Background/Aim: Hepatocellular carcinoma (HCC) is a highly heterogeneous malignancy with poor prognosis due to drug resistance and recurrence. Tumor-associated macrophages (TAMs) are pivotal in the HCC tumor microenvironment, but their prognostic and therapeutic relevance remains incompletely defined. This study aimed to identify macrophage-related genomic signatures, delineate HCC molecular subtypes, and construct a prognostic model to predict survival and therapy response. Materials and Methods: We integrated scRNA-seq (GSE151530) and bulk RNA-seq (HCCDB18, TCGA-HCC) data. Macrophage-related genes were identified via differential expression analysis of scRNA-seq data. Consensus clustering (Euclidean distance, hierarchical clustering) was used for subtype delineation. A prognostic model was constructed using PCA (Principal Component Analysis) on 25 OS-related differentially expressed genes (DEGs; univariate Cox regression), with z-scored normalization and 3 principal components. Immune infiltration (ssGSEA) and drug sensitivity [immunophenoscore (IPS) scores, pRRophetic] were analyzed. Results: Four HCC subtypes were identified; Cluster C showed the most favorable survival. The PCA-derived score strongly correlated with OS (p<0.001) and immunotherapy responsiveness (higher scores=enhanced sensitivity). High scores were associated with increased effector T cell infiltration and reduced T cell exhaustion. Drug sensitivity analyses revealed divergent responses to immunotherapy and conventional agents across subgroups. Conclusion: Macrophage-related genomic signatures are critical for HCC prognosis and therapy response. The PCAbased model holds promise as a biomarker for personalized therapy, warranting larger cohort validation and mechanistic exploration.

Surgical electrodes, essential tools in various medical procedures, perform dual functions in tissue cutting and simultaneous hemostasis. While recent studies have focused on mitigating tissue adhesion and thermal damage through surface micro-/nanostructure engineering, the electrode service dynamics and the underlying mechanisms responsible for these adverse effects remain inadequately elucidated. This study systematically investigates the electro-thermo-mechanical multiphysics interactions between conventional rounded-corner electrodes and liver tissue during cutting and coagulation processes. In the cutting mode, we present the first segmented numerical model to match the cutting force (Fx) by integrating electrothermal energy input with mechanical compression. This model quantifies the correlation between Fx, cutting speed (v) and electrode-tissue voltage (U), validated through experimental force signal analysis. Moreover, we unveil the formation mechanism of a built-up edge (BuE)-like adhesion on the non-cutting side of the electrode, contrasting with traditional machining tools where BuE typically forms near the cutting edge. Additionally, the evolution law of pore-associated surface morphologies on adhesive tissue is explained in relation to cutting power and speed. The counterintuitive attenuation of thermal damage on tissue surfaces along the cutting trajectory is attributed to a transition from high-frequency alternating current dominance to thermal conduction dominance, as evidenced by maximum temperature evolution curves. Optimal cutting parameters are established by evaluating maximum cutting force, adhesion mass, and thermal damage depth. During coagulation, we observe and mechanistically explain the critical transition from Joule heating to the discharge phase. Motivated by this transition, a novel dielectric-integrated composite (DIC) electrode is proposed and subsequently fabricated to achieve active discharge regulation, featuring a microgroove array substrate. Gradient groove-width experiments demonstrate that the DIC electrode significantly reduces thermal damage depth by up to 76.0% while maintaining coagulation quality and weakening tissue adhesion. This work provides new insights into electrode-tissue interaction mechanisms and lays a foundation for the development of next-generation high-performance surgical electrodes.

Surgical electrodes are frequently associated with disadvantages such as high surface adhesion and severe thermal damage to adjacent normal tissues, which threaten operation quality and patient safety. In this study, by mimicking the micromorphology and bio-anti-adhesion of shark skin, we proposed a strategy that utilized nanoscale aluminium oxide (Al _2 O _3 ) films deposited on bioinspired shark skin (BSS) microstructures to design a composite surface (Al _2 O _3 @BSS) and integrated it into both flat sides of the surgical electrodes. Micro/nano-manufacturing of the Al _2 O _3 @BSS surface was sequentially accomplished using nanosecond laser texturing, atomic layer deposition, and low-temperature annealing, endowing it with excellent blood-repellent properties. Visualisation experiments revealed that the tensile stress gradient of the blood coagulum with increasing thickness under a thermal field prompted it to separate from the Al _2 O _3 @BSS surface, resulting in anti-adhesion. Furthermore, it was observed for the first time that Al _2 O _3 films could transiently excite discharge along a dielectric surface (DADS) to ablate tissues while suppressing Joule heat, thereby minimising thermal damage. A combination of ex vivo tissue and living mouse experiments demonstrated that the Al _2 O _3 @BSS electrodes exhibited optimal comprehensive performance in terms of anti-adhesion, damage minimisation, and drag reduction. In addition, the Al _2 O _3 @BSS electrodes possessed remarkable antibacterial efficacy against E. coli and S. aureus . The proposed strategy can meet the extreme application requirements of surgical electrodes to improve operation quality and offer valuable insights for future studies.

The emergence of resistance to tyrosine kinase inhibitors (TKIs) compromises their clinical benefits in patients with hepatocellular carcinoma (HCC), in part due to adaptive responses triggered by tumor hypoxia. In this study, we leverage hyperbaric oxygen (HBO) therapy as a sensitizing strategy in sorafenib-resistant HCC. We demonstrate that HBO significantly enhances the anti-tumor effect of sorafenib by stimulating calcium transfer from the endoplasmic reticulum (ER) to mitochondria, resulting in ER stress and mitochondrial dysfunction. Mechanistically, we show that hypoxia upregulates HNF4A, a transcriptional suppressor of RCN1, and HBO therapy effectively inhibits this hypoxia-driven HNF4A/RCN1 axis. Downregulation of RCN1, a calcium-binding protein overexpressed in sorafenib-resistant HCC, strengthens ER-mitochondria coupling. Subsequently, RCN1 suppression attenuates its interaction with IP3R1 through the EFh1/2 domain, facilitating IP3R1-GRP75 dissociation and the activation of mitochondrial calcium-uptake machinery. Using its EF-hand domains, RCN1 senses fluctuations in ER calcium concentration and accordingly employs a feedback mechanism to fine-tune its binding to IP3R1. In xenograft and spontaneous models, combined HBO-TKIs treatment delays tumor progression and modulates the HNF4A/RCN1 axis. Taken together, our findings elucidate a hitherto uncharacterized role of HBO in regulating ER-mitochondria calcium homeostasis and support its clinical application as an adjunctive therapy in TKI-resistant HCC.

BACKGROUND:This study compares robotic-assisted pancreatic surgery (R-PS) and laparoscopic pancreatic surgery (L-PS) outcomes in patients with pancreatic malignancies and medium- to high-risk pancreatic fistulas. MATERIALS AND METHODS:A retrospective cohort study was conducted at Guangdong Provincial People's Hospital (2021-2023). The primary endpoints were major complications (Clavien-Dindo grade ≥ III) and postoperative morbidity. RESULTS:200 R-PS and 400 L-PS patients were included, with 163 pairs matched. R-PS showed lower conversion rates (2.5% vs. 17.2%, p < 0.001), less blood loss (119 vs. 179 mL, p = 0.013), and faster function recovery (8.2 vs. 9.6 days, p = 0.038). Postoperatively, R-PS had fewer pancreatic fistulas in malignant (4.1% vs. 32.6%, p < 0.001) and moderate to high-risk cases (8.3% vs. 16.7%, p = 0.026). R-PS benefits are not procedure-specific. CONCLUSION:R-PS offers advantages in blood loss, complications, and fistula prevention, suggesting it may be preferable for complex pancreatic surgeries.

Surgical electrodes (SE) are widely used for soft tissues cutting while simultaneously providing haemostasis through energy applied. However, this energy application often leads to severe tissue adhesion and thermal damage, highlighting the need for a deeper understanding of cutting mechanisms and performance enhancements. To address these challenges, this study proposes replacing the traditional-rounded-edge surgical electrode (R-SE) with sharp-cutting-edge surgical electrode (C-SE) to improve cutting performance. Analysis of cutting force and temperature signals, along with assessments of tissue adhesion and thermal damage, reveals distinct thermal effects and electric field behaviours between the R-SE and C-SE, providing a more comprehensive understanding of the cutting mechanisms. The sharp edge leverages the tip effect to modify the energy field, altering the electric field and concentrating the current. This significantly optimizes the thermal effects and the interaction between the SE and the tissue. As a result, the C-SE reduces mechanical resistance during tissue penetration and cutting compared to the R-SE, leading to lower cutting forces across all tested power levels. Although the peak temperatures of the C-SE were similar to those of the R-SE, the C-SE consistently produced a thinner thermal damage zone and significantly reduced tissue adhesion. Furthermore, the C-SE demonstrated efficient cutting at lower power levels where the R-SE was ineffective. Overall, this study demonstrated that the C-SE exhibited significantly enhanced performance and provided a deeper understanding of the cutting process. These advancements contribute to more efficient and safer electrosurgery, which is crucial for a broader range of applications, especially in precision minimally invasive surgery.

Nerves are integral to tumor biology, yet the peri- and intra-neural microenvironment and their roles in cancer-neural invasion (NI) remain underexplored. Here, we perform single-cell/single-nucleus RNA sequencing (sc/snRNA-seq) and spatial transcriptomics on 62 samples from 25 pancreatic ductal adenocarcinoma (PDAC) patients, mapping cellular composition, lineage dynamics, and spatial organization across varying NI statuses. Tertiary lymphoid structures are abundant in low-NI tumor tissues and co-localize with non-invaded nerves, while NLRP3+ macrophages and cancer-associated myofibroblasts surround invaded nerves in high-NI tissues. We identify a unique endoneurial NRP2+ fibroblast population and characterize three distinct Schwann cell subsets. TGFBI+ Schwann cells locate at the leading edge of NI, can be induced by transforming growth factor β (TGF-β) signaling, promote tumor cell migration, and correlate with poor survival. We also identify basal-like and neural-reactive malignant subpopulations with distinct morphologies and heightened NI potential. This landscape depicting tumor-associated nerves highlights critical cancer-immune-neural interactions in situ and enlightens treatment development targeting NI.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, notably resistant to existing therapies. Current research indicates that PDAC patients deficient in homologous recombination (HR) benefit from platinum-based treatments and poly-ADP-ribose polymerase inhibitors (PARPi). However, the effectiveness of PARPi in HR-deficient (HRD) PDAC is suboptimal, and significant challenges remain in fully understanding the distinct characteristics and implications of HRD-associated PDAC. We analyzed 16 PDAC patient-derived tissues, categorized by their homologous recombination deficiency (HRD) scores, and performed high-plex immunofluorescence analysis to define 20 cell phenotypes, thereby generating an in-situ PDAC tumor-immune landscape. Spatial phenotypic-transcriptomic profiling guided by regions-of-interest (ROIs) identified a crucial regulatory mechanism through localized tumor-adjacent macrophages, potentially in an HRD-dependent manner. Cellular neighborhood (CN) analysis further demonstrated the existence of macrophage-associated high-ordered cellular functional units in spatial contexts. Using our multi-omics spatial profiling strategy, we uncovered a dynamic macrophage-mediated regulatory axis linking HRD status with SIGLEC10 and CD52. These findings demonstrate the potential of targeting CD52 in combination with PARPi as a therapeutic intervention for PDAC.

Summary: Alternative polyadenylation (APA) is an important post-transcriptional regulatory mechanism and is involved in many diseases, but its function and mechanism in regulating pancreatic cancer (PC) pathogenesis remain unclear. In this study, we found that the 3′ UTR shortening of MZT1 was the most prominent APA event in PC liver metastases. The short-3′UTR isoform exerted a stronger effect in promoting cell proliferation and migration both in vitro and in vivo. NUDT21, a core cleavage factor involved in APA, promoted the usage of proximal polyadenylation sites (PASs) on MZT1 mRNA by binding to the UGUA element located upstream of the proximal PAS. High percentage of distal polyA site usage index of MZT1 was significantly associated with a better prognosis. These findings demonstrate a crucial mechanism that NUDT21-mediated APA of MZT1 could promote the progression of PC. Our findings provided a better understanding of the connection between PC progression and APA machinery.

Understanding cellular crosstalk in the complex tumor microenvironment (TME) is crucial for unraveling the molecular mechanisms behind disease progression and response to therapies. Recent technological advancements enable spatial single-cell transcriptomic analysis of the TME; however, spatial transcriptomic data at true single-cell resolution are inadequate for dissecting the intricate architecture of the TME in breast and other cancers. The purpose of this study was to apply the latest spatial single-cell transcriptomics technology to dissect the breast cancer TME and identify potential biomarkers of therapeutic responses. We employed the cutting-edge Xenium technology to analyze the TME of various types of breast cancer including luminal-type, HER2+/HR-, and triple-negative breast cancer (TNBC). Our findings validated the effectiveness of the technology in achieving spatial cell annotation in the TME at the single-cell resolution. Notably, despite the diverse intrinsic features of various breast cancer types, spatial single-cell analysis of the TME revealed a prominent interplay among macrophages and T cells mediated by the CD274/CD80 interaction. This interplay aligns with the observed improvement in clinical responses to PD1 blockade therapies. Additionally, our results revealed that effector T cells, proliferative T cells, and macrophages localize closer to tumor cells in responders compared to non-responders of PD1 blockade therapy. Therefore, the CD274/CD80 ligand-receptor interaction, as well as the spatial localization of specific immune cells, represents potential biomarkers for future development for the advancement of immunotherapies in breast cancer.

Many patients with hepatocellular carcinoma (HCC) respond poorly to radiotherapy despite remarkable advances in treatment. A deeper insight into the mechanism of sensitivity of HCC to this therapy is urgently required. It is demonstrated that RECQL4 is upregulated in the malignant cells of patients with HCC. Elevated RECQL4 levels reduce the sensitivity of HCC to radiotherapy by repairing radiation-induced double-stranded DNA (dsDNA) fragments. Mechanistically, the inhibitory effect of RECQL4 on radiotherapy is due to the reduced recruitment of dendritic cells and CD8+ T cells in the tumor microenvironment (TME). RECQL4 disrupts the radiation-induced transformation of the TME into a tumoricidal niche by inhibiting the cGAS-STING pathway in dendritic cells. Knocking out STING in dendritic cells can block the impact of RECQL4 on HCC radiosensitivity. Notably, high RECQL4 expressions in HCC is significantly associated with poor prognosis in multiple independent cohorts. In conclusion, this study highlights how HCC-derived RECQL4 disrupts cGAS-STING pathway activation in dendritic cells through DNA repair, thus reducing the radiosensitivity of HCC. These findings provide new perspectives on the clinical treatment of HCC.

Perineural invasion (PNI) represents a unique biological feature associated with poor prognosis in pancreatic ductal adenocarcinoma (PDAC), especially in the presence of KRAS mutations. Extracellular vesicle (EV)-packaged circular RNAs (circRNAs) function as essential mediators of tumor microenvironment communication, triggering PDAC cell invasion and distant metastasis. However, the regulatory mechanisms of EV-packaged circRNAs in the PNI of KRAS-mutant PDAC have not yet been elucidated. Herein, a KRASG12D mutation-responsive EV-packaged circRNA, circPNIT, which positively correlated with PNI in PDAC patients is identified. Functionally, KRASG12D PDAC-derived EV-packaged circPNIT promoted axonogenesis and PNI both in vitro and in vivo. Mechanistically, the circPNIT-mediated Rab5B-CD109 interplay bypassed traditional endosomal trafficking to anchor Rab5B to the lipid rafts of multivesicular bodies and packaged circPNIT into CD109+ EVs. Subsequently, CD109+ EVs delivered circPNIT to neurons by binding to TRPV1 and facilitating DSCAML1 transcription-induced axonogenesis, which in turn enhanced the PNI by activating the GFRα1/RET pathway. Importantly, circPNIT-loaded CD109+ EVs are established to dramatically promote PNI in a KRASG12D/+ Trp53R172H/+ Pdx-1-Cre mouse model. Collectively, the findings highlight the mechanism underlying how EV-packaged circRNAs mediate the PNI of KRAS-mutant PDAC cells through the Rab5B endosomal bypass, identifying circPNIT as an effective target for the treatment of neuro-metastatic PDAC.

Aims: DNA damage repair (DDR) plays a pivotal role in hepatocellular carcinoma (HCC), driving oncogenesis, progression, and therapeutic response. However, the mechanisms of DDR mediated immune cells and immunomodulatory pathways in HCC are yet ill-defined. Methods: Our study introduces an innovative deep machine learning framework for precise DDR assessment, utilizing single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data. Single-cell RNA sequencing data were obtained and in total 85,628 cells of primary or post-immunotherapy cases were analyzed. Large-scale HCC datasets, including 1027 patients in house together with public datasets, were used for 101 machine-learning models and a novel DDR feature was derived at single-cell resolution (DDRscore). Druggable targets were predicted using the reverse phase protein array (RPPA) proteomic profiling of 169 HCC patients and RNA-seq data from 22 liver cancer cell lines. Results: Our investigation reveals a dynamic interplay of DDR with natural killer cells and B cells in the primary HCC microenvironment, shaping a tumor-promoting immune milieu through metabolic programming. Analysis of HCC post-immunotherapy demonstrates elevated DDR levels that induces epithelial-mesenchymal transition and fibroblast-like transformation, reshaping the fibrotic tumor microenvironment. Conversely, attenuated DDR promotes antigen cross-presentation by dendritic cells and CD8+ T cells, modulating the inflammatory tumor microenvironment. Regulatory network analysis identifies the CXCL10-CXCR3 axis as a key determinant of immunotherapeutic response in low DDR HCC, potentially regulated by transcription factors GATA3, REL, and TBX21. Using machine learning techniques by combining bulk RNA-seq data in house together with public datasets, we introduce DDRscore, a robust consensus DDR scoring system to predict overall survival and resistance to PD-1 therapy in HCC patients. Finally, we identify BRAF as a potential therapeutic target for high DDRscore patients. Conclusion: Our comprehensive findings advance our understanding of DDR and the tumor microenvironment in HCC, providing insights into immune regulatory mechanisms mediated via DDR pathways.

BACKGROUD: Hepatocellular carcinoma (HCC) is characterized by occult onset, rapid progression and poor prognosis. CXC chemokines play an important role in tumor microenvironment and development. OBJECTIVE: The potential mechanistic values of CXC chemokines as clinical biomarkers and therapeutic targets in HCC have not been fully clarified. METHODS: ONCOMINE, UALCAN, GEPIA, cBioPortal, SurvExpress, MethSurv, SurvivalMeth, String, GeneMANIA, DAVID, Metascape, TRRUST, LinkedOmics, and Timer were applied in this study. RESULTS: The transcriptional levels of CXCL9/16/17 in HCC tissues were significantly elevated while CXCL1/2/5/6/7/12/14 were significantly reduced. Significant correlation was found between the expression of CXC3/5 and the pathological stage of HCC patients. High level of CXCL4 was associated with a longer disease-free survival. For overall survival, lower expressions of CXCL1/3/5/8 and higher expressions of CXCL2 were associated with a better outcome. In addition, the prognostic values of CXC chemokines signature in HCC were explored in four independent cohorts, the high-risk group displayed unfavorable survival outcome compared with the low-risk group. And for the prognostic value of the DNA methylation of CXC chemokines, we identified the CpGs which were significantly associated with prognosis in HCC patients. DNA methylation signature analysis also showed a statistically significant association between the high- and low-risk groups. For potential mechanism, the neighbor gene networks, interaction analyses, functional enrichment analyses of CC chemokine receptors in HCC were performed, the transcription factor targets, kinase targets, and miRNA targets of CXC chemokines were also identified in HCC. We also found significant correlations among CXC chemokines expression and the infiltration of immune cells, the tumor infiltration levels among HCC with different somatic copy number alterations of these chemokine receptors were also assessed. Moreover, the Cox proportional hazard model showed that CCR2/6/8/12, B cell, macrophage and dendritic cell were significantly related to the clinical outcome of HCC patients. CONCLUSION: CXC chemokines might serve as therapeutic targets and prognostic biomarkers in HCC.

Aiming at the problem that the existing models have a poor segmentation effect on imbalanced data sets with small-scale samples, a bilateral U-Net network model with a spatial attention mechanism is designed. The model uses the lightweight MobileNetV2 as the backbone network for feature hierarchical extraction and proposes an Attentive Pyramid Spatial Attention (APSA) module compared to the Attenuated Spatial Pyramid module, which can increase the receptive field and enhance the information, and finally adds the context fusion prediction branch that fuses high-semantic and low-semantic prediction results, and the model effectively improves the segmentation accuracy of small data sets. The experimental results on the CamVid data set show that compared with some existing semantic segmentation networks, the algorithm has a better segmentation effect and segmentation accuracy, and its mIOU reaches 75.85%. Moreover, to verify the generality of the model and the effectiveness of the APSA module, experiments were conducted on the VOC 2012 data set, and the APSA module improved mIOU by about 12.2%.

The hallmark of pancreatic ductal adenocarcinoma (PDAC) is an exuberant tumor microenvironment (TME) comprised of diverse cell types that play key roles in carcinogenesis, chemo-resistance, and immune evasion. Here, we propose a gene signature score through the characterization of cell components in TME for promoting personalized treatments and further identifying effective therapeutic targets. We identified three TME subtypes based on cell components quantified by single sample gene set enrichment analysis. A prognostic risk score model (TMEscore) was established based on TME-associated genes using a random forest algorithm and unsupervised clustering, followed by validation in immunotherapy cohorts from the GEO dataset for its performance in predicting prognosis. Importantly, TMEscore positively correlated with the expression of immunosuppressive checkpoints and negatively with the gene signature of T cells' responses to IL2, IL15, and IL21. Subsequently, we further screened and verified F2R-like Trypsin Receptor1 (F2RL1) among the core genes related to TME, which promoted the malignant progression of PDAC and has been confirmed as a good biomarker with therapeutic potential in vitro and in vivo experiments. Taken together, we proposed a novel TMEscore for risk stratification and selection of PDAC patients in immunotherapy trials and validated effective pharmacological targets.

Severe adhesion of biological fluids occurs on surgical electrodes due to a temperature-induced physical mechanism. By constructing surface microstructures and improving their hydrophobicity, it becomes a favorable choice for electrode anti-adhesion, but the related mechanisms are still not fully understood. Herein, we investigated the dynamic behavior of water and biological droplets on superhydrophobic microstructured sur-faces (SMSs) heated over 100 & DEG;C. The design inspiration of SMSs is derived from purple orchid leaves with excellent self-cleaning properties. The SMSs with Cassie-Baxter and Cassie impregnating states were selected and a flat surface was employed for comparison. Results show that the SMSs with the Cassie-Baxter state could reduce the Leidenfrost point to form a pseudo-Leidenfrost effect for water droplets. Furthermore, the dynamic evolution mechanism of plasma droplets on heated surfaces was first proposed, including base shrinkage, coagulation growth, and cap convergence. For the SMSs with the Cassie-Baxter state, the heat was carried away by vapor from the cavities at the contact interface, so that the growth height of the coagulation was lower than that of other surfaces. Additionally, the mentioned SMSs exhibited outstanding anti-adhesion performance and thermal stability. This study may contribute to understanding the anti-adhesion mechanism of surgical electrodes at the microscopic level.

Purpose The crucial role of N 6 -methyladenosine (m 6 A) methylation in anti-tumor immunity and immunotherapy has been broadly depicted. However, the molecular phenotypic linkages between m 6 A modification pattern and immunological ecosystem are expected to be disentangled in hepatocellular carcinoma (HCC), for immunotherapeutic unresponsiveness circumvention and combination with promising drug agents. Methods Modification patterns of m 6 A methylation were qualitatively dissected according to the large-scale HCC samples profiling. We then determined the immune phenotypic linkages by systematically evaluating their tumor microenvironment composition, immune/stromal-relevant signature, immune checkpoints correlation, and prognostic value. Individual quantification of m 6 A methylation pattern was achieved by m 6 Ascore construction, intensified by longitudinal single-cell analysis of immunotherapy cohort and validated by the transcriptomic profiles of our in-hospital GDPH-HCC cohort. Candidate therapeutic agents were also screened out. Results Three distinct m 6 A methylation patterns were determined in high accordance with inflamed-, excluded-, and desert-immunophenotype. To be precise, Immune-inflamed high-m 6 Ascore group was characterized by activated immunity with favorable prognosis. Stromal activation and absence of immune cell infiltration were observed in low-m 6 Ascore phenotype, linked to impaired outcome. Patients with low-m 6 Ascore demonstrated diminished responses and clinical benefits for cohorts receiving immunotherapy. The above credible linkage between m 6 A methylation pattern and tumor immune microenvironment was robustly validated in our GDPH-HCC cohort. Single-cell dynamic change of m 6 A methylation level in exhausted CD8 T cell and fibroblast was depicted in immunotherapy cohort fore and art. Derived from m 6 A methylation pattern, seven potential frontline drug agents were recognized as promising choice for high-m 6 Ascore patients. Conclusion Our work bridged the credible linkage between epigenetics and anti-tumor immunity in HCC, unraveling m 6 A modification pattern as immunological indicator and predictor for immunotherapy. Individualized m 6 Ascore facilitated strategic choices to maximize therapy-responsive possibility.

The high temperature induced by surgical electrodes is highly susceptible to severe surface adhesion and thermal damage to adjacent tissues, which is a major challenge in improving the quality of electrosurgery. Herein, we reported a coupled electrode with micro/nano hierarchical structures fabricated by depositing nanoscale hafnium oxide (HfO2) coatings on bionic microstructures (BMs) via laser texturing, acid washing, and atomic layer deposition (ALD) techniques. The synergistic effect of HfO2 coatings and BMs greatly enhanced the hemophobicity of the electrode with a blood contact angle of 162.15 ± 3.16°. Furthermore, the coupled surface was proven to have excellent antiadhesive properties to blood when heated above 100 °C, and the underlying mechanism was discussed. Further experiments showed that the coupled electrode had significant advantages in reducing cutting forces, thermal damage, and tissue adhesion mass. Moreover, the antibacterial rates against Escherichia coli and Staphylococcus aureus were 97.2% and 97.9%, respectively. In addition, the noncytotoxicity levels of HfO2 coatings were verified by cell apoptosis and cycle assays, indirectly endowing the coupled electrode with biocompatibility. Overall, the coupled electrode was shown to have broad potential for application in the field of electrosurgery, and this work could provide new insights into antiadhesion properties under high-temperature conditions.

Droplet behavior involving electrothermal coupling fields has gradually attracted the attention of researchers, one of which includes electrosurgical scalpels that often contact biofluids. However, the evolution of bio-droplets exposed to the surface of electrosurgical scalpels is not yet well understood. Here, we experimentally studied the effect of different heating temperatures on plasma droplets on the laser-patterned surface (LPS) and the original surface (OS) under defined direct-current (DC) or alternating-current (AC) electric fields. The results show that at a lower heating temperature, the evolution of plasma droplets was dominated by electrolysis. Oxygen bubbles generated on the papillae on the LPS in the DC field inhibited the targeted adsorption of plasma proteins on this surface. In contrast, in the AC field, only a small number of bubbles was generated, which is not sufficient to inhibit protein adsorption, leading to the formation of coagulation on the papillae after heating. At higher heating temperatures, the rapid formation of coagulation resulted in the suppression of electrolysis. The plasma proteins were then transported by the Marangoni flow causing coagulation to reach a thickness of stress mutation. Stress release over the entire coagulation caused its edges to bend and then detach from the papillae. Thus, the LPS exhibited excellent anti-adhesive properties to plasma droplets under electrothermal excitations compared to the OS. This study provides valuable information for understanding the mechanisms of contact behavior between biofluids and electrosurgical scalpels and demonstrates great promise for their anti-adhesive performance.