Understanding liposomal drug nanocrystal formulations and their potential in oral drug delivery

Tang's PhD study focuses on investigating the potential oral drug delivery application of a novel type of liposomal nano drug delivery carrier. These carriers with drug crystallised inside the liposomes are proven to have great potentials in oral drug delivery applications

Image2_Identification of a Pyroptosis-Related Prognostic Signature Combined With Experiments in Hepatocellular Carcinoma.TIF

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with poor prognosis. There is a necessary search for improvement in diagnosis and treatment methods to improve the prognosis. Some useful prognostic markers of HCC are still lacking. Pyroptosis is a type of programmed cell death caused by the inflammasome. It is still unknown whether pyroptosis-related genes (PRGs) are involved in the prognosis in HCC. The gene expression and clinical data of LIHC (liver hepatocellular carcinoma) patients were downloaded from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium database (ICGC). In this study, we identified 40 PRGs that were differentially expressed between LIHC and normal liver tissues. Based on the TCGA-LIHC cohort, a 9-gene prediction model was established with the Least absolute shrinkage and selection operator (LASSO)-penalized Cox regression. The risk score was calculated according to the model in the TCGA-LIHC cohort and the ICGC-LIHC cohort. Utilizing the median risk score from the TCGA cohort, LIHC patients from the ICGC-LIHC cohort were divided into two risk subgroups. The Kaplan–Meier (KM) survival curves demonstrated that patients with lower risk scores had significantly favorable overall survival (OS). Combined with the clinical characteristics, the risk score was an independent factor for predicting the OS of LIHC patients in both the TCGA-LIHC cohort and the ICGC-LIHC cohort. Functional enrichment and immune function analysis were carried out. Furthermore, a nomogram based on risk score, age, gender, and tumor stage was used to predict mortality of patients with LIHC. Moreover, KM survival analysis was performed for 9 genes in the risk model, among which CHMP4A, SCAF11, and GSDMC had significantly different results and the ceRNA network was constructed. Based on the core role of SCAF11, we performed loss-of-function experiments to explore the function of SCAF11 in vitro. Suppression of SCAF11 expression inhibited the proliferation, attenuated the migration and invasion, and induced apoptosis of liver cancer cell lines. In conclusion, the pyroptosis-related model and nomogram can be utilized for the clinical prognostic prediction in LIHC. This study has demonstrated for the first time that SCAF11 promotes the progression of liver cancer.</p

Image3_Identification of a Pyroptosis-Related Prognostic Signature Combined With Experiments in Hepatocellular Carcinoma.TIF

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with poor prognosis. There is a necessary search for improvement in diagnosis and treatment methods to improve the prognosis. Some useful prognostic markers of HCC are still lacking. Pyroptosis is a type of programmed cell death caused by the inflammasome. It is still unknown whether pyroptosis-related genes (PRGs) are involved in the prognosis in HCC. The gene expression and clinical data of LIHC (liver hepatocellular carcinoma) patients were downloaded from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium database (ICGC). In this study, we identified 40 PRGs that were differentially expressed between LIHC and normal liver tissues. Based on the TCGA-LIHC cohort, a 9-gene prediction model was established with the Least absolute shrinkage and selection operator (LASSO)-penalized Cox regression. The risk score was calculated according to the model in the TCGA-LIHC cohort and the ICGC-LIHC cohort. Utilizing the median risk score from the TCGA cohort, LIHC patients from the ICGC-LIHC cohort were divided into two risk subgroups. The Kaplan–Meier (KM) survival curves demonstrated that patients with lower risk scores had significantly favorable overall survival (OS). Combined with the clinical characteristics, the risk score was an independent factor for predicting the OS of LIHC patients in both the TCGA-LIHC cohort and the ICGC-LIHC cohort. Functional enrichment and immune function analysis were carried out. Furthermore, a nomogram based on risk score, age, gender, and tumor stage was used to predict mortality of patients with LIHC. Moreover, KM survival analysis was performed for 9 genes in the risk model, among which CHMP4A, SCAF11, and GSDMC had significantly different results and the ceRNA network was constructed. Based on the core role of SCAF11, we performed loss-of-function experiments to explore the function of SCAF11 in vitro. Suppression of SCAF11 expression inhibited the proliferation, attenuated the migration and invasion, and induced apoptosis of liver cancer cell lines. In conclusion, the pyroptosis-related model and nomogram can be utilized for the clinical prognostic prediction in LIHC. This study has demonstrated for the first time that SCAF11 promotes the progression of liver cancer.</p

Table2_Identification of a Pyroptosis-Related Prognostic Signature Combined With Experiments in Hepatocellular Carcinoma.XLSX

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with poor prognosis. There is a necessary search for improvement in diagnosis and treatment methods to improve the prognosis. Some useful prognostic markers of HCC are still lacking. Pyroptosis is a type of programmed cell death caused by the inflammasome. It is still unknown whether pyroptosis-related genes (PRGs) are involved in the prognosis in HCC. The gene expression and clinical data of LIHC (liver hepatocellular carcinoma) patients were downloaded from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium database (ICGC). In this study, we identified 40 PRGs that were differentially expressed between LIHC and normal liver tissues. Based on the TCGA-LIHC cohort, a 9-gene prediction model was established with the Least absolute shrinkage and selection operator (LASSO)-penalized Cox regression. The risk score was calculated according to the model in the TCGA-LIHC cohort and the ICGC-LIHC cohort. Utilizing the median risk score from the TCGA cohort, LIHC patients from the ICGC-LIHC cohort were divided into two risk subgroups. The Kaplan–Meier (KM) survival curves demonstrated that patients with lower risk scores had significantly favorable overall survival (OS). Combined with the clinical characteristics, the risk score was an independent factor for predicting the OS of LIHC patients in both the TCGA-LIHC cohort and the ICGC-LIHC cohort. Functional enrichment and immune function analysis were carried out. Furthermore, a nomogram based on risk score, age, gender, and tumor stage was used to predict mortality of patients with LIHC. Moreover, KM survival analysis was performed for 9 genes in the risk model, among which CHMP4A, SCAF11, and GSDMC had significantly different results and the ceRNA network was constructed. Based on the core role of SCAF11, we performed loss-of-function experiments to explore the function of SCAF11 in vitro. Suppression of SCAF11 expression inhibited the proliferation, attenuated the migration and invasion, and induced apoptosis of liver cancer cell lines. In conclusion, the pyroptosis-related model and nomogram can be utilized for the clinical prognostic prediction in LIHC. This study has demonstrated for the first time that SCAF11 promotes the progression of liver cancer.</p

Table3_Identification of a Pyroptosis-Related Prognostic Signature Combined With Experiments in Hepatocellular Carcinoma.XLSX

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with poor prognosis. There is a necessary search for improvement in diagnosis and treatment methods to improve the prognosis. Some useful prognostic markers of HCC are still lacking. Pyroptosis is a type of programmed cell death caused by the inflammasome. It is still unknown whether pyroptosis-related genes (PRGs) are involved in the prognosis in HCC. The gene expression and clinical data of LIHC (liver hepatocellular carcinoma) patients were downloaded from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium database (ICGC). In this study, we identified 40 PRGs that were differentially expressed between LIHC and normal liver tissues. Based on the TCGA-LIHC cohort, a 9-gene prediction model was established with the Least absolute shrinkage and selection operator (LASSO)-penalized Cox regression. The risk score was calculated according to the model in the TCGA-LIHC cohort and the ICGC-LIHC cohort. Utilizing the median risk score from the TCGA cohort, LIHC patients from the ICGC-LIHC cohort were divided into two risk subgroups. The Kaplan–Meier (KM) survival curves demonstrated that patients with lower risk scores had significantly favorable overall survival (OS). Combined with the clinical characteristics, the risk score was an independent factor for predicting the OS of LIHC patients in both the TCGA-LIHC cohort and the ICGC-LIHC cohort. Functional enrichment and immune function analysis were carried out. Furthermore, a nomogram based on risk score, age, gender, and tumor stage was used to predict mortality of patients with LIHC. Moreover, KM survival analysis was performed for 9 genes in the risk model, among which CHMP4A, SCAF11, and GSDMC had significantly different results and the ceRNA network was constructed. Based on the core role of SCAF11, we performed loss-of-function experiments to explore the function of SCAF11 in vitro. Suppression of SCAF11 expression inhibited the proliferation, attenuated the migration and invasion, and induced apoptosis of liver cancer cell lines. In conclusion, the pyroptosis-related model and nomogram can be utilized for the clinical prognostic prediction in LIHC. This study has demonstrated for the first time that SCAF11 promotes the progression of liver cancer.</p

Table1_Identification of a Pyroptosis-Related Prognostic Signature Combined With Experiments in Hepatocellular Carcinoma.XLSX

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with poor prognosis. There is a necessary search for improvement in diagnosis and treatment methods to improve the prognosis. Some useful prognostic markers of HCC are still lacking. Pyroptosis is a type of programmed cell death caused by the inflammasome. It is still unknown whether pyroptosis-related genes (PRGs) are involved in the prognosis in HCC. The gene expression and clinical data of LIHC (liver hepatocellular carcinoma) patients were downloaded from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium database (ICGC). In this study, we identified 40 PRGs that were differentially expressed between LIHC and normal liver tissues. Based on the TCGA-LIHC cohort, a 9-gene prediction model was established with the Least absolute shrinkage and selection operator (LASSO)-penalized Cox regression. The risk score was calculated according to the model in the TCGA-LIHC cohort and the ICGC-LIHC cohort. Utilizing the median risk score from the TCGA cohort, LIHC patients from the ICGC-LIHC cohort were divided into two risk subgroups. The Kaplan–Meier (KM) survival curves demonstrated that patients with lower risk scores had significantly favorable overall survival (OS). Combined with the clinical characteristics, the risk score was an independent factor for predicting the OS of LIHC patients in both the TCGA-LIHC cohort and the ICGC-LIHC cohort. Functional enrichment and immune function analysis were carried out. Furthermore, a nomogram based on risk score, age, gender, and tumor stage was used to predict mortality of patients with LIHC. Moreover, KM survival analysis was performed for 9 genes in the risk model, among which CHMP4A, SCAF11, and GSDMC had significantly different results and the ceRNA network was constructed. Based on the core role of SCAF11, we performed loss-of-function experiments to explore the function of SCAF11 in vitro. Suppression of SCAF11 expression inhibited the proliferation, attenuated the migration and invasion, and induced apoptosis of liver cancer cell lines. In conclusion, the pyroptosis-related model and nomogram can be utilized for the clinical prognostic prediction in LIHC. This study has demonstrated for the first time that SCAF11 promotes the progression of liver cancer.</p

Table4_Identification of a Pyroptosis-Related Prognostic Signature Combined With Experiments in Hepatocellular Carcinoma.XLSX

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with poor prognosis. There is a necessary search for improvement in diagnosis and treatment methods to improve the prognosis. Some useful prognostic markers of HCC are still lacking. Pyroptosis is a type of programmed cell death caused by the inflammasome. It is still unknown whether pyroptosis-related genes (PRGs) are involved in the prognosis in HCC. The gene expression and clinical data of LIHC (liver hepatocellular carcinoma) patients were downloaded from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium database (ICGC). In this study, we identified 40 PRGs that were differentially expressed between LIHC and normal liver tissues. Based on the TCGA-LIHC cohort, a 9-gene prediction model was established with the Least absolute shrinkage and selection operator (LASSO)-penalized Cox regression. The risk score was calculated according to the model in the TCGA-LIHC cohort and the ICGC-LIHC cohort. Utilizing the median risk score from the TCGA cohort, LIHC patients from the ICGC-LIHC cohort were divided into two risk subgroups. The Kaplan–Meier (KM) survival curves demonstrated that patients with lower risk scores had significantly favorable overall survival (OS). Combined with the clinical characteristics, the risk score was an independent factor for predicting the OS of LIHC patients in both the TCGA-LIHC cohort and the ICGC-LIHC cohort. Functional enrichment and immune function analysis were carried out. Furthermore, a nomogram based on risk score, age, gender, and tumor stage was used to predict mortality of patients with LIHC. Moreover, KM survival analysis was performed for 9 genes in the risk model, among which CHMP4A, SCAF11, and GSDMC had significantly different results and the ceRNA network was constructed. Based on the core role of SCAF11, we performed loss-of-function experiments to explore the function of SCAF11 in vitro. Suppression of SCAF11 expression inhibited the proliferation, attenuated the migration and invasion, and induced apoptosis of liver cancer cell lines. In conclusion, the pyroptosis-related model and nomogram can be utilized for the clinical prognostic prediction in LIHC. This study has demonstrated for the first time that SCAF11 promotes the progression of liver cancer.</p

Image1_Identification of a Pyroptosis-Related Prognostic Signature Combined With Experiments in Hepatocellular Carcinoma.TIF

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with poor prognosis. There is a necessary search for improvement in diagnosis and treatment methods to improve the prognosis. Some useful prognostic markers of HCC are still lacking. Pyroptosis is a type of programmed cell death caused by the inflammasome. It is still unknown whether pyroptosis-related genes (PRGs) are involved in the prognosis in HCC. The gene expression and clinical data of LIHC (liver hepatocellular carcinoma) patients were downloaded from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium database (ICGC). In this study, we identified 40 PRGs that were differentially expressed between LIHC and normal liver tissues. Based on the TCGA-LIHC cohort, a 9-gene prediction model was established with the Least absolute shrinkage and selection operator (LASSO)-penalized Cox regression. The risk score was calculated according to the model in the TCGA-LIHC cohort and the ICGC-LIHC cohort. Utilizing the median risk score from the TCGA cohort, LIHC patients from the ICGC-LIHC cohort were divided into two risk subgroups. The Kaplan–Meier (KM) survival curves demonstrated that patients with lower risk scores had significantly favorable overall survival (OS). Combined with the clinical characteristics, the risk score was an independent factor for predicting the OS of LIHC patients in both the TCGA-LIHC cohort and the ICGC-LIHC cohort. Functional enrichment and immune function analysis were carried out. Furthermore, a nomogram based on risk score, age, gender, and tumor stage was used to predict mortality of patients with LIHC. Moreover, KM survival analysis was performed for 9 genes in the risk model, among which CHMP4A, SCAF11, and GSDMC had significantly different results and the ceRNA network was constructed. Based on the core role of SCAF11, we performed loss-of-function experiments to explore the function of SCAF11 in vitro. Suppression of SCAF11 expression inhibited the proliferation, attenuated the migration and invasion, and induced apoptosis of liver cancer cell lines. In conclusion, the pyroptosis-related model and nomogram can be utilized for the clinical prognostic prediction in LIHC. This study has demonstrated for the first time that SCAF11 promotes the progression of liver cancer.</p

Isoselective Polymerization of <i>rac</i>-Lactide by Magnesium Initiators Bearing Achiral Di(2-pyridyl)methyl Substituted Aminophenolate Ligands

Reactions of achiral di(2-pyridyl)methyl substituted aminophenols L1–6H (2-{N-R3-N-[di(2-pyridyl)methyl]aminomethyl}-4-R1-6-R2-C6H2OH: R1 = R2 = tBu, R3 = nBu (L1H), R3 = nhexyl (L2H), R3 = cyclohexyl (L3H); R1 = R2 = cumyl, R3 = nBu (L4H), R3 = nhexyl (L5H), R3 = cyclohexyl (L6H)) with {Mg[N(SiMe3)2]2}2 ([L1–6H]:[Mg] = 1:1) afforded a series of magnesium silylamido complexes 1–6. In the solid state, the magnesium center of 3, 4, and 6 is penta-coordinated by the tetradentate aminophenloate ligand and one silylamido ligand to form a seriously distorted square-pyramidal geometry as confirmed by X-ray crystallography diffraction analysis. VT 1H NMR and ROESY experiments further indicate that these magnesium complexes are also five-coordinated in solutions where the coordination of either of the two pyridyl pendants to the magnesium center is maintained. Complexes 1–6 are highly active toward the ring-opening polymerization of rac-lactide (rac-LA) at r.t. both in toluene and in tetrahydrofuran, capable of polymerizing 500 equiv of monomer to high conversions just within minutes. Among them, complex 3 exhibited the highest iso-stereoselectivity, affording moderately isotactic polylactide in toluene (Pm = 0.75). It is found that the isoselectivities and activities of these magnesium complexes toward the polymerization of rac-LA are closely associated with the substituents at the ortho-position of the phenoxide unit and on the skeleton nitrogen atom of the ligand. On the basis of NMR spectroscopic studies, the formation of isotactic PLAs with dominant stereoblock sequences was witnessed by using these magnesium complexes as initiators, and the inequivalent coordination of two pyridyl pendant arms in these magnesium complexes might be the source of exerting isoselective control

Design, synthesis and biological activity evaluation of novel inhibitors targeting TNKS2, based on docking, virtual screening and molecular dynamics simulation studies

In recent years, tankyrases (TNKS) have garnered substantial interest as a promising new drug target. An escalating amount of research has been dedicated to the development of TNKS-targeting drugs, highlighting the substantial potential in anti-cancer therapeutics. In this study, a potential TNKS2 lead compound, ZINC11726230, was identified through docking-based virtual screening, molecular dynamics simulation and bioassay. Structural modification of the lead compound, ZINC11726230, yielded two new TNKS2 inhibitors (compound 1-2), which exhibited remarkable inhibitory activity, with an IC50 value of 0.013 μM, outperforming the positive control compound G007-LK (IC50 = 0.035 μM). This study offers unique insights into the discovery of effective TNKS2 inhibitors.</p