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We present a novel, eco-friendly and one-pot approach for synthesizing unsymmetrical oxalamides with the aid of dichloroacetamide and amine/amides in the presence of CBr4 in a basic medium. The use of water as a potent supplement for the oxygen atom source and the detailed mechanism have been disclosed. Moreover, the protocol involves triple cleavage of CCl2Br and the formation of new C–O/C–N bonds, with the advantage of achieving selective bromination using CBr4 with good to excellent yield under mild conditions. The method also demonstrates promise for industrial use, as proven by its effective implementation in gram-scale synthesis conducted in a batch process, along with its utilization in a continuous-flow system. [ABSTRACT FROM AUTHOR]

Anionic redox activity can trigger structural instability in Li‐rich Mn‐based cathodes. Lattice oxygen activity can be tuned through liquid acid‐induced spinel phases and oxygen vacancies. However, the liquid‐acid‐modified surface is still attacked by the electrolyte. Besides, the underlying mechanism of spinel phase suppression of lattice oxygen activity is controversial. Here, a solid acid strategy for modification is proposed and the underlying mechanism is investigated in detail. Unique solid acid can in situ generate an interface protection layer and remarkably stabilize the structure. Theoretical calculations and experimental characterizations reveal that the spinel phase suppresses the irreversible loss of lattice oxygen by decreasing the O 2p non‐bonding energy level and enriching electrons at the layered/spinel phase interface. The inert layer on the surface prevents highly active On− from being attacked by electrolytes. The obtained material exhibits significantly reduced irreversible lattice oxygen release and improved electrochemical performance. After 300 cycles, a slow capacity fading of 0.177 mAh g−1 per cycle and suppressed voltage fading are achieved. This study reveals the regulation method and mechanism for the anion activity of oxide cathodes in next‐generation Li‐ion batteries. [ABSTRACT FROM AUTHOR]

Abstract:Aiming to design a simulate software of human tissue modeling and analysis，Visual Studio 2010 is selected as a development tool to develop a 3 D reconstruction software of human tissue with language C++.It can be used alone. It also can be a module of the virtual surgery systems. The system includes medical image segmentation modules and 3 D reconstruction modules，and can realize the model visualization. This software system has been used to reconstruct hip muscles，femur and hip bone accurately. The results show these geometry models can simulate the structure of hip tissues.

The resistance and the surface morphology of the graphene films were studied after atomic oxygen exposure. The graphene films can be etched away during atomic oxygen exposure, the resistance of graphene films decreases at first and then increases. It shows that the adsorption of oxygen atom may play an important role in the change of the resistance of graphene films at the beginning of the exposure and then the change of the resistance conforms to the law of resistance. The atomic oxygen erosion rate which is about 1.2×10-25cm3/atom to 1.3×10-25cm3/atom can be obtained. A kind of new atomic oxygen detector was put forward based on the relationship between the resistance of graphene films and atomic oxygen fluence.

Simple Summary: Boron neutron capture therapy (BNCT) is a target radiotherapy and image-guided intensity-modulated radiotherapy (IG-IMRT) that has been used for recurrent head and neck cancer. To procure better results, the current study designed to combine both as salvage treatment for this challenging problem. For the 14 patients enrolled, a high response rate and low incidence of grade 4 toxicity were seen at follow-up. Further local recurrence was the main cause of failure in spite of the larger radiation volumes and extra dose given with IG-IMRT after BNCT than with BNCT alone. Further revision of this protocol is suggested to improve our results. Background: This trial investigated the efficacy and safety of salvage boron neutron capture therapy (BNCT) combined with image-guided intensity-modulated radiotherapy (IG-IMRT) for recurrent head and neck cancer after prior radiotherapy (RT). Methods: BNCT was administered using an intravenous boronophenylalanine–fructose complex (500 mg/kg) in a single fraction; multifractionated IG-IMRT was administered 28 days after BNCT. For BNCT, the mucosa served as the dose-limiting organ. For IG-IMRT, the clinical target volume (CTV) and the planning target volume (PTV) were generated according to the post-BNCT gross tumor volume (GTV) with chosen margins. Results: This trial enrolled 14 patients, and 12 patients received combined treatment. The median BNCT average dose for the GTV was 21.6 Gy-Eq, and the median IG-IMRT dose for the PTV was 46.8 Gy/26 fractions. After a median (range) follow-up period of 11.8 (3.6 to 53.2) months, five patients had a complete response and four had a partial response. One patient had grade 4 laryngeal edema; another patient had a grade 4 hemorrhage. Most tumor progression occurred within or adjacent to the CTV. The 1-year overall survival and local progression-free survival rates were 56% and 21%, respectively. Conclusion: Despite the high response rate (64%) of this trial, there was a high incidence of in-field and marginal failure with this approach. Future studies combining BNCT with modalities other than radiation may be tried. [ABSTRACT FROM AUTHOR]

Background: We aimed to analyze the radiation dose and compare survival among combined modality therapy using modern radiation techniques for patients with esophageal squamous cell carcinoma (ESCC). Methods: This retrospective study included patients with clinically staged T1‐4N0‐3M0 ESCC from 2014 to 2018. Patients who received combined modality therapies with curative intent were enrolled. The overall survival (OS) rates among combined modality therapy were compared. The clinical variables and impacts of radiation dose on survival were analyzed by the Kaplan–Meier method and Cox regression model. Results: Of the 259 patients, 141 (54.4%) received definitive concurrent chemoradiotherapy (DCCRT); 67 (25.9%) underwent neoadjuvant chemoradiotherapy followed by surgery (NCRT+S); 51 (19.7%) obtained surgery followed by adjuvant chemoradiotherapy (S+ACRT). Two‐year OS rates of the DCCRT, NCRT+S and S+ACRT group were 48.9, 61.5 and 51.2%. In the subgroup analysis of DCCRT group, the 2‐year OS of patients receiving radiation dose 55–60 Gy was 57.1%. Multivariate analyses showed that clinical stage (p = 0.004), DCCRT with 55–60 Gy (p = 0.043) and NCRT+S with pathological complete response (pCR) (p = 0.014) were significant prognostic factors for better OS. The radiation dose–survival curve demonstrated a highly positive correlation between higher radiation dose and better survival. Conclusion: Our results suggest that NCRT+S can provide a favorable survival for patients with ESCC, especially in patients who achieved pCR. The optimal radiation dose might be 55–60 Gy for patients receiving DCCRT via modern radiation techniques. Further randomized clinical studies are required to confirm the survival benefits between NCRT+S and DCCRT with escalated dose. [ABSTRACT FROM AUTHOR]

Background: To evaluate the clinical relative biological effectiveness (RBE) of carbon‐ion radiotherapy (C‐ion RT) for prostate cancer. Methods: The records of 262 patients with low‐risk prostate cancer (median age, 65 [47–80] years) treated with C‐ion RT at QST Hospital, National Institutes for Quantum Science and Technology in Japan during 2000–2018 were reviewed retrospectively. Four different protocol outcomes and prostate‐specific antigen (PSA) responses were evaluated. The median follow‐up was 8.4 years. The Kaplan–Meier method was used to estimate the biochemical or clinical failure‐free rate (BCFFR). Clinical RBE was calculated using the tumor control probability model. Results: The 5‐, 7‐, and 10‐year BCFFRs were 91.7%, 83.8%, and 73.2%, respectively. The 10‐year BCFFRs of patients who received C‐ion RT at 66 Gy (RBE) in 20 fractions, 63 Gy (RBE) in 20 fractions, and 57.6 Gy (RBE) in 16 fractions were 81.4%, 70.9%, and 68.9%, respectively. The PSA level and density during follow‐up were better in the patients treated with the lower fraction size. A higher PSA nadir and shorter time to PSA nadir were risk factors for biochemical or clinical failure by multivariate Cox regression. The tumor control probability analysis showed that the estimated clinical RBE values to achieve an 80% BCFFR at 10 years for 20, 16, and 12 fractions were 2.19 (2.18–2.24), 2.16 (2.14–2.23), and 2.12 (2.09–2.21), respectively. Conclusions: Using clinical data from low‐risk prostate cancer patients, we showed the clinical RBE of C‐ion RT decreased with increasing dose per fraction. [ABSTRACT FROM AUTHOR]

The major railroad projects in complex and difficult areas have characteristics of complex geological conditions, high incidence of natural disasters, high plateau, high cold and lack of oxygen, low level of existing infrastructure, and extremely long construction period, etc. In order to ensure high quality construction and to solve important problems such as high worker turnover rate, significant aging, and vocational skills and quality to be improved, it is imperative to promote industrialized workers. Based on major railroad projects in complex and dangerous areas, this paper conducts in-depth interviews with front-line railroad construction workers and relevant enterprise leaders. 12 influencing factors of industrialized worker training by applying rooting theory are analyzed and summarized into 6 main categories. Based on the analysis and category, a ISM-MICMAC model is constructed to analyze the interrelationship between influencing factors. The key factors are combined with the driving force dependency matrix to find out 4 key root influencing factors and put forward countermeasure suggestions to reduce their influence. This research provides reference suggestions for industrialized worker training of major railroad projects in complex and difficult areas. [ABSTRACT FROM AUTHOR]

A series of novel 4-N-phenylaminoquinoline derivatives containing a morpholine group were designed and synthesized, and their anti-cholinesterase activities and ABTS radical-scavenging activities were tested. Among them, compounds 11a, 11g, 11h, 11j, 11l, and 12a had comparable inhibition activities to reference galantamine in AChE. Especially, compound 11g revealed the most potent inhibition on AChE and BChE with IC50 values of 1.94 ± 0.13 μM and 28.37 ± 1.85 μM, respectively. The kinetic analysis demonstrated that both the compounds 11a and 11g acted as mixed-type AChE inhibitors. A further docking comparison between the 11a- and 12a-AChE complexes agreed with the different inhibitory potency observed in experiments. Besides, compounds 11f and 11l showed excellent ABTS radical-scavenging activities, with IC50 values of 9.07 ± 1.34 μM and 6.05 ± 1.17 μM, respectively, which were superior to the control, Trolox (IC50 = 11.03 ± 0.76 μM). It is worth noting that 3-aminoquinoline derivatives 12a–12d exhibited better drug-like properties. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the clinical relevance of the immune microenvironment in patients with combined hepatocellular carcinoma and cholangiocarcinoma (cHCC‐ICC). Patients and Methods: The density of tumor‐infiltrating CD3+, CD8+, CD163+, and Foxp3+ immune cells, as well as Programmed cell death 1, Programmed cell death‐ligand 1, and Tumor necrosis factor receptor superfamily member 4, was measured in the peritumor liver, tumor invasive margin, and intratumor subregions of 56 cHCC‐ICC by immunohistochemistry. The immune index was established to stratify patients. Prognostic significance of immune cell subsets and immune indices was evaluated. Results: The distribution of immune cells was highly heterogeneous among different subregions of cHCC‐ICC. As compared with the hepatocellular carcinoma (HCC) component, the lower density of CD8+ T cells and higher intensity of Foxp3+ Tregs and immune checkpoints in the intrahepatic cholangiocarcinoma (ICC) component may indicate a stronger immune evasive ability of ICC. Based on clustering classification or a combination of random forest and lasso‐cox, two models of immune indices were established and both were identified as independent prognostic factors for cHCC‐ICC patients. The selected immune variables in the immune prognostic models derived from both HCC and ICC subregions, indicating that the prognosis of cHCC‐ICC patients was a complex interaction of both components. Conclusions: The immune contexture was heterogeneous among different subregions of cHCC‐ICC patients and contributed differently to patient prognosis. Immune score based on the densities of immune cells might serve as a promising prognostic predictor for cHCC‐ICC patients. [ABSTRACT FROM AUTHOR]

The adoption of the PPP model in urban infrastructure construction is a new feature that drives the dual benefits of urban economy and society. The cooperation between public and private sectors needs to use incentive and restraint mechanisms to motivate the enthusiasm of stakeholders to participate in project construction investment, thereby obtaining economic and social benefits. Through the empirical case study, this study found that the effectiveness of incentive mechanism is mainly determined by the government's reward to the private sector in the project and its active efforts. The utility of incentive mechanism is the key to determine the unique constraint control power of the government. In order to demonstrate the validity of the research method in project implementation, a model based on incentive and constraint mechanism in PPP projects is established. The results show that there are differences in the decision standards during project operation phase. The incentive and restraint mechanism has the strongest role and risk sharing ability in the PPP projects, and has the highest difficulties on supervision of income constraint. The findings of this study can help stakeholders avoid the risk sharing and improve social equity of the PPP model in urban construction and operation. [ABSTRACT FROM AUTHOR]

Chinese alkaline noodle (CAN) is one of popular staple foods in Asia. Whole wheat flour (WWF) is healthier than refined wheat flour (WF). This study investigated the effect of substitution level of WWF on physicochemical and sensory properties of CAN. Results showed that increasing WWF amount significantly reduced tensile strength (TS) and extensibility (E) of cooked CAN, but increased TS/E ratio from 6.05 to 13.22 mN/mm. High WWF substitution (>60 %) significantly increased cooking loss and decreased the elasticity of CAN. CAN prepared with WWF had darker, redder and yellower color than control. However, free and bound phenolics and DPPH radical scavenging capacity of CAN obviously increased with the amount of WWF. CAN with 0-40 % WWF had similar sensory scores in color, flavor, texture and overall preferences. The study suggests that healthy whole grain CAN with higher phytochemicals and acceptable eating quality can be produced by using 20-40 % WWF. [ABSTRACT FROM AUTHOR]

Purpose: Selective internal radiation therapy (SIRT) is an effective treatment strategy for unresectable hepatocellular carcinoma (HCC) patients. However, the prognoses of patients with portal vein thrombosis, extra-hepatic metastases, or residual tumors remain poor when treated with SIRT alone. In these patients, sequential external beam radiotherapy (EBRT) may offer a chance of salvage. Here, we reported the clinical outcomes and the detailed dosimetry analysis of 22 patients treated with combination therapy. Methods: Between October 2011 and May 2015, 22 consecutive patients who underwent EBRT after yttrium-90 (90Y) SIRT were included in this study. The post-SIRT 90Y bremsstrahlung SPECT/CT of each patient was transferred to dose distribution by adopting the local deposition hypothesis. The patient-specific 3-dimensional biological effective dose distribution of combined SIRT and EBRT was generated. The overall survival and safety were evaluated. The relationship between dosimetric parameters and liver toxicity was analyzed. Results: The mean administered activity of SIRT was 1.50 GBq (range: 0.5–2.8). The mean prescribed dose of EBRT was 42.3 Gy (range: 15–63) in 14 fractions (range: 5–15) and was targeted to the residual liver tumor in 12 patients (55%), portal vein thrombosis in 11 patients (50%), and perihilar lymphadenopathies in 4 patients (18%). The overall 1-, 2-, and 3-year survival rates were 59.8%, 47.9%, and 47.9%, respectively. Overall, 8 patients (36%) developed > grade 2 liver toxicities, and the Child-Pugh score prior to EBRT strongly affected the toxicity risk. A dosimetry analysis restricted to 18 Child-Pugh A/B patients showed that the V100 (The fraction of normal liver exposed to more than 100 Gy) to V140 significance differed between patients who did or did not experience hepatotoxicity. The V110 was the strongest predictor of hepatotoxicity (18.6±11.6% vs 29.5±5.8%; P = 0.030). Conclusion: Combined therapy is feasible and safe if patients are carefully selected. Specifically, 3-dimensional dosimetry is crucial for the evaluation of efficacy and toxicity. The normal liver V100 to V140 values of the combined dose should be as low as possible to minimize the risk of liver toxicity. [ABSTRACT FROM AUTHOR]

Horizontal wells have been widely used to exploit unconventional oil and gas reservoirs across the world. Insufficient hole cleaning has been recognized as one of the main difficulties in drilling horizontal wells. Drilling incidents caused by insufficient hole cleaning increase unproductive drilling time, induce a great amount of additional drilling costs and may even lead to the loss of the well. Drilling a well while maintaining efficient hole cleaning is a systematic process that requires various parameters to implement hole cleaning and requires cooperative effort rather than separate work. Therefore, optimizing multiple parameters to achieve the best hole cleaning effect is of great importance. However, to the author's knowledge, few research studies in this area have been undertaken. The objective of this study is to develop a new method to optimize multiple hole cleaning parameters by introducing the ant colony algorithm. The flow rate, consistency coefficient in power law model and nozzle flow area, which are three easily-adjusted parameters to control the hole cleaning on drilling site, are selected as the optimization variables. The hydraulic constraints that affect hole cleaning optimization are proposed. The mechanism and procedures of ant colony algorithm optimization are described. The practical usefulness of the developed method is demonstrated with a field example. The effect of the selected parameters on hole cleaning is analyzed, and the hole cleaning result after optimization is compared to the data before optimization. The result of the optimization shows that hole cleaning is greatly improved and all constraints are satisfied after optimization. By analyzing the optimization results, it can be concluded that the ant colony algorithm can be used to optimize the hole cleaning problem for horizontal wells. Artificial intelligence can help optimize the drilling of horizontal wells to reduce the risk of unproductive time and decrease drilling costs. The flow rate, consistency coefficient and nozzle flow area should cooperate with one another to minimize the cutting bed height while satisfying all of the constraints. Increasing the flow rate is the most efficient way to reduce the cutting bed height. Decreasing the consistency coefficient and increasing the nozzle flow area can reduce the total pressure loss and enlarge the capacity for increasing the flow rate. Increasing the pressure-bearing capacity of the system is favorable for improving the hole cleaning of horizontal wells. The cutting bed height can be further reduced and the jet velocity can be further increased when increasing the pressure-bearing capacity of the system. [ABSTRACT FROM AUTHOR]

Highlights: [•] Two rare indazole-type alkaloids, nigeglapine (1) and nigeglaquine (2) were isolated from the seeds of Nigella glandulifera. [•] The structures were confirmed on the basis of chemical and spectroscopic data. [•] This is the first report of the natural occurrence of glycosylated indazole-type alkaloids. [•] Compounds 1 and 2 were highly applicable as chemical markers. [•] Indazole-type alkaloids show significant role in the chemotaxonomy of Nigella. [Copyright &y& Elsevier]

Abstract: U–Pb–Hf isotopic analyses have been carried out on detrital zircons from Late Permian–Jurassic strata in the Western Shandong–Bohai Bay (WSBB) basins with aims of constraining the paleogeography and evolution of the eastern North China Craton (NCC). Four major groups of U–Pb ages (namely, 3.0–2.3Ga, 2.2–1.4Ga, 1250–430Ma and 410–150Ma) are recognized for zircons from the fine-grained sandstones. The post-Paleoproterozoic zircons of the Late Permian sample show an age cluster of 344–255Ma with εHf(t) values of −18 to −8, being similar to those extracted from Late Paleozoic igneous rocks from the Yinshan–Yanshan Orogenic Belt (YYOB) on the northern margin of the NCC. However, the Devonian–Jurassic zircons (390–150Ma) from the Jurassic sediments have εHf(t) values from −45 to +14, very similar to the mixture of Phanerozoic zircons from the Xing–Meng Orogenic Belt (XMOB) and the YYOB, but significantly different from those of the Liaodong Peninsula, Jiaodong Peninsula and the Western Shandong Uplift. In addition, Cambrian–Silurian zircons (535–430Ma) of the Jurassic samples have εHf(t) values from −27 to +7, resembling the Early Paleozoic zircons extracted from the Northern Qinling Orogen (NQO). The U–Pb age spectra and Hf isotope of Devonian–Jurassic zircons as well as bulk Nd isotopes suggest that the central eastern NCC received some juvenile materials from the XMOB, the YYOB and the NQO during the Jurassic. This indicates widespread prototype basins and a low elevation during the Jurassic, arguing against the presence of a paleo-plateau in the eastern NCC at that time. The lack of evidence predicted by lithospheric delamination (e.g., large-scale elevation or doming after Late Triassic) makes the delamination unlikely to be a viable mechanism of lithospheric thinning of the NCC. The subsidence rather than elevation of the eastern NCC after Late Triassic might be related to thermo-chemical erosion of the lithosphere by underlying convective mantle in a back-arc setting. [Copyright &y& Elsevier]

Browser with Rich Internet Application (RIA) Web pages could be a powerful user interface for handling sophisticated data and applications. Then the RIA solutions would be a potential method for viewing and manipulating the most data generated in clinical processes, which can accomplish the main functionalities as general picture archiving and communication system (PACS) viewing systems. The aim of this study is to apply the RIA technology to present medical images. Both Digital Imaging and Communications in Medicine (DICOM) and non-DICOM data can be handled by our RIA solutions. Some clinical data that are especially difficult to present using PACS viewing systems, such as ECG waveform, pathology virtual slide microscopic image, and radiotherapy plan, are as well demonstrated. Consequently, clinicians can use browser as a unique interface for acquiring all the clinical data located in different departments and information systems. And the data could be presented appropriately and processed freely by adopting the RIA technologies. [ABSTRACT FROM AUTHOR]

A new flavonol glycoside, kaempferol 3-O-α-L-rhamnopyranosyl (1 → 6)-O-[β-D-glucopyranosyl (1 → 2)-O-β-D-galactopyranosyl (1→2)]-O-β-D-glucopyranoside (1), together with a known compound, kaempferol 3-O-β-D-glucopyranosyl (1 → 2)-O-β-D-galactopyranosyl (1 → 2)-O-β-D-glucopyranoside (2) was isolated from the seeds of Nigella glandulifera. Their structures were elucidated on the basis of spectral analysis, including ESI–MS, ESI–MS/MS, HR-ESI–MS, DQF–COSY, TOCSY, HSQC and HMBC techniques. [ABSTRACT FROM PUBLISHER]

Purpose: To investigate the intensity-modulated radiotherapy (IMRT) strategy in dose escalation of prostate and pelvic lymph nodes. Methods and Materials: Plan dosimetric data of 10 prostate cancer patients were compared with two-dimensional (2D) or IMRT techniques for pelvis (two-dimensional whole pelvic radiation therapy [2D-WPRT] or IM-WPRT) to receive 50 Gy or 54 Gy and additional prostate boost by three-dimensional conformal radiation therapy or IMRT (3D-PBRT or IM-PBRT) techniques up to 72 Gy or 78 Gy. Dose-volume histograms (DVHs), normal tissue complication probabilities (NTCP) of critical organ, and conformity of target volume in various combinations were calculated. Results: In DVH analysis, the plans with IM-WPRT (54 Gy) and additional boost up to 78 Gy had lower rectal and bladder volume percentage at 50 Gy and 60 Gy, compared with those with 2D-WPRT (50 Gy) and additional boost up to 72 Gy or 78 Gy. Those with IM-WPRT (54 Gy) also had better small bowel sparing at 30 Gy and 50 Gy, compared with those with 2D-WPRT (50 Gy). In NTCP, those with IM-WPRT and total dose of 78 Gy achieved lower complication rates in rectum and small bowel, compared with those of 2D-WPRT with total dose of 72 Gy. In conformity, those with IM-WPRT had better conformity compared with those with 2D-WPRT with significance (p < 0.005). No significant difference in DVHs, NTCP, or conformity was found between IM-PBRT and 3D-PBRT after IM-WPRT. Conclusions: Initial pelvic IMRT is the most important strategy in dose escalation and critical organ sparing. IM-WPRT is recommended for patients requiring WPRT. There is not much benefit for critical organ sparing by IMRT after 2D-WPRT. [ABSTRACT FROM AUTHOR]

Two rare guanidine-type alkaloids, Buthutin A (1) and Buthutin B (2), along with two other compounds (3, 4), were isolated from Buthus martensii Karsch, and determined using extensive spectroscopic data analysis and high resolution-mass spectrometry. Compound 1 showed the most potent inhibition on AChE and BChE with IC50 values of 7.83 ± 0.06 and 47.44 ± 0.95 μM, respectively. Kinetic characterization of compound 1 confirmed a mixed-type of AChE inhibition mechanism in accordance with the docking results, which shows its interaction with both catalytic active (CAS) and peripheral anionic (PAS) sites. The specific binding of compound 1 to PAS domain of AChE was also confirmed experimentally. Moreover, compounds 1 and 3 exhibited satisfactory biometal binding abilities toward Cu2+, Fe2+, Zn2+ and Al3+ ions. These results provide a new evidence for further development and utilization of B. martensii in health and pharmaceutical products. [ABSTRACT FROM AUTHOR]

Four phenolic compounds, including two new ones, Nigephenol A and B ( 1 – 2 ), and a new natural product, Nigephenol C ( 3 ), were isolated from the seeds of Nigella glandulifera . Their structures were elucidated on the basis of spectroscopic analyses using HR-ESI-MS, 1D and 2D NMR spectra. All compounds were evaluated by MTT method for in vitro cytotoxicity against four human cancer cell lines (Bel7402, HepG2, HCT-8 and A549). The results revealed that Compounds 1 – 4 showed more selective activities against HepG2 cells, and that Compound 2 showed significant inhibitory effects against four human tumor cell lines with IC 50 values comparable to those of 5-fluorouracil. [ABSTRACT FROM AUTHOR]

AbstractHerein, we designed a series of guanidinobenzoic acid ester derivatives on the basis of approved AP drugs, such as nafamostat, gabexate and camostat, and evaluated their inhibitory effects on trypsin and anti-inflammatory activity. Among them, five compounds (6a, 6c–6e, 7j) showed excellent inhibitory effects on trypsin with IC50 values of 0.0756 μM to 0.1227 μM, which are more potent than nafamostat and gabexate. Moreover, compounds 6a, 6b and 6c also showed significant inhibitory potency against the pro-inflammatory molecule NO with IC50 values of 1.618 μM, 2.276 μM, and 3.022 μM, respectively. Consequently, the potential lead compounds simultaneously with anti-trypsin and anti-inflammatory activities were identified, which would profit further structural optimization for the treatment of AP. [ABSTRACT FROM AUTHOR]