Comprehensive multi-omics profiling identifies novel molecular subtypes of pancreatic ductal adenocarcinoma.

Pancreatic cancer, a highly fatal malignancy, is predicted to rank as the second leading cause of cancer-related death in the next decade. This highlights the urgent need for new insights into personalized diagnosis and treatment. Although molecular subtypes of pancreatic cancer were well established in genomics and transcriptomics, few known molecular classifications are translated to guide clinical strategies and require a paradigm shift. Notably, chronically developing and continuously improving high-throughput technologies and systems serve as an important driving force to further portray the molecular landscape of pancreatic cancer in terms of epigenomics, proteomics, metabonomics, and metagenomics. Therefore, a more comprehensive understanding of molecular classifications at multiple levels using an integrated multi-omics approach holds great promise to exploit more potential therapeutic options. In this review, we recapitulated the molecular spectrum from different omics levels, discussed various subtypes on multi-omics means to move one step forward towards bench-to-beside translation of pancreatic cancer with clinical impact, and proposed some methodological and scientific challenges in store.

Identification and Quantification of Precursory Changes of Rheumatoid Vasculitis in the Dorsalis Pedis Artery.

OBJECTIVE: Rheumatoid arthritis (RA) is a systemic connective tissue autoimmune disease that can infiltrate arterial walls. The delay in diagnosis and treatment of rheumatoid vasculitis (RV) in patients with RA may lead to irreversible damage to the arterial walls of small-to-medium vessels, which has serious and devastating consequences, most notably lung and cardiac damage. In this work an ultrasound image-based biomarker was developed to detect precursory changes in RV. METHODS: The ground truth was initiated from a medical diagnosis of RA, with arterial wall thickening of the proximal dorsalis pedis artery (DPA) indicating precursory changes of RV identified with ultrasound scanning. Ultrasound images of the DPA from 49 healthy subjects in the control group and 46 patients in the RA group were obtained. In total, 187 texture features were extracted from the images, followed by principal component analysis and linear discriminant analysis. RESULTS: The proposed biomarker detected a significant difference between the two groups (p = 5.74 × 10-18) with an area under the receiver operating characteristic curve of 0.85. Ten major textural features contributing most heavily to the biomarker were identified, with these textures being consistent with clinical observations of RV identified in previous studies. Interscan reproducibility was assessed by computing the biomarker twice based on repeated scans of each ankle. High interscan reproducibility was demonstrated by a strong and significant Pearson's coefficient (r = 0.85, p < 0.01) between the two repeated measurements of the proposed biomarker. CONCLUSION: The proposed biomarker can discriminate image textural differences seen in images acquired from RA patients, demonstrating precursory changes in RV compared with healthy controls. The major discriminative features identified in this study may facilitate the early identification and treatment of RV.

Insights into the Pathogenesis and Treatment of Chemotherapy-Induced Neuropathy: A Focus on Oxidative Stress and Neuroinflammation.

Cancer is a high-morbidity disease prevalent worldwide. Chemotherapy is the primarily used regimen for cancer treatment; however, it also brings severe side effects. Chemotherapy-induced Peripheral Neuropathy (CIPN) and Chemotherapy-induced Cognitive Impairment (CICI) are two main complications occurring in chemotherapy. They are both associated with nervous system injury and are therefore collectively referred to as Chemotherapy-induced Neuropathy (CIN). CIPN induces neuralgia and numbness in limbs, while CICI causes amnesia and cognitive dysfunction. Currently, there are no effective therapeutics to prevent or cure CIN, so research into new drugs to alleviate CIN becomes urgent. Oxidative stress and neuroinflammation are the common pathogenic mechanisms of CIPN and CICI. Excessive Reactive Oxygen Species (ROS) and pro-inflammatory cytokines cause peripheral nervous system damage and hence CIPN. Peripheral ROS and cytokines also change the permeability of the blood-brain barrier, thereby increasing oxidative stress and neuroinflammation in the central nervous system, ultimately leading to CICI. Several antidepressants have been used to treat CIN and exhibited good clinical effects. Their potential pharmacological mechanism has been reported to ameliorate oxidative stress and neuroinflammation, guiding a new feasible way for effective therapeutic development against CIN. This mini-review has summarized the latest advances in the research on CIN with respect to clinical status, pathogenesis, and treatment. It has also discussed the potential of repurposing antidepressants for CIN treatment and prospected the strategy of developing therapeutics by targeting oxidative stress and neuroinflammation against CIN.

Comparisons of laparoscopic and robotic pancreaticoduodenectomy using barbed and conventional sutures for pancreaticojejunostomy: a propensity score matching study.

BACKGROUND: There are limited data on the effect of different sutures and surgical approaches on the quality of pancreaticojejunostomy in minimally invasive pancreaticoduodenectomy (MIPD). This study compares the incidence of clinically relevant postoperative pancreatic fistula (CR-POPF) between the use of barbed sutures (BSs) and conventional sutures (CSs). METHODS: A retrospective cohort study was conducted on 253 consecutive patients who had undergone MIPD from July 2016 to April 2023. Patients were excluded if conversion to open surgery or open anastomosis was necessary. 220 patients were enrolled and divided into BS (n = 148) and CS (n = 72) groups. After 1:1 propensity score matching (PSM), 67 cases remained in each group. Univariate and multivariate analyses identified factors associated with CR-POPF. Comparisons were also made between laparoscopic (LPD) and robotic (RPD) pancreaticoduodenectomy. RESULTS: After PSM, BSs were associated with significantly lower rates of CR-POPF (7.5 vs. 22.4%, P = 0.015) and severe complications (Clavien-Dindo ≥ III) (7.5vs. 19.4%, P = 0.043). No significant differences were found in operative time, length of postoperative hospital stay, or other major morbidities. Multivariate analyses revealed BMI ≥ 22 kg/m2 (OR = 5.048, 95% CI: 1.256-20.287, P = 0.023) and the use of BSs (OR = 0.196, 95% CI: 0.059-0.653, P = 0.008) as the independent predictors of CR-POPF. There were no significant differences in postoperative outcomes between the LPD and RPD groups, but RPD was associated with significantly shorter operative time (402.8 min vs. 429.4 min, P = 0.015). CONCLUSIONS: In conclusion, using BSs for PJ during MIPD is feasible and has the potential to reduce CR-POPF and severe complications.

Iron-copper bimetallic photo-Fenton system promoted photothermal-hydrogen peroxide production for efficient low-temperature wastewater treatment.

Enhancing the velocity of the oxidation-reduction cycle is crucial for improving the catalytic efficiency of Fenton processes. Therefore, the development of an effective strategy for wastewater degradation at low temperatures is essential. In this context, we present the preparation of an NH2-MIL-88B (Fe)/CuInS2 S-scheme heterojunction. Specifically, CuInS2 nanoparticles are introduced onto the Ferro-organic skeleton, resulting in the exposure of a significant number of active surface sites. Furthermore, NH2-MIL-88B (Fe)/CuInS2 demonstrates an extended photoresponse into the long-wavelength region, which contributes to its excellent photothermal properties. Notably, the degradation rate of tetracycline in low-temperature aqueous environments reaches as high as 99.7 %, several times higher than that of the original sample. Additionally, the hydrogen production of NH2-MIL-88B (Fe)/CuInS2 is 2.23 times that of single NH2-MIL-88B (Fe) and 3.46 times that of single CuInS2. Moreover, the system exhibits good H2O2 evolution performance, forming an efficient photo-Fenton system. The charge transfer process in S-scheme heterojunction is confirmed using in-situ X-ray photoelectron spectroscopy and electron paramagnetic resonance. Both transient photoluminescence and photo electrochemical tests further validate the enhanced photoelectrochemical properties of the NH2-MIL-88B (Fe)/CuInS2 S-scheme heterojunction. The exceptional performance of this system can be attributed to the synergistic effects of the S-scheme heterojunction and the bimetallic codoped photo-Fenton system. This research presents a novel approach for the breakdown of low-temperature wastewater using an improved photocatalytic Fenton system.

Principles and Methods for Improving the Thermoelectric Performance of SiC: A Potential High-Temperature Thermoelectric Material.

Thermoelectric materials that can convert thermal energy to electrical energy are stable and long-lasting and do not emit greenhouse gases; these properties render them useful in novel power generation devices that can conserve and utilize lost heat. SiC exhibits good mechanical properties, excellent corrosion resistance, high-temperature stability, non-toxicity, and environmental friendliness. It can withstand elevated temperatures and thermal shock and is well suited for thermoelectric conversions in high-temperature and harsh environments, such as supersonic vehicles and rockets. This paper reviews the potential of SiC as a high-temperature thermoelectric and third-generation wide-bandgap semiconductor material. Recent research on SiC thermoelectric materials is reviewed, and the principles and methods for optimizing the thermoelectric properties of SiC are discussed. Thus, this paper may contribute to increasing the application potential of SiC for thermoelectric energy conversion at high temperatures.

Antidepressant Sertraline Synergistically Enhances Paclitaxel Efficacy by Inducing Autophagy in Colorectal Cancer Cells.

Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. It is important to discover new therapeutic regimens for treating CRC. Depression is known to be an important complication of cancer diseases. Repurposing antidepressants into anticancer drugs and exploring the combinational efficacy of antidepressants and chemotherapy are potentially good options for developing CRC treatment regimens. In this study, sertraline, an antidepressant drug, and paclitaxel, an anticancer drug, were chosen to study their antitumor effects in the treatment of colorectal cancer, alone or in combination, and to explore their underlying mechanisms. The data showed that sertraline exerted a dose-dependent cytotoxic effect on MC38 and CT26 colorectal cancer cell lines with IC50 values of 10.53 µM and 7.47 µM, respectively. Furthermore, sertraline synergistically sensitized chemotherapeutic agent paclitaxel efficacy in CRC cells with combination index (CI) values at various concentrations consistently lower than 1. Sertraline remarkably augmented paclitaxel-induced autophagy by increasing autophagosome formation indicated by elevated LC3-II/I ratio and promoting autophagic flux by degrading autophagy cargo receptor SQSTM1/p62, which may explain the synergistically cytotoxic effect of sertraline and paclitaxel combination therapy on CRC cells. This study provides important evidence to support repurposing sertraline as an anticancer agent and suggests a novel combinational regimen for effectively treating CRC as well as in the simultaneous treatment of CRC and depression.

Counterfactual Causal-Effect Intervention for Interpretable Medical Visual Question Answering.

Medical Visual Question Answering (VQA-Med) is a challenging task that involves answering clinical questions related to medical images. However, most current VQA-Med methods ignore the causal correlation between specific lesion or abnormality features and answers, while also failing to provide accurate explanations for their decisions. To explore the interpretability of VQA-Med, this paper proposes a novel CCIS-MVQA model for VQA-Med based on a counterfactual causal-effect intervention strategy. This model consists of the modified ResNet for image feature extraction, a GloVe decoder for question feature extraction, a bilinear attention network for vision and language feature fusion, and an interpretability generator for producing the interpretability and prediction results. The proposed CCIS-MVQA introduces a layer-wise relevance propagation method to automatically generate counterfactual samples. Additionally, CCIS-MVQA applies counterfactual causal reasoning throughout the training phase to enhance interpretability and generalization. Extensive experiments on three benchmark datasets show that the proposed CCIS-MVQA model outperforms the state-of-the-art methods. Enough visualization results are produced to analyze the interpretability and performance of CCIS-MVQA.

Advances in nano-preparations for improving tetrandrine solubility and bioavailability.

Tetrandrine (TET) is a natural bis-benzylisoquinoline alkaloid isolated from Stephania species with a wide range of biological and pharmacologic activities; it mainly serves as an anti-inflammatory agent or antitumor adjuvant in clinical applications. However, limitations such as prominent hydrophobicity, severe off-target toxicity, and low absorption result in suboptimal therapeutic outcomes preventing its widespread adoption. Nanoparticles have proven to be efficient devices for targeted drug delivery since drug-carrying nanoparticles can be passively transported to the tumor site by the enhanced permeability and retention (EPR) effects, thus securing a niche in cancer therapies. Great progress has been made in nanocarrier construction for TET delivery due to their outstanding advantages such as increased water-solubility, improved biodistribution and blood circulation, reduced off-target irritation, and combinational therapy. Herein, we systematically reviewed the latest advancements in TET-loaded nanoparticles and their respective features with the expectation of providing perspective and guidelines for future research and potential applications of TET.

High Strength UV-Resistant Composite Film of Fe3+-Coordination Lignin/PVA.

The literature on polyvinyl alcohol (PVA) films is extensive, however, these methods often necessitate intricate synthesis processes or the addition of plasticizers to modify the strength and water solubility of the PVA material. A high-strength UV radiation-resistant composite film by chelating Fe3+ with lignin and PVA, which exhibits excellent hydrolysis resistance is developed. This composite film is prepared simply by incorporating a small amount of dealkalized lignin (APPL) and ferric chloride (FeCl3) into PVA through a straightforward composite process. During the scanning test, it is noted that the film exhibits a high density of uniformly dispersed particles, endowing it with efficient ultraviolet absorption capabilities. The infrared and anti-dissolution tests reveal that the coordination of Fe3+ with lignin imparts an outstanding hydrolysis resistance to the film, obviating the need for any extender, curing agent, acid or base. The tensile fracture strength reaches an impressive 187.81Mpa in the tensile test. UV and indicator card tests unequivocally demonstrate that the film achieves a remarkable 100% anti-UV efficiency. This Fe3+ chelated lignin/PVA composite film, with its facile preparation, environmental sustainability, high strength, and outstanding anti-ultraviolet efficiency, can be deployed across diverse applications requiring robust protection against ultraviolet radiation.

The significant role of amino acid metabolic reprogramming in cancer.

Amino acid metabolism plays a pivotal role in tumor microenvironment, influencing various aspects of cancer progression. The metabolic reprogramming of amino acids in tumor cells is intricately linked to protein synthesis, nucleotide synthesis, modulation of signaling pathways, regulation of tumor cell metabolism, maintenance of oxidative stress homeostasis, and epigenetic modifications. Furthermore, the dysregulation of amino acid metabolism also impacts tumor microenvironment and tumor immunity. Amino acids can act as signaling molecules that modulate immune cell function and immune tolerance within the tumor microenvironment, reshaping the anti-tumor immune response and promoting immune evasion by cancer cells. Moreover, amino acid metabolism can influence the behavior of stromal cells, such as cancer-associated fibroblasts, regulate ECM remodeling and promote angiogenesis, thereby facilitating tumor growth and metastasis. Understanding the intricate interplay between amino acid metabolism and the tumor microenvironment is of crucial significance. Expanding our knowledge of the multifaceted roles of amino acid metabolism in tumor microenvironment holds significant promise for the development of more effective cancer therapies aimed at disrupting the metabolic dependencies of cancer cells and modulating the tumor microenvironment to enhance anti-tumor immune responses and inhibit tumor progression.

Comparison of Fusion Rate and Clinical Outcomes in Minimally Invasive and Conventional Posterior Fusion for Lumbar Degenerative Disease: A Network Meta-Analysis.

BACKGROUND: The fusion rate, clinical efficacy, and complications of minimally invasive fusion surgery and open fusion surgery in the treatment of lumbar degenerative disease are still unclear. METHODS: We conducted a literature search using PubMed, Embase, Cochrane Library, CNKI, and WANFANG databases. RESULTS: This study included 38 retrospective studies involving 3097 patients. Five intervention modalities were considered: unilateral biportal endoscopic-lumbar interbody fusion (UBE-LIF), percutaneous endoscopic-lumbar interbody fusion (PE-LIF), minimally invasive-transforaminal lumbar interbody fusion (MIS-TLIF), transforaminal lumbar interbody fusion (TLIF), and posterior lumbar interbody fusion (PLIF). Quality assessment indicated that each study met acceptable quality standards. PE-LIF demonstrated reduced low back pain (Odds Ratio = 0.50, Confidence Interval: 0.38-0.65) and lower complication rate (Odds Ratio = 0.46, Confidence Interval: 0.25-0.87) compared to PLIF. However, in indirect comparisons, PE-LIF showed the lowest fusion rates, with the ranking as follows: UBE-LIF (83.2%) > MIS-TLIF (59.6%) > TLIF (44.3%) > PLIF (39.8%) > PE-LIF (23.1%). With respect to low back pain relief, PE-LIF yielded the best results, with the order of relief as follows: PE-LIF (96.4%) > MIS-TLIF (64.8%) > UBE-LIF (62.6%) > TLIF (23.0%) > PLIF (3.2%). Global and local consistency tests showed satisfactory results, and heterogeneity tests indicated good stability. CONCLUSIONS: Compared to conventional open surgery, minimally invasive fusion surgery offered better scores for low back pain and Oswestry Disability Index, lower complication rates, reduced bleeding, and shorter hospital stays. However, minimally invasive fusion surgery did not show a significant advantage in terms of fusion rate and had a longer operative time.

The Synergy Reinforcement Effect of Sm0.85Zn0.15MnO3 and ZrMgMo3O12 on Sm0.85Zn0.15MnO3-ZrMgMo3O12/Al-20Si Composites.

Negative thermal expansion (NTE) ceramics Sm0.85Zn0.15MnO3 (SZMO) and ZrMgMo3O12 (ZMMO) were selected to prepare Sm0.85Zn0.15MnO3-ZrMgMo3O12/Al-20Si (SZMO-ZMMO/Al-20Si) composites using ball milling and vacuum heating-press sintering processes in this study. The synergistic effect of the SZMO and ZMMO NTE ceramic reinforcements on the microstructure, mechanical properties, and coefficient of thermal expansion (CTE) of the composites was investigated. The results show that the processes of ball milling and sintering did not induce the decomposition of SZMO or ZMMO NTE ceramic reinforcements, nor did they promote a reaction between the Al-20Si matrix and SZMO or ZMMO NTE ceramic reinforcements. However, the excessive addition of SZMO and ZMMO NTE ceramics led to their aggregation within the composite. Adding a small amount of SZMO in combination with ZMMO effectively increased hardness and yield strength while reducing CTE in the Al-20Si alloy. The improvement in strength was primarily provided by SZMO, while the inhibition effect on CTE was primarily provided by ZMMO. An evaluation parameter denoted as α was proposed to evaluate the synergy effects of SZMO and ZMMO NTE ceramic reinforcements on the mechanical properties and CTE of the composites. Based on this parameter, among all composites fabricated, adding 2.5 vol% SZMO NTE ceramic and 10 vol% ZMMO NTE ceramic resulted in an optimal balance between CTE and strength for these composites with a compressive yield strength of 349.72 MPa and a CTE of 12.55 × 10-6/K, representing a significant increase in yield strength by 79.20% compared to that of Al-20Si alloy along with a notable reduction in CTE by 26.44%.

Current research progress, opportunities, and challenges of Limosillactobacillus reuteri-based probiotic dietary strategies.

Limosillactobacillus reuteri (L. reuteri), a type of Lactobacillus spp., stands out as the most extensively researched probiotic. Its remarkable intestinal adhesion has led to widespread applications in both the food and medical sectors. Notably, recent research highlights the probiotic efficacy of L. reuteri sourced from breast milk, particularly in influencing social behavior and mitigating atopic dermatitis. In this review, our emphasis is on surveying recent literature regarding the promotion of host's health by L. reuteri. We aim to provide a concise summary of the latest regulatory effects and potential mechanisms attributed to L. reuteri in the realms of metabolism, brain- and immune-related functions. The mechanism through which L. reuteri promotes host health by modulating the intestinal microenvironment primarily involves promoting intestinal epithelial renewal, bolstering intestinal barrier function, regulating gut microbiota and its metabolites, and suppressing inflammation and immune responses. Additionally, this review delves into new technologies, identifies shortcomings, and addresses challenges in current L. reuteri research. Finally, the application prospects of L. reuteri are provided. Therefore, a better understanding of the role and mechanisms of L. reuteri will contribute significantly to the development of new probiotic functional foods and enable precise, targeted interventions for various diseases.

αO-Conotoxin GeXIVA[1,2] Suppresses In Vivo Tumor Growth of Triple-Negative Breast Cancer by Inhibiting AKT-mTOR, STAT3 and NF-κB Signaling Mediated Proliferation and Inducing Apoptosis.

Breast cancer is one of the leading causes of cancer mortality worldwide, and triple-negative breast cancer (TNBC) is the most problematic subtype. There is an urgent need to develop novel drug candidates for TNBC. Marine toxins are a valuable source for drug discovery. We previously identified αO-conotoxin GeXIVA[1,2] from Conus generalis, which is a selective antagonist of α9 nicotinic acetylcholine receptors (nAChRs). Recent studies indicated that α9 nAChR expression is positively correlated with breast cancer development; thus, α9 nAChR could serve as a therapeutic target for breast cancer. In this study, we aimed to investigate the in vivo antitumor effects of GeXIVA[1,2] on TNBC and to elucidate its underlying anticancer mechanism. Our data showed that GeXIVA[1,2] effectively suppressed 4T1 tumor growth in vivo at a very low dose of 0.1 nmol per mouse. Our results uncovered that the antitumor mechanism of GeXIVA[1,2] simultaneously induced apoptosis and blocked proliferation. Further investigations revealed that GeXIVA[1,2]-induced Caspase-3-dependent apoptosis was achieved through regulating Bax/Bcl-2 balance, and GeXIVA[1,2]-inhibited proliferation was mediated by the downregulation of the AKT-mTOR, STAT3 and NF-κB signaling pathways. Our study provides valuable arguments to demonstrate the potential of GeXIVA[1,2] as a novel marine-derived anticancer drug candidate for the treatment of TNBC.

A novel LD-targeting cysteine-activated fluorescent probe for diagnosis of APAP-induced liver injury and its application in food analysis.

Cysteine (Cys) not only plays an indispensable role in maintaining the redox balance in organisms, but is also an important nutrient in the food industry. Fluorescence-based detection systems have emerged as an effective method to track the locations and concentrations of different species. To achieve efficient monitoring of Cys in both food samples and biological systems, a novel lipid droplet (LD) targeted fluorescent probe (namely NIT-Cys) was constructed for the turn-on detection of Cys, characterized by a large Stokes shift (142 nm), a short response time (<8 min), and a low Cys detection limit (39 nM). Furthermore, the NIT-Cys probe has been successfully used not only to quantify the amounts of Cys in selected food samples, but also to enable the visualization of endogenous Cys in acetaminophen (APAP)-induced drug-induced liver injury cells, zebrafish larvae and mice models. Consequently, the work presented here provides an efficient tool for monitoring Cys.

Coherent beam combining of two all-PM thulium-doped fiber chirped pulse amplifiers.

In this paper, we report a coherent beam combining (CBC) system that involves two thulium-doped all-polarization maintaining (PM) fiber chirped pulse amplifiers. Through phase-locking the two channels via a fiber stretcher by using the stochastic parallel gradient descent (SPGD) algorithm, a maximum average power of 265 W is obtained, with a CBC efficiency of 81% and a residual phase error of λ/17. After de-chirping by a pair of diffraction gratings, the duration of the combined laser pulse is compressed to 690 fs. Taking into account the compression efficiency of 90% and the main peak energy proportion of 91%, the corresponding peak power is calculated to be 4 MW. The laser noise characteristics before and after CBC are examined, and the results indicate that the CBC would degrade the low frequency relative intensity noise (RIN), of which the integration is 1.74% in [100 Hz, 2 MHz] at the maximum combined output power. In addition, the effects of the nonlinear spectrum broadening during chirped pulse amplification on the CBC efficiency are also investigated, showing that a higher extent of pulse stretching is effective in alleviating the spectrum broadening and realizing a higher output power with decent combining efficiency.

Emerging anticancer potential and mechanisms of snake venom toxins: A review.

Animal-derived venom, like snake venom, has been proven to be valuable natural resources for the drug development. Previously, snake venom was mainly investigated in its pharmacological activities in regulating coagulation, vasodilation, and cardiovascular function, and several marketed cardiovascular drugs were successfully developed from snake venom. In recent years, snake venom fractions have been demonstrated with anticancer properties of inducing apoptotic and autophagic cell death, restraining proliferation, suppressing angiogenesis, inhibiting cell adhesion and migration, improving immunity, and so on. A number of active anticancer enzymes and peptides have been identified from snake venom toxins, such as L-amino acid oxidases (LAAOs), phospholipase A2 (PLA2), metalloproteinases (MPs), three-finger toxins (3FTxs), serine proteinases (SPs), disintegrins, C-type lectin-like proteins (CTLPs), cell-penetrating peptides, cysteine-rich secretory proteins (CRISPs). In this review, we focus on summarizing these snake venom-derived anticancer components on their anticancer activities and underlying mechanisms. We will also discuss their potential to be developed as anticancer drugs in the future.

System optimization study of hybrid K-edge/XRF densitometer for uranium-plutonium solution measurement.

In this paper, a comprehensive hybrid K-edge/XRF densitometer (HKED) device model is constructed using MCNP simulation. After the modeling process, a systematic simulation study is conducted to analyze the physical parameters and material selection of KED and XRF. The simulation results reveal that the optimal parameters for the X-ray tube are an X-ray source voltage of 160 kV and a 1 mm Fe filter. The sample should be placed in a vial with an inner diameter of 1.4 cm and an outer diameter of 2 cm. For the KED technique, the determined main parameters are a 1.9 cm Fe filter rod and an inner diameter of 0.08 cm for the collimator. For the XRF technique, the determined main parameters are a 0.01 cm Gd filter and an inner diameter of 0.3 cm for the collimator, with a detector angle of 150°. After selecting appropriate parameters, the average calibration factor Δµ of the KED technique was found to be 3.301 cm2 g-1, with a relative standard deviation (RSD) of 3.36%. Additionally, the comparison between the simulated and calculated values of uranium concentration revealed a minimum measurement error of 0.4%. The minimum detection concentration of KED for uranium solutions is approximately 1 g/L. For plutonium solutions ranging from 0.5 to 20 g/L, linear fitting of the Ka1 net peak area and plutonium concentration showed a coefficient of determination (R2) of 0.999. The detection limit of XRF for plutonium measurement was 2.33✕10-4 g/L. The linear fitting coefficients (R2) of uranium concentration versus K-edge transmission rate and plutonium concentration versus Ka1 net peak area for the hybrid technique in measuring uranium-plutonium mixed solutions are determined as 0.999 and 0.996, respectively, demonstrating the response relationship of the HKED device to uranium and plutonium under different concentrations.