Multimodal deep learning using on-chip diffractive optics with in situ training capability.

Multimodal deep learning plays a pivotal role in supporting the processing and learning of diverse data types within the realm of artificial intelligence generated content (AIGC). However, most photonic neuromorphic processors for deep learning can only handle a single data modality (either vision or audio) due to the lack of abundant parameter training in optical domain. Here, we propose and demonstrate a trainable diffractive optical neural network (TDONN) chip based on on-chip diffractive optics with massive tunable elements to address these constraints. The TDONN chip includes one input layer, five hidden layers, and one output layer, and only one forward propagation is required to obtain the inference results without frequent optical-electrical conversion. The customized stochastic gradient descent algorithm and the drop-out mechanism are developed for photonic neurons to realize in situ training and fast convergence in the optical domain. The TDONN chip achieves a potential throughput of 217.6 tera-operations per second (TOPS) with high computing density (447.7 TOPS/mm2), high system-level energy efficiency (7.28 TOPS/W), and low optical latency (30.2 ps). The TDONN chip has successfully implemented four-class classification in different modalities (vision, audio, and touch) and achieve 85.7% accuracy on multimodal test sets. Our work opens up a new avenue for multimodal deep learning with integrated photonic processors, providing a potential solution for low-power AI large models using photonic technology.

DosR's multifaceted role on Mycobacterium bovis BCG revealed through multi-omics.

Mycobacterium tuberculosis (Mtb) is an intracellular bacterium that causes a highly contagious and potentially lethal tuberculosis (TB) in humans. It can maintain a dormant TB infection within the host. DosR (dormancy survival regulator) (Rv3133c) has been recognized as one of the key transcriptional proteins regulating bacterial dormancy and participating in various metabolic processes. In this study, we extensively investigate the still not well-comprehended role and mechanism of DosR in Mycobacterium bovis (M. bovis) Bacillus Calmette-Guérin (BCG) through a combined omics analysis. Our study finds that deleting DosR significantly affects the transcriptional levels of 104 genes and 179 proteins. Targeted metabolomics data for amino acids indicate that DosR knockout significantly upregulates L-Aspartic acid and serine synthesis, while downregulating seven other amino acids, including L-histidine and lysine. This suggests that DosR regulates amino acid synthesis and metabolism. Taken together, these findings provide molecular and metabolic bases for DosR effects, suggesting that DosR may be a novel regulatory target.

DosR Regulates the Transcription of the Arginine Biosynthesis Gene Cluster by Binding to the Regulatory Sequences in Mycobacterium bovis Bacille Calmette-Guerin.

l-Arginine serves as a carbon and nitrogen source and is critical for Mycobacterium tuberculosis (Mtb) survival in the host. Generally, ArgR acts as a repressor regulating arginine biosynthesis by binding to the promoter of the argCJBDFGH gene cluster. In this study, we report that the dormancy regulator DosR is a novel arginine regulator binding to the promoter region of argC (rv1652), which regulates arginine synthesis. Phosphorylation modification promoted DosR binding to a region upstream of the promoter. Cofactors, including arginine and metal ions, had an inhibitory effect on this association. Furthermore, DosR regulatory function relies on the interaction of the 167, 181, 182, and 197 amino acid residues with an inverse complementary sequence. Arginine also binds to DosR and directly affects its DNA-binding ability. Together, the results demonstrate that DosR acts as a novel transcriptional regulator of arginine synthesis in Mycobacterium bovis bacille Calmette-Guerin.

Vitamin B and Vitamin C Affect DNA Methylation and Amino Acid Metabolism in Mycobacterium bovis BCG.

Vitamins are essential nutrients and key cofactors of enzymes that regulate cellular metabolism, and also activate the immune system. Recent studies have shown that vitamin B1 (VB 1) and vitamin C (Vc) can inhibit Mycobacterium tuberculosis growth, but the precise mechanism is still not well understood. In the present study, we have used RNA-sequencing (RNA-seq), liquid chromatography coupled to mass spectrometry (LC-MS) and single-molecule real-time (SMRT) sequencing to analyze the transcriptional, metabolic and methylation profiles of Mycobacterium bovis BCG when treated with VB 1 and Vc. Our results show that, after vitamin treatment, variant metabolites were mainly clustered in pathways related to amino acid metabolism. Treatment with both vitamins significantly up-regulated the gene encoding cysteine synthase A. Additionally, only BCG that was treated with VC showed m4c modifications. Genes harboring this methylation were up-regulated, suggesting that m4c methylation can promote gene transcription to some extent. Overall, this study contributes to the understanding of the effects of VB 1 and VC, and suggests that these vitamins constitute potential anti-tuberculosis drugs.