Short-term and long-term outcomes after robotic versus open hepatectomy in patients with large hepatocellular carcinoma: a multicenter study.

BACKGROUND: Robotic hepatectomy (RH) is currently widely accepted and it is associated with some benefits when compared to open hepatectomy (OH). However, whether such benefits can still be achieved for patients with large hepatocellular carcinoma (HCC) remain unclear. This study aimed to evaluate the short-term and long-term outcomes of patients undergoing RH or OH. METHODS: Perioperative and survival data from patients with large HCC who underwent RH or OH between January 2010 and December 2020 were collected from eight centres. Propensity score matching (PSM) was performed to minimise potential biases. RESULTS: Using predefined inclusion criteria, 797 patients who underwent OH and 309 patients who underwent RH were enroled in this study. After PSM, 280 patients in the robotic group had shorter operative time (median 181 vs. 201 min, P <0.001), lower estimated blood loss (median 200 vs. 400 ml, P <0.001), and shorter postoperative length of stay (median 6 vs. 9 days, P <0.001) than 465 patients in the open group. There were no significant differences between the two groups in overall survival and recurrence-free survival. Cox analysis showed AFP greater than 400 ng/ml, tumour size greater than 10 cm, and microvascular invasion were independent risk factors for overall survival and recurrence-free survival. After PSM, subgroup analysis showed that patients with a huge HCC (diameter >10 cm) who underwent RH had significantly lower estimated blood loss (median 200.0 vs. 500.0 min, P <0.001), and shorter length of stay (median 7 vs. 10 days, P <0.001) than those who underwent OH. CONCLUSION: Safety and feasibility of RH and OH for patients with large HCC were comparable. RH resulted in similar long-term survival outcomes as OH.

Identification of catalytically active domain epitopes in neuraminidase protein of H9N2 subtype of avian influenza virus.

H9N2 subtype of avian influenza virus (AIV) is primarily a bird virus, which is widespread in clinical avian disease, and reported in cases of human infection. As one of the surface proteins of AIV, the neuraminidase (NA) protein plays an important role mainly in viral budding. However, vaccine development and detection methods for NA of H9N2 AIVs are in urgent clinical need. In this study, a truncated NA gene (205-900 bp) was cloned from the NA sequence of H9N2 strain, and then expressed using pET-28a (+) vector. This purified recombinant NA protein was used to immunize BALB/c mice, and the monoclonal antibodies were screened through the indirect enzyme-linked immunosorbent assay (ELISA). Next, eight prokaryotic expression vectors were constructed for epitope identification. After cell fusion, three hybridoma cell lines producing the antibodies special to NA protein were screened by ELISA, western blotting, and indirect immunofluorescence; these were named 1B10, 2B6, and 5B2, respectively. Epitope scanning techniques were used to identify three B-cell epitopes recognized by these three monoclonal antibodies, 196KNATASIIYDGMLVD210, 210DSIGSWSKNIL220 and 221RTQESECVCI230. The subsequent homology analysis revealed the three epitopes were highly conserved in H9N2 AIV strains. The structural predictions of the antigenic epitopes indicated that all three epitopes were located in the catalytic region of NA. These results provide a basis for studying the function of the NA protein of H9N2 AIV and technical support for the development of a universal detection method based on anti-NA monoclonal antibodies.

KRT10 plays an important role in the release of viral genome from endosomes during H9N2 subtype AIV replication in HeLa cells.

The infection and replication of avian influenza virus (AIV) in host cells is a complex biological process that involves the transport of viral genes through the host cell's transport systems. Actin, microtubules and vimentin are known to facilitate transport of endosomes to the perinuclear region, but the biological role of Keratin, another intermediate filament, in viral transport during AIV replication is not well understood. In this study, the viral NS2 protein was used as the target protein to identify the potential interacting proteins following GST-Pulldown method and protein mass spectrometry. It was discovered that Keratin10 interacted with NS2. Subsequently, it was found AIV infection did not affect the gene level or protein level of keratin10 in HeLa cells, but when Keratin10 was knocked down, the expressions of viral NP mRNA and protein were reduced, and the generation of offspring virus also was also decreased. Furthermore, in early viral infection, Keratin10 could aggregate and co-localize with NP proteins, suggesting that Keratin10 might be connected to early viral transport. Additionally, it was demonstrated that Keratin10 co-localized with Lamp1 and that AIV particles were trapped in late endosomes/Lysosomes after Keratin10 was knocked down. Finally, it was discovered that the knocking down Keratin10 in HeLa cells led to an increase in the acidic pH of endosomes and lysosomes, which prevented AIV from undergoing fusion and uncoating, and then inhibited the process of the viral infection. Overall, the results suggested that Keratin10 might play the critical role in the release of vRNPs from LEs/Ls and can affect the generation of offspring virus. The study provides the novel insights into the role of Keratin10 in the process of AIV infection and transmission, which may have implications for developing new strategies to against AIV infections.

Line intensity calculation of laser-induced breakdown spectroscopy during plasma expansion in nonlocal thermodynamic equilibrium.

We present a new, to the best of our knowledge, simulation method for laser-induced breakdown spectroscopy during the plasma expansion phase in nonlocal thermodynamic equilibrium. Our method uses the particle-in-cell/Monte Carlo collision model to calculate dynamic processes and line intensity of nonequilibrium laser-induced plasma (LIP) in the afterglow phase. The effects of ambient gas pressure and type on LIP evolution are investigated. This simulation provides an added way to understand the nonequilibrium processes in more detail than the current fluid and collision radiation models. Our simulation results are compared with experimental and SimulatedLIBS package results and show good agreement.

[Retracted] MicroRNA­526a targets p21­activated kinase 7 to inhibit tumorigenesis in hepatocellular carcinoma.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the data shown for the Transwell cell migration and invasion assays in Fig. 2C and D were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 16: 837­844, 2017; DOI: 10.3892/mmr.2017.6658].

Knockdown of KDM5B Leads to DNA Damage and Cell Cycle Arrest in Granulosa Cells via MTF1.

KDM5B is essential for early embryo development, which is under the control of maternal factors in oocytes. Granulosa cells (GCs) play a critical role during oocyte mature. However, the role of KDM5B in GCs remains to be elucidated. In the current study, we found that KDM5B expressed highly in the ovaries and located in goat GCs. Using an RNA sequence, we identified 1353 differentially expressed genes in the KDM5B knockdown GCs, which were mainly enriched in cell cycle, cell division, DNA replication and the cellular oxidative phosphorylation regulation pathway. Moreover, we reported a decrease in the percentage of proliferated cells but an increase in the percentage of apoptotic cells in the KDM5B knockdown GCs. In addition, in the KDM5B knockdown GCs, the percentage of GCs blocked at the S phase was increased compared to the NC group, suggesting a critical role of KDM5B in the cell cycle. Moreover, in the KDM5B knockdown GCs, the reactive oxygen species level, the mitochondrial depolarization ratio, and the expression of intracellular phosphorylated histone H2AX (γH2AX) increased, suggesting that knockdown of KDM5B leads to DNA damage, primarily in the form of DNA double-strand breaks (DSBs). Interestingly, we found a down-regulation of MTF1 in the KDM5B knockdown GCs, and the level of cell proliferation, as well as the cell cycle block in the S phase, was improved. In contrast, in the group with both KDM5B knockdown and MTF1 overexpression, the level of ROS, the expression of γH2AX and the number of DNA DSB sites decreased. Taken together, our results suggest that KDM5B inhibits DNA damage and promotes the cell cycle in GCs, which might occur through the up-regulation of MTF1.

Significance of anatomical resection and resection margin status in patients with HBV-related hepatocellular carcinoma and microvascular invasion: a multicenter propensity score-matched study.

BACKGROUND: Microvascular invasion (MVI) is a risk factor for postoperative survival outcomes for patients with hepatocellular carcinoma (HCC) after hepatectomy. This study aimed to evaluate the impact of anatomical resection (AR) versus nonanatomical resection (NAR) combined with resection margin (RM) (narrow RM <1 cm vs. wide RM ≥1 cm) on long-term prognosis in hepatitis B virus-related HCC patients with MVI. MATERIALS AND METHODS: Data from multicenters on HCC patients with MVI who underwent hepatectomy was analyzed retrospectively. Propensity score matching analysis was performed in these patients. RESULTS: The 1965 enrolled patients were divided into four groups: AR with wide RM ( n =715), AR with narrow RM ( n =387), NAR with wide RM ( n =568), and NAR with narrow RM ( n =295). Narrow RM ( P <0.001) and NAR ( P <0.001) were independent risk factors for both overall survival and recurrence-free survival in these patients based on multivariate analyses. For patients in both the AR and NAR groups, wide RM resulted in significantly lower operative margin recurrence rates than those patients in the narrow RM groups after propensity score matching ( P =0.002 and 0.001). Patients in the AR with wide RM group had significantly the best median overall survival (78.9 vs. 51.5 vs. 48.0 vs. 36.7 months, P <0.001) and recurrence-free survival (23.6 vs. 14.8 vs. 17.8 vs. 9.0 months, P <0.001) than those in the AR with narrow RM, NAR with wide RM or with narrow RM groups, respectively. CONCLUSIONS: If technically feasible and safe, AR combined with wide RM should be the recommended therapeutic strategy for HCC patients who are estimated preoperatively with a high risk of MVI.

Dietary potential probiotics and enzymes complex modulates the performance and rumen microbiota in weaned goats.

AIMS: This trial was performed to investigate the effects of combined feeding of Candida utilis CICC 31170, Bacillus coagulans R11, and Lactobacillus acidophilus NCFM and a multi-enzyme complex on the growth performance, immune parameters, feed digestibility, and rumen microbiota of weaned goats. METHODS AND RESULTS: Thirty weaned goats were randomly divided into CON, PRB, and COB groups and fed different diets. End weight and ADG increased significantly in the PRB and COB groups (P < 0.05), and ADFI increased significantly in COB (P < 0.05). On day 80, there was a significant increase in IL-10 content in PRB and COB compared to the CON (P < 0.05). Highly significant increases in rumen papilla width, epithelial cell thickness, stratum spinosum+basale thickness, and stratum corneum thickness were found in PRB and COB (P < 0.05). COB group significantly increased the gene expression of HMGCL and MCT1 in rumen epithelium (P < 0.001). The COB group had the tendency to increase the feed digestibility of dry matter and crude fat compared with the CON group (P < 0.10). The abundance of Prevotellaceae_unclassified was significantly higher in PRB (P < 0.05), and the abundance of Fibrobacteres was significantly higher in COB in comparison to those in CON (P < 0.05). CONCLUSIONS: The results indicate that the dietary potential probiotics and enzymes complex could modulate the growth performance, immunity, feed digestibility, and rumen microbiota in weaned goats.

Two Divergent Enyne Cycloisomerization Routes Mediated by Monoallenylidene Pd(II) Catalysts.

The catalytic application of four monoallenylidene bisphosphine Pd(II) catalysts, which were developed using alkynyl triazole salt as the allenylidene source, in the cycloisomerization of 1,6-enyne was explored. Two divergent reaction pathways, including a new type of intramolecular Alder-ene (IMAE) route and a routine cycloisomerization route, were developed using either complex TAA(Et3P)2-PdCl·BF4- 3b or TAA(Ph3P)2-PdCl·BF4- 3c as the catalyst precursor.

Oleanane-Type Triterpene Conjugates with 1H-1,2,3-Triazole Possessing of Fungicidal Activity.

The triazole pesticide is an organic nitrogen-containing heterocyclic compound with a 1,2,3-Triazole ring. In order to develop a potential glucosamine-6-phosphate synthase (GlmS) inhibitor bactericide, 18 triazole-derivative compounds were synthesized efficiently. In addition, these compounds have not been reported in the literature. The structure was confirmed by high-resolution mass spectrometry (HRMS), 1H NMR and 13C NMR. The potential use of the most promising derivatives has been investigated by testing their antifungal activity and enzyme inhibitory activity, revealing inhibitory activities in the low micromolar range. Among them, the antifungal effects of compounds 1e, 1f, 1g, 2e, 2f, and 2g on Sclerotinia sclerotiorum were particularly significant, all of which were above 83%. These compounds will be further investigated as potential antifungal lead compounds. Their structure-activity relationships are discussed based on the effects of substituted phenyl groups on compounds.

Soluble Solids Content Binary Classification of Miyagawa Satsuma in Chongming Island Based on Near Infrared Spectroscopy.

Citrus is one of the most important fruits in China. Miyagawa Satsuma, one kind of citrus, is a nutritious agricultural product with regional characteristics of Chongming Island. Near-infrared Spectroscopy (NIR) is a proper method for studying the quality of fruits, because it is low-cost, efficient, non-destructive, and repeatable. Therefore, the NIR technique is used to detect citrus's soluble solid content (SSC) in this study. After obtaining the original spectral data, the first 70% of them are divided into the training set and 30% into the test set. Then, the Random Frog algorithm is chosen to select characteristic wavelengths, which reduces the dimension of the data and the complexity of the model, and accordingly makes the generalization of the classification model better. After comparing the performance of various classifiers (AdaBoost, KNN, LS-SVM, and Bayes) under different characteristic wavelength numbers, the AdaBoost classifier outperforms using 275 characteristic wavelengths for modeling eventually. The accuracy, precision, recall, and F 1-score are 78.3%, 80.5%, 78.3%, and 0.780, respectively and the ROC (Receiver Operating Characteristic Curve, ROC curve) is close to the upper left corner, suggesting that the classification model is acceptable. The results demonstrate that it is feasible to use the NIR technique to estimate whether the citrus is sweet or not. Furthermore, it is beneficial for us to apply the obtained models for identifying the quality of citrus correctly. For fruit traders, the model helps them to determine the growth cycle of citrus more scientifically, improve the level of citrus cultivation and management and the final fruit quality, and thus increase the economic income of fruit traders.

Influence of Paste Strength on the Strength of Expanded Polystyrene (EPS) Concrete with Different Densities.

Concrete in which EPS (expanded polystyrene) particles partially or completely replace concrete aggregates is called EPS concrete. Compared to traditional concrete, EPS concrete has a controllable low density and good thermal-insulation performance, which make it promising for prospective applications. At present, research on EPS concrete mostly focuses on increasing its strength and EPS surface modifications. Few researchers have studied the influence of cementitious material strength and EPS-concrete density on the strength of EPS concrete. In this research, cement was used as the main material, and fly ash, silica fumes, and blast furnace slag were selected as admixtures. By changing the mixing proportions of the admixtures, the basic properties, such as the paste strength, change. Based on the mix proportions of the above different raw materials, EPS concrete with different density levels was prepared to explore the influence of the density of EPS concrete and the strength of cementitious materials on the strength of EPS concrete. The influence of the slurry strength on EPS-concrete strength was weaker than that of the density of EPS concrete. When the strength range of the cementitious materials is 35.7~70.5 MPa, the compressive strength range of 1000 kg/m3, 1200 kg/m3, and 1400 kg/m3 EPS concrete is 8.8~17.6 MPa, 11.4~18.0 MPa, and 15.7~26.6 MPa, respectively. Based on the experiments, the fitting equation to determine the EPS-concrete strength-EPS-concrete density-cementitious material strength is z = 69.00087 + 0.0244x - 0.1746y - 0.00189x2 + 0.0000504706y2 + 0.00028401xy. Additionally, a strength-increasing design method for EPS concrete with different densities prepared by conventional Portland cement is clarified. This study can guide the preparation of EPS concrete.

A Review of the Role of the Antiplatelet Drug Ticagrelor in the Management of Acute Coronary Syndrome, Acute Thrombotic Disease, and Other Diseases.

P2Y12 inhibitors, including aspirin, are key components of dual-antiplatelet therapy (DAPT), which is the optimal therapeutic strategy for preventing arterial thrombosis in patients with acute coronary syndromes (ACS) who underwent stent implantation. Ticagrelor is a cyclopentyl-triazole pyrimidine antiplatelet drug that was the first reversible oral P2Y12 receptor antagonist. Compared with clopidogrel, ticagrelor exerts a faster onset and offset of function by reversible and selective inhibition of platelet aggregation in ACS patients, including those with coronary artery blood revascularization. Despite improvement in stent materials, stent thrombosis (ST) due to high on-treatment platelet reactivity (HPR) to clopidogrel continues to occur. In addition to antiplatelet aggregation, ticagrelor displays pleiotropic cardioprotective effects, including improving coronary blood flow, reducing myocardial necrosis after an ischemic event, and anti-inflammatory effects. The benefits of ticagrelor over clopidogrel were consistent in the PLATO results, with lower incidence of the primary endpoint. Also, in 2020, the findings from the phase 3 THALES trial (NCT03354429) showed that aspirin combined with 90 mg of ticagrelor significantly reduced the rates of stroke and death compared with aspirin alone in patients with AIS or TIA. Here, we review recent research on the superiority of ticagrelor over clopidogrel, discuss the pharmacological mechanism, and present future perspectives. This review aims to present the roles of ticagrelor in the management of acute coronary syndrome, acute thrombotic disease, and other diseases.

Ubiquitin-specific protease 1 acts as an oncogene and promotes lenvatinib efficacy in hepatocellular carcinoma by stabilizing c-kit.

INTRODUCTION AND OBJECTIVES: Ubiquitin-specific proteases (USPs) act as proto-oncogenes or tumor suppressors in a wide variety of cancers. In this study, we intended to explore the role of USP1 in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The clinical significance of USP1 in HCC was analyzed based on The Cancer Genome Atlas (TCGA) data and immunohistochemical staining. siRNAs and lentivirus were used to knock down and overexpress indicated genes, respectively. qRT-PCR and immunoblotting were performed to examine mRNA and protein expression, respectively. CCK8, colony formation and PI/Annexin V-APC staining were performed to examine cellular function. Immunoprecipitation, coomassie blue staining, mass spectrum and immunoblotting were conducted to evaluate the interaction between USP1 and c-kit. RESULTS: USP1 was over-expressed in HCC patients. Patients with high expression of USP1 had shorter overall and disease free survival than those with low expression of USP1. Functional results showed that USP1 was critical for HCC cell growth and proliferation. Immunoprecipitation and immunoblotting results suggested that USP1 interacted with c-kit and promoted the stability of c-kit, which is an important target of lenvatinib in HCC. Knockdown of c-kit reversed the oncogenic function of USP1 on HCC cell growth. Lastly, USP1 upregulation conferred higher sensitivity of HCC cells to lenvatinib treatment. CONCLUSIONS: Our study demonstrated that USP1 acted as an oncogene in HCC. It also promoted lenvatinib efficacy by stabilizing c-kit.

Gold catalyzed efficient preparation of dihydrobenzofuran from 1,3-enyne and phenol.

A gold catalyzed formal intermolecular [2+3] cyclo-coupling of 1,3-enynes with phenols was developed to prepare dihydrobenzofuran derivatives with the addition of 2,6-dichloropyridine N-oxide, in which, a highly ortho-selective phenol SEAr functionalization was achieved by using 1,3-enynes as α-oxo vinyl gold carbenoid surrogates.

Effect of Microbial Inoculation on Carbon Preservation during Goat Manure Aerobic Composting.

Carbon is the crucial source of energy during aerobic composting. There are few studies that explore carbon preservation by inoculation with microbial agents during goat manure composting. Hence, this study inoculated three proportions of microbial agents to investigate the preservation of carbon during goat manure composting. The microbial inoculums were composed of Bacillus subtilis, Bacillus licheniformis, Trichoderma viride, Aspergillus niger, and yeast, and the proportions were B1 treatment (1:1:1:1:2), B2 treatment (2:2:1:1:2), and B3 treatment (3:3:1:1:2). The results showed that the contents of total organic carbon were enriched by 12.21%, 4.87%, and 1.90% in B1 treatment, B2 treatment, and B3 treatment, respectively. The total organic carbon contents of B1 treatment, B2 treatment, and B3 treatment were 402.00 ± 2.65, 366.33 ± 1.53, and 378.33 ± 2.08 g/kg, respectively. B1 treatment significantly increased the content of total organic carbon compared with the other two treatments (p < 0.05). Moreover, the ratio of 1:1:1:1:2 significantly reduced the moisture content, pH value, EC value, hemicellulose, and lignin contents (p < 0.05), and significantly increased the GI value and the content of humic acid carbon (p < 0.05). Consequently, the preservation of carbon might be a result not only of the enrichment of the humic acid carbon and the decomposition of hemicellulose and lignin, but also the increased OTU amount and Lactobacillus abundance. This result provided a ratio of microbial agents to preserve the carbon during goat manure aerobic composting.

AM1241 alleviates myocardial ischemia-reperfusion injury in rats by enhancing Pink1/Parkin-mediated autophagy.

AIMS: The purpose of this study was to reveal the therapeutic efficacy and underlying mechanism of cannabinoid type 2 receptor agonist (AM1241) on myocardial ischemia-reperfusion injury (MIRI) in rats. MAIN METHODS: We established a rat myocardial ischemia/reperfusion (I/R) model and H9c2 hypoxia/reoxygenation (H/R) model. ELISA was used to determine the concentrations of cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) in plasma. EB/TTC staining was performed to observe the myocardial infarct size. Besides, the pathological changes of myocardial tissue were identified via H&E staining and Masson's trichrome staining. TUNEL assay was performed to examine myocardial apoptosis. Then, the protein expression of Pink1, Parkin and autophagy-related markers (Beclin-1, P62 and LC3) were detected by Western blot, and autophagy was evaluated by Mitotracker staining. KEY FINDINGS: The results of EB/TTC staining, H&E staining, Masson's trichrome staining and cardiac enzymes measuring showed that AM1241 treatment significantly diminished infarct size, the structural abnormalities and the activities of cardiac enzymes (cTnI, CK-MB, AST and LDH). AM1241 also significantly reduced the number of TUNEL-positive cells induced by I/R in a dose-dependent manner. Furthermore, AM1241 activated Pink1/Parkin signaling pathway and upregulated autophagy level. SIGNIFICANCE: AM1241 exerts a protective effect against MIRI in rats by inducing autophagy through the activation of Pink1/Parkin pathway.

microRNA-139-3p Inhibits Malignant Behaviors of Laryngeal Cancer Cells via the KDM5B/SOX2 Axis and the Wnt/ß-Catenin Pathway.

BACKGROUND: Laryngeal cancer (LCA) is a common head and neck cancer. Lysine demethylase 5B (KDM5B) knockdown is expected as a new target for cancer prevention. We investigated the molecular mechanism of KDM5B in LCA. MATERIALS AND METHODS: The levels of KDM5B, microRNA (miR)-139-3p and high-mobility-group box 2 (SOX2) in LCA tissues and cells, normal tissues and cells were detected. The effect of KDM5B on LCA was evaluated. The upstream miR of KDM5B and the downstream gene and pathway of KDM5B were predicted and their effects on LCA were analyzed. The Wnt/ß-catenin pathway-specific activator agonist was delivered into LCA cells expressing miR-139-3p mimic to evaluate the role of the Wnt/ß-catenin pathway. RESULTS: KDM5B was highly expressed in LCA, and inhibition of KDM5B suppressed LCA progression. miR-139-3p, downregulated in LCA tissues, was a regulatory miR of KDM5B. Overexpression of miR-139-3p significantly inhibited the malignant biological behaviors of LCA cells. KDM5B promoted SOX2 expression via histone demethylation. SOX2 was highly expressed in LCA, and overexpression of SOX2 promoted LCA progression by inducing the Wnt/ß-catenin pathway. Activated Wnt/ß-catenin pathway attenuated the inhibitory effect of miR-139-3p mimic on the malignant biological behaviors of LCA cells. CONCLUSION: miR-139-3p overexpression inhibited LCA development via regulating the KDM5B/SOX2 axis and inhibiting the Wnt/ß-catenin pathway.

Design, synthesis and bioevaluation of novel substituted triazines as potential dual PI3K/mTOR inhibitors.

A series of novel substituted triazines bearing a benzimidazole scaffold were designed and synthesized based on the structures of known anti-cancer agents, namely gedatolisib and alpelisib. All the target compounds were screened for inhibitory activity against PI3Kα and mTOR kinases. Notably, most analogs exhibited IC50 in the nanomolar range. Investigation of the isozyme selectivity indicated that the compounds exhibited remarkable inhibitory activity against PI3Kδ, especially compound 19f showed an IC50 value of 2.3 nM for PI3Kδ and moderate δ-isozyme selectivity over other class I PI3K isoforms and mTOR (with IC50 values of 14.6, 34.0, 849.0 and 15.4 nM for PI3Kα, ß, γ and mTOR, respectively). An in vitro MTT assay was conducted to assess the antiproliferative and cytotoxic effects of the prepared analogs. It was revealed that the compounds displayed significant inhibitory activities against the HCT116 human colon cancer cell line. Compound 19i showed 4.7-fold higher potency than the positive control gedatolisib (0.3 vs. 1.4 µM, IC50 values). Phosphoblot studies demonstrated that 19c and 19i could significantly suppress the PI3K/Akt/mTOR signaling pathway at 10 µM. Moreover, analogs 19b, 19c and 19i displayed better stability in artificial gastric fluids than gedatolisib, while 19i was indicated not very stable in rat liver microsomes, and may occur phase I metabolic transformations.