Discovery of novel co-degradation CK1α and CDK7/9 PROTACs with p53 activation for treating acute myeloid leukemia.

Reactivating p53 activity to restore its anticancer function is an attractive cancer treatment strategy. In this study, we designed and synthesized a series of novel PROTACs to reactivate p53 via the co-degradation of CK1α and CDK7/9 proteins. Bioactivity studies showed that the selected PROTAC 13i exhibited potency antiproliferative activity in MV4-11 (IC50 = 0.096 ± 0.012 µM) and MOLM-13 (IC50 = 0.072 ± 0.014 µM) cells, and induced apoptosis of MV4-11 cells. Western-blot analysis showed that PROTAC 13i triple CK1α and CDK7/9 protein degradation resulted in the significantly increased expression of p53. At the same time, the transcriptional repression due to the degradation significantly reduced downstream gene expression of MYC, MDM2, BCL-2 and MCL-1, and reduced the inflammatory cytokine levels of TNF-α, IL-1ß and IL-6 in PMBCs. These results indicate the beneficial impact of simultaneous CK1α and CDK7/9 degradation for acute myeloid leukemia therapy.

Cross-kingdom RNA interference mediated by insect salivary microRNAs may suppress plant immunity.

Communication between insects and plants relies on the exchange of bioactive molecules that traverse the species interface. Although proteinic effectors have been extensively studied, our knowledge of other molecules involved in this process remains limited. In this study, we investigate the role of salivary microRNAs (miRNAs) from the rice planthopper Nilaparvata lugens in suppressing plant immunity. A total of three miRNAs were confirmed to be secreted into host plants during insect feeding. Notably, the sequence-conserved miR-7-5P is specifically expressed in the salivary glands of N. lugens and is secreted into saliva, distinguishing it significantly from homologues found in other insects. Silencing miR-7-5P negatively affects N. lugens feeding on rice plants, but not on artificial diets. The impaired feeding performance of miR-7-5P-silenced insects can be rescued by transgenic plants overexpressing miR-7-5P. Through target prediction and experimental testing, we demonstrate that miR-7-5P targets multiple plant genes, including the immune-associated bZIP transcription factor 43 (OsbZIP43). Infestation of rice plants by miR-7-5P-silenced insects leads to the increased expression of OsbZIP43, while the presence of miR-7-5P counteracts this upregulation effect. Furthermore, overexpressing OsbZIP43 confers plant resistance against insects which can be subverted by miR-7-5P. Our findings suggest a mechanism by which herbivorous insects have evolved salivary miRNAs to suppress plant immunity, expanding our understanding of cross-kingdom RNA interference between interacting organisms.

Studying the impact of marital status on diagnosis and survival prediction in pancreatic ductal carcinoma using machine learning methods.

Pancreatic cancer is a commonly occurring malignant tumor, with pancreatic ductal carcinoma (PDAC) accounting for approximately 95% of cases. According of its poor prognosis, identifying prognostic factors of pancreatic ductal carcinoma can provide physicians with a reliable theoretical foundation when predicting patient survival. This study aimed to analyze the impact of marital status on survival outcomes of PDAC patients using propensity score matching and machine learning. The goal was to develop a prognosis prediction model specific to married patients with PDAC. We extracted a total of 206,968 patient records of pancreatic cancer from the SEER database. To ensure the baseline characteristics of married and unmarried individuals were balanced, we used a 1:1 propensity matching score. We then conducted Kaplan-Meier analysis and Cox proportional-hazards regression to examine the impact of marital status on PDAC survival before and after matching. Additionally, we developed machine learning models to predict 5-year CSS and OS for married patients with PDAC specifically. In total, 24,044 PDAC patients were included in this study. After 1:1 propensity matching, 8043 married patients and 8,043 unmarried patients were successfully enrolled. Multivariate analysis and the Kaplan-Meier curves demonstrated that unmarried individuals had a poorer survival rate than their married counterparts. Among the algorithms tested, the random forest performed the best, with 0.734 5-year CSS and 0.795 5-year OS AUC. This study found a significant association between marital status and survival in PDAC patients. Married patients had the best prognosis, while widowed patients had the worst. The random forest is a reliable model for predicting survival in married patients with PDAC.

Enhancing Fat Transplantation Efficiency in a Mouse Model through Pretreatment of Adipose-Derived Stem Cells with RIP3 Inhibitors.

BACKGROUND: Autologous fat transplantation, widely used in cosmetic and reparative surgery for volumetric enhancements, faces challenges with its inconsistent long-term survival rates. The technique's efficacy, crucial for its development, is hindered by unpredictable outcomes. Enriching fat grafts with adipose-derived stem cells (ADSCs) shows promise in improving survival efficiency. OBJECTIVES: This study aimed to explore the potential of receptor-interacting protein kinase 3 (RIP3) kinase inhibitors as a pretreatment for ADSCs in enhancing autologous fat graft retention over a long term. METHODS: ADSCs were isolated, cultured under normal or oxygen-glucose deprivation conditions, and mixed with particulate fat grafts to form distinct experimental groups in female nude mice. Fat graft mass and volume, along with underlying mechanisms, were evaluated using quantitative reverse transcription polymerase chain reaction (RT-qPCR), immunohistochemistry, and Western blot analysis. RESULTS: The experimental group, pretreated with RIP3 kinase inhibitors, had higher graft mass and volume, greater adipocyte integrity, and increased peroxisome proliferator-activated receptor gamma (PPARγ) mRNA levels than control groups. Furthermore, the experimental group demonstrated lower expression of necroptosis pathway proteins in the short term and an ameliorated inflammatory response as indicated by interleukin-1 beta (IL-1ß), interleukin-10 (IL-10) mRNA levels, and histological analyses. Notably, enhanced neovascularization was evident in the experimental group. CONCLUSIONS: These findings suggest that RIP3 kinase inhibitor pretreatment of ADSCs can improve fat graft survival, promote adipocyte integrity, potentially decrease inflammation, and enhance neovascularization. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Multimodal Engineering of Catalytic Interfaces Confers Multi-Site Metal-Organic Framework for Internal Preconcentration and Accelerating Redox Kinetics in Lithium-Sulfur Batteries.

The development of highly efficient catalysts to address the shuttle effect and sluggish redox kinetics of lithium polysulfides (LiPSs) in lithium-sulfur batteries (LSBs) remains a formidable challenge. In this study, a series of multi-site catalytic metal-organic frameworks (MSC-MOFs) were elaborated through multimodal molecular engineering to regulate both the reactant diffusion and catalysis processes. MSC-MOFs were crafted with nanocages featuring collaborative specific adsorption/catalytic interfaces formed by exposed mixed-valence metal sites and surrounding adsorption sites. This design facilitates internal preconcentration, a coadsorption mechanism, and continuous efficient catalytic conversion toward polysulfides concurrently. Leveraging these attributes, LSBs with an MSC-MOF-Ti catalytic interlayer demonstrated a 62 % improvement in discharge capacity and cycling stability. This resulted in achieving a high areal capacity (11.57 mAh cm-2 ) at a high sulfur loading (9.32 mg cm-2 ) under lean electrolyte conditions, along with a pouch cell exhibiting an ultra-high gravimetric energy density of 350.8 Wh kg-1 . Lastly, this work introduces a universal strategy for the development of a new class of efficient catalytic MOFs, promoting SRR and suppressing the shuttle effect at the molecular level. The findings shed light on the design of advanced porous catalytic materials for application in high-energy LSBs.

Metabolomics and machine learning approaches for diagnostic and prognostic biomarkers screening in sepsis.

BACKGROUND: Sepsis is a life-threatening disease with a poor prognosis, and metabolic disorders play a crucial role in its development. This study aims to identify key metabolites that may be associated with the accurate diagnosis and prognosis of sepsis. METHODS: Septic patients and healthy individuals were enrolled to investigate metabolic changes using non-targeted liquid chromatography-high-resolution mass spectrometry metabolomics. Machine learning algorithms were subsequently employed to identify key differentially expressed metabolites (DEMs). Prognostic-related DEMs were then identified using univariate and multivariate Cox regression analyses. The septic rat model was established to verify the effect of phenylalanine metabolism-related gene MAOA on survival and mean arterial pressure after sepsis. RESULTS: A total of 532 DEMs were identified between healthy control and septic patients using metabolomics. The main pathways affected by these DEMs were amino acid biosynthesis, phenylalanine metabolism, tyrosine metabolism, glycine, serine and threonine metabolism, and arginine and proline metabolism. To identify sepsis diagnosis-related biomarkers, support vector machine (SVM) and random forest (RF) algorithms were employed, leading to the identification of four biomarkers. Additionally, analysis of transcriptome data from sepsis patients in the GEO database revealed a significant up-regulation of the phenylalanine metabolism-related gene MAOA in sepsis. Further investigation showed that inhibition of MAOA using the inhibitor RS-8359 reduced phenylalanine levels and improved mean arterial pressure and survival rate in septic rats. Finally, using univariate and multivariate cox regression analysis, six DEMs were identified as prognostic markers for sepsis. CONCLUSIONS: This study employed metabolomics and machine learning algorithms to identify differential metabolites that are associated with the diagnosis and prognosis of sepsis patients. Unraveling the relationship between metabolic characteristics and sepsis provides new insights into the underlying biological mechanisms, which could potentially assist in the diagnosis and treatment of sepsis. TRIAL REGISTRATION: This human study was approved by the Ethics Committee of the Research Institute of Surgery (2021-179) and was registered by the Chinese Clinical Trial Registry (Date: 09/12/2021, ChiCTR2200055772).

Effects of Tropical Cyclone (TC) Hellen on the north-westward movement of chlorophyll in the northern Mozambique Channel.

An intense tropical cyclone (TC), TC Hellen, occurred in the northern Mozambique Channel on March 27, 2014, and moved from the east coast of the African continent to the northern Madagascar island. TC Hellen dramatically altered the marine environment in the northern Mozambique Channel, resulting in a significant chlorophyll-a (Chl-a) bloom. A giant surface Chl-a northwest-ward movement from the northwest coast of Madagascar Island was first observed after the passage of TC Hellen in the northern Mozambique Channel. The dynamic mechanisms of these phenomenon were studied by satellite remote sensing, multisource reanalysis data, and Argo float data. The results show that transient northwestward-moving eddies, upwelling, and winds had important effects on the Chl-a bloom and its northwestward movement. Ekman transport driven by coastal southeasterly winds entrained waters with high Chl-a concentrations to the northwest, while TC Hellen enhanced cyclonic eddy upwelling and uplifted nutrient-rich deep water to the upper ocean. This vertical mixing and upwelling in turn triggered the Chl-a bloom in the offshore surface layer. This study provides insight into the reflection of phytoplankton dynamics by TCs in the northern Mozambique Channel.

Engineered exosomes for tissue regeneration: from biouptake, functionalization and biosafety to applications.

Exosomes are increasingly recognized as important effector molecules that regulate intercellular signaling pathways. Notably, certain types of exosomes can induce therapeutic responses, including cell proliferation, angiogenesis, and tissue repair. The use of exosomes in therapy is a hot spot in current research, especially in regenerative medicine. Despite the therapeutic potential, problems have hindered their success in clinical applications. These shortcomings include low concentration, poor targeting and limited loading capability. To fully realize their therapeutic potential, certain modifications are needed in native exosomes. In the present review, we summarize the exosome modification and functionalization strategies. In addition, we provide an overview of potential clinical applications and highlight the issues associated with the biosafety and biocompatibility of engineered exosomes in applications.

Horizontally Transferred Salivary Protein Promotes Insect Feeding by Suppressing Ferredoxin-Mediated Plant Defenses.

Herbivorous insects such as whiteflies, planthoppers, and aphids secrete abundant orphan proteins to facilitate feeding. Yet, how these genes are recruited and evolve to mediate plant-insect interaction remains unknown. In this study, we report a horizontal gene transfer (HGT) event from fungi to an ancestor of Aleyrodidae insects approximately 42 to 190 million years ago. BtFTSP1 is a salivary protein that is secreted into host plants during Bemisia tabaci feeding. It targets a defensive ferredoxin 1 in Nicotiana tabacum (NtFD1) and disrupts the NtFD1-NtFD1 interaction in plant cytosol, leading to the degradation of NtFD1 in a ubiquitin-dependent manner. Silencing BtFTSP1 has negative effects on B. tabaci feeding while overexpressing BtFTSP1 in N. tabacum benefits insects and rescues the adverse effect caused by NtFD1 overexpression. The association between BtFTSP1 and NtFD1 is newly evolved after HGT, with the homologous FTSP in its fungal donor failing to interact and destabilize NtFD1. Our study illustrates the important roles of horizontally transferred genes in plant-insect interactions and suggests the potential origin of orphan salivary genes.

Comparative Transcriptomic Analysis Reveals Adaptation Mechanisms of Bean Bug Riptortus pedestris to Different Food Resources.

The bean bug, Riptortus pedestris (Hemiptera: Heteroptera), poses a significant threat to soybean production, resulting in substantial crop losses. Throughout the soybean cultivation period, these insects probe and suck on various parts of plants, including leaves, pods, and beans. However, the specific mechanisms by which they adapt to different food resources remain unknown. In this study, we conducted gut transcriptomic analyses of R. pedestris fed with soybean leaves, pods, and beans. A total of 798, 690, and 548 differently expressed genes (DEGs) were monitored in G-pod vs. G-leaf (comparison of insect feeding on pods and leaves), G-bean vs. G-leaf (comparison of insect feeding on beans and leaves), and G-pod vs. G-bean (comparison of insect feeding on pods and beans), respectively. When fed on pods and beans, there was a significant increase in the expression of digestive enzymes, particularly cathepsins, serine proteases, and lipases. Conversely, when soybean leaves were consumed, detoxification enzymes, such as ABC transporters and 4-coumarate-CoA ligase, exhibited higher expression. Our findings indicate that R. pedestris dynamically regulates different metabolic pathways to cope with varying food resources, which may contribute to the development of effective strategies for managing this pest.

Functional analysis of neutral lipases in bug feeding and reproduction.

BACKGROUND: The bean bug, Riptortus pedestris, is known to cause significant economic losses in soybean crops due to its seed-sucking behavior, but the mechanism of its adaptation to lipid-rich seeds remains poorly understood. To exploit potential target genes for controlling this pest, neutral lipases are functionally characterized in this study. RESULTS: In this study, a total of 69 lipases were identified in R. pedestris, including 35 neutral lipases that underwent significant expansion. The phylogeny, expression patterns, and catalytic capacity of neutral lipases were investigated and we selected six salivary gland-specific, eight gut-specific, and three ovary-specific genes for functional analysis. All three ovary-specific neutral lipases (Chr1.3195, Chr1.0994, and Chr5.0087) are critical for insect reproduction, while a few gut-specific neutral lipases (Chr4.0221 and Chr1.3207) influence insect survivorship or weight gain. In contrast, no significant phenotype change is observed when silencing salivary gland-specific neutral lipases. CONCLUSION: The lipases Chr1.3195, Chr1.0994, Chr5.0087, Chr4.0221, and Chr1.3207 are essential for R. pedestris feeding and reproduction, and the insect is highly sensitive to their deficiency, suggesting that neutral lipases are promising candidates for application in RNAi-based control of this destructive pest. © 2023 Society of Chemical Industry.

Biomimetic Liquid Crystal-Modified Mesoporous Silica-Based Composite Hydrogel for Soft Tissue Repair.

The reconstruction of blood vessels plays a critical role in the tissue regeneration process. However, existing wound dressings in tissue engineering face challenges due to inadequate revascularization induction and a lack of vascular structure. In this study, we report the modification of mesoporous silica nanospheres (MSNs) with liquid crystal (LC) to enhance bioactivity and biocompatibility in vitro. This LC modification facilitated crucial cellular processes such as the proliferation, migration, spreading, and expression of angiogenesis-related genes and proteins in human umbilical vein endothelial cells (HUVECs). Furthermore, we incorporated LC-modified MSN within a hydrogel matrix to create a multifunctional dressing that combines the biological benefits of LC-MSN with the mechanical advantages of a hydrogel. Upon application to full-thickness wounds, these composite hydrogels exhibited accelerated healing, evidenced by enhanced granulation tissue formation, increased collagen deposition, and improved vascular development. Our findings suggest that the LC-MSN hydrogel formulation holds significant promise for the repair and regeneration of soft tissues.

Effects of G-CSF on hPDLSC proliferation and osteogenic differentiation in the LPS-induced inflammatory microenvironment.

BACKGROUND: Periodontitis is a chronic infectious disease of periodontal support tissue caused by microorganisms in dental plaque, which causes alveolar bone resorption and tooth loss. Periodontitis treatment goals include prevention of alveolar bone resorption and promotion of periodontal regeneration. We previously found that granulocyte colony-stimulating factor (G-CSF) was involved in periodontitis-related alveolar bone resorption through induction of an immune response and subsequent destruction of periodontal tissue. However, the mechanisms underlying the effects of G-CSF on abnormal bone remodeling have not yet been fully elucidated. Human periodontal ligament stem cells (hPDLSCs) are major modulators of osteogenic differentiation in periodontal tissues. Thus, the aim of this study was to investigated whether G-CSF acts effects on hPDLSC proliferation and osteogenic differentiation, as well as periodontal tissue repair. METHODS: hPDLSCs were cultured and identified by short tandem repeat analysis. The expression patterns and locations of G-CSF receptor (G-CSFR) on hPDLSCs were detected by immunofluorescence analysis. The effects of G-CSF on hPDLSCs in a lipopolysaccharide (LPS)-induced inflammatory microenvironment were investigated. Specifically, Cell-Counting Kit 8 (CCK8) and Alizarin red staining were used to examine hPDLSC proliferation and osteogenic differentiation; reverse transcription-polymerase chain reaction was performed to detect the expression patterns of osteogenesis-related genes (alkaline phosphatase [ALP], runt-related transcription factor 2 [Runx2], and osteocalcin [OCN]) in hPDLSCs; and Western blotting was used to detect the expression patterns of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) of PI3K/Akt signaling pathway. RESULTS: hPDLSCs exhibited a typical spindle-shaped morphology and good clonogenic ability. G-CSFR was mostly localized on the cell surface membrane. Analyses showed that G-CSF inhibited hPDLSC proliferation. Also, in the LPS-induced inflammatory microenvironment, G-CSF inhibited hPDLSC osteogenic differentiation and reduced the expression levels of osteogenesis-related genes. G-CSF increased the protein expression levels of hPDLSC pathway components p-PI3K and p-Akt. CONCLUSIONS: We found that G-CSFR was expressed on hPDLSCs. Furthermore, G-CSF inhibited hPDLSC osteogenic differentiation in vitro in the LPS-induced inflammatory microenvironment.

The Effect of Various Temperatures on the Inflammatory Profile of Fat Graft Storage: An Experimental Study.

Fat tissue has been widely used as a filler material during plastic surgery, but unpredictable fat retention remains a significant concern. Fat tissue is vulnerable to ischemia and hypoxia, but it always has waiting time before injection in the operation theater. Apart from transferring fat tissue as quickly as possible after harvesting, washing the aspirate with cool normal saline is often used. However, the mechanisms of cool temperature acting on adipose tissue have yet to be fully elucidated. Herein, this study aims to explore the effect of preservation at different temperatures on the inflammatory profile of adipose tissue. Inguinal adipose tissue of rats was collected and cultured in vitro under 4°C, 10°C, and room temperature for 2 hours. The proportion of damaged adipocytes and an array of cytokines were determined. We observed that the damage rate of the adipocyte membrane was slightly higher at room temperature, but there was no significant difference, while we noticed increased IL-6 and MCP-1 levels in adipose tissue at room temperature ( P ＜0.01). The 4°C and 10°C cool temperatures may offer protection against proinflammatory states during the adipose tissue preserved in vitro.

The histologic reaction and permanence of hyaluronic acid gel, calcium hydroxylapatite microspheres, and extracellular matrix bio gel.

BACKGROUND: The filling materials on the beauty market can be classified into three types: natural biological materials, synthetic polymer materials, and composites containing bioactive substances. However, comparative experimental data is lacking to compare their biological responses and permanence. AIMS: The main object of this study was to evaluate the biological response of these three types of fillers to provide a theoretical basis for clinical application. METHODS: Six-week-old female mice were injected subcutaneously with hyaluronic acid (HA) gel, calcium hydroxylapatite (CaHA) microspheres, and extracellular matrix (ECM) bio gel to observe the body reaction and permanence. At 1, 4, 8, and 16 weeks, the test sites were excised and analyzed by histopathology and proteomics. RESULTS: Extracellular matrix had a minimal foreign body response. HA had a good volume effect at the early stage but the volume retention rate was lower than CaHA in the long term. CaHA could stimulate neo-collagen formation. CONCLUSION: This study has proven the effectiveness and safety of these fillers and could provide clinical guidance for the plastic surgeon.

Identification of featured necroptosis-related genes and imbalanced immune infiltration in sepsis via machine learning.

Background: The precise diagnostic and prognostic biological markers were needed in immunotherapy for sepsis. Considering the role of necroptosis and immune cell infiltration in sepsis, differentially expressed necroptosis-related genes (DE-NRGs) were identified, and the relationship between DE-NRGs and the immune microenvironment in sepsis was analyzed. Methods: Machine learning algorithms were applied for screening hub genes related to necroptosis in the training cohort. CIBERSORT algorithms were employed for immune infiltration landscape analysis. Then, the diagnostic value of these hub genes was verified by the receiver operating characteristic (ROC) curve and nomogram. In addition, consensus clustering was applied to divide the septic patients into different subgroups, and quantitative real-time PCR was used to detect the mRNA levels of the hub genes between septic patients (SP) (n = 30) and healthy controls (HC) (n = 15). Finally, a multivariate prediction model based on heart rate, temperature, white blood count and 4 hub genes was established. Results: A total of 47 DE-NRGs were identified between SP and HC and 4 hub genes (BACH2, GATA3, LEF1, and BCL2) relevant to necroptosis were screened out via multiple machine learning algorithms. The high diagnostic value of these hub genes was validated by the ROC curve and Nomogram model. Besides, the immune scores, correlation analysis and immune cell infiltrations suggested an immunosuppressive microenvironment in sepsis. Septic patients were divided into 2 clusters based on the expressions of hub genes using consensus clustering, and the immune microenvironment landscapes and immune function between the 2 clusters were significantly different. The mRNA levels of the 4 hub genes significantly decreased in SP as compared with HC. The area under the curve (AUC) was better in the multivariate prediction model than in other indicators. Conclusion: This study indicated that these necroptosis hub genes might have great potential in prognosis prediction and personalized immunotherapy for sepsis.

Effects of an eastward shift in the Agulhas retroflection region on chlorophyll-a bloom on its south flank.

As observed by remote sensing images in December 2013 and January 2014, chlorophyll-a (Chl-a) bloom occurred on the south side of the Agulhas Current (38°S-45°S). The dynamic mechanisms of Chl-a bloom were studied by satellite remote sensing data, reanalysis data and Argo data. The periodic shedding of the Agulhas ring led to a significant eastward shift of the Agulhas retroflection from December 2013 to January 2014, without the obstruction of flowing complex eddies and with increased current flow. Then, the horizontal transfer of Chl-a occurred along the south side of the Agulhas Current (38°S-45°S). Nitrate concentrations reached 10-15 µmol·L-1 on the south side of the Agulhas Current, where a deepened mixed layer and upwelling and the vertical transport of nutrients contributed to the Chl-a bloom. In addition, sufficient light and suitable precipitation provide good conditions for Chl-a bloom on the south side of the Agulhas Current.

Planthopper salivary sheath protein LsSP1 contributes to manipulation of rice plant defenses.

Salivary elicitors secreted by herbivorous insects can be perceived by host plants to trigger plant immunity. However, how insects secrete other salivary components to subsequently attenuate the elicitor-induced plant immunity remains poorly understood. Here, we study the small brown planthopper, Laodelphax striatellus salivary sheath protein LsSP1. Using Y2H, BiFC and LUC assays, we show that LsSP1 is secreted into host plants and binds to salivary sheath via mucin-like protein (LsMLP). Rice plants pre-infested with dsLsSP1-treated L. striatellus are less attractive to L. striatellus nymphs than those pre-infected with dsGFP-treated controls. Transgenic rice plants with LsSP1 overexpression rescue the insect feeding defects caused by a deficiency of LsSP1 secretion, consistent with the potential role of LsSP1 in manipulating plant defenses. Our results illustrate the importance of salivary sheath proteins in mediating the interactions between plants and herbivorous insects.

Combined Synthesis of Cerium Oxide Particles for Effective Anti-Bacterial and Anti-Cancer Nanotherapeutics.

Introduction: Kochiae Fructus has been widely used in Chinese Herbal medicine to treat various diseases. We report a rapid and eco-friendly approach for cerium oxide (CeO2) nanoparticles (NPs) synthesis using the extract of medicinally important plant "Kochiae Fructus", and the synthesized NPs were named KF-CeO2 NPs. Methods: Various spectroscopic approaches such as transmission electron microscope (TEM), powder X-ray diffraction (XRD), and energy-dispersive X-Ray (EDX) were used to characterize the KF-CeO2 NPs effectively. The antibacterial and biofilm inhibition activity of KF-CeO2 NPs against Gram-positive and Gram-negative multi-drug resistant (MDR) bacteria was determined using the serial dilution method and XTT assay. KF-CeO2 NPs were assessed for anticancer activity against HeLa cancer cells using an MTT assay. Cytobiocompatibility was determined in two normal cell lines (3T3 and hMSC). Results and Discussion: The average size of the KF-CeO2 NPs was 11.3 ± 3.9 nm with spherical morphology. KF-CeO2 NPs demonstrated a greater than 95% bactericidal efficacy against MDR microorganisms. In addition, KF-CeO2 NPs strongly suppressed (more than 79%) the biofilms of MDR bacteria, indicating their potential for addressing antibiotic resistance issues. Compared to Kochiae Fructus extract and CH-CeO2 NPs, they exhibited significant cytotoxic effects (35.60% cell viability) on HeLa cancer cells. In addition, the KF-CeO2 NPs were shown to be highly biocompatible with hMSC and 3T3 cell lines (85.13% and 81.17% cell viability, respectively), suggesting that they may be employed in biological systems. Conclusion: These data indicate that KF-CeO2 NPs synthesized using Kochiae Fructus extract are promising alternative treatments for MDR. In addition, this study will give the potential for the sustained development of biocompatible NPs with enhanced biological capabilities derived from vital pharmaceutical plants.