Evaluating the mosquito vector range for two orthobunyaviruses: Oya virus and Ebinur Lake virus.

BACKGROUND: Mosquito-borne viruses cause various infectious diseases in humans and animals. Oya virus (OYAV) and Ebinur Lake virus (EBIV), belonging to the genus Orthobunyavirus within the family Peribunyaviridae, are recognized as neglected viruses with the potential to pose threats to animal or public health. The evaluation of vector competence is essential for predicting the arbovirus transmission risk. METHODS: To investigate the range of mosquito vectors for OYAV (strain SZC50) and EBIV (strain Cu20-XJ), the susceptibility of four mosquito species (Culex pipiens pallens, Cx. quinquefasciatus, Aedes albopictus, and Ae. aegypti) was measured through artificial oral infection. Then, mosquito species with a high infection rate (IR) were chosen to further evaluate the dissemination rate (DR), transmission rate (TR), and transmission efficiency. The viral RNA in each mosquito sample was determined by RT-qPCR. RESULTS: The results revealed that for OYAV, Cx. pipiens pallens had the highest IR (up to 40.0%) among the four species, but the DR and TR were 4.8% and 0.0%, respectively. For EBIV, Cx. pipiens pallens and Cx. quinquefasciatus had higher IR compared to Ae. albopictus (1.7%). However, the EBIV RNA and infectious virus were detected in Cx. pipiens pallens, with a TR of up to 15.4% and a transmission efficiency of 3.3%. CONCLUSIONS: The findings indicate that Cx. pipiens pallens was susceptible to OYAV but had an extremely low risk of transmitting the virus. Culex pipiens pallens and Cx. quinquefasciatus were susceptible to EBIV, and Cx. pipiens pallens had a higher transmission risk to EBIV than Cx. quinquefasciatus.

HSD17B13 liquid-liquid phase separation promotes leukocyte adhesion in chronic liver inflammation.

The rs72613567:TA polymorphism in 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13) has been found to reduce the progression from steatosis to nonalcoholic steatohepatitis. In this study, we sought to define the pathogenic role of HSD17B13 in triggering liver inflammation. Here we find that HSD17B13 forms liquid-liquid phase separation (LLPS) around lipid droplets in the livers of nonalcoholic steatohepatitis patients. The dimerization of HSD17B13 supports the LLPS formation and promotes its enzymatic function. HSD17B13 LLPS increases the biosynthesis of platelet activating factor (PAF), which in turn promotes fibrinogen synthesis and leukocyte adhesion. Blockade of PAFR or STAT3 pathway inhibited the fibrinogen synthesis and leukocyte adhesion. Importantly, adeno-associated viral-mediated xeno-expression of human HSD17B13 exacerbated western diet/carbon tetrachloride-induced liver inflammation in Hsd17b13-/- mice. In conclusion, our results suggest that HSD17B13 LLPS triggers liver inflammation by promoting PAF-mediated leukocyte adhesion, and targeting HSD17B13 phase transition could be a promising therapeutic approach for treating hepatic inflammation in chronic liver disease.

Composite Microparticles from Microfluidics for Chemo-/Photothermal Therapy of Hepatocellular Carcinoma.

Hydrogel microcarrier-based drug delivery systems are of great value in the combination therapy of tumors. Current research directions concentrate on the development of more economic, convenient, and effective combined therapeutic platforms. Herein, we developed novel adhesive composite microparticles (MPPMD) with combined chemo- and photothermal therapy ability via microfluidic electrospray technology for local hepatocellular carcinoma treatment. These composite microparticles consisted of doxorubicin (DOX)-loaded and polydopamine-wrapped mesoporous silicon and alginate. Benefiting from such a strategy of hierarchical structure drug loading, DOX could be gradually released from the system, effectively avoiding the direct toxicity of chemotherapeutics to the body. Additionally, the designed microparticles could not only effectively treat tumors by releasing the chemotherapy drug DOX but also show excellent photothermal properties under the irradiation of near-infrared light, achieving combined chemo- and photothermal treatment effects. Based on these advantages, the MPPMD could remarkably eliminate tumor cells in vitro and enormously restrict tumor development in vivo. These results illustrate that such composite microparticles are ideal combination treatment platforms, possessing promising expectations for cancer therapy.

A naturally isolated symbiotic bacterium suppresses flavivirus transmission by Aedes mosquitoes.

The commensal microbiota of the mosquito gut plays a complex role in determining the vector competence for arboviruses. In this study, we identified a bacterium from the gut of field Aedes albopictus mosquitoes named Rosenbergiella sp. YN46 (Rosenbergiella_YN46) that rendered mosquitoes refractory to infection with dengue and Zika viruses. Inoculation of 1.6 × 103 colony forming units (CFUs) of Rosenbergiella_YN46 into A. albopictus mosquitoes effectively prevents viral infection. Mechanistically, this bacterium secretes glucose dehydrogenase (RyGDH), which acidifies the gut lumen of fed mosquitoes, causing irreversible conformational changes in the flavivirus envelope protein that prevent viral entry into cells. In semifield conditions, Rosenbergiella_YN46 exhibits effective transstadial transmission in field mosquitoes, which blocks transmission of dengue virus by newly emerged adult mosquitoes. The prevalence of Rosenbergiella_YN46 is greater in mosquitoes from low-dengue areas (52.9 to ~91.7%) than in those from dengue-endemic regions (0 to ~6.7%). Rosenbergiella_YN46 may offer an effective and safe lead for flavivirus biocontrol.

Isolation and Genomic Characterization of Kadipiro Virus from Mosquitoes in Yunnan, China.

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.

Effects of environmentally relevant concentration of short-chain chlorinated paraffins on BV2 microglia activation and lipid metabolism, implicating altered neurogenesis.

Short-chain chlorinated paraffins (SCCPs), a class of persistent organic pollutants, have been found to cause diverse organ and systemic toxicity. However, little is known about their neurotoxic effects. In this study, we exposed BV2, a mouse microglia cell line, to environmentally relevant concentration of SCCPs (1 µg/L, 10 µg/L, 100 µg/L) for 24 h to investigate their impacts on the nervous system. Our observations revealed that SCCPs induced the activation of BV2 microglia, as indicated by altered morphology, stimulated cell proliferation, enhanced phagocytic and migratory capabilities. Analysis at the mRNA level confirmed the activation status, with the downregulation of TMEM119 and Tgfbr1, and upregulation of Iba1 and CD11b. The upregulated expression of genes such as cenpe, mki67, Axl, APOE and LPL also validated alterations in cell functions. Moreover, BV2 microglia presented an M2 alternative phenotype upon SCCPs exposure, substantiated by the reduction of NF-κB, TNF-α, IL-1ß, and the elevation of TGF-ß. Additionally, SCCPs caused lipid metabolic changes in BV2 microglia, characterized by the upregulations of long-chain fatty acids and acylcarnitines, reflecting an enhancement of ß-oxidation. This aligns with our findings of increased ATP production upon SCCPs exposure. Intriguingly, cell activation coincided with elevated levels of omega-3 polyunsaturated fatty acids. Furthermore, activated microglial medium remarkably altered the proliferation and differentiation of mouse neural stem cells. Collectively, exposure to environmentally relevant concentrations of SCCPs resulted in activation and lipid metabolic alterations in BV2 microglia, potentially impacting neurogenesis. These findings provide valuable insights for further research on the neurotoxic effect of SCCPs.

Structural elucidation and immunomodulatory activities in vitro of type I and II arabinogalactans from different origins of Astragalus membranaceus.

Astragalus membranaceus polysaccharide (APS) possesses excellent immunomodulatory activity. However, there are several studies on the structural characterization of APS. Here, we aimed to elucidate the repeating units of polysaccharides (APS1, 106.5 kDa; APS2, 114.5 kDa) obtained from different Astragalus membranaceus origins and further investigated their immunomodulatory activities. Based on structural analysis, types of the two polysaccharides were identified as arabinogalactan-I (AG-I) and arabinogalactan-II (AG-II), and co-elution of arabinogalactans (AGs) and α-glucan was observed. The backbone of AG-I was 1,4-linked ß-Galp occasionally substituted by α-Araf at O-2 and/or O-3. AG-II was a highly branched polysaccharide with long branches of α-Araf, which were attached to the O-3 of 1,6-linked ß-Galp of the backbone. The presence of AGs in A. membranaceus was confirmed for the first time. The two polysaccharides could promote the expression of IL-6, IL-1ß and TNF-α in RAW264.7 cells via MAPKs and NF-κB signaling pathways. The constants for APS1 and APS2 binding to Toll-like receptor 4 (TLR4) were 1.83 × 10-5 and 2.08 × 10-6, respectively. Notably, APS2 showed better immunomodulatory activity than APS1, possibly because APS2 contained more AGs. Hence, the results suggested that AGs were the vital components of APS in the immunomodulatory effect.

Biomimetic hepatic lobules from three-dimensional imprinted cell sheets.

Liver-tissue engineering has proven valuable in treating liver diseases, but the construction of liver tissues with high fidelity remains challenging. Here, we present a novel three-dimensional (3D)-imprinted cell-sheet strategy for the synchronous construction of biomimetic hepatic microtissues with high accuracy in terms of cell type, density, and distribution. To achieve this, the specific composition of hepatic cells in a normal human liver was determined using a spatial proteogenomics dataset. The data and biomimetic hepatic micro-tissues with hexagonal hollow cross-sections indicate that cell information was successfully generated using a homemade 3D-imprinted device for layer-by-layer imprinting and assembling the hepatic cell sheets. By infiltrating vascular endothelial cells into the hollow section of the assembly, biomimetic hepatic microtissues with vascularized channels for nutrient diffusion and drug perfusion can be obtained. We demonstrate that the resultant vascularized biomimetic hepatic micro-tissues can not only be integrated into a microfluidic drug-screening liver-on-a-chip but also assembled into an enlarged physiological structure to promote liver regeneration. We believe that our 3D-imprinted cell sheets strategy will open new avenues for biomimetic microtissue construction.

Isolation of Epizootic Hemorrhagic Disease Virus Serotype 10 from Culicoides tainanus and Associated Infections in Livestock in Yunnan, China.

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.

Developing natural polymers for skin wound healing.

Natural polymers are complex organic molecules that occur in the natural environment and have not been subjected to artificial synthesis. They are frequently encountered in various creatures, including mammals, plants, and microbes. The aforementioned polymers are commonly derived from renewable sources, possess a notable level of compatibility with living organisms, and have a limited adverse effect on the environment. As a result, they hold considerable significance in the development of sustainable and environmentally friendly goods. In recent times, there has been notable advancement in the investigation of the potential uses of natural polymers in the field of biomedicine, specifically in relation to natural biomaterials that exhibit antibacterial and antioxidant characteristics. This review provides a comprehensive overview of prevalent natural polymers utilized in the biomedical domain throughout the preceding two decades. In this paper, we present a comprehensive examination of the components and typical methods for the preparation of biomaterials based on natural polymers. Furthermore, we summarize the application of natural polymer materials in each stage of skin wound repair. Finally, we present key findings and insights into the limitations of current natural polymers and elucidate the prospects for their future development in this field.

Protective effect of Angelica sinensis polysaccharide on pregnant rats suffering from iron deficiency anemia via regulation of the hepcidin-FPN1 axis.

Iron deficiency anemia (IDA) is a common micronutrient deficiency among pregnant women with deleterious maternal and fetal outcomes. Angelica sinensis polysaccharide (ASP) has been shown to reduce hepcidin expression in IDA rats. However, the role of ASP in the treatment of IDA during pregnancy and its potential mechanisms have not been investigated. Moreover, the effect of ASP on duodenal iron absorption is not clear. The aim of this study was to investigate the preventive efficacy of ASP against IDA during pregnancy and clarify the underlying mechanisms. Our results showed that ASP improved maternal hematological parameters, increased serum iron, maternal tissue iron, and fetal liver iron content, and improved pregnancy outcomes. Additionally, ASP combated oxidative stress caused by iron deficiency by improving the body's antioxidant capacity. Western blot results demonstrated that ASP downregulated hepcidin expression by blocking the BMP6/SMAD4, JAK2/STAT3 and TfR2/HFE signaling pathways, which in turn increased the expression of FPN1 in the liver, spleen, and duodenum and promoted iron cycling in the body. Furthermore, ASP increased the expression of DMT1 and Dcytb in the duodenum, thereby facilitating duodenal iron uptake. Our results suggest that ASP is a potential agent for the prevention and treatment of IDA during pregnancy.

Sprayable Multifunctional Black Phosphorus Hydrogel with On-Demand Removability for Joint Skin Wound Healing.

Wound healing remains a critical challenge in regenerative engineering. Great efforts are devoted to develop functional patches for wound healing. Herein, a novel sprayable black phosphorus (BP)-based multifunctional hydrogel with on-demand removability is presented as a joints' skin wound dressing. The hydrogel is facilely prepared by mixing dopamine-modified oxidized hyaluronic acid, cyanoacetategroup-functionalized dextran containing black phosphorus, and the catalyst histidine. The catechol-containing dopamine can not only enhance tissue adhesiveness, but also endow the hydrogel with antioxidant capacity. In addition, benefiting from the photothermal conversion ability of the BP and thermally reversible performance of the formed C═C double bonds between aldehyde groups and cyanoacetate groups, the resulting hydrogel displays excellent antibacterial performance and on-demand dissolving ability under NIR irradiation. Moreover, by loading vascular endothelial growth factor into the hydrogel, the promoted migration and angiogenesis effects of endothelial cells can also be achieved. Based on these features, it is demonstrated that such sprayable BP hydrogels can effectively facilitate joint wounds healing by accelerating angiogenesis, alleviating inflammation, and improving wound microenvironment. Thus, it is believed that this NIR-responsive removable BP hydrogel dressing will put forward an innovative concept in designing wound dressings.

Engineering Heterogeneous Tumor Models for Biomedical Applications.

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.

Biopolymer-Assembled Porous Hydrogel Microfibers from Microfluidic Spinning for Wound Healing.

Hydrogels are considered as a promising medical patch for wound healing. Researches in this aspect are focused on improving their compositions and permeability to enhance the effectiveness of wound healing. Here, novel prolamins-assembled porous hydrogel microfibers with the desired merits for treating diabetes wounds are presented. Such microfibers are continuously generated by one-step microfluidic spinning technology with acetic acid solution of prolamins as the continuous phase and deionized water as the dispersed phase. By adjusting the prolamin concentration and flow rates of microfluidics, the porous structure and morphology as well as diameters of microfibers can be well tailored. Owing to their porosity, the resultant microfibers can be employed as flexible delivery systems for wound healing actives, such as bacitracin and vascular endothelial growth factor (VEGF). It is demonstrated that the resultant hydrogel microfibers are with good cell-affinity and effective drug release efficiency, and their woven patches display superior in vivo capability in treating diabetes wounds. Thus, it is believed that the proposed prolamins-assembled porous hydrogel microfibers will show important values in clinic wound treatments.

Toxicity Spectrum of Anti-GD2 Immunotherapy: A Real-World Study Leveraging the US Food and Drug Administration Adverse Event Reporting System.

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 ß, 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 ß 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 ß-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 ß-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.

Engineered stem cells by emerging biomedical stratagems.

Stem cell therapy holds immense potential as a viable treatment for a widespread range of intractable disorders. As the safety of stem cell transplantation having been demonstrated in numerous clinical trials, various kinds of stem cells are currently utilized in medical applications. Despite the achievements, the therapeutic benefits of stem cells for diseases are limited, and the data of clinical researches are unstable. To optimize tthe effectiveness of stem cells, engineering approaches have been developed to enhance their inherent abilities and impart them with new functionalities, paving the way for the next generation of stem cell therapies. This review offers a detailed analysis of engineered stem cells, including their clinical applications and potential for future development. We begin by briefly introducing the recent advances in the production of stem cells (induced pluripotent stem cells (iPSCs), embryonic stem cells (ESCs), mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs)). Furthermore, we present the latest developments of engineered strategies in stem cells, including engineered methods in molecular biology and biomaterial fields, and their application in biomedical research. Finally, we summarize the current obstacles and suggest future prospects for engineered stem cells in clinical translations and biomedical applications.

Advancements in the pathogenesis of hepatic osteodystrophy and the potential therapeutic of mesenchymal stromal cells.

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.

Cuttlefish-Inspired Photo-Responsive Antibacterial Microparticles with Natural Melanin Nanoparticles Spray.

Topical antibiotics can be utilized to treat periodontitis, while their delivery stratagems with controlled release and long-lasting bactericidal inhibition are yet challenging. Herein, inspired by the defensive behavior of cuttlefish expelling ink, this work develops innovative thermal-responsive melanin-integrated porous microparticles (MPs) through microfluidic synthesis for periodontitis treatment. These MPs are composed of melanin nanoparticles (NPs), poly(N-isopropylacrylamide) (PNIPAM), and agarose. Benefiting from the excellent biocompatibility and large surface area ratio of MPs, they can deliver abundant melanin NPs. Under near-infrared irradiation, the melanin NPs can convert photo energy into thermal energy. This leads to agarose melting and subsequent shrinkage of the microspheres induced by pNIPAM, thereby facilitating the release of melanin NPs. In addition, the released melanin NPs can serve as a highly effective photothermal agent, displaying potent antibacterial activity against porphyromonas gingivalis and possessing natural anti-inflammatory properties. These unique characteristics are further demonstrated through in vivo experiments, showing the antibacterial effects in the treatment of infected wounds and periodontitis. Therefore, the catfish-inspired photo-responsive antibacterial MPs with controlled-release drug delivery hold tremendous potential in clinical antibacterial applications.

Full genome characterization and evolutionary analysis of Banna virus isolated from Culicoides, mosquitoes and ticks in Yunnan, China.

Introduction: Banna virus (BAV), a potential pathogen that may cause human encephalitis, is the prototype species of genus Seadornaviru within the family Reoviridae, and has been isolated from a variety of blood-sucking insects and mammals in Asia. Methods: Culicoides, Mosquitoes, and Ticks were collected overnight in Yunnan, China, during 2016-2023 using light traps. Virus was isolated from these collected blood-sucking insects and grown using Aedes albopictus (C6/36) cells. Preliminary identification of the virus was performed by agarose gel electrophoresis (AGE). The full genome sequences of the BAVs were determined by full-length amplification of cDNAs (FLAC) and sequenced using next-generation sequencing. Results: In this study, 13 strains BAV were isolated from Culicoides, Mosquitoes and Ticks. Their viral genome consisted of 12 segments of double-stranded RNA (dsRNA), and with three distinct distribution patterns. Sequence analysis showed that Seg-5 of four strains (SJ_M46, SJ_M49, JC_M19-13 and JC_C24-13) has 435 bases nucleotide sequence insertions in their ORF compared to other BAVs, resulting in the length of Seg-5 up to 2128 nt. There are 34 bases sequence deletion in Seg-9 of 3 strains (WS_T06, MS_M166 and MS_M140). Comparison of the coding sequences of VP1, VP2, VP5, VP9 and VP12 of the 13 BAV strains, the results show that VP1, VP2 and VP12 are characterised by high levels of sequence conservation, while VP9 is highly variable, under great pressure to adapt and may be correlated with serotype. While also variable, VP5 appears to be under less adaptive pressure than VP9. Additionally, phylogenetic analysis indicates that the 13 BAV strains locate in the same evolutionary cluster as BAVs isolated from various blood-sucking insects, and are clustered according to geographical distribution. Conclusion: The data obtained herein would be beneficial for the surveillance of evolutionary characteristics of BAV in China and neighboring countries as well as extend the knowledge about its genomic diversity and geographic distribution.

Protein kinase A regulatory subunit is required for normal growth, zoosporogenesis, and pathogenicity in Phytophthora sojae.

Phytophthora sojae, one of the most devastating Oomycete pathogens, causes severe diseases that lead to economic loss in the soybean industry. The production of zoospores play a crucial role during the development of Phytophthora disease. In this work, CRISPR/Cas9 genome editing technology were used to obtain protein kinase A regulatory subunit (PsPkaR) knockout mutants. The role of PsPkaR in the production of zoospores and pathogenicity of P. sojae was analyzed. The overall findings indicate that PsPkaR is involved in regulating the growth process of P. sojae, primarily affecting the hyphal morphology and growth rate. Additionally, PsPkaR participates in the regulation of the release process of zoospores. Specifically, knocking-out PsPkaR resulted in incomplete cytoplasmic differentiation and uneven protoplast division, leading to abnormal release of zoospores. Furthermore, when the PsPkaR knockout mutants were inoculated on soybean leaves, the pathogenicity was significantly reduced compared to that of the wild-type and control strains. These findings of this study provide important clues and evidence regarding the role of the cAMP-PKA signaling pathway in the interaction between P. sojae and its host. This work contributes to a better understanding of the pathogenic mechanism of P. sojae and the development of corresponding prevention and control strategies.