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Animal gastrointestinal coronaviruses such as porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV) can cause oral infection despite being enveloped viruses, implying that they are capable of passing through the highly acidic gastric lumen. This study focused on the low pH acid resistance of coronaviruses, including PEDV, TGEV and equine coronavirus (ECoV) in fasted-state simulated gastric fluid (FaSSGF) at pH 1.6, which simulated gastric fluid. Interestingly, PEDV, TGEV and ECoV retained infectivity in FaSSGF, whereas SARS-CoV-2 was rapidly inactivated. Although FaSSGF containing surfactants did not affect the acid resistance of these gastrointestinal coronaviruses, FaSSGF including pepsin showed inactivation effects against PEDV, TGEV and ECoV. These findings suggest that animal gastrointestinal coronaviruses possess the potential ability to withstand low pH conditions in gastric acid environments.
West Nile virus (WNV) is a mosquito-borne pathogen of global concern that can cause fatal neuroinvasive disease, and no specific prophylaxis or treatment exists for infections by WNV and most related orthoflaviviruses. Here, we isolated and characterized antibodies from WNV convalescent individuals and report that neutralizing autoantibodies against type I interferons did not impair antiviral antibody development. Among the monoclonal antibodies with potent neutralizing activity against WNV that were identified, W010 targeted a distinct epitope within the envelope protein domain III (EDIII) and conferred both pre- and post-exposure protection in a murine WNV model, even when interferon signaling was impaired. A second protective antibody, W014, exhibited broad cross-neutralization of other pathogenic orthoflavivirus members, including Japanese encephalitis virus, Murray Valley encephalitis virus, Saint Louis encephalitis virus, and Usutu virus. These findings identify key neutralizing epitopes on WNV EDIII and provide candidates for the development of antibody-based interventions against encephalitic orthoflavivirus infections.
Rodents, which account for over 40% of mammalian species and occupy diverse terrestrial ecosystems, are major reservoirs for zoonotic viruses, including Coronaviridae, Hantaviridae, and Arenaviridae. However, the rodent species acting as central hubs for viral diversity and transmission remain poorly defined. To address this, we conducted systematic sampling across 18 counties and cities on Hainan Island between 2023 and 2024. A total of 2550 animals were collected, representing 14 Rodentia species, one Erinaceomorpha species, and one Scandentian species. Based on a statistical sampling framework, 1284 individuals were selected to generate 125 pooled gut samples for virome analysis. We identified 527 viral RNA species and recovered 175 complete or near-complete viral genomes. Remarkably, Rattus norvegicus and Rattus tanezumi accounted for 83.9% (442/527) of detected viral species, 68.6% (72/105) of novel viral sequences, and 88.6% (93/105) of cross-species viruses. Eight novel viruses showed recombination signals, seven originating from these two species. Among 13 human pathogenic viruses identified, 12 were detected in Rattus norvegicus and Rattus tanezumi. These findings suggest that these species may function as hub hosts for viral maintenance and spread, emphasizing the value of targeted surveillance to reduce future potential spillover risks.
Objective: To construct a reverse genetic system for the genotype ON1 of human respiratory syncytial virus subtype A (HRSV-A) expressing fluorescent reporter genes. Methods: Recombinant plasmids encoding EGFP or mCherry were constructed based on the 2019 Beijing HRSV-A ON1 dominant strain (6914). Recombinant viruses, rescued by co-transfecting BSR/T7-9 cells with helper plasmids, were identified via indirect immunofluorescence, whole-genome sequencing, and Western blot. Biological properties were characterized through fluorescent quantitative RT-PCR (qRT-PCR), immunostaining plaque assay and fluorescent focus assays (FFA). Results: Two recombinant viruses expressing EGFP or mCherry (rRSVA6914-EGFP and rRSVA6914-mCherry) were successfully rescued. Western blot analysis confirmed that the expression levels of key structural proteins (G, F, and N) in the recombinant strains were consistent with the parental virus. Multistep growth curve analysis revealed that the replication kinetics of the two recombinant viruses in HEp-2 cells did not differ significantly from those of the parental strain. Two recombinant viruses exhibited substantial neutralizing activity against both palivizumab and nirsevimab used in clinical settings. Furthermore, the viral titer of rRSVA6914-mCherry in A549 cells [(1.19±0.05)×105 PFU/ml] was significantly higher than in HEp-2 cells [(7.60±0.79)×104 PFU/ml] (P<0.001). For rRSVA6914-EGFP, the viral titers determined by immunostaining plaque assay and FFA methods were (1.15±0.17)×105 PFU/ml and (1.36±0.19)×105 FFU/ml. For rRSVA6914-mCherry, the corresponding titers were (3.50±0.23)×104 PFU/ml and (3.37±0.07)×104 FFU/ml. There was no statistically significant difference between the immunostaining plaque assay and FFA methods (both P>0.05). Conclusion: The HRSV-A genotype ON1 reverse genetic system expressing fluorescent reporter genes has been successfully constructed and systematically verified, providing a scientific tool for investigating the pathogenic mechanism of genotype ON1 and for screening antiviral drugs. 目的： 构建携带荧光报告基因的人呼吸道合胞病毒A亚型（HRSV-A）ON1基因型反向遗传学系统。 方法： 利用2019年北京地区分离的HRSV-A优势流行株ON1基因型6914株，构建携带增强型绿色荧光蛋白（EGFP）或红色荧光蛋白（mCherry）报告基因的重组质粒。通过与辅助质粒共转染至BSR/T7-9细胞拯救重组病毒；利用间接免疫荧光、全基因组测序、Western blot等方法鉴定病毒；基于荧光定量RT-PCR、免疫染色空斑试验及荧光灶形成试验（FFA）评价其生物学特性。 结果： 成功拯救出携带EGFP或mCherry报告基因的两株重组病毒（rRSVA6914-EGFP与rRSVA6914-mCherry）。Western blot证实重组病毒关键结构蛋白（G、F、N）表达水平与亲本株一致。多步生长曲线分析显示，两株重组病毒在HEp-2细胞中的复制动力学与亲本株基本一致。重组病毒对临床使用的帕丽珠单抗和尼塞韦单抗均表现出显著的中和活性。rRSVA6914-mCherry在A549细胞［（1.19±0.05）×105 PFU/ml］中的病毒滴度高于HEp-2细胞［（7.60±0.79）×104 PFU/ml］（P<0.001）。rRSVA6914-EGFP采用免疫染色空斑试验法和FFA法测得的病毒滴度为（1.15±0.17）×105 PFU/ml和（1.36±0.19）×105 FFU/ml，rRSVA6914-mCherry为（3.50±0.23）×104 PFU/ml和（3.37±0.07）×104 FFU/ml，两种方法测得的病毒滴度差异均无统计学意义（均P>0.05）。 结论： 成功构建并系统验证了携带荧光报告基因的HRSV-A ON1基因型反向遗传系统，可为ON1基因型致病机制研究及抗病毒药物筛选提供科学工具。.
Hepatitis B virus (HBV), a major human pathogen, replicates its DNA genome by protein-primed reverse transcription of a pregenomic RNA (pgRNA). This process is directed by the pgRNA-borne epsilon (ε) element, which provides the origin for minus-strand DNA synthesis and mediates coencapsidation of pgRNA with the viral polymerase (P protein) into nucleocapsids. ε adopts a thermodynamically stable hairpin structure that is remodeled upon formation of functional ε-P complexes, but the nature of the rearranged RNA structure and its implication for pgRNA encapsidation has remained elusive. Guided by in silico analyses of ε-like elements from distantly related nackednaviruses, we identify a distinct conformation of HBVε whose defining feature is a cryptic stem-loop (cSL), masked within the upper stem of ε. The P-dependent cSL conformation reorganizes key sequences into a compact structural unit that enables initiation of DNA synthesis and packaging of the viral pgRNA-P complex. RNAs engineered to favor cSL formation exhibit increased P protein affinity and strongly enhanced priming activity in vitro while maintaining replication competence in cells. Mutational analyses identify the cSL and its immediate vicinity, but not the remaining upper stem sequence, as the dominant determinants of ε function. Genetic variation in cSL-forming potential across hepadnaviruses links in vitro priming competence to the energetic accessibility of this alternative fold. Together, our findings reveal ε as a P protein-dependent RNA switch that tightly couples pregenome encapsidation to reverse transcription competence. This regulatory mechanism advances our understanding of HBV replication and could be exploited for antiviral intervention.
Positive-sense RNA viruses that constitute a large class of human pathogens employ various strategies to suppress and evade host immune defenses. Understanding the dynamic interaction between the viral life cycle and immune signaling is crucial to designing effective antiviral strategies. Although significant progress has been made, quantitative models that can accurately capture the intricate interactions and the intertwined dynamics during viral infection of cells remain missing. In this study, we develop a comprehensive mathematical model that integrates the intracellular viral life cycle with key cellular innate immune pathways, including RIG-I-mediated detection and JAK-STAT signaling. The model provides mechanistic insights into long-standing observations, capturing both virus-specific dynamics and innate immune response, and the key components driving their coupled dynamics. For example, a comparison of viruses shows how the Japanese Encephalitis virus undergoes a dramatic reduction in viral load in cells, due to its rapid replication that robustly activates the RIG-I pathway, in contrast to the poor immune control of Hepatitis C virus. More importantly, our model demonstrates how virus-host interactions exhibit a sharp transition boundary behavior, where minor differences in immune strength or viral suppression capacity can determine whether infections resolve or persist. We propose that ISG mRNA translation and viral replication predominantly dictate these bimodal infection outcomes. Additionally, the model not only recapitulates IFN desensitization but also identifies the molecular players involved. We demonstrate how our model's ability to capture IFN dynamics allows us to predict optimal timing and dosing strategies for interferon-based prophylactic therapies. Together, our approach reveals fundamental features that govern the delicate balance between the establishment of infection and immune control in RNA virus infections.
In germinal centers, activated B cells modify their antigen receptors through somatic hypermutation (SHM), followed by antigenic selection that favors expansion of high affinity B cells. The affinity maturation process is critical for development of broadly neutralizing antibodies (bnAbs) against the human immunodeficiency virus-1 (HIV-1). BnAbs have been isolated from some people living with HIV-1. Because these antibodies target conserved epitopes of the HIV-1 Envelope (Env) protein, they inhibit a broad spectrum of viruses. Eliciting bnAbs by vaccination is a top priority for HIV-1 prevention, but reproducing the lengthy maturation of bnAbs is a major challenge. The problem is typified by VRC01 class antibodies, which recognize the CD4 binding site of HIV-1 Env protein. To reach the CD4 binding site, antibodies need to navigate through adjacent glycans. Accommodating the glycans requires multiple SHMs in germinal center (GC) B cells, including infrequent events. For this reason, VRC01 vaccine development often stalls at this point. We have generated a mouse model aimed at providing a potential solution for navigating this vaccine design impediment. To this end, we made a mouse model that expresses a stalled VRC01 intermediate conditionally in GC B cells. This system has three advantages: 1) direct expression of the intermediate obviates prior immunization steps, thereby shortening the immunization scheme; 2) the conditional expression system bypasses tolerance control checkpoints that sometimes delete B cells expressing bnAbs; 3) the intermediate responds to immunization in GCs, the physiological site of affinity maturation. With this model, we established an immunization method to mature the VRC01 intermediate into heterologous neutralizing antibodies against viruses with a native glycan shield. Since high mutation load is common among bnAbs, the germinal center conditional expression system could provide a general tool for boost immunogen design to overcome roadblocks in the maturation pathway.
Glioblastoma (GB) is a WHO grade 4 brain cancer with dismal prognosis, yet its aetiology remains poorly defined. Although viral involvement has been proposed, findings across studies remain inconsistent, reflecting inherent limitations of individual technologies and cohort size. Here we applied metaproteomic profiling to a publicly available GB proteome dataset (12 control, 21 adjacent, 159 tumour) and an independent cohort of 81 samples (37 control, 44 tumour) to detect viral proteins in tumour and controls tissues. Across cohorts, we detected viral proteins from diverse species, with human herpesviruses (HHV-1, 2, and 8) more frequently detected in GB tumours compared with control tissues. Analysis of the host tumour proteome revealed differential abundance of proteins related to transcriptional regulation, RNA processing, protein translation, immune responses, and mitochondrial-associated metabolism. Correlation analysis identified associations between viral and human proteins, with several linked to biological processes previously implicated in DNA virus-host interactions. Further stratification of tumour by HHV-1 status showed consistent alterations in proteins associated with mitochondrial-associated metabolism, protein turnover, and cell adhesion/signalling.In summary, this study demonstrates the feasibility of metaproteomics for detecting viral components in archival GB tissues. Using this approach, we observed differences in viral protein landscape across cohorts and identified associations between viral presence and host proteomic features, providing a protein-level framework for future studies of virus-host interactions in GB.
The workshop on 'Reactive and therapy induced BM changes linked to systemic infectious and non-infectious disorders including MAS/HLH' of the 22nd meeting of the European Association for Haematopathology held in Dubrovnik, 2024, included 58 cases. These encompassed a broad range of infections, autoimmune disorders, malignancies and therapy-effects, or a combination of these factors, of which 28 had an associated Hemophagocytic Lymphohistiocytosis (HLH) / Macrophage Activation Syndrome (MAS). Histoplasmosis, the infection mostly associated with HLH, showed a wide variability of BM changes, with or without focal lesions. Leishmaniasis, less often associated with HLH, induced BM changes that mimic myelodysplastic syndrome. BM changes after COVID-19 infection included myeloid and megakaryocytic hypoplasia, erythroid hyperplasia, dyserythropoiesis, hemophagocytosis, and possibly ring granulomas. Other infectious causes included viruses (HHV-8, EBV, Parvovirus B19), mycobacterial infections, and human granulocytic anaplasmosis. HLH may arise in association with the full spectrum of EBV-related disorders, including acute infection, systemic chronic active EBV disease, viral reactivation, and EBV-associated malignancies. BM changes associated with autoimmune diseases included plasmacytosis, myeloid hyperplasia and hemophagocytosis, with or without meeting the criteria of MAS/HLH, the latter often triggered by a secondary infection or exacerbation of the disease. Haematologic malignancies (EBV-positive and negative) with HLH encompassed B-cell, T-/NK-cell, and myeloid neoplasms. In addition, the workshop included therapy-induced BM changes, such as differentiation syndrome, lenalidomide-associated B-ALL, therapy-related dysplasia, gelatinous transformation, CAR-T-induced BM hypoplasia, and CAR-T-associated HLH. Finally, the workshop demonstrated the presence of T-cell expansions in a variety of conditions, which should not be misinterpreted as T-cell malignancy.
Cytochrome P450 (CYP450) enzymes represent a critical class of detoxification enzymes that play essential roles in antioxidant defense, xenobiotic metabolism, and innate immune responses in animals. However, knowledge regarding the gene sequences and functional characteristics of CYP450 genes in mollusks remains limited. In this study, a novel CYP450 gene, designated Cf-CYP450, was cloned from the Zhikong scallop (Chlamys farreri). The open reading frame (ORF) of Cf-CYP450 spans 1497 bp and encodes a polypeptide of 498 amino acids. The N-terminus of the Cf-CYP450 protein contains a transmembrane domain, whereas the C-terminus harbors a conserved P450 domain. Phylogenetic analysis indicates that Cf-CYP450 is a newly identified member of the molluscan CYP450 family. Quantitative real-time PCR analysis revealed that Cf-CYP450 mRNA is ubiquitously expressed across various scallop tissues, with the highest expression observed in gill tissue. Furthermore, the expression of Cf-CYP450 is inducible by multiple stimuli, including pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS), peptidoglycan (PGN), and poly(I:C). As anticipated, infections with bacteria (including various Vibrio species) and viruses (e.g., acute viral necrosis virus) significantly alter Cf-CYP450 expression levels, suggesting its involvement in scallop innate immunity. Dual-luciferase reporter (DLR) assays further demonstrated that overexpression of Cf-CYP450 in HEK293T cells markedly suppresses the activity of multiple immune-related reporter genes. Additionally, Cf-CYP450 dose-dependently inhibits the activation of ISRE (Interferon stimulated response element) reporter genes induced by poly(I:C) or scallop IRF1 (Interferon regulatory factor 1). Notably, Cf-CYP450 expression in HEK293T cells also induces significant phosphorylation of MAPK (Mitogen-activated protein kinase) signaling proteins, such as JNK (c-Jun N-terminal kinase) and Erk1/2 (Extracellular regulated protein kinases 1/2). These findings collectively indicate that Cf-CYP450 plays a pivotal role in scallop defense against exogenous pathogens and may mediate diverse immune responses through participation in distinct signaling pathways or regulation of specific effector genes.
Engineering the genetic code-by reassigning multiple of the 64 natural codons-enables making organisms resistant to all viruses, preventing genetic information exchange, and allowing the biosynthesis of genetically encoded unnatural polymers. However, synonymous codon replacement-recoding-is frequently lethal, and how recoding impacts fitness remains poorly explored. Here, we explore these effects using genome synthesis, directed evolution, and genome-transcriptome-translatome-proteome co-profiling on multiple synthetic Escherichia coli genomes. We construct six partially recoded E. coli strains bearing up to 45.8% of a synthetic genome with a deleterious 57-codon genetic code. As our analyses revealed widespread defects-including unassigned codons in Syn61 and Syn57-we apply multi-omics to revise our genome design and mitigate defects. Using multi-omics, we show that recoding induces transcriptional and translational changes leading to fitness defects under hundreds of conditions. Finally, we develop a multi-omics-guided evolution strategy that rapidly restores fitness, enabling genome synthesis with radical changes.
Susceptibility to infection after solid organ transplantation (SOT) reflects interactions among epidemiologic exposures, allograft-specific factors, pharmacologic immunosuppression and host innate and adaptive immune functions. Substantial variability in susceptibility to viral, bacterial, and fungal infections occurs among recipients despite comparable immunosuppressive regimens. Accumulating evidence demonstrates that allelic variation, including single nucleotide polymorphisms, occurs in genes involved in multiple aspects of innate immune function and influence infectious risk after SOT. These genes encode pattern recognition receptors, complement components, phagocyte and natural killer cells functions, soluble opsonins, and cytokines. These variants are associated with altered susceptibility to bacterial, invasive fungal, and viral infections including cytomegalovirus, Epstein-Barr virus, BK polyomavirus, and hepatitis viruses. The contribution of allelic variation to infectious susceptibility remains incompletely defined. Identification of high-risk genotypes may enable individualized infectious surveillance, tailored antimicrobial prophylaxis, and host-directed interventions to advance precision transplantation.
In insects, two lysozyme types have been described: c-type lysozymes, which are well characterized at both the genetic and functional levels, and i-type lysozymes, whose functions remain comparatively less understood. Although traditionally recognized for their antibacterial activity, insect lysozymes have been implicated in a broad range of biological processes, including defense against fungi, viruses, and parasites, as well as digestion, microbiota regulation, nutrient recycling, and developmental transitions. In this review, we synthesize current knowledge on the diversity, structure, and functions of insect lysozymes across different taxa and feeding strategies. We propose that the multifunctionality of these enzymes positions them at the interface of immunity, metabolism, and development. Finally, we highlight major knowledge gaps, including the limited understanding of i-type lysozymes and the scarcity of studies in hemimetabolous insects, which constrain our understanding of lysozyme evolution and functional diversification.
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Dead-in-shell embryos may result from bacterial contamination of eggs, particularly infections caused by Salmonella spp. This study was conducted to investigate Salmonella prevalence in chicken farms in Ismailia Governorate, Egypt, characterization of serogroups, antimicrobial resistance profiles, biofilm-forming ability, virulence determinants (fimA, fimH, invA, stn, pefA, sopB, sopE1, and hilA), antimicrobial resistance genes (qnrS, qnrA, blaTEM, blaSHV, blaCTX-M, floR, tetA, and mcr-1), integrase genes (intI1 and intI3) and sequence analysis of gene cassettes associated with class 1 integrons. A total of 350 samples were collected, including dead-in-shell embryos (n = 285), egg nests (n = 33), and hatchery environments (n = 32). Bacteriological analysis, serogrouping, antimicrobial sensitivity testing, biofilm formation was performed as well as screening of virulence, antimicrobial resistance and integrase genes using PCR. Adding, sequencing of class 1 integron-associated gene cassettes. The overall prevalence of Salmonella was 9.71%. Salmonella Enteritidis was the predominant serovar (29.41%). Among the recovered isolates, 23.53% were classified as extensively drug-resistant (XDR), while 76.47% exhibited multidrug resistance (MDR), with a notably high resistance to colistin (88.24%). Biofilm was detected in 79.41% of the isolates at varying degrees. All tested isolates (100%) harbored the examined virulence genes (fimA, fimH, invA, stn, pefA, sopB, sopE1, and hilA) as well as the antimicrobial resistance genes qnrS, blaTEM, and blaSHV, with a high prevalence of the mcr-1 gene (87.5%). The class 1 integron integrase gene (intI1) was detected in 87.5% of the tested isolates, whereas all isolates were negative for the class 3 integron gene (intI3). Sequencing of the integron-associated gene cassettes revealed the presence of estX, aadA alleles, purL, dfrA, and lnuF genes. Given the critical role of hatcheries in poultry production chain, the emergence of XDR and MDR Salmonella strains facilitates early colonization of hatched chicks, promoting persistence and dissemination throughout the poultry production system. The emergence of highly virulent XDR and MDR Salmonella strains represents a significant public health threat, underscoring the urgent need for a One Health approach that integrates human, animal, and environmental health strategies to mitigate the spread of antimicrobial resistance and prevent further escalation of this alarming phenomenon.
Lessons and best practices from outbreaks during 2022-25 in Africa were not comprehensively documented or shared to inform future outbreak responses. We conducted a narrative review of published articles and outbreak response reports of mpox, cholera, Ebola virus disease, and Marburg virus disease and captured experts' perspectives and lessons. We analysed and presented the data in themes. Evidence indicates that effective responses are built on routine investments maintained between outbreaks, particularly in decentralised laboratories, digital surveillance systems, community structures, and clinical trial readiness. The institutionalisation of response mechanisms through national public health institutes, incident management systems, and emergency operations centres reflects a maturing continental preparedness architecture, reinforced by rapid regional solidarity, south-south cooperation, and timely partner support. National political leadership was crucial in mobilising resources and ensuring public compliance, whereas innovations such as expanded genomic surveillance, timely deployment of investigational countermeasures, mobility-aware outbreak control, and improved early-warning systems strengthened responses to outbreaks. The successful control of these recent outbreaks highlights the importance of strengthening preparedness, institutionalising response systems, and fostering coordinated, Africa-led health security frameworks to support resilient and sustainable outbreak response.
Since the emergence of Coronavirus Disease 2019 (COVID-19), it has become a global pandemic, profoundly affecting public health and daily life. Many recovering individuals report persistent or recurrent symptoms-fatigue, palpitations, cognitive impairment, shortness of breath, anxiety, and chest discomfort. These lingering effects impair work, daily function, and social interaction, placing a significant burden on individual quality of life and society. This study aims to evaluate the effectiveness of using an induced Incentive Spirometer as a respiratory training tool to relieve long COVID symptoms. This study, conducted from July 1, 2023, to May 11, 2024, at a regional teaching hospital in northern Taiwan, involved participants who had recovered from COVID-19 within the past year and had at least one long COVID respiratory symptom. Participants were assigned to one waiting control group and four experimental groups based on recovery time: within 3 months (Experimental Group 1), 3-6 months (Experimental Group 2), 6-9 months (Experimental Group 3), and 9-12 months (Experimental Group 4). The waiting control group received no interventions, while the experimental groups underwent inspiratory training using an induced Incentive Spirometer three times a week for 6 weeks (30 repetitions per session). Assessments were conducted before and after the intervention. Primary outcomes were the Dyspnoea-12 scale and Post-COVID-19 Functional Status scale. Secondary outcomes included the 6-minute walk distance and CaO₂. Ninety participants were enrolled, with five withdrawing, leaving 85 for final analysis. After 6 weeks of intervention, the waiting control group showed no significant changes in dyspnea (p = 0.463) or post-COVID-19 functional status (p = 0.343). In contrast, all experimental groups showed significant improvements. Dyspnoea-12 scale scores improved in Experimental Groups 1 (p < 0.001), 2 (p = 0.008), 3 (p = 0.011), and 4 (p = 0.001). The Post-COVID-19 Functional Status scale also showed improvements in all Experimental Groups (Group 1: p < 0.001, Group 2: p = 0.003, Group 3: p = 0.002, and Group 4: p = 0.011). Significant improvements in 6-min walk distance were observed in some experimental groups, improvements were seen in Experimental Groups 1 (p < 0.001), 2 (p = 0.027), 3 (p = 0.68), and 4 (p = 0.172). No significant changes in CaO2 were observed (pre-test, p = 0.872 and post-test, p = 0.585). Respiratory training using an induced Incentive Spirometer may help alleviate dyspnea and improve post-COVID-19 functional status in individuals with Long COVID. Earlier intervention appeared to yield better outcomes, although improvements were also observed even 9-12 months after infection. However, further studies with comprehensive pulmonary assessments are needed to confirm these findings. NCT06165835, registered on 9 December 2023.
Indoor air pollution caused by particulate matter, VOCs, and pathogenic microorganisms has become more and more serious. The use of numerous petroleum-based polymer filters also causes environmental pollution. Therefore, it is urgent to develop green, degradable, and long-term-stable indoor air filters with synergistic purification of multiple pollutants. Polylactic acid nonwovens are considered candidates for the next generation of air filters because of their green and degradable properties. Herein, we developed a multistage S-scheme heterojunction (Ag3PO4/MXene/Bi2WO6, AMB)-modified PLA electrospun nanofiber membrane (AMB/PLA ENM) using continuous electrospinning equipment. The AMB/PLA ENMs not only exhibit high-efficiency air-filtration performance but also demonstrate robust photocatalytic activity for formaldehyde, bacteria, and viruses. The filtration performance of AMB/PLA ENMs for PM0.3 achieved 99.99%/77.21 Pa at 32 L/min. Moreover, AMB/PLA ENMs exhibit excellent visible-light-driven photocatalytic activities for gaseous formaldehyde, reaching 76.77% within 200 min, and for liquid ciprofloxacin at 82.25% within 240 min. The establishment of the built-in electric field and the increased oxygen vacancies by MXene in the AMB heterojunction significantly enhance the photocatalytic performance of AMB/PLA ENMs. It also shows a significant killing rate of 99.99% against Escherichia coli, Staphylococcus aureus, and the H1N1 virus. This synergistic purification of multiple pollutants is attributed to a dual-functional strategy that integrates multistage S-scheme heterojunction photocatalysts with a PLA electrospun nanofiber membrane to achieve highly efficient and low-pressure air filtration and long-term stable photocatalytic performance. In addition, the AMB/PLA ENMs maintain self-cleaning, good mechanical properties, and degradability, even after long-term utilization.
The high global prevalence of hepatitis B virus (HBV) poses a significant threat to transfusion safety. In this study, we proposed a rationally designed immunoaffinity membrane for specific removal of HBV from plasma. A single-chain variable fragment (scFv-1) targeting the HBV surface antigen (HBsAg) with high affinity was selected as the functional ligand for specific HBV capture. The scFv-1 was expressed in an E. coli Shuffle T7 system (yield: 125 ± 6 mg/L), purified to high monomeric purity, and covalently immobilized onto cellulose acetate membranes, obtaining the scFv-1 functionalized immunoaffinity membrane of CA-scFv-1. The CA-scFv-1 membrane exhibited Langmuir-type adsorption against HBsAg with a maximum static binding capacity of 10.3 mg/g (KD = 2.11 ×10-7 mol/L). Under dynamic flow conditions, stacked CA-scFv-1 membranes (25 mm in diameter, 1.0 mm in thickness) achieved complete removal of HBsAg from plasma (20 mL, HBsAg concentration: 300 kIU/mL) at 100 L/m2·h. Further study demonstrated that the CA-scFv-1 membrane could reduce HBV in clinical HBV-positive plasma effectively from 1 to 82 kIU/mL to undetectable levels, while normal plasma components and their biological function were well preserved. These results highlight the potential of our CA-scFv-1 immunoaffinity membrane in specific HBV removal for plasma purification.
Although vaccination is recognised as the optimal method to reduce the health burden associated with influenza virus infections, current vaccines regularly demonstrate low efficacy despite annual reformulation. To address the critical need for a more effective vaccine, our group has developed a gamma-irradiated influenza A virus (IAV) vaccine (γ-flu) and illustrated broad-spectrum immunity against drifted and heterosubtypic IAV infections following intranasal vaccination. For clinical development, highly purified vaccine preparations based on clinically relevant IAV isolates are required. Here, we report the structural integrity of a highly purified γ-flu preparation based on A/Brisbane/02/2018-like H1N1pdm09, which was included in recent World Health Organisation (WHO) recommendation for seasonal vaccine formulation. To illustrate immunogenicity and protective efficacy, mice were vaccinated twice via intramuscular injections using low doses of purified γ-flu and challenged with a lethal dose of drifted IAV strain. Analysis of immune serum from vaccinated animals showed significant neutralising antibody responses against both homotypic and closely related drifted IAV strains compared to sera from control unvaccinated mice. This high immunogenicity was also associated with significant protection against a lethal challenge with drifted IAV strain. Overall, this study illustrates the structural integrity and immunogenicity of a highly purified γ-flu vaccine preparation suitable for clinical development.