Advancements and application prospects of three-dimensional models for primary liver cancer: a comprehensive review.

Primary liver cancer (PLC) is one of the most commonly diagnosed cancers worldwide and a leading cause of cancer-related deaths. However, traditional liver cancer models fail to replicate tumor heterogeneity and the tumor microenvironment, limiting the study and personalized treatment of liver cancer. To overcome these limitations, scientists have introduced three-dimensional (3D) culture models as an emerging research tool. These 3D models, utilizing biofabrication technologies such as 3D bioprinting and microfluidics, enable more accurate simulation of the in vivo tumor microenvironment, replicating cell morphology, tissue stiffness, and cell-cell interactions. Compared to traditional two-dimensional (2D) models, 3D culture models better mimic tumor heterogeneity, revealing differential sensitivity of tumor cell subpopulations to targeted therapies or immunotherapies. Additionally, these models can be used to assess the efficacy of potential treatments, providing guidance for personalized therapy. 3D liver cancer models hold significant value in tumor biology, understanding the mechanisms of disease progression, and drug screening. Researchers can gain deeper insights into the impact of the tumor microenvironment on tumor cells and their interactions with the surrounding milieu. Furthermore, these models allow for the evaluation of treatment responses, offering more accurate guidance for clinical interventions. In summary, 3D models provide a realistic and reliable tool for advancing PLC research. By simulating tumor heterogeneity and the microenvironment, these models contribute to a better understanding of the disease mechanisms and offer new strategies for personalized treatment. Therefore, 3D models hold promising prospects for future PLC research.

Application value of mixed reality in hepatectomy for hepatocellular carcinoma.

BACKGROUND: As a new digital holographic imaging technology, mixed reality (MR) technology has unique advantages in determining the liver anatomy and location of tumor lesions. With the popularization of 5G communication technology, MR shows great potential in preoperative planning and intraoperative navigation, making hepatectomy more accurate and safer. AIM: To evaluate the application value of MR technology in hepatectomy for hepatocellular carcinoma (HCC). METHODS: The clinical data of 95 patients who underwent open hepatectomy surgery for HCC between June 2018 and October 2020 at our hospital were analyzed retrospectively. We selected 95 patients with HCC according to the inclusion criteria and exclusion criteria. In 38 patients, hepatectomy was assisted by MR (Group A), and an additional 57 patients underwent traditional hepatectomy without MR (Group B). The perioperative outcomes of the two groups were collected and compared to evaluate the application value of MR in hepatectomy for patients with HCC. RESULTS: We summarized the technical process of MR-assisted hepatectomy in the treatment of HCC. Compared to traditional hepatectomy in Group B, MR-assisted hepatectomy in Group A yielded a shorter operation time (202.86 ± 46.02 min vs 229.52 ± 57.13 min, P = 0.003), less volume of bleeding (329.29 ± 97.31 mL vs 398.23 ± 159.61 mL, P = 0.028), and shorter obstructive time of the portal vein (17.71 ± 4.16 min vs 21.58 ± 5.24 min, P = 0.019). Group A had lower alanine aminotransferas and higher albumin values on the third day after the operation (119.74 ± 29.08 U/L vs 135.53 ± 36.68 U/L, P = 0.029 and 33.60 ± 3.21 g/L vs 31.80 ± 3.51 g/L, P = 0.014, respectively). The total postoperative complications and hospitalization days in Group A were significantly less than those in Group B [14 (37.84%) vs 35 (60.34%), P = 0.032 and 12.05 ± 4.04 d vs 13.78 ± 4.13 d, P = 0.049, respectively]. CONCLUSION: MR has some application value in three-dimensional visualization of the liver, surgical planning, and intraoperative navigation during hepatectomy, and it significantly improves the perioperative outcomes of hepatectomy for HCC.

DNA methylation biomarkers for diagnosis of primary liver cancer and distinguishing hepatocellular carcinoma from intrahepatic cholangiocarcinoma.

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the two most common pathology subtypes of primary liver cancer (PLC). Identifying DNA methylation biomarkers for diagnosis of PLC and further distinguishing HCC from ICC plays a vital role in subsequent treatment options selection. To obtain potential diagnostic DNA methylation sites for PLC, differentially methylated CpG (DMC) sites were first screened by comparing the methylation data between normal liver samples and PLC samples (ICC samples and HCC samples). A random forest algorithm was then used to select specific DMC sites with top Gini value. To avoid overfitting, another cohort was taken as an external validation for evaluating the area under curves (AUCs) of different DMC sites combination. A similar model construction strategy was applied to distinguish HCC from ICC. In addition, we identified DNA Methylation-Driven Genes in HCC and ICC via MethylMix method and performed pathway analysis by utilizing MetaCore. Finally, we not only performed methylator phenotype based on independent prognostic sites but also analyzed the correlations between methylator phenotype and clinical factors in HCC and ICC, respectively. To diagnose PLC, we developed a model based on three PLC-specific methylation sites (cg24035245, cg21072795, and cg00261162), whose sensitivity and specificity achieved 98.8%,94.8% in training set and 97.3%,81% in validation set. Then, to further divide the PLC samples into HCC and ICC, we established another mode through three methylation sites (cg17769836, cg17591574, and cg07823562), HCC accuracy and ICC accuracy achieved 95.8%, 89.8% in the training set and 96.8%,85.4% in the validation set. In HCC, the enrichment pathways were mainly related to protein folding, oxidative stress, and glutathione metabolism. While in ICC, immune response, embryonic hepatocyte maturation were the top pathways. Both in HCC and ICC, methylator phenotype correlated well with overall survival time and clinical factors involved in tumor progression. In summary, our study provides the biomarkers based on methylation sites not only for the diagnosis of PLC but also for distinguishing HCC from ICC.

Enhancer RNA LINC00242-Induced Expression of PHF10 Drives a Better Prognosis in Pancreatic Adenocarcinoma.

Enhancer RNA is a kind of non-coding RNA, which is transcribed from the enhancer region of gene and plays an important role in gene transcription regulation. However, the role of eRNA in pancreatic adenocarcinoma (PAAD) is still unclear. In this study, we identified the key eRNA and its target gene in PAAD. The transcriptome data and clinical information of pancreatic cancer were downloaded from the UCSC Xena platform. A total of 2,695 eRNAs and its target gene predicted by the PreSTIGE method were selected as candidate eRNA-target pairs. After survival analysis, we found that LINC00242 was the eRNA most related to patients' survival, and correlation analysis further indicated that LINC00242 and its target gene PHF10 had a significant co-expression relationship. Downregulation of LINC00242 was significantly associated with unfavorable clinicopathological features. Based on pan-cancer analysis, we found that LINC00242 was associated with the survival of multiple cancers, and LINC00242 was co-expressed with its target genes in multiple cancer types. External experiments further demonstrated that PHF10 was the downstream target gene of LINC00242. After ssGSEA analysis, PAAD patients were classified as high, medium, and low immune cell infiltration clusters. Compared with the low and medium immune infiltration clusters, the expression level of PHF10 was significantly upregulated in the high immune infiltration clusters. After performing the CIBERSORT algorithm, we found that there was a significant difference in the abundance of immune infiltrating cells between the PHF10 high- and low-expression groups. Additionally, the web tool TIMER was used to detect the distribution and expression of PHF10 in pan-cancer.

Pan-Cancer Analysis Identified CD93 as a Valuable Biomarker for Predicting Patient Prognosis and Immunotherapy Response.

Background: The rapid development of immunotherapy has significantly improved patient outcomes in recent years. CD93, a novel biomarker expressed on vascular endothelial cells, is essential for tumor angiogenesis. Recent studies have shown that CD93 is closely related to immune cell infiltration and immunotherapy. However, its role in pan-cancer has not been reported. Methods: The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA), cbioportal, Gene Expression Omnibus (GEO), Tumor Immune Estimation Resource (TIMER2.0), and the Tumor-Immune System Interactions and Drug Bank (TISIDB) databases were used to analyze CD93 in pan-cancers. R software was used for statistical analysis and mapping. Results: There were significant differences in the expression of CD93 between tumor tissues and adjacent normal tissues in pan-cancer. The high expression of CD93 was associated with poor prognosis and high TNM stage in multiple tumor types. However, a high expression of CD93 was a protective factor in kidney renal clear cell carcinoma (KIRC). In addition, CD93 was closely related to immune cell infiltration in tumor tissues. Moreover, CD93 presented a robust correlation with immune modulators and immunotherapeutic markers [e.g., tumor mutation burden (TMB) and microsatellite instability (MSI)]. The results of gene set enrichment analysis (GSEA) showed that CD93 was correlated with tumor angiogenesis. Importantly, patients with a low expression of CD93 were more sensitive to immunotherapy in urothelial cancer. Conclusion: CD93, which is involved in various immune responses, controls immune cell infiltration and impacts on the malignant properties of various cancer types. Therefore, CD93 has potential value to be biomarker for determining the prognosis and immune infiltration in multiple cancers.

High Oxygen Evolution Activity of Tungsten Bronze Oxides Boosted by Anchoring of Co2+ at Nb5+ Sites Accompanied by Substantial Oxygen Vacancy.

The participation of lattice oxygen in the oxygen evolution reaction (OER) process has been proved to be faster in kinetics than the mechanisms where only metal is involved, although activating the lattice oxygen in the traditional rigid structures remains a big challenge. In this work, efforts are devoted to exploring a new flexible structure that is competent in providing large amounts of oxygen vacancies as well as offering the freedom to manipulate the electronic structure of metal cations. This is demonstrated by anchoring low valence state Co at high valence state Nb sites in the tetragonal tungsten bronze (TTB)-structured Sr0.5Ba0.5Nb2- x Co x O6-δ , with different ratios of Co to Nb to optimize the Co substitution proportion. It is found that the occupation of Co in the Nb5+ sites gives rise to the generation of massive surface oxygen vacancies (Ovac), while Co itself is stabilized in Co2+ by adjacent Ovac. The coexistence of Ovac and LS Co2+ enables an oxygen intercalation mechanism in the optimal SBNC45 with specific activity at 1.7 V versus reversible hydrogen electrode that is 20 times higher than for the commercial IrO2. This work illuminates an entirely new avenue to rationally design OER electrocatalysts with ultrafast kinetics.

Sonocatalysis of the magnetic recyclable layered perovskite oxides.

Sonocatalysis fascinates to utilize mechanical energy that universally exists in the environment. A big problem for the practical application of sonocatalysts is the incapability of recyclability, which is necessary for resource saving and secondary pollution control. In this work, Bi7Fe2.75Co0.25Ti3O21 was firstly explored as a new sonocatalyst with magnetic recyclability. The magnetic catalysts can be easily collected with a magnetic bar after sonocatalytic reactions, and the structure and efficiency were kept after being recycled. Since the mechanism of sonocatalysis under ultrasonic vibration is still not fully understood, experiments including samples with different polarization and morphology, under different frequencies and intensities of ultrasonic radiation were conducted. The results suggested that the sonocatalytic efficiency was in proportion to polarization instead of morphology and a possible mechanism of squeezed model was proposed.

Morphology effect on photocatalytic activity in Bi3Fe0.5Nb1.5O9.

In this work, the Aurivillius-phase ferroelectric Bi3Fe0.5Nb1.5O9 were synthesized by hydrothermal (BFNO-H) and solid state methods (BFNO-S), respectively. The BFNO-H shows a hierarchical morphology, which is stacked by intersecting single-crystal nanosheets with {001} and {110} exposed facets, while the BFNO-S shows disorganized micron-scale morphology. BFNO-H shows a much stronger photodegradation activity (10.4 times and 9.8 times) than BFNO-S in the visible-light photodegradation of rhodamine B (RhB) and salicylic acid. The higher photodegradation activity of BFNO-H was firstly ascribed to the hierarchical structure and the larger specific surface area (16.586 m2 g-1) because a large specific surface area can increase reactive sites and shorten photogenerated carrier migration distance. However, after being normalized by the specific surface area, BFNO-H still performs better than BFNO-S, implying that the specific surface area is not the only factor that determines the photocatalytic activity. Considering that the built-in electric field originating from spontaneous polarization in Bi3Fe0.5Nb1.5O9 has existed in both ab plane and c direction, it matches well with the {001} and {110} exposed facets of BFNO-H nanosheets. This appropriate matching in BFNO-H nanosheets may improve the separation and transmission of photogenerated electron-hole pairs and further enhance its photocatalytic activity. Moreover, the trapping experiments reveals that holes (h +) are the main active species and hole-derived oxidation is the main redox reaction during photodegradation of organic pollutions.

Greatly improved dispersibility of Pt quantum dots in hematite nanoarray and enhanced photoelectrochemical performance.

The anchoring of platinum quantum dots (Pt QDs) on the surface of hematite (α-Fe2O3) nanorods is regarded as an efficient way to promote photoelectrochemical activity. To further improve the performance of the Pt-hematite material system, the size and location of the Pt QDs is a key factor to be considered. In this work, an α-Fe2O3 nanorod array film was grown on a transparent conductive FTO substrate by a facile hydrothermal method. Pt QDs with a diameter of ∼2 nm were uniformly deposited on the surface of the α-Fe2O3 nanorod. The dispersibility of the Pt QDs was greatly improved by regulating the surface wettability of the α-Fe2O3 thin film. The dependence of surface wettability on the micro-/nano-structure of the α-Fe2O3 array was revealed. Due to the structure regulation of the α-Fe2O3 nanoarray and the greatly improved dispersibility of the Pt QDs, the photocurrent of the 2.7 wt% Pt QD anchored α-Fe2O3 nanorod array was ten times higher than that of the pure α-Fe2O3 nanorod array. This work points to an efficient approach for dispersing the QDs in a nanoarray thin film by adjusting its micro-/nano-structure and surface wettability.

A Polyketide Synthase Encoded by the Gene An15g07920 Is Involved in the Biosynthesis of Ochratoxin A in Aspergillus niger.

The polyketide synthase gene An15g07920 was known in Aspergillus niger CBS 513.88 as putatively involved in the production of ochratoxin A (OTA). Genome resequencing analysis revealed that the gene An15g07920 is also present in the ochratoxin-producing A. niger strain 1062. Disruption of An15g07920 in A. niger 1062 removed its capacity to biosynthesize ochratoxin ß (OTß), ochratoxin α (OTα), and OTA. These results indicate that the polyketide synthase encoded by An15g07920 is a crucial player in the biosynthesis of OTA, in the pathway prior to the phenylalanine ligation step. The gene An15g07920 reached its maximum transcription level before OTA accumulation reached its highest level, confirming that gene transcription precedes OTA production. These findings will not only help explain the mechanism of OTA production in A. niger but also provide necessary information for the development of effective diagnostic, preventive, and control strategies to reduce the risk of OTA contamination in foods.