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Results for “molecular docking”

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PubMed2026

Multi-omics analysis reveals coordinated epigenetic dysregulation in atrazine-induced dopaminergic neurotoxicity.

Atrazine (ATR), a widely used triazine herbicide, has been linked to neurotoxicity, yet the epigenetic mechanisms underlying its dopaminergic effects remain unclear. This study investigated whether coordinated miRNA dysregulation and DNA methylation alterations contribute to ATR-induced Parkinson's disease (PD)-like neurotoxicity. Male Sprague-Dawley rats were administered ATR (50 mg/kg/day) for 90 days, resulting in motor and cognitive deficits with dopaminergic dysfunction, including increased α-synuclein and reduced tyrosine hydroxylase expression. Small RNA sequencing identified 72 differentially expressed miRNAs in the substantia nigra, enriched in PI3K-Akt, MAPK, and Ras signaling pathways. In a cohort of six PD patients and six matched controls, genome-wide DNA methylation profiling revealed 4694 differentially methylated positions, predominantly hypomethylated, with overlapping enrichment in neuronal signaling pathways. Weighted gene co-expression network analysis identified a PD-associated module strongly correlated with disease status (r = -0.95, P < 0.001). Multi-omics integration identified CASP3 as a central hub gene. External validation supported CASP3 relevance in PD (AUC = 0.833), and molecular docking suggested potential ATR-CASP3 interaction. Further analysis predicted upregulated miR-3552 as a potential upstream regulator of CASP3. These findings indicate that ATR-induced neurotoxicity may be mediated through the miR-3552/CASP3 signaling axis, ultimately regulating apoptosis and contributing to neurodegeneration.

Animals↗

PubMed2006

Computational analysis of plasmepsin IV bound to an allophenylnorstatine inhibitor.

The plasmepsin proteases from the malaria parasite Plasmodium falciparum are attracting attention as putative drug targets. A recently published crystal structure of Plasmodium malariae plasmepsin IV bound to an allophenylnorstatine inhibitor [Clemente, J.C. et al. (2006) Acta Crystallogr. D 62, 246-252] provides the first structural insights regarding interactions of this family of inhibitors with plasmepsins. The compounds in this class are potent inhibitors of HIV-1 protease, but also show nM binding affinities towards plasmepsin IV. Here, we utilize automated docking, molecular dynamics and binding free energy calculations with the linear interaction energy LIE method to investigate the binding of allophenylnorstatine inhibitors to plasmepsin IV from two different species. The calculations yield excellent agreement with experimental binding data and provide new information regarding protonation states of active site residues as well as conformational properties of the inhibitor complexes.

Animals↗

PubMed2026

Free polyphenols and multi-omics traits underlying antioxidant variation across Paeonia lactiflora leaf cultivars.

Leaves of Paeonia lactiflora are underutilized by-products with potential as natural antioxidant sources. In this study, 18 cultivars were evaluated for phytochemical composition and in vitro antioxidant capacity. Total phenolic content correlated strongly with DPPH and ABTS activities, and the comprehensive antioxidant index identified 'Coral Charm' and 'Hangshao' as representative high- and low-antioxidant cultivars, respectively. Untargeted metabolomics detected 2677 metabolites and identified 908 differential metabolites between the two cultivars. Targeted phenolic profiling quantified 27 compounds, among which 11 differed significantly between the two cultivars. Catechin and epicatechin were enriched in 'Coral Charm', with contents of 6.62 and 0.397 ng/mg, respectively, compared with 0.012 and 0.002 ng/mg in 'Hangshao'. (+)-Dihydroquercetin was also more abundant in 'Coral Charm', while caffeic acid showed an upward trend. Proteomic analysis identified 423 differentially expressed proteins, mainly associated with secondary metabolite biosynthesis, redox homeostasis, and central carbon metabolism. Integrated analysis identified pyruvate metabolism as the only pathway significantly enriched in both metabolomic and proteomic datasets. Molecular docking predicted favorable binding between representative phenolics and selected proteins. These findings link cultivar-dependent antioxidant variation in peony leaves with free-phenolic accumulation and pathway-level metabolic differences, supporting the selection and utilization of antioxidant-rich peony leaf resources.

Antioxidants↗

PubMed2025

Targeting the bile acid receptor TGR5 with Gentiopicroside to activate Nrf2 antioxidant signaling and mitigate Parkinson's disease in an MPTP mouse model.

INTRODUCTION: Parkinson's disease (PD) is a common neurodegenerative disorder characterized by classical symptoms including bradykinesia, rest tremor and rigidity. Oxidative stress and mitochondrial dysfunction are recognized as pivotal factors in PD progression. Gentiopicroside (GPS), a secoiridoid derived from Gentiana manshurica Kitagawa, exhibits antioxidant and mitophagy induction properties. Nonetheless, the effects and mechanisms by which GPS mitigates neurodegeneration in PD remain to be thoroughly elucidated. OBJECTIVES: The goal of this study was to investigate the neuroprotective effects and mechanisms of GPS in PD models. METHODS: We established the MPTP/MPP+-induced PD models to measure the neuroprotection of GPS. Transcriptomic analysis, oxidative biochemical kits, western blot and cell immunofluorescence were conducted to elucidate the fundamental mechanisms at play. Subsequently, the targeting and activation of the transmembrane G protein-coupled receptor-5 (TGR5) by GPS were measured by molecular docking, cellular thermal shift assay, microscale thermophoresis (MST) and cyclic adenosine monophosphate (cAMP) quantitation. Finally, we verified whether the neuroprotective and antioxidant effects of GPS were dependent on TGR5 by using specific small interfering RNA (siRNA), pharmacological antagonist and knockout mice. RESULTS: GPS significantly attenuated dopaminergic (DAergic) neuron loss and restored motor function in the MPTP-induced PD mouse model. Whole-genome RNA sequencing and subsequent mechanistic investigations revealed that GPS enhanced the expression and facilitated nuclear entry of factor erythroid-related 2-factor 2 (Nrf2), and reduced oxidative stress and mitochondrial dysfunction stimulated by neurotoxin. Additionally, GPS could target TGR5 and prevent its downregulation in PD model. TGR5's silencing or inhibition weakened the neuroprotective effect of GPS and blocked GPS-mediated activation of Nrf2 antioxidant signaling in PD model. Moreover, the therapeutic effect of GPS in mitigating motor deficits and neurodegeneration was also abolished in Tgr5 knockout mice. CONCLUSION: These findings collectively indicated that GPS targeted TGR5 to activate Nrf2 antioxidant signaling and ultimately ameliorated the pathological progression of PD.

Animals↗

PubMed2005

Inhibition of Naja kaouthia venom activities by plant polyphenols.

Plant polyphenols from the aqueous extracts of Pentace burmanica, Pithecellobium dulce, Areca catechu and Quercus infectoria were tested for their inhibitory activities against Naja kaouthia (NK) venom by in vitro neutralization method. The first three extracts could completely inhibit the lethality of the venom at 4 LD50 concentration and the venom necrotizing activity at the minimum necrotizing dose while also inhibited up to 90% of the acetylcholinesterase activity of NK venom at much lower tannin concentrations than that of Quercus infectoria. The ED50 of plant tannins in inhibiting NK venom activities varied according to condensed tannins and their content in the extracts. Molecular docking of the complexes between alpha-cobratoxin and either hydrolysable or condensed tannins at their lowest energetic conformations were proposed. The anti-venom activities of these plant polyphenols by selectively blocking the nicotinic acetylcholine receptor and non-selectively by precipitation of the venom proteins were suggested.

Animals↗

PubMed2026

In silico genome mining and characterization of putative horse feces-derived bacterial phytases as potential monogastric animal feed additive candidates.

Phytic acid exerts a significant antinutritional effect in poultry, swine, and fish, which can be mitigated by supplementing monogastric feeds with efficient microbial phytases. Accordingly, mining bacterial genomes for novel phytases represents a strategic computational approach to identifying candidates for improving monogastric animal nutrition. In this study, 162 bacterial genomes associated with horse feces were systematically mined using an in silico pipeline to identify and characterize putative phytases.A total of 69 non-redundant sequences were identified and classified as histidine acid phytase (HAPhy) or protein tyrosine phosphatase-like phytase (PTPLPhy). HAPhys were detected in the genomes of Escherichia coli, Klebsiella pneumoniae, Salmonella enterica, Acinetobacter baumannii, and Cutibacterium equinum, whereas PTPLPhys were found in K. pneumoniae, Limosilactobacillus reuteri, Pediococcus acidilactici, Bifidobacterium pseudolongum, and Prescottella equi. Principal component analysis identified glucose-1-phosphatase (CAJ1242485.1) and bifunctional acid phosphatase (NHR17779.1) as the HAPhy candidates exhibiting the most favorable predicted physicochemical properties for potential feed applications. Similarly, among the PTPLPhys, protein tyrosine phosphatase (UNQ40438.1) and a hypothetical protein (CAJ1246072.1) showed the most favorable computational profiles. Biosafety analysis identified potential virulence factors, indicating that sources should be screened prior to feed application. High-quality AlphaFold2 models were obtained for these phytases (90.9-97.2). Molecular docking analysis showed that NHR17779.1 exhibited the strongest binding to phytic acid, whereas CAJ1246072.1 demonstrated the weakest interaction. Overall, this study identifies the horse fecal microbiota as a diverse source of putative phytases that may serve as promising targets for genetic and protein engineering; however, further in vitro and in vivo studies are essential to validate the enzymatic activity and industrial efficacy of these computational candidates.

Bacterial phytase↗

PubMed2026

Nitrilase-mediated degradation of insecticides flonicamid and thiacloprid by immobilized engineered Escherichia coli with a novel pathway.

The nitrile‑containing insecticides flonicamid (FLO) and thiacloprid (THI) are widely used in agriculture, posing risks to the environment and animal health. Nitrilase is a key catalyst for the degradation of nitrile compounds, and immobilized engineered bacteria are preferred in wastewater treatment. However, immobilized engineered bacteria expressing nitrilase have never been investigated for pollutant degradation. Here, engineered Escherichia coli pET28a‑VbNitA harboring the nitrilase gene VbNitA was immobilized by calcium alginate encapsulation. FLO was degraded into N-(4-trifluoromethylnicotinoyl)glycinamide and 4-(trifluoromethyl)nicotinol glycine by the immobilized cells via VbNitA. THI was converted to THI‑amide and THI‑imine using the same system. Notably, this is the first report of a nitrilase converting THI to THI‑amide and of THI‑imine as a biodegradation intermediate. Compared with free cells, the immobilized E. coli pET28a‑VbNitA showed higher tolerance to high temperature, alkaline, and acidic environments, and better long-term storage stability. The substrate inhibition model showed that the optimal initial concentrations of FLO and THI for degradation by immobilized E. coli pET28a‑VbNitA were 45.13 and 127.50 μmol/L, respectively. FLO was degraded more rapidly than THI by the immobilized cells. Molecular docking revealed that both FLO and THI formed stable interactions with VbNitA, with FLO positioned closer to Cys165 of the catalytic triad. This study presents a novel THI degradation pathway and provides a new, efficient immobilized biocatalyst for the remediation of wastewater with nitrile‑containing insecticides.

Escherichia coli↗

PubMed2026

Functional identification of the key gene Eh-fadB in nicosulfuron degradation by Enterobacter hormaechei ES1 based on multi-omics and enzymatic characterization.

Nicosulfuron is a sulfonylurea herbicide with residues that pose ecological risks in agricultural soils. Here we elucidated the degradation mechanism of Enterobacter hormaechei ES1 through whole-genome sequencing, transcriptomics, metabolomics, gene knockout, heterologous expression, and soil bioremediation assays. Under nicosulfuron stress, ES1 upregulated antioxidant enzymes including SOD, POD, and CAT, along with glutathione synthesis, to scavenge excess reactive oxygen species. HPLC-TOF-MS identified degradation intermediates such as ADMP and ASDM, indicating initial cleavage of the sulfonylurea bridge. Integrated multi-omics prioritized Eh-fadB, encoding a fatty acid β-oxidation multifunctional enzyme, as a novel degradative gene. Targeted knockout of Eh-fadB reduced nicosulfuron degradation from 87.6% to 37.04%, while genetic complementation restored nearly full activity. Purified Eh-FadB directly converted nicosulfuron, with optimal performance at 30 °C and pH 5-6; its activity was enhanced by Na+ and Pb2+ but inhibited by Fe3+. Molecular docking and dynamics identified His-450 and Asn-427 as key residues for substrate binding. In contaminated soil, inoculation with ES1 reduced nicosulfuron content within 21 days and promoted recovery of dehydrogenase and urease activities. This study provides the first genetic and biochemical evidence that a FadB-type enzyme participates in nicosulfuron catabolism, supporting sulfonylurea bridge cleavage and its potential for soil bioremediation.

Eh-fadB↗

PubMed2006

The thioesterase domain of the fengycin biosynthesis cluster: a structural base for the macrocyclization of a non-ribosomal lipopeptide.

Many secondary metabolic peptides from bacteria and fungi are produced by non-ribosomal peptide synthetases (NRPS) where the final step of biosynthesis is often catalysed by designated thioesterase domains. Here, we report the 1.8A crystal structure of the fengycin thioesterase (FenTE) from Bacillus subtilis F29-3, which catalyses the regio- and stereoselective release and macrocyclization of the antibiotic fengycin from the NRPS template. A structure of the PMSF-inactivated FenTE domain suggests the location of the oxyanion hole and the binding site of the C-terminal residue l-Ile11 of the lipopeptide. Using a combination of docking, molecular dynamics simulations and in vitro activity assays, a model of the FenTE-fengycin complex was derived in which peptide cyclization requires strategic interactions with residues lining the active site canyon.

Amino Acid Sequence↗

PubMed2026

Targeting pancreatic cancer progression: The formononetin and salvianolic acid B combination suppresses JAK/STAT signaling via MBOAT2 downregulation.

OBJECTIVE: Formononetin and salvianolic acid B (FcS) are the primary bioactive components of the Astragalus mongholicus-Salvia miltiorrhiza herbal pair, a classic combination for treating pancreatic cancer associated with qi deficiency and blood stasis. This study elucidates the therapeutic potential and mechanisms of FcS in the treatment of pancreatic cancer. METHODS: A zebrafish xenograft model was used to screen bioactive combinations derived from A. mongholicus and S. miltiorrhiza, identifying FcS as a candidate with antitumor activity. Its efficacy was evaluated in vivo using the zebrafish model, orthotopic LSL-KrasG12D/+, LSL-Trp53R172H/+ and Pdx-1-Cre (KPC) mice, and subcutaneous xenograft models. Cell viability and proliferation were assessed using cell counting kit-8, 5-ethynyl-2'-deoxyuridine and colony formation assays, and migration and invasion were evaluated by wound healing and transwell assays. Membrane-bound O-acyltransferase 2 (MBOAT2) was identified as a potential target through a molecular docking study and the Cancer Genome Atlas (TCGA) analysis. MBOAT2 knockdown cells were used to explore its roles and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway in FcS-mediated inhibition. RESULTS: In the zebrafish model, FcS strongly inhibited pancreatic tumor growth. FcS reduced tumor volume, the expression of proliferation marker Ki-67, and proliferating cell nuclear antigen in KPC mice. In vitro, FcS inhibited pancreatic cancer cell viability, proliferation, migration and invasion, which was accompanied by downregulation of MBOAT2 expression. TCGA analysis linked high MBOAT2 expression to aggressive phenotypes. MBOAT2 knockdown reduced the survival, proliferation and invasion of BxPC-3 cells. Rescue experiments revealed that MBOAT2 knockdown attenuated the antitumor effects of FcS, possibly through modulation of the JAK/STAT signaling pathway. FcS also inhibited tumor proliferation in xenograft models, and MBOAT2 expression was elevated in tumor tissues from pancreatic cancer patients. CONCLUSION: FcS suppresses pancreatic cancer progression via MBOAT2 downregulation and JAK/STAT pathway inhibition, which highlights MBOAT2 as a potential therapeutic target. Please cite this article as: Xu Y, Xu CS, Jin HB, Gu WG, Shen HZ, Lu L, Chen Y, Xu DC, Zhang XF, Yang JF, Wang Y. Targeting pancreatic cancer progression: The formononetin and salvianolic acid B combination suppresses JAK/STAT signaling via MBOAT2 downregulation. J Integr Med. 2026; 24(5):725-741.

Animals↗

PubMed2006

Role of each residue in catalysis in the active site of pyrimidine nucleoside phosphorylase from Bacillus subtilis: a hybrid QM/MM study.

Pyrimidine nucleoside phosphorylase (PYNP) catalyzes the reversible phosphorolysis of pyrimidines in the nucleotide synthesis salvage pathway. We have built a model of a closed active conformation of the three-dimensional structure of PYNP from Bacillus subtilis. Using docking, molecular dynamics, and hybrid quantum-mechanical/molecular-mechanical methods to study the reaction mechanics between PYNP and a substrate, we identified the role of each residue in the active site during the entire catalytic process. The results indicate that the function of His(82), Arg(169), and Lys(188) is to stabilize the uridine in a high-energy conformation by means of electrostatic interactions and that these residues are involved in catalysis. In addition, the function of Asp(162) is likely to activate Lys(188) for phosphorolytic catalysis through polarization effects.

Amino Acids↗

PubMed2026

Multidimensional Proteomics Reveals the Pro-apoptotic Mechanism of Platycodin D: Targeting RFC4 to Regulate the Notch Signaling Axis in Non-Small Cell Lung Cancer.

Platycodin D (PD), a major bioactive saponin isolated from the traditional Chinese medicine Platycodon grandiflorus, has shown promising therapeutic potential against non-small cell lung cancer (NSCLC). However, the functional mechanisms of PD in NSCLC progression remains unclear. This study aimed to explore the pharmacological mechanism of PD against NSCLC. Thermal proteome profiling approach, molecular docking, cellular thermal shift assay and peptide-centric local stability assay were employed to identify the potential binding target of PD. Subsequent Western Blot and immunoprecipitation-Western Blot experiments were conducted to investigate the downstream signaling pathways of the target. Furthermore, proteomic and ubiquitinomic profiling of PD-treated cells were performed to investigate its functions on global. replication factor C subunit 4 (RFC4) was identified as a potential binding target of PD by thermal proteome profiling and their binding sites were further exposed by peptide-centric local stability assay. PD-RFC4 complex promotes the degradation of Notch1 and Notch3 by reducing nuclear entry of their domains. Compared with control treatment, the differentially expressed proteins induced by PD were found to be primarily involved in ferroptosis, ubiquitination, platinum drug resistance, and ribosome-related processes. The ubiquitin proteome analysis revealed that proteins associated with the Notch pathway underwent ubiquitin modifications. PD binds to RFC4 and inhibits its activity, leading to downregulation of the Notch signaling pathway, ultimately triggering cancer cell apoptosis. PD is a natural product with potential therapeutic value for NSCLC.

Saponins↗

PubMed2004

Structural analysis of the epitopes on erbB2 interacted with inhibitory or non-inhibitory monoclonal antibodies.

erbB2 oncogene encodes a growth factor receptor. The overexpression of erbB2 was correlated with more aggressive tumors and a poorer prognosis. Some antibodies directed to this molecule have an antitumor effect in vivo, but some antibodies do not. In an attempt to understand the molecular basis of the anti-erbB2 antibody interaction with erbB2 ectodomain (ECD), we analyzed binding epitopes on erbB2 for inhibitory and non-inhibitory antibodies, Herceptin and HF by computer-guided protein engineering and site-directed mutagenesis. Two different interaction domains were identified by molecular docking, computer graphics and distance geometry method and confirmed through studies on a series of mutants of erbB2 ECD. Non-inhibitory antibody HF only recognized N-terminal portion of erbB2 ECD, but inhibitory antibody Herceptin bound to C-terminal portion of it exclusively. The region interacted with inhibitory antibody Herceptin can be an important target for anticancer therapies.

Antibodies, Monoclonal↗

PubMed2006

The Kaposi's sarcoma-associated herpesvirus complement control protein (KCP) binds to heparin and cell surfaces via positively charged amino acids in CCP1-2.

The Kaposi's sarcoma-associated herpesvirus (KSHV) complement control protein (KCP) inhibits the human complement system, and is similar in structure and function to endogenous complement inhibitors. Other inhibitors such as C4b-binding protein and factor H, as well as the viral homologue vaccinia virus complement control protein are known to bind heparin and, for the two latter, also to glycosaminoglycans at the surface of cells. We report here that KCP also binds to heparin at physiological ionic strength. With help of site directed mutagenesis, positively charged amino acids in the two N-terminal complement control protein (CCP) domains 1-2 were found to be necessary for heparin binding. In silico molecular docking of heparin to KCP confirmed the experimental data, and further explored the heparin binding site, enabling us to present a model of the KCP-heparin interaction. Furthermore, the docking analysis also yielded insights of the KCP structure, by indicating that the angle between CCP domains 1-2 during the initial binding of heparin is more extended than in the model we have previously presented. We also found that KCP binds to heparan sulfate and weakly to glycosaminoglycans at the surface of cells. This might indicate that KCP at the surface of viral particles aids in the primary attachment to the target cells, which is known to involve binding to heparan sulfate. Therefore, the present study contributes to the knowledge of heparin-protein interactions in general as well as to the understanding of the biology of KSHV.

Amino Acids, Basic↗

PubMed2026

Circular RNAs in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive loss of motor neurons, with most cases lacking a clear genetic basis. Emerging evidence highlights the involvement of non-coding RNAs, particularly circular RNAs (circRNAs), in disease onset and progression. Here, we investigated circRNAs implicated in ALS and related motor neuron diseases (MNDs). Here, we provide a general overview of circular RNA metabolism and cellular functions. We then present our systematic literature review that identified ALS-associated circRNAs, followed by in silico analyses of 15 circular RNA candidates that were selected based on the most compelling data regarding ALS. Our results revealed that several circular RNAs regulate ALS-related genes, such as unfolded protein response, oxidative stress, cell cycle regulation, and apoptosis. Protein-RNA interaction analysis further showed that ALS-related circRNAs can sponge 20 RNA-binding proteins. Additionally, molecular docking analysis demonstrated that ALS-associated FUS variants significantly alter its binding affinity to circular RNAs. RNA-seq data from ALS patients confirmed significant alterations in the expression of host genes of ALS-related circRNAs and hub proteins in ALS-affected CNS tissues. Collectively, our findings identify circRNAs as potential key contributors to ALS pathogenesis.

Amyotrophic Lateral Sclerosis↗

PubMed2026

CD44 gene rs9666607 polymorphism is associated with papillary thyroid carcinoma and interacts with CREB3L1.

BACKGROUND: The incidence of papillary thyroid carcinoma (PTC) has been rising. CD44 is involved in cell adhesion and migration, but the role of its genetic variation in PTC remains unclear. METHODS: This study aimed to investigate the association of CD44 gene polymorphisms with PTC and to examine the interaction between CD44 and CREB3L1. This study enrolled 354 patients with PTC, and the genotype distribution of the CD44 polymorphism (rs9666607) was analyzed. Key PTC genes were screened using the Gene Expression Omnibus (GEO) database (GSE33630). Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on these key genes. CD44 expression was validated using TCGA database, ELISA, qRTPCR, Western blot, and IHC in patient tissues, PTC mouse model, and human cell lines. The direct interactive molecules were screened through a bioinformatics method. RESULTS: The GSE33630 dataset identified a total of 124 upregulated and 85 downregulated differentially expressed genes. Enrichment analysis revealed 12 key PTC genes, including CD44. TCGA database validation revealed that CD44 was significantly overexpressed in PTC patients. The rs9666607‑A allele was associated with an increased risk of PTC and lymph node metastasis under a dominant model. CD44 mRNA and protein levels were significantly higher in PTC tissues versus adjacent tissue and further elevated in metastatic cases. Bioinformatic analysis predicted CD44 interaction with the transcription factor CREB3L1, and this was confirmed by molecular docking. CREB3L1 expression was synchronously upregulated with CD44 in PTC. CONCLUSION: CD44 polymorphisms, particularly the rs9666607-A allele, are significantly associated with PTC risk and metastasis in the studied population. CD44 is overexpressed in PTC, and its interaction with CREB3L1 suggests a potential novel interaction in PTC pathogenesis.

Hyaluronan Receptors↗

PubMed2026

A Multi-omics Regulated Cell Death Framework Defines Immune Phenotypes and Guides Precision Therapy in Colorectal Cancer.

Colorectal cancer (CRC) is molecularly and immunologically heterogeneous, contributing to variable treatment response. Because regulated cell death (RCD) intersects with tumor metabolism, immune regulation, and therapeutic susceptibility, we built an RCD-centered framework for CRC stratification. Multi-cohort transcriptomic data were used to infer RCD subtypes with non-negative matrix factorization (NMF) and non-negative least squares (NNLS). Genomic, bulk RNA-seq, single-cell RNA-seq, and spatial transcriptomic datasets were integrated to characterize subtype-associated biology. Machine-learning models were developed for immunotherapy response and survival-risk estimation. Candidate compounds were screened by GDSC2-based drug-sensitivity modeling and molecular docking, and FSTL3 was functionally assessed in vitro. The framework separated CRC samples into two RCD-related phenotypes resembling immune-hot and immune-cold states. RCD1 showed immune activation and higher mutational burden, whereas RCD2 showed immune-suppressed features, intratumoral heterogeneity, and aggressive biology. RCD-associated signatures showed potential for predicting immunotherapy response and survival risk. Dasatinib was prioritized for immune-cold, high-risk tumors, with preliminary evidence supporting its activity in CRC cells, while functional assays suggested a role for FSTL3 in growth, invasion, epithelial-mesenchymal transition, and apoptosis regulation. These findings suggest that RCD-based multi-omics analysis may refine CRC stratification and help generate therapeutic hypotheses.

Colorectal cancer↗

PubMed1999

Synthesis and acetylcholinesterase inhibitory activity of huperzine A-E2020 combined compound.

The synthesis of huperzine-E2020 combined compound (3) has been accomplished and the activities of 3 and the intermediates 12 and 13 to inhibit the activity of acetylcholinesterase have been measured. Conformation analyses and molecular docking studies of E2020 and the eight isomers of 12 were carried out. The results indicated that binding energies of all isomers of 12 with AChE was much lower than E2020 except for isomer RRZ, which might be the reason that the activity of 12 was lower than that of E2020. Interaction pattern of RRZ in AChE was also studied. Both binding energy and interaction pattern shows that the biological activity of RRZ might be higher than that of E2020.

Alkaloids↗