Design and evaluation of a multi-epitope DNA vaccine against HPV16.

Cervical cancer, among the deadliest cancers affecting women globally, primarily arises from persistent infection with high-risk human papillomavirus (HPV). To effectively combat persistent infection and prevent the progression of precancerous lesions into malignancy, a therapeutic HPV vaccine is under development. This study utilized an immunoinformatics approach to predict epitopes of cytotoxic T lymphocytes (CTLs) and helper T lymphocytes (HTLs) using the E6 and E7 oncoproteins of the HPV16 strain as target antigens. Subsequently, through meticulous selection of T-cell epitopes and other necessary elements, a multi-epitope vaccine was constructed, exhibiting good immunogenic, physicochemical, and structural characteristics. Furthermore, in silico simulations showed that the vaccine not only interacted well with toll-like receptors (TLR2/TLR3/TLR4), but also induced a strong innate and adaptive immune response characterized by elevated Th1-type cytokines, such as interferon-gamma (IFN-γ) and interleukin-2 (IL2). Additionally, our study investigated the effects of different immunization intervals on immune responses, aiming to optimize a time-efficient immunization program. In animal model experiments, the vaccine exhibited robust immunogenic, therapeutic, and prophylactic effects. Administered thrice, it consistently induced the expansion of specific CD4 and CD8 T cells, resulting in substantial cytokines release and increased proliferation of memory T cell subsets in splenic cells. Overall, our findings support the potential of this multi-epitope vaccine in combating HPV16 infection and signify its candidacy for future HPV vaccine development.

Through the stringent selection of T-cell epitopes and other necessary elements, a novel multi-epitope vaccine targeting HPV 16 E6 and E7 oncoproteins was constructed using an immunoinformatics approach.The vaccine designed can induce both cellular and humoral immune responses, encompassing all the required immunogenic, physicochemical, and structural characteristics for an ideal vaccine design. Moreover, it offers decent worldwide coverage.In animal studies, the vaccine demonstrated strong immune responses, including expansion of CD4 and CD8 T cells, cytokine release, and enhanced memory T cell proliferation, resulting in long-term anti-tumor effects, inhibition of tumor growth, and prolonged survival in tumor-bearing mice.The immunological evaluation of the designed vaccine suggests its potential as a novel vaccine candidate against HPV 16.

Charge-density wave mediated quasi-one-dimensional Kondo lattice in stripe-phase monolayer 1T-NbSe2.

The heavy fermion physics is dictated by subtle competing exchange interactions, posing a challenge to their understanding. One-dimensional (1D) Kondo lattice model has attracted special attention in theory, because of its exact solvability and expected unusual quantum criticality. However, such experimental material systems are extremely rare. Here, we demonstrate the realization of quasi-1D Kondo lattice behavior in a monolayer van der Waals crystal NbSe2, that is driven into a stripe phase via Se-deficient line defects. Spectroscopic imaging scanning tunneling microscopy measurements and first-principles calculations indicate that the stripe-phase NbSe2 undergoes a novel charge-density wave transition, creating a matrix of local magnetic moments. The Kondo lattice behavior is manifested as a Fano resonance at the Fermi energy that prevails the entire film with a high Kondo temperature. Importantly, coherent Kondo screening occurs only in the direction of the stripes. Upon approaching defects, the Fano resonance exhibits prominent spatial 1D oscillations along the stripe direction, reminiscent of Kondo holes in a quasi-1D Kondo lattice. Our findings provide a platform for exploring anisotropic Kondo lattice behavior in the monolayer limit.

Manipulating single excess electrons in monolayer transition metal dihalide.

Polarons are entities of excess electrons dressed with local response of lattices, whose atomic-scale characterization is essential for understanding the many body physics arising from the electron-lattice entanglement, yet difficult to achieve. Here, using scanning tunneling microscopy and spectroscopy (STM/STS), we show the visualization and manipulation of single polarons in monolayer CoCl2, that are grown on HOPG substrate via molecular beam epitaxy. Two types of polarons are identified, both inducing upward local band bending, but exhibiting distinct appearances, lattice occupations and polaronic states. First principles calculations unveil origin of polarons that are stabilized by cooperative electron-electron and electron-phonon interactions. Both types of polarons can be created, moved, erased, and moreover interconverted individually by the STM tip, as driven by tip electric field and inelastic electron tunneling effect. This finding identifies the rich category of polarons in CoCl2 and their feasibility of precise control unprecedently, which can be generalized to other transition metal halides.

Lack of association between TLR4 Asp299Gly and Thr399Ile polymorphisms and sepsis susceptibility: a meta-analysis.

Sepsis, a condition of systemic inappropriate inflammation response to the invasion of microorganisms, results in considerable morbidity and mortality in patients. Some, but not all, epidemiological studies have suggested that Toll-like receptor 4 (TLR4) polymorphisms, Asp299Gly and Thr399Ile, may influence the risk of at-risk patients for sepsis. Our work tried to further study the association of the two common polymorphisms with sepsis susceptibility by performing a meta-analysis of previous data. Electronic searches of MEDLINE, EMBASE and Web of Science databases were performed. Original observational studies dealing with the association between polymorphisms Asp299Gly and/or Thr399Ile and sepsis risk were selected. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with random-effects model or fixed-effects model based on the heterogeneity analysis. Seventeen studies including 2212 cases and 3880 controls were included with most subjects of Caucasian ethnicity. The odds ratio for the association of Asp299Gly polymorphism with sepsis risk was 1.22 (95% CI: 0.90-1.65, P=0.21), and the association of Thr399Ile polymorphism was 1.16 (95%CI: 0.70-1.91, P=0.57). Subgroup analysis and sensitivity analysis did not change the results. Our meta-analysis revealed that the two common TLR4 polymorphisms, Asp299Gly and Thr399Ile, have no strong association with the likelihood of sepsis in Caucasian populations. Further studies are needed to investigate the effect of genetic networks and their mutual interactions in TLR4 signaling pathway on sepsis susceptibility.

Identification of autotoxic compounds in fibrous roots of Rehmannia (Rehmannia glutinosa Libosch.).

Rehmannia is a medicinal plant in China. Autotoxicity has been reported to be one of the major problems hindering the consecutive monoculture of Rehmannia. However, potential autotoxins produced by the fibrous roots are less known. In this study, the autotoxicity of these fibrous roots was investigated. Four groups of autotoxic compounds from the aqueous extracts of the fibrous roots were isolated and characterized. The ethyl acetate extracts of these water-soluble compounds were further analyzed and separated into five fractions. Among them, the most autotoxic fraction (Fr 3) was subjected to GC/MS analysis, resulting in 32 identified compounds. Based on literature, nine compounds were selected for testing their autotoxic effects on radicle growth. Seven out of the nine compounds were phenolic, which significantly reduced radicle growth in a concentration-dependent manner. The other two were aliphatic compounds that showed a moderate inhibition effect at three concentrations. Concentration of these compounds in soil samples was determined by HPLC. Furthermore, the autotoxic compounds were also found in the top soil of the commercially cultivated Rehmannia fields. It appears that a close link exists between the autotoxic effects on the seedlings and the compounds extracted from fibrous roots of Rehmannia.

[Clinical phenotype genotype correlation in children with hemoglobin H disease in Zhuhai area of China].

OBJECTIVE: Alpha-thalassemia is one of the most common monogene disorders in the world. Most frequently, it is caused by deletions of alpha-globin gene (-alpha or --), and less commonly resulted from the non-deletional mutation (alpha(T)alpha). Hemoglobin H (HbH) disease is the most severe type among survivors of alpha-thalassemia. The clinical presentation of children with the disease was highly heterogeneous. The aim of this study was to investigate the effect of alpha-globin genotypes in the children with HbH disease on predicting the phenotypic severity and to define the factors involved in the disease progress. METHODS: Forty-three children with the disease in Zhuhai area of Guangdong, China were examined by using established techniques to detect genotypes of alpha-globin and to determine all hematological parameters. All detailed clinical data of the cases were recorded. Then clinical and hematological findings, and the correlation with genotypes were evaluated. RESULTS: Six alpha-thalassemia mutations were detected and interacted to produce 5 HbH disease genotypes. Of these genotypes, -alpha(3.7)/--(SEA)(60%), -alpha(4.2)/--(SEA) (19%) and alpha(CS)alpha/--(SEA) (12%) HbH diseases were prevalent in the area. Compared with -alpha(3.7)/--(SEA) HbH disease, significantly lower red blood cell (RBC) count, hemoglobin (Hb), mean corpuscular hemoglobin (MCHC) and HbA(2) (P < 0.05, 0.01, 0.01 and 0.01, respectively), and significantly higher mean corpuscular hemoglobin volume (MCV) and HbH levels (both P < 0.01), and more severe clinical phenotypes were found in the HbH disease with alpha(T)alpha/--(SEA) genotype. While the differences were much more significant when compared with -alpha(3.7)/--(SEA) then compared with -alpha(4.2)/--(SEA) not only in the hematological parameters, but also in the severity of clinical phenotypes. In addition, HbH levels showed anegatively correlation with the RBC count (r = -0.39, P < 0.01). CONCLUSION: The phenotypes of HbH disease may be mainly related to the underlying genotypes. The children with alpha(T)alpha/--(SEA) genotype presented with more severe hematological and clinical phenotypes followed by the -alpha(4.2)/--(SEA) and then -alpha(3.7)/--(SEA) genotypes. But phenotypic severity was not simply related to the degree of alpha-globin deficiency. HbH levels were found to exacerbate anemia. These data might provide comprehensive and very valuable and basic information for the management of HbH disease, genetic counseling and prenatal diagnosis.

A survey for the incidence of phenylketonuria in Guangdong, China.

A multicenter cooperative investigated the incidence of Phenylketonuria (PKU) in the central, southern and western areas of Guangdong province and its surrounding districts. Tests to measure phenylalanine (Phe) on dried blood spots on filter paper cards used BIA and thefluorescence assay. Four hundred sixty-one thousand eight hundred five (461,805) newborns were screened and 14 cases of persistent hyperphenylalaninemia (PHPA) were detected. The incidence of PHPA was 1/33,000, including 1/77,000 for classical PKU; 1 in 66,000 for hyperphenylalaninemia (HPA) and 1 in 461,805 for BH4 deficiency. A high variation in PKU incidence in the different districts was observed. The differences may be attributed to the variations in gene frequency of PKU in the different districts and to bioethical consideration especially as regards reproduction in different areas.

Evaluation of clinical application of gap-PCR as a routine method for alpha-thalassemia carrier detection.

OBJECTIVE: To evaluate the feasibility of using gap-PCR for routine screening of alpha-thalassemia in clinical laboratory. METHODS: A total of 382 clinical blood samples randomly collected from the population of Zhuhai city were screened for alpha-thalassemia determinants with hematological and gap-PCR method respectively in a double-blind manner. Parallel analysis with Southern blotting was performed to verify the genotyping results by PCR. RESULTS: Of the 382 samples tested, 3 common alpha-thalassemia genes with genotypes of --(SEA)/alpha alpha, -alpha(3.7)/alpha alpha and -alpha(4.2)/alpha alpha were detected in 21 (5.50%), 7 (1.83%) and 3 (0.79%) cases respectively by gap-PCR, including 7 cases with normal phenotype and 3 case of iron-deficiency anemia. The overall incidence of alpha-thalassemia was 8.12% in the population of Zhuhai city, as determined by gap-PCR, in total agreement with the results by Southern blotting. Only 21 of the 31 alpha-thalassemia cases were identified by hematological analysis (besides 2 cases with alpha-thalassemia phenotype undetermined), which had a false-negative rate of 32.3%. Seven silent alpha-thalassemia and 3 mild alpha-thalassemia cases failed to be detected by hematological analysis, resulting in a rate of 2.62% for failure of detection. CONCLUSION: Gap-PCR method is specific and feasible as a better alternative for alpha-thalassemia screening, especially advantageous in detecting silent carriers in comparison with hematological method.