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Abstract Microbial biosynthesis has become the leading commercial approach for large-scale production of terpenoids, a valuable class of natural products. Enhancing terpenoid production, however, requires complex modifications on the host organism. Recently, a two-step isopentenol utilization (IU) pathway relying solely on ATP as the cofactor has been proposed as an alternative to the mevalonate (MVA) pathway, streamlining the synthesis of the common terpenoid precursors. Herein, we find that isopentenol inhibits energy metabolism, leading to reduced efficiency of the IU pathway in Saccharomyces cerevisiae. To overcome this, we engineer an IU pathway-dependent (IUPD) strain, designed for growth-coupled production. The IUPD strain is compelled to enhance the ATP supply, essential for the IU pathway, and incorporates a high-throughput screening method for enzyme evolution. The refined IU pathway surpasses the MVA pathway in synthesizing complex terpenoids. Our work offers valuable insights into developing growth-coupled strains adapted to efficient natural product synthesis.

ObjectivesSubjective cognitive decline (SCD) as a stage between healthy cognition and early neurocognitive disorders, has been proposed to be helpful in the diagnosis of prodromal neurocognitive disorders. To investigate the prevalence of SCD and the related risk factors on the prevalence.MethodsA cross-sectional study involving 1,120 elderly subjects residing in Baotou, China. From June 2021 to June 2023, the data were gathered by research assistants with training utilizing standardized questionnaires. The following factors were evaluated: subjective cognitive decline, physical and cognitive activity levels, past medical history, demographics, instrumental activities of daily living, and cognitive function. Risk factors of SCD were used chi-square tests and multivariate logistic regression analysis.ResultsThe prevalence of SCD was 43.8%. Permanent residence, marital status, BMI, dietary habits, average sleep duration per night, smoking, diabetes, coronary heart disease, and visual impairment were significantly associated with SCD (p

As Earth's climate has varied strongly through geological time, studying the impacts of past climate change on biodiversity helps to understand the risks from future climate change. However, it remains unclear how paleoclimate shapes spatial variation in biodiversity. Here, we assessed the influence of Quaternary climate change on spatial dissimilarity in taxonomic, phylogenetic, and functional composition among neighboring 200-kilometer cells (beta-diversity) for angiosperm trees worldwide. We found that larger glacial-interglacial temperature change was strongly associated with lower spatial turnover (species replacements) and higher nestedness (richness changes) components of beta-diversity across all three biodiversity facets. Moreover, phylogenetic and functional turnover was lower and nestedness higher than random expectations based on taxonomic beta-diversity in regions that experienced large temperature change, reflecting phylogenetically and functionally selective processes in species replacement, extinction, and colonization during glacial-interglacial oscillations. Our results suggest that future human-driven climate change could cause local homogenization and reduction in taxonomic, phylogenetic, and functional diversity of angiosperm trees worldwide.

Abstract Conductive polymer hydrogels exhibit unique electrical, electrochemical, and mechanical properties, making them highly competitive electrode materials for stretchable high‐capacity energy storage devices for cutting‐edge wearable electronics. However, it remains extremely challenging to simultaneously achieve large mechanical stretchability, high electrical conductivity, and excellent electrochemical properties in conductive polymer hydrogels because introducing soft insulating networks for improving stretchability inevitably deteriorates the connectivity of rigid conductive domain and decreases the conductivity and electrochemical activity. This work proposes a distinct confinement self‐assembly and multiple crosslinking strategy to develop a new type of organic–inorganic hybrid conductive hydrogels with biphase interpenetrating cross‐linked networks. The hydrogels simultaneously exhibit high conductivity (2000 S m−1), large stretchability (200%), and high electrochemical activity, outperforming existing conductive hydrogels. The inherent mechanisms for the unparalleled comprehensive performances are thoroughly investigated. Elastic all‐hydrogel supercapacitors are prepared based on the hydrogels, showing high specific capacitance (212.5 mF cm−2), excellent energy density (18.89 µWh cm−2), and large deformability. Moreover, flexible self‐powered luminescent integrated systems are constructed based on the supercapacitors, which can spontaneously shine anytime and anywhere without extra power. This work provides new insights and feasible avenues for developing high‐performance stretchable electrode materials and energy storage devices for wearable electronics.

Abstract Precisely controlling the product selectivity of a reaction is an important objective in organic synthesis. α‐Ketoamides are vital intermediates in chemical transformations and privileged motifs in numerous drugs, natural products, and biologically active molecules. The selective synthesis of α‐ketoamides from feedstock chemicals in a safe and operationally simple manner under mild conditions is a long‐standing catalysis challenge. Herein, an unprecedented TBD‐switched Pd‐catalyzed double isocyanide insertion reaction for assembling ketoamides in aqueous DMSO from (hetero)aryl halides and pseudohalides under mild conditions is reported. The effectiveness and utility of this protocol are demonstrated by its diverse substrate scope (93 examples), the ability to late‐stage modify pharmaceuticals, scalability to large‐scale synthesis, and the synthesis of pharmaceutically active molecules. Mechanistic studies indicate that TBD is a key ligand that modulates the Pd‐catalyzed double isocyanide insertion process, thereby selectively providing the desired α‐ketoamides in a unique manner. In addition, the imidoylpalladium(II) complex and α‐ketoimine amide are successfully isolated and determined by X‐ray analysis, confirming that they are probable intermediates in the catalytic pathway.

Abstract Three‐dimensional (3D) current collectors (CCs) have emerged as an effective strategy to inhibit dendrites and ensure the safety of lithium (Li) metal anodes. However, existing 3D CCs are generally too heavy (typically tens of mg cm−2) or too thick (tens to hundreds of micrometers), making large‐scale production and further application challenging. Additionally, the use of single‐component 3D CCs, whether electrically active or inert, only exhibits limited effects on stabilizing Li anodes. Here, we present a scalable screen‐printing technique for the synthesis of ultralight (~0.4 mg cm−2) and ultrathin (~0.54 μm) SiO2 grids on Cu foil to regulate both the vertical electric field and Li‐ion concentration by forming an electrically active/inert dual‐function architecture. This technology breaks the limitations of traditional 3D CCs in material/fabrication costs, weight, thickness and especially, scalability for large‐scale fabrication. By using this dual‐function architecture, our Cu@SiO2‐grid CCs (~8.31 mg cm−2), which are even lighter than the original Cu‐foil CCs (~8.85 mg cm−2), realize an ultra‐smooth anode surface without Li dendrites, and thus leads to an ultra‐long cyclic life of over 1500 h at 1 mA cm−2. The assembled Li metal batteries demonstrate excellent capacity retention of ~80% over 400 cycles at 1 C and ~ 76% over 250 cycles at 5 C, which highlight the promising 3D CCs for practical applications.

The infralimbic (IL) cortex dysfunction has been implicated in major depressive disorder (MDD), yet the precise cellular and molecular mechanisms remain poorly understood. In this study, we investigated the role of layer V pyramidal neurons in a mouse model of MDD induced by repeated lipopolysaccharide (LPS) administration. Our results demonstrate that three days of systemic LPS administration induced depressive-like behavior and upregulated mRNA levels of interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-β (TGF-β) in the IL cortex. Electrophysiological recordings revealed a significant decrease in the intrinsic excitability of layer V pyramidal neurons in the IL following systemic LPS exposure. Importantly, chemogenetic activation of IL pyramidal neurons ameliorated LPS-induced depressive-like behavior. Additionally, LPS administration significantly increased microglial activity in the IL, as evidenced by a greater number of Ionized calcium binding adaptor molecule-1 (IBA-1)-positive cells. Morphometric analysis further unveiled enlarged soma, decreased branch numbers, and shorter branch lengths of microglial cells in the IL cortex following LPS exposure. Moreover, the activation of pyramidal neurons by clozapine-N-oxide increased the microglia branch length but did not change branch number or cytosolic area. These results collectively suggest that targeted activation of pyramidal neurons in the IL cortex mitigates microglial response and ameliorates depressive-like behaviors induced by systemic LPS administration. Therefore, our findings offer potential therapeutic targets for the development of interventions aimed at alleviating depressive symptoms by modulating IL cortical circuitry and microglial activity.