Xing Zhang

Current methods for imaging glycosylated RNAs (glycoRNAs) rely on sequence‐specific recognition or bulky DNA nanostructures, which compromise spatial fidelity and largely confine applications to simplified cell systems. Here, we report a Co valent M olecular P roximity Ass ay (COMPASS) that enables sequence‐independent visualization of glycoRNAs in complex physiological contexts. COMPASS integrates orthogonal encoding with proximity‐gated signal readout. Through chemoselective precursor uptake, azide groups are installed on terminal sialic acids and alkyne groups on nascent uridine residues, establishing a dual‐encoded chemical framework. Independent analysis confirmed the efficient installation of both functionalities. Subsequent dual‐color click labeling introduces donor and acceptor fluorophores to these orthogonal handles, producing sensitized acceptor emission when they are located in the same glycoRNA molecule. Accordingly, COMPASS reports the metabolically labeled, sialylated, uridine‐containing glycoRNA population generated during the labeling window. This design eliminates the need for bulky nucleic acid probes, reduces probe‐induced signal spreading, and enables glycoRNA imaging across diverse systems, including cell cultures, cerebral organoids, and mouse tissues. COMPASS revealed spatially heterogeneous glycoRNA‐associated signals, including relatively stronger signals near lumen‐adjacent VZ‐like regions of cerebral organoids and lower signals in pulmonary metastatic nodules. These observations establish spatial associations with neurodevelopmental and tumor‐associated states.

Current methods for imaging glycosylated RNAs (glycoRNAs) rely on sequence‐specific recognition or bulky DNA nanostructures, which compromise spatial fidelity and largely confine applications to simplified cell systems. Here, we report a Co valent M olecular P roximity Ass ay (COMPASS) that enables sequence‐independent visualization of glycoRNAs in complex physiological contexts. COMPASS integrates orthogonal encoding with proximity‐gated signal readout. Through chemoselective precursor uptake, azide groups are installed on terminal sialic acids and alkyne groups on nascent uridine residues, establishing a dual‐encoded chemical framework. Independent analysis confirmed the efficient installation of both functionalities. Subsequent dual‐color click labeling introduces donor and acceptor fluorophores to these orthogonal handles, producing sensitized acceptor emission when they are located in the same glycoRNA molecule. Accordingly, COMPASS reports the metabolically labeled, sialylated, uridine‐containing glycoRNA population generated during the labeling window. This design eliminates the need for bulky nucleic acid probes, reduces probe‐induced signal spreading, and enables glycoRNA imaging across diverse systems, including cell cultures, cerebral organoids, and mouse tissues. COMPASS revealed spatially heterogeneous glycoRNA‐associated signals, including relatively stronger signals near lumen‐adjacent VZ‐like regions of cerebral organoids and lower signals in pulmonary metastatic nodules. These observations establish spatial associations with neurodevelopmental and tumor‐associated states.

Metal–organic frameworks (MOFs) are promising host matrices for molecular encapsulation, yet their application is often limited by fixed pore apertures that exclude guest molecules larger than the pore openings. Herein, we overcome this limitation by electronic tuning of dynamic imine bonds to induce reversible pore gating that transiently expands framework accessibility beyond its intrinsic aperture. By incorporating imine-based linkers bearing electron-donating/withdrawing substituents into a robust Zr-based MOF scaffold via postsynthetic linker exchange, we systematically modulate imine dissociation equilibria while preserving crystallinity. A linear correlation between Hammett substituent constants and imine bond stability establishes electronic effects as a predictive handle for programming framework dynamics. Systematic variation of substituents establishes an optimal metastable regime in which reversible linker dissociation permits size-adaptive guest uptake without structural degradation. As a proof of concept, paclitaxel and other therapeutics are efficiently encapsulated, and the resulting materials exhibit good biocompatibility together with programmable, environment-responsive release kinetics under physiological conditions.

Semiconductor biohybrid systems integrate microbial biosynthesis with semiconductor light harvesting to sustainably power energy‐intensive chemical production. Although such systems have been widely explored in photosynthetic bacteria, extending them to non‐photosynthetic biomanufacturing chassis such as Bacillus subtilis ( B. subtilis ) remains substantially more challenging, owing to peptidoglycan‐induced nanoparticle aggregation and mass‐transfer limitations, cytotoxicity, and inefficient interfacial electron transfer from loose adsorption between inorganic semiconductors and cells. Here, we propose a non‐invasive enhancement strategy that leverages the endogenous hydrogen sulfide (H ₂ S) pathway of the B. subtilis host and couples it with semiconductor materials to construct a semi‐artificial photosynthetic biohybrid system. This system harnesses light energy to enhance endogenous nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) regeneration, thereby augmenting microbial production without genetic modification of the target biosynthetic pathways. Applied to engineered B. subtilis for 2’‐fucosyl lactose (2’‐FL) and surfactin production, the biohybrid system increases product titres by two‐ to three‐ fold. This strategy, integrated with metabolic engineering, is effective for rapid and enhanced chemical synthesis in B. subtilis , with potential applicability to other non‐photosynthetic bacteria harboring endogenous H ₂ S pathways.

Docosahexaenoic acid (DHA), a long-chain omega-3 polyunsaturated fatty acid (PUFA), is essential for neural development, cardiovascular protection, and anti-inflammation. Conventional fish-oil supply chains remain vulnerable to ecological pressure, compositional variability, and contaminants. Microbial production offers a controllable alternative, yet commercial feasibility depends on numerous factors beyond the strain yield. This review summarizes DHA-producing microorganisms and their metabolic pathways, including precursor supply, biosynthetic and storage pathways, and downstream separation and purification. Various separation strategies, ranging from crude lipid extraction to high-purity DHA, are evaluated in terms of recovery, selectivity, scale, cost, and oxidation risk. We discussed the synergistic mixed-fermentation and refining strategy that coproduces carotenoids, astaxanthin, and FAs to enhance the economic value. To achieve commercial competitiveness, a comprehensive approach combining metabolic engineering, fermentation optimization, and separation engineering is required to establish a microbial platform as an environmentally friendly and sustainable alternative to DHA from animal sources.

28‐epi‐homobrassinolide (28‐epi‐HBL), a bioactive analog of the steroidal phytohormone brassinolide, exhibits broad biological activities and considerable application potential. However, conventional chemical routes remain limited by tetrahydroxylation step that relies on highly toxic osmium tetroxide in combination with costly chiral ligands, whereas the Baeyer‐Villiger oxidation step requires strong oxidants and often exhibits limited regioselective control. In this work, optimization of tetrahydroxylation was achieved using the Shing‐Plietker reaction, thereby avoiding the use of osmium tetroxide. Moreover, an engineered Baeyer‐Villiger monooxygenase (CpnB_BL) was heterologously expressed and used for regioselective B‐ring lactonization under mild conditions. A ZIF‐8‐based immobilization strategy was established for this engineered enzyme, further improving its stability and solvent tolerance, and increasing the isolated yield of the Baeyer‐Villiger step to 83%. These optimized strategies were subsequently applied to the total synthesis of 28‐epi‐HBL, achieving an overall yield of 44.9%. This represents a marked improvement over the highest previously reported yield in the literature, which stands at approximately 20%. Collectively, this study lays the groundwork for the development of more precise and sustainable synthetic routes to 28‐epi‐HBL.

Metalloids bridge the properties of metals and nonmetals, creating unique opportunities in drug discovery. However, the potential of silicon- and germanium-containing scaffolds in organic synthesis and medicinal chemistry remain underexplored, largely owing to the lack of general stereocontrolled synthetic methods, particularly for value-added chiral α-silylamines and α-germylamines. Here, we report a robust nickel-catalyzed enantioselective decarboxylative cross-coupling of amino acid or peptide-derived redox-active esters with silylzinc and germylzinc reagents. The method exhibits a broad substrate scope and delivers excellent performance under mild conditions. Its efficacy is further demonstrated through the late-stage diversification of complex bioactive peptides, and both enantiomers can be accessed with high stereochemical fidelity. Mechanistic investigations delineate the origin of stereocontrol, while preliminary biological evaluations show promising activities, with Ge substitution in several cases surpassing Si and certain clinically marketed boron-containing drugs. Collectively, this work establishes an efficient and enantioselective route to chiral α-silylamines and α-germylamines, underscoring their potential to expand peptide chemical space and to enable the development of peptide-based therapeutics and diagnostics.

To support dual‐carbon goals and address the limitations of conventional CO ₂ valorization technologies, this review summarizes recent advances in electrochemical–biological coupling systems for high‐value CO ₂ utilization, with emphasis on catalytic fundamentals, system integration, and industrial prospects. We discuss catalyst and reactor design for CO ₂ electroreduction to C ₁ /C ₂ liquid platform molecules, particularly formate, acetate, and methanol, and their subsequent biological conversion. The review further examines metabolic and engineering strategies by which microbial cell factories assimilate electro‐generated substrates to produce high‐value compounds, including amino acids, organic acids, polysaccharides, and polyhydroxybutyrate (PHB). Key bottlenecks in electrocatalyst stability, gas diffusion electrodes, reactor operation, carbonate accumulation, cathode flooding, metabolic compatibility, flux matching, and system‐level coupling are analyzed. We also highlight the roles of artificial intelligence, multiscale modeling, smart control, techno‐economic analysis, and life‐cycle assessment in accelerating scale‐up and industrial translation. Overall, electrochemical–biological coupling provides a “capture‐convert‐valorize” route that integrates renewable‐electricity‐driven electrocatalysis with biomanufacturing, enabling CO ₂ conversion into multicarbon, value‐added products and offering a promising platform for sustainable carbon recycling and carbon‐negative manufacturing.