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Colorectal cancer (CRC) is a common malignant tumor of the digestive system. However, the efficacy of surgery and chemotherapy is limited. Ferroptosis is an iron- and reactive oxygen species (ROS)-dependent form of regulated cell death (RCD) and plays a vital role in tumor suppression. Ferroptosis inducing agents have been studied extensively as a novel promising way to fight against therapy resistant cancers. The aim of this study is to investigate the mechanism of action of tagitinin C (TC), a natural product, as a novel ferroptosis inducer in tumor suppression. The response of CRC cells to tagitinin C was assessed by cell viability assay, clonogenic assay, transwell migration assay, cell cycle assay and apoptosis assay. Molecular approaches including Western blot, RNA sequencing, quantitative real-time PCR and immunofluorescence were employed as well. Tagitinin C, a sesquiterpene lactone isolated from , inhibits the growth of colorectal cancer cells including HCT116 cells, and induced an oxidative cellular microenvironment resulting in ferroptosis of HCT116 cells. Tagitinin C-induced ferroptosis was accompanied with the attenuation of glutathione (GSH) levels and increased in lipid peroxidation. Mechanistically, tagitinin C induced endoplasmic reticulum (ER) stress and oxidative stress, thus activating nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2). As a downstream gene (effector) of Nrf2, heme oxygenase-1 (HO-1) expression increased significantly with the treatment of tagitinin C. Upregulated HO-1 led to the increase in the labile iron pool, which promoted lipid peroxidation, meanwhile tagitinin C showed synergistic anti-tumor effect together with erastin. In summary, we provided the evidence that tagitinin C induces ferroptosis in colorectal cancer cells and has synergistic effect together with erastin. Mechanistically, tagitinin C induces ferroptosis through ER stress-mediated activation of PERK-Nrf2-HO-1 signaling pathway. Tagitinin C, identified as a novel ferroptosis inducer, may be effective chemosensitizer that can expand the efficacy and range of chemotherapeutic agents.

The heel pad, located under the calcaneus of the human foot, is a hidden treasure that has been subjected to harsh mechanical conditions such as impact, vibration, and cyclic loading. This has resulted in a unique compartment structure and material composition, endowed with advanced biomechanical functions including cushioning, vibration reduction, fatigue resistance, and touchdown stability, making it an ideal natural bionic prototype in the field of bionic materials. It has been shown that the highly specialized structure and material composition of the heel pad endows it with biomechanical properties such as hyperelasticity, viscoelasticity, and mechanical anisotropy. These complex biomechanical properties underpin its advanced functions. Although it is known that these properties interact with each other, the detailed influence mechanism remains unclear, which restricts its application as a bionic prototype in the field of bionic materials. Therefore, this study provides a comprehensive review of the structure, materials, biomechanical properties, and functions of the heel pad. It focuses on elucidating the relationships between the structure, materials, biomechanical properties, and functions of heel pads and proposes insights for the study of bionic materials using the heel pad as a bionic prototype. Finally, a research idea to analyze the advanced mechanical properties of heel pads by integrating sophisticated technologies is proposed, aiming to provide directions for further in-depth research on heel pads and inspiration for the innovative design of advanced bionic materials.

Plants have evolved multiple mechanisms to selectively suppress pathogens by production of secondary metabolites with antimicrobial activities. Therefore, direct selections for antiviral compounds from plants can be used to identify new agents with potent antiviral activity but not toxic to hosts. Here, we provide evidence that a class of compounds, seco-pregnane steroid glaucogenin C and its monosugar-glycoside cynatratoside A of Strobilanthes cusia and three new pantasugar-glycosides of glaucogenin C of Cynanchum paniculatum, are effective and selective inhibitors to alphavirus-like positive-strand RNA viruses including plant-infecting tobacco mosaic virus (TMV) and animal-infecting Sindbis virus (SINV), eastern equine encephalitis virus, and Getah virus, but not to other RNA or DNA viruses, yet they were not toxic to host cells. In vivo administration of the compounds protected BALB/c mice from lethal SINV infection without adverse effects on the mice. Using TMV and SINV as models, studies on the action mechanism revealed that the compounds predominantly suppress the expression of viral subgenomic RNA(s) without affecting the accumulation of viral genomic RNA. Our work suggested that the viral subgenomic RNA could be a new target for the discovery of antiviral drugs, and that seco-pregnane steroid and its four glycosides found in the two medicinal herbs have the potential for further development as antiviral agents against alphavirus-like positive-strand RNA viruses.

● Soil aggregates affect soil respiration and its temperature sensitivity. ● Organic matter input boosts soil respiration, affected by temperature and aggregate size. ● Q 10 declines with increasing aggregate size, influenced by soil quality index. ● Microbial CUE drops with organic matter input, temperature and aggregate size increase. Understanding the dynamics of soil respiration, microbial carbon use efficiency (CUE), and temperature sensitivity ( Q 10) in response to exogenous organic matter (EOM) input, soil aggregate size, and incubation temperature is crucial for predicting soil carbon cycling responses to environmental changes. In this study, these interactions were investigated by 180-day incubation of soil aggregates supplemented with EOM at various temperatures (5°C, 15°C and 25°C). The results reveal an ‘L-shaped’ trend in soil respiration on the time scale across all treatments, characterized by initial rapid declines followed by stability. EOM input and higher temperatures significantly enhance respiration rates. Notably, the respiratory rates of soil aggregates of different sizes exhibit distinct patterns based on the presence or absence of EOM. Under conditions without the addition of EOM, larger aggregates show relatively lower respiration rates. Conversely, in the presence of EOM, larger aggregates exhibit higher respiratory rates. Furthermore, Q 10 decreases with increasing aggregate size. The relationship between Q 10 and the substrate quality index (SQI) supports the carbon quality temperature (CQT) hypothesis, highlighting SQI’s influence on Q 10 values, particularly during later incubation stages. Microbial CUE decreases with EOM input and rising temperatures. Meanwhile, aggregate size plays a role in microbial CUE, with smaller aggregates exhibiting higher CUE due to enhanced nutrient availability. In conclusion, the intricate interplay of EOM input, aggregate size, and temperature significantly shapes soil respiration, microbial CUE, and Q 10. These findings underscore the complexity of these interactions and their importance in modeling soil carbon dynamics under changing environmental conditions.

Tomato spotted wilt virus (TSWV) causes major losses of many crops worldwide. Several strategies have been attempted to control disease caused by TSWV. However, many challenges for the effective control of this disease remain. A promising approach is the use of abiotic or biotic inducers to enhance plant resistance to pathogens. We screened a diterpenoid compound from Wedelia trilobata , 3α-Angeloyloxy-9β-hydroxy- ent -kaur-16-en-19-oic acid (AHK), which had higher curative and protective effects against TSWV than the ningnanmycin control. The rapid initiation of the expression of all the TSWV genes was delayed by more than 1d in the curative assay, and the expression of the NSs , NSm and RdRp genes was inhibited. In addition, the replication of all TSWV genes in systemic leaves was inhibited in the protective assay, with an inhibition rate of more than 90%. The concentrations of jasmonic acid (JA) and jasmonic acid isoleucine (JA-ILE) in the AHK-treated and systemic leaves of the treated plants were significantly higher than those observed in the control. The results suggested that AHK can induce systemic resistance in treated plants. The transcription of the NtCOI1 gene, a key gene in the JA pathway, was significantly higher in both the inoculated and systemic leaves of the AHK-treated plants compared to the control. The AHK-induced resistance to TSWV in Nicotiana benthamiana could be eliminated by VIGS-mediated silencing of the NtCOI1 gene. These results indicated that AHK can activate the JA pathway and induce systemic resistance to TSWV infection.

3-Acetonyl-3-hydroxyoxindole (AHO) induces systemic acquired resistance (SAR) in Nicotiana . However, the underlying molecular mechanism is not well understood. To understand the molecular regulation during SAR induction, we examined mRNA levels, microRNA (miRNA) expression, and their regulatory mechanisms in control and AHO-treated tobacco leaves. Using RNA-seq analysis, we identified 1,445 significantly differentially expressed genes (DEGs) at least 2 folds with AHO treatment. The DEGs significantly enriched in six metabolism pathways including phenylpropanoid biosynthesis, sesquiterpenoid and triterpenoid biosynthesis for protective cuticle and wax. Key DEGs including PAL s and PR-10 in salicylic acid pathway involved in SAR were significantly regulated. In addition, we identified 403 miRNAs belonging to 200 miRNA families by miRNA sequencing. In total, AHO treatment led to 17 up- and 6 down-regulated at least 2 folds (Wald test, P < 0.05) miRNAs (DEMs), respectively. Targeting analysis implicated four DEMs regulating three DEGs involved in disease resistance, including miR156, miR172f, miR172g, miR408a, SPL6 and AP2 . We concluded that both mRNA and miRNA regulation enhances AHO-induced SAR. These data regarding DEGs, miRNAs, and their regulatory mechanisms provide molecular evidence for the mechanisms involved in tobacco SAR, which are likely to be present in other plants.

A series of spiro-oxindole derivatives was synthesized by novel regioselective 1,3-dipolar cycloadditions of isatin, α-amino acids, and ( E )-β-aryl-nitro-olefins. Regioisomers were produced in each reaction and the major products showed different regioselectivity compared to previously reported spiro-oxindole derivatives.

Plants have evolved multiple mechanisms to selectively suppress pathogens by production of secondary metabolites with antimicrobial activities. Therefore, direct selections for antiviral compounds from plants can be used to identify new agents with potent antiviral activity but not toxic to hosts. Here, we provide evidence that a class of compounds, seco-pregnane steroid glaucogenin C and its monosugar-glycoside cynatratoside A of Strobilanthes cusia and three new pantasugar-glycosides of glaucogenin C of Cynanchum paniculatum, are effective and selective inhibitors to alphavirus-like positive-strand RNA viruses including plant-infecting tobacco mosaic virus (TMV) and animal-infecting Sindbis virus (STNV), eastern equine encephalitis virus, and Getah virus, but not to other RNA or DNA viruses, yet they were not toxic to host cells. In vivo administration of the compounds protected BALB/c mice from lethal STNV infection without adverse effects on the mice. Using TMV and STNV as models, studies on the action mechanism revealed that the compounds predominantly suppress the expression of viral subgenomic RNA(s) without affecting the accumulation of viral genomic RNA. Our work suggested that the viral subgenomic RNA could be a new target for the discovery of antiviral drugs, and that seco-pregnane steroid and its four glycosides found in the two medicinal herbs have the potential for further development as antiviral agents against alphavirus-like positive-strand RNA viruses. [PUBLICATION ABSTRACT]

A series of spiro-oxindole derivatives was synthesized by novel regioselective 1,3-dipolar cycloadditions of isatin, α-amino acids, and (E)-β-aryl-nitro-olefins. Regioisomers were produced in each reaction and the major products showed different regioselectivity compared to previously reported spiro-oxindole derivatives.A series of spiro-oxindole derivatives was synthesized by novel regioselective 1,3-dipolar cycloadditions of isatin, α-amino acids, and (E)-β-aryl-nitro-olefins. Regioisomers were produced in each reaction and the major products showed different regioselectivity compared to previously reported spiro-oxindole derivatives.

Plants have evolved multiple mechanisms to selectively suppress pathogens by production of secondary metabolites with antimicrobial activities. Therefore, direct selections for antiviral compounds from plants can be used to identify new agents with potent antiviral activity but not toxic to hosts. Here, we provide evidence that a class of compounds, seco-pregnane steroid glaucogenin C and its monosugar-glycoside cynatratoside A of Strobilanthes cusia and three new pantasugar-glycosides of glaucogenin C of Cynanchum paniculatum, are effective and selective inhibitors to alphavirus-like positive-strand RNA viruses including plant-infecting tobacco mosaic virus (TMV) and animal-infecting Sindbis virus (SINV), eastern equine encephalitis virus, and Getah virus, but not to other RNA or DNA viruses, yet they were not toxic to host cells. In vivo administration of the compounds protected BALB/c mice from lethal SINV infection without adverse effects on the mice. Using TMV and SINV as models, studies on the action mechanism revealed that the compounds predominantly suppress the expression of viral subgenomic RNA(s) without affecting the accumulation of viral genomic RNA. Our work suggested that the viral subgenomic RNA could be a new target for the discovery of antiviral drugs, and that seco-pregnane steroid and its four glycosides found in the two medicinal herbs have the potential for further development as antiviral agents against alphavirus-like positive-strand RNA viruses.