Free-Bloom: Zero-Shot Text-to-Video Generator with LLM Director and LDM Animator

Text-to-video is a rapidly growing research area that aims to generate a semantic, identical, and temporal coherence sequence of frames that accurately align with the input text prompt. This study focuses on zero-shot text-to-video generation considering the data- and cost-efficient. To generate a semantic-coherent video, exhibiting a rich portrayal of temporal semantics such as the whole process of flower blooming rather than a set of "moving images", we propose a novel Free-Bloom pipeline that harnesses large language models (LLMs) as the director to generate a semantic-coherence prompt sequence, while pre-trained latent diffusion models (LDMs) as the animator to generate the high fidelity frames. Furthermore, to ensure temporal and identical coherence while maintaining semantic coherence, we propose a series of annotative modifications to adapting LDMs in the reverse process, including joint noise sampling, step-aware attention shift, and dual-path interpolation. Without any video data and training requirements, Free-Bloom generates vivid and high-quality videos, awe-inspiring in generating complex scenes with semantic meaningful frame sequences. In addition, Free-Bloom is naturally compatible with LDMs-based extensions.Comment: NeurIPS 2023; Project available at: https://github.com/SooLab/Free-Bloo

Modeling Method for Increased Precision and Scope of Directly Measurable Fluxes at a Genome-Scale

Metabolic flux analysis (MFA) is considered to be the gold standard for determining the intracellular flux distribution of biological systems. The majority of work using MFA has been limited to core models of metabolism due to challenges in implementing genome-scale MFA and the undesirable trade-off between increased scope and decreased precision in flux estimations. This work presents a tunable workflow for expanding the scope of MFA to the genome-scale without trade-offs in flux precision. The genome-scale MFA model presented here, iDM2014, accounts for 537 net reactions, which includes the core pathways of traditional MFA models and also covers the additional pathways of purine, pyrimidine, isoprenoid, methionine, riboflavin, coenzyme A, and folate, as well as other biosynthetic pathways. When evaluating the iDM2014 using a set of measured intracellular intermediate and cofactor mass isotopomer distributions (MIDs), it was found that a total of 232 net fluxes of central and peripheral metabolism could be resolved in the <i>E. coli</i> network. The increase in scope was shown to cover the full biosynthetic route to an expanded set of bioproduction pathways, which should facilitate applications such as the design of more complex bioprocessing strains and aid in identifying new antimicrobials. Importantly, it was found that there was no loss in precision of core fluxes when compared to a traditional core model, and additionally there was an overall increase in precision when considering all observable reactions

Evolution of gene knockout strains of <i>E-coli</i> reveal regulatory architectures governed by metabolism

The function of metabolic genes in the context of regulatory networks is not well understood. Here, the authors investigate the adaptive responses of E. coli after knockout of metabolic genes and highlight the influence of metabolite levels in the evolution of regulatory function

Multiple Optimal Phenotypes Overcome Redox and Glycolytic Intermediate Metabolite Imbalances in <i>Escherichia coli pgi</i> Knockout Evolutions

A mechanistic understanding of how new phenotypes develop to overcome the loss of a gene product provides valuable insight on both the metabolic and regulatory functions of the lost gene. The pgi gene, whose product catalyzes the second step in glycolysis, was deleted in a growth-optimized Escherichia coli K-12 MG1655 strain. The initial knockout (KO) strain exhibited an 80% drop in growth rate that was largely recovered in eight replicate, but phenotypically distinct, cultures after undergoing adaptive laboratory evolution (ALE). Multi-omic data sets showed that the loss of pgi substantially shifted pathway usage, leading to a redox and sugar phosphate stress response. These stress responses were overcome by unique combinations of innovative mutations selected for by ALE. Thus, the coordinated mechanisms from genome to metabolome that lead to multiple optimal phenotypes after the loss of a major gene product were revealed.IMPORTANCE A mechanistic understanding of how microbes are able to overcome the loss of a gene through regulatory and metabolic changes is not well understood. Eight independent adaptive laboratory evolution (ALE) experiments with pgi knockout strains resulted in eight phenotypically distinct endpoints that were able to overcome the gene loss. Utilizing multi-omics analysis, the coordinated mechanisms from genome to metabolome that lead to multiple optimal phenotypes after the loss of a major gene product were revealed

Design, Synthesis, Biological Evaluation, and Preliminary Mechanistic Study of a Novel Mitochondrial-Targeted Xanthone

&alpha;-Mangostin, a natural xanthone, was found to have anticancer effects, but these effects are not sufficient to be effective. To increase anticancer potential and selectivity, a triphenylphosphonium cation moiety (TPP) was introduced to &alpha;-mangostin to specifically target cancer cell mitochondria. Compared to the parent compound, the cytotoxicity of the synthesized compound 1b increased by one order of magnitude. Mechanistic analysis revealed that the anti-tumor effects were involved in the mitochondrial apoptotic pathway by prompting apoptosis and arresting the cell cycle at the G0/G1 phase, increasing the production of reactive oxygen species (ROS), and reducing mitochondrial membrane potential (&Delta;&psi;m). More notably, the antitumor activity of compound 1b was further confirmed by zebrafish models, which remarkably inhibited cancer cell proliferation and migration, as well as zebrafish angiogenesis. Taken together, our results for the first time indicated that TPP-linked 1b could lead to the development of new mitochondrion-targeting antitumor agents

Design, Synthesis, Biological Evaluation, and Preliminary Mechanistic Study of a Novel Mitochondrial-Targeted Xanthone

α-Mangostin, a natural xanthone, was found to have anticancer effects, but these effects are not sufficient to be effective. To increase anticancer potential and selectivity, a triphenylphosphonium cation moiety (TPP) was introduced to α-mangostin to specifically target cancer cell mitochondria. Compared to the parent compound, the cytotoxicity of the synthesized compound 1b increased by one order of magnitude. Mechanistic analysis revealed that the anti-tumor effects were involved in the mitochondrial apoptotic pathway by prompting apoptosis and arresting the cell cycle at the G0/G1 phase, increasing the production of reactive oxygen species (ROS), and reducing mitochondrial membrane potential (Δψm). More notably, the antitumor activity of compound 1b was further confirmed by zebrafish models, which remarkably inhibited cancer cell proliferation and migration, as well as zebrafish angiogenesis. Taken together, our results for the first time indicated that TPP-linked 1b could lead to the development of new mitochondrion-targeting antitumor agents