Microstructure and Properties of Pressureless-Sintered Zirconium Carbide Ceramics with MoSi2 Addition.

Zirconium carbide (ZrC) ceramics have a high melting point, low neutron absorption cross section, and excellent resistance to the impact of fission products and are considered to be one of the best candidate materials for fourth-generation nuclear energy systems. ZrC ceramics with a high relative density of 99.1% were successfully prepared via pressureless sintering using a small amount of MoSi2 as an additive. The influence of the MoSi2 content on the densification behavior, microstructure, mechanical properties, and thermal properties of ZrC ceramics was systematically investigated. The results show that the densification of ZrC was significantly enhanced by the introduction of MoSi2 due to the formation of a liquid phase during sintering. In addition, the ZrC grains were refined due to the pinning effect of the generated silicon carbide. The flexural strength and Vickers hardness of ZrC ceramics with 2.5 vol% MoSi2 sintered at 1850 °C were 408 ± 12 MPa and 17.1 GPa, respectively, which were approximately 30% and 10% higher compared to the samples without the addition of MoSi2. The improved mechanical properties were mainly attributed to the high relative density (99.1%) and refined microstructure.

Genetic associations between Rapid Eye Movement (REM) sleep behavior disorder and cardiovascular diseases.

BACKGROUND: Previous studies revealed that sleep disorders are potential risk factors for cardiovascular diseases, such as obstructive sleep apnea and rapid eye movement (REM) sleep behavior disorder (RBD). However, the causal associations between RBD and cardiovascular diseases remained unknown. MATERIALS AND METHODS: We used the latest and largest summary-level genome-wide association studies of RBD, stroke and its subtypes, coronary artery disease (CAD), myocardial infarction (MI), and heart failure (HF) to select genetic variants as the instrumental variables. Mendelian randomization (MR) analysis was performed to test the causal associations between RBD and the cardiovascular diseases above. Inverse variance weighted method was used as the main analysis. RESULTS: After multiple comparisons, genetically predicted RBD was significantly associated with the risk of HF [odds ratio (OR) = 1.033, 95% CI 1.013-1.052, p = 0.001]. Leave-one-out analysis further supported the robustness of the causal association. Furthermore, we identified a suggestive association between genetically predicted MI and RBD (OR = 0.716, 95% CI 0.546-0.940, p = 0.016). However, in our study no associations were identified of RBD with CAD or stroke and its subtypes. CONCLUSION: Our study highlighted the potential associations between RBD and cardiovascular diseases at genetic level, including HF and MI. More studies were required to clarify the biological mechanisms involved the associations.

Preparation and Characterization of Mouse-Derived Monoclonal Antibodies Against the Hemagglutinin of the H1N1 Influenza Virus.

H1N1 influenza virus is a significant global public health concern. Monoclonal antibodies (mAbs) targeting specific viral proteins such as hemagglutinin (HA) have become an important therapeutic strategy, offering highly specific targeting to block viral transmission and infection. This study focused on the development of mAbs targeting HA of the A/Victoria/2570/2019 (H1N1pdm09, VIC-19) strain by utilizing hybridoma technology to produce two mAbs with high binding capacity. Notably, mAb 2B2 has demonstrated a strong affinity for HA proteins in recent H1N1 influenza vaccine strains. In vitro assessments showed that both mAbs exhibited broad-spectrum hemagglutination inhibition and potent neutralizing effects against various vaccine strains of H1N1pdm09 viruses. 2B2 was also effective in animal models, offering both preventive and therapeutic protection against infections caused by recent H1N1 strains, highlighting its potential for clinical application. By individually co-cultivating each of the aforementioned mAbs with the virus in chicken embryos, four amino acid substitution sites in HA (H138Q, G140R, A141E/V, and D187E) were identified in escape mutants, three in the antigenic site Ca2, and one in Sb. The identification of such mutations is pivotal, as it compels further investigation into how these alterations could undermine the binding efficacy and neutralization capacity of antibodies, thereby impacting the design and optimization of mAb therapies and influenza vaccines. This research highlights the necessity for continuous exploration into the dynamic interaction between viral evolution and antibody response, which is vital for the formulation of robust therapeutic and preventive strategies against influenza.

Host proteins interact with viral elements and affect the life cycle of highly pathogenic avian influenza A virus H7N9.

Host-virus interactions can significantly impact the viral life cycle and pathogenesis; however, our understanding of the specific host factors involved in highly pathogenic avian influenza A virus H7N9 (HPAI H7N9) infection is currently restricted. Herein, we designed and synthesized 65 small interfering RNAs targeting host genes potentially associated with various aspects of RNA virus life cycles. Afterward, HPAI H7N9 viruses were isolated and RNA interference was used to screen for host factors likely to be involved in the life cycle of HPAI H7N9. Moreover, the research entailed assessing the associations between host proteins and HPAI H7N9 proteins. Twelve key host proteins were identified: Annexin A (ANXA)2, ANXA5, adaptor related protein complex 2 subunit sigma 1 (AP2S1), adaptor related protein complex 3 subunit sigma 1 (AP3S1), ATP synthase F1 subunit alpha (ATP5A1), COPI coat complex subunit alpha (COP)A, COPG1, heat shock protein family A (Hsp70) member 1A (HSPA)1A, HSPA8, heat shock protein 90 alpha family class A member 1 (HSP90AA1), RAB11B, and RAB18. Co-immunoprecipitation revealed intricate interactions between viral proteins (hemagglutinin, matrix 1 protein, neuraminidase, nucleoprotein, polymerase basic 1, and polymerase basic 2) and these host proteins, presumably playing a crucial role in modulating the life cycle of HPAI H7N9. Notably, ANXA5, AP2S1, AP3S1, ATP5A1, HSP90A1, and RAB18, were identified as novel interactors with HPAI H7N9 proteins rather than other influenza A viruses (IAVs). These findings underscore the significance of host-viral protein interactions in shaping the dynamics of HPAI H7N9 infection, while highlighting subtle variations compared with other IAVs. Deeper understanding of these interactions holds promise to advance disease treatment and prevention strategies.

Secondary follicles enable efficient germline mtDNA base editing at hard-to-edit site.

Efficient germline mtDNA editing is required to construct disease-related animal models and future gene therapy. Recently, the DddA-derived cytosine base editors (DdCBEs) have made mitochondrial genome (mtDNA) precise editing possible. However, there still exist challenges for editing some mtDNA sites in germline via zygote injection, probably due to the suspended mtDNA replication during preimplantation development. Here, we introduce a germline mtDNA base editing strategy: injecting DdCBEs into oocytes of secondary follicles, at which stage mtDNA replicates actively. With this method, we successfully observed efficient G-to-A conversion at a hard-to-edit site and also obtained live animal models. In addition, for those editable sites, this strategy can greatly improve the base editing efficiency up to 3-fold, which is more than that in zygotes. More important, editing in secondary follicles did not increase more the risk of off-target effects than that in zygotes. This strategy provides an option to efficiently manipulate mtDNA sites in germline, especially for hard-to-edit sites.

Lipopolysaccharide binding protein resists hepatic oxidative stress by regulating lipid droplet homeostasis.

Oxidative stress-induced lipid accumulation is mediated by lipid droplets (LDs) homeostasis, which sequester vulnerable unsaturated triglycerides into LDs to prevent further peroxidation. Here we identify the upregulation of lipopolysaccharide-binding protein (LBP) and its trafficking through LDs as a mechanism for modulating LD homeostasis in response to oxidative stress. Our results suggest that LBP induces lipid accumulation by controlling lipid-redox homeostasis through its lipid-capture activity, sorting unsaturated triglycerides into LDs. N-acetyl-L-cysteine treatment reduces LBP-mediated triglycerides accumulation by phospholipid/triglycerides competition and Peroxiredoxin 4, a redox state sensor of LBP that regulates the shuttle of LBP from LDs. Furthermore, chronic stress upregulates LBP expression, leading to insulin resistance and obesity. Our findings contribute to the understanding of the role of LBP in regulating LD homeostasis and against cellular peroxidative injury. These insights could inform the development of redox-based therapies for alleviating oxidative stress-induced metabolic dysfunction.

Mechanisms of photoprotection in overwintering evergreen conifers: Sustained quenching of chlorophyll fluorescence.

Evergreen conifers growing in high-latitude regions must endure prolonged winters that are characterized by sub-zero temperatures combined with light, conditions that can cause significant photooxidative stress. Understanding overwintering mechanisms is crucial for addressing winter adversity in temperate forest ecosystems and enhancing the ability of conifers to adapt to climate change. This review synthesizes the current understanding of the photoprotective mechanisms that conifers employ to mitigate photooxidative stress, particularly non-photochemical "sustained quenching", the mechanism of which is hypothesized to be a recombination or deformation of the original mechanism employed by conifers in response to short-term low temperature and intense light stress in the past. Based on this hypothesis, scattered studies in this field are assembled and integrated into a complete mechanism of sustained quenching embedded in the adaptation process of plant physiology. It also reveals which parts of the whole system have been verified in conifers and which have only been verified in non-conifers, and proposes specific directions for future research. The functional implications of studies of non-coniferous plant species for the study of coniferous trees are also considered, as a wide range of plant responses lead to sustained quenching, even among different conifer species. In addition, the review highlights the challenges of measuring sustained quenching and discusses the application of ultrafast-time-resolved fluorescence and decay-associated spectra for the elucidation of photosynthetic principles.

Harnessing accurate mitochondrial DNA base editing mediated by DdCBEs in a predictable manner.

Introduction: Mitochondrial diseases caused by mtDNA have no effective cures. Recently developed DddA-derived cytosine base editors (DdCBEs) have potential therapeutic implications in rescuing the mtDNA mutations. However, the performance of DdCBEs relies on designing different targets or improving combinations of split-DddA halves and orientations, lacking knowledge of predicting the results before its application. Methods: A series of DdCBE pairs for wide ranges of aC or tC targets was constructed, and transfected into Neuro-2a cells. The mutation rate of targets was compared to figure out the potential editing rules. Results: It is found that DdCBEs mediated mtDNA editing is predictable: 1) aC targets have a concentrated editing window for mtDNA editing in comparison with tC targets, which at 5'C8-11 (G1333) and 5'C10-13 (G1397) for aC target, while 5'C4-13 (G1333) and 5'C5-14 (G1397) for tC target with 16bp spacer. 2) G1333 mediated C>T conversion at aC targets in DddA-half-specific manner, while G1333 and G1397 mediated C>T conversion are DddA-half-prefer separately for tC and aC targets. 3) The nucleotide adjacent to the 3' end of aC motif affects mtDNA editing. Finally, by the guidance of these rules, a cell model harboring a pathogenic mtDNA mutation was constructed with high efficiency and no bystander effects. Discussion: In summary, this discovery helps us conceive the optimal strategy for accurate mtDNA editing, avoiding time- and effort-consuming optimized screening jobs.

Juxtaglomerular Cell Tumor Mimicking Renal Cell Carcinoma on 99mTc-MIBI SPECT/CT.

ABSTRACT: Juxtaglomerular cell tumor or reninoma is an extremely rare, typically benign, renin-secreting tumor of the kidney that causes secondary hypertension. We describe 99mTc-MIBI SPECT/CT findings in a case of juxtaglomerular cell tumor. The renal tumor showed isodensity and photopenia on 99mTc-MIBI SPECT/CT. This case indicates that juxtaglomerular cell tumor can appear cold on 99mTc-MIBI SPECT/CT, mimicking renal cell carcinoma.

Effect of Ti Doping on the Microstructure and Properties of SiCp/Al Composites by Pressureless Infiltration.

The effects of Ti doping on the microstructure and properties of SiCp/Al composites fabricated by pressureless infiltration were comprehensively investigated using first-principles calculations and experimental analyses. First-principles calculations revealed that the interface wetting and bonding strength in an Al/SiC system could be significantly enhanced by Ti doping. Subsequently, the Ti element was incorporated into SiC preforms in the form of TiO2 and TiC to verify the influence of Ti doping on the pressureless infiltration performance of SiCp/Al composites. The experimental results demonstrated that the pressureless infiltration of molten Al into SiC preforms was promoted by adding TiC or TiO2 due to the improved wettability. However, incorporating TiO2 leads to the growth of AlN whiskers under a N2 atmosphere, thereby hindering the complete densification of the composites. On the other hand, TiC doping can improve wettability and interface strength without deleterious reactions. As a consequence, the TiC-doped SiCp/Al composites exhibited excellent properties, including a high relative density of 99.4%, a bending strength of 287 ± 18 MPa, and a thermal conductivity of 142 W·m-1·K-1.

Knowledge, Attitude, and Practice About Antibiotic Use and Antimicrobial Resistance Among Nursing Students in China: A Cross Sectional Study.

Purpose: The knowledge, attitude, and practices (KAP) concerning antibiotics by healthcare students have the potential impact on controlling antibiotic abuse and antimicrobial resistance (AMR) growth. This study aims to evaluate the levels and explore the associated factors with KAP on antibiotic use and AMR in Chinese nursing students. Methods: A cross-sectional survey using a self-administered questionnaire consisting of demographics and selected features and KAP on antibiotic use and AMR was conducted to measure KAP levels among nursing students at various universities in Hubei Province, China. The logistic regression analyses were performed to analyze the potential factors associated with the KAP. Results: The survey eventually included a total of 1959 nursing students. The mean scores for KAP were 57.89 ±26.32, 55.00 ±12.50, and 71.88 ±15.63, respectively. Regarding knowledge, 54.3% of participants were unaware that antibiotic was ineffective against viral infections. Regarding attitude, 36% of participants agreed that current antibiotic abuse existed; 96.2% of participants thought it necessary to set up a special course on antibiotics. Regarding practice, only 48.4% of participants usually purchased antibiotics with a prescription. Multivariable analyses indicated that lack of discussion on AMR in school courses was an independent risk factor against KAP, respectively. The main knowledge sources of antibiotic being outside the classroom was an independent risk factor related to knowledge and practice. The average score >80 points was an independent protective factor related to knowledge and practice. Conclusion: The KAP level on antibiotic use and AMR among Hubei nursing students was general and required further strengthening. Nursing students with risk factors should be prioritized in educational interventions. The findings of our study pointed out some directions for tailored interventions to improve the training on antibiotics.

Accurate diagnosis and treatment of sacral meningeal cysts without spinal nerve root fibres: identifying leakage orificium using high-resolution spherical arbitrary-dimensional reconstructing magnetic resonance imaging.

Objective: This study aimed to develop an arbitrary-dimensional nerve root reconstruction magnetic resonance imaging (ANRR-MRI) technique for identifying the leakage orificium of sacral meningeal cysts (SMCs) without spinal nerve root fibres (SNRFs). Methods: This prospective study enrolled 40 consecutive patients with SMCs without SNRFs between March 2021 and March 2022. Magnetic resonance neural reconstruction sequences were performed for preoperative evaluation. The cyst and the cyst-dura intersection planes were initially identified based on the original thin-slice axial T2-weighted images. Sagittal and coronal images were then reconstructed by setting each intersecting plane as the centre. Then, three-dimensional reconstruction was performed, focusing on the suspected leakage point of the cyst. Based on the identified leakage location and size of the SMC, individual surgical plans were formulated. Results: This cohort included 30 females and 10 males, with an average age of 42.6 ± 12.2 years (range, 17-66 years). The leakage orificium was located at the rostral pole of the cyst in 23 patients, at the body region of the cyst in 12 patients, and at the caudal pole in 5 patients. The maximum diameter of the cysts ranged from 2 cm to 11 cm (average, 5.2 ± 1.9 cm). The leakage orificium was clearly identified in all patients and was ligated microscopically through a 4 cm minimally invasive incision. Postoperative imaging showed that the cysts had disappeared. Conclusion: ANRR-MRI is an accurate and efficient approach for identifying leakage orificium, facilitating the precise diagnosis and surgical treatment of SMCs without SNRFs.

Predicting Severity in Hypertriglyceridemia-Induced Acute Pancreatitis: The Role of Neutrophils, Calcium, and Apolipoproteins.

BACKGROUND Hypertriglyceridemia-induced acute pancreatitis (HTG-AP), representing 10% of all acute pancreatitis cases, is characterized by younger onset age and more severe progression, often leading to higher ICU admission rates. This condition poses a significant challenge due to its rapid progression and the potential for severe complications, including multiple organ failure. HTG-AP is distinct from other forms of pancreatitis, such as those caused by cholelithiasis or alcohol, in terms of clinical presentation and outcomes. It's essential to identify early markers that can predict the severity of HTG-AP to improve patient management and outcomes. MATERIAL AND METHODS This study divided 127 HTG-AP patients into mild acute pancreatitis (MAP, n=71) and moderate-to-severe acute pancreatitis (MSAP/SAP, n=56) groups. Blood biological indicators within the first 24 hours of admission were analyzed. Risk factors for HTG-AP progression were determined using binary logistic regression and ROC curves. RESULTS Elevated levels of HCT, NLR, TBI, DBI, AST, Cre, and AMS were noted in the MSAP/SAP group, with lower levels of LYM, Na⁺, Ca²âº, ApoA, and ApoB compared to the MAP group (p<0.05). NEUT%, Ca²âº, ApoA, and ApoB were significantly linked with HTG-AP severity. Their combined ROC analysis yielded an area of 0.81, with a sensitivity of 61.8% and specificity of 90%. CONCLUSIONS NEUT%, Ca²âº, ApoA, and ApoB are significant risk factors for progressing to MSAP/SAP in HTG-AP. Their combined assessment provides a reliable predictive measure for early intervention in patients at risk of severe progression.

An intranasal live-attenuated SARS-CoV-2 vaccine limits virus transmission.

The development of effective SARS-CoV-2 vaccines has been essential to control COVID-19, but significant challenges remain. One problem is intramuscular administration, which does not induce robust mucosal immune responses in the upper airways-the primary site of infection and virus shedding. Here we compare the efficacy of a mucosal, replication-competent yet fully attenuated virus vaccine, sCPD9-ΔFCS, and the monovalent mRNA vaccine BNT162b2 in preventing transmission of SARS-CoV-2 variants B.1 and Omicron BA.5 in two scenarios. Firstly, we assessed the protective efficacy of the vaccines by exposing vaccinated male Syrian hamsters to infected counterparts. Secondly, we evaluated transmission of the challenge virus from vaccinated and subsequently challenged male hamsters to naïve contacts. Our findings demonstrate that the live-attenuated vaccine (LAV) sCPD9-ΔFCS significantly outperformed the mRNA vaccine in preventing virus transmission in both scenarios. Our results provide evidence for the advantages of locally administered LAVs over intramuscularly administered mRNA vaccines in preventing infection and reducing virus transmission.

Prevalence and Risk Factors of Non-Alcoholic Fatty Liver Disease (NAFLD) in Non-Obese Patients with Schizophrenia: A Retrospective Study.

Background: To assess the prevalence and risk factors of NAFLD in non-obese patients with schizophrenia in a public psychiatric hospital in China. Methods: A total of 1,305 adult inpatients with schizophrenia in 2019 were included in this retrospective study. Body mass index (BMI) ≥ 25 kg/m2 was considered obese, and BMI < 25 kg/m2 was considered non-obese. We obtained the data from electronic records of the Affiliated Brain Hospital of Guangzhou Medical University. Results: A total of 1,045 non-obese patients and 260 obese patients were included in this study. The prevalence of NAFLD in non-obese patients was 25.0%, and it was much lower that in the obese patients (25.0% vs 64.6%, p < 0.001). Among the non-obese patients, there were significant differences in age, BMI, alanine aminotransferase (ALT), metabolic indices, and the prevalence of diabetes and hypertension between patients with NAFLD and patients without NAFLD. According to the results of binary logistic regression analysis, age, BMI, ALT, triglyceride (TG) and diabetes were significantly related to NAFLD among non-obese patients with schizophrenia. In contrast, HDL-C was was negatively associated with NAFLD among non-obese patients. Conclusion: This study suggested that NAFLD was common in patients with schizophrenia, even in non-obese patients with schizophrenia. In non-obese patients with schizophrenia, age, BMI, ALT, TG and diabetes are significantly associated with NAFLD. Moreover, HDL-C level was an independent protective factor against NAFLD. Given the adverse outcomes of NAFLD, it is necessary to increase awareness of NAFLD in patients with schizophrenia, especially in non-obese patients with schizophrenia.

Structure-Based Discovery of the SARS-CoV-2 Main Protease Noncovalent Inhibitors from Traditional Chinese Medicine.

Traditional Chinese medicine (TCM) has been extensively employed for the treatment of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is demand for discovering more SARS-CoV-2 Mpro inhibitors with diverse scaffolds to optimize anti-SARS-CoV-2 lead compounds. In this study, comprehensive in silico and in vitro assays were utilized to determine the potential inhibitors from TCM compounds against SARS-CoV-2 Mpro, which is an important therapeutic target for SARS-CoV-2. The ensemble docking analysis of 18263 TCM compounds against 15 SARS-CoV-2 Mpro conformations identified 19 TCM compounds as promising candidates. Further in vitro testing validated three compounds as inhibitors of SARS-CoV-2 Mpro and showed IC50 values of 4.64 ± 0.11, 7.56 ± 0.78, and 11.16 ± 0.26 µM, with EC50 values of 12.25 ± 1.68, 15.58 ± 0.77, and 29.32 ± 1.25 µM, respectively. Molecular dynamics (MD) simulations indicated that the three complexes remained stable over the last 100 ns of production run. An analysis of the binding mode revealed that the active compounds occupy different subsites (S1, S2, S3, and S4) of the active site of SARS-CoV-2 Mpro via specific poses through noncovalent interactions with key amino acids (e.g., HIS 41, ASN 142, GLY 143, MET 165, GLU 166, or GLN 189). Overall, this study provides evidence indicating that the three natural products obtained from TCM could be further used for anti-COVID-19 research, justifying the investigation of Chinese herbal medicinal ingredients as bioactive constituents for therapeutic targets.

Stabilization of Pin1 by USP34 promotes Ubc9 isomerization and protein sumoylation in glioma stem cells.

The peptidyl-prolyl cis-trans isomerase Pin1 is a pivotal therapeutic target in cancers, but the regulation of Pin1 protein stability is largely unknown. High Pin1 expression is associated with SUMO1-modified protein hypersumoylation in glioma stem cells (GSCs), but the underlying mechanisms remain elusive. Here we demonstrate that Pin1 is deubiquitinated and stabilized by USP34, which promotes isomerization of the sole SUMO E2 enzyme Ubc9, leading to SUMO1-modified hypersumoylation to support GSC maintenance. Pin1 interacts with USP34, a deubiquitinase with preferential expression and oncogenic function in GSCs. Such interaction is facilitated by Plk1-mediated phosphorylation of Pin1. Disruption of USP34 or inhibition of Plk1 promotes poly-ubiquitination and degradation of Pin1. Furthermore, Pin1 isomerizes Ubc9 to upregulate Ubc9 thioester formation with SUMO1, which requires CDK1-mediated phosphorylation of Ubc9. Combined inhibition of Pin1 and CDK1 with sulfopin and RO3306 most effectively suppresses orthotopic tumor growth. Our findings provide multiple molecular targets to induce Pin1 degradation and suppress hypersumoylation for cancer treatment.

Liquid-Liquid phase separation in bacteria.

Cells are the essential building blocks of living organisms, responsible for carrying out various biochemical reactions and performing specific functions. In eukaryotic cells, numerous membrane organelles have evolved to facilitate these processes by providing specific spatial locations. In recent years, it has also been discovered that membraneless organelles play a crucial role in the subcellular organization of bacteria, which are single-celled prokaryotic microorganisms characterized by their simple structure and small size. These membraneless organelles in bacteria have been found to undergo Liquid-Liquid phase separation (LLPS), a molecular mechanism that allows for their assembly. Through extensive research, the occurrence of LLPS and its role in the spatial organization of bacteria have been better understood. Various biomacromolecules have been identified to exhibit LLPS properties in different bacterial species. LLPS which is introduced into synthetic biology applies to bacteria has important implications, and three recent research reports have shed light on its potential applications in this field. Overall, this review investigates the molecular mechanisms of LLPS occurrence and its significance in bacteria while also considering the future prospects of implementing LLPS in synthetic biology.

Photochemical Halogen-Bonding Promoted Synthesis of Vinyl Sulfones via Vinyl and Sulfonyl Radicals.

A photochemical halogen-bonding-assisted synthesis of vinyl sulfones via radical-radical cross-coupling of vinyl bromines and sodium sulfinates is developed. This methodology offers a facile and efficient approach to various vinyl sulfones with excellent functional group tolerance under metal-, photocatalyst-, base-, and oxidant-free conditions. The reaction is also applicable for the late-stage functionalization of drug molecules and the hectogram scale. Moreover, instead of sodium sulfites being prepared, these reactions could also be conducted using sulfonyl chlorides in a one-pot method.

The relationship between Listeria infections and host immune responses: Listeriolysin O as a potential target.

Listeria monocytogenes (Lm), a foodborne bacterium, can infect people and has a high fatality rate in immunocompromised individuals. Listeriolysin O (LLO), the primary virulence factor of Lm, is critical in regulating the pathogenicity of Lm. This review concludes that LLO may either directly or indirectly activate a number of host cell viral pathophysiology processes, such as apoptosis, pyroptosis, autophagy, necrosis and necroptosis. We describe the invasion of host cells by Lm and the subsequent removal of Lm by CD8 T cells and CD4 T cells upon receipt of the LLO epitopes from major histocompatibility complex class I (MHC-I) and major histocompatibility complex class II (MHC-II). The development of several LLO-based vaccines that make use of the pore-forming capabilities of LLO and the immune response of the host cells is then described. Finally, we conclude by outlining the several natural substances that have been shown to alter the three-dimensional conformation of LLO by binding to particular amino acid residues of LLO, which reduces LLO pathogenicity and may be a possible pharmacological treatment for Lm.