Background Hepatocellular carcinoma (HCC) is one of the most common malignant tumors of the digestive system and has high morbidity and mortality rates. It is essential to search new biomarkers to improve the accuracy of early HCC diagnosis. Therefore, we evaluated the diagnostic value of prothrombin induced by vitamin K deficiency or antagonist- II (PIVKA-II) as a potential biomarker that complements α-fetoprotein (AFP) in HCC by detecting the serum PIVKA-II levels. Methods Serum PIVKA-II levels were compared in 168 HCC patients, 150 benign liver disease patients and 153 healthy controls to investigate the PIVKA-II potential to be a HCC biomarker. Receiver operating characteristic curve (ROC) analysis was used to evaluate the value of PIVKA-II in the diagnosis of HCC and its complementary role of AFP. The correlation between serum PIVKA-II levels and clinicopathological characteristics was analyzed to study the value of PIVKA-II in assessing HCC progression and prognosis. Finally, the ability of PIVKA-II in assessing the surgical treatment effects of HCC was studied by comparing the pre- and post-operative serum PIVKA-II levels in 89 HCC patients. Results Serum PIVKA-II levels in HCC patients were significantly higher than that in patients with benign liver disease and healthy controls. The PIVKA-II performance in the diagnosing HCC as an individual biomarker was remarkable. The combined detection of PIVKA-II and AFP improved the diagnostic efficiency of HCC. PIVKA-II retained significant diagnosis capabilities for AFP-negative HCC patients. Significant correlations were found between PIVKA-II expression levels and some clinicopathological characteristics, including tumor size, tumor stage, tumor metastasis, differentiation degree and complications. PIVKA-II expression obviously decreased after surgical resection. Conclusions PIVKA-II is a promising serum biomarker for the HCC diagnosis that can be used as a supplement for AFP. The combined diagnosis of the two markers greatly improved the diagnostic efficiency of HCC. The PIVKA-II levels in HCC patients were widely associated with clinicopathological characteristics representing tumor cell dissemination and/or poor prognosis. PIVKA-II can be used to evaluate the curative effects of HCC resection.

Polyoxometalates (POMs) are widely used in catalysis, energy storage, biomedicine, and other research fields due to their unique acidity, photothermal, and redox features. However, the leaching and agglomeration problems of POMs greatly limit their practical applications. Confining POMs in a host material is an efficient tool to address the above‐mentioned issues. POM@host materials have received extensive attention in recent years. They not only inherent characteristics of POMs and host, but also play a significant synergistic effect from each component. This review focuses on the recent advances in the development and applications of POM@host materials. Different types of host materials are elaborated in detail, including tubular, layered, and porous materials. Variations in the structures and properties of POMs and hosts before and after confinement are highlighted as well. In addition, an overview of applications for the representative POM@host materials in electrochemical, catalytic, and biological fields is provided. Finally, the challenges and future perspectives of POM@host composites are discussed.

This study aimed to apply a physiologically based pharmacokinetic (PBPK) model to predict optimal dosing regimens of pazopanib (PAZ) for safe and effective administration when co-administered with CYP3A4 inhibitors, acid-reducing agents, food, and administered in patients with hepatic impairment. Here, we have successfully developed the population PBPK model and the predicted PK variables by this model matched well with the clinically observed data. Most ratios of prediction to observation were between 0.5 and 2.0. Suitable dosage modifications of PAZ have been identified using the PBPK simulations in various situations, i.e., 200 mg once daily (OD) or 100 mg twice daily (BID) when co-administered with the two CYP3A4 inhibitors, 200 mg BID when simultaneously administered with food or 800 mg OD when avoiding food uptake simultaneously. Additionally, the PBPK model also suggested that dosing does not need to be adjusted when co-administered with esomeprazole and administration in patients with wild hepatic impairment. Furthermore, the PBPK model also suggested that PAZ is not recommended to be administered in patients with severe hepatic impairment. In summary, the present PBPK model can determine the optimal dosing adjustment recommendations in multiple clinical uses, which cannot be achieved by only focusing on AUC linear change of PK.

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Prion disorders are a group of lethal infectious neurodegenerative diseases caused by the spontaneous aggregation of misfolded prion proteins (PrPSc). The oxidation of such proteins by chemical reagents can significantly modulate their aggregation behavior. Herein, we exploit a series of vanadium-substituted Keggin-type tungsten and molybdenum POMs (W- and Mo-POMs) as chemical tools to oxidize PrP106–126 (denoted as PrP), an ideal model for studying PrPSc. Due to the band gaps being larger than that of Mo-POMs, W-POMs possess higher structural stability and show stronger binding and oxidation effect on PrP. Additionally, the substitution of W/Mo by vanadium elevates the local electron distribution on the bridged O(26) atom, thereby strengthening the hydrogen bonding of POMs with the histidine site. Most importantly, with the number of substituted vanadium increases, the LUMO energy level of POMs decreases, making it easier to accept electrons from methionine. As a result, PW10V2 displays the strongest oxidation on the methionine residue of PrP, leading to an excellent inhibitory effect on PrP aggregation and a significant attenuation on its neurotoxicity.

For the treatment of bacterial infections, photodynamic antimicrobial chemotherapy (PACT) has the advantage of circumventing multi-drug resistance. In this work, new cationic photosensitizers against multi-drug resistant Proteus mirabilis (MRPM) were designed and synthesized by the conjugation of amino phenyl porphyrin with basic amino acid L-ornithine. Their photoinactivation efficacies against MRPM in vitro were reported and include the influence of laser energy, uptake, MIC and MBC, dose-dependent photoinactivation effects, membrane integrity, and fluorescence imaging. The PACT in vivo was evaluated using a wound mouse model infected by MRPM. Photosensitizer 4d displayed high photo inactivation efficacy against MRPM at 7.81 μM under illumination, and it could accelerate wound healing via bactericidal effect. These ornithine-porphyrin conjugates are potential photosensitizers for PACT in the treatment of MRPM infection.

The efficient induction of peony embryogenic callus is of great significance to the improvement and establishment of its regeneration technology system. In this study, the in vitro embryos of ‘Fengdanbai’ at different developmental stages were selected as explants, the effects of different concentrations and types of plant growth regulator combinations on the induction and proliferation of embryonic callus at different developmental stages were investigated, and comparative transcriptome analysis of callus with different differentiation potentials were performed to explore the molecular mechanisms affecting callus differentiation. The results showed that the germination rate of 90d seed embryo was the best, which was 94.17%; the 70d and 80d cotyledon callus induction effect was the best, both reaching 100%, but the 80d callus proliferation rate was higher, the proliferation rate reached 5.31, and the optimal induction medium was MS+0.1 mg·L–1NAA+0.3 mg·L–1TDZ+3 mg·L–12,4-D, the callus proliferation multiple was 4.77. Based on the comparative transcriptomic analysis, we identified 3470 differentially expressed genes (DEGs) in the callus with high differentiation rate and low differentiation rate, including 1767 up-regulated genes and 1703 down-regulated genes. Pathway enrichment analysis showed that the “Phenylpropanoid biosynthesis” metabolic pathway was significantly enriched, which is associated with promoting further development of callus shoots and roots. This study can provide reference for genetic improvement and the improvement of regeneration technology system of peony.

Background: Nowadays, non-small cell lung cancer (NSCLC) is a common and highly fatal malignancy in worldwide. Therefore, to identify the potential prognostic markers and therapeutic targets is urgent for patients. Objective: This study aims to find hub targets associated with NSCLC using multiple databases. Methods: Differentially expressed genes (DEGs) from Genome Expression Omnibus (GEO) cohorts were employed for the enrichment analyses of Gene Ontology (GO) terms and the Kyoto Encyclopedia of Genes and Genome (KEGG) pathways. Candidate key genes, filtered from the topological parameter 'Degree' and validated using the The Cancer Genome Atlas (TCGA) cohort, were analyzed for their association with clinicopathological features and prognosis of NSCLC. Meanwhile, immunohistochemical cohort analyses and biological verification were further evaluated. Results: A total of 146 DEGs were identified following data preprocessing, and a protein-protein interaction (PPI) systematic network was constructed based on them. The top ten candidate core genes were further extracted from the above PPI network by using 'Degree' value, among which COL1A1 was shown to associate with overall survival (OS) of NSCLC as determined by using the Kaplan-Meier analysis (p=0.028), and could serve as an independent prognostic factor for OS in NSCLC patients (HR, 0.814; 95% CI, 0.665-0.996; p=0.046). We then analyzed the clinical stages, PPI, mutations, potential biological functions and immune regulations of COL1A1 in NSCLC patients using multiple bioinformatics tools, including GEPIA, GeneMANIA, cBioPortal, GESA and TISIDB. Finally, we further experimentally validated the overexpression of COL1A1 in NSCLC samples, and found that inhibition of COL1A1 expression moderately sensitized NSCLC cells to cisplatin. Conclusion: Thus, our results show that COL1A1 may serve as a potential prognostic marker and therapeutic target in NSCLC.