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The development of safe and effective vaccines to respond to COVID-19 pandemic/endemic remains a priority. We developed a novel subunit protein-peptide COVID-19 vaccine candidate (UB-612) composed of: (i) receptor binding domain of SARS-CoV-2 spike protein fused to a modified single-chain human IgG1 Fc; (ii) five synthetic peptides incorporating conserved helper and cytotoxic T lymphocyte (Th/CTL) epitopes derived from SARS-CoV-2 structural proteins (three from S2 subunit, one from membrane and one from nucleocapsid), and one universal Th peptide; (iii) aluminum phosphate as adjuvant. The immunogenicity and protective immunity induced by UB-612 vaccine were evaluated in four animal models: Sprague–Dawley rats, AAV-hACE2 transduced BALB/c mice, rhesus and cynomolgus macaques. UB-612 vaccine induced high levels of neutralizing antibody and T-cell responses, in all animals. The immune sera from vaccinated animals neutralized the SARS-CoV-2 original wild-type strains and multiple variants of concern, including Delta and Omicron. The vaccination significantly reduced viral loads, lung pathology scores, and disease progression after intranasal and intratracheal challenge with SARS-CoV-2 in mice, rhesus and cynomolgus macaques. UB-612 has been tested in primary regimens in Phase 1 and Phase 2 clinical studies and is currently being evaluated in a global pivotal Phase 3 clinical study as a single dose heterologous booster.

Most forest soils contain substantial amounts of gravel. However, unlike the more widely known root resource uptake behaviors which respond to resource patches in substrate without gravels, how roots respond to substrate containing different gravel levels is poorly understood. We grew roots in substrates with five gravel levels (0%, 10%, 20%, 30%, and 40% of volume) in a subtropical Schima superba Gardn. et Champ plantation, determined fine root dynamics and turnover rate with minirhizotrons, measured fine root morphological, architectural, mycorrhizal colonization, chemistry, and mass allocation. The presence of gravel in the substrate delayed the timing of peak root growth. In the substrate with higher gravel content, plants produced more in roots in autumn, but there were fewer roots in summer and the roots tended to exhibit lower fine root turnover rate and mycorrhizal colonization, but higher root biomass allocation. The higher root biomass in the substrate with higher gravel content was associated with higher root carbon/nitrogen ratio. Our findings emphasize the complexity of root resource uptake behavior in response to gravel content and suggest that incorporating substrate gravel content into root studies may help to improve the prediction of patch exploitation and nutrient acquisition in stony soils. Key words: heterogeneous patches, root phenology, root morphology, root architecture, mycorrhizal colonization. La plupart des sols forestiers contiennent des quantites substantielles de gravier. Cependant, contrairement aux comportements plus largement connus concernant le prelevement des ressources par les racines qui reagissent a des ilots riches en ressources dans un substrat exempt de gravier, la facon dont les racines reagissent a un substrat qui contient differentes quantites de gravier est mal connue. Nous avons fait croitre les racines dans des substrats contenant differentes proportions (cinq) de gravier (0%, 10%, 20%, 30% et 40% du volume) dans une plantation subtropicale de Schima superba Gardn. et Champ; determine la dynamique et le taux de renouvellement des racines fines a l'aide de minirhizotrons; mesure la morphologie, l'architecture, la colonisation mycorhizienne et les caracteristiques chimiques des racines fines ainsi que la repartition de la biomasse. La presence de gravier dans le substrat a retarde le moment ou la croissance des racines a atteint son niveau maximum. Dans le substrat contenant le plus de gravier, la plus forte croissance est survenue dans les racines a l'automne. Par contre les racines etaient moins abondantes durant l'ete et le taux de renouvellement ainsi que la colonisation mycorhizienne des racines fines avaient tendance a etre plus faibles, mais l'allocation de biomasse racinaire etait plus prononcee. La biomasse racinaire plus elevee dans le substrat contenant le plus de gravier etait associee a un rapport carbone:azote plus eleve dans les racines. Nos resultats font ressortir la complexite du comportement relie au prelevement des ressources par les racines en reaction a la teneur en gravier et indiquent que l'incorporation de la teneur en gravier du substrat dans les etudes portant sur les racines pourrait contribuer a ameliorer la prediction de l'exploitation des ilots riches en ressources et l'acquisition des elements nutritifs dans les sols pierreux. [Traduit par la Redaction] Mots-cles : ilots heterogenes, phenologie racinaire, morphologie racinaire, architecture racinaire, colonisation mycorhizienne., 1. Introduction Resources in soil are heterogeneously distributed. Understanding fine root resource uptake strategies in heterogeneous patches is of primary importance for predicting plant growth and adaptation to changing environments [...]

The performance of the beamformer, especially the beamformer based on the interference plus noise covariance matrix (INCM) reconstruction which needs accurate array manifold knowledge, will degrade dramatically in the presence of gain-phase errors. To solve this problem, we propose a robust adaptive beamforming method based on partly calibrated arrays (PCA). The main idea of this method is to estimate the gain-phase errors more accurately using the higher signal-to-noise ratio (SNR) signal sources and the PCA. After that, we calibrate the interference signal steering vector (SV) and reconstruct the more accurate INCM based on the estimation results. Finally, the SV of the desired signal is estimated by the intersection of two special subspaces. On the basis of the above research, the optimal weight vector is obtained. Numerical simulation results demonstrate the superior performance of the proposed beamformer relative to other existing beamformers in the presence of gain-phase errors. [ABSTRACT FROM AUTHOR]

Introduction: Microglia are the main phagocytes in the brain and can induce neuroinflammation. Moreover, they are critical to alpha‐synuclein (α‐syn) aggregation and propagation. Plasma exosomes derived from patients diagnosed with Parkinson's disease (PD‐exo) reportedly evoked α‐syn aggregation and inflammation in microglia. In turn, microglia internalized and released exosomal α‐syn, enhancing α‐syn propagation. However, the specific mechanism through which PD‐exo influences α‐syn degradation remains unknown. Methods: Exosomes were extracted from the plasma of patients with PD by differential ultracentrifugation, analyzed using electron microscopy (EM) and nanoparticle flow cytometry, and stereotaxically injected into the unilateral striatum of the mice. Transmission EM was employed to visualize lysosomes and autophagosomes in BV2 cells, and lysosome pH was measured with LysoSensor Yellow/Blue DND‐160. Cathepsin B and D, lysosomal‐associated membrane protein 1 (LAMP1), ATP6V1G1, tumor susceptibility gene 101 protein, calnexin, α‐syn, ionized calcium binding adaptor molecule 1, and NLR family pyrin domain containing 3 were evaluated using quantitative polymerase chain reaction or western blotting, and α‐syn, LAMP1, and ATP6V1G1 were also observed by immunofluorescence. Small interfering ribonucleic acid against V1G1 was transfected into BV2 cells and primary microglia using Lipofectamine® 3000. A PD mouse model was established via injection with 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) into mice. A lentiviral‐mediated strategy to overexpress ATP6V1G1 in the brain of MPTP‐treated mice was employed. Motor coordination was assessed using rotarod and pole tests, and neurodegeneration in the mouse substantia nigra and striatum tissues was determined using immunofluorescence histochemical and western blotting of tyrosine hydroxylase. Results: PD‐exo decreased the expression of V1G1, responsible for the acidification of intra‐ and extracellular milieu. This impairment of lysosomal acidification resulted in the accumulation of abnormally swollen lysosomes and decreased lysosomal enzyme activities, impairing lysosomal protein degradation and causing α‐syn accumulation. Additionally, V1G1 overexpression conferred the mice neuroprotection during MPTP exposure. Conclusion: Pathogenic protein accumulation is a key feature of PD, and compromised V‐type ATPase dysfunction might participate in PD pathogenesis. Moreover, V1G1 overexpression protects against neuronal toxicity in an MPTP‐based PD mouse model, which may provide opportunities to develop novel therapeutic interventions for PD treatment. [ABSTRACT FROM AUTHOR]