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Ma, Rui

Publications and source records attributed to Ma, Rui.

At least 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

A combined designed CSP and Pfs48/45 infection and transmission blocking vaccine for malaria

Abstract The multiple stages of the malaria parasite life cycle hampers vaccine development. Combining a pre-erythrocytic antigen with a transmission-blocking antigen would target two independent stages of the life cycle for disease control, resulting in a multistage vaccine that can prevent infection and disease transmission simultaneously. Here, we generated a self-assembled ferritin nanoparticle vaccine that simultaneously presents designed immunogens CSPj5c and 17-4 from the infection-blocking circumsporozoite and the transmission-blocking Pfs48/45 antigens. These immunogens were designed, through structure-based approaches, to retain protective epitopes and confer protection upon vaccination. Immunization with CSPj5c-17-4-ferritin nanoparticles conferred protection against challenge with transgenic sporozoites expressingPlasmodium falciparumCSP in mice, and purified IgGs from immunized rabbits elicited potent transmission-reducing activity. Addition of the engineered 17-4 improved the immune responses to CSPj5c and protection from sporozoite challenge. CSPj5c-17-4-ferritin is therefore a promising multistage malaria vaccine with a potential role in malaria control.

Immunology↗
DOE OSTI2024

A Self-Assembling Pfs230D1-Ferritin Nanoparticle Vaccine Has Potent and Durable Malaria Transmission-Reducing Activity

Malaria is caused by eukaryotic protozoan parasites of the genus Plasmodium. There are 249 million new cases and 608,000 deaths annually, and new interventions are desperately needed. Malaria vaccines can be divided into three categories: liver stage, blood stage, or transmission-blocking vaccines. Transmission-blocking vaccines prevent the transmission of disease by the mosquito vector from one human to another. Pfs230 is one of the leading transmission-blocking vaccine antigens for malaria. Here, we describe the development of a 24-copy self-assembling nanoparticle vaccine comprising domain 1 of Pfs230 genetically fused to H. pylori ferritin. The single-component Pfs230D1-ferritin construct forms a stable and homogenous 24-copy nanoparticle with good production yields. The nanoparticle is highly immunogenic, as two low-dose vaccinations of New Zealand White rabbits elicited a potent and durable antibody response with high transmission-reducing activity when formulated in two distinct adjuvants suitable for translation to human use. This single-component 24-copy Pfs230D1-ferritin nanoparticle vaccine has the potential to improve production pipelines and the cost of manufacturing a potent and durable transmission-blocking vaccine for malaria control.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

A potent and durable malaria transmission-blocking vaccine designed from a single-component 60-copy Pfs230D1 nanoparticle

Malaria transmission-blocking vaccines (TBVs) reduce disease transmission by breaking the continuous cycle of infection between the human host and the mosquito vector. Domain 1 (D1) of Pfs230 is a leading TBV candidate and comprises the majority of transmission-reducing activity (TRA) elicited by Pfs230. Here we show that the fusion of Pfs230D1 to a 60-copy multimer of the catalytic domain of dihydrolipoyl acetyltransferase protein (E2p) results in a single-component nanoparticle composed of 60 copies of the fusion protein with high stability, homogeneity, and production yields. The nanoparticle presents a potent human transmission-blocking epitope within Pfs230D1, indicating the antigen is correctly oriented on the surface of the nanoparticle. Two vaccinations of New Zealand White rabbits with the Pfs230D1 nanoparticle elicited a potent and durable antibody response with high TRA when formulated in two distinct adjuvants suitable for translation to human use. This single-component nanoparticle vaccine may play a key role in malaria control and has the potential to improve production pipelines and the cost of manufacturing of a potent and durable TBV.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Profile of Twenty-Three Human Milk Oligosaccharides in Han Chinese Mothers throughout Postpartum 1 year

Human milk oligosaccharides (HMOs) are multifunctional carbohydrates in breast milk, which are composed by a variety of structures. This study aimed to identified HMOs concentration profile, milk microbiota composition, and the associations with major maternal characteristics in Han Chinese mothers in the one-year lactation period. Seventeen healthy mothers aged from 28 to 36 years, who gave birth to healthy term infants, were recruited. Carbohydrates were detected using the MIRIS human milk analyzer (HMA), and twenty-three HMOs were quantified using ultra-performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-MS). Results showed that carbohydrates were relatively stable, while total HMO concentrations ranged from 1.74 to 9.72 g/L and decreased gradually over lactation in breast milk. Based on the structure, seven sialylated HMOs concentration showed the significant decline ( p < 0.05 ) after three months in lactation. In addition, the relationships between maternal factors, containing the lactation period, genetic status, delivery mode, parity, and milk microbiota profile, and the HMO composition in healthy women, which still need further investigations, were observed.

Xun, Yiping↗
DOE OSTI2021

Structural and Catalytic Properties of Isolated Pt 2+ Sites in Platinum Phosphide (PtP 2 )

This article describes the synthesis and catalytic properties of supported, 2-3 nm platinum phosphide (PtP 2 ) nanoparticles (NPs). Depending on the P loading, two PtP 2 structures are formed, that is, a PtP 2 surface on a (metallic) Pt core (Pt@PtP 2 ) and single-phase PtP 2 NPs. The structures were determined using extended X-ray absorption fine structure , in situ synchrotron X-ray diffraction, and scanning transmission electron microscopy. In PtP 2 NPs, Pt 2+ ions are geometrically isolated by P 2 2- ions, at a Pt-Pt distance of 4.02 Å, which is much longer than 2.78 Å in (metallic) Pt NPs. The oxidation state of Pt in PtP 2 NPs was determined by in situ X-ray absorption near-edge structure and in situ X-ray photoelectron spectroscopy and was found to be consistent with Pt 2+ ions even after treatment in H 2 at 550 °C. Unlike Pt NPs, which are highly active for propylene hydrogenation at room temperature, PtP 2 NPs are not active below about 150 °C, suggesting the absence of metallic surface Pt. In contrast to metallic Pt, which is poorly selective for acetylene hydrogenation, PtP 2 NPs display high selectivity toward ethylene. PtP 2 , also has high olefin selectivity for propane dehydrogenation, although the rate per g Pt is about 7 times lower than that of metallic Pt NPs of the same size. In situ resonant inelastic X-ray scattering spectroscopy shows that the energy of the filled Pt 5d valence orbitals is 1.5 eV lower than that of metallic Pt, which leads to weaker adsorbate binding consistent with its catalytic properties. Here, a H 2 -stable Pt 2+ site suggests different catalytic applications for these catalysts as compared to Pt NPs.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

Simultaneous gentamicin-mediated damage and Atoh1 overexpression promotes hair cell regeneration in the neonatal mouse utricle

Highlights: • Type I hair cells were the primary target of gentamicin. • Simultaneous induction of gentamicin and Atoh1 promoted hair cell generation. • Type II-like hair cells regenerated in the striola via direct transdifferentiation. • Type I/II hair cells generated in the ectopic region in mitotic and non-mitotic way. • Mitosis enhanced type I hair cell production. Loss of hair cells from vestibular epithelium results in balance dysfunction. The current therapeutic regimen for vestibular diseases is limited. Upon injury or Atoh1 overexpression, hair cell replacement occurs rapidly in the mammalian utricle, suggesting a promising approach to induce vestibular hair cell regeneration. In this study, we applied simultaneous gentamicin-mediated hair cell ablation and Atoh1 overexpression to induce neonatal utricular hair cell formation in vitro. We confirmed that type I hair cells were the primary targets of gentamicin. Furthermore, injury and Atoh1 overexpression promoted hair cell regeneration in a timely and efficient manner through robust viral transfection. Hair cells regenerated with type II characteristics in the striola and type I/II characteristics in non-sensory regions. Rare EdU{sup +}/myosin7a{sup +} cells in sensory regions and robust EdU{sup +}/myosin7a{sup +} signals in ectopic regions indicate that transdifferentiation of supporting cells in situ, and mitosis and differentiation of non-sensory epithelial cells in ectopic regions, are sources of regenerative hair cells. Distinct regeneration patterns in in situ and ectopic regions suggested robust plasticity of vestibular non-sensory epithelium, generating more developed hair cell subtypes and thus providing a promising stem cell-like source of hair cells. These findings suggest that simultaneously causing injury and overexpressing Atoh1 promotes hair cell regeneration efficacy and maturity, thus expanding the understanding of ectopic plasticity in neonatal vestibular organs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

An iboga alkaloid chemotaxonomic marker from endemic Tabernaemontana ternifolia with antitubercular activity

In this work, coronaridine (1) was isolated from the CH 2 Cl 2 root extract of Tabernaemontana ternifolia. The structure of 1 was established from 1D- and 2D-NMR and HR-ESIMS experiments, and by comparison with reported spectroscopic data. To date, this is the first report of compound 1 from T. ternifolia, introduced as new Tabernaemontana species from Philippines in 2005 on the basis of morphological characters. Coronaridine, an iboga-type indole alkaloid, has been isolated from over 50 Tabernaemontana species and can thus be inferred as a chemotaxonomic marker of the genus. T. ternifolia has a distinct arrangement of leaves not known in the genus, but is variable in other genera. Its isolation from endemic T. ternifolia establishes its position in the genus and supports the claim that coronaridine is a chemical marker of the genus Tabernaemontana. Interestingly, coronaridine exhibited relatively weak activity against Mycobacterium tuberculosis H 37 Rv (MIC 82.64 μg/mL) (Rifampicin MIC 0.05 μg/mL).

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Isolation of Tryptanthrin and Reassessment of Evidence for Its Isobaric Isostere Wrightiadione in Plants of the Wrightia Genus

A series of Wrightia hanleyi extracts was screened for activity against M. tuberculosis. One active fraction contained a compound that appeared to be either the isoflavonoid wrightiadione or the alkaloid tryptanthrin, both of which have been previously reported in other Wrightia species. Characterization by NMR and high resolution MS as well as evaluation of the literature describing these compounds suggests wrightiadione was misidentified in the first report of its isolation from W. tomentosa 1992 and again in 2015 when reported in W. pubescens and W. religiosa. Instead, the molecule described in these reports and in the present work is almost certainly the isobaric (same nominal mass) and isosteric (same number of atoms, valency, and shape) tryptanthrin, a well-known alkaloid found in a variety of plants including Wrightia species. Tryptanthrin is also accessible synthetically via several routes, and has been thoroughly characterized. True wrightiadione has been synthesized and characterized and may have useful biological activity; however this compound can no longer be said to be known to exist in nature. To our knowledge, this misidentification of wrightiadione has heretofore been unrecognized.

NMR, Alkaloid, Flavanoid, SLIM-MS, Plants, Metabol↗
DOE OSTI2018

Crystal structures of pan-IDH inhibitor AG-881 in complex with mutant human IDH1 and IDH2

Some mutations of isocitrate dehydrogenase 1 and 2 observed in multiple kinds of malignant tumors can lead to a neomorphic enzyme activity that converts alpha-ketoglutarate (α-KG) to 2-hydroxyglutarate (2-HG). As an oncometabolite, 2-HG can cause epigenetic changes and impair cell differentiation. Inhibiting the activity of isocitrate dehydrogenase mutants (mIDH) is considered to be an effective therapy for the treatment of mIDH positive cancers, including glioma and acute myeloid leukemia (AML). The presently disclosed allosteric inhibitors work only on one of the mIDH1 and mIDH2, and it is shown that mIDH1 and mIDH2 have different allosteric inhibition pockets. However, AG-881 from Agios Pharmaceuticals was found to be a pan-IDH inhibitor against both mIDH1 and mIDH2, and is undergoing Phase I clinical trials for tumors with an IDH1 and/or IDH2 mutation. To understand the binding mode of AG-881 to mIDHs, we solved the crystal structures of IDH1-R132H/NADPH/AG-881 and IDH2-R140Q/NADPH/AG-881 complexes, and acquired the IC{sub 50} values of AG-881 for IDH1-R132H and IDH2-R140Q homodimers after different pre-incubation times. Our data show that AG-881 binds IDH1-R132H and IDH2-R140Q in the same allosteric pockets and that the subtle difference in the pockets of these two proteins may contribute to their remarkably different inhibitory kinetics by AG-881. The structural pharmacological data provided in this report may benefit the future development of pan-IDH inhibitors targeting mIDH1 and mIDH2.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Groundwater sustainability and groundwater/surface-water interaction in arid Dunhuang Basin, northwest China

The Dunhuang Basin, a typical inland basin in northwestern China, suffers a net loss of groundwater and the occasional disappearance of the Crescent Lake. Within this region, the groundwater/surface-water interactions are important for the sustainability of the groundwater resources. A three-dimensional transient groundwater flow model was established and calibrated using MODFLOW 2000, which was used to predict changes to these interactions once a water diversion project is completed. The simulated results indicate that introducing water from outside of the basin into the Shule and Danghe rivers could reverse the negative groundwater balance in the Basin. River-water/groundwater interactions control the groundwater hydrology, where river leakage to the groundwater in the Basin will increase from 3,114 × 10{sup 4} m{sup 3}/year in 2017 to 11,875 × 10{sup 4} m{sup 3}/year in 2021, and to 17,039 × 10{sup 4} m{sup 3}/year in 2036. In comparison, groundwater discharge to the rivers will decrease from 3277 × 10{sup 4} m{sup 3}/year in 2017 to 1857 × 10{sup 4} m{sup 3}/year in 2021, and to 510 × 10{sup 4} m{sup 3}/year by 2036; thus, the hydrology will switch from groundwater discharge to groundwater recharge after implementing the water diversion project. The simulation indicates that the increased net river infiltration due to the water diversion project will raise the water table and then effectively increasing the water level of the Crescent Lake, as the lake level is contiguous with the water table. However, the regional phreatic evaporation will be enhanced, which may intensify soil salinization in the Dunhuang Basin. These results can guide the water allocation scheme for the water diversion project to alleviate groundwater depletion and mitigate geo-environmental problem.

58 GEOSCIENCES↗