Light-induced programmable solid-liquid phase transition of biomolecular condensates for improved biosynthesis.

Keeping condensates in liquid-like states throughout the biosynthesis process in microbial cell factories remains an ongoing challenge. Here, we present a light-controlled phase regulator, which maintains the liquid-like features of synthetic condensates on demand throughout the biosynthesis process upon light induction, as demonstrated by various live cell-imaging techniques. Specifically, the tobacco etch virus (TEV) protease controlled by light cleaves intrinsically disordered proteins (IDPs) to alter their valency and concentration for controlled phase transition and programmable fluidity of cellular condensates.

Multiplexed engineering of cytochrome P450 enzymes for promoting terpenoid synthesis in Saccharomyces cerevisiae cell factories: A review.

Terpenoids, also known as isoprenoids, represent the largest and most structurally diverse family of natural products, and their biosynthesis is closely related to cytochrome P450 enzymes (P450s). Given the limitations of direct extraction from natural resources, such as low productivity and environmental concerns, heterologous expression of P450s in microbial cell factories has emerged as a promising, efficient, and sustainable strategy for terpenoid production. The yeast expression system is a preferred selection for terpenoid synthesis because of its inner membrane system, which is required for eukaryotic P450 expression, and the inherent mevalonate pathway providing precursors for terpenoid synthesis.

CarveAdornCurate: a versatile cloud-based platform for constructing multiscale metabolic models.

Multiscale modeling is a promising approach for understanding cellular behaviors. However, existing multiscale modeling tools require meticulously curated genome-scale metabolic models (GEMs) as inputs, limiting the broad applications of multiscale models due to complex and time-consuming construction processes. To this end, we developed a novel workflow named CarveAdornCurate (CAC) for de novo multiscale modeling.

Production of caproate from lactate by chain elongation under electro-fermentation: Dual role of exogenous ethanol electron donor.

Ethanol and lactate as co-electron donors (co-EDs) on chain elongation (CE) have been studied, however, the effects of ethanol on lactate-driven CE remain unknown. This study evaluated the caproate production performance from lactate under different ethanol additions (7.67-23.

Investigating shared risk variants and genetic etiology between Alzheimer's disease and three stress-related psychiatric disorders: a large-scale genome-wide cross-trait analysis.

Introduction: Observational studies have reported that patients with Alzheimer's disease (AD) have a greater burden of comorbidities typically associated with stress-related psychiatric disorders. However, the contribution of hereditary factors to this comorbidity remains unclear. We evaluated phenotypic associations using observational data from the UK Biobank.

Pharmacogenomics-based subtype decoded implications for risk stratification and immunotherapy in pancreatic adenocarcinoma.

Background: With fatal malignant peculiarities and poor survival rate, outcomes of pancreatic adenocarcinoma (PAAD) were frustrated by non-response and even resistance to therapy due to heterogeneity across clinical patients. Nevertheless, pharmacogenomics has been developed for individualized-treatment and still maintains obscure in PAAD.

Methods: A total of 964 samples from 10 independent multi-center cohorts were enrolled in our study.

Assessing physical literacy and establishing normative reference curves for 8-12-year-old children from South Punjab, Pakistan: The PAK-IPPL cross-sectional study.

Background: Physical literacy (PL) encompasses an individual's motivation, confidence, physical competence, and knowledge, all of which foster lifelong engagement in physical activities. In developing countries like Pakistan, there is a pressing need to assess PL status using culturally valid tools. This study aims to evaluate PL among children aged 8-12 in South Punjab, Pakistan while developing normative reference curves and exploring factors influencing PL.

Acid/halide co-mediated transesterification of unactivated carboxylic esters with O-H nucleophiles.

The transesterification of unactivated carboxylic esters with alcohols was achieved in one pot through acid/halide cooperative catalysis. By this strategy, various weakly nucleophilic phenols could react with unactivated methyl esters to produce the corresponding phenolic esters in good to high yields. Aliphatic alcohols could also be used as the nucleophiles and showed higher reactivity.

An evolved, orthogonal ssDNA generator for targeted hypermutation of multiple genomic loci.

Achieving targeted hypermutation of specific genomic sequences without affecting other regions remains a key challenge in continuous evolution. To address this, we evolved a T7 RNA polymerase (RNAP) mutant that synthesizes single-stranded DNA (ssDNA) instead of RNA in vivo, while still exclusively recognizing the T7 promoter. By increasing the error rate of the T7 RNAP mutant, it generates mutated ssDNA that recombines with homologous sequences in the genome, leading to targeted genomic hypermutation.

Efficient discovery of robust prognostic biomarkers and signatures in solid tumors.

Recent advancements in multi-omics and big-data technologies have facilitated the discovery of numerous cancer prognostic biomarkers and gene signatures. However, their clinical application remains limited due to poor reproducibility and insufficient independent validation. Despite the availability of high-quality datasets, achieving reliable biomarker identification across multiple cohorts continues to be a significant challenge.

[Metabolic engineering of for efficient biosynthesis of L-citrulline].

L-citrulline is a nonprotein amino acid that plays an important role in human health and has great market demand. Although microbial cell factories have been widely used for biosynthesis, there are still challenges such as genetic instability and low efficiency in the biosynthesis of L-citrulline. In this study, an efficient, plasmid-free, non-inducible L-citrulline-producing strain of BL21(DE3) was engineered by combined strategies.

Analysis of the service needs of outpatients undergoing thyroid fine needle aspiration biopsy based on the Kano model.

Background: Thyroid nodules are common, and fine needle aspiration biopsy (FNAB) is essential for diagnosis and treatment. Patients' service needs are rarely addressed and discussed. This study was to analyze the nursing service needs of patients undergoing outpatient thyroid FNAB.

A cross-species inducible system for enhanced protein expression and multiplexed metabolic pathway fine-tuning in bacteria.

Inducible systems are crucial to metabolic engineering and synthetic biology, enabling organisms that function as biosensors and produce valuable compounds. However, almost all inducible systems are strain-specific, limiting comparative analyses and applications across strains rapidly. This study designed and presented a robust workflow for developing the cross-species inducible system.

De novo biosynthesis of mogroside V by multiplexed engineered yeasts.

High sugar intake has become a global health concern due to its association with various diseases. Mogroside V (MG-V), a zero-calorie sweetener with multiple medical properties, is emerging as a promising sugar substitute. However, its application is hindered by low natural abundance and the inefficiency of conventional plant extraction methods.

CRISPR/Cas13X-assisted programmable and multiplexed translation regulation for controlled biosynthesis.

Developing efficient gene regulation tools is essential for optimizing microbial cell factories, but most existing tools only modulate gene expression at the transcriptional level. Regulation at the translational level provides a faster dynamic response, whereas developing a programmable, efficient and multiplexed translational regulation tool remains a challenge. Here, we have developed CRISPRi and CRISPRa systems based on hfCas13X that can regulate gene translation in Bacillus subtilis.

Correlation Among Psoriasis, Iridocyclitis, and Non-alcoholic Fatty Liver Disease: Insights from Mendelian Randomization and Mediation Analysis.

The aim of this study is to utilize two-sample Mendelian randomization (MR) to investigate the potential causal relationship among psoriasis, iridocyclitis, and non-alcoholic fatty liver disease (NAFLD), and to explore any potential mediation effects. Pooled data were derived from the public genome-wide association study (GWAS) in NAFLD (finn-b-NAFLD), iridocyclitis (finn-b-H7_IRIDOCYCLITIS) and psoriasis (finn-b-L12_PSORI_VULG). Univariable MR (UVMR) analysis was implemented to explore the causal relationship among psoriasis, iridocyclitis, and NAFLD, and inverse variance weighting (IVW) was used as the primary analytical method.

THBS2 + cancer-associated fibroblasts promote EMT leading to oxaliplatin resistance via COL8A1-mediated PI3K/AKT activation in colorectal cancer.

Cancer-associated fibroblasts (CAFs) exert multiple tumor-promoting functions and are key contributors to drug resistance. The mechanisms by which specific subsets of CAFs facilitate oxaliplatin resistance in colorectal cancer (CRC) have not been fully explored. This study found that THBS2 is positively associated with CAF activation, epithelial-mesenchymal transition (EMT), and chemoresistance at the pan-cancer level.

Improving Cellular Protein Content of Based on Adaptive Evolution and Flow Cytometry-Aided High Throughput Screening.

Enhancing the protein content and production efficiency of is crucial as an alternative protein source. This study screened nongenetically modified yeast strains with high protein content for food ingredient production and explored the underlying mechanisms. Yeast protein levels were found to correlate with RNA, leading to a high-throughput screening method using RNA fluorescence and flow cytometry.

De novo 2'-fucosyllactose biosynthesis using glucose as the sole carbon source by multiple engineered Bacillus subtilis.

2'-Fucosyllactose (2'-FL) is the most abundant human milk oligosaccharide and plays significant roles in gut microbiome balance, neural development, and immunoregulation. However, current fermentation schemes using multiple carbon sources increase production cost and metabolism burden. This study reported the development of an engineered Bacillus subtilis strain that produces 2'-FL using glucose as the sole carbon source.

Harnessing microbial heterogeneity for improved biosynthesis fueled by synthetic biology.

Metabolic engineering-driven microbial cell factories have made great progress in the efficient bioproduction of biochemical and recombinant proteins. However, the low efficiency and robustness of microbial cell factories limit their industrial applications. Harnessing microbial heterogeneity contributes to solving this.

Engineering microbial cell factories by multiplexed spatiotemporal control of cellular metabolism: Advances, challenges, and future perspectives.

Generally, the metabolism in microbial organism is an intricate, spatiotemporal process that emerges from gene regulatory networks, which affects the efficiency of product biosynthesis. With the coming age of synthetic biology, spatiotemporal control systems have been explored as versatile strategies to promote product biosynthesis at both spatial and temporal levels. Meanwhile, the designer synthetic compartments provide new and promising approaches to engineerable spatiotemporal control systems to construct high-performance microbial cell factories.

The T cell-mediated tumor killing patterns revealed tumor heterogeneous and proposed treatment recommendation in ovary cancer.

Background: Immune checkpoint inhibitors (ICIs) have greatly improved cancer treatment, but the role of genes related to T cell-mediated tumor killing (TTK) sensitivity in ovarian cancer (OV) is unclear.

Methods: This study analyzed 1367 OV patients and 11 independent cohorts. The unsupervised clustering was conducted to identify three tumor subtypes based on genes that regulate tumor cell sensitivity to TTK (GSTTKs).