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1.
Nucleic Acids Res ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33045737

RESUMO

Drug-metabolizing enzymes (DMEs) are critical determinant of drug safety and efficacy, and the interactome of DMEs has attracted extensive attention. There are 3 major interaction types in an interactome: microbiome-DME interaction (MICBIO), xenobiotics-DME interaction (XEOTIC) and host protein-DME interaction (HOSPPI). The interaction data of each type are essential for drug metabolism, and the collective consideration of multiple types has implication for the future practice of precision medicine. However, no database was designed to systematically provide the data of all types of DME interactions. Here, a database of the Interactome of Drug-Metabolizing Enzymes (INTEDE) was therefore constructed to offer these interaction data. First, 1047 unique DMEs (448 host and 599 microbial) were confirmed, for the first time, using their metabolizing drugs. Second, for these newly confirmed DMEs, all types of their interactions (3359 MICBIOs between 225 microbial species and 185 DMEs; 47 778 XEOTICs between 4150 xenobiotics and 501 DMEs; 7849 HOSPPIs between 565 human proteins and 566 DMEs) were comprehensively collected and then provided, which enabled the crosstalk analysis among multiple types. Because of the huge amount of accumulated data, the INTEDE made it possible to generalize key features for revealing disease etiology and optimizing clinical treatment. INTEDE is freely accessible at: https://idrblab.org/intede/.

2.
Health Place ; 66: 102463, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33070105

RESUMO

Despite growing evidence of the relationship between residential environment and depressive symptoms, little is known about this longitudinal relationship for elderly. Based on the follow-up survey (2011, 2013, and 2015) of the China Health and Retirement Longitudinal Study (CHARLS), this study investigated the association between residential environment and depressive symptoms among Chinese middle- and old-aged adults using repeated measures mixed models and Cox proportional hazards regression models. We found that external building characteristics, indoor space layout, household facilities, and indoor environment have significant effects on depressive symptoms in the elderly. Therefore, residential environment interventions such as external built environments promotion, reasonable indoor space layout, and indoor household facilities and environment improvement can be effective ways to reduce risk of depressive symptoms among Chinese middle- and old-aged adults as well as decrease related public health burden.

3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1585-1591, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067958

RESUMO

OBJECTIVE: To identify the molecular pathogenesis of diffuse large B cell lymphoma (DLBCL) and to screen potential biomarkers or therapeutic targets for diagnosis, treatment and prognosis evaluation of patients with DLBCL. METHODS: Gene expression profiles of GSE56315 were downloaded from GEO database. Analysis of differentially expressed genes (DEGs) in the microarray was performed using"R"software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of up-regulated DEGs were performed using DAVID database. The survival analysis of up-regulated DEGs was performed using GEPIA database. RESULTS: There were 55 DLBCL biopsy tissue specimes and 33 normal tonsil tissue specimes in the datasets. A total of 2001 differentially expressed genes were identified, including 1 079 up-regulated DEGs and 922 down-regulated DEGs. Function enrichment analysis indicated that the up-regulated DEGs were involved in 425 GO terms, including 31 genes of FDR<0.05 (P<0.05) and 17 pathways. In the GEPIA database, the expression levels of 12 up-regulated DEGs (AK8、AP2M1、ATOX1、 CSF2RA、CYP27A1、HEBP1、HTRA1、HTRA4、IGFBP3、PTGDS、SIGLEC15、UQCRC1) were found to be significantly correlated with shorter overall survival of DLBCL patients. CONCLUSION: The internal biological information in DLBCL revealed by integrative bioinformatical analysis may provide an important theoretical basis for further research on molecular mechanism of DLBCL, screening of potential therapeutic targets and evaluation of prognosis.


Assuntos
Biologia Computacional , Linfoma Difuso de Grandes Células B , Perfilação da Expressão Gênica , Ontologia Genética , Serina Peptidase 1 de Requerimento de Alta Temperatura A , Humanos , Linfoma Difuso de Grandes Células B/genética , Transcriptoma
4.
Cell Discov ; 6: 70, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33083005

RESUMO

Murine caspase-11 is the centerpiece of the non-canonical inflammasome pathway that can respond to intracellular LPS and induce pyroptosis. Caspase-11 contains two components, an N-terminal caspase recruitment domain (CARD) and a C-terminal catalytic domain. The aggregation of caspase-11 is thought to promote the auto-processing and activation of caspase-11. However, the activation mechanism of caspase-11 remains unclear. In this study, we purified the caspase-11 CARD fused to an MBP tag and found it tetramerizes in solution. Crystallographic analysis reveals an extensive hydrophobic interface formed by the H1-2 helix mediating homotypic CARD interactions. Importantly, mutations of the helix H1-2 hydrophobic residues abolished the tetramerization of MBP-tagged CARD in solution and failed to induce pyroptosis in cells. Our study provides the first evidence of the homotypic interaction mode for an inflammatory caspase by crystal model. This finding demonstrates that the tetramerization of the N-terminal CARD can promote releasing of the catalytic domain auto-inhibition, leading to the caspase-11 activation.

5.
Adv Radiat Oncol ; 5(5): 1042-1050, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33083666

RESUMO

Purpose: We report on the clinical performance of a fully automated approach to treatment planning based on a Pareto optimal, constrained hierarchical optimization algorithm, named Expedited Constrained Hierarchical Optimization (ECHO). Methods and materials: From April 2017 to October 2018, ECHO produced 640 treated plans for 523 patients who underwent stereotactic body radiation therapy (RT) for paraspinal and other metastatic tumors. A total of 182 plans were for 24 Gy in a single fraction, 387 plans were for 27 Gy in 3 fractions, and the remainder were for other prescriptions or fractionations. Of the plans, 84.5% were for paraspinal tumors, with 69, 302, and 170 in the cervical, thoracic, and lumbosacral spine, respectively. For each case, after contouring, a template plan using 9 intensity modulated RT fields based on disease site and tumor location was sent to ECHO through an application program interface plug-in from the treatment planning system. ECHO returned a plan that satisfied all critical structure hard constraints with optimal target volume coverage and the lowest achievable normal tissue doses. Upon ECHO completion, the planner received an e-mail indicating the plan was ready for review. The plan was accepted if all clinical criteria were met. Otherwise, a limited number of parameters could be adjusted for another ECHO run. Results: The median planning target volume size was 84.3 cm3 (range, 6.9-633.2). The median time to produce 1 ECHO plan was 63.5 minutes (range, 11-340 minutes) and was largely dependent on the field sizes. Of the cases, 79.7% required 1 run to produce a clinically accepted plan, 13.3% required 1 additional run with minimal parameter adjustments, and 7.0% required ≥2 additional runs with significant parameter modifications. All plans met or bettered the institutional clinical criteria. Conclusions: We successfully implemented automated stereotactic body RT paraspinal and other metastatic tumors planning. ECHO produced high-quality plans, improved planning efficiency and robustness, and enabled expedited treatment planning at our clinic.

6.
Chem Asian J ; 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33084191

RESUMO

The first allylic alkylation of difluoroenoxysilanes with MBH carbonates catalyzed by triethylenediamine (DABCO) is developed, which allows rapid access to multifunctional α- gem- difluoroketones with up to 97% yields. Moreover, the gram-scale synthesis and the diversifying transformation of products to valuable gem -difluorinated molecules highlighted the practicality of this methodology.

7.
Sci Total Environ ; 755(Pt 1): 142499, 2020 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-33039887

RESUMO

5-Hydroxymethylfurfural (HMF) and levulinic acid (LA) are regarded as value-added platform chemicals that can be derived from biomass waste. However, humins are inevitably produced during valorization processes, reducing the product yields. Previous studies indicated that microwave heating combined with acidic seawater as a reaction medium promotes HMF formation. The present work therefore investigated the relationship between the production of HMF and LA in the liquid phase and that of insoluble humins (that is, hydrochar) under microwave heating in acidic seawater. The selectivities for HMF and LA were found to decrease as the reaction time was increased, as a result of hydrochar formation, and both dehydration and decarboxylation evidently dominated the production of hydrochar in succession. HMF evidently played the most important role in hydrochar formation, and was consumed approximately seven times more rapidly than either fructose or LA. The hydrochar formation mechanism reported herein may be applicable to other similar hydrothermal processes.

8.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(10): 1073-1078, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33059803

RESUMO

OBJECTIVE: To study the risk factors and treatment outcome of hypothyroidism in very low birth weight/extremely low birth weight (VLBW/ELBW) infants. METHODS: The VLBW/ELBW infants who were diagnosed with hypothyroidism from September 2018 to December 2019 were enrolled as the case group (n=29). The children with normal thyroid function, matched at a ratio of 1 : 3, were enrolled as the control group (n=87). Clinical features were compared between the two groups. The correlation of thyroid function with gestational age and birth weight and the risk factors for hypothyroidism were analyzed. RESULTS: A total of 162 VLBW/ELBW infants who met the inclusion criteria were enrolled, with 29 infants in the case group (an incidence rate of hypothyroidism of 17.9%). The lower the birth weight, the higher the incidence rate of hypothyroidism (P<0.05). Triiodothyronine (T3) and free T3 were positively correlated with gestational age (P<0.05). T3 and free thyroxine were positively correlated with birth weight (P<0.05). Small for gestational age, multiple birth, maternal age ≥ 35 years, and use of dopamine were independent risk factors for hypothyroidism (P<0.05). In the case group, 16 infants were treated with levothyroxine (5-10 µg/kg daily), and the thyroid function returned to normal after 2 weeks of treatment. CONCLUSIONS: There is a high incidence rate of hypothyroidism in VLBW/ELBW infants. Small for gestational age, multiple birth, advanced maternal age, and use of dopamine are risk factors for hypothyroidism. The infants treated with levothyroxine should be followed up regularly to ensure an appropriate dose.

9.
Int J Mol Sci ; 21(19)2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33028029

RESUMO

In response to hypoxia under submergence, plants switch from aerobic respiration to anaerobic fermentation, which leads to the accumulation of the end product, ethanol. We previously reported that Arabidopsis thaliana autophagy-deficient mutants show increased sensitivity to ethanol treatment, indicating that ethanol is likely involved in regulating the autophagy-mediated hypoxia response. Here, using a transcriptomic analysis, we identified 3909 genes in Arabidopsis seedlings that were differentially expressed in response to ethanol treatment, including 2487 upregulated and 1422 downregulated genes. Ethanol treatment significantly upregulated genes involved in autophagy and the detoxification of reactive oxygen species. Using transgenic lines expressing AUTOPHAGY-RELATED PROTEIN 8e fused to green fluorescent protein (GFP-ATG8e), we confirmed that exogenous ethanol treatment promotes autophagosome formation in vivo. Phenotypic analysis showed that deletions in the alcohol dehydrogenase gene in adh1 mutants result in attenuated submergence tolerance, decreased accumulation of ATG proteins, and diminished submergence-induced autophagosome formation. Compared to the submergence-tolerant Arabidopsis accession Columbia (Col-0), the submergence-intolerant accession Landsberg erecta (Ler) displayed hypersensitivity to ethanol treatment; we linked these phenotypes to differences in the functions of ADH1 and the autophagy machinery between these accessions. Thus, ethanol promotes autophagy-mediated submergence tolerance in Arabidopsis.

10.
Anal Chem ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33054154

RESUMO

Herein, the boron radical active sites of boron carbon oxynitride quantum dots (BCNO QDs) are electrically excited to produce boron radicals (B•) for catalyzing peroxydisulfate (S2O82-) as a coreactant to accelerate the generation of abundant sulfate radicals (SO4•-) for significant enhancement in the electrochemiluminescence (ECL) efficiency of BCNO QDs, which overcome the defect of traditional carbon-based QDs with low ECL efficiency. Impressively, under extremely low concentration of S2O82- solution, the BCNO QDs/S2O82- system could exhibit high ECL emission, realizing environmental friendliness and excellent biocompatibility for sensitive bioanalysis. As a proof-of-concept, BCNO QDs, a new generation of ECL emitters with high ECL efficiency, were successfully used in the ultrasensitive determination of microRNA-21, which pushes the exploration of new ECL emitters and broadens the application in the field of clinical diagnosis, ECL imaging, and molecular devices.

11.
Org Biomol Chem ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33057546

RESUMO

This review summarizes the advances in catalytic enantioselective reactions using CO2 as a C1 synthon, introduces major synthetic strategies and discusses their advantages and limitations, highlights the application of known protocols, and outlines the synthetic opportunities.

12.
Biochem Cell Biol ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33058690

RESUMO

This study aimed to certify the hypothesis that miR-138-5p is expected to reduced osteodifferentiation of human bone mesenchymal stem cells (hBMSCs) by FOXC1 down-regulation. hBMSCs were separated from bone marrow and osteogenic induction medium was added to stimulate osteogenic differentiation. Flow cytometric analysis was applied to evaluate the expression of cell surface antigens associated with hBMSCs, including CD29, CD44, CD90, CD45 and CD34. qRT-PCR assay and western blot assay were determined to measure the mRNA and protein expression of miR-138-5p, OCN, RUNX2, BSP, ALP and FOXC1. Alkaline phosphatase (ALP) staining assay and Alizarin Red Staining (ARS) assay were determined to validate the osteogenic differentiation. Luciferase assay was applied to test the interaction of miR-138-5p and FOXC1. We demonstrated miR-138-5p is downregulated in osteogenic differentiated hBMSCs. Besides, miR-138-5p overexpression diminished osteodifferentiated markers expression, ALP activity and ARS activity. Furthermore, we revealed that forkhead transcription factor C1 (FOXC1) was a downstream target gene of miR-138-5p and knockdown of miR-138-5p improved the osteogenesis differentiation of hBMSCs by upregulating FOXC1. miR-138-5p knockdown promoted osteogenic differentiation in hBMSCs via directly targeting FOXC1. This study suggested miR-138-5p may be a new target for hBMSCs osteogenic differentiation and the treatment of bone defects.

13.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(9): 1142-1148, 2020.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-33051431

RESUMO

Somatic symptom disorder (SSD) is a somatic disorder characterized by excessive anxiety over various somatic symptoms for a long time, which makes patients feel very painful and the quality of personal life significantly decreased. Previous studies have shown that there is a connection between the clinical manifestations of SSD patients and their cultural background. The patient in this case report was highly affected by Chinese yin-yang culture, displaying obvious Chinese characteristics.We report a patient with SSD, whose clinical manifestations were mainly sexual dysfunction and mood symptoms which were closely related to the Traditional Chinese culture of Yin and Yang. In this case, Hamilton Anxiety Scale, Hamilton Depression Scale, and International Erectile Function Questionnaire were used to evaluate the patients' anxiety, depression, and sexual function, and the scores were 32, 33, and 9, respectively. The patient was treated with a combination of venlafaxine and mirtazapine. After 5 weeks of treatment, the patient's clinical symptoms improved significantly.The clinical manifestations of some Chinese SSD patients have obvious characteristic relevance to Chinese theory of Yin and Yang, making SSD easily to be misdiagnosed. Therefore, clinicians should pay atlention to this situation. In addition, the combination of venlafaxine and mirtazapine may have a better effect on SSD patients with chronic pain and sexual dysfunction.


Assuntos
Sintomas Inexplicáveis , Yin-Yang , Ansiedade , Transtornos de Ansiedade , China , Características Culturais , Humanos , Masculino , Medicina Tradicional Chinesa , Inquéritos e Questionários
14.
Org Lett ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33048558

RESUMO

An efficient Fe(OTf)3-catalyzed nucleophilic substitution of cyclic or acyclic tertiary alcohols with difluoroenoxysilanes is developed, which provides a facile protocol for assembling structurally diverse α,α-gem-difluoroketones featuring a quaternary carbon center in good to excellent yields under mild conditions. Moreover, the diverse product elaborations highlight the utility of this protocol, as exemplified by the preparation of valuable difluorinated tricyclic indolines.

15.
Arch Osteoporos ; 15(1): 164, 2020 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-33070238

RESUMO

Based on the use of Osteoporosis Self-Assessment Tool for Asians (OSTA) to assess osteoporosis risk, we found that short sleep duration and taking a daytime nap had an increased risk of osteoporosis. PURPOSE: To explore the associations between different sleep patterns with osteoporosis. METHODS: 3659 postmenopausal women (average age of 60 years) were divided into low, middle, and high osteoporosis risk categories based on the Osteoporosis Self-Assessment Tool for Asians (OSTA). After having collected by a standard questionnaire, total and nocturnal sleep duration was collapsed to form categories of ≤ 6 h, > 6 h and ≤ 7 h, > 7 h and ≤ 8 h, > 8 h and ≤ 9 h, > 9 h, and daytime nap duration of 0 h and > 0 h. RESULTS: As a categorical variable, the total sleep duration of ≤ 6 h per day (OR = 1.34, 95% CI 1.04-1.72), nocturnal sleep duration of ≤ 6 h per night (OR = 1.65, 95% CI 1.24-2.18), and taking a daytime nap (OR = 1.33, 95% CI 1.09-1.64) had higher osteoporosis risk after adjustment for covariates. As a continuous variable, after the adjustment for covariates, both longer total (OR = 0.86, 95% CI 0.78-0.94) and nocturnal sleep duration (OR = 0.83, 95% CI 0.76-0.91) had lower risk of osteoporosis risk while taking longer daytime nap (OR = 1.10, 95% CI 1.02-1.19) had higher osteoporosis risk. CONCLUSIONS: Postmenopausal women with both short total and nocturnal sleep duration (6 h or less) and taking a daytime nap had increased osteoporosis risk as assessed by OSTA.

16.
PLoS Pathog ; 16(10): e1008899, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33091073

RESUMO

Neonatal herpes simplex virus type 1 (HSV-1) infections contribute to various neurodevelopmental disabilities and the subsequent long-term neurological sequelae into the adulthood. However, further understanding of fetal brain development and the potential neuropathological effects of the HSV-1 infection are hampered by the limitations of existing neurodevelopmental models due to the dramatic differences between humans and other mammalians. Here we generated in vitro neurodevelopmental disorder models including human induced pluripotent stem cell (hiPSC)-based monolayer neuronal differentiation, three-dimensional (3D) neuroepithelial bud, and 3D cerebral organoid to study fetal brain development and the potential neuropathological effects induced by the HSV-1 infections. Our results revealed that the HSV-1-infected neural stem cells (NSCs) exhibited impaired neural differentiation. HSV-1 infection led to dysregulated neurogenesis in the fetal neurodevelopment. The HSV-1-infected brain organoids modelled the pathological features of the neurodevelopmental disorders in the human fetal brain, including the impaired neuronal differentiation, and the dysregulated cortical layer and brain regionalization. Furthermore, the 3D cerebral organoid model showed that HSV-1 infection promoted the abnormal microglial activation, accompanied by the induction of inflammatory factors, such as TNF-α, IL-6, IL-10, and IL-4. Overall, our in vitro neurodevelopmental disorder models reconstituted the neuropathological features associated with HSV-1 infection in human fetal brain development, providing the causal relationships that link HSV biology with the neurodevelopmental disorder pathogen hypothesis.

17.
Adv Healthc Mater ; : e2001342, 2020 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-33103357

RESUMO

3D printing is now popular in tissue engineering as it provides a facile route to the fabrication of scaffolds with/without living cells with a predesigned geometry. The properties of the ink constituents are critical for printing structures to meet both mechanical and biological requirements. Despite recent advances in ink development, it remains a challenge to print biopolymer based tough and elastic hydrogels. These hydrogels are in great demand as they can mimic the biomechanics of soft tissues such as skin, muscle, and cartilage. In this study, a catechol functionalized ink system is developed for 3D coaxial printing tough and elastic hydrogels. The ink is based on biopolymers including catechol modified hyaluronic acid (HACA) and alginate. A novel crosslinking strategy is proposed, involving simple ionic crosslinking, catechol mediated crosslinking, and Michael addition that are all induced under mild conditions. The HACA and alginate form a double network with high fracture toughness and elasticity, while proteins such as gelatin can be integrated with the HACA/alginate hydrogel during printing to improve cell interactions. The printed constructs demonstrate high cytocompatibility and support the differentiation of myoblasts into aligned myotubes. The catechol functionalized ink can be further modified to target various applications in soft tissue engineering.

18.
Sci Adv ; 6(43)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33097545

RESUMO

Epidermal electrophysiology is widely carried out for disease diagnosis, performance monitoring, human-machine interaction, etc. Compared with thick, stiff, and irritating gel electrodes, emerging tattoo-like epidermal electrodes offer much better wearability and versatility. However, state-of-the-art tattoo-like electrodes are limited in size (e.g., centimeters) to perform electrophysiology at scale due to challenges including large-area fabrication, skin lamination, and electrical interference from long interconnects. Therefore, we report large-area, soft, breathable, substrate- and encapsulation-free electrodes designed into transformable filamentary serpentines that can be rapidly fabricated by cut-and-paste method. We propose a Cartan curve-inspired transfer process to minimize strain in the electrodes when laminated on nondevelopable skin surfaces. Unwanted signals picked up by the unencapsulated interconnects can be eliminated through a previously unexplored electrical compensation strategy. These tattoo-like electrodes can comfortably cover the whole chest, forearm, or neck for applications such as multichannel electrocardiography, sign language recognition, prosthetic control or mapping of neck activities.

19.
Food Chem ; 340: 128198, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33032147

RESUMO

In this study, potential of dielectric-barrier discharge (DBD) plasma treatment (40 kV, 12 kHz at 1, 2, 3 and 4 min) to eliminate soybean agglutinin (SBA) activity was investigated in a SBA model system and soymilk. The plasma treatment decreased the SBA in the model system and hemagglutination activity was decreased by 87.31%. SDS-PAGE analysis confirmed the degradation of the SBA polypeptide chain. The multi-spectroscopic analysis revealed a two-stage structure alteration in the SBA upon exposure to the plasma treatment. Oxidation of NH-/NH2- at the peptide bond disrupted the hydrogen bonds and altered the secondary structure of SBA. Further oxidation of aromatic amino acid, cleavage of peptide bonds and the breakage of polypeptide led to the SBA fragmentation and complete unfolding of the protein. The SBA inactivation by the plasma treatment was confirmed in soymilk. Plasma treatment is a promising technology for the elimination of SBA in soybean product.

20.
Sci Rep ; 10(1): 16984, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046728

RESUMO

Fighting smart diseases requires smart vaccines. Novel ways to present protective immunogenic peptide epitopes to human immune systems are needed. Herein, we focus on Self Assembling Protein Nanoparticles (SAPNs) as scaffolds/platforms for vaccine delivery that produce strong immune responses against Toxoplasma gondii in HLA supermotif, transgenic mice. Herein, we present a useful platform to present peptides that elicit CD4+, CD8+ T and B cell immune responses in a core architecture, formed by flagellin, administered in combination with TLR4 ligand-emulsion (GLA-SE) adjuvant. We demonstrate protection of HLA-A*11:01, HLA-A*02:01, and HLA-B*07:02 mice against toxoplasmosis by (i) this novel chimeric polypeptide, containing epitopes that elicit CD8+ T cells, CD4+ T helper cells, and IgG2b antibodies, and (ii) adjuvant activation of innate immune TLR4 and TLR5 pathways. HLA-A*11:01, HLA-A*02:01, and HLA-B*07:02q11 transgenic mouse splenocytes with peptides demonstrated predicted genetic restrictions. This creates a new paradigm-shifting vaccine approach to prevent toxoplasmosis, extendable to other diseases.

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