Ultrasmall Metal TPZ Complexes with Deep Tumor Penetration for Enhancing Radiofrequency Ablation Therapy and Inducing Antitumor Immune Responses.

Radiofrequency ablation (RFA) is one of the most common minimally invasive techniques for the treatment of solid tumors, but residual malignant tissues or small satellite lesions after insufficient RFA (iRFA) are difficult to remove, often leading to metastasis and recurrence. Here, Fe-TPZ nanoparticles are designed by metal ion and (TPZ) ligand complexation for synergistic enhancement of RFA residual tumor therapy. Fe-TPZ nanoparticles are cleaved in the acidic microenvironment of the tumor to generate Fe2+ and TPZ. TPZ, an anoxia-dependent drug, is activated in residual tumors and generates free radicals to cause tumor cell death. Elevated Fe2+ undergoes a redox reaction with glutathione (GSH), inducing a strong Fenton effect and promoting the production of the highly toxic hydroxyl radical (•OH). In addition, the ROS/GSH imbalance induced by this treatment promotes immunogenic cell death (ICD), which triggers the release of damage-associated molecular patterns, macrophage polarization, and lymphocyte infiltration, thus triggering a systemic antitumor immune response and noteworthy prevention of tumor metastasis. Overall, this integrated treatment program driven by multiple microenvironment-dependent pathways overcomes the limitations of the RFA monotherapy approach and thus improves tumor prognosis. Furthermore, these findings aim to provide new research ideas for regulating the tumor immune microenvironment.

Experimental demonstration of wavefront reconstruction and correction techniques for variable targets based on distorted grating and deep learning.

This research presents a practical approach for wavefront reconstruction and correction adaptable to variable targets, with the aim of constructing a high-precision, general extended target adaptive optical system. Firstly, we delve into the detailed design of a crucial component, the distorted grating, simplifying the optical system implementation while circumventing potential issues in traditional phase difference-based collection methods. Subsequently, normalized fine features (NFFs) and structure focus features (SFFs) which both are independent of the imaging target but corresponded precisely to the wavefront aberration are proposed. The two features provide a more accurate and robust characterization of the wavefront aberrations. Then, a Noise-to-Denoised Generative Adversarial Network (N2D-GAN) is employed for denoising real images. And a lightweight network, Attention Mechanism-based Efficient Network (AM-EffNet), is applied to achieve efficient and high-precision mapping between features and wavefronts. A prototype of object-independent adaptive optics system is demonstrated by experimental setup, and the effectiveness of this method in wavefront reconstruction for different imaging targets has been verified. This research holds significant relevance for engineering applications of adaptive optics, providing robust support for addressing challenges within practical systems.

Multi-line-of-sight Hartmann-Shack wavefront sensing based on image segmentation and K-means sorting.

Multi-line-of-sight wavefront sensing, crucial for next-generation astronomy and laser applications, often increases system complexity by adding sensors. This research introduces, to the best of our knowledge, a novel method for multi-line-of-sight Hartmann-Shack wavefront sensing by using a single sensor, addressing challenges in centroid estimation and classification under atmospheric turbulence. This method contrasts with existing techniques that rely on multiple sensors, thereby reducing system complexity. Innovations include combining edge detection and peak extraction for precise centroid calculation, improved k-means clustering for robust centroid classification, and a centroid filling algorithm for subapertures with light loss. The method's effectiveness was confirmed through simulations for a five-line-of-sight system and experimental setup for two-line and three-line-of-sight systems, demonstrating its potential in real atmospheric aberration correction conditions. Experimental findings indicate that, when implemented in a closed-loop configuration, the method significantly reduces wavefront residuals from 1 λ to 0.1 λ under authentic atmospheric turbulence conditions. Correspondingly, the quality of the far-field spot is enhanced by a factor of 2 to 4. These outcomes collectively highlight the method's robust capability in enhancing optical system performance in environments characterized by genuine atmospheric turbulence.

Performance of the neural network-based prediction model in closed-loop adaptive optics.

Adaptive optics (AO) technology is an effective means to compensate for atmospheric turbulence, but the inherent delay error of an AO system will cause the compensation phase of the deformable mirror (DM) to lag behind the actual distortion, which limits the correction performance of the AO technology. Therefore, the feed-forward prediction of atmospheric turbulence has important research value and application significance to offset the inherent time delay and improve the correction bandwidth of the AO system. However, most prediction algorithms are limited to an open-loop system, and the deployment and the application in the actual AO system are rarely reported, so its correction performance improvement has not been verified in practice. We report, to our knowledge, the first successful test of a deep learning-based spatiotemporal prediction model in an actual 3 km laser atmospheric transport AO system and compare it with the traditional closed-loop control methods, demonstrating that the AO system with the prediction model has higher correction performance.

Earthworm gut digestion drives the transfer behavior of antibiotic resistance genes in layers of extracellular polymeric substances during vermicomposting of dewatered sludge.

Gut digestion by earthworms (GDE) is a crucial step in vermicomposting, affecting the fate of antibiotic resistance genes (ARGs) in vermicompost sludge. The extracellular polymeric substance (EPS) matrix of sludge is an important space for ARG transfer. However, the effect of GDE on EPS-associated ARGs remains unclear. Therefore, this study explored the role of GDE in driving the transfer of ARGs within different EPS layers in sludge. For this, the changes in intracellular ARGs and EPS-associated ARGs in sludge were analyzed after 5 days of the GDE process. The results showed that after the GDE process, both nitrate and dissolved organic carbon significantly increased in all EPS layers of sludge, while the proteins and polysaccharides only enhanced in soluble and loosely bound EPS of sludge. In addition, a 7.0% decrease in bacterial diversity was recorded after the GDE process, with a functional bacterial community structure emerging. Moreover, the absolute abundance of total ARGs and mobile genetic elements decreased by 90.71% and 61.83%, respectively, after the GDE process. Intracellular ARGs decreased by 92.1%, while EPS-associated ARGs increased by 4.9%, indicative of intracellular ARG translocation into the EPS during the GDE process. Notably, the ARGs exhibited significant enrichment in both the soluble and loosely bound EPS, whereas they were reduced in the tightly bound EPS. The structural equation modeling revealed that the GDE process effectively mitigated the ARG dissemination risk by modulating both the EPS structure and microenvironment, with the organic structure representing a primary factor influencing ARGs in the EPS.

In situ anchored ternary hierarchical hybrid nickel@cobaltous sulfide on poly(3,4-ethylenedioxythiophene)-reduced graphene oxide for highly efficient non-enzymatic glucose sensing.

A ternary hierarchical hybrid Ni@CoxSy/poly(3,4-ethylenedioxythiophene)-reduced graphene oxide (Ni@CoxSy/PEDOT-rGO) is rationally designed and in situ facilely synthesized as electrocatalyst to construct a binder-free sensing platform for non-enzymatic glucose monitoring through traditional electrodeposition procedure. The as-prepared Ni@CoxSy/PEDOT-rGO presents unique hierarchical structure and multiple valence states as well as strong and robust adhesion between Ni@CoxSy/PEDOT-rGO and GCE. Profiting from the aforementioned merits, the sensing platform constructed under optimal conditions achieved a wide detection range (0.2 µM ~ 2.0 mM) with high sensitivity (1546.32 µA cm-2 mM-1), a rapid response time (5 s), an ultralow detection limit (0.094 µM), superior anti-interference performance, excellent reproducibility and considerable stability. Furthermore, the sensor demonstrates an acceptable accuracy and appreciable recoveries ranging from 90.0 to 102.0% with less than 3.98% RSD in human blood serum samples, indicating the prospect of the sensor for the real samples analysis. It will provide a strategy to rationally design and fabricate ternary hierarchical hybrid as nanozyme for glucose assay.

Object-independent wavefront sensing method based on an unsupervised learning model for overcoming aberrations in optical systems.

This Letter introduces the idea of unsupervised learning into object-independent wavefront sensing for the first time, to the best of our knowledge, which can achieve fast phase recovery of arbitrary objects without labels. First, a fine feature extraction method which only depends on the wavefront aberrations is proposed. Then, a lightweight neural network and an optical feature system are combined to form an unsupervised learning model, and the neural network is promoted to be well trained by reversely outputting fine features. Simulation results prove that the proposed method can effectively overcome the aberrations (static or variable) existing in the optical system and achieve wavefront sensing of different objects with high precision and efficiency.

Efficacy, mechanism, and safety of melatonin-loaded on thermosensitive nanogels for rabbit VX2 tumor embolization: A novel design.

Transarterial chemoembolization (TACE) has been widely used for hepatocellular carcinoma. Reducing hypoxia in the tumor microenvironment after TACE remains a challenge as tumor progression is common in post-TACE patients due to the hypoxic tumor microenvironment. In this study, melatonin loaded on p(N-isopropyl-acrylamide-co-butyl methylacrylate) (PIB-M) was used for tumor embolism. Two types of human hepatoma cell lines were used to explore the mechanism by which melatonin prevents the growth and metastasis of cancer cells in vitro. A VX2 rabbit tumor model was used to evaluate the efficacy, mechanism, and safety of PIB-M in vivo. We found that under hypoxic condition, melatonin could inhibit tumor cell proliferation and migration by targeting hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor A (VEGF-A) in vitro. In vivo, PIB-M inhibited tumor growth and metastasis in rabbit VX2 tumors by promoting apoptosis of tumor cells and targeting related angiogenic proteins and vascular permeability proteins. A high concentration of melatonin in the PIB-M group could be maintained in tumor tissue for 72 h after embolization. The liver and kidney functions were most damaged on the first day but recovered to normal on the seventh day after embolization in the PIB-M group. This novel method may open avenues for reduction of tumor growth and metastasis after TACE and is efficacy and safety, which may be used for treatment for other solid tumors and clinical translation.

Highly Stable Spatio-Temporal Prediction Network of Wavefront Sensor Slopes in Adaptive Optics.

Adaptive Optics (AO) technology is an effective means to compensate for wavefront distortion, but its inherent delay error will cause the compensation wavefront on the deformable mirror (DM) to lag behind the changes in the distorted wavefront. Especially when the change in the wavefront is higher than the Shack-Hartmann wavefront sensor (SHWS) sampling frequency, the multi-frame delay will seriously limit its correction performance. In this paper, a highly stable AO prediction network based on deep learning is proposed, which only uses 10 frames of prior wavefront information to obtain high-stability and high-precision open-loop predicted slopes for the next six frames. The simulation results under various distortion intensities show that the prediction accuracy of six frames decreases by no more than 15%, and the experimental results also verify that the open-loop correction accuracy of our proposed method under the sampling frequency of 500 Hz is better than that of the traditional non-predicted method under 1000 Hz.

Fabrication and Investigation of the Microwave Absorption of Nonwovens Modified by Carbon Nanotubes and Graphene Flakes.

This study aims to investigate the influences of carbon nanotubes (CNTs) and graphene flakes (GFs) on the microwave absorption performance of nonwovens. Nonwovens were modified with CNTs and GFs through an impregnation method, creating a series of absorption samples with different carbon nanomaterial contents. Then the absorption performance of the samples was tested on both sides in the X-band (8.2~12.4 GHz) and the Ku-band (12~18 GHz) using the arch method. The experimental results showed that the absorption performance of GF-impregnated nonwovens was superior to that of CNT-impregnated nonwovens, and the overall absorption performance in the Ku-band was better than in the X-band. At a CNT content of 5 wt.%, the reflection loss of the impregnated nonwovens on the backside reached a minimum of -14.06 dB and remained below -10 dB in the 17.42~17.88 GHz frequency range. The sample fabricated with 4 wt.% GFs in the impregnation solution exhibited the best absorption performance, with minimum reflection losses of -15.33 dB and -33.18 GHz in the X-band and Ku-band, respectively. When the GFs were at 3 wt.%, the absorption bandwidth below -10 dB reached 4.16 GHz. In contrast to CNT-impregnated nonwovens, the frontside of GF-impregnated nonwovens demonstrated better absorption performance in the Ku-band. The results of this work provide experimental data support for the fabrication and application of microwave absorption materials.

Transarterial chemoembolization combined with camrelizumab for recurrent hepatocellular carcinoma.

PURPOSE: To evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with camrelizumab (hereafter, TACE-camrelizumab) in the treatment of patients with recurrent hepatocellular carcinoma (R-HCC) after curative resection. PATIENTS AND METHODS: R-HCC patients who underwent TACE plus camrelizumab or TACE-alone from January 2016 to August 2021 were retrospectively evaluated. Patients were assessed for tumor response, progression-free survival, survival rates and adverse events. RESULTS: Seventy-one patients were included in this study, including 20 patients in the TACE- camrelizumab group and 51 patients in the TACE-alone group. The objective response rate was 56.9% in the TACE-alone group and 40% in the TACE-camrelizumab group at 3 months (P = 0.201). The disease control rates were 84.3% in TACE-alone group and 80% in TACE-camrelizumab group at 3 months (P = 0.663). The progression-free survival (PFS) of the TACE-alone group was slightly longer than those of the TACE- camrelizumab group (9 months vs. 6 months). However, there were no statistically significant differences in the median PFS (P = 0.586). Similarly, there were no significant differences in the half-year and one-year survival rates (P = 0.304, P = 0.430). Multivariate analysis revealed that Neutrophil-to-lymphocyte ratio (NLR) was associated with PFS significantly. 75% patients developed at least one type of AEs related to camrelizumab in TACE-camrelizumab group, and no patients developed severe AEs. CONCLUSION: Comparing with TACE-Alone, the efficacy of TACE-camrelizumab for patients with R-HCC was similar. Meanwhile, the results of this study also indicated that TACE is still a better choice for patients with R-HCC.

Efficacy of Drug-Eluting Beads Transarterial Chemoembolization Plus Camrelizumab Compared With Conventional Transarterial Chemoembolization Plus Camrelizumab for Unresectable Hepatocellular Carcinoma.

OBJECTIVES: The purpose of this study was to compare the efficacy and safety of drug-eluting beads transarterial chemoembolization plus camrelizumab (D-TACE-C) with conventional transarterial chemoembolization plus camrelizumab (C-TACE-C) in the treatment of patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This was a retrospective study that evaluated the consecutive medical records of patients with unresectable HCC who had undergone D-TACE-C or C-TACE-C from April 2020 to August 2021. Efficacy of treatment was evaluated using tumor response, progression-free survival (PFS) and survival rates. The adverse events were recorded. RESULTS: A total of 54 patients were included in this study, including 27 patients who had received D-TACE-C treatment, and 27 patients who had received C-TACE-C treatment. The median PFS and DCR in the D-TACE-C group were significantly longer than those for the C-TACE-C group (PFS: 10 vs. 3 months, P=.017; DCR: 70.4% vs. 40.7%, P = .028). Cox regression analysis showed that D-TACE-C was the only protective factor for PFS. The 6-month and 12-month survival rates in D-TACE-C group and C-TACE-C group were 85.2% versus 79.4% (P = .646) and 65.2% versus 65.1% (P = .903), respectively. Reactive cutaneous capillary endothelial proliferation was the most common adverse event associated with the treatment. There was no significant difference in the adverse events related to TACE and camrelizumab between the two groups. No treatment-related deaths occurred in this study. CONCLUSIONS: D-TACE-C is a safe and well-tolerated treatment, and may produce better PFS and tumor response in patients with unresectable HCC than C-TACE-C.

Coupled dynamic reaction force study of a large-aperture piezoelectric fast steering mirror.

The reaction force of a large-aperture piezoelectric fast steering mirror (PFSM) has adverse coupling interference for the stability and pointing accuracy of laser beams, and the dynamic characteristics of the reaction force are coupled with the inner components of the PFSM. In order to compensate for and eliminate the reaction force, it is essential to accurately analyze the dynamic characteristics. In this paper, a simplified piezoelectric-coupling model of PFSM is established. The coupling mathematical equations for investigating the characteristics of the reaction force are deducted based on the piezoelectric constitutive equation and Hamiltonian's principle. Then the coupling characteristics of the reaction force are probed by a finite element (FE) piezoelectric-coupling method. The simulations for three large apertures' (250, 320, and 400 mm) FE models show that the reaction force has a linear positive correlation with the actuating voltage, and coupled with the materials of the central flexure hinge, the relationship between the reaction force and driving frequency is not completely quadratic. Experiments with the 320 mm aperture are completed, and the testing results are consistent with the mathematical model and the FE piezoelectric-coupling simulation. The dynamic characteristics of the reaction force demonstrated in this paper are significance for the accurate estimation of the reaction force, the design of compensation structure, and the optimization of algorithm for beam jitter controlling.

Occlusion-aware light field depth estimation using side window angular coherence.

Depth estimation is crucial in many light field applications. However, the accuracy of light field depth estimation is prone to be affected by occlusions. In this paper, a method of side window angular coherence is proposed to handle different types of occlusions, and the ability of the proposed method to resist occlusions is theoretically analyzed. The angular patch is divided into several discrete side window subsets. These subsets are a pure occluder-type subset, a pure object point-type subset, and a hybrid-type subset. The photo-consistency of the pure object point-type subset can reflect the true depth. Meanwhile, the occlusion edges can be detected to identify occluded points and nonoccluded points so the robustness of the algorithm can be further enhanced by processing the two types of points. Moreover, fast guided filtering is applied to cost volume for improving the accuracy of depth estimation. Experimental results demonstrate that our method outperforms the state-of-the-art depth estimation methods on both synthetic and real scenes, especially near occlusion boundaries.

Chrysin Alleviates Monocrotaline-Induced Pulmonary Hypertension in Rats Through Regulation of Intracellular Calcium Homeostasis in Pulmonary Arterial Smooth Muscle Cells.

Chrysin (CH) is the main ingredient of many medicinal plants. Our previous study showed that CH could suppress hypoxia-induced pulmonary arterial smooth muscle cells proliferation and alleviate chronic hypoxia-induced pulmonary hypertension by targeting store-operated Ca entry (SOCE)-[Ca]i pathway. In this study, we investigated the effect of CH on monocrotaline-induced pulmonary hypertension (MCTPH) and the mechanism behind it. Results show that, in MCTPH model rats, (1) CH significantly reduced the enhancement of right ventricular pressure, right ventricular hypertrophy, and pulmonary vascular remodeling; (2) CH markedly suppressed the promotion of SOCE and [Ca]i in pulmonary arterial smooth muscle cells; and (3) CH obviously inhibited the MCT-upregulated proliferating cell nuclear antigen, TRPC1, TRPC4, and TRPC6 expression in distal pulmonary arteries. These results demonstrate that CH likely alleviates MCTPH by targeting TRPC1,4,6-SOCE-[Ca]i pathway.

Phenytoin sodium-ameliorated gingival fibroblast aging is associated with autophagy.

BACKGROUND AND OBJECTIVE: Human gingival fibrolasts aging is an important cause of periodontal disease. Phenytoin sodium (phenytoin) has a side effect of gingival hyperplasia and an effect on the autophagy progress. This study investigated whether the effect of phenytoin on aging gingival fibroblast is related to the autophagy pathway. MATERIAL AND METHODS: The aging model of gingival fibroblast cell line HGF-1 was induced by hydrogen peroxide (H2 O2 ), and the treatment of phenytoin and 3-methyladenine (3-MA) was performed simultaneously. Cell viability, cell cycle, and intracellular calcium ion were measured by flow cytometry. Changes in expression of basic fibroblast growth factor (bFGF), P16INK4A , P21cip1 , and bFGF, P16INK4A , P21cip1 , LC3II, p62, and Beclin were tested by using reverse transcription polymerase chain reaction, western blot, and immunofluorescence staining. RESULTS: The results showed that aging HGF-1 proliferation was inhibited by H2 O2 , gene, protein expression of bFGF, P16INK4A , and P21cip1 were decreased, autophagy-related proteins LC3II, p62, and Becline were decreased, and the proportion of G0/G1 phase and intracellular calcium ion of cell cycle was increased. Phenytoin treatment could recovery above changes, but the effect of phenytoin could be blocked by 3-MA. CONCLUSION: We propose that phenytoin alleviates the aging of gingival fibroblasts induced by H2 O2 . This condition is related to the enhancement of autophagy pathway.

First critical repressive H3K27me3 marks in embryonic stem cells identified using designed protein inhibitor.

The polycomb repressive complex 2 (PRC2) histone methyltransferase plays a central role in epigenetic regulation in development and in cancer, and hence to interrogate its role in a specific developmental transition, methods are needed for disrupting function of the complex with high temporal and spatial precision. The catalytic and substrate recognition functions of PRC2 are coupled by binding of the N-terminal helix of the Ezh2 methylase to an extended groove on the EED trimethyl lysine binding subunit. Disrupting PRC2 function can in principle be achieved by blocking this single interaction, but there are few approaches for blocking specific protein-protein interactions in living cells and organisms. Here, we describe the computational design of proteins that bind to the EZH2 interaction site on EED with subnanomolar affinity in vitro and form tight and specific complexes with EED in living cells. Induction of the EED binding proteins abolishes H3K27 methylation in human embryonic stem cells (hESCs) and at all but the earliest stage blocks self-renewal, pinpointing the first critical repressive H3K27me3 marks in development.

Relaxin combined with transarterial chemoembolization achieved synergistic effects and inhibited liver cancer metastasis in a rabbit VX2 model.

OBJECTIVE: To explore the effect and mechanism of relaxin (RLX) in the growth and metastasis of livercancer after combination treatment with transarterial chemoembolization (TACE). MATERIALS AND METHODS: HCCLM3 and Huh-7 cells were adopted to evaluate the effect of tumor proliferation, migration, and invasion after RLX administration in vitro. The rabbit VX2 model was used to evaluate the biosafety, doxorubicin penetration, local tumor response, tumor metastasis, and survival benefit of RLX combined with TACE treatment. RESULTS: RLX did not affect the proliferation, migration, or invasion of HCCLM3 and Huh-7 cells, and the expression of E-cadherin and HIF-1α also remained unchanged while the MMP-9 protein was upregulated in vitro. In the rabbit VX2 model, compared to the normal saline group (NS), RLX group (RLX) and TACE mono-therapy group (TACE), the group that received TACE combined with RLX (TACE + RLX) showed an improved local tumor response and survival benefit. Furthermore, TACE combined with RLX was found to reduce tumor metastasis. This combination therapy reduced the fibrotic extracellular matrix in the tumor microenvironment, allowing for better penetration of doxorubicin, improved infiltration of CD8+ T cells and affected the secretion of cytokines. Additionally, RLX combined with TACE was able to decrease the expression of HIF-1α and PD-L1. The biosafety of TACE combined with RLX was also confirmed. CONCLUSION: RLX synergized with TACE by mitigating the fibrotic extracellular matrix and tumor hypoxic microenvironment, improving the therapeutic effect and inhibiting metastasis during the treatment of liver cancer.

Effect of metformin on hepatocellular carcinoma patients with type II diabetes receiving transarterial chemoembolization: a multicenter retrospective cohort study.

BACKGROUND: Diabetes is prevalent among patients with hepatocellular carcinoma (HCC) and is associated with a poor prognosis. Although the hypoglycemic drug metformin has shown anti-tumor effects, its potential positive effect on patients with HCC and diabetes undergoing transarterial chemoembolization (TACE) remains unclear. Therefore, this study aimed to investigate the efficacy and safety of metformin in patients with HCC and type II diabetes who are receiving TACE. MATERIALS AND METHODS: This retrospective study involved 372 consecutive patients with HCC and type II diabetes across three medical centers between January 2014 and June 2021. All patients underwent TACE. Propensity score matching (PSM) was used to reduce selection bias. Cox proportional hazards regression was employed to compare all-cause death between the metformin and non-metformin groups, while competing risk regression was performed to assess cancer-specific death. RESULTS: Among 372 patients included in the study, 208 patients (177 male patients and 31 female patients) with mean age 59.6 (10.3) years received metformin and 164 patients (139 male patients and 25 female patients) with mean age 60.3 (10.0) years did not. Before PSM, patients with metformin had significantly longer median overall survival (mOS) and median progression-free survival (mPFS) than those without metformin (mOS: 34 months, 95% CI: 25.6-42.4 vs. 20 months, 95% CI: 15.3-24.7; P<0.001; mPFS: 11 months, 95% CI: 9.3-12.7 vs. 8 months, 95% CI: 5.9-10.1; P<0.001). Similar results were observed after PSM. Multivariate regression analysis indicated that metformin was associated with a reduced risk of all-cause mortality (HR: 0.589, 95% CI: 0.454-0.763; P<0.001) and tumor progression (HR: 0.667, 95% CI: 0.526-0.845; P=0.001) before PSM. After excluding deaths related to other factors, metformin continued to demonstrate a reduction in cancer-specific mortality risk among the patients. Subgroup analysis further revealed that patients using metformin had lower all-cause mortality risk and tumor progression risk than those without metformin in most subgroups. Adverse event evaluation suggested that metformin could lead to elevated nausea incidence. CONCLUSION: Metformin may confer survival benefits to patients with HCC and type II diabetes undergoing TACE. Metformin may simultaneously address multiple aspects of treatment in these patients.

Multiscale Static Compressive Damage Characteristics of Kiwifruit Based on the Finite Element Method.

In the handling or processing process, fruits are easily crushed by external loads. This type of damage in fruit often leads to the internal pulp browning and rotting, with the severity largely dependent on the fruit tissue's geometric and mechanical properties. In kiwifruits, with their thin skin and dark-colored flesh, it is particularly challenging to observe and analyze the damage caused by extrusion through traditional experimental methods. The objective of this research is to construct a multi-scale finite element model encompassing the skin, flesh, and core by measuring the geometric and mechanical properties of kiwifruit, to assess and predict the damage characteristics under compression, and to verify the accuracy of the finite element model through experiments. The results indicated that kiwifruits demonstrated different compressive strengths in different directions during compression. The compressive strength in the axial direction was higher than that in the radial direction, and there was little difference between the long and short radial directions. The flesh tissue is the most vulnerable to mechanical damage under external compression, followed by the core. At strain levels below 5%, there was no noticeable damage in the axial or radial directions of the kiwifruit. However, when strain exceeded 5%, damage began to manifest in some of the flesh tissue. To maintain fruit quality during storage and transportation, the stacking height should not exceed 77 fruits in the axial direction, 48 in the long direction, and 53 in the short direction. The finite element analysis showed that the established model can effectively simulate and predict the internal damage behavior of kiwifruits under compression loads, which is helpful for a deeper understanding of the mechanical properties of fruits and provides a theoretical basis and technical guidance for minimizing mechanical damage during fruit handling.