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Cadmium (Cd) poses a threat to plants and humans. As a commonly used Chinese medicinal material, Salvia miltiorrhiza (SM) roots have been investigated in many studies, but few studies have investigated SM flowers. In particular, there is a lack of research on the response of SM flowers to Cd stress. Here, the metabolomic mechanisms underlying the response of SM flowers to Cd stress were analyzed. Six kinds of metabolites were detected: amino acids, organic acids, sugars, lipids, alcohols, and others. Among them, organic acids accounted for the largest proportion, followed by sugars and amino acids. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) clearly differentiated the control from the Cd-treated groups. A total of 31, 40, and 49 differential metabolites (DMs) were detected in 25 (HT1), 50 (HT2), and 100 (HT3) mg·kg-1 Cd-treated groups, respectively. These DMs were mainly enriched in alanine, aspartate and glutamate metabolism, glyoxylate and dicarboxylate metabolism, butanoate metabolism, citrate cycle (TCA cycle), and glycine, serine and threonine metabolism. Among the metabolites, oxamic acid and citric acid contributed most to the down-regulated differential amino acids and differential organic acids, respectively; xylose and 1-kestose contributed most to the up-regulated differential sugars; tryptophan and arachidic acid contributed most to the up-regulated amino acids and organic acids, respectively. These findings suggested that SM flowers might resist Cd stress through restructuring the cell-wall framework, modulating membrane fluidity, and regulating intracellular soluble components. These findings provide new avenues for exploring how medicinal plant resources cope with heavy-metal stress.

Palladium-catalyzed β and γ-C-H arylation of free carboxylic acids with both aryl boron reagents and aryl iodides has been extensively developed in recent years. Replacing these aryl coupling partners with simple arenes remains a significant challenge. By developing pyridone-morpholine ligands, we disclosed the β-methylene C-H (hetero)arylation of acyclic aliphatic acids and the γ-(hetero)arylation of cycloalkane carboxylic acids using benzene, furan, thiophene, and C-2 substituted pyridine as coupling partners. Preliminary mechanistic studies suggest that the reaction proceeds via ligand-promoted dehydrogenation of aliphatic carboxylic acids, C(sp2)-H activation of (hetero)arenes, and subsequent hydroarylation. Building on the mechanistic insights, we developed a dual-ligand catalysis system with one ligand promoting dehydrogenation and the other enhancing subsequent steps to enable coupling of C(sp3)-H bonds with indoles and pyrroles as reaction partners.

Indonesia's rich macroalgal biodiversity offers valuable resources for functional food development, particularly ulvan, a sulfated polysaccharide derived from Ulva lactuca. While ulvan shows promising prebiotic potential, its extraction efficiency and structure-function relationships are strongly influenced by processing conditions. This study optimized ulvan recovery from U. lactuca harvested from the Bolok coastal waters (Kupang, Indonesia) and evaluated its chemical composition, structural characteristics, and in vitro prebiotic functionality. Three extraction strategies were compared: mild hydrothermal-enzymatic (cellulase)-ultrasonication (HEU-C), mild hydrothermal-multienzyme-ultrasonication (HEU-Mix), and a nonenzymatic hydrothermal-ultrasonication (HU) method. The HEU-C method achieved the highest yield (29.85%), significantly exceeding that of HU (12.22%). Chemical analyses revealed that HEU-C extracts contained the highest levels of polysaccharides, reducing sugars, and uronic acids, whereas HU extracts retained the greatest sulfate content. FTIR and SEM analyses demonstrated that different extraction methods induced distinct structural modifications and changes in surface morphology. Ulvan extracted via HEU-C exhibited the strongest antioxidant activity (DPPH radical scavenging capacity: 50.58%), followed by HEU-Mix and HU. In vitro fermentation assays showed that HEU-C extracts (1%-5% w/v) significantly promoted the growth of Lactobacillus rhamnosus RAL43, Lactobacillus plantarum RAL25, and Lactococcus lactis SwR14, with performance comparable to or exceeding that of fructooligosaccharides. Fermentation was further characterized by soluble sugar consumption and the production of short-chain fatty acids (SCFAs), including acetic, propionic, and butyric acids. Overall, enzyme-assisted extraction enhanced ulvan bioactivity, structural accessibility, and prebiotic performance, positioning it as a promising functional ingredient for microbiota-targeted food applications and marine-derived nutraceutical development.

Allergic rhinitis (AR) is a common clinical chronic inflammatory respiratory disease, in which immune imbalance serves as a core component of its complex pathogenesis. In recent years, the gut-nose axis has emerged as a novel pathway mediating immune crosstalk between the intestinal tract and the nasal cavity, garnering significant academic attention. Gut microbial metabolites (such as short-chain fatty acids, tryptophan metabolites, bile acids, and polyamines) are profoundly involved in the pathophysiology of AR by reshaping the nasal mucosal immune microenvironment via systemic circulation and neural pathways and regulating the Th2/Treg balance, innate lymphoid cells (ILC2s), and mast cell functions. This article systematically reviews the immunomodulatory mechanisms of core gut microbial metabolites, explores their impact on nasal mucosal epithelial barrier function and immune cell activity, and summarizes metabolite-based clinical intervention strategies, including postbiotic therapy (bioactive compounds derived from microbial cells or metabolites), precision nutritional interventions, and fecal microbiota transplantation. Additionally, the paper analyzes current challenges such as heterogeneity and dose-response effects, aiming to provide a theoretical foundation for understanding the immunomodulatory mechanisms of the gut-nose axis and a reference for developing novel precision strategies for the prevention and treatment of AR.

Survival during infection depends on both pathogen clearance and the ability to tolerate infection-induced physiological changes. Metabolic adaptations are a central component of this tolerance, but the mechanisms underlying these responses remain incompletely defined. Here, we identify white adipose tissue (WAT) lipolysis as a central regulator of metabolic tolerance to infection. In patients with sepsis, higher circulating non-esterified fatty acid (NEFA) levels were associated with reduced mortality. In mouse models of polymicrobial sepsis, infection induced robust adipose lipolysis and increased circulating NEFAs. Genetic ablation of adipose triglyceride lipase (ATGL) in adipose tissue impaired lipolysis, leading to hypothermia, bradycardia, and increased mortality without altering immune cell populations or pathogen burden, consistent with a defect in tolerance rather than resistance. Mechanistically, lipolysis-derived NEFAs, but not glycerol, were required for protection, as restoring circulating NEFAs rescued autonomic stability and survival in adipose tissue ATGL-deficient mice. Infection-induced lipolysis was redundantly regulated and did not depend on any single upstream signaling pathway. Both pharmacologic activation of lipolysis using a β3-adrenergic agonist and exogenous fatty acid supplementation increased circulating NEFAs, improved survival, and promoted tolerance in mice. Consistent with these findings, analysis of real-world electronic health record data demonstrated that septic patients receiving FDA-approved β3-adrenergic agonists had reduced mortality or hospice discharge in a propensity-matched cohort. Together, these results identify WAT lipolysis and circulating fatty acids as key mediators of tolerance to infection and support a therapeutic strategy based on repurposing clinically available β3-adrenergic agonists to improve outcomes in sepsis. White adipose tissue lipolysis promotes metabolic tolerance to infection through circulating fatty acids and is associated with improved survival in sepsis.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its inflammatory-fibrotic phenotype (MASH) exhibit pronounced immunometabolic coupling. This review synthesizes evidence along the gut-liver axis, from epithelial tight-junction and gut vascular barrier (GVB) failure to TLR4-MyD88/TRIF-NF-κB amplification and NLRP3 inflammasome activation and outlines the logic of the gut-derived exposure spectrum-lipopolysaccharide (LPS), endogenous ethanol, bile acids (BAs), short-chain fatty acids (SCFAs), and trimethylamine N-oxide (TMAO). We position BA-FXR/TGR5, SCFAs-GPR41/43, and AMPK/Nrf2 as upstream/downstream modulators that reset inflammatory thresholds and confer stage-dependent druggability. Based on node-to-pathway mapping, we summarize mechanisms and translational signals for berberine (BBR), Qushihuayu (QSHY), Da-Chai-Hu Decoction (DCHD), and polysaccharides (e.g., Astragalus, Ganoderma), emphasizing pharmacokinetic and site-of-exposure constraints that support "gut-first" actions. We propose a minimal companion biomarker set-LBP/sCD14, BA profiles with FGF19-C4 dynamics, and IL-1β/GSDMD-N-paired with hierarchical imaging gates (≥30% relative MRI-PDFF decline; MRE/ELF) to underpin response typing and go/no-go decisions. Finally, we highlight critical gaps (direct human GVB readouts; longitudinal multi-omics bridged to clinical outcomes) and outline a biomarker-driven multi-arm multi-stage (MAMS) pathway for adaptive, stratified development of multi-target traditional medicine interventions in MASLD/MASH.

Sepsis frequently involves early gastrointestinal dysfunction, in which intestinal barrier breakdown and microbiota dysbiosis amplify systemic inflammation and contribute to multi-organ failure. Emerging evidence indicates that the gut is not merely a bystander in sepsis but an active driver of pathogenic cascades through epithelial injury, mucosal immune dysregulation, ischemia-reperfusion stress, and impaired motility, collectively promoting microbial translocation and immune deviation. In parallel, sepsis is associated with profound remodeling of the gut microbiome, characterized by reduced commensal diversity, expansion of pathobionts, and functional shifts in key microbial metabolites, including short-chain fatty acids, bile acids, and tryptophan-derived products, which further compromise mucosal integrity and host immune tone. This narrative review synthesizes experimental, translational, and clinical findings to elucidate the bidirectional interaction gut barrier-microbiota interplay in sepsis and to summarize mechanistic links across epithelial, immune, and metabolic signaling pathways, including gut-liver and gut-brain axes relevant to sepsis-associated organ dysfunction. dysfunctional microbial community leads to systemic immune deviation, multi-organ dysfunction and sepsis-associated encephalopathy, a common and severe neurological complication of sepsis. We also discuss emerging therapeutic strategies targeting the gut-microbiota axis-such as early enteral nutrition, prebiotics/postbiotics, defined microbial consortia, fecal microbiota transplantation, and metabolite-based supplementation-and evaluate their potential and limitations in septic populations. Finally, we highlight key challenges, including unresolved causality, inter-individual variability, context-dependent responses, and safety concerns, underscoring the need for longitudinal multi-omic profiling, host-microbiome phenotyping, and mechanism-informed interventional trials to enable precision microbiome-based approaches for sepsis.

A photoredox-neutral approach to cyclopropanes from in situ generated non-stabilized carbenes via a new acridine-iron dual catalytic system is reported. This strategy merges the oxidative decarboxylation of bench-stable carboxylic acids with the reduction of an iron porphyrin under mild photochemical conditions. Bespoke acridine photocatalysts efficiently shuttle electrons between carboxylic acids and iron complexes, obviating the need for a sacrificial reductant. Mechanistic studies reveal that, contrary to prevailing assumptions, decarboxylation does not proceed through a concerted PCET pathway but instead via a stepwise proton transfer followed by a highly exergonic electron transfer and decarboxylation event. Density functional theory calculations further support the formation of a key Fe(IV)-carbenoid intermediate, which engages alkenes through a stepwise, radical-type carbene transfer mechanism.

In recent years, concerns over declining biodiversity in urban spaces have increased. Urban Bokashi composting (i.e. microaerobic or anaerobic fermentation of food waste indoors) has been suggested as a possibility to promote microbial diversity in the domestic environment. However, studies on microbial communities in household-scale Bokashi and their potential impacts on health and environment are lacking. Thus, the present pilot study investigated microbial communities in different stages of the Bokashi composting process in collaboration with six Bokashi practitioners by looking into physicochemical characteristics as well as microbial community composition (16S amplicon sequencing, 34 samples) and functional potential (shotgun metagenome sequencing, 11 samples). The collective results indicate that i) microbial communities in Bokashi compost differed between stages, but also between households, ii) microbial communities were dominated by lactic acid bacteria like Lentilactobacillus or Lacticaseibacillus, iii) metabolic pathways for the production of diverse organic acids were detected, iv) application of Bokashi ferment or leachate to soil can supply nutrients and organic acids to promote plant growth but does not substantially affect soil microbial community composition, and v) potentially pathogenic organisms were detected in extremely low abundances. Thus, urban Bokashi is likely not associated with increased health risks and positive impacts are feasible.

The principle "hard acids prefer hard bases" from the Hard and Soft Acid-Base (HSAB) theory, has gained extensive validation. However, the interaction mechanisms between borderline acid metals and hard base groups remain unclear, limiting the rational design of highly selective adsorption. This study systematically investigates the synthesis of hard base-functionalized UiO-66 materials (UiO-66-X, X = -NH2, -OH, and -COOH) and their efficacy in adsorbing borderline acid metal (Cu(II), Co(II), Ni(II), Pb(II)). Comprehensive characterization confirms the preservation of the parent framework and the successful introduction of functional groups. Batch adsorption experiments reveal that the solution pH and the pairing between functional groups and metal ions are critical factors affecting adsorption capacity and selectivity. The -OH group exhibits strong affinity for Cu(II), Co(II), and Pb(II), -COOH for Pb(II) and Cu(II), and -NH2 is exceptionally selective for Ni(II). The mechanism, elucidated through XPS and DFT calculations (ESP, DOS, and adsorption energy), verifies coordination between metal ions and the N/O atoms of hard base groups. Additionally, the introduction of -COOH groups through para-functionalization improves the adsorption rate and selectivity per functional group by modulating the electronic structure. This study provides fundamental insights into the structure-activity relationship, aiding in the design of highly selective MOF-based adsorbents.

Soybeans serve as excellent sources of vegetable oil, protein, and other valuable nutrients for human consumption, materials for diverse industries, including the cosmetics and medical industries, and feedstocks for animals. Nevertheless, some people do not favor soy oil or other various food products derived from soybeans, due to inadequate levels of oleic acid in the oil and the presence of undesirable grassy and beany flavors associated with oxidation products of polyunsaturated fatty acids in the seeds. In this study, we developed soybean cultivars with very high levels of oleic acid in the seeds, and without grassy and beany flavors. We achieved this by using CRISPR-Cas-SF01 to edit genes in the elite cultivar Xudou 18 (XD18), targeting two microsomal Δ-12 fatty acid desaturase 2 (GmFAD2-1A and GmFAD2-1B) and three lipoxygenase (GmLOX1, GmLOX2, and GmLOX3) genes. Our findings showed that fad2-1a/b and fad2-1a/b/lox1/2/3 plants performed similarly to XD18 plants in the field, indicating no obvious growth penalties. Overall, this research has demonstrated that the development of soybean germplasms with high levels of oleic acid and without undesirable beany flavors through gene-editing of multiple relevant genes is effective, and this endeavor can contribute to the health of a broader global consumer population.

Producing short-chain carboxylic acids like formic acid (FA) from biomass in the OxFA process is a promising strategy for a green and sustainable chemical industry. Herein, we employed spectroscopic (NMR, UV-vis, and GC-MS), electrochemical (CV and SWV), and thermodynamic (gas solubility) measurements in combination with theoretical modelling by DFT for rationalizing the dominating effects of co-solvents on the catalytic efficiency of xylose oxidation to FA in the modified OxFA process catalyzed by H8PV5Mo7O40 (HPA-5) polyoxometalate. Specifically, the effect of oxygen solubility in different solvent mixtures in combination with the redox potential of the first reduction event of HPA-5 during the electrochemical treatment revealed the combined effect of both thermodynamic and catalytic properties on the effective reaction kinetics for xylose oxidation to FA. Therefore, the ease of xylose oxidation is directly linked to the redox potential observed in different co-solvent mixtures. Based on these insights, systematic optimization of the reaction parameters in the most promising water-acetonitrile solvent mixture using design of experiments (DoE) and a central composite design (CCD) achieved an FA yield of 90% at full xylose conversion, with only 5% CO2 formation after 2 hours of reaction. The insights from this study provide a strong foundation for future process intensification in biomass valorisation technologies.

The synthesis of aromatic amines requires harsh conditions or the use of fossil-derived hydrogen (H2). Here, we address this limitation by demonstrating photocatalytic transfer hydrogenation (PTH) of nitroarenes into anilines employing plastic hydrolysates as electron and proton (hydrogen) donors under ambient temperature and pressure. PTH is achieved using a cobalt-promoted molybdenum sulfide (CoMoS2) electrocatalyst integrated with a carbon nitride (CNx) semiconductor photocatalyst in acidic aqueous solution. CoMoS2 reduces nitroarenes to anilines at -0.7 V versus RHE with a Faradaic yield of 70% and superior activity to platinum. The CoMoS2-CNx photocatalyst produces anilines under simulated solar light (AM 1.5 G, 25°C), achieving 83%-99% yield from 24 nitroarenes using 4-methylbenzyl alcohol as a model hydrogen donor. Acid hydrolysis of condensation polymers provides a source of alcoholic monomers in aqueous solution that can be used as a sustainable hydrogen donor for PTH in >80% yield using AM 1.5G or LED (405 nm, 33 mW cm-2) irradiation. A technoeconomic analysis (TEA) at pilot scale producing 1 t aniline day- 1 using polyethylene terephthalate (PET) reveals a cut in cradle-to-gate emissions by ∼77% using PTH with CoMoS2-CNx compared to conventional Pd/C hydrogenation with H2 from steam methane reforming (SMR-H2) and a revenue-generating levelized cost of aniline (LCOA) when co-produced with terephthalic, acetic, and formic acids.

Chimeric antigen receptor (CAR)-T cell therapy has demonstrated curative potential against hematologic malignancies, but its clinical application remains constrained by the risk of uncontrolled immune activation. To address this, we engineered a translational control system for CAR expression based on Genetic Code Expansion (GCE), enabling tight, dose-dependent, and function-preserving regulation through nonsense codon suppression via noncanonical amino acids (ncAAs). By introducing amber stop codons into CAR constructs and engineered aminoacyl-tRNA synthetase and tRNA pair, we developed a leak-free regulatory module applicable in both Jurkat and primary human T cells. NcAA-treated GCE-CAR-T cells exhibited antigen-specific cytotoxicity and cytokine secretion comparable to wild-type CAR-T cells. In a xenograft mouse model, tumor-specific immune responses were observed only upon ncAA administration, with untreated controls showing no therapeutic effect. This work establishes a stringent, fast-acting translational switch that enables precise modulation of CAR-T cell function without compromising efficacy, offering a promising platform for next-generation programmable cell therapies.

Fuping goat milk powder is a kind of geographical indication protected food in China. To realize a rapid and accurate identification of Fuping goat milk, in this paper, an identification method was proposed based on nuclear magnetic resonance and machine learning to accurately distinguish Fuping goat milk on small scale geographical authenticity. Deuterated chloroform was selected as extraction solvent, partial least squares discriminant analysis (PLSDA), random forest (RF) and support vector machine (SVM) models were constructed using seven different geographical origin goat milk samples in Shaanxi Province. The identification based on PLS-DA model was unsatisfactory, the RF model performed better, and the SVM model showed best performance with accuracy rate reached 100% based on selected 17 features, and the 5-fold cross-validation accuracy was 94.7% ± 7.2%. It is disclosed that different geographic samples have different chemical compositions, particularly unsaturated fatty acids, such as conjugated linoleic acid.