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1.
Trends Biotechnol ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38604879

RESUMO

Molecular imprints, which are crosslinked architectures containing specific molecular recognition cavities for targeting compounds, have recently transitioned from in vitro diagnosis to in vivo treatment. In current application scenarios, it has become an important topic to create new biomolecular recognition pathways through molecular imprinting, thereby inhibiting the pathogenesis and regulating the development of diseases. This review starts with a pathological analysis, mainly focusing on the corresponding artificial enzymes, enzyme inhibitors and antibody mimics with enhanced functions that are created by molecular imprinting strategies. Recent advances are highlighted in the use of molecular imprints as tailor-made nanomedicines for the prevention of three major diseases: metabolic syndrome, cancer, and bacterial/viral infections.

2.
BMC Infect Dis ; 24(1): 413, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38641791

RESUMO

Considering that neutralizing antibody levels induced by two doses of the inactivated vaccine decreased over time and had fallen to low levels by 6 months, and homologous and heterologous booster immunization programs have been implemented in adults in China. The booster immunization of recombinant COVID-19 vaccine (ZF2001) after priming with inactivated vaccine in healthy children and adolescents has not been reported. We performed an open-labeled, single-arm clinical trial to evaluate the safety and immunogenicity of heterologous booster immunization with ZF2001 after priming with inactivated vaccine among 240 population aged 3-17 years in China. The primary outcome was immunogenicity, including geometric mean titers (GMTs), geometric mean ratios (GMRs) and seroconversion rates of SARS-CoV-2 neutralizing antibodies against prototype SARS-CoV-2 and Omicron BA.2 variant at 14 days after vaccination booster. On day 14 post-booster, a third dose booster of the ZF2001 provided a substantial increase in antibody responses in minors, and the overall occurrence rate of adverse reactions after heterologous vaccination was low and all adverse reactions were mild or moderate. The results showed that the ZF2001 heterologous booster had high immunogenicity and good safety profile in children and adolescents, and can elicit a certain level of neutralizing antibodies against Omicron.Trial registration NCT05895110 (Retrospectively registered, First posted in ClinicalTrials.gov date: 08/06/2023).


Assuntos
Vacinas contra COVID-19 , COVID-19 , Vacinas de Subunidades , Adulto , Criança , Humanos , Adolescente , Vacinas contra COVID-19/efeitos adversos , Vacinas de Produtos Inativados/efeitos adversos , COVID-19/prevenção & controle , SARS-CoV-2 , Anticorpos Neutralizantes , Anticorpos Antivirais , Imunogenicidade da Vacina
3.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(1): 88-97, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38433637

RESUMO

Lumbar intervertebral disc degeneration is a common pathological process in the spine,with the main clinical symptoms of low back pain,numbness of lower limbs,and defecation dysfunction.The occurrence and development of lumbar intervertebral disc degeneration are determined by multiple factors,and the pathophysiological and cellular mechanisms remain to be fully understood.Nucleus pulposus tissue engineering is a new biotherapy that combines biological histology with material science to treat diseases including lumbar intervertebral disc degeneration.Clinicians should fully learn the complex relationship between nucleus pulposus tissue engineering and lumbar intervertebral disc degeneration,which will facilitate the clinical treatment of lumbar intervertebral disc degeneration,the rehabilitation of lumbar intervertebral disc after treatment,and the prevention of this disease in the population.


Assuntos
Degeneração do Disco Intervertebral , Núcleo Pulposo , Humanos , Degeneração do Disco Intervertebral/terapia , Engenharia Tecidual , Coluna Vertebral
4.
Math Biosci Eng ; 21(2): 3364-3390, 2024 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-38454732

RESUMO

In order to meet the efficiency and smooth trajectory requirements of the casting sorting robotic arm, we propose a time-optimal trajectory planning method that combines a heuristic algorithm inspired by the behavior of the Genghis Khan shark (GKS) and segmented interpolation polynomials. First, the basic model of the robotic arm was constructed based on the arm parameters, and the workspace is analyzed. A matrix was formed by combining cubic and quintic polynomials using a segmented approach to solve for 14 unknown parameters and plan the trajectory. To enhance the smoothness and efficiency of the trajectory in the joint space, a dynamic nonlinear learning factor was introduced based on the traditional Particle Swarm Optimization (PSO) algorithm. Four different biological behaviors, inspired by GKS, were simulated. Within the premise of time optimality, a target function was set to effectively optimize within the feasible space. Simulation and verification were performed after determining the working tasks of the casting sorting robotic arm. The results demonstrated that the optimized robotic arm achieved a smooth and continuous trajectory velocity, while also optimizing the overall runtime within the given constraints. A comparison was made between the traditional PSO algorithm and an improved PSO algorithm, revealing that the improved algorithm exhibited better convergence. Moreover, the planning approach based on GKS behavior showed a decreased likelihood of getting trapped in local optima, thereby confirming the effectiveness of the proposed algorithm.

6.
Front Endocrinol (Lausanne) ; 15: 1340625, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38532900

RESUMO

The intervertebral disc is not isolated from other tissues. Recently, abundant research has linked intervertebral disc homeostasis and degeneration to various systemic diseases, including obesity, metabolic syndrome, and diabetes. Organokines are a group of diverse factors named for the tissue of origin, including adipokines, osteokines, myokines, cardiokines, gastrointestinal hormones, and hepatokines. Through endocrine, paracrine, and autocrine mechanisms, organokines modulate energy homeostasis, oxidative stress, and metabolic balance in various tissues to mediate cross-organ communication. These molecules are involved in the regulation of cellular behavior, inflammation, and matrix metabolism under physiological and pathological conditions. In this review, we aimed to summarize the impact of organokines on disc homeostasis and degeneration and the underlying signaling mechanism. We focused on the regulatory mechanisms of organokines to provide a basis for the development of early diagnostic and therapeutic strategies for disc degeneration.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Humanos , Adipocinas/metabolismo , Obesidade/metabolismo , Homeostase
7.
Sci Rep ; 14(1): 6568, 2024 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-38503887

RESUMO

While Phorbol-12-myristate-13-acetate-induced protein 1 (Noxa/PMAIP1) assumes a pivotal role in numerous tumors, its clinical implications and underlying mechanisms of gastric cancer (GC) are yet enigmatic. In this investigation, our primary objective was to scrutinize the clinical relevance and potential mechanisms of Noxa in gastric cancer. Immunohistochemical analysis was conducted on tissue microarrays comprising samples from a meticulously characterized cohort of 84 gastric cancer patients, accompanied by follow-up data, to assess the expression of Noxa. Additionally, Noxa expression levels in gastric cancer clinical samples and cell lines were measured through quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. The effect of Noxa expression on the prognosis of patients with gastric cancer was evaluated using Kaplan-Meier survival. Further insight into the role of Noxa in driving gastric cancer progression was gained through an array of experimental techniques, including cell viability assays (CCK8), plate cloning assays, transwell assays, scratch assays, and real-time cell analysis (RTCA). Potential upstream microRNAs (miRNAs) that might modulate Noxa were identified through rigorous bioinformatics analysis, substantiated by luciferase reporter assays and Western blot experiments. Additionally, we utilized RNA sequencing, qRT-PCR, and Western blot to identify proteins binding to Noxa and potential downstream target. Finally, we utilized BALB/c nude mice to explore the role of Noxa in vivo. Our investigation unveiled a marked downregulation of Noxa expression in gastric cancer and underscored its significance as a pivotal prognostic factor influencing overall survival (OS). Noxa overexpression exerted a substantial inhibitory effect on the proliferation, migration and invasion of GC cells. Bioinformatic analysis and dual luciferase reporter assays unveiled the capacity of hsa-miR-200b-3p to interact with the 3'-UTR of Noxa mRNA, thereby orchestrating a downregulation of Noxa expression in vitro, consequently promoting tumor progression in GC. Our transcriptome analysis, coupled with mechanistic validation, elucidated a role for Noxa in modulating the expression of ZNF519 in the Mitophagy-animal pathway. The depletion of ZNF519 effectively reversed the oncogenic attributes induced by Noxa. Upregulation of Noxa expression suppressed the tumorigenesis of GC in vivo. The current investigation sheds light on the pivotal role of the hsa-miR-200b-3p/Noxa/ZNF519 axis in elucidating the pathogenesis of gastric cancer, offering a promising avenue for targeted therapeutic interventions in the management of this challenging malignancy.


Assuntos
MicroRNAs , Neoplasias Gástricas , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transformação Celular Neoplásica/genética , Regulação Neoplásica da Expressão Gênica , Luciferases/metabolismo , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Gástricas/patologia
8.
Stem Cell Res Ther ; 15(1): 44, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38360740

RESUMO

BACKGROUND: Mesenchymal stem cells (MSCs) are attracting attention as a promising cell-based therapy for the treatment of liver fibrosis or cirrhosis. However, the strategies and potential mechanisms of MSCs therapy need further investigation. The CXCL12/CXCR4/CXCR7 chemokine axis is well known to regulate cell migration and is involved in the regulation of liver fibrosis. This study aims to treat MSCs with a CXCR7-specific agonist to evaluate its therapeutic effects on hepatic fibrosis and potential mechanisms. METHODS: TC14012, a potent agonist of CXCR7, has been used to pretreat human umbilical cord-derived MSCs (UC-MSCs) and assess its effect on proliferation, apoptosis, migration, immunoregulation, and gene regulatory network. Then, CCl4-induced liver fibrosis mice models were used to evaluate the therapeutic effect and mechanism of TC14012-treated UC-MSCs for treating hepatic fibrosis. RESULTS: TC14012 increased CXCR7 expression in UC-MSCs. Notably, co-culture of liver sinusoidal endothelial cells (LSEC) with TC14012-pretreated UC-MSCs increased CXCR7 expression in LSEC. Additionally, TC14012 promoted cell migration and mediated the immunoregulation of UC-MSCs. Compared to UC-MSCs without TC14012 pretreatment, UC-MSCs treated with TC14012 ameliorated live fibrosis by restoring CXCR7 expression, reducing collagen fibril accumulation, inhibiting hepatic stellate cells activation, and attenuating the inflammatory response. CONCLUSION: This study suggests that TC14012 pretreatment can enhance the therapeutic effects of UC-MSCs on liver fibrosis, mainly by promoting the migration and immunoregulation of MSCs.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Oligopeptídeos , Camundongos , Humanos , Animais , Células Endoteliais/metabolismo , Fibrose , Inflamação/terapia , Inflamação/metabolismo , Cirrose Hepática/terapia , Cirrose Hepática/metabolismo , Colágeno/metabolismo , Quimiocina CXCL12/genética , Quimiocina CXCL12/metabolismo , Células-Tronco Mesenquimais/metabolismo , Cordão Umbilical
9.
Biomed Pharmacother ; 171: 116116, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38181715

RESUMO

Fibrosis is a process of tissue repair that results in the slow creation of scar tissue to replace healthy tissue and can affect any tissue or organ. Its primary feature is the massive deposition of extracellular matrix (mainly collagen), eventually leading to tissue dysfunction and organ failure. The progression of fibrotic diseases has put a significant strain on global health and the economy, and as a result, there is an urgent need to find some new therapies. Previous studies have identified that inflammation, oxidative stress, some cytokines, and remodeling play a crucial role in fibrotic diseases and are essential avenues for treating fibrotic diseases. Among them, matrix metalloproteinases (MMPs) are considered the main targets for the treatment of fibrotic diseases since they are the primary driver involved in ECM degradation, and tissue inhibitors of metalloproteinases (TIMPs) are natural endogenous inhibitors of MMPs. Through previous studies, we found that MMP-9 is an essential target for treating fibrotic diseases. However, it is worth noting that MMP-9 plays a bidirectional regulatory role in different fibrotic diseases or different stages of the same fibrotic disease. Previously identified MMP-9 inhibitors, such as pirfenidone and nintedanib, suffer from some rather pronounced side effects, and therefore, there is an urgent need to investigate new drugs. In this review, we explore the mechanism of action and signaling pathways of MMP-9 in different tissues and organs, hoping to provide some ideas for developing safer and more effective biologics.


Assuntos
Metaloproteinase 9 da Matriz , Metaloproteinases da Matriz , Humanos , Metaloproteinase 9 da Matriz/metabolismo , Fibrose , Metaloproteinases da Matriz/metabolismo , Inibidores Teciduais de Metaloproteinases/metabolismo , Inflamação/metabolismo , Matriz Extracelular/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz
10.
J Hazard Mater ; 466: 133540, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38241834

RESUMO

The effect of microplastics (MPs) on the allocation of rice photosynthetic carbon (C) in paddy systems and its utilization by soil microorganisms remain unclear. In this study, 13C-CO2 pulse labeling was used to quantify the input and allocation of photosynthetic C in a rice-soil system under MPs amendment. Rice was pulse-labeled at tillering growth stage under 0.01% and 1% w/w polyethylene (PE) and polyvinyl chloride (PVC) MP amendments. Plants and soils were sampled 24 h after pulse labeling. Photosynthesized C in roots in MP treatments was 30-54% lower than that in no-MP treatments. The 13C in soil organic C (SOC) in PVC-MP-amended bulk soil was 4.3-4.7 times higher than that in no-MP treatments. PVC and high-dose PE increased the photosynthetic C in microbial biomass C in the rhizosphere soil. MPs altered the allocation of photosynthetic C to microbial phospholipid fatty acid (PLFA) groups. High-dose PVC increased the 13C gram-positive PLFAs. Low-dose PE and high-dose PVC enhanced 13C in fungal PLFAs in bulk soil (including arbuscular mycorrhizal fungi (AMF) and Zygomycota) by 175% and 197%, respectively. The results highlight that MPs alter plant C input and microbial utilization of rhizodeposits, thereby affecting the C cycle in paddy ecosystems.


Assuntos
Oryza , Solo , Microplásticos , Plásticos , Ecossistema , Microbiologia do Solo , Carbono , Polietilenos
11.
RSC Adv ; 14(1): 433-444, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38173571

RESUMO

Cadmium (Cd) is a common and toxic non-essential heavy metal that must be effectively treated to reduce its threat to the environment and public health. Adsorption with an adsorbent, such as agricultural waste, is widely used to remove heavy metals from wastewater. Sweet potato, the sixth most abundant food crop worldwide, produces a large amount of waste during postharvest processing that could be used as an economic adsorbent. In this study, the feasibility of using sweet potato residue (SPR) as an adsorbent for Cd2+ adsorption was assessed. To enhance the removal rate, SPR was modified with NaOH, and the effects of the modification and adsorption conditions on the removal of Cd2+ from wastewater were investigated. The results showed that modified sweet potato residue (MSPR) could be adapted to various pH and temperatures of simulated wastewater, implying its potential for multi-faceted application. Under optimized conditions, the removal of Cd2+ by MSPR was up to 98.94% with a maximum adsorption capacity of 19.81 mg g-1. Further investigation showed that the MSPR exhibited rich functional groups, a loose surface, and a mesoporous structure, resulting in advantageous characteristics for the adsorption of Cd2+. In addition, the MSPR adsorbed Cd2+ by complexation, ion exchange, and precipitation during a monolayer chemisorption adsorption process. This work demonstrates a sustainable and environment friendly strategy for Cd2+ removal from wastewater and a simple approach for the preparation of MSPR and also revealed the adsorption mechanism of Cd2+ by MSPR, thus providing a suitable adsorbent and strategy for the removal of other heavy metals.

12.
Glob Chang Biol ; 30(1): e17092, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38273481

RESUMO

Mineral-associated soil organic matter (MAOM) is the largest, slowest cycling pool of carbon (C) in the terrestrial biosphere. MAOM is primarily derived from plant and microbial sources, yet the relative contributions of these two sources to MAOM remain unresolved. Resolving this issue is essential for managing and modeling soil carbon responses to environmental change. Microbial biomarkers, particularly amino sugars, are the primary method used to estimate microbial versus plant contributions to MAOM, despite systematic biases associated with these estimates. There is a clear need for independent lines of evidence to help determine the relative importance of plant versus microbial contributions to MAOM. Here, we synthesized 288 datasets of C/N ratios for MAOM, particulate organic matter (POM), and microbial biomass across the soils of forests, grasslands, and croplands. Microbial biomass is the source of microbial residues that form MAOM, whereas the POM pool is the direct precursor of plant residues that form MAOM. We then used a stoichiometric approach-based on two-pool, isotope-mixing models-to estimate the proportional contribution of plant residue (POM) versus microbial sources to the MAOM pool. Depending on the assumptions underlying our approach, microbial inputs accounted for between 34% and 47% of the MAOM pool, whereas plant residues contributed 53%-66%. Our results therefore challenge the existing hypothesis that microbial contributions are the dominant constituents of MAOM. We conclude that biogeochemical theory and models should account for multiple pathways of MAOM formation, and that multiple independent lines of evidence are required to resolve where and when plant versus microbial contributions are dominant in MAOM formation.


Assuntos
Minerais , Solo , Solo/química , Florestas , Carbono , Biomassa , Plantas , Microbiologia do Solo
13.
Int J Biol Macromol ; 259(Pt 1): 129259, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38191112

RESUMO

The influenza A virus (IAV) is a ubiquitous and continuously evolving respiratory pathogen. The intranasal vaccination mimicking natural infections is an attractive strategy for controlling IAVs. Multiepitope vaccines accurately targeting multiple conserved domains have the potential to broaden the protective scope of current seasonal influenza vaccines and reduce the risk of generating escape mutants. Here, multiple linear epitopes from the matrix protein 2 ectodomain (M2e) and the hemagglutinin stem domain (HA2) are fused with the Helicobacter pylori ferritin, a self-assembled nanocarrier and mucosal adjuvant, to develop a multiepitope nanovaccine. Through intranasal delivery, the prokaryotically expressed multiepitope nanovaccine elicits long-lasting mucosal immunity, broad humoral immunity, and robust cellular immunity without any adjuvants, and confers complete protection against H3N2 and H1N1 subtypes of IAV in mice. Importantly, this intranasal multiepitope nanovaccine triggers memory B-cell responses, resulting in secretory immunoglobulin A (sIgA) and serum immunoglobulin G (IgG) levels persisting for more than five months post-immunization. Therefore, this intranasal ferritin-based multiepitope nanovaccine represents a promising approach to combating respiratory pathogens.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A , Vacinas contra Influenza , Infecções por Orthomyxoviridae , Animais , Camundongos , Infecções por Orthomyxoviridae/prevenção & controle , Vírus da Influenza A Subtipo H3N2 , 60547 , Imunidade nas Mucosas , Ferritinas , Anticorpos Antivirais , Adjuvantes Imunológicos/farmacologia , Administração Intranasal , Adjuvantes Farmacêuticos , Camundongos Endogâmicos BALB C
14.
World Neurosurg ; 181: e163-e176, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37757950

RESUMO

OBJECTIVE: The purpose of this study was to compare the accuracy and safety of robot-assisted (RA) cervical screw placement with conventional freehand (FH) technique. METHODS: Computer-based searches were conducted on various databases including PubMed, Embase, Cochrane Library, Web of Science, the China Biology Medicine, the China National Knowledge Infrastructure, and Wanfang Database. Inclusion criteria were studies reporting the use of RA techniques for cervical screw placement and providing data on safety and accuracy outcomes. Primary outcome indicators focused on the accuracy of screw placement, while secondary outcome indicators included operative time, intraoperative blood loss, length of hospital stay, complication rate, and radiation dose. Data from eligible studies were extracted and synthesized using a forest plot analysis. RESULTS: A total of 312 patients (1233 screws) from 6 studies were included, with 148 patients (47.4% with 567 screws) in the RA group. Perfect screw accuracy, as categorized by Gertzbein-Robbins grade A, was significantly superior with RA surgery compared to FH technique. RA screw implantation significantly reduced complication rates, intraoperative blood loss, length of hospitalization, and radiation dose compared to the conventional FH group. However, there was no statistically significant difference in surgery time between the RA and FH groups. CONCLUSIONS: RA surgery significantly improves the accuracy of cervical screw insertion and offers potential advantages in terms of reduced complications and blood loss, shorter hospital stays, and decreased radiation exposure. However, the impact on operative time remains uncertain. Further high-quality studies, including large-scale randomized controlled trials, are needed to strengthen the evidence base.


Assuntos
Parafusos Pediculares , Exposição à Radiação , Procedimentos Cirúrgicos Robóticos , Robótica , Fusão Vertebral , Humanos , Perda Sanguínea Cirúrgica , Procedimentos Cirúrgicos Robóticos/métodos , Fusão Vertebral/métodos , Estudos Retrospectivos
15.
Parasitol Int ; 98: 102818, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37848126

RESUMO

The study of immune regulation mechanisms induced by parasites may help develop new treatment methods for inflammatory diseases including type 1 diabetes, which is related to type 1 immune responses. The negative correlation between schistosomiasis infection and type 1 diabetes has been confirmed, and the mechanism of Schistosoma-mediated prevention of type 1 diabetes may be related to the adaptive and innate immune systems. Schistosoma-related molecules affect immune cell composition and macrophage polarization and stimulate an increase in natural killer T cells. Furthermore, Schistosoma-related molecules can regulate the adaptive immune responses related to the prevention of type 1 diabetes and change the Th1/Th2 and Th17/Treg axis. Our previous review showed the role of regulatory T cells in the protective of type 1 diabetes mediated by Schistosoma. Here, we aim to review the other mechanisms of schistosomiasis infection and Schistosoma-related products in regulating the immune response associated with the treatment of type 1 diabetes.


Assuntos
Diabetes Mellitus Tipo 1 , Esquistossomose , Animais , Diabetes Mellitus Tipo 1/prevenção & controle , Schistosoma , Linfócitos T Reguladores , Antígenos de Helmintos , Citocinas
16.
Int J Environ Health Res ; : 1-15, 2023 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-38153391

RESUMO

Existing evidence suggested that the risk of tuberculosis (TB) infection was associated to the variations in temperature and PM2.5. A total of 9,111 cases of TB were reported in Ningxia Hui Autonomous Region, China from 2013 to 2015 on a daily basis, and 57.2% of them were male. The TB risk was more prominent for a lower temperature in males (RR of 1.724, 95% CI: 1.241, 2.394), the aged over 64 years (RR of 2.241, 95% CI: 1.554, 3.231), and the high mobility occupation subpopulation (RR of 2.758, 95% CI: 1.745, 4.359). High concentration of PM2.5 showed a short-term effect and was only associated with an increased risk in the early stages of exposure for the female, and aged 36-64 years group. There were 15.06% (1370 cases) of cases of TB may be attributable to the temperature, and 2.94% (268 cases) may be attributable to the increase of PM2.5 exposures. Low temperatures may be associated with significantly increase in the risk of TB, and high PM2.5 concentrations have a short-term association on increasing the risk of TB. Strengthening the monitoring and regular prevention and control of high risk groups will provide scientific guidance to reduce the incidence of TB.

17.
Adv Healthc Mater ; : e2303531, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37983728

RESUMO

Seasonal influenza vaccines typically provide strain-specific protection and are reformulated annually, which is a complex and time-consuming process. Multiepitope vaccines, combining multiple conserved antigenic epitopes from a pathogen, can trigger more robust, diverse, and effective immune responses, providing a potential solution. However, their practical application is hindered by low immunogenicity and short-term effectiveness. In this study, multiple linear epitopes from the conserved stem domain of hemagglutinin and the ectodomain of matrix protein 2 are combined with the Helicobacter pylori ferritin, a stable self-assembled nanoplatform, to develop an influenza multiepitope nanovaccine, named MHF. MHF is prokaryotically expressed in a soluble form and self-assembles into uniform nanoparticles. The subcutaneous immunization of mice with adjuvanted MHF induces cross-reactive neutralizing antibodies, antibody-dependent cell-mediated cytotoxicity, and cellular immunity, offering complete protection against H3N2 as well as partial protection against H1N1. Importantly, the vaccine cargo delivered by ferritin triggers epitope-specific memory B-cell responses, with antibody level persisting for over 6 months post-immunization. These findings indicate that self-assembled multiepitope nanovaccines elicit potent and long-lasting immune responses while significantly reducing the risk of vaccine escape mutants, and offer greater practicality in terms of scalable manufacturing and genetic manipulability, presenting a promising and effective strategy for future vaccine development.

18.
BMC Microbiol ; 23(1): 330, 2023 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-37936059

RESUMO

BACKGROUND: Heavy metal contamination has been a severe worldwide environmental issue. For industrial pollutions, heavy metals rarely exist as singular entities. Hence, researches have increasingly focused on the detrimental effect of mixed heavy metal pollution. Genome analysis of Lampropedia strains predicted a repertoire of heavy metal resistance genes. However, we are still lack of experimental evidence regarding to heavy metal resistance of Lampropedia, and their potential in mixed heavy metal removal remain elusive. RESULTS: In this study, a Lampropedia aestuarii strain GYF-1 was isolated from soil samples near steel factory. Heavy metal tolerance assay indicated L. aestuarii GYF-1 possessed minimal inhibition values of 2 mM, 10 mM, 6 mM, 4 mM, 6 mM, 0.8 mM, and 4 mM for CdCl2, K2CrO4, CuCl2, NiCl2, Pb(CH3COO)2, ZnSO4, and FeCl2, respectively. The biosorption assay demonstrated its potential in soil remediation from mixed heavy metal pollution. Next the draft genome of L. aestuarii GYF-1 was obtained and annotated, which revealed strain GYF-1 are abundant in heavy metal resistance genes. Further evaluations on differential gene expressions suggested adaptive mechanisms including increased lipopolysaccharides level and enhanced biofilm formation. CONCLUSION: In this study, we demonstrated a newly isolated L. aestuarii GYF-1 exhibited mixed heavy metal resistance, which proven its capability of being a potential candidate strain for industrial biosorption application. Further genome analysis and differential gene expression assay suggest enhanced LPS and biofilm formation contributed to the adaptation of mixed heavy metals.


Assuntos
Metais Pesados , Poluentes do Solo , Biodegradação Ambiental , Metais Pesados/toxicidade , Metais Pesados/metabolismo , Solo , Poluentes do Solo/análise
19.
Biomater Sci ; 11(20): 6770-6774, 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37665299

RESUMO

This work reports a polymeric adenosine triphosphate (ATP)-responsive trypsin inhibitor. The polymeric inhibitor was rationally obtained by optimizing the benzamidine and phenylboronic acid monomers, which could synergistically bind with the phosphate and ribose groups in ATP. The ATP-responsive trypsin activity shows its potential as a therapeutic drug for cancer-targeting cell inhibition.

20.
Water Res ; 245: 120581, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37703757

RESUMO

Polyethylene film mulching is a key technology for soil water retention in dryland agriculture, but the aging of the films can generate a large number of microplastics with different shapes. There exists a widespread misunderstanding that the concentrations of microplastics might be the determinant affecting the diversity and assembly of soil bacterial communities, rather than their shapes. Here, we examined the variations of soil bacteria community composition and functioning under two-year field incubation by four shapes (ball, fiber, fragment and powder) of microplastics along the concentration gradients (0.01%, 0.1% and 1%). Data showed that specific surface area of microplastics was significantly positively correlated with the variations of bacterial community abundance and diversity (r=0.505, p<0.05). The fragment- and fiber-shape microplastics displayed more pronounced interfacial continuity with soil particles and induced greater soil bacterial α-diversity, relative to the powder- and ball-shape ones. Strikingly, microplastic concentrations were not significantly correlated with bacterial community indices (r=0.079, p>0.05). Based on the variations of the ßNTI, bacterial community assembly actually followed both stochastic and deterministic processes, and microplastic shapes significantly modified soil biogeochemical cycle and ecological functions. Therefore, the shapes of microplastics, rather than the concentration, significantly affected soil bacterial community assembly, in association with microplastic-soil-water interfaces.

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