Numerical Investigation of Layered Homogeneous Skull Model for Simulations of Transcranial Focused Ultrasound.

BACKGROUND AND OBJECTIVES: The influence of the intracranial pressure field must be discussed with the development of a single-element transducer for low-intensity transcranial focused ultrasound because the skull plays a significant role in blocking and dispersing ultrasound wave propagation. Ultrasound propagation is mainly affected by the structure and acoustic properties of the skull; thus, we aimed to investigate the impact of simplifying the acoustic properties of the skull on the simulation of the transcranial pressure field to present guidance for efficient skull modeling in full-wave simulations. MATERIALS AND METHODS: We constructed a three-dimensional computational model for ultrasound transmission with the same structure but varying acoustic properties of the skull. The structural information and heterogeneous acoustic properties of the skull were acquired from computed tomography images, and we segmented the skull into three layers (3 L), including spongy and compact bones. We then assigned homogeneous acoustic properties to a single layer (1 L) or 3 L of the skull. In addition, we investigated the influence of different types of transducers and different ultrasound frequencies (1.1 MHz, 0.5 MHz, and 0.25 MHz) on the intracranial pressure field to provide a comparison of the heterogenous and homogeneous models. RESULTS: We indicated the importance of numerical simulations in estimating the intracranial pressure field of the skull owing to beam distortions. When we simplified the skull model, both the 1 L and 3 L models showed contours of the acoustic focus comparable to those of the heterogeneous model. When we evaluated the peak pressure and volume of the acoustic focus, the 1 L model produced a better estimation of peak pressure with a difference <10%, and the 3 L model is suitable to obtain smaller errors in the volume of the acoustic focus. CONCLUSIONS: In conclusion, we examined the possibility of simplification of skull models using 1 L and 3 L homogeneous properties in the numerical simulation for focused ultrasound. The results show that the layered homogeneous model can provide characteristics comparable to those of the acoustic focus in heterogeneous models.

A lipid nanoparticle platform incorporating trehalose glycolipid for exceptional mRNA vaccine safety.

The rapid development of messenger RNA (mRNA) vaccines formulated with lipid nanoparticles (LNPs) has contributed to control of the COVID-19 pandemic. However, mRNA vaccines have raised concerns about their potential toxicity and clinical safety, including side effects, such as myocarditis, anaphylaxis, and pericarditis. In this study, we investigated the potential of trehalose glycolipids-containing LNP (LNP S050L) to reduce the risks associated with ionizable lipids. Trehalose glycolipids can form hydrogen bonds with polar biomolecules, allowing the formation of a stable LNP structure by replacing half of the ionizable lipids. The efficacy and safety of LNP S050L were evaluated by encapsulating the mRNA encoding the luciferase reporter gene and measuring gene expression and organ toxicity, respectively. Furthermore, mice immunized with an LNP S050L-formulated mRNA vaccine expressing influenza hemagglutinin exhibited a significant reduction in organ toxicity, including in the heart, spleen, and liver, while sustaining gene expression and immune efficiency, compared to conventional LNPs (Con-LNPs). Our findings suggest that LNP S050L, a trehalose glycolipid-based LNP, could facilitate the development of safe mRNA vaccines with improved clinical safety.

Chiral Materials for Optics and Electronics: Ready to Rise?

Chiral materials have gained burgeoning interest in optics and electronics, beyond their classical application field of drug synthesis. In this review, we summarize the diverse chiral materials developed to date and how they have been effectively applied to optics and electronics to get an understanding and vision for the further development of chiral materials for advanced optics and electronics.

The ß2-adrenergic receptor associates with CXCR4 multimers in human cancer cells.

While the existence and functional role of class C G-protein-coupled receptors (GPCR) dimers is well established, there is still a lack of consensus regarding class A and B GPCR multimerization. This lack of consensus is largely due to the inherent challenges of demonstrating the presence of multimeric receptor complexes in a physiologically relevant cellular context. The C-X-C motif chemokine receptor 4 (CXCR4) is a class A GPCR that is a promising target of anticancer therapy. Here, we investigated the potential of CXCR4 to form multimeric complexes with other GPCRs and characterized the relative size of the complexes in a live-cell environment. Using a bimolecular fluorescence complementation (BiFC) assay, we identified the ß2 adrenergic receptor (ß2AR) as an interaction partner. To investigate the molecular scale details of CXCR4-ß2AR interactions, we used a time-resolved fluorescence spectroscopy method called pulsed-interleaved excitation fluorescence cross-correlation spectroscopy (PIE-FCCS). PIE-FCCS can resolve membrane protein density, diffusion, and multimerization state in live cells at physiological expression levels. We probed CXCR4 and ß2AR homo- and heteromultimerization in model cell lines and found that CXCR4 assembles into multimeric complexes larger than dimers in MDA-MB-231 human breast cancer cells and in HCC4006 human lung cancer cells. We also found that ß2AR associates with CXCR4 multimers in MDA-MB-231 and HCC4006 cells to a higher degree than in COS-7 and CHO cells and in a ligand-dependent manner. These results suggest that CXCR4-ß2AR heteromers are present in human cancer cells and that GPCR multimerization is significantly affected by the plasma membrane environment.

Assessing the impact of mRNA vaccination in chronic inflammatory murine model.

The implications of administration of mRNA vaccines to individuals with chronic inflammatory diseases, including myocarditis, rheumatoid arthritis (RA), and inflammatory bowel disease (IBD), are unclear. We investigated mRNA vaccine effects in a chronic inflammation mouse model implanted with an LPS pump, focusing on toxicity and immunogenicity. Under chronic inflammation, mRNA vaccines exacerbated cardiac damage and myocarditis, inducing mild heart inflammation with heightened pro-inflammatory cytokine production and inflammatory cell infiltration in the heart. Concurrently, significant muscle damage occurred, with disturbances in mitochondrial fusion and fission factors signaling impaired muscle repair. However, chronic inflammation did not adversely affect muscles at the vaccination site or humoral immune responses; nevertheless, it partially reduced the cell-mediated immune response, particularly T-cell activation. These findings underscore the importance of addressing mRNA vaccine toxicity and immunogenicity in the context of chronic inflammation, ensuring their safe and effective utilization, particularly among vulnerable populations with immune-mediated inflammatory diseases.

Glycerol-derived organic carbonates: environmentally friendly plasticizers for PLA.

Polylactic acid (PLA) stands as a promising material, sourced from renewables and exhibiting biodegradability-albeit under stringent industrial composting settings. A primary challenge impeding PLA's broad applications is its inherent brittleness, as it fractures with minimal elongation despite its commendable tensile strength. A well-established remedy involves blending PLA with plasticizers. In this study, a range of organic carbonates-namely, 4-ethoxycarbonyloximethyl-[1,3]dioxolan-2-one (1), 4-methoxycarbonyloximethyl-[1,3]dioxolan-2-one (2), glycerol carbonate (3), and glycerol 1-acetate 2,3-carbonate (4)-were synthesized on a preparative scale (∼100 g), using renewable glycerol and CO2-derived diethyl carbonate (DEC) or dimethyl carbonate (DMC). Significantly, 1-4 exhibited biodegradability under ambient conditions within a week, ascertained through soil exposure at 25 °C-outpacing the degradation of comparative cellulose. Further investigations revealed 1's efficacy as a PLA plasticizer. Compatibility with PLA, up to 30 phr (parts per hundred resin), was verified using an array of techniques, including DSC, DMA, SEM, and rotational rheometry. The resulting blends showcased enhanced ductility, evident from tensile property measurements. Notably, the novel plasticizer 1 displayed an advantage over conventional acetyltributylcitrate (ATBC) in terms of morphological stability. Slow crystallization, observed in PLA/ATBC blends over time at room temperature, was absent in PLA/1 blends, preserving amorphous domain dimensions and mitigating plasticizer migration-confirmed through DMA assessments of aged and unaged specimens. Nevertheless, biodegradation assessments of the blends revealed that the biodegradable organic carbonate plasticizers did not augment PLA's biodegradation. The PLA in the blends remained mostly unchanged under ambient soil conditions of 25 °C over a 6 month period. This work underscores the potential of organic carbonates as both eco-friendly plasticizers for PLA and as biodegradable compounds, contributing to the development of environmentally conscious polymer systems.

Ductile Copolyesters Prepared Using Succinic Acid, 1,4-Butanediol, and Bis(2-hydroxyethyl) Terephthalate with Minimizing Generation of Tetrahydrofuran.

Poly(1,4-butylene succinate) (PBS) is a promising sustainable and biodegradable synthetic polyester. In this study, we synthesized PBS-based copolyesters by incorporating 5-20 mol% of -O2CC6H4CO2- and -OCH2CH2O- units through the polycondensation of succinic acid (SA) with 1,4-butanediol (BD) and bis(2-hydroxyethyl) terephthalate (BHET). Two different catalysts, H3PO4 and the conventional catalyst (nBuO)4Ti, were used comparatively in the synthesis process. The copolyesters produced using the former were treated with M(2-ethylhexanoate)2 (M = Mg, Zn, Mn) to connect the chains through ionic interactions between M2+ ions and either -CH2OP(O)(OH)O- or (-CH2O)2P(O)O- groups. By incorporating BHET units (i.e., -O2CC6H4CO2- and -OCH2CH2O-), the resulting copolyesters exhibited improved ductile properties with enhanced elongation at break, albeit with reduced tensile strength. The copolyesters prepared with H3PO4/M(2-ethylhexanoate)2 displayed a less random distribution of -O2CC6H4CO2- and -OCH2CH2O- units, leading to a faster crystallization rate, higher Tm value, and higher yield strength compared to those prepared with (nBuO)4Ti using the same amount of BHET. Furthermore, they displayed substantial shear-thinning behavior in their rheological properties due to the presence of long-chain branches of (-CH2O)3P=O units. Unfortunately, the copolyesters prepared with H3PO4/M(2-ethylhexanoate)2, and hence containing M2+, -CH2OP(O)(OH)O-, (-CH2O)2P(O)O- groups, did not exhibit enhanced biodegradability under ambient soil conditions.

Preparation of Well-Defined Double-Metal Cyanide Catalysts for Propylene Oxide Polymerization and CO2 Copolymerization.

Reevaluating the composition of the double metal cyanide catalyst (DMC) as a salt of (NC)6Co3- anions with 1:1 Zn2+/(X)Zn+ cations (X = Cl, RO, AcO), we prepared a series of well-defined DMCs, [ClZn+][Zn2+][(NC)6Co3-][ROH], [(RO)Zn+][Zn2+][(NC)6Co3-], [(AcO)Zn+][Zn2+][(NC)6Co3-], [(RO)Zn+]p[ClZn+](1-p)[Zn2+][(NC)6Co3-], [(AcO)Zn+]p[(tBuO)Zn+]q[Zn2+][(NC)6Co3-], and [(AcO)Zn+]p[(tBuO)Zn+]q[ClZn+]r[Zn2+][(NC)6Co3-]. The structure of [(MeOC3H6O)Zn+][Zn2+][(NC)6Co3-] was precisely determined at the atomic level through Rietveld refinement of the synchrotron X-ray powder diffraction data. By evaluating the catalyst's performance in both propylene oxide (PO) polymerization and PO/CO2 copolymerization, a correlation between structure and performance was established on various aspects including activity, dispersity, unsaturation level, and carbonate fraction in the resulting polyols. Ultimately, our study identified highly efficient catalysts that outperformed the state-of-the-art benchmark DMC not only in PO polymerization [DMC-(OAc/OtBu/Cl)(0.59/0.38/0.15)] but also in PO/CO2 copolymerization [DMC-(OAc/OtBu)(0.95/0.08)].

Effect of additional cytoplasm injection on the cloned bovine embryo organelle distribution and stress mitigation.

Although somatic cell nuclear transfer (SCNT) is a critical component of animal cloning, this approach has several issues. We previously introduced the cytoplasm injection cloning technology (CICT), which significantly improves the quality and quantity of cloned embryos. This study examined the residual status of fused cytoplasmic organelles, such as the endoplasmic reticulum (ER) and lysosomes, in the CICT group during early embryo development. We found that extra-cytoplasmic organelles stained using the ER-Tracker™ Green dye and LysoTracker™ Deep Red probe were fused and dispersed throughout the recipient oocyte and were still visible in day 8 blastocysts. We screened for ER stress, autophagy, and apoptosis-related genes to elucidate the association between the added organelles and improved embryo quality in CICT-cloned embryos. We found that CHOP, ATF4, ATG5, ATG7, and LC3 genes showed non-significantly up- or downregulated expression between CICT- and in vitro fertilization (IVF)-derived embryos but showed significantly (p < 0.05) upregulated expression in SCNT-cloned embryos. Surprisingly, a non-significant difference in the expression of some genes, such as ATF6 and caspase-3, was observed between the CICT- and SCNT-cloned embryos. Our findings imply that compared to conventional SCNT cloning, CICT-derived cloned embryos with additional cytoplasm have much higher organelle activity, lower autophagy, lower rates of apoptosis, and higher embryo development rates.

The effect of deep brain structure modeling on transcranial direct current stimulation-induced electric fields: An in-silico study.

To study transcranial direct current stimulation (tDCS) and its effect on the brain, it could be useful to predict the distribution of the electric field induced in the brain with given tDCS parameters. As a solution, simulation with realistic computational models using magnetic resonance images (MRIs) have been widely used in the fields. With the recent advance of deep learning-based segmentation techniques of the brain, questions have been raised about if tDCS-induced electric field is affected by the deep brain structures. This study aimed to investigate the effect of the deep brain structure modeling on the induced electric field. To this end, we generated models with and without the deep brain structures by using an open MRI dataset comprising tDCS parameters, electric field simulation results and in-vivo intracranial recordings in the deep brain structures. We investigated the difference between the simulation results of the two models with a statistical analysis. Our results indicated that tDCS-induced electric fields and current flow in the brain are significantly different when the deep brain structures are considered.

mRNA-HPV vaccine encoding E6 and E7 improves therapeutic potential for HPV-mediated cancers via subcutaneous immunization.

The E6 and E7 proteins of specific subtypes of human papillomavirus (HPV), including HPV 16 and 18, are highly associated with cervical cancer as they modulate cell cycle regulation. The aim of this study was to investigate the potential antitumor effects of a messenger RNA-HPV therapeutic vaccine (mHTV) containing nononcogenic E6 and E7 proteins. To achieve this, C57BL/6j mice were injected with the vaccine via both intramuscular and subcutaneous routes, and the resulting effects were evaluated. mHTV immunization markedly induced robust T cell-mediated immune responses and significantly suppressed tumor growth in both subcutaneous and orthotopic tumor-implanted mouse model, with a significant infiltration of immune cells into tumor tissues. Tumor retransplantation at day 62 postprimary vaccination completely halted progression in all mHTV-treated mice. Furthermore, tumor expansion was significantly reduced upon TC-1 transplantation 160 days after the last immunization. Immunization of rhesus monkeys with mHTV elicited promising immune responses. The immunogenicity of mHTV in nonhuman primates provides strong evidence for clinical application against HPV-related cancers in humans. All data suggest that mHTV can be used as both a therapeutic and prophylactic vaccine.

Object-stable unsupervised dual contrastive learning image-to-image translation with query-selected attention and convolutional block attention module.

Recently, contrastive learning has gained popularity in the field of unsupervised image-to-image (I2I) translation. In a previous study, a query-selected attention (QS-Attn) module, which employed an attention matrix with a probability distribution, was used to maximize the mutual information between the source and translated images. This module selected significant queries using an entropy metric computed from the attention matrix. However, it often selected many queries with equal significance measures, leading to an excessive focus on the background. In this study, we proposed a dual-learning framework with QS-Attn and convolutional block attention module (CBAM) called object-stable dual contrastive learning generative adversarial network (OS-DCLGAN). In this paper, we utilize a CBAM, which learns what and where to emphasize or suppress, thereby refining intermediate features effectively. This CBAM was integrated before the QS-Attn module to capture significant domain information for I2I translation tasks. The proposed framework outperformed recently introduced approaches in various I2I translation tasks, showing its effectiveness and versatility. The code is available at https://github.com/RedPotatoChip/OSUDL.

Design of a Miniature Observation Robot for Light Emitting Diode Irradiation and Indocyanine Green Fluorescence-emission Guided Lymph Node Monitoring in Operating Rooms.

MOTIVATION: Typical surgical microscopes used for fluorescence-based lymph node detection experience limitations such as weight and restricted adjustability of the integrated light emitting diode (LED) and camera. This restricts the capture of detailed images of specific regions within the lesion. RESEARCH GOAL: This study proposes a miniature observation robot design that offers adjustable working distance (WD) and rotational radius, along with zoom-in/zoom-out functionality. METHODS: A five-degree-of-freedom manipulator was designed, with the end effector incorporating an LED and concave lens to widen the beam width for comprehensive lesion illumination. Additionally, a long-pass filter was integrated into the camera system to enhance image resolution. EXPERIMENTAL RESULTS: Experiments were conducted using a fluorescence-expressing phantom to evaluate the performance of the robot. Results demonstrated a captured image resolution of 9600 × 3240 pixels and a zoom-in/zoom-out capacity of up to 3.68 times. CONCLUSION: The proposed robot design is cost-effective and highly adjustable, enabling suitability for rapid and accurate detection of fresh lymph nodes during surgeries. The robot's capability to detect small lesions (<1 cm), as validated by phantom tests, holds promise for the detection of minute lymph nodes.

Analysis of the immunostimulatory effects of cytokine-expressing internal ribosome entry site-based RNA adjuvants and their applications.

Developing new adjuvants that can effectively induce both humoral and cellular immune responses while broadening the immune response is of great value. In this study, we aimed to develop GM-CSF- or IL-18-expressing single-stranded RNA (ssRNA) adjuvants based on the encephalomyocarditis virus (EMCV) internal ribosome entry site (IRES) and tested their efficacy in combination with ovalbumin (OVA) or inactivated influenza vaccines. Notably, cytokine-expressing RNA adjuvants increased the expression of antigen-presenting cell activation markers. Specifically, GM-CSF-expressing RNA adjuvants increased CD4+T cell responses, while IL-18-expressing RNA adjuvants increased CD8+T cell responses in mice when combined with OVA. In addition, cytokine-expressing RNA adjuvants increased the frequency of polyclonal T cells in combination with the influenza vaccine and reduced the clinical illness scores and weight loss of mice after viral challenge. Collectively, our results suggest that cytokine-expressing RNA adjuvants can be applied to protein-based or inactivated vaccines to increase their efficacy.

Relationship between metabolic syndrome and intake of ultra-processed foods in Korean adults: based on 6th and 7th Korea National Health and Nutrition Examination Survey (2013-2018).

BACKGROUND/OBJECTIVES: Metabolic syndrome is closely associated with lifestyle factors, including diet and nutritional intake. Modern trends show a shift in food consumption from healthy home-cooked meals to processed and instant foods. Therefore, this study analyzed the association between ultra-processed food intake and the development of metabolic syndrome in Korean adults based on the data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2013-2018. SUBJECTS/METHODS: The subjects of this study were 17,414 adults aged 19-80 years who participated in the 6th-7th KNHANES. Processed food was classified into four categories, NOVA1 to NOVA4, using 24-h recall data. The higher the NOVA category, the more processed the food. Statistical analysis was conducted using logistic regression to investigate the prevalence of metabolic syndrome according to the consumption of ultra-processed foods. RESULTS: Among the diagnostic criteria for metabolic syndrome, hypertension (odds ratio [OR], 0.72; 95% confidence interval [CI], 0.62-0.85; Q4 vs. Q1, P-trend < 0.001) and high triglycerides (OR, 0.83; 95% CI, 0.72-0.94; Q4 vs. Q1, P-trend < 0.001) showed a correlation with the percentages of energy consumed from ultra-processed foods. The OR for metabolic syndrome, according to the percentages of energy consumed from ultra-processed foods, is shown only for men. The OR showed that the percentages of energy consumed from ultra-processed foods were associated with increased metabolic syndrome. CONCLUSIONS: This study suggests that consumption of ultra-processed foods raises the risk of metabolic syndrome especially among men. To prevent metabolic syndrome, it is necessary to prepare appropriate dietary guidelines for Korean adults.

Receptor-specific contributions of caveolae, PKC, and Src tyrosine kinase to serotonergic and adrenergic regulation of Kv channels and vasoconstriction.

AIMS: Caveolae are invaginated, Ω-shaped membrane structures. They are now recognized as portals for signal transduction of multiple chemical and mechanical stimuli. Notably, the contribution of caveolae has been reported to be receptor-specific. However, details of how they differentially contribute to receptor signaling remain unclear. MAIN METHODS: Using isometric tension measurements, patch-clamping, and western blotting, we examined the contribution of caveolae and their related signaling pathways to serotonergic (5-HT2A receptor-mediated) and adrenergic (α1-adrenoceptor-mediated) signaling in rat mesenteric arteries. KEY FINDINGS: Disruption of caveolae by methyl-ß-cyclodextrin effectively blocked vasoconstriction mediated by the 5-HT2A receptor (5-HT2AR), but not by the α1-adrenoceptor. Caveolar disruption selectively impaired 5-HT2AR-mediated voltage-dependent K+ channel (Kv) inhibition, but not α1-adrenoceptor-mediated Kv inhibition. In contrast, both serotonergic and α1-adrenergic effects on vasoconstriction, as well as Kv currents, were similarly blocked by the Src tyrosine kinase inhibitor PP2. However, inhibition of protein kinase C (PKC) by either GO6976 or chelerythrine selectively attenuated the effects mediated by the α1-adrenoceptor, but not by 5-HT2AR. Disruption of caveolae decreased 5-HT2AR-mediated Src phosphorylation, but not α1-adrenoceptor-mediated Src phosphorylation. Finally, the PKC inhibitor GO6976 blocked Src phosphorylation by the α1-adrenoceptor, but not by 5-HT2AR. SIGNIFICANCE: 5-HT2AR-mediated Kv inhibition and vasoconstriction are dependent on caveolar integrity and Src tyrosine kinase, but not on PKC. In contrast, α1-adrenoceptor-mediated Kv inhibition and vasoconstriction are not dependent on caveolar integrity, but rather on PKC and Src tyrosine kinase. Caveolae-independent PKC is upstream of Src activation for α1-adrenoceptor-mediated Kv inhibition and vasoconstriction.

Analyzing immune responses to varied mRNA and protein vaccine sequences.

In response to the COVID-19 pandemic, different types of vaccines, such as inactive, live-attenuated, messenger RNA (mRNA), and protein subunit, have been developed against SARS-CoV-2. This has unintentionally created a unique scenario where heterologous prime-boost vaccination against a single virus has been administered to a large human population. Here, we aimed to analyze whether the immunization order of vaccine types influences the efficacy of heterologous prime-boost vaccination, especially mRNA and protein-based vaccines. We developed a new mRNA vaccine encoding the hemagglutinin (HA) glycoprotein of the influenza virus using the 3'-UTR and 5'-UTR of muscle cells (mRNA-HA) and tested its efficacy by heterologous immunization with an HA protein vaccine (protein-HA). The results demonstrated higher IgG2a levels and hemagglutination inhibition titers in the mRNA-HA priming/protein-HA boosting (R-P) regimen than those induced by reverse immunization (protein-HA priming/mRNA-HA boosting, P-R). After the viral challenge, the R-P group showed lower virus loads and less inflammation in the lungs than the P-R group did. Transcriptome analysis revealed that the heterologous prime-boost groups had differentially activated immune response pathways, according to the order of immunization. In summary, our results demonstrate that the sequence of vaccination is critical to direct desired immune responses. This study demonstrates the potential of a heterologous vaccination strategy using mRNA and protein vaccine platforms against viral infection.

The effects of cycloastragenol on bovine embryo development, implantation potential and telomerase activity.

CONTEXT: Telomerase reverse transcriptase is a key factor responsible for structural and cellular alterations in aged oocytes and changes in the structure of the zona pellucida and mitochondria. Telomerase expression is reduced in aged cumulus oocyte complexes, and its activation or enhanced expression would be beneficial for in vitro oocyte maturation and in vitro embryo development. AIMS: This study aimed to investigate telomerase activation by cycloastragenol and its effect on bovine oocyte in vitro maturation, fertilisation, and early embryo development. METHODS: We used qPCR, Western blot, immunofluorescence, reactive oxygen species (ROS) assay,TUNEL assay, JC-1 assay, and invasion assay to analyse the affect of cycloastragenol (CAG) on bovine oocyte maturation, embryo development, embryo quality and implantation potential. KEY RESULTS: Cycloastragenol treatment of oocytes in in vitro maturation (IVM) media significantly (P <0.05) improved oocyte IVM (90.87%), embryo cleavage (90.78%), blastocyst hatching (27.04%), and embryo implantation potential. Telomerase also interacts with mitochondria, and JC-1 staining results showed significantly (P <0.05) higher mitochondrial membrane potential (ΔΨ m) in the CAG-treated group. Furthermore, the inner cell mass (OCT4 and SOX2) and trophoblasts (CDX2) of the control and CAG groups were examined. Moreover, CAG treatment to primary cultured bovine cumulus cells substantially enhanced telomerase activity. CONCLUSIONS: Telomerase activation via cycloastragenol is beneficial for bovine oocyte IVM and for the production of high-quality bovine embryos. IMPLICATIONS: Cycloastragenol is a natural telomerase activator, and could be useful as a permanent component of oocyte maturation media.

Heterologous vaccination utilizing viral vector and protein platforms confers complete protection against SFTSV.

Severe fever with thrombocytopenia syndrome virus was first discovered in 2009 as the causative agent of severe fever with thrombocytopenia syndrome. Despite its potential threat to public health, no prophylactic vaccine is yet available. This study developed a heterologous prime-boost strategy comprising priming with recombinant replication-deficient human adenovirus type 5 (rAd5) expressing the surface glycoprotein, Gn, and boosting with Gn protein. This vaccination regimen induced balanced Th1/Th2 immune responses and resulted in potent humoral and T cell-mediated responses in mice. It elicited high neutralizing antibody titers in both mice and non-human primates. Transcriptome analysis revealed that rAd5 and Gn proteins induced adaptive and innate immune pathways, respectively. This study provides immunological and mechanistic insight into this heterologous regimen and paves the way for future strategies against emerging infectious diseases.