effect in cancer treatment, thus many studies have been focused on developing functional systems to generate ROS in tumor. Here, inspired by the multi‐enzyme biocatalysis in organisms, novel ultrasound‐triggered temporospatial catalytic cascades systems are presented based on barium titanate (BTO) and platinum (Pt) co‐loaded multi‐component microparticles (Pt/BTO@MCMPs) to successively achieve oxygen and ROS production for tumor sonodynamic therapy. By using a customized capillary microfluidic device, the Pt/BTO@MCMPs are fabricated with Pt nanoparticles located in their core part and BTO nanocubes located in their peripheral part, alternating with blank porous hydrogel components for increasing interaction areas between the encapsulated nanomaterials and the ambient substrates. In the microparticles, the Pt can catalyze hydrogen peroxide from the tumor microenvironment to generate O2 and H2O serving as substrates for piezoelectric catalytic reactions, contributing to additional generation of ROS under US activation. Based on the system, it is demonstrated that the Pt/BTO@MCMPs are featured with excellent biocompatibility under normal biological conditions and show desired tumor eradication properties under ultrasound irradiation in mice carrying pancreatic tumors. These results indicate that the proposed ultrasound‐triggered temporospatial catalytic cascades systems are promising for clinic anti‐tumor applications. [ABSTRACT FROM AUTHOR]

Background: Kadipiro virus (KDV) is a species of the new 12 segmented RNA virus grouped under the genus Seadornavirus within the Reoviridae family. It has previously been isolated or detected from mosquito, Odonata, and bat feces in Indonesia, China, and Denmark, respectively. Here, we describe the isolation and characterization of a viral strain from mosquitoes in Yunnan Province, China. Methods: Mosquitoes were collected overnight using light traps in Shizong county, on July 17, 2023. Virus was isolated from the mosquito homogenate and grown using baby hamster kidney and Aedes albopictus (C6/36) cells. Preliminary identification of the virus was performed by agarose gel electrophoresis (AGE). The full-genome sequences of the strain were determined by full-length amplification of cDNAs and sequenced using next-generation sequencing. Results: We isolated a viral strain (SZ_M48) from mosquitoes (Culex tritaeniorhynchus Giles) that caused cytopathogenic effects in C6/36 cells. AGE analysis indicated a genome consisting of 12 segments of double-stranded RNA that demonstrated a "6-5-1" pattern, similar to the migrating bands of KDV. Phylogenetic analysis based on the full-genome sequence revealed that SZ_M48 is more clustered with KDV isolates from Hubei and Shangdong in China than with Indonesian and Danish strains. The identity between SZ_M48 and SDKL1625 (Shandong, China) is slightly lower than that of QTM27331 (Hubei, China), and the identity with JKT-7075 (Indonesia) and 21164-6/M.dau/DK (Denmark) is the lowest. Conclusion: The full-genome sequence of the new KDV strain described in this study may be useful for surveillance of the evolutionary characteristics of KDVs. Moreover, these findings extend the knowledge about the genomic diversity, potential vectors, and the distribution of KDVs in China. [ABSTRACT FROM AUTHOR]

Controllable protein nanoarchitectonics refers to the process of manipulating and controlling the assembly of proteins at the nanoscale to achieve domain‐limited and accurate spatial arrangement. In nature, many proteins undergo precise self‐assembly with other structural domains to engage in synergistic physiological activities. Protein nanomaterials prepared through protein nanosizing have received considerable attention due to their excellent biocompatibility, low toxicity, modifiability, and versatility. This review focuses on the fundamental strategies used for controllable protein nanoarchitectinics, which include computational design, self‐assembly induction, template introduction, complexation induction, chemical modification, and in vivo assembly. Precise controlling of the nanosizing process has enabled the creation of protein nanostructures with different dimensions, including 0D spherical oligomers, 1D nanowires, nanorings, and nanotubes, as well as 2D nanofilms, and 3D protein nanocages. The unique biological properties of proteins hold promise for diverse applications of these protein nanomaterials, including in biomedicine, the food industry, agriculture, biosensing, environmental protection, biocatalysis, and artificial light harvesting. Protein nanosizing is a powerful tool for developing biomaterials with advanced structures and functions. [ABSTRACT FROM AUTHOR]

Harmony Search (HS) algorithm is a swarm intelligence algorithm inspired by musical improvisation. Although HS has been applied to various engineering problems, it faces challenges such as getting trapped in local optima, slow convergence speed, and low optimization accuracy when applied to complex problems. To address these issues, this paper proposes an improved version of HS called Equilibrium Optimization-based Harmony Search Algorithm with Nonlinear Dynamic Domains (EO-HS-NDD). EO-HS-NDD integrates multiple leadership-guided strategies from the Equilibrium Optimizer (EO) algorithm, using harmony memory considering disharmony and historical harmony memory, while leveraging the hidden guidance direction information from the Equilibrium Optimizer. Additionally, the algorithm designs a nonlinear dynamic convergence domain to adaptively adjust the search space size and accelerate convergence speed. Furthermore, to balance exploration and exploitation capabilities, appropriate adaptive adjustments are made to Harmony Memory Considering Rate (HMCR) and Pitch Adjustment Rate (PAR). Experimental validation on the CEC2017 test function set demonstrates that EO-HS-NDD outperforms HS and nine other HS variants in terms of robustness, convergence speed, and optimization accuracy. Comparisons with advanced versions of the Differential Evolution (DE) algorithm also indicate that EO-HS-NDD exhibits superior solving capabilities. Moreover, EO-HS-NDD is applied to solve 15 real-world optimization problems from CEC2020 and compared with advanced algorithms from the CEC2020 competition. The experimental results show that EO-HS-NDD performs well in solving real-world optimization problems. [ABSTRACT FROM AUTHOR]

Clostridium perfringens alpha toxin (CPA), which causes yellow lamb disease in sheep and gas gangrene and food poisoning in humans, is produced by all types of C. perfringens and is the major virulence determinant of C. perfringens type A. CPA induces hemolysis in many species, including humans, murines, sheep and rabbits, through its enzymatic activity, which dissolves the cell membrane. Recent studies have shown that some pore-forming toxins cause hemolysis, which is achieved by the activation of purinergic receptors (P2). However, the relationship between P2 receptors and non-pore-forming toxin hemolysis has not been investigated. In the present study, we examined the function of P2 receptors in CPA toxin hemolysis and found that CPA-induced hemolysis was dependent on P2 receptor activation, and this was also true for Staphylococcus aureus β-Hemolysin, another non-pore-forming toxin. Furthermore, we use selective P2 receptor antagonists to demonstrate that P2X1 and P2X7 play important roles in the hemolysis of human and murine erythrocytes. In addition, we found that redox metabolism was mainly involved in CPA-induced hemolysis using metabolomic analysis. We further demonstrate that CPA activates P2 receptors and then activates NADPH oxidase through the PI3K/Akt and MEK1/ERK1 pathways, followed by the production of active oxygen to induce hemolysis. These findings contribute to our understanding of the pathological effects of CPA, clarify the relationship between P2 activation and non-pore-forming toxin-induced hemolysis, and provide new insights into CPA-induced hemolysis. [ABSTRACT FROM AUTHOR]

Food poisoning caused by Staphylococcal enterotoxins (SEs) is prevalent globally, making efficient detection of these toxins very important. Traditionally, liquid chromatography–mass spectrometry required immunosorbent enrichment by magnetic bead-coupled antibodies obtained by animal-specific immunization. However, this method is time-consuming and costly. In this study, two recombinant protein capture molecules were designed based on the principle of toxins binding to Major Histocompatibility Complex (MHCII) and T cell receptor (TCR) molecules. The two capture molecules are called MHCII and MHCII-D10. The design of the MHCII and TCR-D10 was achieved through searching for the binding site protein sequence of Staphylococcal enterotoxins in the relevant literature, and MHCII-D10 was to link MHCII sequence with TCR-D10 sequence using linker (G4S)3 linking peptide. These capture molecules were shown to effectively bind to seven types of toxins and to capture SEs in various matrices. The digestion time, ratio, and temperature were further optimized, reducing the overall digestion time to just 2 h. The specificity, linearity, sensitivity, precision (RSD%), and recovery of the two methods were verified by liquid chromatography–mass spectrometry. When the MHCII and MHCII-D10 captured the toxins, the limit of quantification (LOD) in the 1 × PBS, plasma, and milk matrices ranged from 1.5625 to 100 fmol/µL, with the recovery rate ranging from 18.4% to 96%. The design of these capture molecules eliminates the need for animal-specific immunization, simplifying the pre-detection process and avoiding ethical concerns. This development holds significant promise for clinical diagnosis and reference. [ABSTRACT FROM AUTHOR]

Background: Anti-disialoganglioside (anti-GD2) monoclonal antibodies are effective immunotherapeutic drugs for treating neuroblastoma, yet their toxicity spectrum is unclear. Objective: This study aimed to assess the toxicity profiles of three anti-GD2 monoclonal antibodies (dinutuximab, dinutuximab β, and naxitamab) in clinical applications by mining and evaluating the adverse drug reaction (ADR) signals from the US Food and Drug Administration Adverse Event Reporting System. Methods: Data in the US Food and Drug Administration Adverse Event Reporting System from the time anti-GD2 monoclonal antibodies became available in the market to the first quarter of 2023 were searched. The signals of anti-GD2 monoclonal antibody-associated ADRs were quantified using four types of algorithms, including the reporting odds ratio, the proportional reporting ratio, the combination of the proportional reporting ratio and χ2 statistic method used by the UK Medicines and Healthcare Products Regulatory Agency, and the Bayesian confidence propagation neural network. The ADRs were categorized by System Organ Class based on the Medical Dictionary for Regulatory Activities, and were sorted according to the frequency and signal strength of ADRs. Results: A total of 370 adverse drug event reports with anti-GD2 monoclonal antibodies listed as the 'primary suspected drugs' were identified, with 116 ADR signals detected, of which 22 were not in the drug labels. Among the adverse drug event reports, 276 reports concerned dinutuximab/dinutuximab β as primary suspected drugs with 90 ADR signals, involving 19 System Organ Classes, of which 21 signals were not in the label; 94 adverse drug event reports concerned naxitamab as the primary suspected drug with 26 ADR signals, involving 11 System Organ Classes, of which one was not in the label. For dinutuximab/dinutuximab β-related ADRs, the top five most frequent were "fever", "abdominal pain", "elevated aspartate aminotransferase (AST)", "elevated alanine aminotransferase (ALT)" and "hypotension"; the top five most intensive signals were "hypoalbuminemia", "elevated AST", "capillary leakage syndrome", "hypoxia" and "elevated ALT". For naxitamab-related ADRs, the top five most frequent were "hypotension", "pain", "urticarial", "hypertension" and "rash"; the top five most intensive signals were "hypotension", "urticaria", "hypoxemia", "bronchospasm" and "hypertension". Involved System Organ Classes included "investigations" and "respiratory, thoracic and mediastinal disorders" containing the most types of ADR signals in dinutuximab/dintuximab β-related ADRs and naxitamab-related ADRs, respectively. Conclusions: Our study comprehensively analyzed the toxicity profiles of anti-GD2 monoclonal antibodies and provides an important reference for clinical monitoring and ADR identification of these drugs. [ABSTRACT FROM AUTHOR]

This article, published in the journal Cell Discovery, discusses the potential vulnerability of the African swine fever virus (ASFV) and the identification of its major protective antigen, p72. The authors used flow cytometry to sort plasmablasts from infected swine and produced recombinant monoclonal antibodies (mAbs) for structural and functional investigations. They determined the epitopes of the antibodies and found that they recognize conformational epitopes on the exposed regions of p72. The study provides insights into the neutralization mechanism of ASFV and offers a framework for the development of vaccines to combat the virus. [Extracted from the article]

Two strains of viruses, JC13C644 and JC13C673, were isolated from Culicoides tainanus collected in Jiangcheng County, Yunnan Province, situated along the border area shared by China, Laos, and Vietnam. JC13C644 and JC13C673 viruses can cause cytopathic effect (CPE) in mammalian cells BHK21 and Vero cells, and cause morbidity and mortality in suckling mice 48 h after intracerebral inoculation. Whole-genome sequencing was performed, yielding complete sequences for all 10 segments from Seg-1 (3942nt) to Seg-10 (810nt). Phylogenetic analysis of the sub-core-shell (T2) showed that the JC13C644 and JC13C673 viruses clustered with the Epizootic Hemorrhagic Disease Virus (EHDV) isolated from Japan and Australia, with nucleotide and amino acid homology of 93.1% to 98.3% and 99.2% to 99.6%, respectively, suggesting that they were Eastern group EHDV. The phylogenetic analysis of outer capsid protein (OC1) and outer capsid protein (OC2) showed that the JC13C644 and JC13C673 viruses were clustered with the EHDV-10 isolated from Japan in 1998, with the nucleotide homology of 98.3% and 98.5%, and the amino acid homology of 99.6% and 99.6–99.8%, respectively, indicating that they belong to the EHDV-10. Seroepidemiological survey results demonstrated that JC13C644 virus-neutralizing antibodies were present in 29.02% (177/610) of locally collected cattle serum and 11.32% (89/786) of goat serum, implying the virus's presence in Jiangcheng, Yunnan Province. This finding suggests that EHDV-10 circulates not only among blood-sucking insects in nature but also infects local domestic animals in China. Notably, this marks the first-ever isolation of the virus in China and its discovery outside of Japan since its initial isolation from Japanese cattle. In light of these results, it is evident that EHDV Serotype 10 exists beyond Japan, notably in the natural vectors of southern Eurasia, with the capacity to infect local cattle and goats. Therefore, it is imperative to intensify the surveillance of EHDV infection in domestic animals, particularly focusing on the detection and monitoring of new virus serotypes that may emerge in the region and pose risks to animal health. [ABSTRACT FROM AUTHOR]

Tumor tissue engineering holds great promise for replicating the physiological and behavioral characteristics of tumors in vitro. Advances in this field have led to new opportunities for studying the tumor microenvironment and exploring potential anti‐cancer therapeutics. However, the main obstacle to the widespread adoption of tumor models is the poor understanding and insufficient reconstruction of tumor heterogeneity. In this review, the current progress of engineering heterogeneous tumor models is discussed. First, the major components of tumor heterogeneity are summarized, which encompasses various signaling pathways, cell proliferations, and spatial configurations. Then, contemporary approaches are elucidated in tumor engineering that are guided by fundamental principles of tumor biology, and the potential of a bottom‐up approach in tumor engineering is highlighted. Additionally, the characterization approaches and biomedical applications of tumor models are discussed, emphasizing the significant role of engineered tumor models in scientific research and clinical trials. Lastly, the challenges of heterogeneous tumor models in promoting oncology research and tumor therapy are described and key directions for future research are provided. [ABSTRACT FROM AUTHOR]

Hepatic osteodystrophy (HOD) is a metabolically associated bone disease mainly manifested as osteoporosis with the characteristic of bone loss induced by chronic liver disease (CLD). Due to its high incidence in CLD patients and increased risk of fracture, the research on HOD has received considerable interest. The specific pathogenesis of HOD has not been fully revealed. While it is widely believed that disturbance of hormone level, abnormal secretion of cytokines and damage of intestinal barrier caused by CLD might jointly affect the bone metabolic balance of bone formation and bone absorption. At present, the treatment of HOD is mainly to alleviate the bone loss by drug treatment, but the efficacy and safety are not satisfactory. Mesenchymal stromal cells (MSCs) are cells with multidirectional differentiation potential, cell transplantation therapy based on MSCs is an emerging therapeutic approach. This review mainly summarized the pathogenesis and treatment of HOD, reviewed the research progress of MSCs therapy and the combination of MSCs and scaffolds in the application of osteoporotic bone defects, and discussed the potential and limitations of MSCs therapy, providing theoretical basis for subsequent studies. [ABSTRACT FROM AUTHOR]

Hyaluronic acid (HA) is an attractive anionic polysaccharide polymer with inherent pharmacological properties and versatile chemical groups for modification. Due to their water retention ability, biocompatibility, biodegradation, cluster of differentiation‐44 targeting, and highly designable capacity, HA hydrogels have been an emerging biomaterial, showing tailoring performance in terms of chemical modifications and hydrogel forms. Various preparation technologies have been developed for the fabrication of the tailoring HA hydrogels with unique structures and functions. They have been utilized in diverse biomedical applications like drug delivery and tissue engineering scaffolds. Herein, this review comprehensively summarizes the HA derivatives with different molecule weights and functional modifications. Then the various fabrication methods to obtain tailoring hydrogels in the forms of nanogel, nanofiber, microparticle, microneedle patch, injectable hydrogel, and scaffold are reviewed as well. The emphasis is focused on the shining biomedical applications of these tailoring HA hydrogels in anti‐bacteria, anti‐inflammation, wound healing, cancer treatment, regenerative medicine, psoriasis treatment, diagnosis, etc. The potentials and prospects are subsequently given to inspire further investigation, aiming at accelerating product translation from research to clinic. [ABSTRACT FROM AUTHOR]

This correction notice addresses errors in an article titled "Mesenchymal stem cell-secreted prostaglandin E2 ameliorates acute liver failure via attenuation of cell death and regulation of macrophage polarization." The authors clarify that the term "PI" should be changed to "Cleaved PARP (Asp214)" in reference to a specific protein used to detect apoptosis or necrosis. The correction also includes changes to the labeling and description of figures in the article. The authors apologize for any inconvenience caused by these errors. [Extracted from the article]

Chronic infection of hepatitis B virus (HBV) is the major cause of hepatocellular carcinoma (HCC). Notably, 90% of HBV‐positive HCC cases exhibit detectable HBV integrations, hinting at the potential early entanglement of these viral integrations in tumorigenesis and their subsequent oncogenic implications. Nevertheless, the precise chronology of integration events during HCC tumorigenesis, alongside their sequential structural patterns, has remained elusive thus far. In this study, we applied whole‐genome sequencing to multiple biopsies extracted from six HBV‐positive HCC cases. Through this approach, we identified point mutations and viral integrations, offering a blueprint for the intricate tumor phylogeny of these samples. The emergent narrative paints a rich tapestry of diverse evolutionary trajectories characterizing the analyzed tumors. We uncovered oncogenic integration events in some samples that appear to happen before and during the initiation stage of tumor development based on their locations in reconstituted trajectories. Furthermore, we conducted additional long‐read sequencing of selected samples and unveiled integration‐bridged chromosome rearrangements and tandem repeats of the HBV sequence within integrations. In summary, this study revealed premalignant oncogenic and sequential complex integrations and highlighted the contributions of HBV integrations to HCC development and genome instability. [ABSTRACT FROM AUTHOR]

Constructed wetlands (CWs) widely applied for wastewater treatment release significant greenhouse gases (GHGs), contributing to global warming. It is essential to characterize the comprehensive source-sink effects and affecting factors of GHGs in CWs, offering references and guidance for designing and operating CWs to better control GHG emissions. However, current reviews focus on individual GHG emission mechanisms. With the aid of the Web of Science Core Collection database, the relevant literature on carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O) emissions in CWs after 2010 was collected and organized. As highlighted in the review, CWs can produce and transmit these GHGs into the atmosphere, forming sources of GHGs and sequestration CO2 through plants photosynthesis, forming sinks of GHGs. Their overall performance depends on many factors. Hybrid CWs, Cyperus papyrus, Cyperus alternifolius, and Iris pseudacorus, adsorption substrates like Fe-C, low temperatures, and a C/N ratio of five are beneficial for GHG mitigation in CWs. Future studies should focus on in-depth research into the mechanisms and overall source-sink benefits of plants and microorganisms in relation to GHGs. This review provided a comprehensive understanding of the emission mechanisms and affecting factors of the major GHGs in CWs, bridging the research gap in this field, helping researchers to clarify the context, and providing valuable in-sights for further scientific investigations. [ABSTRACT FROM AUTHOR]

Shortest path problems are encountered in many engineering applications, e.g., intelligent transportation, robot path planning, and smart logistics. The environmental changes as sensed and transmitted via the Internet of Things make the shortest path change frequently, thus posing ever-increasing difficulty for traditional methods to meet the real-time requirements of many applications. Therefore, developing more efficient solutions has become particularly important. This paper presents an improved discrete Jaya algorithm (IDJaya) to solve the shortest path problem. A local search operation is applied to expand the scope of solution exploration and improve solution quality. The time complexity of IDJaya is analyzed. Experiments are carried out on seven real road networks and dense graphs in transportation-related processes. IDJaya is compared with the Dijkstra and ant colony optimization (ACO) algorithms. The results verify the superiority of the IDJaya over its peers. It can thus be well utilized to meet real-time application requirements. [ABSTRACT FROM AUTHOR]

Biting midges of the genus Culicoides are important in both medicine and veterinary medicine because their blood-feeding regime enable them to transmit a variety of pathogens. In this study, the morphological characteristics of the new species of Culicoides (Sinocoides) jiangchengensis Wang et Liu sp. nov are described and compared with the other species of female Culicoides in the subgenus Sinocoides. Three morphological characteristics of C. jiangchengensis, such as without sensory pit in 3rd palpus segment, sensilla coeloconica on flagellomeres 1,9–13, and m1 and m2 cell of the wings with pale spots, were different from the other nine species of culicoides in subgenus Sinocoides. Genetically, C. jiangchengensis are most closely related to C. malipoensis, but they were located in different branches and the minimum interspecific distance between them was 12.6%. In addition, a checklist of 10 species in the subgenus Sinocoides Chu, 1983 (Diptera: Ceratopogonidae: Culicoides) in China, including the new species C. jiangchengensis Wang et Liu sp. nov., is provided, and an updated key to species of the subgenus Sinocoides Chu, 1983 was presented. [ABSTRACT FROM AUTHOR]

Epsilon toxin (ETX) is an exotoxin produced by type B and D Clostridium perfringens that causes enterotoxemia or necrotic enteritis in animals such as goats, sheep, and cattle. Vaccination is a key method in preventing such diseases. In this study, we developed a new type of dissolving microneedle patch (dMN) with a nanoparticle adjuvant for enhanced immune response to deliver the rETXY196E-C protein vaccine. We chose FDA-approved poly(lactic-co-glycolic acid) (PLGA) to prepare nanospheres as the vaccine adjuvant and introduced dimethyldioctadecylammonium bromide (DDAB) to make the surface of PLGA nanoparticles (PLGA NPs) positively charged for antigen adsorption. PLGA NPs with a diameter of 100~200 nm, a surface ZETA potential of approximately +40 mV, and good safety were successfully prepared and could effectively adsorb rETXY196E-C protein. Using non-toxic and antibacterial fish gelatin as the microneedle (MN) matrix, we prepared a PLGA-DDAB dMN vaccine with good mechanical properties that successfully penetrated the skin. After immunization of subcutaneous (SC) and dMN, antibody titers of the PLGA and Al adjuvant groups were similar in both two immune ways. However, in vivo neutralization experiments showed that the dMN vaccines had a better protective effect. When challenged with 100 × LD50 GST-ETX, the survival rate of the MN group was 100%, while that of the SC Al group was 80%. However, a 100% protective effect was achieved in both immunization methods using PLGA NPs. In vitro neutralization experiments showed that the serum antibodies from the dMN and SC PLGA NPs groups both protect naive mice from 10 × LD50 GST-ETX attack after being diluted 20 times and could also protect MDCK cells from 20 × CT50 GST-ETX attack. In conclusion, the PLGA-DDAB dMN vaccine we prepared has good mechanical properties, immunogenicity, and protection, and can effectively prevent ETX poisoning. This provides a better way of delivering protein vaccines. [ABSTRACT FROM AUTHOR]

Hemolysis is the process of rupturing erythrocytes (red blood cells) by forming nanopores on their membranes using hemolysins, which then impede membrane permeability. However, the self‐assembly process before the state of transmembrane pores and underlying mechanisms of conformational change are not fully understood. In this work, theoretical and experimental evidence of the pre‐pore morphology of Clostridium perfringens epsilon toxin (ETX), a typical hemolysin, is provided using in situ atomic force microscopy (AFM) complemented by molecular dynamics (MD) simulations to detect the conformational distribution of different states in Mica. The AFM suggests that the ETX pore is formed in two stages: ETX monomers first attach to the membrane and form a pre‐pore in no special conditions required, which then undergo a conformational change to form a transmembrane pore at temperatures above the critical point in the presence of receptors. The authors' MD simulations reveal that initial nucleation occurs when specific amino acids adsorb to negatively charged mica cavities. This work fills the knowledge gap in understanding the early stage of hemolysis and the oligomerization of hemolysins. Moreover, the newly identified pre‐pore of ETX holds promise as a candidate for nanopore applications. [ABSTRACT FROM AUTHOR]

Biting midges are one of the most common hematophagous insects. They are capable of transmitting a wide range of arboviruses and have a significant impact on public health and veterinary medicine. Herein, from midge samples collected in 2013 in Yunnan, China, one sample induced a cell cytopathic effect (CPE) in BHK-21, MA104, and PK15 cell lines. Next-generation sequencing data, RACE and PCR determined the genome sequence of the sample and designated as an Oya virus (OYAV) isolate SZC50. Phylogenetic analysis of the sample revealed that it was cluster into viruses from species Orthobunyavirus catqueense. The open reading frames of S, M, and L segment of OYAV SZC50 were closest to those of OYAV SC0806. Moreover, 831 serum samples (736 pigs, 45 cattle, and 50 sheep) were gathered from 13 cities in Yunnan Province to detect neutralizing antibody of OYAV SZC50. A significant proportion of OYAV SZC50 antibody (more than 30%) was found in Yunnan pig populations, with the positive rate of OYAV SZC50 antibody in pigs from Malipo reaching 95%. To determine the pathogenicity of OYAV SZC50, we chose three animal models: specific pathogen-free Kunming mice, C57BL/6 mice lacking the interferon α/β receptor, and chicken embryos. At 5, 6, and 7 days post-infection, all adult and suckling C57BL/6 mice, and specific pathogen-free suckling Kunming mice were dead. Our finding was expanding the knowledge about the infection and pathogenic risk of the neglected virus in the Orthobunyavirus. Author summary: Culicoides are an important component of arbovirus ecology and should be studied and watched over in order to the potential spread of emerging and re-emerging viruses. A novel OYAV isolate (SZC50), isolated from midge samples was sequenced in this study, and the virus's putative host tropism was also tested in vitro, and cell lines derived from pig showed a highly susceptible to OYAV SZC50. Notably, high prevalence of OYAV SZC50 neutralization antibody was found in Yunnan pig serum samples. Moreover, the pathogenicity of OYAV SZC50 in animal models was first shown using mice and chicken embryos. Adult C57BL/6 and suckling mice were shown to be extremely sensitive to OYAV SZC50 infection, in contrast to adult Kunming mice, who can survive following infection. The maximum fatality rate of chicken embryos was 37.5%. In summary, regarding the potential infection risk of OYAV to animal or human, systematic investigation of OYAV, its vector and reservoir in nature should be conducted. [ABSTRACT FROM AUTHOR]

Harmony search (HS) is a new swarm intelligent algorithm inspired by the process of music improvisation. Over the past decade, HS algorithm has been applied to many practical engineering problems. However, for some complex practical problems, there are some remaining issues such as premature convergence, low optimization accuracy and slow convergence speed. To address these issues, this paper proposes a novel intelligent global harmony search algorithm based on improved search stability strategy (NIGHS). In the search process, NIGHS uses the adaptive mean of harmony memory library to build a stable trust region around the global best harmony, and proposes a new coupling operation based on linear proportional relation, so that the algorithm can adaptively adjust the ability of exploration and exploitation in the search process and avoid premature convergence. In addition, the dynamic Gauss fine-tuning is adopted in the stable trust region to accelerate the convergence speed and improve the optimization accuracy. The common CEC2017 test functions are employed to test the proposed algorithm, the results show that NIGHS algorithm has a faster convergence speed and better optimization accuracy compared to the HS algorithm and its improved versions. [ABSTRACT FROM AUTHOR]

A total of six genes were integrated to calculate the lipid-derived prognostic risk score (LPRS) by the linear combination of gene expressions weighted by corresponding coefficients (Figure 1E). (M) Variations of LPRS among immune subtypes, and (N) distributions of immune subtypes between LPRS-stratified cohorts. gl Drawing on canonical gene insights,[7] we examined the expression of immunomodulators and immunostimulators in LPRS-stratified subtypes (Figure 4A). The Upset plot illustrated gene list intersection, and three GO terms were integrated to generate the union set that recapitulated lipid-related genes (Figure S2A). Dear Editor Hepatocellular carcinoma (HCC) ranks as the third most lethal cancer with 15% 5-year survival.[1] Lipid metabolism dysfunction is a pivotal feature in hepatocarcinogenesis.[2] Integrating lipid-related transcriptomics with clinicopathological data is crucial for HCC precision medicine and personalized therapy.[3] Hitherto, limited research on hepatic lipid metabolism hindered identifying unique HCC subtypes for tailored therapies. [Extracted from the article]

In July 2019, a novel viral strain (JH2019C603) was isolated from sentinel cattle in Jinghong City, in the subtropical region of Yunnan Province, China. The virus replicated and caused cytopathological effects in both Aedes albopictus (C6/36) and Baby Hamster Syrian Kidney (BHK-21) cells. Agarose gel electrophoresis analysis revealed a viral genome comprised of 10 segments of double-stranded RNA, with a 1-2-2-1-1-1-1-1 migration pattern. Complete genome sequences of the JH2019C603 virus were determined through full-length cDNA amplification. Phylogenetic analysis based on the amino acid (aa) sequences of RNA-dependent RNA Polymerase (Pol), Major subcore (T2) and Major core-surface (T13) showed that JH2019C603 clustered with Yonaguni orbivirus (YONOV) from Japan, with aa identities relative to YONOV of 97.7% (Pol), 99.0% (T2) and 98.5% (T13). However, phylogenetic analysis based on the aa sequences of the outer capsid protein one and two (OC1 and OC2) showed that JH2019C603 formed an independent branch in the phylogenetic tree, and its aa identity with YONOV was only 55.4% (OC1) and 80.8% (OC2), respectively. Compared with the prototype of YONOV, a notable sequence deletion was observed in the 3′ non-coding region of NS1, with the NS1 of JH2019C603 encoded within segment 7 (Seg-7), in contrast to YONOV, which contains NS1 in Seg-6. These results indicate that JH2019C603 belongs to the YONOV lineage and might be a novel serotype or a highly variant strain of YONOV. These findings will facilitate the identification of new isolates and clarify their geographical distribution, epidemiology, genetic diversity and possible disease associations. [ABSTRACT FROM AUTHOR]

The excessive and unreasonable use of pesticides has adversely affected the environment and human health. The soil, one of the most critical natural resources supporting human survival and development, accumulates large amounts of pesticide residues. Compared to traditional spectrophotometry analytical methods, nanoparticle-based sensors stand out for their simplicity of operation as well as their high sensitivity and low detection limits. In this review, we focus primarily on the functions that various nanoparticles have and how they can be used to detect various pesticide residues in soil. A detailed discussion was conducted on the properties of nanoparticles, including their color changeability, Raman enhancement, fluorescence enhancement and quenching, and catalysis. We have also systematically reviewed the methodology for detecting insecticides, herbicides, and fungicides in soil by using nanoparticles. [ABSTRACT FROM AUTHOR]

Clostridium perfringens ε-toxin (ETX) is the main toxin leading to enterotoxemia of sheep and goats and is classified as a potential biological weapon. In addition, no effective treatment drug is currently available in clinical practice for this toxin. We developed membrane-camouflaged nanoparticles (MNPs) with different membrane origins to neutralize ETX and protect the host from fatal ETX intoxication. We evaluated the safety and therapeutic efficacy of these MNPs in vitro and in vivo. Compared with membranes from karyocytes, such as Madin-Darby canine kidney (MDCK) cells and mouse neuroblastoma N2a cells (N2a cells), membrane from erythrocytes, which do not induce any immune response, are superior in safety. The protective ability of MNPs was evaluated by intravenous injection and lung delivery. We demonstrate that nebulized inhalation is as safe as intravenous injection and that both modalities can effectively protect mice against ETX. In particular, pulmonary delivery of nanoparticles more effectively treated the challenge of inhaled toxins than intravenously injected nanoparticles. Moreover, MNPs can alter the biological distribution of ETX among different organs in the body, and ETX was captured, neutralized and slowly delivered to the liver and spleen, where nanoparticles with ETX could be phagocytized and metabolized. This demonstrates how MNPs treat toxin infections in vivo. Finally, we injected the MNPs into mice in advance to find out whether MNPs can provide preventive protection, and the results showed that the long-cycle MNPs could provide at least a 3-day protection in mice. These findings demonstrate that MNPs provide safe and effective protection against ETX intoxication, provide new insights into membrane choices and delivery routes of nanoparticles, and new evidence of the ability of nanoparticles to provide preventive protection against infections. [ABSTRACT FROM AUTHOR]

Epsilon toxin (ETX), produced by type B and D strains of Clostridium perfringens, can cause fatal enterotoxaemia in ruminant animals, particularly sheep, cattle, and goats. Previous studies show that the cytotoxicity of ETX is dependent on the integrity of lipid rafts, the maintenance of which is ensured by cholesterol. Zaragozic acid (ZA) is a statin drug that reduces the synthesis of squalene, which is responsible for cholesterol synthesis. In this study, ZA significantly reduced the toxicity of ETX in Madin–Darby canine kidney (MDCK) cells. We show that ZA does not affect the binding of ETX to MDCK cells, but propidium iodide staining (PI) and Western blotting confirmed that ZA significantly disrupts the ability of ETX to form pores or oligomers in MDCK cells. Additionally, ZA decreased the phosphatidylserine exposure on the plasma membrane and increased the Ca2+ influx of the cells. Results of density gradient centrifugation suggest that ZA decreased the number of lipid rafts in MDCK membranes, which probably contributed to the attenuation of pore-formation. Moreover, ZA protected mice against ETX in vivo. All mice pre-treated with ZA for 48 h before exposure to an absolute lethal dose of ETX (6400 ng/kg) survived. In summary, these findings provide an innovative method to prevent ETX intoxication. Considering many pore-forming toxins require lipid rafts, we tested and found ZA also inhibited the toxicity of other toxins such as Clostridium perfringens Net B and β-toxin (CPB) and Staphylococcus aureus α-hemolysin (Hla). We expect ZA can thus be developed as a broad-spectrum medicine for the treatment of multiple toxins. In addition, other statins, such as lovastatin (LO), also reduced the toxicity of ETX. These findings indicate that statin medicines are potential candidates for preventing and treating multiple toxin-induced diseases. [ABSTRACT FROM AUTHOR]

Relevance Vector Machine (RVM) is a supervised learning algorithm extended from Support Vector Machine based on the Bayesian sparsity model. Relevance Vector Machine classification suffers from theoretical limitations and computational inefficiency mainly because there is no closed‐form solution for the posterior of the weight parameters. We propose two advanced Bayesian approaches for RVM classification, namely the Enhanced RVM and the Reinforced RVM, to perfect the theoretic framework of RVM and extend the algorithm to the imbalanced data problem, which has an arresting skew in data size between classes. First, the Enhanced RVM conducts a strict Bayesian sampling process instead of the approximation method in the original one to remedy its theoretic limitations, especially the non‐convergence of the iterations. Secondly, we conjecture that the hierarchical prior makes the Reinforced RVM achieve consistent estimations of the quantities of interest compared with the non‐consistent estimations of the original RVM. Consistency is necessary for RVM classification since it makes the model more stable and localises the relevant vectors more accurately in the imbalanced data problem. The two‐level prior also renders the Reinforced one competitive in the imbalanced data problem by building the inner connection of parameter dimensions and alloting a more vital relevance to the small class data weight parameter. The theoretic proofs and several numeric studies demonstrate the merits of our two proposed algorithms. [ABSTRACT FROM AUTHOR]

To accurately locate rotor–stator rubbing faults in aero-engine, a method combining intrinsic time scale decomposition (ITD), Hjorth parameter and cepstrum analysis has been proposed. First, the method works by decomposing vibration signals from casing into proper rotation components (PRCs) based on ITD; second, calculates the autocorrelation function of each rotation component and the complexity parameters of autocorrelation functions; third, chooses PRCs for signal reconstruction according to complexity from Hjorth parameters and reconstructs the signals based on chosen PRCs; at last, considering that with different positions of rubbing, transfer paths of signals collected by the sensors from the same position are different, cepstrum analysis has been made according to reconstructed signals, and the transfer paths characteristics from cepstrum are taken as feature vectors and inputted into support vector machine for identifying the positions of rotor-stator rubbing faults. The results indicate proposed ITD-Hjorth-Cepstrum method can work well in the identification rate of training and test samples as for the identification rate for an unknown sample. [ABSTRACT FROM AUTHOR]

Marine organisms provide novel and broad sources for the preparations and applications of biomaterials. Since the urgent requirement of bio‐hydrogels to mimic tissue extracellular matrix (ECM), the natural biomacromolecule hydrogels derived from marine sources have received increasing attention. Benefiting from their outstanding bioactivity and biocompatibility, many attempts have been made to reconstruct ECM components by applying marine‐derived natural hydrogels. Moreover, marine hydrogels have been successfully applied in biomedicine by means of microfluidics, electrospray, and bioprinting. In this review, the classification and characteristics of marine‐derived hydrogels are summarized. In particular, their role in the development of biomaterials is also introduced. Then, the recent advances in bio‐fabrication strategies for various hydrogel materials are focused upon. Besides, the influences of hydrogel types on their functions in biomedical applications are discussed in depth. Finally, critical reflections on the limitations and future development of marine‐derived hydrogels are presented. [ABSTRACT FROM AUTHOR]

Organophosphorus flame retardants (OPFRs) are widely used in various industrial manufacturing processes; thus, their environmental impact in agglomerated industrial areas is of great concern. In this study, seventeen kinds of OPFRs and five kinds of organophosphate diesters (Di-OPs) in water and upper sediment samples from two urban rivers in the agglomerated industrial area of Shenzhen city, China, were investigated. The results showed that the total concentrations of detectable OPFRs ranged from 3438.83 to 12,838.87 ng/L with an average of 6494.94 ng/L in water samples and from 47.16 to 524.46 ng/g (dry weight, dw) with an average of 181.48 ng/g dw in sediment. The values were higher than those in other rivers worldwide. Tris(2-chloroethyl) phosphate (TCEP) is the predominant OPFRs in water and upper sediment, up to 10,664.23 ng/L in water and 414.12 ng/g dw in sediment. The total concentration of OPFRs of sediment samples in the Maozhou River was around twice as high as in the Guanlan River. The results indicated that the level of OPFRs was associated with the industrial activity intensity. Di-OPs exhibited lower concentrations than their parent compounds, and can be attributed to the degradation/metabolism of their parent compounds in the river. The sediment–water partition of OPFRs is significantly correlated with their log Kow values. Risk assessment revealed moderate ecological risks posed by OPFRs in water to aquatic organisms. The present study revealed the pollution status of OPFRs in rivers from agglomerated industrial and residential areas. [ABSTRACT FROM AUTHOR]

Background: In August 2013, a virus strain (DH13M98) was isolated from Culex tritaeniorhynchus Giles collected in Mangshi, the southwestern border area of Yunnan Province, China. The virus replicated and caused cytopathic effects (CPE) in Aedes albopictus (C6/36) cells, but not in baby hamster Syrian kidney (BHK-21) cells. Materials and Methods: Agarose gel electrophoresis (AGE) analysis revealed that the DH13M98 virus was a 10-segment double-stranded RNA (dsRNA) virus, with a "1-1-1-2-1-1-2-1" pattern. The full genome of the DH13M98 virus was sequenced by full-length amplification of complementary DNAs (FLAC). Results: Phylogenetic analysis of the viral RNA-dependent RNA polymerase (Pol), major subcore-shell (T2), and major core-surface (T13) protein showed that DH13M98 clustered with Umatilla virus (UMAV), and the amino acid (aa) sequences of DH13M98 shared more than 89.5% (Pol), 95% (T2), and 91.1% (T13) identity with UMAV. However, the aa identity of outer capsid protein one (OC1) of DH13M98 with other UMAV was 57.1–79.2%, suggesting that DH13M98 was UMAV, but distinct from other strains of UMAV from the United States, Japan, and Germany at OC1, and it may be a high variant strain of UMAV, even a new serotype. Conclusion: This is the first isolation of UMAV in China, which enriches the resources of virus species in China and provides new insights into the genetic diversity and geographical distribution of the virus. [ABSTRACT FROM AUTHOR]

Background: As a Class A bioterrorism agent, botulinum neurotoxin serotype A (BoNT/A) carries the risk of being used by terrorists to cause mass poisoning. The microneedle (MN) patch has a great potential for application as a novel vaccine delivery method. The aim of this study is to develop a thermally stable, dissolving microneedle patch for the delivery of a recombinant protein vaccine using a recombinant C-terminal heavy chain of BoNT/A (Hc of BoNT/A, AHc) to prevent botulism. Methods: Fish gelatin, a natural non-toxic and bacteriostatic material, was selected as the microneedle matrix for the preparation of the dissolving microneedle vaccine. Subsequently, the mechanical performance, bacteriostatic properties, vaccination effect, and stability of the microneedle patches were evaluated using instruments such as the displacement-force test station and optical coherence tomography (OCT) scanner. Results: Fish gelatin matrix at high concentrations has good bacteriostatic properties, and excellent mechanical performance and vaccination effect, meeting the necessities of a vaccine. In both in vivo and in vitro neutralization experiments, MN vaccines containing different antigen doses achieved the same protective efficacy as subcutaneous vaccinations, protecting mice against 106 LD50 of BoNT/A injected intraperitoneally. Thermal stability analysis of the MN vaccines revealed that the fish gelatin matrix protected the AHc vaccine from protein denaturation even after 7 days of storage at 37 °C and enabled the vaccine patches to maintain good immunogenicity and protective efficacy even after 6 months of storage at room temperature. Conclusion: In this study, we successfully prepared a bacteriostatic MN patch using a fish gelatin matrix that not only has a good vaccination effect, but also obviates the need for a cold chain for the AHc vaccine, providing the possibility of rapid, painless, and large-scale vaccination. [ABSTRACT FROM AUTHOR]

As a distinguished Chinese indigenous pig breed that exhibits disease resistance and high meat quality, the Anqing six-end-white (AQ) pig represents a valuable germplasm resource for improving the quality of the pig breeding industry. In this study, 24 AQ pigs that were distantly blood-related and 6 Asian Wild Boar (AWB) were selected for 10× deep-genome resequencing. The signatures of the selection were analyzed to explore the genetic basis of their germplasm characteristics and to identify excellent germplasm-related functional genes based on NGS data. A total of 49,289,052 SNPs and 6,186,123 indels were detected across the genome in 30 pigs. Most of the genetic variations were synonym mutations and existed in the intergenic region. We identified 275 selected regions (top 1%) harboring 85 genes by applying a crossover approach based on genetic differentiation (FST) and polymorphism levels (π ratio). Some genes were found to be positively selected in AQ pigs' breeding. The SMPD4 and DDX18 genes were involved in the immune response to pseudorabies virus (PRV) and porcine reproductive and respiratory syndrome virus (PRRSV). The BCL6 and P2RX6 genes were involved in biological regulation of immune T cells and phagocytes. The SLC7A4 and SPACA4 genes were related to reproductive performance. The MSTN and HIF1A genes were related to fat deposition and muscle development. Moreover, 138 overlapping regions were detected in selected regions and ROH islands of AQ pigs. Additionally, we found that the QTLs with the most overlapping regions were related to back fat thickness, meat color, pH value, fatty acid content, immune cells, parasitic immunity, and bacterial immunity. Based on functional enrichment analysis and QTLs mapping, we conducted further research on the molecular genetic basis of germplasm traits (disease resistance and excellent meat quality). These results are a reliable resource for conserving germplasm resources and exploiting molecular markers of AQ pigs. [ABSTRACT FROM AUTHOR]