Sorafenib is the first-line treatment of advanced hepatocellular carcinoma (HCC). However, there is a lack of validated biomarkers to predict sorafenib sensitivity. In this study we investigated the ...role of ACSL4, a positive-activating enzyme of ferroptosis, in sorafenib-induced cell death and HCC patient outcome. We showed that ACSL4 protein expression was negatively associated with IC
values of sorafenib in a panel of HCC cell lines (R = -0.952, P < 0.001). Knockdown of ACSL4 expression by specific siRNA/sgRNA significantly attenuated sorafenib-induced lipid peroxidation and ferroptosis in Huh7 cells, and also rescued sorafenib-induced inhibition of xenograft tumor growth in vivo. We selected 29 HCC patients with surgery as primary treatment and sorafenib as postoperative adjunct therapy from a hospital-based cohort. A high proportion (66.7%) of HCC patients who had complete or partial responses to sorafenib treatment (according to the revised RECIST guideline) had higher ACSL4 expression in the pretreated HCC tissues, compared with those who had stable or progressed tumor growth (23.5%, P = 0.029). Since ACSL4 expression was independent of sorafenib treatment, it could serve as a useful predictive biomarker. Taken together, this study demonstrates that ACSL4 is essential for sorafenib-induced ferroptosis and useful for predicting sorafenib sensitivity in HCC. This study may have important translational impacts in precise treatment of HCC.
The direct epitaxial growth of graphene on semi‐insulating SiC presents significant potential for a variety of technologically important applications, including next‐generation electronics, ...photonics, and quantum metrology. However, this approach also poses a competitive disadvantage in terms of quality and cost, primarily due to the uncontrollable and time‐consuming nature of the annealing process. Herein, a thermal shock annealing (TSA) method is reported that enables kinetics‐controlled epitaxial growth of graphene on SiC within 10 s, which efficiently fulfills the requirements for producing high‐quality, few‐layer, and low‐cost graphene on SiC. The epitaxial graphene (EG) grown on both β‐SiC nanoparticles (SiC@EG NPs) and centimeter‐scale α‐SiC wafer (EG/SiC) exhibits mono‐ or bi‐layer features with negligible structural defects. Moreover, the findings indicate that the TSA method can efficiently mitigate the persistent issue of step bunching conundrum and improve the flatness of EG/SiC. As an application demonstration, the significant enhancement of surface‐enhanced infrared absorption (SEIRA) by SiC@EG NPs is exhibited. The graphene plasmon arising on SiC@EG NPs enables SEIRA detection sensitivity of up to a monolayer of p‐nitrobenzenethiol (p‐NTP). Consequently, the precise regulation and comprehensive comprehension of TSA afford an exceedingly desirable approach to produce cost‐effective, high‐quality EG growth on SiC for diverse emerging application scenarios.
A thermal shock annealing method that enables kinetics‐controlled epitaxial growth of graphene on SiC within 10 s is reported, which efficiently fulfills the requirements for producing high‐quality, few‐layer, and low‐cost graphene on SiC.
Carbon-supported nanoparticles are indispensable to enabling new energy technologies such as metal-air batteries and catalytic water splitting. However, achieving ultrasmall and high-density ...nanoparticles (optimal catalysts) faces fundamental challenges of their strong tendency toward coarsening and agglomeration. Herein, we report a general and efficient synthesis of high-density and ultrasmall nanoparticles uniformly dispersed on two-dimensional porous carbon. This is achieved through direct carbothermal shock pyrolysis of metal-ligand precursors in just ~100 ms, the fastest among reported syntheses. Our results show that the in situ metal-ligand coordination (e.g., N → Co
) and local ordering during millisecond-scale pyrolysis play a crucial role in kinetically dominated fabrication and stabilization of high-density nanoparticles on two-dimensional porous carbon films. The as-obtained samples exhibit excellent activity and stability as bifunctional catalysts in oxygen redox reactions. Considering the huge flexibility in coordinated precursors design, diversified single and multielement nanoparticles (M = Fe, Co, Ni, Cu, Cr, Mn, Ag, etc) were generally fabricated, even in systems well beyond traditional crystalline coordination chemistry. Our method allows for the transient and general synthesis of well-dispersed nanoparticles with great simplicity and versatility for various application schemes.
Hepatocellular carcinoma (HCC) is one of the most prevalent and life-threatening malignancies worldwide. There are few diagnostic and prognostic biomarkers and druggable targets for HCC. Aldehyde ...dehydrogenase 1 (ALDH1) is a marker of stem cells in a variety of cancers, but the mRNA levels and prognostic value of ALDH1 isoforms in HCC patients remain unknown. In the present study, gene ontology annotation of the ALDH1 family was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID), and the gene pathway analsis was performed using GeneMANIA software. The initial prognostic value of ALDH1 expression in 360 HCC patients was assessed using the OncoLnc database. The expression levels of ALDH1 isoforms in normal liver tissues and clinical specimens of cancer vs. normal control datasets were determined using the GTEx and Oncomine databases, respectively. We then analyzed the prognostic value of ALDH1 expression in 212 hepatitis B virus (HBV)-related HCC patients using the GEO database. We found that the ALDH1 isoform showed high aldehyde dehydrogenase activity. The ALDH1A1, ALDH1B1, and ALDH1L1 genes encoded for the ALDH1 enzyme. High ALDH1B1 expression had protective qualities in HCC patients. Moreover, HBV-related HCC patients who showed high ALDH1L1 gene expression had a better clinical outcomes. In addition, high ALDH1A1 expression was associated with a 57-month recurrence-free survival in HBV-related HCC patients. High ALDH1B1 expression was protective for HCCs with multiple nodules and high serum alpha-fetoprotein (AFP) level. Furthermore, high serum AFP levels contributed to lower ALDH1L1. ALDH1A1, ALDH1B1, and ALDH1L1, all of which were considered promising diagnostic and prognostic markers as well as potential drug targets.
Hepatocellular carcinoma (HCC) is a lethal malignancy worldwide. HCC has traits of late diagnosis and high recurrence. This study explored potential diagnosis and prognosis significance of ...phospholipase C epsilon 1 (PLCE1) in HCC. The messenger RNA (mRNA) levels and diagnostic value of PLCE1 were determined by real‐time polymerase chain reaction and online databases GEPIA, oncomine, and GSE14520 data set. Survival analysis used the Kaplan–Meier Plotter website. Cell cycle, proliferation, migration, and invasion assays were performed with downregulated PLCE1 expression in HCC‐M and HepG2 cell lines. PLCE1 was differentially expressed and highly expressed in tumors and had low expression in nontumor tissues (all p < .05). The diagnostic value of PLCE1 was validated with the datasets (all p < .01, all areas under curves > 0.7). PLCE1 mRNA expression was associated with the overall and relapse‐free survival (both p < .05). Functional experiments indicated that downregulation of PLCE1 expression led to increased G1 stage in cell cycle and decreased cell proliferation, migration, and invasion compared with a negative control group (all p ≤ .05). The oncogene PLCE1 was differentially expressed in HCC and non‐HCC tissues. It is a candidate for diagnosis and serves as prognosis biomarker. PLCE1 influenced survival by affecting the cell cycle, proliferation, migration, and invasion ability.
We found that PLCE1 served as an oncogene and differentially expressed in HCC and non‐HCC tissues. It is a candidate for diagnosis and serves as prognosis biomarker. PLCE1 influenced survival by affecting the cell cycle, proliferation, migration, and invasion ability.
Rational design and precise fabrication of advanced functional materials are intimately linked to the technological advances in synthetic methodologies. The high-temperature shock (HTS) method, which ...involves an ultrafast heating/cooling rate (>105 K s–1) and features kinetics-dominated characteristics in material synthesis, exhibits high superiority in exploring and controllable preparation of novel materials that are typically unobtainable, such as high-entropy composition, thermodynamically metastable phases, and defect-rich surfaces. Among these significant advances, high-entropy alloy (HEA) nanoparticles are particularly prominent in heterogeneous catalytic reactions with remarkable activity, selectivity, and stability owing to their flexible composition space and high-entropy mixing structure. In this review, the physicochemical principles of HTS are presented, and the equipment and mechanisms of representative HTS techniques (e.g., Joule heating, laser heating, microwave heating) are comprehensively introduced, with the aim of accelerating the development of burgeoning HTS techniques. The concept and features of HEAs are also briefly introduced, and recent progress in the synthesis of HEAs using the HTS techniques is reviewed to provide a focused view on the unique advantages of HTS synthesis for HEAs and the exploration of novel materials. Finally, conclusions and perspectives are also provided for future investigations of HTS and HEAs, which have great significance in guiding their development and integrating their strengths.
The characteristics of high-temperature shock (HTS) are matched with those of the fabrication of catalytic high-entropy alloys (HEAs). We present the physicochemical principles of HTS, introduce three typical methods (Joule heating, laser heating, and microwave heating), and review the progress of HEAs prepared by HTS.
This study explored the prognostic significance of Glypican (GPC) family genes in patients with pancreatic ductal adenocarcinoma (PDAC) after pancreaticoduodenectomy using data from The Cancer Genome ...Atlas (TCGA) and Gene Expression Omnibus (GEO).
A total of 112 PDAC patients from TCGA and 48 patients from GEO were included in the analysis. The relationship between overall survival and the expression of GPC family genes as well as basic clinical characteristics was analyzed using the Kaplan-Meier method with the log-rank test. Joint effects survival analysis was performed to further examine the relationship between GPC genes and prognosis. A prognosis nomogram was established based on clinical characteristics and prognosis-related genes. Prognosis-related genes were investigated by genome-wide co-expression analysis and gene set enrichment analysis (GSEA) was carried out to identify potential mechanisms of these genes affecting prognosis.
In TCGA database, high expression of GPC2, GPC3, and GPC5 was significantly associated with favorable survival (log-rank P = 0.031, 0.021, and 0.028, respectively; adjusted P value = 0.005, 0.022, and 0.020, respectively), and joint effects analysis of these genes was effective for prognosis prediction. The prognosis nomogram was applied to predict the survival probability using the total scores calculated. Genome-wide co-expression and GSEA analysis suggested that the GPC2 may affect prognosis through sequence-specific DNA binding, protein transport, cell differentiation and oncogenic signatures (KRAS, RAF, STK33, and VEGFA). GPC3 may be related to cell adhesion, angiogenesis, inflammatory response, signaling pathways like Ras, Rap1, PI3K-Akt, chemokine, GPCR, and signatures like cyclin D1, p53, PTEN. GPC5 may be involved in transcription factor complex, TFRC1, oncogenic signatures (HOXA9 and BMI1), gene methylation, phospholipid metabolic process, glycerophospholipid metabolism, cell cycle, and EGFR pathway.
GPC2, GPC3, and GPC5 expression may serve as prognostic indicators in PDAC, and combination of these genes showed a higher efficiency for prognosis prediction.
Abstract
Background
Bony fusion rate was significantly lower in patients with type 3 Modic change than patients with normal endplates. It is not known whether there are relevant differences in fusion ...efficiency among patients with type 2 sclerotic Modic change or non-sclerotic Modic change, or no Modic change.
Methods
A retrospective study contained 196 lumbar segments in 123 subjects undergoing posterior lumbar interbody fusion (PLIF) with pedicle screw instrumentation (PSI) to assess the effect of type 2 sclerotic Modic change on fusion efficiency. These endplates were allocated into groups A, B, and C, according to their Modic changes. Group A had endplates with type 2 Modic change and endplate sclerosis. Group B had type 2 Modic change without endplate sclerosis. Group C had neither Modic change nor endplate sclerosis. The presence of Modic change was determined by magnetic resonance imaging (MRI). Endplate sclerosis in type 2 Modic change was detected by computed tomography (CT) before the operation. We collected CT data 3 months to more than 24 months after operation in patients to assess bony fusion.
Results
Incidences of bony fusion were 58.8% in group A, 95.0% in group B, 94.3% in group C. The bony fusion rate was significantly lower in group A than in either group B or C. There was no significant difference between groups B and C. Thus, endplates with type 2 sclerotic Modic change had a lower fusion rate in patients undergoing PLIF with PSI.
Conclusion
Type 2 sclerotic Modic change could be an important factor that affects solid bony fusion in patients undergoing PLIF with PSI. CT may help diagnose endplate sclerosis in patients with type 2 change and inform the choice of the best site for spinal fusion.
Refractory carbides are attractive candidates for support materials in heterogeneous catalysis because of their high thermal, chemical, and mechanical stability. However, the industrial applications ...of refractory carbides, especially silicon carbide (SiC), are greatly hampered by their low surface area and harsh synthetic conditions, typically have a very limited surface area (<200 m
g
), and are prepared in a high-temperature environment (>1,400 °C) that lasts for several or even tens of hours. Based on Le Chatelier's principle, we theoretically proposed and experimentally verified that a low-pressure carbothermal reduction (CR) strategy was capable of synthesizing high-surface area SiC (569.9 m
g
) at a lower temperature and a faster rate (∼1,300 °C, 50 Pa, 30 s). Such high-surface area SiC possesses excellent thermal stability and antioxidant capacity since it maintained stability under a water-saturated airflow at 650 °C for 100 h. Furthermore, we demonstrated the feasibility of our strategy for scale-up production of high-surface area SiC (460.6 m
g
), with a yield larger than 12 g in one experiment, by virtue of an industrial viable vacuum sintering furnace. Importantly, our strategy is also applicable to the rapid synthesis of refractory metal carbides (NbC, Mo
C, TaC, WC) and even their emerging high-entropy carbides (VNbMoTaWC
, TiVNbTaWC
). Therefore, our low-pressure CR method provides an alternative strategy, not merely limited to temperature and time items, to regulate the synthesis and facilitate the upcoming industrial applications of carbide-based advanced functional materials.
Hepatocellular carcinoma (HCC) with a dismal prognosis is the second most deadly malignancy globally. Surgery is believed to be a curative approach. Nevertheless, there is still a considerable ...probability of postoperative recurrence. Most patients present in advanced stages with a surgically and oncologically unresectable disease. Systemic medicines are increasingly important to downstage the disease and further improve survival.
A 67-year-old Chinese man with uncontrolled hepatitis B was discovered to have liver masses with abnormal serum vitamin K absence or antagonist-II (PIVKA-II) level during checkup for upper abdominal discomfort. Abdominal multiphase computerized tomography (CT) and gadoxetate disodium-enhanced magnetic resonance imaging (MRI) showed the bulky bilobar HCCs of Barcelona Clinic Liver Cancer stage B and China Liver Cancer Staging stage IIa. Furthermore, the aberrant right hepatic artery (RHA) originates from the superior mesenteric artery. Due to the location being adjacent to important vasculatures and massive size of the right-sided lesion, curative resection appears to be challenging. To achieve a favorable surgical margin, repeated hepatic arterial infusion chemotherapy (HAIC) was adopted through the variant RHA, while transarterial chemoembolization (TACE) was delivered to the left lobe to arrest tumor growth. Furthermore, sintilimab plus lenvatinib served as the sequential systemic therapy. After 5 months of conversion treatment, the partial response with a decreased serum PIVKA-II level was attained. The R0 hepatectomy was then performed without postoperative complications. The immunohistochemistry and next-generation sequencing results suggested that the two-side HCCs existing tumor heterogeneity were not completely consistent. The patient continues to be without evidence of disease.
Our case highlights a favorable outcome in a man with bilobar bulky HCC after undergoing the comprehensive therapeutic schedule that includes personalized intervention and systemic drug therapy. In terms of conversion therapy, our case provides a secure and practical reference for managing unresectable bilobar HCC coexisting with the aberrant hepatic artery.
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