Active polysaccharides from food-medicine homologous sources are pivotal for the modernization of Food-Medicine Homologous substances. However, their clinical translation and efficacy exertion are hindered by three critical bottlenecks: inadequate targeting ability (prone to dispersion in non-target tissues, thus limiting efficient accumulation at lesion sites), low bioavailability (some polysaccharides with large molecular weights are susceptible to glycosidase degradation or unable to penetrate physiological barriers), and poor stability (vulnerable to pH fluctuations and enzymatic hydrolysis in the gastrointestinal tract). This paper proposes a "carrier adaptation-targeted modification-environmental response" synergistic strategy. Carrier adaptation provides a stable transportation foundation for polysaccharides, targeted modification achieves precise positioning, and environmental response ensures on-demand release at target sites. The synergistic effect of the three constructs a precise delivery system for active polysaccharides. This strategy not only addresses the delivery dilemmas of these polysaccharides but also enhances their targeting precision, bioavailability, and stability, advancing functional foods toward precision nutrition and aiding chronic disease prevention.

Ulcerative colitis (UC) has long defied safe and curative treatment. Opuntia Milpa Alta-derived exosome-like vesicles (ODV) have been isolated with lipid-wrapped messengers, and loaded with anti-inflammatory phenols, lipids, and proteins. When given orally to mice with DSS-induced colitis, these plant-derived vesicles (PDV) ignored healthy tissue but homed to inflamed colon, where they quietly rebuilt the broken barrier. Colon length was restored, weight loss halted, goblet cells returned, and pro-inflammatory storms (TNF-α, IL-6, and IL-1β) were silenced as effectively as the standard drug 5-ASA–yet without toxicity. ODV reshaped the chaotic gut microbiota, reviving SCFAs-producing heroes (Lactobacillus, Akkermansia, and Muribaculaceae) while banishing pathogens; three absorbed phenolic phytochemicals (piscidic acid, eucomic acid, and p-hydroxybenzoic acid) then reprogrammed colonic fatty acid metabolism via key genes (Acsl1, Acaca, and Fabp4a), turning inflammation off at its metabolic roots. Thus, ODV offers a safe, natural, and mechanistically innovative path forward for colitis and beyond.

Alcoholic liver disease (ALD) has emerged as a critical global health concern. Dendrobium officinale polysaccharide (DOP) shows therapeutic potential against ALD. However, despite its promising effects, the protective mechanism of DOP on the ALD is unclear. To investigate the protective mechanisms of DOP, we successfully established an ethanol-induced liver injury model in mice and treated ALD mice with DOP. The results demonstrate that DOP treatment significantly reduced hepatic TG, TC, AST, ALT and MDA levels, while enhancing antioxidant capacity through elevated SOD, GST and GPx, reduced GSH and CAT activities. Mechanistically, DOP activates the KEAP1-Nrf2 signalling pathway, reduces the expression of Keap1, and simultaneously upregulates the expression of Nrf2 and its downstream target NQO1. Furthermore, DOP restored lipid homeostasis in ALD mice. In summary, these findings provide strong scientific evidence for the therapeutic potential of DOP in the treatment of ALD and establish a foundation for developing DOP based natural hepatoprotective agents.

This study aims to reveal the spatial distribution patterns of effective components in different parts of morel mushrooms, analyse the impact of cultivation on soil factors, and explore the intrinsic relationship between soil factors and effective components, providing a theoretical basis for precision cultivation and ecological agriculture. Samples were collected from two regions, Daozhen and Shuicheng, and 28 soil factors and five effective components were measured. Correlation analysis was conducted to study the coupling relationships between variables. The results showed that post-planting, soil alkali-hydrolysable nitrogen (AN), total nitrogen (TN), available potassium (AK), total humic acid (THA), C/P and N/P levels increased at both sites, with respective increases of 8.5%-48.1%, 1.2%-26.8%, 40.2%-84.7%, 6.5%-23.4%, 10.5%-51.1% and 12.8%-41.3%; while pH, total phosphorus (TP), water-soluble humic acid (WSH), Na, Fe, Zn, Mn and Se decreased by 2.4%-4.6%, 10.1%-10.8%, 4.1%-21.9%, 0.6%-5.5%, 0.7%-4.9%, 2.3%-2.9%, 5.3%-21% and 15.5%- 21.2%, respectively. Both region are primarily nitrogen-limited with accompanying phosphorus mineralisation, while carbon limitation is not significant. Cap content is generally higher than stalk content, but the difference between the two parts within the same region is within 5%, indicating significant development potential for the stalk. The Daozhen region exhibits superior accumulation of total phenols and total saponins, while the Shuicheng region stands out for its higher polysaccharide and protein content. The two origins show little difference in total flavonoids. Soil factors total potassium (TK), Mg, Na, Fe, Cu, Zn, Mn, Co, Be and Ni all showed positive correlations (p <= 0.05) with total phenolics, total saponins and protein content. These factors collectively promoted the accumulation of these three effective components in morel mushrooms, while TK, Mg, Na, Fe, Co and Ni all showed negative correlations with total polysaccharides (p > 0.05). Increased levels of these soil factors inhibit the accumulation of total polysaccharides in morel (p > 0.05). Total flavonoids are minimally affected by soil factors, exhibiting only a negative correlation with SOM. Soil factors are the key limiting factors for effective components, and production management should be adjusted according to local conditions.

Quercetin, jatrorrhizine, berberine, dehydrocostus lactone, and magnolol are prominent compounds known for their antitumor properties. A series of chemical reactions such as protection, hydrolysis, Michael addition and substitution were conducted using rutin as the initial material to synthesize methyl-quercetin conjugates with berberine, jatrorrhizine, and dehydrocostus lactone. Additionally, jatrorrhizine and magnolol conjugates were synthesized through a two-step substitution process. The resulting products were structurally confirmed using 1H-NMR, 13C-NMR, ESI-MS and ESI-HRMS techniques. The MTT assay was employed to preliminarily assess the in vitro antiproliferative effects of these compounds on four tumor cell lines: MHCC97H, HCC827, Hela, and HEL. Results indicated that the final conjugated products generally showed more potent inhibitory effects on tumor cell proliferation than the original lead compounds. In particular, final product 7 exhibited an inhibitory effect on the MHCC97H tumor cell line that was comparable to a positive control drug, highlighting its potential as a candidate for antitumor drug development. Molecular docking studies were conducted on final product 7 to explore its affinity and binding interactions with VEGFR-2 and TrxR1 proteins, aiming to elucidate its binding characteristics and possible antitumor mechanisms.

Cadmium (Cd) is a highly toxic and mobile heavy metal of environmental concern, while calcium (Ca) is essential for plant cell metabolism and signal transduction. This study aimed to explore the effect of exogenous Ca application on Cd enrichment and transport in a Cd-enriched crop, pepper (Capsicum annuum L.), grown on a high-Cd acidic soil in a karst region. The biological concentration factors were all greater than 1 in plant roots, stems, and leaves at different growth stages. The Cd sequestered by roots accounted for 56%-73% of the total Cd accumulation in the whole plant, while the fruits showed Cd accumulation of only 1%-5% of the total. As the plant grew, the Cd accumulation in the aboveground parts decreased in the high Ca/Cd treatments (6 mg kg-1 Cd with 1.6 or 3.2 g kg-1 Ca). Plant accumulation of Cd at the harvesting stage exhibited a significantly inverse correlation with the level of Ca added exogenously to soil. The results of this study elucidate the effect of elevated soil Ca levels on Cd accumulation in plants in karst regions and provide valuable insights into the remediation of Cd contamination in acid yellow soils with a geologically high background Cd level.

Abstract Premma puberula Pamp. is a kind of medicinal and edible plant that is widely distributed in Southwest of China. The content of pectin in different tissues is different, but the reason for the difference is unknown. In this study, we detected and found that pectin content varies greatly in roots, stems and leaves of P. puberula and we carried out microstructure of leaves, stems and roots, detected histochemical localization, galacturonic acid (GalA) content, degree of esterification (DE), scanning electron microscopy (SEM), X-ray diffraction (XRD) of pectin and binding transcriptomics to investigate the pectin polysaccharide biosynthesis and related genes from different tissues at the molecular level. A total of 26.04 Gb clean data of the high-quality reads were successfully mapped to the reference genome of P. puberula and assembled into 107,250 nonredundant genes. We mapped all of the genes to reference pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database to identify pectin biosynthesis pathways in which the genes might be involved, which provide understanding of the regulation of P. puberula pectin at the molecular level. The pectin-related key enzyme genes were identified, and these studies have important value for understanding the biosynthesis mechanism of pectin in different tissues.

A multicolored supramolecular assembly was constructed by co-assembling a dibromoanthraquinone-9-one phenylpyridine cationic derivative (DBXPY) with cucurbit[8]uril (Q[8]) and tetramethylcucurbit[6]uril (TMeQ[6]). It achieved white-light emission and tunable fluorescence, with applications in anti-counterfeiting, LEDs and cell imaging.

BackgroundMetabolic dysfunction-associated steatohepatitis (MASH) is a progressive form of metabolic dysfunction-associated steatotic liver disease with limited pharmacological treatment options. Wogonoside (WOG), a flavonoid isolated from Scutellaria baicalensis, exhibits anti-inflammatory, antioxidant, and lipid-lowering activities; however, its effects and underlying mechanisms in MASH remain unclear.MethodsA high-fat and high-fructose diet (HFFD)-induced mouse model of MASH and free fatty acid (FFA)-induced HepG2 cell steatosis model were used to evaluate the hepatoprotective effects of WOG. Liver histopathology, serum biochemical parameters, glucose tolerance, lipid accumulation, oxidative stress, ferroptosis-associated indicators, transcriptomic profiling, and expression of relevant proteins were assessed. The anti-ferroptotic effects of WOG were further examined using erastin and ferrostatin-1 in HepG2 cells.ResultsWOG administration ameliorated HFFD-induced obesity, hepatic steatosis, hepatocellular ballooning, liver injury, dyslipidemia, insulin resistance, oxidative stress, and inflammatory responses in mice. Transcriptomic analysis indicated that WOG-responsive genes were enriched in lipid metabolism, peroxisome proliferator-activated receptor signaling, AMPK signaling, and ferroptosis-related pathways. In liver tissues and FFA-treated HepG2 cells, WOG increased AMPK phosphorylation and upregulated the expression of PGC-1α, PPARα, and CPT-1, while reducing the expression of SREBP-1c and its downstream lipogenic proteins, including ACLY, ACACA, FASN, and SCD-1. These changes were accompanied by decreased hepatic and intracellular triglyceride accumulation. In addition, WOG reduced reactive oxygen species, restored mitochondrial membrane potential, increased Nrf2 and HO-1 expression, and attenuated inflammatory responses. WOG also decreased Fe2+ accumulation and lipid peroxidation, restored glutathione homeostasis, and increased xCT and GPX4 expression in vivo and in vitro. Moreover, WOG counteracted erastin-induced ferroptosis-related changes and exhibited effects similar to those of ferrostatin-1 in FFA-treated HepG2 cells.ConclusionWOG alleviates experimental MASH by improving hepatic lipid metabolic homeostasis and suppressing ferroptosis-associated injury. These protective effects are associated with activation of AMPK signaling and restoration of the xCT/GPX4 antioxidant defense axis. WOG may therefore represent a promising candidate for the pharmacological management of MASH.

A purely organic supramolecular assembly emitting room-temperature phosphorescence (RTP) was constructed from 1-(3-(bis(pyridin-2-ylmethyl)amino)propyl)-4-(4-bromophenyl)pyridin-1-ium bromide (BP-DPA) by complexing with cucurbit[8]uril (Q[8]) and Zn2+ through a supramolecular assembly. Benefiting from the strong affinity and the macrocyclic restriction effect of Q[8], phosphorescence emission was achieved by encapsulating BP-DPA in the Q[8] cavity. Notably, secondary assembly with Zn2+ formed the supramolecular complex BP-DPA@Q[8]⊂Zn2+, which greatly contributed to the enhancement of the phosphorescence quantum yield and lifetime from 1.75% to 6.25% and from 0.48 to 1.25 ms, respectively. Meanwhile, BP-DPA@Q[8] specifically recognizes Zn2+ with a low detection limit without interference from common metal ions, anions, and biomolecules. It permeates the plasma membrane of cells and emits a specific phosphorescence response signal in the presence of Zn2+. In addition, this material can also be utilized for the development of portable indicator papers, enabling the rapid and visualized detection of Zn2+. This work provides a route for constructing multilevel supramolecular assemblies of RTP, extending the biological applications of purely organic RTP materials and offering additional possibilities for the potential utilization of cucurbit[n]uril-based room-temperature phosphorescence materials.

The aim of this study was to design and synthesize 17 novel 1,2,4-triazole thioether derivatives containing 1,3,4-thiadiazole thioether.

INTRODUCTION:Phosphatidylinositol 5-phosphate 4-kinase type II gamma (PI5P4Kγ) has emerged as a promising therapeutic target in oncology due to its key role in cancer progression. However, currently available inhibitors targeting either the orthosteric or allosteric sites of PI5P4Kγ suffer from limited in vitro activity and in vivo validation. OBJECTIVES:This study aimed to develop a highly potent and selective PI5P4Kγ inhibitor capable of simultaneously engaging both the orthosteric and allosteric sites, as well as to validate their potential in therapy for non-small cell lung cancer (NSCLC) were investigated. METHODS:Through the structural modification of the propionamide side chain of the pyridine ring and the N3 substituent of the quinazolinone, the structure-activity relationship (SAR) was elucidated, leading to the identification of the target compound n40. The binding mode of n40 to PI5P4Kγ, was elucidated by X-ray crystallography. In vitro effects were assessed through KINOMEscan Technology, cell proliferation, apoptosis, and EMT analysis. In vivo efficacy was evaluated using an HCC827 xenograft mouse model. Both single-dose (up to 400 mg/kg) and repeated-dose (20-180 mg/kg/day for 28 days) toxicity studies of n40 were conducted in mice, with comprehensive monitoring of physiological parameters and organ toxicity indices. RESULTS:Compound n40 exhibited a strong binding affinity for PI5P4Kγ (Kd = 6.55 nM), with 3,000-fold selectivity over other two isoforms. Additionally, it displayed sub-50 nM antiproliferative activity in NSCLC cells with higher PI5P4Kγ levels. X-ray crystallography revealed n40 simultaneously binds to both orthosteric and a novelallosteric pocket. Functionally, n40 induced S-phase arrest, apoptosis, and EMT reversal and PI3K/AKT/mTOR signaling inhibition in a PI5P4Kγ-dependent manner. In HCC827 xenografts, n40 achieved > 60 % tumor growth inhibition without any observed toxicity. CONCLUSION:This study establishes PI5P4Kγ as a druggable target in NSCLC and demonstrates that dual orthosteric-allosteric targeting is a viable strategy to achieve potent and selective PI5P4Kγ inhibitors.

Overexpression of EphB3 has been documented across various cancers and essential for cell proliferation, survive and metastasis, making it a valuable therapeutic target. In this study, a series of novel penta-1,4-dien-3-one and quinoxaline conjugates were designed and synthesized using pharmacophore fusion strategies to explore potential EphB3 inhibitors. CCK-8 experiments revealed significant anti-cancer activity of most newly synthesized compounds against hepatocellular carcinoma (HCC). Among them, compound W8 displaying the highest inhibitory activity against MHCC97H (IC50 = 1.87 μM), which arrests MHCC97H cells in the G0/G1 phase and induces apoptosis. Furthermore, compound W8 suppresses tumor growth in an MHCC97H xenograft model in vivo by suppressing phosphorylation level of EphB3 and down-regulating the SRC-AKT signaling pathway, leading to a dose-dependent reduction in tumor volumes and weights, with a 40 mg/kg dose achieving decreases of 68.4 % and 65.3 %, respectively. Given its ability to modulate EphB3 signaling, W8 represents a promising lead compound for further drug development, particularly for cancers characterized by EphB3 overexpression, and may offer new opportunities for targeted therapy in precision oncology.

The poor prognosis of hepatocellular carcinoma (HCC) is mainly due to its high metastatic properties. Hence, metastasis inhibition might provide a reliable strategy for HCC treatment. As its pivotal role in the tumor cell proliferation, survival and metastasis, a disintegrin and metalloproteinase 17 (ADAM17) has become an attractive target for cancer therapy. Nevertheless, the role of ADAM17 in HCC metastasis and its underlying mechanisms remain enigmatic. In the present study, we discovered a novel ADAM17 inhibitor FLF-15, with an IC50 value of 10.43 nM. Further mechanistic studies showed that FLF-15 inhibits HCC migration and invasion in vitro and in vivo mainly by reducing interleukin-6 receptor (IL-6R) shedding, which inhibits IL-6 trans-signaling, while also leading to a reduction in IL-6 levels and downregulation of IL-6 classic-signaling. Furthermore, we revealed an overlapping but distinct biological effects of IL-6 classic and trans-signaling in HCC. Specifically, JAK2/STAT3 and ERK1/2 signaling can be stimulated by both IL-6 classic and trans-signaling pathway. However, AKT appears to be only activated by IL-6 trans-signaling pathway, suggesting its essential role for FLF-15 induced metastasis suppression in HCC. Taken together, our study identified FLF-15 as a novel ADAM17 inhibitor and elucidated its underlying mechanism of HCC metastasis suppression. These findings indicated FLF-15 might be a promising candidate for the development of HCC therapeutic agents.

To understand the degree of contamination, the concentrations of heavy metals, and the associated risks in different parts of wild and cultivated morel mushrooms from various origins, this study quantified seven heavy metals and conducted evaluations of safety, pollution levels, and health risks. The concentrations of Pb, Hg, Cu, and Zn were higher in wild morel mushrooms than in cultivated ones, while the concentrations of As, Hg, Cu, and Zn were higher in the caps than in the stalks. Overall, wild morel mushrooms exhibited a stronger capacity for bioaccumulating heavy metals, especially in the caps. The contents of As and Hg were both below the maximum limit values, indicating a safe level. However, Cu, Pb, and Cd in different samples, suggested varying degrees of contamination and these elements were identified as the main pollution contributors. The total non-carcinogenic risk (HI) value for children is higher than that for adults. Cd and Cu are the primary contributors to the total non-carcinogenic risk (HI) in both cultivated and wild morel mushrooms. The carcinogenic risk (CR) values of Cd, As, and Cr in all samples indicated potential carcinogenic risks. The carcinogenic risk for children is approximately twice that for adults. In summary, the heavy metal risk in morel mushrooms is higher in wild than in cultivated ones, higher in the caps than in the stalks, and higher for children than for adults. Therefore, it is necessary to strengthen environmental control and consumption guidance in production areas to reduce health risks.

Berberine represents a prominent compound with commendable antitumor activity, a novel berberine derivative with substituted o-diaminobenzene moiety linked at the 9-position through oxadiazole and alkyl chain is designed, synthesized by reference to the histone deacetylase (HDAC) inhibitor structure mode through selective demethylation, substitution, hydrazolysis, acylation, cyclization, elimination, condensation reaction. The structures of these synthetic derivatives were characterized and confirmed by 1H NMR (nuclear magnetic resonance), 13C NMR, and MS (mass spectrometry) spectral data and finally evaluated for antitumor activities against MHCC97H, HCC827, HELA, and HEL cell in vitro by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) method. The results demonstrated that target compound 8 exhibited better antiproliferative activity against the MHCC97H cell line, with a half maximal inhibitory concentration (IC50) = 5.4 ± 0.45 μM L–1 superior to berberine, and the activity against MHCC97H was nearly close to the reference drug doxorubicin. Through the dynamics of molecular docking and simulation, further analysis has demonstrated that the target compound 8 can form effective interactions with the HDAC6 target protein, and the results of binding free energy also revealed a strong affinity between the compound 8 and the HDAC6 protein. The results of this study suggest that compound 8 may be a potential inhibitor of HDAC6, which could have promising applications in the treatment of certain cancers.

Andrographis paniculata (Burm. f.) and its products have a long history of medicinal use in Asia. A. paniculata products are mainly made from the root extraction of stems, leaves and parts, but there may be differences in the proportion of different parts and different harvest times, which ultimately leads to certain differences in product quality. In this study, the chemical components and non-targeted metabolomics were characterized, and the characteristic compounds in different parts of A. paniculata at various growth stages were analyzed. By utilizing polygonal mass defect filtering, precursor ion lists, and a self-built compound library, a total of 225 components were identified in A. paniculata. Notably, spermidine derivatives and phosphatidylcholines were reported for the first time in this plant species. In total, 41 differential components were identified in different parts of A. paniculata. These findings provide scientific evidence for the selection of quality markers in A. paniculata and its products.

Aims This study aimed to investigate where acidification occurred in soil profiles of Guizhou tea gardens, and the influence of acidification on the availability of soil mineral elements in order to inform soil nutrient management and improvement practices in tea gardens. Methods The acidification characteristics were investigated in soils from plantations grown for various numbers of years and across different soil layer profiles. Moreover, the pH buffering capacities (pHBC) of soils were evaluated and changes of mineral elements’ contents due to soil acidification were explored. Key results With increased tea plantation age, the acidification rate of 0–20-cm soil layers reached 0.025 pH unit/year. Soil acidification extended from the surface layer downwards through profiles, while the pH of entire soil layers were <4.5 after 40 years of tea plantation. The pHBC of soils were <30 mmol/kg, remaining at a weak sensitive level. Fe, Mn, Cu, Zn, Mo, and B concentrations exhibited decreasing trends in soils, while As, Pb, Cr, and Cd exhibited enrichment at the surface. Tea plantation age and soil depth were significantly correlated with the available concentrations of soil mineral elements. Conclusions Soil acidification gradually increased downward from the surface and soil minerals were lost in acidic environments, while the acid buffering capacity was reduced. Implications These results suggest that organic fertilisers and trace elements should be supplemented as needed in the management of tea gardens to achieve long-term stability of quality and yields.