Accurate estimation of biological age and its application in disease prediction using a multimodal image Transformer system.

Aging in an individual refers to the temporal change, mostly decline, in the body's ability to meet physiological demands. Biological age (BA) is a biomarker of chronological aging and can be used to stratify populations to predict certain age-related chronic diseases. BA can be predicted from biomedical features such as brain MRI, retinal, or facial images, but the inherent heterogeneity in the aging process limits the usefulness of BA predicted from individual body systems. In this paper, we developed a multimodal Transformer-based architecture with cross-attention which was able to combine facial, tongue, and retinal images to estimate BA. We trained our model using facial, tongue, and retinal images from 11,223 healthy subjects and demonstrated that using a fusion of the three image modalities achieved the most accurate BA predictions. We validated our approach on a test population of 2,840 individuals with six chronic diseases and obtained significant difference between chronological age and BA (AgeDiff) than that of healthy subjects. We showed that AgeDiff has the potential to be utilized as a standalone biomarker or conjunctively alongside other known factors for risk stratification and progression prediction of chronic diseases. Our results therefore highlight the feasibility of using multimodal images to estimate and interrogate the aging process.

Homologous or heterogenous vaccination boosters enhance neutralizing activities against SARS-CoV-2 Omicron BA.1 variant.

The SARS-CoV-2 Omicron BA.1 variant of concern contains more than 30 mutations in the spike protein, with half of these mutations localized in the receptor-binding domain (RBD). Emerging evidence suggests that these large number of mutations impact the neutralizing efficacy of vaccines and monoclonal antibodies. We investigated the relative contributions of spike protein and RBD mutations in Omicron BA.1 variants on infectivity, cell-cell fusion, and their sensitivity to neutralization by monoclonal antibodies or vaccinated sera from individuals who received homologous (CoronaVac, SinoPharm) or heterologous (CoronaVac-BNT162b2, BioNTech) and nonhuman primates that received a recombinant RBD protein vaccine. Our data overall reveal that the mutations in the spike protein reduced infectivity and cell-cell fusion compared to the D614G variant. The impaired infectivity and cell-cell fusion were dependent on non-RBD mutations. We also find reduced sensitivity to neutralization by monoclonal antibodies and vaccinated sera. However, our results also show that nonhuman primates receiving a recombinant RBD protein vaccine show substantial neutralization activity. Our study sheds light on the molecular differences in neutralizing antibody escape by the Omicron BA.1 variant, and highlights the promise of recombinant RBD vaccines in neutralizing the threat posed by the Omicron BA.1 variant.

A bivalent vaccine containing D614G and BA.1 spike trimer proteins or a BA.1 spike trimer protein booster shows broad neutralizing immunity.

The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, sublineages BA.1 and BA.2, recently became the dominant variants of concern (VOCs) with significantly higher transmissibility than any other variant appeared and markedly greater resistance to neutralization antibodies and original ancestral WA1 spike-matched vaccine. Therefore, it is urgent to develop vaccines against VOCs like Omicron. Unlike the new booming messenger RNA (mRNA) vaccine, protein vaccines have been used for decades to protect people from various kinds of viral infections and have advantages with their inexpensive production protocols and their relative stability in comparison to the mRNA vaccine. Here, we show that sera from BA.1 spike protein vaccinated mice mainly elicited neutralizing antibodies against BA.1 itself. However, a booster with BA.1 spike protein or a bivalent vaccine composed of D614G and BA.1 spike protein-induced not only potent neutralizing antibody response against D614G and BA.1 pseudovirus, but also against BA.2, other four SARS-CoV-2 VOCs (Alpha, Beta, Gamma, and Delta) and SARS-CoV-2-related coronaviruses (pangolin CoV GD-1 and bat CoV RsSHC014). The two recombinant spike protein vaccines method described here lay a foundation for future vaccine development for broad protection against pan-sarbecovirus.

Construction of hybrid DNAs@CP for the rapid synchronous sensing of multiplex microRNAs based on experimental studies and molecular simulation.

A water stable one-dimensional (1D) ladder-shaped coordination polymer (CP) has been synthesized and exhibits a strong affinity to two fluorescein-tagged single-stranded probe DNAs (P-DNAs), giving a sensing platform of P-DNAs@1. Such a hybrid sensing platform is capable of simultaneous detection of breast cancer related microRNA-221 (miRNA-221) and miRNA-222 in a specific and synchronous manner, without observable cross-reactions, as supported by experimental evidences. The interaction mode and the electronic energy between CP 1 with nucleic acid were confirmed by molecular simulation and the universal force field (UFF).

A metal-organic framework based PCR-free biosensor for the detection of gastric cancer associated microRNAs.

We report herein five sensing platforms for the detection of five gastric cancer associated microRNAs (miRNAs). The sensing platforms are hybrids formed from a water-stable metal organic framework (MOF) {[Cu(dcbb)2(H2O)2]·10H2O}n (1, H2dcbbBr=1-(3,5-dicarboxybenzyl)-4,4'-bipyridinium bromide), respectively with five carboxyfluorescein (FAM) labeled probe single-stranded DNA (probe ss-DNA, denoted as P-DNA). Within the hybrid, MOF 1 tightly interacts with the P-DNA through electrostatic and/or π-stacking interactions and results in fluorescence quenching of FAM via a photo-induced electron transfer (PET) process. In the presence of the complementary target miRNAs miR-185, miR-20a, miR-92b, miR-25 and miR-210, which are expressed abnormally in the plasma of gastric carcinoma patients, P-DNA is released from the surface of MOF 1 ascribed to the stronger base pair matching, leading to the FAM fluorescence recovery. Each P-DNA@1 system is effective and reliable for the detection of its complementary target miRNA with the detection limits from 91 to 559pM, and is not interfered by other four miRNA sequences.