Joint metabolomic and transcriptomic analysis identify unique phenolic acid and flavonoid compounds associated with resistance to fusarium wilt in cucumber (Cucumis sativus L.).

Introduction: Fusarium wilt (FW) caused by Fusarium oxysporum f. sp. cucumerinum (Foc) is a destructive soil-borne disease in cucumber (Cucumis sativus. L). However, there remains limited knowledge on the molecular mechanisms underlying FW resistance-mediated defense responses in cucumber. Methods: In this study, metabolome and transcriptome profiling were carried out for two FW resistant (NR) and susceptible (NS), near isogenic lines (NILs) before and after Foc inoculation. NILs have shown consistent and stable resistance in multiple resistance tests conducted in the greenhouse and in the laboratory. A widely targeted metabolomic analysis identified differentially accumulated metabolites (DAMs) with significantly greater NR accumulation in response to Foc infection, including many phenolic acid and flavonoid compounds from the flavonoid biosynthesis pathway. Results: Transcriptome analysis identified differentially expressed genes (DEGs) between the NILs upon Foc inoculation including genes for secondary metabolite biosynthesis and transcription factor genes regulating the flavonoid biosynthesis pathway. Joint analysis of the metabolomic and transcriptomic data identified DAMs and DEGs closely associated with the biosynthesis of phenolic acid and flavonoid DAMs. The association of these compounds with NR-conferred FW resistance was exemplified by in vivo assays. These assays found two phenolic acid compounds, bis (2-ethylhexyl) phthalate and diisooctyl phthalate, as well as the flavonoid compound gallocatechin 3-O-gallate to have significant inhibitory effects on Foc growth. The antifungal effects of these three compounds represent a novel finding. Discussion: Therefore, phenolic acids and flavonoids play important roles in NR mediated FW resistance breeding in cucumber.

The underlying mechanisms by which boron mitigated copper toxicity in Citrus sinensis leaves revealed by integrated analysis of transcriptome, metabolome, and physiology.

Both copper (Cu) excess and boron (B) deficiency are often observed in some citrus orchard soils. The molecular mechanisms by which B alleviates excessive Cu in citrus are poorly understood. Seedlings of sweet orange (Citrus sinensis (L.) Osbeck cv. Xuegan) were treated with 0.5 (Cu0.5) or 350 (Cu350 or Cu excess) µM CuCl2 and 2.5 (B2.5) or 25 (B25) µM HBO3 for 24 weeks. Thereafter, this study examined the effects of Cu and B treatments on gene expression levels revealed by RNA-Seq, metabolite profiles revealed by a widely targeted metabolome, and related physiological parameters in leaves. Cu350 upregulated 564 genes and 170 metabolites, and downregulated 598 genes and 58 metabolites in leaves of 2.5 µM B-treated seedlings (LB2.5), but it only upregulated 281 genes and 100 metabolites, and downregulated 136 genes and 40 metabolites in leaves of 25 µM B-treated seedlings (LB25). Cu350 decreased the concentrations of sucrose and total soluble sugars, and increased the concentrations of starch, glucose, fructose, and total nonstructural carbohydrates (TNC) in LB2.5, but it only increased the glucose concentration in LB25. Further analysis demonstrated that B addition reduced the oxidative damage and alterations in primary and secondary metabolisms caused by Cu350; and alleviated the impairment of Cu350 to photosynthesis and cell wall metabolism, thus improving leaf growth. LB2.5 exhibited some adaptive responses to Cu350 to meet the increasing need for the dissipation of excessive excitation energy (EEE) and the detoxification of reactive oxygen species (reactive aldehydes) and Cu. Cu350 increased photorespiration, xanthophyll cycle-dependent thermal dissipation, nonstructural carbohydrate accumulation, and secondary metabolite biosynthesis and abundances; and upregulated tryptophan metabolism and related metabolite abundances, and some antioxidant-related gene expression, and some antioxidant abundances. Additionally, this study identified some metabolic pathways, metabolites, and genes that might lead to Cu tolerance in leaves.

NCAPD2 augments the tumorigenesis and progression of human liver cancer via the PI3K­Akt­mTOR signaling pathway.

Non­SMC condensin I complex subunit D2 (NCAPD2) is a newly identified oncogene; however, the specific biological function and molecular mechanism of NCAPD2 in liver cancer progression remain unknown. In the present study, the aberrant expression of NCAPD2 in liver cancer was investigated using public tumor databases, including TNMplot, The Cancer Genome Atlas and the International Cancer Genome Consortium based on bioinformatics analyses, and it was validated using a clinical cohort. It was revealed that NCAPD2 was significantly upregulated in liver cancer tissues compared with in control liver tissues, and NCAPD2 served as an independent prognostic factor and predicted poor prognosis in liver cancer. In addition, the expression of NCAPD2 was positively correlated with the percentage of Ki67+ cells. Finally, single­cell sequencing data, gene­set enrichment analyses and in vitro investigations, including cell proliferation assay, Transwell assay, wound healing assay, cell cycle experiments, cell apoptosis assay and western blotting, were carried out in human liver cancer cell lines to assess the biological mechanisms of NCAPD2 in patients with liver cancer. The results revealed that the upregulation of NCAPD2 enhanced tumor cell proliferation, invasion and cell cycle progression at the G2/M­phase transition, and inhibited apoptosis in liver cancer cells. Furthermore, NCAPD2 overexpression was closely associated with the phosphatidylinositol 3­kinase (PI3K)­Akt­mammalian target of rapamycin (mTOR)/c­Myc signaling pathway and epithelial­mesenchymal transition (EMT) progression in HepG2 and Huh7 cells. In addition, upregulated NCAPD2 was shown to have adverse effects on overall survival and disease­specific survival in liver cancer. In conclusion, the overexpression of NCAPD2 was shown to lead to cell cycle progression at the G2/M­phase transition, activation of the PI3K­Akt­mTOR/c­Myc signaling pathway and EMT progression in human liver cancer cells.

Sinigrin reduces the virulence of Staphylococcus aureus by targeting coagulase.

Multi-resistant Staphylococcus aureus (S. aureus) infection is a significant global health concern owing to its high mortality and morbidity rates. Coagulase (Coa), a key enzyme that activates prothrombin to initiate host coagulation, has emerged as a promising target for anti-infective therapeutic approaches. This study identified sinigrin as a potent Coa inhibitor that significantly inhibited S. aureus-induced coagulation at concentration as low as 32 mg/L. Additionally, at a higher concentration of 128 mg/L, sinigrin disrupted the self-protection mechanism of S. aureus. Thermal shift and fluorescence-quenching assays confirmed the direct binding of sinigrin to the Coa protein. Molecular docking analysis predicted specific binding sites for sinigrin in the Coa molecule, and point mutation experiments highlighted the importance of Arg-187 and Asp-222 as critical binding sites for both Coa and sinigrin. In vivo studies demonstrated that the combination of sinigrin with oxacillin exhibited greater antibacterial efficacy than oxacillin alone in the treatment of S. aureus-induced pneumonia in mice. Furthermore, sinigrin was shown to reduce bacterial counts and inflammatory cytokine levels in the lung tissues of S. aureus-infected mice. In summary, sinigrin was shown to directly target Coa, resulting in the attenuation of S. aureus virulence, which suggests the potential of sinigrin as an adjuvant for future antimicrobial therapies.

A new isocoumarin derivative from endophytic fungus Pezicula neosporulosa VDB39 from Vaccinium dunalianum.

Four isocoumarin derivatives (1-4) and five phenols (5-9) were obtained from the endophytic fungus Pezicula neosporulosa VDB39, which was isolated from the branches of Vaccinium dunalianum Wight (Ericaceae). Compound 1 is a new derivative of isocoumarin. The structures were elucidated by spectroscopic methods. Single X-ray crystallography confirmed the absolute configuration of compound 1. Additionally, the antiphytopathogenic fungi activity of isocoumarin derivatives (1-4) was evaluated.

Bacteria-Like Gaiella Accelerate Soil Carbon Loss by Decomposing Organic Matter of Grazing Soils in Alpine Meadows on the Qinghai-Tibet Plateau.

The alpine meadows of the Qinghai-Tibet Plateau have significant potential for storing soil carbon, which is important to global carbon sequestration. Grazing is a major threat to its potential for carbon sequestration. However, grazing poses a major threat to this potential by speeding up the breakdown of organic matter in the soil and releasing carbon, which may further lead to positive carbon-climate change feedback and threaten ecological security. Therefore, in order to accurately explore the driving mechanism and regulatory factors of soil organic matter decomposition in grazing alpine meadows on the Qinghai-Tibet Plateau, we took the grazing sample plots of typical alpine meadows as the research object and set up grazing intensities of different life cycles, aiming to explore the relationship and main regulatory factors of grazing on soil organic matter decomposition and soil microorganisms. The results show the following: (1) soil microorganisms, especially Acidobacteria and Acidobacteria, drove the decomposition of organic matter in the soil, thereby accelerating the release of soil carbon, which was not conducive to soil carbon sequestration in grassland; (2) the grazing triggering effect formed a positive feedback with soil microbial carbon release, accelerating the decomposition of organic matter and soil carbon loss; and (3) the grazing ban and light grazing were more conducive to slowing down soil organic matter decomposition and increasing soil carbon sequestration.

Emerging role of sirtuins in non­small cell lung cancer (Review).

Non­small cell lung cancer (NSCLC) is a highly prevalent lung malignancy characterized by insidious onset, rapid progression and advanced stage at the time of diagnosis, making radical surgery impossible. Sirtuin (SIRT) is a histone deacetylase that relies on NAD+ for its function, regulating the aging process through modifications in protein activity and stability. It is intricately linked to various processes, including glycolipid metabolism, inflammation, lifespan regulation, tumor formation and stress response. An increasing number of studies indicate that SIRTs significantly contribute to the progression of NSCLC by regulating pathophysiological processes such as energy metabolism, autophagy and apoptosis in tumor cells through the deacetylation of histones or non­histone proteins. The present review elaborates on the roles of different SIRTs and their mechanisms in NSCLC, while also summarizing novel therapeutic agents based on SIRTs. It aims to present new ideas and a theoretical basis for NSCLC treatment.

Ribosome Biogenesis and Cancer: Insights into NOB1 and PNO1 Mechanisms.

Post-transcriptional modifications (PTMs) are pivotal in the regulation of gene expression, and pseudouridylation is emerging as a critical player. This modification, facilitated by enzymes such as NOB1 (PNO1), is integral to ribosome biogenesis. PNO1, in collaboration with the NIN1/RPN12 binding protein 1 homolog (NOB1), is vital for the maturation of ribosomes, transitioning 20S pre-rRNA into functional 18S rRNA. Recent studies have highlighted PNO1's potential involvement in cancer progression; however, its underlying mechanisms remain unclear. Relentless growth characterizing cancer underscores the burgeoning significance of epitranscriptomic modifications, including pseudouridylation, in oncogenesis. Given PNO1's emerging role, it is imperative to delineate its contribution to cancer development to identify novel therapeutic interventions. This review summarizes the current literature regarding the role of PNO1 in cancer progression and its molecular underpinnings in oncogenesis. Overexpression of PNO1 was associated with unfavorable prognosis and increased tumor malignancy. At the molecular level, PNO1 facilitates cancer progression by modulating mRNA stability, alternative splicing, and translation efficiency. Its role in pseudouridylation of oncogenic and tumor-suppressor transcripts further underscores its significance in cancer biology. Although disruption of ribosome biogenesis is known to precipitate oncogenesis, the precise mechanisms by which these alterations contribute to cancer remain unclear. This review elucidates the intricate process of ribosomal small subunit maturation, highlighting the roles of crucial ribosomal proteins (RPs) and RNA-binding proteins (RBPs) as well as the positioning and function of NOB1 and PNO1 within the 40S subunit. The involvement of these components in the maturation of the small subunit (SSU) and their significance in the context of cancer therapeutics has been thoroughly explored. PNO1's burgeoning significance in oncology makes it a potential target for cancer therapies. Strategies aimed at modulating PNO1-mediated pseudouridylation may provide new avenues for cancer treatment. However, further research is essential to unravel the complete spectrum of PNO1 mechanisms in cancer and harness this knowledge for the development of targeted and more efficacious anticancer therapies.

Risk Factors Related to Postoperative Dizziness Among Patients Who Underwent General Anesthesia and Intraoperative Analgesics: A Prospective Cohort Study.

PURPOSE: To describe postoperative dizziness for patients who received analgesics during general anesthesia and to investigate the factors related to the trend of dizziness within 3 days after surgery. DESIGN: A prospective cohort study. METHODS: This is a longitudinal study. The severity of dizziness was assessed from the day of the surgery until the third day post surgery. Generalized estimation equation models were created to determine the predictive effect of each independent variable separately. FINDINGS: After surgery, the incidence of dizziness was 42.1%. Approximately 10% of participants experienced severe dizziness. Participants with postoperative nausea and vomiting were more likely to experience postoperative dizziness. In addition, age, education level, history of motion sickness, surgical specialties, laparoscopic surgery, and long-acting analgesic use had an impact on the trend of postoperative dizziness. More than 25% of participants who used long-acting analgesics experienced dizziness on the third postoperative day. CONCLUSIONS: Postoperative dizziness was common among participants who received analgesics during general anesthesia. Monitoring for postoperative dizziness may need to be prolonged, especially in patients taking long-acting analgesics. For patients at high risk for postoperative dizziness, preventive measures such as adjusting analgesic and anesthetic medications may be necessary.

Hounsfield units in assessing bone mineral density in ankylosing spondylitis patients with cervical fracture-dislocation.

BACKGROUND: Cervical spine fracture-dislocations in patients with ankylosing spondylitis (AS) are mostly unstable and require surgery. However, osteoporosis, one of the comorbidities for AS, could lead to detrimental prognoses. There are few accurate assessments of bone mineral density in AS patients. AIM: To analyze Hounsfield units (HUs) for assessing bone mineral density in AS patients with cervical fracture-dislocation. METHODS: The HUs from C2 to C7 of 51 patients obtained from computed tomography (CT) scans and three-dimensional reconstruction of the cervical spine were independently assessed by two trained spinal surgeons and statistically analyzed. Inter-reader reliability and agreement were assessed by interclass correlation coefficient. RESULTS: The HUs decreased gradually from C2 to C7. The mean values of the left and right levels were significantly higher than those in the middle. Among the 51 patients, 25 patients (49.02%) may be diagnosed with osteoporosis, and 16 patients (31.37%) may be diagnosed with osteopenia. CONCLUSION: The HUs obtained by cervical spine CT are feasible for assessing bone mineral density with excellent agreement in AS patients with cervical fracture-dislocation.

Multi-Scale Depthwise Separable Capsule Network for hyperspectral image classification.

Addressing the challenges in effectively extracting multi-scale features and preserving pose information during hyperspectral image (HSI) classification, a Multi-Scale Depthwise Separable Capsule Network (MDSC-Net) is proposed in this article for HSI classification. Initially, hierarchical features are extracted by MDSC-Net through the employment of parallel multi-scale convolutional kernels, while computational complexity is reduced via depthwise separable convolutions, thus reducing the overall computational load and achieving efficient feature extraction. Subsequently, to enhance the translational invariance of features and reduce the loss of pose information, features of various scales are processed in parallel by independent capsule networks, with improvements in max pooling achieved through dynamic routing. Lastly, features of different scales are concatenated and integrated through the concatenate operation, thereby facilitating precise analysis of multi-level information in the hyperspectral image classification process. Experimental comparisons demonstrate that MDSC-Net achieves average accuracies of 94%, 98%, and 99% on the Kennedy Space Center, University of Pavia, and Salinas datasets, respectively, indicating a significant performance advantage over recent HSI classification models and validating the effectiveness of the proposed model.

Impact of slit compared with nonslit mesh in laparoscopic groin hernia repairs-A comprehensive propensity score analysis of a cohort of 611 hernias.

BACKGROUND: The slit-mesh technique for laparoscopic groin hernia repair remains controversial. We present the largest cohort of patients to date that have undergone laparoscopic hernia repair with this technique and aim to evaluate the impact of both techniques on postoperative recurrence and other secondary outcomes. METHODS: A retrospective, single-institution cohort study of patients who underwent a laparoscopic groin hernia repair over a 5.5-year period was performed. Univariate and multivariate analyses were performed to identify factors associated with recurrence, chronic pain, complications, length of stay, and operative time. A propensity score analysis also was performed. Time to recurrence was then subsequently plotted on a Kaplan-Meier survival analysis. RESULTS: In total, 611 laparoscopic groin hernia repairs (nonslit: n = 353; slit: n = 258) were reviewed. Mean follow-up duration was 6.6 months. On the multivariate analysis, body mass index was inversely correlated with recurrence (odds ratio, 0.792; 95% confidence interval, 0.656-0.956), whereas a slit mesh had lower recurrence (odds ratio, 0.228; 95% confidence interval, 0.064-0.809). In the propensity score-adjusted analysis, slit mesh remained significantly associated with reduced recurrence (adjusted odds ratio, 0.251; 95% confidence interval, 0.070-0.900), with no differences in chronic pain (adjusted odds ratio, 1.297; 95% confidence interval, 0.275-6.128) or postoperative complications (adjusted odds ratio, 1.808; 95% confidence interval, 0.429-7.620). Operative time also was reduced in the slit-mesh group (P = .009). CONCLUSIONS: The slit-mesh technique was associated with a reduced likelihood of postoperative recurrence and shorter operative time, with no impact on postoperative chronic pain or complications. A lower body mass index was also correlated with increased likelihood of postoperative recurrence.

Trajectory on postpartum depression of Chinese women and the risk prediction models: A machine-learning based three-wave follow-up research.

BACKGROUND: Our study delves into postpartum depression (PPD) extending observation up to six months postpartum, addressing the gap in long-term follow-ups and uncover critical intervention points. METHOD: Through a continuous three-wave cohort study involving 3174 of 10,730 invited postpartum women, we utilized machine learning to predict PPD risk, incorporating self-reported surveys and health records from October 2021 to Jan 2023. RESULTS: PPD prevalence slightly decreased from 30.9 % to 29.1 % over six months. The Random Forest model emerged as the most effective, identifying key predictors of PPD at different stages. The top three factors at first month were newborn's birth weight, maternal weight before delivery and before pregnancy. The EPDS scores of last time, newborn's birth weight and maternal weight before pregnancy and before delivery were main predictors for EPDS scores at third and sixth months postpartum. LIMITATION: The study faces limitations such as potential selection bias due to the convenience sampling method and the reliance on self-reported measures, which may introduce reporting bias. Furthermore, the high attrition rate could affect the representativeness of the sample and the generalizability of the findings. CONCLUSION: There is a slight decrease in PPD rates over six months, yet the prevalence remains high. This underscores the need for early and ongoing mental health support for new mothers. Our study highlights the efficacy of machine learning in enhancing PPD risk assessment and tailoring intervention strategies, paving the way for more personalized healthcare approaches in postpartum care.

Electroacupuncture activates AMPKα1 to improve learning and memory in the APP/PS1 mouse model of early Alzheimer's disease by regulating hippocampal mitochondrial dynamics.

OBJECTIVE: Studies have shown that electroacupuncture (EA) can alleviate cognitive impairments from Alzheimer's disease (AD) by regulating the expression of adenosine monophosphate-activated protein kinase (AMPK), but the specific mechanism involved remains to be elucidated. Therefore, this study explores the potential mechanism by which EA improves cognitive function from the perspective of mitochondrial dynamics. METHODS: The four-month-old transgenic mice with amyloid precursor protein (APP)/presenilin 1 (PS1) and AMPKα1-subunit conditional knockout (AMPKα1-cKO) were used for experiments. To evaluate the effects of EA treatment on cognitive function, the T-maze and Morris water maze were used. In addition, chemical exchange saturation transfer, thioflavin staining, transmission electron microscopy, mitochondrial membrane potential, and Western blotting were used to examine the potential mechanisms underlying the effects of EA on APP/PS1 mice. RESULTS: Both APP/PS1 mice and AMPKα1-cKO mice exhibited dysfunction in mitochondrial dynamics accompanied by learning and memory impairment. Inactivation of the AMPK/peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) pathway increased pathological amyloid-ß (Aß) deposition and aggravated the dysfunction in mitochondrial dynamics. In addition, EA rescued learning and memory deficits in APP/PS1 mice by activating the AMPK/PGC-1α pathway, specifically by reducing pathological Aß deposition, normalizing energy metabolism, protecting the structure and function of mitochondria, increasing the levels of mitochondrial fusion proteins, and downregulating the expression of fission proteins. However, the therapeutic effect of EA on cognition in APP/PS1 mice was hindered by AMPKα1 knockout. CONCLUSION: The regulation of hippocampal mitochondrial dynamics and reduction in Aß deposition via the AMPK/PGC-1α pathway are critical for the ability of EA to ameliorate cognitive impairment in APP/PS1 mice. Please cite this article as: Jia WW, Lin HW, Yang MG, Dai YL, Ding YY, Xu WS, Wang SN, Cao YJ, Liang SX, Wang ZF, Chen C, Liu WL. Electroacupuncture activates AMPKα1 to improve learning and memory in the APP/PS1 mouse model of early Alzheimer's disease by regulating hippocampal mitochondrial dynamics. J Integr Med. 2024; Epub ahead of print.

Electrostatic microfiltration (EM) enriches and recovers viable microorganisms at low-abundance in large-volume samples and enhances downstream detection.

Rapid and sensitive detection of pathogens in various samples is crucial for disease diagnosis, environmental surveillance, as well as food and water safety monitoring. However, the low abundance of pathogens (<10 CFU) in large volume (1 mL-1 L) samples containing vast backgrounds critically limits the sensitivity of even the most advanced techniques, such as digital PCR. Therefore, there is a critical need for sample preparation that can enrich low-abundance pathogens from complex and large-volume samples. This study develops an efficient electrostatic microfiltration (EM)-based sample preparation technique capable of processing ultra-large-volume (≥500 mL) samples at high throughput (≥10 mL min-1). This approach achieves a significant enrichment (>8000×) of extremely-low-abundance pathogens (down to level of 0.02 CFU mL-1, i.e., 10 CFU in 500 mL). Furthermore, EM-enabled sample preparation facilitates digital amplification techniques sensitively detecting broad pathogens, including bacteria, fungi, and viruses from various samples, in a rapid (≤3 h) sample-to-result workflow. Notably, the operational ease, portability, and compatibility/integrability with various downstream detection platforms highlight its great potential for widespread applications across diverse settings.

Artificial organic afferent nerves enable closed-loop tactile feedback for intelligent robot.

The emulation of tactile sensory nerves to achieve advanced sensory functions in robotics with artificial intelligence is of great interest. However, such devices remain bulky and lack reliable competence to functionalize further synaptic devices with proprioceptive feedback. Here, we report an artificial organic afferent nerve with low operating bias (-0.6 V) achieved by integrating a pressure-activated organic electrochemical synaptic transistor and artificial mechanoreceptors. The dendritic integration function for neurorobotics is achieved to perceive directional movement of object, further reducing the control complexity by exploiting the distributed and parallel networks. An intelligent robot assembled with artificial afferent nerve, coupled with a closed-loop feedback program is demonstrated to rapidly implement slip recognition and prevention actions upon occurrence of object slippage. The spatiotemporal features of tactile patterns are well differentiated with a high recognition accuracy after processing spike-encoded signals with deep learning model. This work represents a breakthrough in mimicking synaptic behaviors, which is essential for next-generation intelligent neurorobotics and low-power biomimetic electronics.

Construction of cationic meso-thiazolium-BODIPY AIE fluorescent probes for viscosity imaging in dual organelles.

Two new cationic meso-thiazolium-BODIPY-based water-soluble and red-shifted fluorescent probes were constructed for the first time. They can monitor cellular viscosity in dual organelles and show aggregation-induced emission (AIE), which is ascribed to the efficient restricted rotation of meso-thiazolium in viscous or hindered systems. Probe 3 with an N-benzyl group shows better AIE as compared to probe 2 with an N-methyl group.

Structural characterisation and anti-colon cancer activity of an arabinogalactan RSA-1 from Raphani semen.

RSA-1 is a polysaccharide obtained from Raphani semen with a relatively clear structure and anti-colon cancer activity. In this study, high-performance liquid chromatography (HPLC), gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR) spectroscopy were applied to characterise the complex chain structure of RSA-1. Subsequently, the inhibitory effect on colon cancer growth through apoptosis induction in colon cancer cells was explored. The findings indicate that the main chain of RSA-1 consists of →3)-ß-D-Galp-(1 â†’ and 3,6)-ß-D-Galp-(1 â†’ substituted at C-6 with branched α-L-Araf side chains. RSA-1 disrupts the Bax/Bcl-2 ratio and thus inhibits the viability of colon cancer cells in vitro. Furthermore, it inhibits colon cancer migration by attenuating epithelial-mesenchymal transition. Notably, RSA-1 exhibited negligible impact on the growth of human intestinal epithelial cells within a relevant concentration range. This study establishes a theoretical foundation and provides technical support for the prospective development and application of RSA-1 as a dual-purpose anti-colon cancer drug and functional food.

De novo design of mini-binder proteins against IL-2 receptor ß chain.

IL-2 regulates the immune response by interacting with different IL-2 receptor (IL-2R) subunits. High dose of IL-2 binds to IL-2Rßγc heterodimer, which induce various side effects while activating immune function. Disrupting IL-2 and IL-2R interactions can block IL-2 mediated immune response. Here, we used a computational approach to de novo design mini-binder proteins against IL-2R ß chain (IL-2Rß) to block IL-2 signaling. The hydrophobic region where IL-2 binds to IL-2Rß was selected and the promising binding mode was broadly explored. Three mini-binders with amino acid numbers ranging from 55 to 65 were obtained and binder 1 showed the best effects in inhibiting CTLL-2 cells proliferation and STAT5 phosphorylation. Molecular dynamics simulation showed that the binding of binder 1 to IL-2Rß was stable; the free energy of binder1/IL-2Rß complex was lower, indicating that the affinity of binder 1 to IL-2Rß was higher than that of IL-2. Free energy decomposition suggested that the ARG35 and ARG131 of IL-2Rß might be the key to improve the affinity of binder. Our efforts provided new insights in developing of IL-2R blocker, offering a potential strategy for ameliorating the side effects of IL-2 treatment.