Confinement Effect in Metal-Organic Framework Cu3(BTC)2 for Enhancing Shape Selectivity of Radical Difunctionalization of Alkenes.

The radical difunctionalization of alkenes plays a vital role in pharmacy, but the conventional homogeneous catalytic systems are challenging in selectivity and sustainability to afford the target molecules. Herein, the famous readily available metal-organic framework (MOF), Cu3(BTC)2, has been applied to cyano-trifluoromethylation of alkenes as a high-performance and recyclable heterogeneous catalyst, which possesses copper(II) active sites residing in funnel-like cavities. Under mild conditions, styrene derivatives and various unactivated olefins could be smoothly transformed into the corresponding cyano-trifluoromethylation products. Moreover, the transformation brought about by the active copper center in confined environments achieved regio- and shape selectivity. To understand the enhanced selectivity, the activation manner of the MOF catalyst was studied with control catalytic experiments such as FT-IR and UV-vis absorption spectroscopy of substrate-incorporated Cu3(BTC)2, which elucidated that the catalyst underwent a radical transformation with the intermediates confined in the MOF cavity, and the confinement effect endowed the method with pronounced selectivities.

A Multiplex Recombinase-Aided qPCR Assay for Highly Sensitive and Rapid Detection of khe, blaKPC -2, and blaNDM -1 Genes in Klebsiella pneumoniae.

OBJECTIVE: This study aimed to establish a highly sensitive and rapid single-tube, two-stage, multiplex recombinase-aided qPCR (mRAP) assay to specifically detect the khe, blaKPC-2, and blaNDM-1 genes in Klebsiella pneumoniae. METHODS: mRAP was carried out in a qPCR instrument within 1 h. The analytical sensitivities of mRAP for khe, blaKPC-2, and blaNDM-1 genes were tested using recombinant plasmids and dilutions of reference strains. A total of 137 clinical isolates and 86 sputum samples were used to validate the clinical performance of mRAP. RESULTS: mRAP achieved the sensitivities of 10, 8, and 14 copies/reaction for khe, blaKPC-2, and blaNDM-1 genes, respectively, superior to qPCR. The Kappa value of qPCR and mRAP for detecting khe, blaKPC-2, and blaNDM-1 genes was 1, 0.855, and 1, respectively (p < 0.05). CONCLUSION: mRAP is a rapid and highly sensitive assay for potential clinical identification of khe, blaKPC-2, and blaNDM-1 genes in K. pneumoniae.

[Characteristics of Microplastic Pollution in Sediment of Silty Coast in Culture Bay].

Microplastic pollution is a central issue of great concern in the current environmental field. Microplastic pollution in marine environmental media is widely reported, but the characteristics of microplastic pollution in deep sediments are rarely reported. Based on this, three sampling points were set up on the muddy coast near the Haizhou Bay, a typical aquaculture sea area, to analyze the characteristics of microplastic pollution in sediment column samples. The study showed that the abundance of microplastics in the sediments of the study area was(0.12 ± 0.07)n·g-1, which was at the medium pollution level. The total amount of microplastics in the sediment column was 3.43-6.00 times the abundance of microplastics in the surface sediment (5 cm). The abundance of microplastics in the sediment column samples showed regional differences. There was no significant difference in the abundance of microplastics in the sediment at different depths, but the index decreased with the increase in depth. The relationship between sediment moisture content, depth, and microplastics indicated that the abundance of microplastics in sediment was related to the physical properties of the sediment. Transparent and black microplastics accounted for the highest proportion in each station. Fiber was the most common form of microplastics in the sediment, and microplastics with small particle size accounted for the majority. The density of microplastics did not prevent its appearance in the sediment. The pollution characteristics of microplastics varied greatly in different depths of sediments.

Adsorption behavior and the potential risk of As(V) in soils: exploring the effects of representative surfactants.

Arsenic contamination in soils poses a critical global challenge, yet the influence of surfactants on arsenic adsorption behavior is often underestimated. This study aims to investigate the effects of three representative surfactants, namely cetyltrimethylammonium bromide (CTAB), sodium dodecyl sulfate (SDS), and polyethylene glycol anhydrous sugar alcohol monooleate (Tween 80), on arsenic adsorption behavior in soils. The adsorption isotherm shifts from a single Temkin model without surfactants to both the Langmuir and Temkin models in the presence of surfactants, indicating the simultaneous occurrence of monolayer and multilayer adsorption for arsenic in soils. Moreover, the surfactants can inhibit the adsorption and hasten the attainment of adsorption equilibrium. SDS displayed the most inhibitory effect on arsenic adsorption, followed by Tween 80 and CTAB, due to the competitive adsorption, electrostatic interaction, and hydrophobic interaction. Variations in zeta potential with different surfactants further elucidate this inhibitory phenomenon. Through orthogonal experiment analyses, pH emerges as a primary factor influencing arsenic adsorption in soils, with surfactant concentration and type identified as secondary factors. Temperature notably affects CTAB, with the adsorption inhibition rate plummeting to a mere 0.88% at 50 °C. Sequential extraction analysis revealed that surfactants enhanced the bioavailability of arsenic. The FTIR, XRD, SEM, and CA analyses further support the mechanism underlying the effect of surfactants on arsenic adsorption in soil. These analyses indicate that surfactants modify the composition and abundance of functional groups, hinder the formation of arsenic-containing substances, and improve soil compactness, smoothness, and hydrophilicity. This study provides valuable insights into the effect of surfactants in arsenic-contaminated soils, which is often ignored in previous work.

Association Between Preoperative Sleep Disturbance and Postoperative Delirium in Elderly: A Retrospective Cohort Study.

Purpose: Postoperative sleep disturbance, characterized by diminished postoperative sleep quality, is a risk factor for postoperative delirium (POD); however, the association between pre-existing sleep disturbance and POD remains unclear. This study aimed to evaluate the association between preoperative sleep disturbance and POD in elderly patients after non-cardiac surgery. Patients and methods: This retrospective cohort study was conducted at a single center and enrolled 489 elderly patients who underwent surgery between May 1, 2020, and March 31, 2021. Patients were divided into the sleep disorder (SD) and non-sleep disorder (NSD) groups according to the occurrence of one or more symptoms of insomnia within one month or sleep- Numerical Rating Scale (NRS)≥6 before surgery. The primary outcome was the incidence of POD. Propensity score matching analysis was performed between the two groups. Multiple logistic regression analysis was performed to identify the risk factors for POD. Results: In both the unmatched cohort (16.0% vs 6.7%, P=0.003) and the matched cohort (17.0% vs 6.2%, P=0.023), the incidence of POD was higher in the SD group than in the NSD group. In addition, the postoperative sleep quality and the VAS score at postoperative 24 h were significantly lower in the SD group than in the NSD group. Multivariate logistic regression analysis indicated that age (Odds Ratio, 1.13 [95% CI: 1.04-1.23], P=0.003) and preoperative sleep disturbance (Odds Ratio, 3.03 [95% CI: 1.09-9.52], P=0.034) were independent risk factors for the development of POD. Conclusion: The incidence of POD was higher in patients with pre-existing sleep disturbance than those without it. Whether improving sleep quality for preoperative sleep disturbance may help prevent POD remains to be determined.

Effect of systemic lupus erythematosus on the ovarian reserve: A systematic review and meta-analysis.

OBJECTIVE: Systemic Lupus Erythematosus (SLE) is an autoimmune disease that occurs at higher rates in young women. Evidence suggests that SLE may be associated with ovarian dysfunction. Therefore, it is crucial to investigate the possible effects of SLE on ovarian reserve function. METHODS: PubMed, Embase, Web of Science, Scopus, Cochrane Library, and ClinicalTrials.gov databases were searched from inception to July 2023 to identify studies that compared ovarian reserve in patients with SLE to that of healthy individuals. The study examined anti-müllerian hormone (AMH), antral follicle count (AFC), and follicle-stimulating hormone (FSH) as outcomes. RESULTS: Thirteen studies (n=1017) were eligible for meta-analysis. Females with SLE had significantly lower levels of AMH (weighted mean difference [WMD]: -1.07, 95% confidence interval [CI]: -1.37 to -0.76, P<0.001) and AFC (WMD: -3.46, 95% CI: -4.57 to -2.34, P<0.001). There was no significant difference in FSH levels. Subgroup analyses by age of onset revealed that SLE patients with adult-onset had significantly lower AMH levels (WMD: -1.44, 95% CI: -1.71 to -1.18, P<0.001), lower AFCs (WMD: -3.11, 95% CI: -3.60 to -2.61, P<0.001) and higher FSH levels (WMD: 0.60, 95% CI: 0.15 to 1.05, P<0.01). However, SLE patients with juvenile-onset did not exhibit significant differences in their AMH and FSH levels, except for AFCs (WMD: -7.27, 95% CI: -12.39 to -2.14, P<0.01). CONCLUSION: The impact of SLE on ovarian reserve is significant, and the effect may be particularly severe in cases of adult-onset SLE.

Gut microbiota plays a significant role in gout.

With the development of social economy, the incidence of gout is increasing, which is closely related to people's increasingly rich diet. Eating a diet high in purine, fat, sugar and low-fibre for a long time further aggravates gout by affecting uric acid metabolism. The renal metabolism mechanism of uric acid has been thoroughly studied. To find a new treatment method for gout, increasing studies have recently been conducted on the mechanism of intestinal excretion, metabolism and absorption of uric acid. The most important research is the relationship between intestinal microbiota and the risk of gout. Gut microbiota represent bacteria that reside in a host's gastrointestinal tract. The composition of the gut microbiota is associated with protection against pathogen colonization and disease occurrence. This review focuses on how gut microbiota affects gout through uric acid and discusses the types of bacteria that may be involved in the occurrence and progression of gout. We also describe potential therapy for gout by restoring gut microbiota homeostasis and reducing uric acid levels. We hold the perspective that changing intestinal microbiota may become a vital method for effectively preventing or treating gout.

Evaluation of water ecological health of Yanhe River based on benthic fauna integrity index.

Yanhe River Basin is located in the hilly gully area of the Loess Plateau with serious soil erosion. Strong human activities in the middle and lower reaches lead to fragile ecological environment. Soil erosion status varies among different geomorphic units within the watershed (loess liang hilly and gully region, loess mao hilly and gully region, and broken platform region). In this study, we surveyed the benthic community from the Yanhe River Basin in April (spring) and October (autumn) of 2021. To evaluate the water ecological health status of the watershed and investigate the effects of different geomorphic units on the benthic integrity of the benthos, we constructed the benthic-index of biotical integrity (B-IBI) based on the biological data. We identified a total of 113 species of 73 genera in 4 phyla of benthic fauna, with aquatic insects as the dominant taxa in both seasons. Through screening 26 candidate indicators, we found that the spring B-IBI consisted of three indicators: relative abundance of individuals of dominant taxonomic units, family biotic index (FBI), and relative abundance of predator individuals, and that autumn B-IBI was composed of the number of taxonomic units of Ephemeroptera, FBI value, and the relative abundance of predator individuals. Results of the B-IBI evaluation showed that 83.3% of the sampling sites in the upper mainstem and tributaries were at a healthy condition, while only 28.6% sampling sites in the middle and lower mainstem and tributaries were at a healthy condition. In addition, the health status of the watershed was better in spring than in autumn. The Kruskal-Wallis nonparametric tests showed that benthic density, species number, and B-IBI percentile scores in the fragmented loess area were significantly higher in spring than in autumn, and significantly lower in autumn than in the loess liang hilly and gully region and loess mao hilly and gully region, being mainly caused by the increasing erosion due to the concentrated rainfall in wet season. Results of the redundancy analysis showed that key environmental factors affecting benthic community structure in spring were boulder substrate, chlorophyll-a, oxidation reduction potential, turbidity, conductivity, and dissolved oxygen, and were nitrate-nitrogen, oxidation reduction potential, and pH in autumn.

Unraveling Key m6A Modification Regulators Signatures in Postmenopausal Osteoporosis through Bioinformatics and Experimental Verification.

OBJECTIVE: Bone marrow mesenchymal stem cells (BMSCs) show significant potential for osteogenic differentiation. However, the underlying mechanisms of osteogenic capability in osteoporosis-derived BMSCs (OP-BMSCs) remain unclear. This study aims to explore the impact of YTHDF3 (YTH N6-methyladenosine RNA binding protein 3) on the osteogenic traits of OP-BMSCs and identify potential therapeutic targets to boost their bone formation ability. METHODS: We examined microarray datasets (GSE35956 and GSE35958) from the Gene Expression Omnibus (GEO) to identify potential m6A regulators in osteoporosis (OP). Employing differential, protein interaction, and machine learning analyses, we pinpointed critical hub genes linked to OP. We further probed the relationship between these genes and OP using single-cell analysis, immune infiltration assessment, and Mendelian randomization. Our in vivo and in vitro experiments validated the expression and functionality of the key hub gene. RESULTS: Differential analysis revealed seven key hub genes related to OP, with YTHDF3 as a central player, supported by protein interaction analysis and machine learning methodologies. Subsequent single-cell, immune infiltration, and Mendelian randomization studies consistently validated YTHDF3's significant link to osteoporosis. YTHDF3 levels are significantly reduced in femoral head tissue from postmenopausal osteoporosis (PMOP) patients and femoral bone tissue from PMOP mice. Additionally, silencing YTHDF3 in OP-BMSCs substantially impedes their proliferation and differentiation. CONCLUSION: YTHDF3 may be implicated in the pathogenesis of OP by regulating the proliferation and osteogenic differentiation of OP-BMSCs.

Hyperbaric oxygen therapy promotes the browning of white fat and contributes to the healing of diabetic wounds.

Non-healing wounds are one of the chronic complications of diabetes and have remained a worldwide challenge as one of the major health problems. Hyperbaric oxygen (HBO) therapy is proven to be very successful for diabetic wound treatment, for which the molecular basis is not understood. Adipocytes regulate multiple aspects of repair and may be therapeutic for inflammatory diseases and defective wound healing associated with aging and diabetes. Endothelial cell-derived extracellular vesicles could promote wound healing in diabetes. To study the mechanism by which HBO promotes wound healing in diabetes, we investigated the effect of HBO on fat cells in diabetic mice. A diabetic wound mouse model was established and treated with HBO. Haematoxylin and eosin (H&E) staining and immunofluorescence were used for the analysis of wound healing. To further explore the mechanism, we performed whole-genome sequencing on extracellular vesicles (EVs). Furthermore, we conducted in vitro experiments. Specifically, exosomes were collected from human umbilical vein endothelial cell (HUVEC) cells after HBO treatment, and then these exosomes were co-incubated with adipose tissue. The wound healing rate in diabetic mice treated with HBO was significantly higher. HBO therapy promotes the proliferation of adipose precursor cells. HUVEC-derived exosomes treated with HBO significantly promoted fat cell browning. These data clarify that HBO therapy may promote vascular endothelial cell proliferation and migration, and promote browning of fat cells through vascular endothelial cells derived exosomes, thereby promoting diabetic wound healing. This provides new ideas for the application of HBO therapy in the treatment of diabetic trauma.

TANGO6 regulates cell proliferation via COPI vesicle-mediated RPB2 nuclear entry.

Coat protein complex I (COPI) vesicles mediate the retrograde transfer of cargo between Golgi cisternae and from the Golgi to the endoplasmic reticulum (ER). However, their roles in the cell cycle and proliferation are unclear. This study shows that TANGO6 associates with COPI vesicles via two transmembrane domains. The TANGO6 N- and C-terminal cytoplasmic fragments capture RNA polymerase II subunit B (RPB) 2 in the cis-Golgi during the G1 phase. COPI-docked TANGO6 carries RPB2 to the ER and then to the nucleus. Functional disruption of TANGO6 hinders the nuclear entry of RPB2, which accumulates in the cytoplasm, causing cell cycle arrest in the G1 phase. The conditional depletion or overexpression of TANGO6 in mouse hematopoietic stem cells results in compromised or expanded hematopoiesis. Our study results demonstrate that COPI vesicle-associated TANGO6 plays a role in the regulation of cell cycle progression by directing the nuclear transfer of RPB2, making it a potential target for promoting or arresting cell expansion.

Spatiotemporal dual-periodic soliton pulsation in a multimode fiber laser.

Spatiotemporal mode-locked (STML) fiber lasers have become a new platform for investigating nonlinear phenomena. In this work, spatiotemporal dual-periodic soliton pulsation (SDSP) is firstly observed in an STML fiber laser. It is found that in the SDSP, the long-period pulsations (LPPs) of different transverse modes are synchronous, while the short-period pulsations (SPPs) exhibit asynchronous modulations. The numerical simulation confirms the experimental results and further reveals that the proportion of transverse mode components can manipulate the periods of the LPP and SPP but does not affect the synchronous and asynchronous pulsations of different transverse modes. The obtained results bring the study of spatiotemporal dissipative soliton pulsation into the multi-period modulation stage, which helps to understand the complex spatiotemporal dynamics in STML fiber lasers and discover new dynamics in high-dimensional nonlinear systems.

IKK2 controls the inflammatory potential of tissue-resident regulatory T cells in a murine gain of function model.

Loss-of-function mutations have provided crucial insights into the immunoregulatory actions of Foxp3+ regulatory T cells (Tregs). By contrast, we know very little about the consequences of defects that amplify aspects of Treg function or differentiation. Here we show that mice heterozygous for an Ikbkb gain-of-function mutation develop psoriasis. Doubling the gene dose (IkbkbGoF/GoF) results in dactylitis, spondylitis, and characteristic nail changes, which are features of psoriatic arthritis. IkbkbGoF mice exhibit a selective expansion of Foxp3 + CD25+ Tregs of which a subset express IL-17. These modified Tregs are enriched in both inflamed tissues, blood and spleen, and their transfer is sufficient to induce disease without conventional T cells. Single-cell transcriptional and phenotyping analyses of isolated Tregs reveal expansion of non-lymphoid tissue (tissue-resident) Tregs expressing Th17-related genes, Helios, tissue-resident markers including CD103 and CD69, and a prominent NF-κB transcriptome. Thus, IKK2 regulates tissue-resident Treg differentiation, and overactivity drives dose-dependent skin and systemic inflammation.

p24-Tango1 interactions ensure ER-Golgi interface stability and efficient transport.

The eukaryotic p24 family, consisting of α-, ß-, γ- and δ-p24 subfamilies, has long been known to be involved in regulating secretion. Despite increasing interest in these proteins, fundamental questions remain about their role. Here, we systematically investigated Drosophila p24 proteins. We discovered that members of all four p24 subfamilies are required for general secretion and that their localizations between ER exit site (ERES) and Golgi are interdependent in an α→ßδ→γ sequence. We also found that localization of p24 proteins and ERES determinant Tango1 requires interaction through their respective GOLD and SH3 lumenal domains, with Tango1 loss sending p24 proteins to the plasma membrane and vice versa. Finally, we show that p24 loss expands the COPII zone at ERES and increases the number of ER-Golgi vesicles, supporting a restrictive role of p24 proteins on vesicle budding for efficient transport. Our results reveal Tango1-p24 interplay as central to the generation of a stable ER-Golgi interface.

The effect of Tween 80 on monochlorobenzene migration in bentonite.

Several studies conducted at industrial sites have documented the infiltration of dense non-aqueous phase liquids (DNAPLs) into clay layers, a phenomenon potentially influenced by the coexistence of chemicals like surfactants in some common pollutants. Bentonite (Ben), monochlorobenzene (MCB), and Tween 80 (T80) were selected as reference components to investigate the influences of nonionic surfactants on DNAPLs migration in clays. Results showed that T80 promotes MCB dissolution and encourages MCB adsorption on Ben. This process reduces the hydrophilicity of Ben, resulting in water loss and shrinkage, which creates cracks and facilitates the migration of MCB within the clay. Tw80 notably enhances MCB solubility, as indicated by a molar solubilization ratio of 7.80. The MCB adsorption on Ben (QMCB) displays a linear increase with raising the T80 adsorption on Ben (QT80), especially when QT80 are below the thresholds, e.g., 408.4 mg/g at pH 3 and 339.3 mg/g at pH 7; however, QMCB is decreased with increasing adsorbed T80 further. The average fracture ratio, crack length, and crack width of cracked samples in the cracking experiments were 0.794%, 11.29 mm, and 0.209 mm, respectively. The findings here contribute to understanding the role of surfactants in VOC transport in contaminated sites.

Tandem Sulfonylative Annulation/Halogenation of 1,7-Enynes with Sodium Sulfinate and TBAX for the Assembly of 4-Methylenechromanes.

An effective and stereoselective synthesis of halogenated (E)-4-methylenechromanes with a sulfonyl group was developed via the copper-catalyzed sulfonylative annulation/halogenation of 1,7-enynes, in which sodium sulfinates were used as the sulfonyl reagents and tetrabutylammonium halide provided the halogen sources. The formed alkenyl C-X bonds were valuable and can efficiently undergo the subsequent hydrolysis, alkenylation, alkynylation, arylation, alkylthiolation, and alkoxylation to furnish a series of highly functionalized 4-methylenechromanes.

Improvement of the nutritional support management system for patients in intensive care units.

BACKGROUND: Nutritional support for patients hospitalized in the intensive care unit (ICU) is an important part of clinical treatment and care, but there are significant implementation difficulties. AIM: To introduce a modified nutritional support management system for ICU patients based on closed-loop information management and psychological counseling. METHODS: The division of functions, personnel training, system construction, development of an intelligent decision-making software system, quality control, and improvement of the whole process were carried out to systematically manage nutritional support for ICU patients. RESULTS: Following the implementation of the whole process management system, the scores of ICU medical staff's knowledge, attitudes/beliefs, and practices regarding nutritional support were comprehensively enhanced. The proportion of hospital bed-days of total enteral nutrition (EN) in ICU patients increased from 5.58% to 11.46%, and the proportion of EN plus parenteral nutrition increased from 42.71% to 47.07%. The rate of EN initiation within 48 h of ICU admission increased from 37.50% to 48.28%, and the EN compliance rate within 72 h elevated from 20.59% to 31.72%. After the implementation of the project, the Self-rating Anxiety Scale score decreased from 61.07 ± 9.91 points to 52.03 ± 9.02 points, the Self-rating Depression Scale score reduced from 62.47 ± 10.50 points to 56.34 ± 9.83 points, and the ICU stay decreased from 5.76 ± 2.77 d to 5.10 ± 2.12 d. CONCLUSION: The nutritional support management system based on closed-loop information management and psychological counseling achieved remarkable results in clinical applications in ICU patients.

Mesenchymal stem cells-based therapies for severe ARDS with ECMO: a review.

Acute respiratory distress syndrome (ARDS) is the primary cause of respiratory failure in critically ill patients. Despite remarkable therapeutic advances in recent years, ARDS remains a life-threatening clinical complication with high morbidity and mortality, especially during the global spread of the coronavirus disease 2019 (COVID-19) pandemic. Previous studies have demonstrated that mesenchymal stem cell (MSC)-based therapy is a potential alternative strategy for the treatment of refractory respiratory diseases including ARDS, while extracorporeal membrane oxygenation (ECMO) as the last resort treatment to sustain life can help improve the survival of ARDS patients. In recent years, several studies have explored the effects of ECMO combined with MSC-based therapies in the treatment of ARDS, and some of them have demonstrated that this combination can provide better therapeutic effects, while others have argued that some critical issues need to be solved before it can be applied to clinical practice. This review presents an overview of the current status, clinical challenges and future prospects of ECMO combined with MSCs in the treatment of ARDS.

Andrographolide sensitizes KRAS-mutant colorectal cancer cells to cetuximab by inhibiting the EGFR/AKT and PDGFRß/AKT signaling pathways.

BACKGROUND: Cetuximab, an inhibitor targeting EGFR, is widely applied in clinical management of colorectal cancer (CRC). Nevertheless, drug resistance induced by KRAS-mutations limits cetuximab's anti-cancer effectiveness. Furthermore, the persistent activation of EGFR-independent AKT is another significant factor in cetuximab resistance. Nevertheless, the mechanism that EGFR-independent AKT drives cetuximab resistance remains unclear. Thus, highlighting the need to optimize therapies to overcome cetuximab resistance and also to explore the underlying mechanism. PURPOSE: This work aimed to investigate whether and how andrographolide enhance the therapeutic efficacy of cetuximab in KRAS-mutant CRC cells by modulating AKT. METHODS: The viabilities of CRC cell lines were analyzed by CCK-8. The intracellular proteins phosphorylation levels were investigated by Human Phospho-kinase Antibody Array analysis. Knockdown and transfection of PDGFRß were used to evaluate the role of andrographolide on PDGFRß. The western blotting was used to investigate Wnt/ß-catenin pathways, PI3K/AKT, and EMT in KRAS-mutant CRC cells. The animal models including subcutaneous tumor and lung metastasis were performed to assess tumor response to therapy in vivo. RESULTS: Andrographolide was demonstrated to decrease the expression of PI3K and AKT through targeting PDGFRß and EGFR, and it enhanced cetuximab effect on KRAS-mutant CRC cells by this mechanism. Meanwhile, andrographolide helped cetuximab to inhibit Wnt/ß-catenin, CRC cell migration and reduced Vimentin expression, while increasing that of E-cadherin. Lastly, co-treatment with cetuximab and andrographolide reduced the growth of KRAS-mutant tumors and pulmonary metastases in vivo. CONCLUSIONS: Our findings suggest that andrographolide can overcome the KRAS-mutant CRC cells' resistance to cetuximab through inhibiting the EGFR/PI3K/AKT and PDGFRß /AKT signaling pathways. This research provided a possible theory that andrographolide sensitizes KRAS-mutant tumor to EGFR TKI.