Natural products and their derivatives are important sources for drug discovery. However, most exhibit suboptimal druggability profiles and insufficient bioactivity. Amino acids, with their structural diversity and rich biological activities, serve as highly valuable modification fragments in this field. As an efficient structural optimization strategy, amino acid fragment-based modification has achieved significant progress in natural product derivatization in recent years. Therefore, this review systematically summarizes research since 2020 on the application of amino acid fragments in the structural modification and biological activity enhancement of phenylpropanoids, flavonoids, terpenoids, steroids, alkaloids, and other natural products. It focuses on detailing the optimization of druggability, enhancement of biological activity, and structure-activity relationships of various natural products modified with different amino acid fragments, aiming to provide a theoretical basis and strategic insights for addressing poor druggability and insufficient activity, as well as for developing multi-target, multifunctional natural product-amino acid derivatives.
Ovarian cancer (OC) remains the most common cancer among women, with high incidence and mortality rates, prompting extensive investigation across in vivo, in vitro, and clinical settings. In this context, in vitro cell culture models have been widely used to study drug response, tumor progression, and the development of novel therapeutic strategies. Among these, three-dimensional (3D) culture systems have emerged as advanced platforms capable of more accurately recapitulating tumor complexity. Concurrently, the exploration of complementary therapeutic approaches, especially natural products, has gained attention for their potential to enhance antitumoral efficacy while reducing adverse effects. In this interpretative narrative review, we examine the application of 3D culture models to evaluate the effects of natural compounds in OC. Based on 21 selected studies, we highlight that 3D systems, including spheroid formation via droplet suspension, ultra-low adhesion plates, coated surfaces, hydrogels, and rotary culture, enable more physiologically relevant modeling of the tumor microenvironment. Within these systems, a wide range of natural compounds (e.g., epigallocatechin gallate, withaferin A, lycopene, cucurbitacins, genistein, and others) consistently exhibited antitumor activity. These effects include inhibition of migration and invasion, induction of apoptosis, modulation of oxidative and inflammatory pathways, and disruption of cell-matrix interactions. Mechanistically, these natural compounds target key signaling pathways involved in tumor progression, although significant gaps remain regarding standardization, reproducibility, and clinical translation. Importantly, this review underscores the superiority of 3D in vitro models in recapitulating tumor biology and highlights the promising role of natural products as adjuvant strategies alongside conventional therapies. Collectively, these findings provide a robust framework for advancing experimental, translational, and clinical research aimed at improving therapeutic outcomes in OC.
Our study explored the histological and histo-functional characteristics of the testis and seminal vesicles of Jaculus jaculus, collected from the Biskra (34° 51' 0" N 5° 43' 59.999" E) and M'sila regions in Algeria (35°42'20.99" N 4°32'30.98" E) from autumn to early spring, corresponding to activity and transitional periods of the reproductive cycle. An immunohistochemical analysis of matrix metalloproteinases (MMP-2 and MMP-9) was conducted on the seminal vesicles and testes during the active reproductive. The study utilized an indirect immunohistochemistry protocol with amplification through streptavidin-biotin-peroxidase. Histologically, seminiferous tubules in Jaculus jaculus, captured during the transitional period of the reproductive cycle, multinucleated giant cells of germinal origin were observed during the transitional phase of the reproductive cycle, reflecting a process of seasonal testicular remodelling. The histological structure of seminal vesicles appears highly characteristic of the studied species, with the vesicular epithelium organized into complex acinar glands surrounded by basal lamina and connective tissue. Gland cells secrete a heterogeneous product. In the testis, cells of the seminiferous epithelium express MMP-2 and MMP-9 in their cytoplasm, with a strong expression of MMP-2; however, both proteins are absent from the extracellular matrix. During the active period, in seminal vesicles, a significant immunohistochemical signal of MMP-2 and MMP-9 was observed in epithelial cells, smooth muscle cells, with no immunoexpression in the extracellular matrix. MMP-2 and MMP-9 are expressed in a pattern consistent with a potential role in the seasonal reproductive cycle.
The macromolecular monoclonal antibodies targeting CTLA-4/PD-1/PD-L1 have revolutionized cancer immunotherapy. However, their clinical efficacy is limited by poor tissue penetration, strong immunogenicity and frequent cytokine release syndrome (CRS) risk. In contrast, natural small molecules can effectively overcome these challenges due to their strong penetration, minimal immunogenicity and low CRS risk. Developing natural small molecule-mediated immunotherapeutic drugs represents a promising strategy for improving current cancer immunotherapy. A non-traditional T-cell immunomodulatory anti-tumor model was utilized to explore these potential molecules. LDH release assays and ELISA were used to assess T-cell immune killing activity against tumor cells and cytokine production. The mouse colon cancer lung metastasis model was used to evaluate anti-tumor efficacy in vivo through emodinanthrone monotherapy and combined with anti-PD-1 treatment. Proteomic and phosphoproteomic analyses, combined with blocking and rescue experiments, were employed to investigate the underlying mechanism. The natural product emodinanthrone (EA), a precursor of emodin, was first identified as a potential T-cell immunomodulator. Mechanistic studies revealed that EA exerts immunomodulatory effects on T cells to eliminate multiple tumor cells, mainly by enhancing the JAK3-STAT1/3 signaling axis, leading to increased expression of granzyme B, perforin, and IFN-γ. In vivo, EA treatment significantly reduced the number of lung metastatic nodules by approximately 72.4% and extended overall survival by approximately 42.8%. Furthermore, combination treatment with anti-PD-1 antibody markedly decreased the metastasis rate from 59% to 12.8% and improved the survival rate from 30% to 70%. This study first reveals that emodinanthrone possesses T-cell immunomodulatory anti-tumor activity. In vivo findings further support its development as a promising candidate to improve anti-PD-1 efficacy.
Thaumatin is a natural sweet-tasting protein derived from the plant Thaumatococcus daniellii, renowned for its high sweetness intensity, low caloric value, and favorable thermal and pH stability. As it can be degraded into natural amino acids, thaumatin represents a potentially safer alternative sweetener. However, plant-based extraction of this protein is constrained by low endogenous content, as well as geographical and seasonal limitations. Meanwhile, existing microbial cell factories often struggle to simultaneously achieve high expression levels and ensure high product purity with natural conformation. To address this bottleneck, this study designed and constructed a thaumatin precursor protein (pThaumatin) incorporating an affinity purification tag and a traceless cleavage site. Using Pichia pastoris as the expression host, the folding and secretory expression efficiency of this precursor protein was enhanced through engineering of the protein folding and secretion pathways in the cell factory, combined with fed-batch fermentation. Following affinity chromatography purification, 126 mg of high-purity thaumatin precursor protein was obtained per liter of fermentation broth. Subsequent downstream processing using residue-free protease cleavage enabled the removal of the fusion tag, yielding mature thaumatin (mThaumatin) with a sequence identical to that of the native protein, achieving a conversion efficiency of nearly 100%. The resulting protein exhibited secondary structure consistent with that of native thaumatin. Circular dichroism spectroscopy revealed that the thaumatin protein released by enzymatic cleavage exhibited high consistency in secondary structure with native thaumatin. Preliminary sensory evaluation confirmed that the protein displayed a pronounced sweet taste, indicating function integrity. This study establishes a technical pipeline encompassing "precursor protein design-cell factory secretory expression-traceless enzymatic post-processing" for the production of high-purity, native-conformation thaumatin via microbial fermentation. This study provides a reference for achieving high-purity expression and the restoration of the native conformation of sweet-tasting proteins. 索马甜(thaumatin)是一种源于植物丹尼尔奇异果(Thaumatococcus daniellii)的天然甜味蛋白,具有高甜度、低热量、较好的热稳定性与pH稳定性。索马甜可降解为天然氨基酸,是更安全的潜在甜味剂。植物提取该蛋白质面临含量低、作物区域及季节限制等问题,现有微生物细胞工厂通常难以在提高表达量的同时,保证产物的高纯度与天然构象。为解决这一问题,本研究设计并构建了一种融合亲和纯化标签与无痕切除位点的索马甜前体(pThaumatin)蛋白。以毕赤酵母作为表达宿主,通过改造细胞工厂折叠分泌蛋白质的过程与分批补料发酵,提升前体蛋白的折叠与分泌表达效率。经过亲和层析纯化,每升发酵液获得了126 mg高纯度索马甜前体蛋白。随后通过下游无残留蛋白酶切处理去除融合标签,获得与天然序列完全一致的成熟索马甜蛋白(mThaumatin),转化率接近100%。圆二色谱分析表明,酶切释放所得的索马甜蛋白在二级结构上与天然索马甜高度一致。初步感官评估证实该蛋白甜味显著,功能正常。本研究建立了一条“蛋白质前体设计-细胞工厂分泌表达-无痕酶切后处理”的技术路线,实现了基于微生物发酵的高纯度、天然构象索马甜的制备,为实现甜味蛋白的高纯度表达及天然构象恢复提供了参考。.
The high-value utilization of underutilized plant resources and waste materials is of considerable significance for the sustainable resource development, agricultural by-product valorization, and the circular economy. In this study, machine learning was integrated with natural deep eutectic solvent (NADES), using Syringa oblata Lindl (S. oblata) leaf residue polysaccharides (SOLP) as a case study, to establish a green and efficient ultrasound-assisted NADES extraction strategy. Based on multiple machine learning models, the polysaccharide extraction yield and key process parameters were accurately predicted and optimized. The optimal extraction conditions predicted by the model were as follows: NADES water content of 51.4%, NADES to S. oblata leaf residue ratio (DSR) of 42.9 mL/g, ultrasonic time of 41.7 min, and ultrasonic power of 250.0 W. Among the machine learning models, the XGB model exhibited the highest prediction accuracy (test set, R2 > 0.92). SHAP analysis further revealed that DSR, water content, ultrasonic time, and ultrasonic power contributed 58.57%, 21.31%, 12.82%, and 7.29% to the polysaccharide yield, respectively. Density functional theory (DFT) calculation was performed to further explore the NADES extraction mechanism. The results demonstrated that the binding energy between NADES-6 and SOLP was significantly better than that in the traditional solvent. The formation of hydrogen-bond interactions promoted dissolution and release of polysaccharides, thereby enhancing extraction efficiency. Structural characterization showed that SOLP was mainly composed of galacturonic acid, galactose, and rhamnose, with minor amount of glucuronic acid, glucose, and arabinose. In addition, SOLP exhibited ABTS and hydroxyl radical scavenging activities. Overall, this study establishes a data-driven research framework integrating machine learning, DFT analysis, and NADES-based extraction. In addition to improving polysaccharide extraction efficiency and prediction accuracy, this study also provides a promising strategy for the high-value utilization of natural polysaccharides derived from underutilized plant resources and agricultural residues.
In order to solve the dispersion of nano-CaCO3 in the latex system and the instability of latex caused by high calcium ion activity, this paper proposes an efficient, mild and environmentally friendly method to prepare CaCO3@SiO2 core-shell nanostructured composites by sonochemical reaction, which obtains extremely low calcium ion activity and good dispersion in the latex system. The unique sonochemical process rapidly coats a dense SiO2 shell onto the nano-CaCO3 surface. The resulting product comprises a calcite-phase CaCO3 core and an amorphous SiO2 shell, which are covalently bonded through Ca-O-Si chemical bonds. The uniform and continuous SiO2 shell not only effectively improves the dispersion of nano-CaCO3 but also shields the surface calcium ion activity. The prepared CaCO3@SiO2 composite particles were dispersed into natural latex as fillers to prepare medical examination gloves with an extremely high addition amount of 30 phr. Owing to the effective shielding of surface calcium ion activity by the CaCO3@SiO2 core-shell structure and its good dispersion, the filler exhibits excellent processing stability and interfacial compatibility in the natural latex matrix, resulting in significantly improved mechanical properties including tensile strength, elongation at break and thermal aging resistance. This study provides a novel and efficient approach for the preparation of high-performance fillers for medical examination gloves.
The escalating global temperatures and increased frequency of heatwaves associated with climate change have intensified the risk of chronic dehydration, particularly in the Arab Gulf, Sahara, Sub-Saharan regions, and in some part of Europe and North America during Summer. This study presents the development, biomaterial synthesis process, and comprehensive physicochemical characterization of a novel nanocomposite-based vitamin-fortified water designed as a potential approach to address hydration and nutritional needs in populations at risk of dehydration, with the vitamins included selected for their established roles in immune function and antioxidant defense. The formulation centers on a biopolymer-stabilized lipid nanocomposite incorporating concentrated vitamin extracts comprising Ascorbic Acid (Vitamin C), Riboflavin (Vitamin B2), 25-Hydroxycholecalciferol (Vitamin D3), and α-Tocopherol Acetate (Vitamin E). The bioactive nanocomposite is stabilized using Polyethylene Glycol (PEG)-based biocompatible surfactants and Rosmarinic acid as a natural antioxidant preservative, forming a microemulsion-based nanocomposite with a mean droplet diameter of 89.3 ± 4.7 nm and polydispersity index of 0.187, confirming colloidal stability and homogeneous nanoparticle size distribution. This Vitamin Extract concentrate is subsequently dispersed in biologically activated water (prepared using sucrase-catalyzed enzymatic treatment followed by UV-C irradiation, pH 6.9) to produce the final functional beverage. Comprehensive stability studies conducted over 12 weeks under varying storage conditions (4 °C, 25 °C, 40 °C; light-protected vs. exposed) demonstrated >90% vitamin retention under refrigeration and >85% retention at room temperature, with accelerated degradation observed at 40 °C and under light exposure. The resulting product is a colorless, palatable liquid with a pH of 6.0, designed as a biomaterial-based functional beverage to support hydration, bolster immune function, and deliver essential micronutrients. This work outlines both conventional solution preparation and a non-conventional, sequential adiabatic mixing process for formulating the vitamin-loaded nanocomposite, with full analytical validation including nanoparticle size analysis, zeta potential measurement, and quantitative HPLC-DAD vitamin quantification.
Current understanding of the biological activities and metabolism of raffinose remains limited. This study aimed to elucidate its digestive behavior and anti-allergic potential by integrating fluorescence imaging in mice, in vitro digestion simulation, human fecal fermentation, and RBL-2H3 cells detection. The results showed that following oral gavage in mice, raffinose was primarily distributed in the gastrointestinal tract and reached the colon within 2-6 h. In addition, raffinose was hardly degraded during in vitro simulated gastric and intestinal digestion. Analysis of human fecal microbiota demonstrated that microbial richness and diversity were lower in food-allergic individuals than in healthy individuals. In the in vitro fermentation system using human fecal samples, raffinose supplementation increased short-chain fatty acid concentrations in the group involving fecal fermentation from healthy volunteers with raffinose. Furthermore, raffinose inhibited the growth of Escherichia-Shigella and Weissella. In the RBL-2H3 cell degranulation model, raffinose promoted cell proliferation, suppressed degranulation, and reduced the release of β-hexosaminidase and histamine, demonstrating its anti-degranulation capacity. Our results verify that raffinose is indigestible in the upper gastrointestinal tract using a mouse model. It modulates gut microbiota and short-chain fatty acids in in vitro human fecal fermentation systems and produces anti-allergic effects in cell models. These findings provide a foundation for expanding the applications of raffinose in deep processing as a value-added functional product. © 2026 Society of Chemical Industry.
The Chinese herbal medicine Rhizoma Alismatis is the dried tuber of Alisma orientale (Sam.) Juzep. or Alisma plantago-aquatica Linn., perennial aquatic or marsh herbaceous plants belonging to the family Alismataceae. It is a commonly used herb for inducing diuresis and eliminating dampness. It is rich in terpenoids, especially sesquiterpenoids as important active ingredients, which exhibit various pharmacological activities such as anticancer and anti-inflammatory effects. To date, studies on the sesquiterpenoid biosynthetic pathway in Alisma orientale (Sam.) Juzep. remain insufficient. This study aimed to elucidate the sesquiterpenoid biosynthetic pathway in Rhizoma Alismatis, identify and characterize key functional genes involved in sesquiterpenoid biosynthesis, and provide a theoretical basis for clarifying its pharmacodynamic material basis and the subsequent screening and application of quality markers. Therefore, employing approaches of transcriptomics and molecular biology, identified and cloned nine functional sesquiterpene synthase genes (AoTPSs) from A. orientale. Using a yeast heterologous expression system, we characterized their biochemical functions, confirming that these genes can catalyze the biosynthesis of sesquiterpenoids such as β-elemene, α-caryophyllene, (E)-nerolidol, β-caryophyllene, and α-farnesene. This study lays a foundation for in-depth elucidation of the biosynthetic mechanism and resource development of Alisma sesquiterpenoids. 中药泽泻为泽泻科泽泻属多年生水生或沼生草本植物东方泽泻[Alisma orientale (Sam.) Juzep.]或泽泻(Alisma plantago-aquatica Linn.)的干燥块茎,是常用利水渗湿药,其富含萜类成分,尤以倍半萜类化合物为重要活性物质,具有抗癌、抗炎等多种药理作用。截至目前,东方泽泻倍半萜生物合成通路的研究较为匮乏,本研究旨在解析泽泻倍半萜的生物合成通路,挖掘并鉴定参与倍半萜合成的关键功能基因,为阐明泽泻药效物质基础及后续质量标志物筛选与利用提供理论依据。因此,采用转录组学和分子生物学手段,挖掘并克隆出9个具有功能的东方泽泻倍半萜合酶基因AoTPSs,通过酵母异源表达体系,鉴定其生物化学功能,证实这些基因可催化合成β-榄香烯(β-elemene)、α-石竹烯(α-caryophyllene)、反式-橙花叔醇[(E)-nerolidol]、β-石竹烯(β- caryophyllene)、α-法尼烯(α-farnesene)等倍半萜类化合物。本研究为深入解析泽泻倍半萜的生物合成机制及资源开发奠定了基础。.
Cyclopropanes are prevalent motifs in pharmaceuticals and natural products; however, the construction of complex cyclopropanes remains a longstanding issue owing to low intrinsic reactivity and steric congestion. Herein, we report a visible-light-mediated cyclopropanation of unactivated alkenes with diazo compounds via an energy-transfer (EnT) pathway. This protocol provides direct access to a range of cyclopropanes, including spirocyclic, fused and those bearing quaternary carbon centers. Notably, a broad spectrum of unactivated alkenes-spanning endocyclic, bridged, polysubstituted, and terminal systems, along with diverse diazo reagents-are well tolerated, underscoring the generality of the method. The practicality is demonstrated by gram-scale synthesis and late-stage modification of natural products such as valencene, β-caryophyllene and flavanone. Moreover, in a preliminary in vitro assay, the caryophyllene oxide derivative exhibits promising anti-atopic dermatitis activity, showing nearly twice as high inhibition of CCL17 and CCL22 compared to its precursor, while exhibiting no detectable cytotoxicity. Finally, mechanistic studies support the involvement of triplet carbene species. These findings highlight the potential of this photochemical strategy for the rapid construction of challenging cyclopropanes and its utility in the development of bioactive natural product analogues.
Inflammation is a primary driver of skin ageing. Mussel mucin, a naturally occurring anti-inflammatory protein, suffers from inefficient extraction from its natural source. To overcome the yield limitation of natural sources and to verify the biological activity of the recombinant protein, this study employed synthetic biology techniques to efficiently produce and purify the recombinant mussel mucin Mfp151 and subsequently evaluated its anti-inflammatory and skin barrier repair functions. Using human immortalized keratinocytes (HaCaT), human foreskin fibroblasts (HFF-1), and human monocyte leukemia cells (THP-1) as models, we assessed the skin-repairing, antioxidant, and anti-inflammatory effects of Mfp151 via the CCK-8 assay, qPCR, transmembrane resistance measurement, scratch assay, ELISA, and free radical scavenging assays. In vivo validation was conducted with a zebrafish sunburn model. The results demonstrated that Mfp151 significantly promoted cell proliferation (80 μg/mL treatment increased HaCaT cell proliferation by approximately 32%) and migration, while upregulating the expression of key skin barrier genes IVL, OVOL1, and AQP3 by 2.14-3.88 folds. Mfp151 effectively scavenged DPPH and ABTS free radicals while enhancing cellular antioxidant capacity by activating the Nrf2 pathway. Regarding anti-inflammatory effects, Mfp151 significantly suppressed lipopolysaccharide-induced production of pro-inflammatory factors IL-6, TNF-α, and IL-1β (80 μg/mL treatment reduced expression levels to 59.87%-79.12% of that in the model group), while significantly downregulating the expression of key inflammatory mediators COX-2 and iNOS and their downstream product PGE2 (80 μg/mL treatment reduced COX-2, iNOS expression and PGE2 secretion to 48.91%-67.30% those in the model group.) Zebrafish experiments confirmed the significant promotion of Mfp151 on caudal fin repair following sunburn. The data indicate that the recombinant Mfp151 obtained through synthetic biology techniques possesses skin-repairing functions alongside antioxidant and anti-inflammatory activities, thus demonstrating promising application prospects in fields such as anti-ageing cosmetic ingredients and wound dressings. 炎症是导致皮肤衰老的主要诱因,贻贝黏蛋白是一种天然来源的抗炎蛋白,但其天然提取效率低下。为突破天然来源的产量限制,并验证重组蛋白的生物活性,本研究通过合成生物学技术高效制备并分离纯化得到重组贻贝黏蛋白Mfp151,并对其抗炎和皮肤屏障修复功能进行评价。以人永生化角质形成细胞(human immortalized keratinocytes, HaCaT)、人包皮成纤维细胞(human foreskin fibroblasts, HFF-1)及人单核细胞白血病细胞(human monocytic leukemia cells, THP-1)为模型,采用细胞计数试剂盒-8 (cell counting kit-8, CCK-8)、反转录实时荧光定量聚合酶链式反应(reverse transcription quantitative real-time polymerase chain reaction, RT-qPCR)、跨膜电阻测量、划痕实验、ELISA及自由基清除等方法,评估Mfp151在修复、抗氧化及抗炎方面的功效,同时利用斑马鱼晒伤模型进行体内验证。结果表明,Mfp151可显著促进细胞增殖(80 μg/mL处理使HaCaT细胞增殖率提高约32%)与迁移,并上调皮肤屏障关键基因IVL、OVOL1和AQP3的表达(相比正常对照组,上调2.14-3.88倍)。Mfp151能有效清除1,1-二苯基-2-三硝基苯肼(1,1-diphenyl-2-picrylhydrazyl, DPPH)和2,2′-联氮-双(3-乙基苯并噻唑啉-6-磺酸)[2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), ABTS]自由基,并通过激活Nrf2通路增强细胞抗氧化能力。在抗炎方面,Mfp151能有效抑制脂多糖(lipopolysaccharide, LPS)诱导的THP-1细胞产生促炎因子白细胞介素-6 (interleukin-6, IL-6)、肿瘤坏死因子-α (tumor necrosis factor-alpha, TNF-α)和白细胞介素-1β (interleukin-1β, IL-1β) (80 μg/mL处理使其表达水平降低至模型组的59.87%-79.12%),并显著下调关键炎症介质环氧合酶-2 (cyclooxygenase-2, COX-2)与诱导型一氧化氮合酶(inducible nitric oxide synthase, iNOS)的编码基因表达及其下游产物前列腺素E2 (prostaglandin E2, PGE2)的水平(80 μg/mL处理使COX-2和iNOS表达及PGE2的分泌降低至模型组的48.91%-67.30%)。斑马鱼实验证实其可显著促进晒伤后的尾鳍修复。本研究结果表明,通过合成生物学技术获得的重组Mfp151蛋白具有促进皮肤修复的功能和抗氧化抗炎活性,在皮肤抗衰化妆品原料及创面敷料等领域展现出良好的应用前景。.
Cordyceps militaris polysaccharides (CMPs) are food-relevant bioactive macromolecules attracting increasing interest in functional foods, nutrition, and health-promoting agricultural products. This review summarizes recent advances in the extraction, purification, structural characterization, biological activities, structure-activity relationships, safety evaluation, pharmacokinetics, potential applications, and bibliometric trends of CMPs. Current evidence shows that the monosaccharide composition, molecular weight, glycosidic linkages, branching degree, and conformational features of CMPs are closely associated with their antioxidant, immunomodulatory, anti-inflammatory, lipid-lowering, glucose-regulating, gut microbiota-modulating, and other health-related activities. These properties support the potential use of CMPs as natural ingredients for functional foods, nutritional products, feed additives, and food-related biomaterials. However, further progress is limited by insufficient standardization of extraction and purification methods, incomplete structural elucidation, limited pharmacokinetic and digestion data, and a lack of clinical validation. In particular, the scarcity of long-term safety data and a poor understanding of the oral absorption, metabolic fate, and systemic bioavailability of CMPs represent critical bottlenecks that must be resolved before translational development can proceed. This review provides a scientific basis for the quality control, functional evaluation, and food-oriented application of CMPs while underscoring the urgent need for rigorous safety and pharmacokinetic investigations to support their future development in nutrition and agricultural product sectors. © 2026 Society of Chemical Industry.
Degenerative cervical myelopathy (DCM) is a challenging neurological disorder characterized by chronic spinal cord compression, and surgical decompression is the only established treatment to relieve this compression. However, post-decompression spinal cord ischemia-reperfusion (IR) injury paradoxically worsens neurological function, and effective therapeutic treatments remain lacking. In this study, we purified a homogeneous and structurally well-defined Astragalus polysaccharide (APS) from Astragali Radix through sequential water extraction, alcohol precipitation, ion-exchange, and gel-filtration chromatography. Structural analysis revealed that this APS is a unique, low-molecular-weight, branched neutral polysaccharide with a (1 → 4)-α-D-glucan backbone. In a decompressive DCM rat model, 28 days of APS gavage improved motor function recovery (BBB scale and inclined plane test) in a dose-dependent manner, increased neuronal survival, reduced cavity area, and modulated apoptosis and ferroptosis without systemic toxicity. Mechanistically, as indicated by single-nucleus RNA sequencing and metabolomic profiling of rats, APS exerts neuroprotective effects by activating the neuronal Nrf2/HO-1 pathway, enhancing oxidative phosphorylation, subsequently inhibiting ferroptosis and apoptosis, and enhancing the tricarboxylic acid (TCA) cycle. In vivo, APS reduces ROS accumulation, enhances oxidative phosphorylation, upregulates the Nrf2/HO-1 pathway, and protects mitochondrial ultrastructure. In vitro, APS increases ATP production, restores mitochondrial membrane potential, and upregulates HO-1 expression, and the causal role of Nrf2 was demonstrated by Nrf2 knockdown or ML385 inhibition abolished APS-induced protection. This study systematically reveals the structure-activity relationship of this well-defined APS and its underlying molecular mechanisms, supporting its translational development as a candidate drug for spinal cord IR injury and providing a research paradigm for natural product-based investigations.
Plastic drinking straws are a visible single-use plastic product, yet selecting suitable substitutes remains challenging because literature-derived climate evidence and reported user experience are rarely evaluated together. This study develops and demonstrates an interpretable AI-enabled decision-support workflow that integrates literature-derived per-use greenhouse gas (GHG) indicators with review-derived user evidence extracted from online customer reviews using natural language processing (NLP). Drinking-straw alternatives were used as an information-rich case study. The integrated assessment combined a GHG-derived score, a user-experience feature score, and rating-based consumer approval within a transparent multi-criteria decision analysis (MCDA) under four predefined decision-priority scenarios. Among the five shortlisted materials and within the evaluated dataset, the selected per-use GHG assumptions, review-derived user evidence, normalization procedure, and scenario-specific weights resulted in Silicone achieving the highest integrated MCDA score across all four scenarios, whereas Paper ranked lowest. Silicone combined a low per-use GHG indicator with the highest user-experience feature score and high consumer approval. Paper had the highest per-use GHG indicator and a moderate user-experience feature score, while lexical analysis identified recurring functionality-related expressions in its reviews. A shallow decision tree identified a 0.081 kg CO₂e/use threshold separating Paper from the lower-per-use-GHG reusable alternatives within the evaluated decision matrix. The study is not a new process-based life-cycle assessment or comprehensive sustainability assessment. Instead, it demonstrates decision support limited to per-use GHG indicators and review-derived user evidence; broader sustainability dimensions were outside the scope. Future studies may adapt and evaluate the workflow for other product categories using product-appropriate environmental criteria and relevant user-derived evidence.
Glycosylation is an important post-translational modification that can alter the biological activities of antibodies. In monoclonal antibody biotherapeutic products, glycosylation of the Fc-domain, which is often sensitive to manufacturing conditions, can alter product potency by affecting its interactions with host immune cells. Improving control of antibody glycosylation to produce more chemically defined products and to better understand glycan function is gaining interest, with chemoenzymatic glycan engineering emerging as a powerful technique. This chapter describes methods to obtain purified glycans, including isomers with asymmetric antennae, their enzymatic incorporation into monoclonal antibodies, and a natural killer T cell-based binding assay to determine FcγRIIIA (CD16A) binding affinity.
Nonoxidative ethane dehydrogenation (NOEDH) is a carbon efficient but thermodynamically severe route for ethene production. Solar-driven NOEDH offers a promising alternative, yet achieving both high activity and high ethene selectivity over noble metal-free catalysts without external heating remains unresolved. Here, we reported that Ti3+-O acid-base pairs on reduced rutile TiO2 enabled highly efficient full-spectrum solar-driven photothermal NOEDH without any external heating. The optimally reduced TiO2 at 750 °C delivered an ethene production rate of 392.0 mmol g-1 h-1, which was 1107 times higher than that of pristine TiO2 without reduction pretreatment. The high activity with a C2H4 selectivity of 94.9% surpassed the thermodynamic equilibrium limit and outperformed previously reported systems. Comprehensive characterizations identified surface Ti3+ sites adjacent to lattice oxygen as Lewis acid-base pairs that enhanced light absorption, promoted charge carrier separation, and directly participated in the C-H bond cleavage. Photogenerated electrons also preferentially accumulated on the coordinatively unsaturated Ti3+-O sites, which weakened ethene adsorption, thereby accelerating product desorption and suppressing deep dehydrogenation and coke formation. The synergy between photogenerated hot carriers and localized photothermal heating lowered the apparent activation energy from 157.6 kJ mol-1 in the dark to 75.0 kJ mol-1 under illumination. This work establishes surface acid-base pairs on noble metal-free catalyst as a powerful platform for sustainable light-driven alkane upgrading.
The efficacy of bio-organic fertilizers is strongly dependent on functional microbial strains; however, systematic frameworks for candidate strain acquisition, functional screening, application validation, and strain characterization remain insufficiently developed for bio-organic fertilizer research and product development. This review synthesizes the major functional microbial groups used in bio-organic fertilizers and their mechanisms of action, with particular emphasis on strain selection strategies, functional screening and application-validation pathways, and methods for strain identification and functional characterization. Current evidence indicates that conventional culture-based isolation, oligotrophic screening, extreme-habitat screening, and modern molecular and data-driven approaches each occupy distinct methodological niches. These strategies are respectively suited to pure-culture resource acquisition, discovery of strains adapted to resource-limited environments, identification of stress-tolerant and process-adaptive strains, and candidate discovery coupled with functional analysis. Importantly, optimization of functional strains should not rely solely on single in vitro trait-based screening. Instead, it should integrate formulation-related adaptability, robustness-oriented microbial phenotyping, and application-context validation into a tiered evaluation framework spanning strain acquisition, functional screening, application validation, and strain identification and functional characterization. This review provides a systematic methodological reference for the selection, evaluation, and product development of functional strains for bio-organic fertilizers (BOFs).
Selective C-H functionalization of small molecule leads is a powerful approach for efficient chemical space exploration and medicinal chemistry optimization. Here, we report a screening strategy for early- and late-stage chemoenzymatic oxidation of steroid-inspired compounds using a panel of P450BM3 variants. Late-stage oxidation of sterol transport protein inhibitors and their intermediates revealed enzyme- and substrate-dependent regioselectivity, which was rationalized by docking studies, and yielded hydroxylated analogues that provided rapid structure-activity relationship insights into the spirooxepinoindole as a privileged scaffold and its potential metabolic products. Early-stage functionalization of steroidal building blocks, including the Wieland-Miescher ketone and acetyl-cis-decalone, furnished hydroxylated derivatives with high diastereoselectivity. Notably, both enantiomers of both diastereoisomers of the C6-hydroxylated Wieland-Miescher ketone were obtained in preparative quantities, providing access to valuable early-stage building blocks for further derivatization. This work highlights the potential of chemoenzymatic approaches to deliver regio- and stereoselective oxidations of challenging steroid-like scaffolds, complementing classical synthetic methods and expanding opportunities in medicinal chemistry and natural product synthesis.
Catalyzing ammonium perchlorate (AP) thermal decomposition is essential for improving the energy release of composite solid propellants. Single-atom catalysts (SACs) show great potential in AP catalysis, but systematic research on their regulation of AP decomposition and propellant combustion remains insufficient. Herein, four carbon black-supported transition metal single-atom catalysts (M-SACs, M = Fe, Co, Ni, Cu) were prepared via a coordination adsorption-pyrolysis strategy, and their atomic dispersion and coordination structure were systematically characterized. Thermal tests demonstrate that Cu-SAC delivers the best catalytic performance, reducing AP's high-temperature decomposition peak by 103.6°C, increasing heat release by 4.1 times, and lowering activation energy by 96.3 kJ/mol. Molecular dynamics simulations confirm that Cu-N active sites strongly adsorb key intermediates (NH3 and HClO) and weakly bind final products, providing a thermodynamic basis for its superior catalytic activity. In AP-based propellants, Cu-SAC increases burning rate by 25.6% and shortens ignition delay by 23.1%, while effectively suppressing molten aluminum agglomeration and reducing condensed combustion product size by 61%. This work establishes the multi-scale structure-activity relationship of Cu-N coordination, offering a new route for the design of high-performance propellant combustion catalysts.