HMG-CoA reductase inhibitor from the endophytic fungus Colletotrichum Capsici.

Two new fungal polyketides with unusual skeleton, collecapsins A and B (1-2), along with two known macrolactins A and B (3-4), were isolated from the rice cultures of an endophytic fungus Colletotrichum capsici obtained from the fresh Siegesbeckia pubescens Makino. Their structures were established by a combination of NMR, HRESIMS, and IR analysis. The absolute configurations of 1 and 2 were determined on the detailed analysis of the modified Mosher's derivatives' spectra and its key NOEs correlations. In this case, the absolute configurations of all chiral centres of 1 were determined for the first time, showed that 1 is a C-6/C-8 epimer of colletruncoic acid methyl ester. Compounds 1-2 demonstrated promising lipid lowing activity via the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase with IC50 values of 8.72 and 15.28 µM. Compounds 3-4 exhibited antibacterial activity with MIC values ranging from 0.25-25.8 µM.

Effects of Whey Peptides on the Quality of Pork Ball Preprepared Dishes during Repeated Freezing-Thawing.

This study evaluated the effect of FI (Fraction I, molecular weight < 1 kDa), which is separated from natural whey protein, on the antioxidant activity, sensory quality, color, texture characteristics, and microbial growth of pork balls during repeated freeze-thaw cycles (F-T cycles). The results indicated that pork balls mixed with FI significantly improved in quality after repeating the F-T cycle, especially with the addition of 10% FI. The quality was improved significantly after repeated F-T cycles by adding 10% FI, and the antioxidant activity after seven F-T cycles decreased by 40.78%, a similar result to that obtained with the addition of 0.02% BHA. In addition, FI effectively reduced the sensory damage of pork balls caused by repeated freezing-thawing and also significantly inhibited the growth of microorganisms. In summary, FI not only has excellent antioxidant capacity under repeated freeze-thaw conditions but also has significant antibacterial and quality preservation effects and is expected to be quantified as a kind of natural food additive with antibacterial and antioxidant properties. This paper not only explores the effect of FI on the quality characteristics of frozen and thawed pork balls in prepared dishes but also provides a theoretical basis for the application of whey polypeptides in prepared meat.

Three-dimensional visualization and evaluation of hilar cholangiocarcinoma resectability and proposal of a new classification.

BACKGROUND: As digital medicine has exerted profound influences upon diagnosis and treatment of hepatobiliary diseases, our study aims to investigate the accuracy of three-dimensional visualization and evaluation (3DVE) system in assessing the resectability of hilar cholangiocarcinoma (hCCA), and explores its potential clinical value. MATERIALS AND METHODS: The discovery cohort, containing 111 patients from April 2013 to December 2019, was retrospectively included to determine resectability according to revised criteria for unresectability of hCCA. 3D visualization models were reconstructed to evaluate resectability parameters including biliary infiltration, vascular involvement, hepatic atrophy and metastasis. Evaluation accuracy were compared between contrast-enhanced CT and 3DVE. Logistic analysis was performed to identify independent risk factors of R0 resection. A new comprehensive 3DVE classification of hCCA based on factors influencing resectability was proposed to investigate its role in predicting R0 resection and prognosis. The main outcomes were also analyzed in cohort validation, including 34 patients from January 2020 to August 2022. RESULTS: 3DVE showed an accuracy rate of 91% (95%CI 83.6-95.4%) in preoperatively evaluating hCCA resectability, significantly higher than 81% (95%CI 72.8-87.7%) of that of CT (p = 0.03). By multivariable analysis, hepatic artery involvement in 3DVE was identified an independent risk factor for R1 or R2 resection (OR = 3.5, 95%CI 1.4,8.8, P < 0.01). New 3DVE hCCA classification was valuable in predicting patients' R0 resection rate (p < 0.001) and prognosis (p < 0.0001). The main outcomes were internally validated. CONCLUSIONS: 3DVE exhibited a better efficacy in evaluating hCCA resectability, compared with contrast-enhanced CT. Preoperative 3DVE demonstrated hepatic artery involvement was an independent risk factor for the absence of R0 margin. 3DVE classification of hCCA was valuable in clinical practice.

Whey Protein Hydrolysate Improved the Structure and Function of Myofibrillar Protein in Ground Pork during Repeated Freeze-Thaw Cycles.

Whey protein hydrolysate (WPH) has made a breakthrough in inhibiting oxidative deterioration and improving the quality of meat products during storage. Based on our previous study of extracting the most antioxidant active fraction I (FI, the molecular weight < 1 kDa) from whey protein hydrolysates of different molecular weights, the present study continued to delve into the effects of WPH with fraction I on the structure and function of myofibrillar proteins (MP) in ground pork during the freeze-thaw (F-T) cycles. With the number of F-T cycles raised, the total sulfhydryl content, the relative contents of α-helix, Ca2+-ATPase activity, K+-ATPase activity, solubility, emulsion activity index (EAI), and emulsion stability index (ESI) of MP gradually decreased. Conversely, the carbonyl content and the relative content of random curl showed an increasing trend. In particular, the damage to the structure and the function of MP became more pronounced after three F-T cycles. But, during F-T cycles, FI stabilized the structure of MP. Compared to the control group, the 10% FI group showed a remarkable improvement (p < 0.05) in the total sulfhydryl content, Ca2+-ATPase activity, K+-ATPase activity, solubility, EAI and ESI after multiple F-T cycles, suggesting that 10% FI could effectively inhibit protein oxidation and had the influence of preserving MP function properties. In conclusion, WPH with fraction I can be used as a potential natural antioxidant peptide for maintaining the quality of frozen processed meat products.

An invasive zone in human liver cancer identified by Stereo-seq promotes hepatocyte-tumor cell crosstalk, local immunosuppression and tumor progression.

Dissecting and understanding the cancer ecosystem, especially that around the tumor margins, which have strong implications for tumor cell infiltration and invasion, are essential for exploring the mechanisms of tumor metastasis and developing effective new treatments. Using a novel tumor border scanning and digitization model enabled by nanoscale resolution-SpaTial Enhanced REsolution Omics-sequencing (Stereo-seq), we identified a 500 µm-wide zone centered around the tumor border in patients with liver cancer, referred to as "the invasive zone". We detected strong immunosuppression, metabolic reprogramming, and severely damaged hepatocytes in this zone. We also identified a subpopulation of damaged hepatocytes with increased expression of serum amyloid A1 and A2 (referred to collectively as SAAs) located close to the border on the paratumor side. Overexpression of CXCL6 in adjacent malignant cells could induce activation of the JAK-STAT3 pathway in nearby hepatocytes, which subsequently caused SAAs' overexpression in these hepatocytes. Furthermore, overexpression and secretion of SAAs by hepatocytes in the invasive zone could lead to the recruitment of macrophages and M2 polarization, further promoting local immunosuppression, potentially resulting in tumor progression. Clinical association analysis in additional five independent cohorts of patients with primary and secondary liver cancer (n = 423) showed that patients with overexpression of SAAs in the invasive zone had a worse prognosis. Further in vivo experiments using mouse liver tumor models in situ confirmed that the knockdown of genes encoding SAAs in hepatocytes decreased macrophage accumulation around the tumor border and delayed tumor growth. The identification and characterization of a novel invasive zone in human cancer patients not only add an important layer of understanding regarding the mechanisms of tumor invasion and metastasis, but may also pave the way for developing novel therapeutic strategies for advanced liver cancer and other solid tumors.

Circulating immune index predicting the prognosis of patients with hepatocellular carcinoma treated with lenvatinib and immunotherapy.

Background: Immune checkpoint inhibitor (ICI)-based combination therapy has opened a new avenue for the treatment of multiple malignancies including hepatocellular carcinoma (HCC). However, considering the unsatisfactory efficacy, biomarkers are urgently needed to identify the patients most likely to benefit from ICI-based combination therapy. Methods: A total of 194 patients undergoing ICI-based combination therapy for unresectable HCC were retrospectively enrolled and divided into a training cohort (n = 129) and a validation cohort (n = 65) randomly. A novel circulating immune index (CII) defined as the ratio of white blood cell count (×109/L) to lymphocyte proportion (%) was constructed and its prognostic value was determined and validated. Results: Patients with CII ≤ 43.1 reported prolonged overall survival (OS) compared to those with CII > 43.1 (median OS: 24.7 vs 15.1 months; 6-, 12-, 18-month OS: 94.2%, 76.7%, 66.1% vs 86.4%, 68.2%, 22.8%, P = 0.019), and CII was identified as an independent prognostic factor for OS (hazard ratio, 2.24; 95% confidence interval, 1.17-4.31; P = 0.015). These results were subsequently verified in the validation cohort. Additionally, patients with low CII levels had improved best radiological tumor response (complete response, partial response, stable disease, progressive disease: 3%, 36%, 50%, 11% vs 0%, 27%, 46%, 27%; P = 0.037) and disease control rate (89% vs 73%; P = 0.031) in the pooled cohort and better pathologic response (pathologic complete response, major pathologic response, partial pathologic response, no pathologic response: 20%, 44%, 28%, 8% vs 0%, 0%, 40%, 60%; P = 0.005) in the neoadjuvant cohort. Detection of lymphocyte subsets revealed that an elevated proportion of CD4+ T cells was related to better OS, while the proportion of CD8+ T cells was not. Conclusions: We constructed a novel circulating immune biomarker that was capable of predicting OS and therapeutic efficacy for HCC patients undergoing ICI and lenvatinib combination therapy.

Prognostic model for predicting outcome and guiding treatment decision for unresectable hepatocellular carcinoma treated with lenvatinib monotherapy or lenvatinib plus immunotherapy.

Background: Lenvatinib monotherapy and combination therapy with immune checkpoint inhibitors (ICI) were widely applied for unresectable hepatocellular carcinoma (uHCC). However, many patients failed to benefit from the treatments. A prognostic model was needed to predict the treatment outcomes and guide clinical decisions. Methods: 304 patients receiving lenvatinib monotherapy or lenvatinib plus ICI for uHCC were retrospectively included. The risk factors derived from the multivariate analysis were used to construct the predictive model. The C-index and area under the receiver-operating characteristic curve (AUC) were calculated to assess the predictive efficiency. Results: Multivariate analysis revealed that protein induced by vitamin K absence or antagonist-II (PIVKA-II) (HR, 2.05; P=0.001) and metastasis (HR, 2.07; P<0.001) were independent risk factors of overall survival (OS) in the training cohort. Herein, we constructed a prognostic model called PIMET score and stratified patients into the PIMET-low group (without metastasis and PIVKA-II<600 mAU/mL), PIMET-int group (with metastasis or PIVKA-II>600 mAU/mL) and PIMET-high group (with metastasis and PIVKA-II>600 mAU/mL). The C-index of PIMET score for the survival prediction was 0.63 and 0.67 in the training and validation cohort, respectively. In the training cohort, the AUC of 12-, 18-, and 24-month OS was 0.661, 0.682, and 0.744, respectively. The prognostic performances of the model were subsequently validated. The AUC of 12-, 18-, and 24-month OS was 0.724, 0.726, and 0.762 in the validation cohort. Subgroup analyses showed consistent predictive value for patients receiving lenvatinib monotherapy and patients receiving lenvatinib plus ICI. The PIMET score could also distinguish patients with different treatment responses. Notably, the combination of lenvatinib and ICI conferred survival benefits to patients with PIMET-int or PIMET-high, instead of patients with PIMET-low. Conclusion: The PIMET score comprising metastasis and PIVKA-II could serve as a helpful prognostic model for uHCC receiving lenvatinib monotherapy or lenvatinib plus ICI. The PIMET score could guide the treatment decision and facilitate precision medicine for uHCC patients.

Efficacy and safety of lenvatinib for preventing tumor recurrence after liver transplantation in hepatocellular carcinoma beyond the Milan criteria.

Background: Lenvatinib is one of the first-line treatments for unresectable hepatocellular carcinoma (HCC). However, data are lacking on lenvatinib in the postoperative setting. Methods: This retrospective analysis enrolled 242 patients with HCC who underwent liver transplantation (LTx). Eligible patients were divided into 2 groups according to their use of adjuvant lenvatinib following LTx (lenvatinib, n=42; control, n=200). The primary outcome measures were overall survival (OS), time to recurrence (TTR), and safety. Kaplan-Meier analysis was applied to calculate the OS, while a competing risk model was used to estimate the cumulative incidence of recurrence. Results: The lenvatinib group showed more advanced tumors and a higher proportion of HCC beyond the Milan criteria (P<0.001) than the control group. There were no significant differences in both the OS and TTR between the 2 groups. After focusing on the patients with HCC beyond the Milan criteria, baseline characteristics were similar in the lenvatinib group (n=38) and the control group (n=102). Competing risk analysis showed lenvatinib significantly prolonged TTR after LTx versus the control group [sub-hazard ratio (sHR), 0.40; 95% confidence interval (CI): 0.17 to 0.93; P=0.031]. In the multivariate competing risk model, adjuvant lenvatinib was an independent protective factor for tumor recurrence after LTx in patients with HCC beyond the Milan criteria (sHR, 0.33; 95% CI: 0.13 to 0.83; P=0.018). The rate of early recurrence within t2 years after LTx was also significantly decreased in the lenvatinib group (15.8% vs. 33.3%, P=0.041). However, the lenvatinib group exhibited comparable OS with the control group in patients with HCC beyond the Milan criteria. Treatment-related adverse events (TRAEs) and Grade ≥3 TRAEs occurred in 40 (95.2%) and 13 (31%) patients who received adjuvant lenvatinib, respectively. No treatment-related death was reported. Conclusions: Postoperative lenvatinib administration may provide clinical benefits and is well tolerated in patients with HCC beyond the Milan criteria who undergo LTx.

IGF2BP3 promotes progression of gallbladder carcinoma by stabilizing KLK5 mRNA in N6-methyladenosine-dependent binding.

Background: Recent studies have reported that IGF2BP3 is linked to the pathogenesis of various malignancies. Since IGF2BP3 is associated with poor outcomes of gallbladder carcinoma (GBC), we aimed to explore the association between its N6-methyladenosine (m6A) RNA methylation and GBC progression. Methods: Bioinformatic analysis of GSE136982, GSE104165, and RNA-seq was performed. In vitro and in vivo gain- and loss-of-function assays were done. qPCR, Western blotting, and IHC were conducted in cells or in collected clinical tissue samples. RNA immunoprecipitation, RNA stability measurement, methylated RNA immunoprecipitation, and dual-luciferase reporter assays were performed in this study. Results: The expression of IGF2BP3 was higher in GBC tissues than in peritumoral tissues. Functions such as cell proliferation and migration, both in vitro and in vivo, were inhibited by downregulation of IGF2BP3. The analysis of RNA-seq indicated that KLK5 was a downstream target of IGF2BP3. The expression of KLK5 was measured in GBC cells and tumor samples. It was found to be positively correlated with IGF2BP3 level. Upon IGF2BP3 depletion, ectopic expression of KLK5 could rescue cell function in part. Mechanistically, we found that IGF2BP3 directly binds to KLK5 mRNA and regulates its stability in an m6A-dependent manner. As a result, inhibition of KLK5 decreased the expression of PAR2, and deregulated phospho-Akt. Using bioinformatic prediction combined with miRNA microarray analysis, we identified that let-7g-5p is an inhibitor of IGF2BP3, and let-7g-5p expression was negatively correlated with IGF2BP3. Overexpression of let-7g-5p affected the aggressive phenotype of GBC cells by deregulating IGF2BP3, and inhibiting the KLK5/PAR2/AKT axis. Conclusions: Our data showed that IGF2BP3 is associated with the aggressive phenotype of GBC. Mechanistically, IGF2BP3 activated the PAR2/AKT axis by stabilizing KLK5 mRNA in an m6A-dependent manner. The loss of let-7g-5p enhanced the expression of IGF2BP3 and improved GBC progression. Thus, IGF2BP3 plays a crucial role in GBC, and the let-7g-5p/IGF2BP3/KLK5/PAR2 axis may be a therapeutic target for GBC.

Sorafenib-Loaded Cu2-xSe Nanoparticles Boost Photothermal-Synergistic Targeted Therapy against Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) accounts for the predominant form of liver malignancy and presents a leading cause of cancer-related death globally. Sorafenib (SOR), a first-line targeted drug for advanced HCC treatment, has a battery of untoward side effects. Photothermal therapy (PTT) has been utilized as an effective adjuvant in synergy with other approaches. However, little is known about the tumoricidal efficacy of combining SOR with PTT for HCC. Herein, a novel versatile nanoparticle, Cu2-xSe@SOR@PEG (CSP), that is based on a photothermal Cu2-xSe core and SOR for simultaneously reinforcing PTT and reducing the adverse effects of SOR was constructed. The synthesized CSP exhibited a remarkably enhanced therapeutic effect upon 808 nm laser irradiation via dampening HCC cell propagation and metastasis and propelling cell apoptosis. The intravenous administration of CSP substantially suppressed tumor growth in a xenograft tumor mouse model. It was noted that the CSP manifested low toxicity and excellent biocompatibility. Together, this work indicates a promising and versatile tool that is based on synergistic PTT and molecular-targeted therapy for HCC management.

Integration of Inflammation-Immune Factors to Build Prognostic Model Predictive of Prognosis and Minimal Residual Disease for Hepatocellular Carcinoma.

Background: Tumor recurrence after hepatectomy is high for hepatocellular carcinoma (HCC), and minimal residual disease (MRD) could be the underlying mechanism. A predictive model for recurrence and presence of MRD is needed. Methods: Common inflammation-immune factors were reviewed and selected to construct novel models. The model consisting of preoperative aspartate aminotransferase, C-reactive protein, and lymphocyte count, named ACLR, was selected and evaluated for clinical significance. Results: Among the nine novel inflammation-immune models, ACLR showed the highest accuracy for overall survival (OS) and time to recurrence (TTR). At the optimal cutoff value of 80, patients with high ACLR (> 80) had larger tumor size, higher Edmondson's grade, more vascular invasion, advanced tumor stage, and poorer survival than those with low ACLR (≤ 80) in the training cohort (5-year OS: 43.3% vs. 80.1%, P < 0.0001; 5-year TTR: 74.9% vs. 45.3%, P < 0.0001). Multivariate Cox analysis identified ACLR as an independent risk factor for OS [hazard ratio (HR) = 2.22, P < 0.001] and TTR (HR = 2.36, P < 0.001). Such clinical significance and prognostic value were verified in validation cohort. ACLR outperformed extant models, showing the highest area under receiver operating characteristics curve for 1-, 3-, and 5-year OS (0.737, 0.719, and 0.708) and 1-, 3-, and 5-year TTR (0.696, 0.650, and 0.629). High ACLR correlated with early recurrence (P < 0.001) and extremely early recurrence (P < 0.001). In patients with high ACLR, wide resection margin might confer survival benefit by decreasing recurrence (median TTR, 25.5 vs. 11.4 months; P = 0.037). Conclusions: The novel inflammation-immune model, ACLR, could effectively predict prognosis, and the presence of MRD before hepatectomy and might guide the decision on resection margin for patients with HCC.

The molecular biology of pancreatic adenocarcinoma: translational challenges and clinical perspectives.

Pancreatic cancer is an increasingly common cause of cancer mortality with a tight correspondence between disease mortality and incidence. Furthermore, it is usually diagnosed at an advanced stage with a very dismal prognosis. Due to the high heterogeneity, metabolic reprogramming, and dense stromal environment associated with pancreatic cancer, patients benefit little from current conventional therapy. Recent insight into the biology and genetics of pancreatic cancer has supported its molecular classification, thus expanding clinical therapeutic options. In this review, we summarize how the biological features of pancreatic cancer and its metabolic reprogramming as well as the tumor microenvironment regulate its development and progression. We further discuss potential biomarkers for pancreatic cancer diagnosis, prediction, and surveillance based on novel liquid biopsies. We also outline recent advances in defining pancreatic cancer subtypes and subtype-specific therapeutic responses and current preclinical therapeutic models. Finally, we discuss prospects and challenges in the clinical development of pancreatic cancer therapeutics.

Correction to: Long non-coding RNA PXN-AS1 suppresses pancreatic cancer progression by acting as a competing endogenous RNA of miR-3064 to upregulate PIP4K2B expression.

In the original publication of this manuscript [1], there are errors in Fig. 3. The authors declare that the identified errors do not change the results or conclusions of this paper.

Long non-coding RNA PXN-AS1 suppresses pancreatic cancer progression by acting as a competing endogenous RNA of miR-3064 to upregulate PIP4K2B expression.

BACKGROUND: Dysregulation of microRNAs (miRNAs) play critical roles in cancerous processes. Although miR-3064 was reported to be an important tumor suppressor in ovarian cancer, the cellular impact of miR-3064 on pancreatic cancer (PC) progression, its downstream target genes and upstream mechanisms that control the expression of miR-3064 remain to be fully clarified. METHODS: We compared miRNA expression profiles between PC tissues compared with normal tissues using a miRNA microarray analysis of clinical samples, and screened the identified miRNAs for their influence on cell proliferation. We measured the expression of miR-3064 in PC tissues and PC cell lines using quantitative real-time PCR assays. Gain- and loss-of-function experiments were conducted to explore the biologic significance of miR-3064 in PC progression both in vitro and in vivo. The interactions between miR-3064 and long noncoding RNA (lncRNA) PXN-AS1 was verified using the luciferase reporter assay and RNA immunoprecipitation assay. RESULTS: We showed that miR-3064 was significantly overexpressed in PC tissues compared to normal tissues. High miR-3064 was associated with worse prognosis in patients with PC. Functionally, ectopic expression of miR-3064 promoted the proliferation, invasion, clone formation and sphere formation of PC cells in vitro and stimulated PC growth in vivo, while specific knockdown of miR-3064 or CRISPR/Cas9-mediated knockout of miR-3064 resulted in opposite phenotypes. Further investigation revealed that miR-3064 directly targeted PIP4K2B, which was reduced in PC tissues and attenuated PC cell proliferation, invasion and sphere formation induced by miR-3064. Importantly, lncRNA PXN-AS1 expression was downregulated in PC samples, and it directly interacted with miR-3064 and suppressed its levels in PC cells. Enforced expression of PXN-AS1 remarkably decreased cell proliferation, invasion and sphere formation, while re-expression of miR-3064 abrogated these effects of PXN-AS1. CONCLUSIONS: MiR-3064, a key oncogenic miRNA, could promote PC cell growth, invasion and sphere formation via downregulating the levels of tumor suppressor PIP4K2B. PXN-AS1 functioned as a sponge to suppress the expression of miR-3064. These observations offer fresh insight into the mechanisms through which miR-3064 modulates the development of PC.

Characterization of the Biosynthetic Gene Cluster for the Antibiotic Armeniaspirols in Streptomyces armeniacus.

Armeniaspirols (1-3) are potent antibiotics against Gram-positive pathogens. Through a biosynthetic investigation, we identified four enzymes involved in the structural modification of 1-3. Manipulation of their activity led to the generation of 4-6 and nine novel analogues, 7-15. Bioactivity assessments revealed that the pyrrole chloro group and the methyl group are important for the antimicrobial activities of armeniaspirols, which lays the foundation for future structure optimization and mechanism of action studies of armeniaspirols.

Genomic Features and Clinical Characteristics of Adolescents and Young Adults With Cholangiocarcinoma.

Background: Adolescents and young adults (AYAs) diagnosed with cancer between ages 15 and 45 years may exhibit unique biologic and genomic characteristics as well as clinical features, resulting in differences in clinical characters and drug resistance. However, compared to other solid cancers, relatively few studies have been conducted in this age group in cholangiocarcinoma (CCA). This study is performed to investigate the clinical and molecular features of AYAs with CCA. Methods: Three cohorts, including the external dataset (TCGA and MSKCC) and the perihilar CCA databank of Chinese tertiary hospitals, were contained in this study. Pathway and process enrichment analysis had been carried out with the following ontology sources: KEGG Pathway, GO Biological Processes, Reactome Gene Sets, Canonical Pathways, and CORUM. Metascape and GEPIA datasets were used for bioinformatic analysis. P < 0.05 was considered statistically significant. All statistical analyses were performed with GraphPad Prism (version 7.0; GraphPad Software, La Jolla, California) and R studio (version 3.6.1; R studio, Boston, Massachusetts). Results: Compared to older adults, AYAs with CCA presented with worse overall survival, although the difference was not significant. Specific to patients with stage IV CCAs who underwent chemotherapy, AYAs were associated with significantly poorer overall survival (OS) (p = 0.03, hazards ratio (HR) 3.01, 95% confidence interval (CI) 1.14-4.91). From the anatomical perspective, more extrahepatic CCA was detected in the AYA group. Microsatellite instability (MSI) occurred in 3% of older patients in the present study. Nevertheless, none of the AYAs had MSI status. In this study, AYAs gained an enhanced frequency of additional sex combs like 1 (ASXL1) (p = 0.02) and KMT2C (p = 0.02) mutation than their older counterparts. Besides ASXL1 and KMT2C, the genes enriched in AYAs with CCA were analyzed by pathway and process enrichment analysis. And those genes were found to be associated with poorer differentiation, deubiquitination, and WNT signal pathway. Moreover, AYAs were relevant to poor differentiation and advanced tumor stage. Conclusion: This study offered a preliminary landscape of the clinical and molecular features of early-onset biliary cancers. Further studies including more samples are essential to investigate whether ASXL1 and KMT2C could be considered as potentially targetable genomic signatures for young patients.

[Syntheses and luminescence investigation of CaAl12O19:xMn(4+) red phosphors].

CaAl12O19:xMn(4+) (x=0.0~0.00184 mol) red phosphors were prepared by high-temperature solid state method. Different influencing factors, i. e. the doping amount of Mn(4+), and sintering temperature, were investigated by the orthogonal experiment design. The optimum conditions for preparing CaAl12O19:xMn(4+) phosphors are: sintering temperature 1500 °C, and x=0.0147 mol. It emits strong deep red light with emission maximal peak at 656 nm, and two shoulder peaks (643 and 666 nm), the corresponding excitation peak is located at 470 nm. The 656 nm emission peak is ascribed to the (2)E-->(4)A2 transition, and the shoulder peaks (643 and 666 nm) are attributed to phonon sideband transitions. The 470 nm excitation peak is ascribed to the ligand-field (4)A2-->(4)T2 transition (d-->d band). Owing to the fact that the excitation peak (470 nm) is near the emission (460 nm) of commercial LED chips, it is quite suitable for red light candidate for LED light resources.