Achieving ZT > 1 in Cu and Ga Co-doped Ag6Ge10P12 with Superior Mechanical Performance and Its Fundamental Physical Properties toward Practical Thermoelectric Device Applications.

Recently, phosphorus-based compounds have emerged as potential candidates for thermoelectric materials. One of the key challenges facing this field is to achieve ZT > 1, which is the benchmark for thermoelectric device applications. In this study, it is demonstrated that the thermoelectric performance of environmentally friendly Ag6Ge10P12 is enhanced by co-doping Cu and Ga. The mechanical properties, coefficient of linear thermal expansion, work function, and compatibility factor are comprehensively clarified to provide guidelines for reliable device applications. The peak and average dimensionless figures of merit of Ag5.85Cu0.15Ge9.875Ga0.125P12 reach 1.04 at 723 K and 0.63 at 300-723 K, respectively, which are the highest values for phosphorus-based thermoelectric materials. The Young's modulus, Vickers microhardness, fracture toughness, and compressive strength of Ag5.85Cu0.15Ge9.875Ga0.125P12 are 132 GPa, 589, 1.23 MPa m1/2, and 219 MPa, respectively, which are superior to those of typical state-of-the-art thermoelectric materials. The remarkable thermoelectric and mechanical performance of Ag5.85Cu0.15Ge9.875Ga0.125P12 mean that it is a promising candidate for medium-temperature thermoelectric conversion. Ti, V, Rh, and Pt are suitable for electrodes without exfoliation under thermal expansion and with ohmic contacts to Ag5.85Cu0.15Ge9.875Ga0.125P12 in terms of the coefficient of linear thermal expansion and work function. Considering that the compatibility factor of Ag5.85Cu0.15Ge9.875Ga0.125P12 is approximately 2.8, half-Heusler, skutterudite, and magnesium silicide-stannide compounds are suitable n-type thermoelectric counterpart materials in thermoelectric devices. These insights will lead to the development of phosphorus-based thermoelectric materials toward practical thermoelectric device applications.

UQCRB and LBH are correlated with Gleason score progression in prostate cancer: Spatial transcriptomics and experimental validation.

Prostate cancer (PCa) is a multifocal disease characterized by genomic and phenotypic heterogeneity within a single gland. In this study, Visium spatial transcriptomics (ST) analysis was applied to PCa tissues with different histological structures to infer the molecular events involved in Gleason score (GS) progression. The spots in tissue sections were classified into various groups using Principal Component Analysis (PCA) and Louvain clustering analysis based on transcriptome data. Anotation of the spots according to GS revealed notable similarities between transcriptomic profiles and histologically identifiable structures. The accuracy of macroscopic GS determination was bioinformatically verified through malignancy-related feature analysis, specifically inferred copy number variation (inferCNV), as well as developmental trajectory analyses, such as diffusion pseudotime (DPT) and partition-based graph abstraction (PAGA). Genes related to GS progression were identified from the differentially expressed genes (DEGs) through pairwise comparisons of groups along a GS gradient. The proteins encoded by the representative oncogenes UQCRB and LBH were found to be highly expressed in advanced-stage PCa tissues. Knockdown of their mRNAs significantly suppressed PCa cell proliferation and invasion. These findings were validated using The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) dataset, as well as through histological and cytological experiments. The results presented here establish a foundation for ST-based evaluation of GS progression and provide valuable insights into the GS progression-related genes UQCRB and LBH.

Effect of AFM ordering on ThermoelectricResponses of Mg3X2 (X : C, Si, Ge) monolayers : ADFT Insight.

Two-dimensional materials have gained a lot of attention in the last few decades due to their potential applications in thermoelectric and nano-electronic devices. This study systematically presents the mechanical, electronic and thermoelectric characteristics of two-dimensional honeycomb-kagome Mg3X2 (X : C, Si, Ge) structures in the framework of Density Functional Theory (DFT) computations and by solving semiclassical Boltzmann transport equation. The geometrical stability of these structures is validated by phonon spectrum and molecular dynamics simulations. Following the elastic constants, we have inferred that all the systems are mechanically stable and brittle in nature. Lower values of Debye temperature of all structures suggest that Mg3X2 monolayers should have lower values of lattice thermal conductivity compared to graphene. Electronic structure calculations indicate that these materials are semimetallic in their nonmagnetic (NM) phase. All the structures display remarkably low lattice thermal conductivity (0.9-1.5 W/mK) due to a large scattering factor and higher anharmonicity. The presence of sharp density of states (DOS) peaks close to the Fermi level, arising from nearly flat and dispersionless band in the antiferromagnetic (AFM) arrangement, is poised to enhance the Seebeck coefficient, thereby potentially boosting the thermoelectric performance. The estimated values of thermoelectric figure of merit (ZT) are around 0.78 and 0.67 for Mg3Si2 and Mg3Ge2 structure respectively in AFM phase at T = 700 K. These outcomes of our findings suggest that Mg3X2 monolayers exhibit substantial promise for thermoelectric device application.

Nanoheteroepitaxy of Ge and SiGe on Si: role of composition and capping on quantum dot photoluminescence.

We investigate the nanoheteroepitaxy of SiGe and Ge quantum dots (QDs) grown on nanotips substrates realized in Si(001) wafers. Due to the lattice strain compliance, enabled by the nanometric size of the tip and the limited dot/substrate interface area, which helps to reduce dot/substrate interdiffusion, the strain and SiGe composition in the QDs could be decoupled. This demonstrates a key advantage of the nanoheteroepitaxy over the Stranski-Krastanow growth mechanism. Nearly semi-spherical, defect-free, ∼100 nm wide SiGe QDs with different Ge contents were successfully grown on the nanotips with high selectivity and size uniformity. On the dots, thin dielectric capping layers were deposited, improving the optical properties by the passivation of surface states. Intense photoluminescence was measured from all samples investigated with emission energy, intensity, and spectral linewidth dependent on the SiGe composition of the QDs and the different capping layers. Radiative recombination occurs in the QDs, and its energy matches the results of band-structure calculations that consider strain compliance between the QD and the tip. The nanotips arrangement and the selective growth of QDs allow to studying the PL emission from only 3-4 QDs, demonstrating a bright emission and the possibility of selective addressing. These findings will support the design of optoelectronic devices based on CMOS-compatible emitters.

Antler size in red deer: declining selection and increasing genetic variance with age, but little senescence.

While senescence is a common occurrence in wild populations, not all traits decline with age simultaneously and some do not show any senes- cence. A lack of senescence in secondary sexual traits is thought to be due to their importance for reproductive success. However, if reproduc- tive success senesces, why would secondary sexual traits apparently not senesce? Here we explored this question in a wild population of red deer (Cervus elaphus) using antler form (number of points), a secondary sexual trait which shows little senescence, despite the occurrence of reproductive senescence. In line with expectations for traits that senesce, genetic vari- ance in antler form increased with age and selection weakened with age. Therefore, there was no indication that stronger selection on individu- als that survived to older ages was countering the dilution of selection due to fewer individuals being alive. Furthermore, the effect of selec- tive disappearance masking a slight decline in antler form in the oldest years was small. Interestingly, although genetic variance and positive se- lection of antler form were found, there was no evidence of a response to selection, supporting a genetic decoupling of antler senescence and re- productive senescence. Finally, a positive genetic covariance in antler form among age classes provides a possible explanation for the the lack of senescence. These findings suggest that antler form is under a genetic constraint that prevents it from senescing, providing an interesting evolu- tionary explanation for negligible senescence in a secondary sexual trait, and consequently, the existence of asynchrony in senescence among traits within populations.

Pseudorabies Virus Glycoproteins E and B Application in Vaccine and Diagnosis Kit Development.

Background: Pseudorabies virus (PRV) is a highly infectious pathogen that affects a wide range of mammals and imposes a significant economic burden on the global pig industry. The viral envelope of PRV contains several glycoproteins, including glycoprotein E (gE) and glycoprotein B (gB), which play critical roles in immune recognition, vaccine development, and diagnostic procedures. Mutations in these glycoproteins may enhance virulence, highlighting the need for updated vaccines. Method: This review examines the functions of PRV gE and gB in vaccine development and diagnostics, focusing on their roles in viral replication, immune system interaction, and pathogenicity. Additionally, we explore recent findings on the importance of gE deletion in attenuated vaccines and the potential of gB to induce immunity. Results: Glycoprotein E (gE) is crucial for the virus's axonal transport and nerve invasion, facilitating transmission to the central nervous system. Deletion of gE is a successful strategy in vaccine development, enhancing the immune response. Glycoprotein B (gB) plays a central role in viral replication and membrane fusion, aiding viral spread. Mutations in these glycoproteins may increase PRV virulence, complicating vaccine efficacy. Conclusion: With PRV glycoproteins being essential to both vaccine development and diagnostic approaches, future research should focus on enhancing these components to address emerging PRV variants. Updated vaccines and diagnostic tools are critical for combating new, more virulent strains of PRV.

Exploring charge transfer and schottky barrier modulation at monolayer Ge2Sb2Te5-metal interfaces.

Monolayer Ge2Sb2Te5exhibits great potential in non-volatile memory technology due to its excellent electronic properties and phase-change characteristics, while the fundamental nature of Ge2Sb2Te5-metal contacts has not been well understood yet. Here, we provide a comprehensiveab initiostudy of the electronic properties between monolayer Ge2Sb2Te5and Pt, Pd, Au, Cu, Cr, Ag, and W contacts based on first-principles calculations. We find that the strong interaction interfaces formed between monolayer Ge2Sb2Te5and Pt, Pd, Cr, and W contacts show chemical bonding and strong charge transfer. In contrast, no apparent chemical bonding and weak charge transfer are observed in the weak interaction interfaces formed with Au, Cu, and Ag. Additionally, our study reveals the presence of a pronounced Fermi level pinning effect between monolayer Ge2Sb2Te5and metals, with pinning factors ofSn=0.325andSp=0.350. By increasing the interlayer distance, an effective transition fromn-type Ohmic contact ton-type Schottky contact is facilitated because the band edge of Ge2Sb2Te5is shifted upwards. Our study not only provides a theoretical basis for selecting suitable metal electrodes in Ge2Sb2Te5-based devices but also holds significant implications for understanding Schottky barrier height modulation between semiconductors and metals.

Causal interpretations of family GWAS in the presence of heterogeneous effects.

Family-based genome-wide association studies (GWASs) are often claimed to provide an unbiased estimate of the average causal effects (or average treatment effects; ATEs) of alleles, on the basis of an analogy between the random transmission of alleles from parents to children and a randomized controlled trial. We show that this claim does not hold in general. Because Mendelian segregation only randomizes alleles among children of heterozygotes, the effects of alleles in the children of homozygotes are not observable. This feature will matter if an allele has different average effects in the children of homozygotes and heterozygotes, as can arise in the presence of gene-by-environment interactions, gene-by-gene interactions, or differences in linkage disequilibrium patterns. At a single locus, family-based GWAS can be thought of as providing an unbiased estimate of the average effect in the children of heterozygotes (i.e., a local average treatment effect; LATE). This interpretation does not extend to polygenic scores (PGSs), however, because different sets of SNPs are heterozygous in each family. Therefore, other than under specific conditions, the within-family regression slope of a PGS cannot be assumed to provide an unbiased estimate of the LATE for any subset or weighted average of families. In practice, the potential biases of a family-based GWAS are likely smaller than those that can arise from confounding in a standard, population-based GWAS, and so family studies remain important for the dissection of genetic contributions to phenotypic variation. Nonetheless, their causal interpretation is less straightforward than has been widely appreciated.

Transport diagrams of germanium double quantum dots/Si barriers using photocurrent measurement.

We reported transport diagrams of self-assembled germanium (Ge) double quantum-dots (DQDs) using direct current measurement under illumination at wavelength (λ) of 850 nm and at the base temperature of 4.5 K. Ge DQDs with a coupling-barrier of Si, tunneling-barriers of Si3N4, and self-aligned p+-Si reservoirs were fabricated in a self-organized CMOS approach. Charge transport through the Ge-DQDs is facilitated by photon-assisted tunneling. Characteristic gate-controlled hexagonal-shaped cells over a wide range of hole occupancy are acquired thanks to hard-wall confinement. Large dimensions (ΔVG > 200 mV) of hexagonal-shaped cells are favored for the operation of charge states, indicating that our Ge DQDs system is less susceptible to shot noises arising from external voltage sources. Estimated intra-QD and inter-QD charging energies are EC,R/EC,L = 48.9 meV/42.7 meV and ECm = 7.8 meV, respectively.

Interaction of family SES with children's genetic propensity for cognitive and noncognitive skills: No evidence of the Scarr-Rowe hypothesis for educational outcomes.

This study examines the role of genes and environments in predicting educational outcomes. We test the Scarr-Rowe hypothesis, suggesting that enriched environments enable genetic potential to unfold, and the compensatory advantage hypothesis, proposing that low genetic endowments have less impact on education for children from high socioeconomic status (SES) families. We use a pre-registered design with Netherlands Twin Register data (426 ≤ N individuals ≤ 3875). We build polygenic indexes (PGIs) for cognitive and noncognitive skills to predict seven educational outcomes from childhood to adulthood across three designs (between-family, within-family, and trio) accounting for different confounding sources, totalling 42 analyses. Cognitive PGIs, noncognitive PGIs, and parental education positively predict educational outcomes. Providing partial support for the compensatory hypothesis, 39/42 PGI × SES interactions are negative, with 7 reaching statistical significance under Romano-Wolf and 3 under the more conservative Bonferroni multiple testing corrections (p-value < 0.007). In contrast, the Scarr-Rowe hypothesis lacks empirical support, with just 2 non-significant and 1 significant (not surviving Romano-Wolf) positive interactions. Overall, we emphasise the need for future replication studies in larger samples. Our findings demonstrate the value of merging social-stratification and behavioural-genetic theories to better understand the intricate interplay between genetic factors and social contexts.

Two-dimensional pair-interacting hole gas thermodynamics: Exactly solvable Moshinsky model for lens-shaped quantum dots.

The thermodynamic characteristics of a pair-interacting hole gas localized in a Ge/Si lens-shaped quantum dot are studied. The pair-interaction potential is modeled by the oscillator function, which depends on the distance between the particles. The analytical form of the spectra makes it possible to calculate the partition function in Boltzmann approximation. Based on the partition function mean and free energies, heat capacity and entropy of the interacting gas are calculated. Interaction between particles substantially changes the behavior of the thermodynamic properties in comparison with the non-interacting gas case. In particular, the gas undergoes a first-order phase transition driven by the height of the upper (or lower) section of QD, resulting in a changing symmetry of the lens-shaped QD.

On curve fitting between topological indices and Gibb's energy for semiconducting carbon nitrides network.

Quantitative structure relationships linked to a chemical structure that shed light on its properties and chemical reactions are called topological indices. This structure is upset by the addition of silicon (Si) doping, which changes the electrical and optical characteristics. In this article, we examine the connection between a chemical structure's Gibbs energy (GE) and K-Banhatti indices. In this article, we compute the K-Banhatti indices and then show the correlation between the indices and Gibb's energy of the molecule using curve fitting. Through the curve fitting, we see that there is a strong correlation between indices and Gibb's energy of a molecule. We use the polynomial curve fitting approach to see the correlation between indices and Gibb's energy.

The eco-evolutionary dynamics of stoichiometric homeostasis.

Stoichiometric homeostasis is the ability of life to maintain inner chemical constancy despite changes in the environment and resources. Organisms can be stoichiometrically homeostatic to different degrees. This variation can be substantial even within species, but is ignored in most studies of ecological stoichiometry. Recent studies suggest that resource limitations are an important selective pressure behind homeostasis, but are contradictory in direction, likely owing to differences in nutrient storage strategies. Understanding the selective pressures underlying stoichiometric homeostasis, and its potential for rapid evolution, are key to predicting eco-evolutionary dynamics. This calls for the development of an evolutionary theory of stoichiometric homeostasis that incorporates rapid evolution, as well as for empirical studies to test the underlying mechanisms.

Genotype-by-Environment Interactions in Nonalcoholic Fatty Liver Disease and Chronic Illness among Mexican Americans: The Role of Acculturation Stress.

This study examines the complex interplay of genetic and environmental interactions that shape chronic illness risk. Evidence is mounting for the role of genetic expression and the immune response in the pathogenesis of chronic disease. In the Rio Grande Valley of south Texas, where 90% of the population is Mexican American, chronic illnesses (including obesity, diabetes, nonalcoholic liver disease, and depression) are reaching epidemic proportions. This study leverages an ongoing family study of the genetic determinants of risk for obesity, diabetes, hypertension, hyperlipidemia, and depression in a Mexican American population. Data collected included blood pressure, BMI, hepatic transaminases, HbA1c, depression (BDI-II), acculturation/marginalization (ARSMA-II), and liver health as assessed by elastography. Heritability and genotype-by-environment (G×E) interactions were analyzed, focusing on the marginalization/separation measure of the ARSMA-II. Significant heritabilities were found for traits such as HbA1c (h2 = 0.52), marginalization (h2 = 0.30), AST (h2 = 0.25), ALT (h2 = 0.41), and BMI (h2 = 0.55). Genotype-by-environment interactions were significant for HbA1c, AST/ALT ratio, BDI-II, and CAP, indicating that genetic factors interact with marginalization to influence these traits. This study found that acculturation stress exacerbates the genetic response to chronic illness. These findings underscore the importance of considering G×E interactions in understanding disease susceptibility and may inform targeted interventions for at-risk populations. Further research is warranted to elucidate the underlying molecular pathways and replicate these findings in diverse populations.

Electrical, Optical and Thermal Properties of Ge-Si-Sn-O Thin Films.

This work evaluates the electrical, optical and thermal properties of Sn-doped GexSi1-xOy thin films for use as microbolometer sensing materials. The films were prepared using a combination of a radio frequency (RF) magnetron and direct current (DC) sputtering using a Kurt J Leskar Proline PVD-75 series sputtering machine. Thin films were deposited in an O2+Ar environment at a chamber pressure of 4 mTorr. The thicknesses of the thin films were varied between 300 nm-1.2 µm by varying the deposition time. The morphology and microstructure of thin films were investigated by atomic force microscope (AFM) imaging and X-ray diffraction (XRD), while the atomic composition was determined using the energy dispersive spectroscopy (EDS) function of a scanning electron microscope. The thin film with an atomic composition of Ge0.45Si0.05Sn0.15O0.35 was found to be amorphous. We used the Arrhenius relationship to determine the activation energy as well as temperature coefficient of resistance of the thin films, which were found to be 0.2529 eV and -3.26%/K, respectively. The noise voltage power spectral density (PSD) of the film was analyzed using a Primarius-9812DX noise analyzer using frequencies ranging from 2 Hz to 10 kHz. The noise voltage PSD of the film was found to be 1.76 × 10-11 V2/Hz and 2.78 × 10-14 V2/Hz at 2 Hz and 1KHz frequencies, respectively. The optical constants were determined using the ellipsometry reflection data of samples using an RC2 and infrared (IR) VASE Mark-II ellipsometer from J A Woollam. Absorption, transmission and reflection data for a wavelength range of 900 nm-5000 nm were also determined. We also determined the optical constant values such as the real and imaginary parts of refractive index (n and k, respectively) and real and imaginary part of permittivity (ε1 and ε2, respectively) for wavelength ranges between 193 nm to 35 µm. An optical band gap of 1.03 eV was determined from absorption data and using Tauc's equation. In addition, the thermal conductivity of the film was analyzed using a Linseis thin film analyzer employing the 3ω method. The thermal conductivity of a 780 nm thick film was found to be 0.38 Wm-1K-1 at 300 K. From the data, the Ge-Si-Sn-O alloy was found to be a promising material for use as a sensing material for microbolometers.

Stable chalcogenide Ge-Sb-Te heterostructures with minimal Ge segregation.

Matching of various chalcogenide films shows the advantage of delivering multilayer heterostructures whose physical properties can be tuned with respect to the ones of the constituent single films. In this work, (Ge-Sb-Te)-based heterostructures were deposited by radio frequency sputtering on Si(100) substrates and annealed up to 400 °C. The as-deposited and annealed samples were studied by means of X-ray fluorescence, X-ray diffraction, scanning transmission electron microscopy, electron energy loss spectroscopy and Raman spectroscopy. The heterostructures, combining thermally stable thin layers (i. e. Ge-rich Ge5.5Sb2Te5, Ge) and films exhibiting fast switching dynamics (i. e. Sb2Te3), show, on the one side, higher crystallization-onset temperatures than the standard Ge2Sb2Te5 alloy and, on the other side, none to minimal Ge-segregation.

Clearance of residual genome editing components used for ex vivo genome-editing of allogeneic cell therapy products.

BACKGROUND AIMS: Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated genome editing (GE) components (e.g., nucleases, guide RNAs (gRNAs), and plasmids) are used to genetically modify cells during development of ex vivo genome-edited cell therapies. Prolonged presence of GE components may increase the risk of unintended genome modifications (e.g., off-target editing and chromosomal rearrangements). This risk is a function of the stability of the GE components, culture conditions (i.e., culture length, media changes, etc.), and the nature of the GE component (i.e., only plasmids can be integrated into a cell's genome). Testing for residual GE components on ex vivo genetically edited drug products is generally recommended in current regulatory guidance (CBER 2024). For allogenic cell therapies derived from induced pluripotent stem cells (iPSC), cells typically undergo clonal selection and extensive culturing following completion of genome editing. This post-engineering clonal selection substantially reduces the amount of residual GE components while the long-duration cell culture significantly reduces the presence of active residual GE components. Here we present a case in which the need for testing of the drug product for residual GE components has been eliminated. METHODS: In silico modeling was used to estimate clearance mechanisms across a variety of relevant assumptions, including disposition of extracellular GE components via media changes and dilution of intracellular GE components via cell expansion. Determining the ability of each GE component-alone or in complex with other GE components-to modify genomic material was assessed by a series of both in vitro and ex vivo (i.e., engineering cells) studies. For the in vitro studies, a DNA cutting assay was developed to assess the ability of the component to cut a representative DNA strand. For the ex vivo modification of cells, an assessment of the knock-out of the relevant gene was completed by flow cytometry specifically assessing the presence or absence of protein expression on the modified cells. The persistence and stability of GE components were examined under cell-mimicking conditions and in ex vivo modified cells. The components were stressed under multiple conditions mimicking a range of culture conditions and tested in the aforementioned DNA cutting assay. The presence of residual gRNA was directly assessed in the ex vivo modified cells via a gRNA-specific digital droplet polymerase chain reaction (ddPCR) assay. RESULTS: Simulations estimating genome editing residual clearance via dilution for extracellular residuals (via media changes) or intracellular residuals (via cell doubling) demonstrate clearance of measurable residuals within 28 days of cell culture. Studies simulating the stability of genome editing residuals estimate less than 7 days for the nuclease, gRNA and ribonucleoprotein (RNP) complex. gRNA was undetectable by 8 days post-engineering under actual engineering conditions. Additionally, without gRNA present, CRISPR Cas12a nucleases did not demonstrate evidence of cutting. In contrast, plasmid DNA can be randomly integrated into the genome and free plasmid is highly stable under cell culture-like conditions (50+ days). Additionally, plasmid DNA integrated in cells will propagate during mitosis, leading to the additional risk of expansion of an unintentional integration event. CONCLUSIONS: Both the gRNA and nuclease in the RNP complex are required for DNA cutting. Neither individual component nor the complex are stable beyond 7 days in culture-mimicking conditions. These findings suggest that the risk of unplanned genomic modification resulting from residual gRNA or nuclease is minimal for processes in which extensive culture is performed after the completion of genome editing and clonal selection. However, the risk of residual plasmid DNA integration is significantly higher regardless of the manufacturing process. The residual plasmid itself is quite stable (at least 50 days) and the risk of random, off-target integration is present. By establishing the stability of these components, we have demonstrated that testing for residual gRNA or nuclease is not warranted for clonally derived allogeneic cell therapies.

Structural, elastic, electronic, optical and anisotropy properties of newly quaternary Tl2HgGeSe4 via DFPT predictions associated to XPES and RS experiments.

In the present work, we report on theoretical studies of thermodynamic properties, structural and dynamic stabilities, dependence of unit-cell parameters and elastic constants upon hydrostatic pressure, charge carrier effective masses, electronic and optical properties, contributions of interband transitions in the Brillouin zone of the novel Tl2HgGeSe4 crystal. The theoretical calculations within the framework of the density-functional perturbation theory (DFPT) are carried out employing different approaches to gain the best correspondence to the experimental data. The present theoretical data indicate the dynamical stability of the title crystal and they reveal that, under hydrostatic pressure, it is much more compressible along the a-axis than along the c-axis. Strikingly, the charge effective mass values ( m e ∗ and m h ∗ ) vary considerably when the high symmetry direction changes indicating a relative anisotropy of the charge-carrier's mobility. Furthermore, the Young modulus and compressibility are characterized by the maximum and minimum values ( E max and E min ) and ( ß max and ß min ) that are equal to (62.032 and 28.812) GPa and (13.672 and 6.7175) TPa-1, respectively. Additionally, we have performed calculations of the Raman spectra (RS) and reached a good correspondence with the experimental RS spectra of the Tl2HgGeSe4 crystal. The XPES associated to RS constitutes powerful techniques to explore the oxidized states of Se and Ge in Tl2HgGeSe4 system.

Comparison of the Immunogenicity of the LZ901 Vaccine and HZ/su Vaccine in a Mouse Model.

Herpes zoster (HZ) is an infectious disease caused by the reactivation of varicella zoster virus (VZV), with 68% of cases occurring in adults over 50 years of age. HZ/su (Shingrix®) was approved by the Food and Drug Administration in 2017 for the prevention of HZ in individuals ≥ 50 years of age and showed very good protection from HZ. However, due to the use of the adjuvant AS01B, adverse reactions caused by Shingrix are a concern. Aluminum hydroxide is the most commonly used adjuvant and is widely used in a variety of vaccines. We developed a recombinant zoster vaccine (code: LZ901) consisting of a tetramer of VZV glycoprotein E (gE) and a human Fc fusion protein expressed in CHO cells, an immune complex-like molecule that can be adsorbed with an aluminum hydroxide adjuvant. We compared the immunogenicity of LZ901 with that of HZ/su in BALB/c mice. The results showed that LZ901 induced levels of gE-specific IgG antibodies comparable to those induced by HZ/su, and the results of FAMA titers further demonstrated their similar neutralizing antibody abilities. Most importantly, LZ901 induced higher levels of cell-mediated immunity (CMI) (which plays a decisive role in the efficacy of zoster vaccines) than HZ/su in BALB/c mice. The numbers of cytokine-producing T cells in LZ901-vaccinated mice were significantly greater than those in v-vaccinated mice, and the proportions of CD4+ and CD8+ T cells producing at least two types of cytokines in LZ901-vaccinated mice were significantly greater than those in HZ/su-vaccinated mice.

A nanoparticle vaccine displaying varicella-zoster virus gE antigen induces a superior cellular immune response than a licensed vaccine in mice and non-human primates.

Herpes zoster (HZ), also known as shingles, remains a significant global health issue and most commonly seen in elderly individuals with an early exposure history to varicella-zoster virus (VZV). Currently, the licensed vaccine Shingrix, which comprises a recombinant VZV glycoprotein E (gE) formulated with a potent adjuvant AS01B, is the most effective shingles vaccine on the market. However, undesired reactogenicity and increasing global demand causing vaccine shortage, prompting the development of novel shingles vaccines. Here, we developed novel vaccine candidates utilising multiple nanoparticle (NP) platforms to display the recombinant gE antigen, formulated in an MF59-biosimilar adjuvant. In naïve mice, all tested NP vaccines induced higher humoral and cellular immune responses than Shingrix, among which, the gEM candidate induced the highest cellular response. In live attenuated VZV (VZV LAV)-primed mouse and rhesus macaque models, the gEM candidate elicited superior cell-mediated immunity (CMI) over Shingrix. Collectively, we demonstrated that NP technology remains a suitable tool for developing shingles vaccine, and the reported gEM construct is a highly promising candidate in the next-generation shingles vaccine development.