Mechanisms of conjugative transfer of antibiotic resistance genes induced by extracellular polymeric substances: Insights into molecular diversities and electron transfer properties.

Dissemination of antibiotic resistance genes (ARGs) has become a critical threat to public health. Activated sludge, rich in extracellular polymeric substances (EPS), is an important pool of ARGs. In this study, mechanisms of conjugation transfer of ARGs induced by EPS, including tightly bound EPS (TBEPS), soluble EPS (SEPS), and loosely bound EPS (LBEPS), were explored in terms of molecular diversities and electron transfer properties of EPS. Conjugation transfer frequency was increased by 9.98-folds (SEPS), 4.21-folds (LBEPS), and 15.75-folds (TBEPS) versus the control, respectively. Conjugation-related core genes involving SOS responses (9 genes), membrane permeability (18 genes), intercellular contact (17 genes), and energy metabolism pathways (13 genes) were all upregulated, especially in the presence of TBEPS. Carbohydrates and aliphatic substances in SEPS and LBEPS were contributors to ARG transfer, via influencing reactive oxygen species (ROS) formation (SEPS) and ROS and adenosine triphosphate (ATP) production (LBEPS). TBEPS had the highest redox potential and greatest lability and facilitated electron transfer and alternated respiration between cells, thus promoting ARG transfer by producing ATP. Generally, the chemical molecular characteristics and redox properties of EPS facilitated ARG transfer mainly by influencing lipid peroxidation and ATP, respectively.

Compound electrolyte intraocular irrigating solution produces better effects on vision recovery of cataract patients after surgery than Ringer lactate solution.

PURPOSE: Intraocular irrigating solution is extensively applied in cataract surgery. This paper explored the difference and relationship between optical coherence tomography (OCT) and optical quality analysis system (OQAS) parameters induced by compound electrolyte intraocular irrigating solution (CEIIS) or Ringer lactate (RL) solution during uncomplicated cataract surgery. METHODS: Totally 200 senior cataract patients were randomly divided into the CEIIS and RL groups (N = 100 patients/group). The anterior chamber was irrigated by CEIIS or RL during phacoemulsification. Patients were subdivided into diabetes mellitus (DM)+ and DM- groups. The central macular thickness (CMT), hyper reflective foci (HF), modulation transfer function cutoff frequency (MTF cutoff), Strehl ratio (SR), objective scatter index (OSI), and OQAS values (OVs) at 100%, 20%, and 9% contrast levels were measured preoperatively and 1 day and 1 week after operation using spectral-domain optical coherence tomography and OQAS II, respectively. Best-corrected visual acuity (BCVA) was assessed using the Snellen scale, followed by statistical analysis of its logarithm of the minimal angle of resolution. RESULTS: There were no significant differences in clinical characteristics between the CEIIS and RL groups. Both groups exhibited notably increased postoperative CMT, MTF cutoff, SR, OV at 100%, 20%, and 9% contrast levels, and reduced OSI, indicating CEIIS and RL improved postoperative visual quality. CEIIS surpassed RL solution in improving postoperative visual quality, decelerating the increase of macular HF numbers and CMT in DM+ patients and postoperative BCVA. There was no difference between CEIIS and RL in long-term vision improvement. CONCLUSION: CEIIS surpasses RL in postoperative visual recovery and retards increases of macular HF numbers and CMT in senior DM+ cataract patients.

A systematic pan-cancer analysis identifies LDHA as a novel predictor for immunological, prognostic, and immunotherapy resistance.

Lactate dehydrogenase A (LDHA), a critical enzyme involved in glycolysis, is broadly involved multiple biological functions in human cancers. It is reported that LDHA can impact tumor immune surveillance and induce the transformation of tumor-associated macrophages, highlighting its unnoticed function of LDHA in immune system. However, in human cancers, the role of LDHA in prognosis and immunotherapy hasn't been investigated. In this study, we analyzed the expression pattern and prognostic value of LDHA in pan-cancer and explored its association between tumor microenvironment (TME), immune infiltration subtype, stemness scores, tumor mutation burden (TMB), and immunotherapy resistance. We found that LDHA expression is tumor heterogeneous and that its high expression is associated with poor prognosis in multiple human cancers. In addition, LDHA expression was positively correlated with the presence of mononuclear/macrophage cells, and also promoted the infiltration of a range of immune cells. Genomic alteration of LDHA was common in different types of cancer, while with prognostic value in pan-cancers. Pan-cancer analysis revealed that the significant correlations existed between LDHA expression and tumor microenvironment (including stromal cells and immune cells) as well as stemness scores (DNAss and RNAss) across cancer types. Drug sensitivity analysis also revealed that LDHA was able to predict response to chemotherapy and immunotherapy. Furthermore, it was confirmed that knockdown of LDHA reduced proliferation and migration ability of lung cancer cells. Taken together, LDHA could serve as a prognostic biomarker and a potential immunotherapy marker.

A Bacterium-like Particle Vaccine Displaying Envelope Proteins of Canine Distemper Virus Can Induce Immune Responses in Mice and Dogs.

Canine distemper virus (CDV) can cause fatal infections in giant pandas. Vaccination is crucial to prevent CDV infection in giant pandas. In this study, two bacterium-like particle vaccines F3-GEM and H4-GEM displaying the trimeric F protein or tetrameric H protein of CDV were constructed based on the Gram-positive enhanced-matrix protein anchor (GEM-PA) surface display system. Electron microscopy and Western blot results revealed that the F or H protein was successfully anchored on the surface of GEM particles. Furthermore, one more bacterium-like particle vaccine F3 and H4-GEM was also designed, a mixture consisting of F3-GEM and H4-GEM at a ratio of 1:1. To evaluate the effect of the three vaccines, mice were immunized with F3-GEM, H4-GEM or F3 and H4-GEM. It was found that the level of IgG-specific antibodies and neutralizing antibodies in the F3 and H4-GEM group was higher than the other two groups. Additionally, F3 and H4-GEM also increased the secretion of Th1-related and Th2-related cytokines. Moreover, F3 and H4-GEM induce IgG and neutralizing antibodies' response in dogs. Conclusions: In summary, F3 and H4-GEM can provoke better immune responses to CDV in mice and dogs. The bacterium-like particle vaccine F3 and H4-GEM might be a potential vaccine candidate for giant pandas against CDV infection.

Characterization of a pangolin SARS-CoV-2-related virus isolate that uses the human ACE2 receptor.

Various SARS-CoV-2-related coronaviruses have been increasingly identified in pangolins, showing a potential threat to humans. Here we report the infectivity and pathogenicity of the SARS-CoV-2-related virus, PCoV-GX/P2V, which was isolated from a Malayan pangolin (Manis javanica). PCoV-GX/P2V could grow in human hepatoma, colorectal adenocarcinoma cells, and human primary nasal epithelial cells. It replicated more efficiently in cells expressing human angiotensin-converting enzyme 2 (hACE2) as SARS-CoV-2 did. After intranasal inoculation to the hACE2-transgenic mice, PCoV-GX/P2V not only replicated in nasal turbinate and lungs, but also caused interstitial pneumonia, characterized by infiltration of mixed inflammatory cells and multifocal alveolar hemorrhage. Existing population immunity established by SARS-CoV-2 infection and vaccination may not protect people from PCoV-GX/P2V infection. These findings further verify the hACE2 utility of PCoV-GX/P2V by in vivo experiments using authentic viruses and highlight the importance for intensive surveillance to prevent possible cross-species transmission.

Isolation and characterization of a pangolin-borne HKU4-related coronavirus that potentially infects human-DPP4-transgenic mice.

We recently detected a HKU4-related coronavirus in subgenus Merbecovirus (named pangolin-CoV-HKU4-P251T) from a Malayan pangolin1. Here we report isolation and characterization of pangolin-CoV-HKU4-P251T, the genome sequence of which is closest to that of a coronavirus from the greater bamboo bat (Tylonycteris robustula) in Yunnan Province, China, with a 94.3% nucleotide identity. Pangolin-CoV-HKU4-P251T is able to infect human cell lines, and replicates more efficiently in cells that express human-dipeptidyl-peptidase-4 (hDPP4)-expressing and pangolin-DPP4-expressing cells than in bat-DPP4-expressing cells. After intranasal inoculation with pangolin-CoV-HKU4-P251, hDPP4-transgenic female mice are likely infected, showing persistent viral RNA copy numbers in the lungs. Progressive interstitial pneumonia developed in the infected mice, characterized by the accumulation of macrophages, and increase of antiviral cytokines, proinflammatory cytokines, and chemokines in lung tissues. These findings suggest that the pangolin-borne HKU4-related coronavirus has a potential for emerging as a human pathogen by using hDPP4.

Current Status and Prospects of Artificial Intelligence Technology Application in Oil and Gas Field Development.

Artificial intelligence technology will be increasingly applied in the oil and gas industry. The rapid development of artificial intelligence technology can solve problems such as high environmental sensitivity and complex production processes in the oil and gas industry. In recent years, emerging technologies represented by artificial intelligence have developed rapidly, assisting petroleum enterprises in digital transformation and intelligent upgrading. This article elaborates on the development trend of artificial intelligence technology. Based on the business scenarios and characteristics of the oil and gas industry, the application status of artificial intelligence technology in domestic and foreign petroleum technology service enterprises was summarized and analyzed. The application scenarios of artificial intelligence technology in the fields of dynamic analysis of oil and gas reservoirs, intelligent historical fitting, numerical simulation proxy models, and production plan optimization were analyzed with emphasis. Based on the problems and challenges faced in the development process of oil and gas reservoirs, it is proposed that petroleum enterprises should attach importance to the "three modernizations" innovation of data standardization, oil and gas field intelligence, and platform collaboration, in order to achieve more refined intelligent analysis and management of oil and gas reservoirs and quickly develop more targeted oil and gas reservoir development plans to assist in the intelligent transformation of oil and gas reservoir development. On this basis, prospects for future artificial intelligence technology are proposed, pointing out that the development of artificial intelligence technology will be faster and faster, and there will be higher demand for artificial intelligence technology in the construction of digital oil and gas fields in China in the future. The research results have important reference value for the development of the oil and gas industry.

Antiviral activity of theaflavins against Zika virus in vivo and in vitro.

INTRODUCTION: The prevalence and infection of the Zika virus (ZIKV) have recently posed a major threat to global public health security. However, there is currently a lack of specific vaccines and effective antiviral drugs for ZIKV infection. METHODS: Theaflavins TF1 and TF2 were selected by evaluating the anti-Zika virus activity of four kinds of theaflavins in vitro. Subsequently, in vivo, we investigated the effects of TF1 and TF2 on weight, survival, tissue viral load, and cytokines in ZIKV-infected mice. RESULTS: We compared the anti-ZIKV activity of four theaflavins (TFs) in cells and found that TF1 and TF2b significantly inhibited the replication of ZIKV/Z16006 toxic strain in BHK and Vero cells by inhibiting the replication and release of ZIKV, while no similar effects were observed for TF2a and TF3. In vivo assay, we only found that TF2b improved the survival rate of infected mice. In tissues of ZIKV-infected mice, the viral load was higher in spleen and blood, followed by liver, epididymis, and testis, the lowest in muscle. Additionally, TF2b treatment significantly reduced the expression of cytokines (IL-6, IL-1ß, TNF-α) and chemokines (CCL2, CCL5, CXCL10) induced by ZIKV infection. CONCLUSIONS: These findings suggest that TF2b has a potent antiviral effect and can be used as a potential candidate for the treatment of ZIKV infection.

CD97 negatively regulates the innate immune response against RNA viruses by promoting RNF125-mediated RIG-I degradation.

The G protein-coupled receptor ADGRE5 (CD97) binds to various metabolites that play crucial regulatory roles in metabolism. However, its function in the antiviral innate immune response remains to be determined. In this study, we report that CD97 inhibits virus-induced type-I interferon (IFN-I) release and enhances RNA virus replication in cells and mice. CD97 was identified as a new negative regulator of the innate immune receptor RIG-I, and RIG-1 degradation led to the suppression of the IFN-I signaling pathway. Furthermore, overexpression of CD97 promoted the ubiquitination of RIG-I, resulting in its degradation, but did not impact its mRNA expression. Mechanistically, CD97 upregulates RNF125 expression to induce RNF125-mediated RIG-I degradation via K48-linked ubiquitination at Lys181 after RNA virus infection. Most importantly, CD97-deficient mice are more resistant than wild-type mice to RNA virus infection. We also found that sanguinarine-mediated inhibition of CD97 effectively blocks VSV and SARS-CoV-2 replication. These findings elucidate a previously unknown mechanism through which CD97 negatively regulates RIG-I in the antiviral innate immune response and provide a molecular basis for the development of new therapeutic strategies and the design of targeted antiviral agents.

Microplastics affect C, N, and P cycling in natural environments: Highlighting the driver of soil hydraulic properties.

As microplastics (MPs) are organic polymers with a carbon-based framework, they may affect nutrient cycling. Information regarding how MPs influence N, P, and C cycling and the underlying driving force remains lacking. N, P, and C cycling induced by soil hydraulic properties under MPs exposure (including polyethylene (PE), polyvinyl chloride (PVC), polystyrene (PS), polypropylene (PP)) in the natural environment were investigated in this study. MPs exposure increased the soil water content (11.2-84.5%) and reduced bulk density (11.4-42.8%); soil saturated hydraulic conductivity increased by 7.3-69.4% under PP and PE exposure. MPs exposure led to increases in available phosphorus, NO3--N, NH4+-N, and soil organic matter; the bacterial communities related to N and C cycling were significantly changed. Expression levels of soil N and C cycling-related genes were enhanced under low concentrations (0.5% and 2%) of MPs, except PVC; consequently, soil nitrogen storage and organic carbon storage increased by 12-75% and 6.7-93%, respectively. Correlation analyses among soil hydraulic properties, bacterial communities, and functional genes related to nutrient cycling revealed that soil hydraulic properties (including soil water content, saturated water capacity, and soil saturated hydraulic conductivity) were the dominant factors affecting soil N and C storage under MPs exposure.

Effect of barbed versus standard sutures on wound complications in total knee arthroplasty: A meta-analysis.

A barbed suture has been demonstrated to be effective in shortening the stitching time and improving the aesthetic appearance of the stitches during the entire knee replacement. However, no meta-analyses have been conducted specifically to evaluate the effect of the barbed thread on wound complications relative to the conventional suture. A comprehensive search of the PubMed database, the Embase database, the Cochrane Library and the Web of Science was performed to obtain search data up to June 2023, and only randomised controlled trials were included in this meta-analysis. We used Review Manager 5.3 for data synthesis and analysis. This meta-analysis included eight studies. It was found that the use of barbed sutures did not improve the incidence of the disease, the infection of the wound, the closure of the abscess and the injury. However, because of the limited sample size of the randomised controlled trials for this meta-analysis, the data should be handled with caution. More high-quality, large-sample studies will be required to confirm the results.

A Newly Identified Spike Protein Targeted Linear B-Cell Epitope Based Dissolvable Microneedle Array Successfully Eliciting Neutralizing Activities against SARS-CoV-2 Wild-Type Strain in Mice.

Vaccination is a cost-effective medical intervention. Inactivated whole virusor large protein fragments-based severe acute respiratory syndrome coronavirus (SARS-CoV-2) vaccines have high unnecessary antigenic load to induce allergenicity and/orreactogenicity, which can be avoided by peptide vaccines of short peptide fragments that may induce highly targeted immune response. However, epitope identification and peptide delivery remain the major obstacles in developing peptide vaccines. Here, a multi-source data integrated linear B-cell epitope screening strategy is presented and a linear B-cell epitope enriched hotspot region is identified in Spike protein, from which a monomeric peptide vaccine (Epitope25) is developed and applied to subcutaneously immunize wildtype BALB/c mice. Indirect ELISA assay reveals specific and dose-dependent binding between Epitope25 and serum IgG antibodies from immunized mice. The neutralizing activity of sera from vaccinated mice is validated by pseudo and live SARS-CoV-2 wild-type strain neutralization assays. Then a dissolvable microneedle array (DMNA) is developed to pain-freely deliver Epitope25. Compared with intramuscular injection, DMNA and subcutaneous injection elicit neutralizing activities against SARS-CoV-2 wild-type strain as demonstrated by live SARS-CoV-2 virus neutralization assay. No obvious damages are found in major organs of immunized mice. This study may lay the foundation for developing linear B-cell epitope-based vaccines against SARS-CoV-2.

Role and Mechanism of Cold Plasma in Inactivating Alicyclobacillus acidoterrestris in Apple Juice.

A. acidoterrestris has been identified as the target bacterium in fruit juice production due to its high resistance to standard heat treatment. Multiple studies have shown that cold plasma can effectively inactivate pathogenic and spoilage microorganisms in juices. However, we are aware of only a few studies that have used cold plasma to inactivate A. acidoterrestris. In this study, the inactivation efficacy of cold plasma was determined using the plate count method and described using a biphasic model. The effects of the food matrix, input power, gas flow rate, and treatment time on inactivation efficacy were also discovered. Scavenging experiments with reactive oxygen species (•OH, •O2-, and 1O2), scanning electron microscopy (SEM), Raman spectra, as well as an in vitro toxicology assay kit, were used to determine the inactivation mechanism. According to the plate count method, a maximum reduction of 4.14 log CFU/ mL could be achieved within 7 s, and complete inactivation could be achieved within 240 s. The scavenging experiments showed that directly cold plasma-produced singlet oxygen plays the most crucial role in inactivation, which was also confirmed by the fluorescence probe SOSG. The scanning electron microscopy (SEM) and Raman spectra showed that the cold plasma treatment damaged the membrane integrity, DNA, proteins, lipids, and carbohydrates of A. acidoterrestris. The plate count results and the apple juice quality evaluation showed that the cold plasma treatment (1.32 kV) could inactivate 99% of A. acidoterrestris within 60 s, with no significant changes happening in apple juice quality, except for slight changes in the polyphenol content and color value.

Viral vectored vaccines: design, development, preventive and therapeutic applications in human diseases.

Human diseases, particularly infectious diseases and cancers, pose unprecedented challenges to public health security and the global economy. The development and distribution of novel prophylactic and therapeutic vaccines are the prioritized countermeasures of human disease. Among all vaccine platforms, viral vector vaccines offer distinguished advantages and represent prominent choices for pathogens that have hampered control efforts based on conventional vaccine approaches. Currently, viral vector vaccines remain one of the best strategies for induction of robust humoral and cellular immunity against human diseases. Numerous viruses of different families and origins, including vesicular stomatitis virus, rabies virus, parainfluenza virus, measles virus, Newcastle disease virus, influenza virus, adenovirus and poxvirus, are deemed to be prominent viral vectors that differ in structural characteristics, design strategy, antigen presentation capability, immunogenicity and protective efficacy. This review summarized the overall profile of the design strategies, progress in advance and steps taken to address barriers to the deployment of these viral vector vaccines, simultaneously highlighting their potential for mucosal delivery, therapeutic application in cancer as well as other key aspects concerning the rational application of these viral vector vaccines. Appropriate and accurate technological advances in viral vector vaccines would consolidate their position as a leading approach to accelerate breakthroughs in novel vaccines and facilitate a rapid response to public health emergencies.

Taurolidine improved protection against highly pathogenetic avian influenza H5N1 virus lethal-infection in mouse model by regulating the NF-κB signaling pathway.

Taurolidine (TRD), a derivative of taurine, has anti-bacterial and anti-tumor effects by chemically reacting with cell-walls, endotoxins and exotoxins to inhibit the adhesion of microorganisms. However, its application in antiviral therapy is seldom reported. Here, we reported that TRD significantly inhibited the replication of influenza virus H5N1 in MDCK cells with the half-maximal inhibitory concentration (EC50) of 34.45 â€‹µg/mL. Furthermore, the drug inhibited the amplification of the cytokine storm effect and improved the survival rate of mice lethal challenged with H5N1 (protection rate was 86%). Moreover, TRD attenuated virus-induced lung damage and reduced virus titers in mice lungs. Administration of TRD reduced the number of neutrophils and increased the number of lymphocytes in the blood of H5N1 virus-infected mice. Importantly, the drug regulated the NF-κB signaling pathway by inhibiting the separation of NF-κB and IκBa, thereby reducing the expression of inflammatory factors. In conclusion, our findings suggested that TRD could act as a potential anti-influenza drug candidate in further clinical studies.

Anti-inflammatory effects of theaflavin-3'-gallate during influenza virus infection through regulating the TLR4/MAPK/p38 pathway.

Severe pathological damage caused by the influenza virus is one of the leading causes of death. However, the prevention and control strategies for influenza virus infection have certain limitations, and the exploration for new influenza antiviral drugs has become the major research direction. This study evaluated the antiviral activities of four theaflavin derivatives (TFs). Cytopathic effect (CPE) reduction assay revealed that theaflavin-3'-gallate (TF2b) and theaflavin (TF1) could effectively inhibit the replication of influenza viruses H1N1-UI182, H1N1-PR8, H3N2, and H5N1, and TF2b exhibited the most significant antiviral activity in vivo. Intraperitoneal injection of TF2b at 40 mg/kg/d effectively alleviated viral pneumonia, maintained body weight, and improved the survival rate of mice infected with a lethal dose of H1N1-UI182 to 55.56%. Hematological analysis of peripheral blood further showed that TF2b increased the number of lymphocytes and decreased the number of neutrophils, monocytes, and platelets in the blood of infected mice. RT-qPCR results showed that TF2b reduced the mRNA expression levels of inflammatory cytokines (IL-6, TNF-α, and IL-1ß), chemokines (CXCL-2 and CCL-3), and interferons (IFN-α and IFN-γ) after influenza virus infection. In addition, TF2b significantly down-regulated the expression levels of TLR4, p-p38, p-ERK, and cytokines IL-6, TNF-α, IL-1ß, and IL-10. These results suggest that TF2b not only significantly inhibits viral replication and proliferation in vitro, but also alleviates pneumonia injury in vivo. Its antiviral effect might be attributed to the down-regulation of influenza virus-induced inflammatory cytokines by regulating the TLR4/MAPK/p38 signaling pathway.

Underlying Mechanisms for Low-Molecular-Weight Dissolved Organic Matter to Promote Translocation and Transformation of Chlorinated Polyfluoroalkyl Ether Sulfonate in Wheat.

Dissolved organic matter (DOM) such as fulvic acid (FA) and humic acid (HA) in soil considerably affects the fate of per- and polyfluoroalkyl substances (PFASs). However, the effect of DOM on their behavior in plants remains unclear. Herein, hydroponic experiments indicate that FA and HA reduce the accumulation of an emerging PFAS of high concern, 6:2 chlorinated polyfluoroalkyl ether sulfonate (6:2 Cl-PFESA), in wheat roots by reducing its bioavailability in the solution. Nevertheless, FA with low molecular weight (MW) promotes its absorption and translocation from the roots to the shoots by stimulating the activity and the related genes of the plasma membrane H+-ATPase, whereas high-MW HA shows the opposite effect. Moreover, in vivo and in vitro experiments indicate that 6:2 Cl-PFESA undergoes reductive dechlorination, which is regulated mainly using nitrate reductase and glutathione transferase. HA and FA, particularly the latter, promote the dechlorination of 6:2 Cl-PFESA in wheat by enhancing electron transfer efficiency and superoxide production. Transcriptomic analysis indicates that FA also stimulates catalytic activity, cation binding, and oxidoreductase activity, facilitating 6:2 Cl-PFESA transformation in wheat.

Proteomic and Metabolomic Characterization of SARS-CoV-2-Infected Cynomolgus Macaque at Early Stage.

Although tremendous effort has been exerted to elucidate the pathogenesis of severe COVID-19 cases, the detailed mechanism of moderate cases, which accounts for 90% of all patients, remains unclear yet, partly limited by lacking the biopsy tissues. Here, we established the COVID-19 infection model in cynomolgus macaques (CMs), monitored the clinical and pathological features, and analyzed underlying pathogenic mechanisms at early infection stage by performing proteomic and metabolomic profiling of lung tissues and sera samples from COVID-19 CMs models. Our data demonstrated that innate immune response, neutrophile and platelet activation were mainly dysregulated in COVID-19 CMs. The symptom of neutrophilia, lymphopenia and massive "cytokines storm", main features of severe COVID-19 patients, were greatly weakened in most of the challenged CMs, which are more semblable as moderate patients. Thus, COVID-19 model in CMs is rational to understand the pathogenesis of moderate COVID-19 and may be a candidate model to assess the safety and efficacy of therapeutics and vaccines against SARS-CoV-2 infection.

A bacterium-like particle vaccine displaying Zika virus prM-E induces systemic immune responses in mice.

The emergence of Zika virus (ZIKV) infection, which is unexpectedly associated with congenital defects, has prompted the development of safe and effective vaccines. The Gram-positive enhancer matrix-protein anchor (GEM-PA) display system has emerged as a versatile and highly effective platform for delivering target proteins in vaccines. In this study, we developed a bacterium-like particle vaccine, ZI-△-PA-GEM, based on the GEM-PA system. The fusion protein ZI-△-PA, which contains the prM-E-△TM protein of ZIKV (with a stem-transmembrane region deletion) and the protein anchor PA3, was expressed. The fusion protein was successfully displayed on the GEM surface to form ZI-△-PA-GEM. Moreover, the intramuscular immunization of BALB/c mice with ZI-△-PA-GEM combined with ISA 201 VG and poly(I:C) adjuvants induced durable ZIKV-specific IgG and protective neutralizing antibody responses. Potent B-cell/DC activation was also stimulated early after immunization. Notable, splenocyte proliferation, the secretion of multiple cytokines, T/B-cell activation and central memory T-cell responses were elicited. These data indicate that ZI-△-PA-GEM is a promising bacterium-like particle vaccine candidate for ZIKV.

Environmental free radicals efficiently inhibit the conjugative transfer of antibiotic resistance by altering cellular metabolism and plasmid transfer.

Spread of antibiotic-resistant genes (ARGs) is a global public safety issue and inhibition their transfer is imperative. In this study, a novel strategy using environmental free radical exposure was developed to inhibit conjugative transfer of ARGs (RP4 plasmid) in aqueous solutions. Long-time free radical (·OH, 1O2, and O2·-) exposure significantly suppressed the conjugative transfer frequency of ARGs between Escherichia coli (E. coli) strains, and ·OH was more likely to attack ARG, thereby inhibiting the conjugate transfer frequency, compared to 1O2 and O2·-. Compared with the control, the conjugative transfer frequency significantly decreased from 4.08 × 10-5 to 1.2 × 10-8 after 10 min free radical exposure, confirming that the transfer and proliferation of ARGs were well inhibited. Correspondingly, the number of transconjugant significantly decreased by 61.7% after 10 min free radical exposure. Significant reductions in reactive oxygen species levels (ROS content and enzyme levels) and DNA damage-induced responses in the donor strains were observed after 10 min free radical exposure. Concurrently, intercellular contact was also weakened via inhibiting the synthesis of polysaccharides in extracellular polymeric substances. Moreover, the expressions of plasmid transfer genes were down-regulated after 10 min exposure due to the shortage of adenosine-triphosphate supply. This study firstly disclosed the underneath mechanisms for depressing ARGs transfer and dissemination via environmental free radical exposure.