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1.
Artigo em Inglês | MEDLINE | ID: mdl-31913007

RESUMO

The output voltage of triboelectric nanogenerators (TENGs) is much higher than the overload capacity of most commercial electronics, making it hard to power them directly; so the power-management solution is indispensable. In the meanwhile, it is critical for practical applications to enhance the output performance of the TENG toward its breakdown limit, which is usually ignored before. Here, an inductor-free output multiplier (OM) for power promotion and management of TENGs is proposed, with the breakdown effect considered. This OM, as expanded based on bennet's doubler, is theoretically studied and experimentally demonstrated to significantly enhance the output performance of the TENG within only a few working cycles. The charge output was enhanced by 7.6 times experimentally with the OM. An external capacitor and a switch are applied to realize a high energy extraction ratio of up to 196%, with the average charge output per cycle of ∼3-3.75 µC achieved. This OM circuit with the smart switch is suitable for power promotion of TENGs with variable capacitance and for power management of all TENGs. The OM circuit is demonstrated to ensure the high output performance of TENGs even at a low triboelectric charge density, which is crucial for broad applications of the TENG toward self-powered systems, potentially to be a solution for improving the output performance of TENGs working in harsh environments.

2.
Postgrad Med ; 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31962051

RESUMO

Objectives: Hyperuricemia and Hypertension are 2 independent risk factors of renal function damage. Our research aimed to investigate the synergistic interaction between hyperuricemia and hypertension towards reduced eGFR.Methods: Our analyses included 11,694 participants from a cross-sectional population-based Northeast China Rural Cardiovascular Health Study. Interaction was assessed on both multiplicative and additive scales.Results: The prevalence of reduced estimated glomerular infiltration rate (eGFR) was 2.11% in our population. After adjustment of age, sex, race, education level, family income, current smoking and drinking status, body mass index, total cholesterol, high-density lipoprotein cholesterol, and diabetes, subjects with both hyperuricemia and hypertension suffered from a 11.004 (95% CI: 7.080-17.102) times risk of reduced eGFR than the healthy reference group, greater than that in participants with only hyperuricemia (5.741, 95% CI: 3.045-10.825) or hypertension (1.145, 95% CI: 0.764-1.715). Furthermore, additive interaction between hyperuricemia and hypertension was statistically significant and synergistic (relative excess risk due to interaction: 5.118, 95% CI: 0.611-9.624; the attributable proportion due to interaction: 0.465, 95% CI: 0.151-0.779; Synergy index: 2.047, 95% CI: 1.017-4.120). However, our results revealed no significant interaction on the multiplicative scale.Conclusions: Hyperuricemia and hypertension may have a synergistic interaction towards renal function loss in addition to their independent impacts. Our findings may provide a straightforward illustration which is easy for the public to realize the hazard of coexistent hypertension and hyperuricemia on renal injury.

4.
J Diabetes Complications ; : 107447, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31818688

RESUMO

BACKGROUND: Hypertension and diabetes mellitus are 2 major risk factors for chronic kidney disease (CKD). However, whether hypertension and diabetes have a synergistic interaction towards greater renal damage remains unclear. Our study aimed to investigate whether hypertension and diabetes act synergistically towards CKD. METHODS: 13,693 subjects from the cross-sectional National Health and Nutritional Examination Survey 1999-2006 were included in our analyses. The associations were investigated by multivariate logistic regression models. The interaction was evaluated on both additive and multiplicative scale. RESULTS: The prevalence of CKD was 17.62%. After adjustment, subjects with both hypertension and diabetes had a 4.710 (3.652-6.073) times risk of CKD than non-hypertensive non-diabetic subjects, higher than that of subjects with only hypertension or diabetes (1.732, 95% CI: 1.502-1.997 and 2.407, 95% CI: 1.815-3.194, respectively). Furthermore, significant interaction was observed between hypertension and diabetes towards CKD in the additive scale (relative excess risk due to interaction: 1.570, 95% CI: 0.507-2.633; the attributable proportion due to interaction: 0.333, 95% CI: 0.168-0.499; Synergy index: 1.734, 95% CI: 1.239-2.426). Additionally, analyses of the associations with components of the primary endpoint demonstrated that the interaction was also applicable to those with reduced eGFR, albuminuria or normoalbuminuric CKD. CONCLUSIONS: The joint effect of hypertension and diabetes was significantly larger than the sum of their independent impact on CKD. Our findings may provide intuitionistic and straightforward illustrations for the public to understand the danger of combined hypertension and diabetes on the renal injury.

5.
AAPS PharmSciTech ; 21(1): 20, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31820224

RESUMO

Thermal extrusion (TE) 3D printing is a thermoplastic semisolid-based rapid prototyping process, which is capable of building complex structures. The aim of this study was to manufacture rapid-release puerarin tablets without solvent through TE 3D printing. Novel rapid-release tablets were fabricated with polyethylene glycol (PEG 4000) as the carrier at appropriate puerarin/PEG 4000 ratios, assessed through differential scanning calorimetry (DSC), solubility, and dissolution tests. The novel structures of 3D-printed tablets with five different values were formed by printing paths, which established a flexible way of adjusting in vitro drug release. An obvious acceleration (85% of cumulative release about 7.5 min at the soonest) was observed for the tablets with internal structural design. It was inferred that puerarin formed simple eutectic mixtures with PEG 4000 and that puerarin dispersed into the carrier based on DSC and X-Ray powder diffraction (XRD). This highlights the combined advantage of PEG as a soluble polymer with TE 3D printing and provides a suitable system for rapid puerarin release.

7.
Breast ; 49: 33-40, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31677531

RESUMO

OBJECTIVES: Triple negative breast cancer (TNBC) is a heterogenous disease and associated with unfavorable outcomes. The role of sonographic features and its association with disease outcome in TNBC is uncertain. Our study aimed to determine the prognosis predictive value of sonographic features in TNBC. METHODS: Women with TNBC patients treated between January 2009 and December 2015 were retrospectively included. Patients' clinic-pathological, sonographic features, recurrence-free survival (RFS), and breast cancer-specific survival (BCSS) events were reviewed and analyzed. Kaplan-Meier analysis and multivariable Cox regression were used to determine the prognostic factors in TNBC. RESULTS: A total of 433 TNBC patients were included. With a median follow-up of 4.8 years, 58 (13.4%) RFS and 35(8.1%) BCSS events were detected. Besides lymphatic vascular invasion (LVI), nuclear grade III, tumor >2.0 cm, and positive axillary lymph node (ALN), multivariable analysis found that vertical orientation in ultrasound imaging was independently associated with worse RFS (Hazard Ratio (HR) = 3.238; 95% Confidential Interval (CI), 1.661-6.312; P = 0.001) and BCSS (HR = 7.028; 95% CI, 3.199-15.436; P < 0.001). TNBC with vertical orientation in ultrasound imaging had higher ALN metastasis burden than those with sonographic parallel features (2.7 ±â€¯1.0 vs 1.5 ±â€¯0.2, P = 0.003). CONCLUSIONS: TNBC presenting with vertical orientation in ultrasound imaging was associated with worse disease outcome and a greater number of ALN metastasis.

8.
Plant J ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31680357

RESUMO

The rapid selection of salinity-tolerant crops to increase food production in salinized lands is important for sustainable agriculture. Recently, high-throughput plant phenotyping technologies have been adopted that use plant morphological and physiological measurements in a non-destructive manner to accelerate plant breeding processes. Here, a hyperspectral imaging (HSI) technique was implemented to monitor the plant phenotypes of 13 okra (Abelmoschus esculentus L.) genotypes after 2 and 7 days of salt treatment. Physiological and biochemical traits, such as fresh weight, SPAD, elemental contents and photosynthesis-related parameters, which require laborious, time-consuming measurements, were also investigated. Traditional laboratory-based methods indicated the diverse performance levels of different okra genotypes in response to salinity stress. We introduced improved plant and leaf segmentation approaches to RGB images extracted from HSI imaging based on deep learning. The state-of-the-art performance of the deep-learning approach for segmentation resulted in an intersection over union score of 0.94 for plant segmentation and a symmetric best dice score of 85.4 for leaf segmentation. Moreover, deleterious effects of salinity affected the physiological and biochemical processes of okra, which resulted in substantial changes in the spectral information. Four sample predictions were constructed based on the spectral data, with correlation coefficients of 0.835, 0.704, 0.609 and 0.588 for SPAD, sodium concentration, photosynthetic rate and transpiration rate, respectively. The results confirmed the usefulness of high-throughput phenotyping for studying plant salinity stress using a combination of HSI and deep-learning approaches.

9.
Nat Commun ; 10(1): 4620, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31604958

RESUMO

Implanted scaffolds with inductive niches can facilitate the recruitment and differentiation of host cells, thereby enhancing endogenous tissue regeneration. Extracellular matrix (ECM) scaffolds derived from cultured cells or natural tissues exhibit superior biocompatibility and trigger favourable immune responses. However, the lack of hierarchical porous structure fails to provide cells with guidance cues for directional migration and spatial organization, and consequently limit the morpho-functional integration for oriented tissues. Here, we engineer ECM scaffolds with parallel microchannels (ECM-C) by subcutaneous implantation of sacrificial templates, followed by template removal and decellularization. The advantages of such ECM-C scaffolds are evidenced by close regulation of in vitro cell activities, and enhanced cell infiltration and vascularization upon in vivo implantation. We demonstrate the versatility and flexibility of these scaffolds by regenerating vascularized and innervated neo-muscle, vascularized neo-nerve and pulsatile neo-artery with functional integration. This strategy has potential to yield inducible biomaterials with applications across tissue engineering and regenerative medicine.

10.
Sci Rep ; 9(1): 13277, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31527693

RESUMO

Accurate dosimetry of a specific brain region in rats exposed to an electromagnetic field (EMF) is essential for studies focusing on dose-effect relationship of the region. However, only dosimetry of whole brain or whole body were evaluated in most of previous studies. In this study, a numerical voxel rat model with 10 segmented brain regions was constructed. Then, the effects of frequency, incidence direction, and E-polarization direction of plane wave EMF on brain region averaged specific absorption rate (BRSAR) of rats were investigated. At last, the reliability of using whole-body averaged SAR (WBDSAR) and whole-brain averaged SAR (WBRSAR) as estimations of BRSAR were also evaluated. Our results demonstrated that the BRSAR depended on the frequency, incidence direction, and E-polarization direction of the EMF. Besides, the largest deviation could be up to 13.1 dB between BRSAR and WBDSAR and 9.59 dB between BRSAR and WBRSAR. The results suggested that to establish an accurate dose-effect relationship, the variance of the BRSAR induced by alteration of frequency, incidence direction, and E-polarization direction of EMF should be avoided or carefully evaluated. Furthermore, the use of WBDSAR and WBRSAR as estimations of BRSAR should be restricted to certain conditions such that the deviations are not too large.

11.
Biomed Pharmacother ; 118: 109336, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545260

RESUMO

Significant advances in the treatment of non-small cell lung cancer (NSCLC) have been made over the past decade, and they predominantly involve molecular targets such as epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements. However, despite the initial good response, drug resistance eventually develops. The Wnt signaling pathway has recently been considered important in embryonic development and tumorigenesis in many cancers, particularly NSCLC. Moreover, the aberrant Wnt pathway plays a significant role in NSCLC and is associated with cancer cell proliferation, metastasis, invasion and drug resistance, and the suppression of canonical or noncanonical Wnt signaling through various biological or pharmacological negative regulators has been proven to produce specific anticancer effects. Thus, blocking the Wnt pathway via its negative regulators may overcome the resistance of current treatment methods and lead to new treatment strategies for NSCLC. Therefore, in this review, we summarize recent studies on the role of negative regulators in Wnt signaling in NSCLC and the therapeutic potency of these molecules as agents and targets for NSCLC treatments.

12.
J Clin Hypertens (Greenwich) ; 21(10): 1567-1577, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31523928

RESUMO

Hypertension and hyperhomocysteinemia are two independent risk factors of chronic kidney disease (CKD). Our study aimed to evaluate whether hypertension and hyperhomocysteinemia act synergistically toward renal injury. Our analysis included 13 693 subjects from the National Health and Nutritional Survey (NHANES) 1999-2006. Association was assessed by multivariate logistic regressions. The interaction was investigated on both additive and multiplicative scales. CKD had a prevalence of 17.62% in the NHANES population. After adjusting for age, sex, race, education, physical activity, drinking frequency, current smoking status, poverty-to-income ratio, Total cholesterol, high-density lipoprotein cholesterol, serum folate, vitamin B12, body mass index, waist circumference, and diabetes mellitus, patients with both hypertension and hyperhomocysteinemia had a 5.072 (3.967-6.486) times risk of CKD than their healthy compartments, higher than that in patients with only hypertension or hyperhomocysteinemia. Moreover, additive interaction of hypertension and hyperhomocysteinemia was significant (relative excess risk due to interaction: 2.107, 95% CI: 1.071-3.143; the attributable proportion due to interaction: 0.415, 95% CI: 0.270-0.561; synergy index: 2.072, 95% CI: 1.449-2.962). Finally, subgroup analyses elucidated the interaction was robust in those with only reduced estimated glomerular filtration rate or albuminuria, and stratification analyses based on gender showed consistency with the main results. Hypertension and hyperhomocysteinemia may act synergistically toward a greater renal injury than the sum of their independent effects. Our findings suggest the coexistence itself also correlates with a deteriorative impact on renal function in addition to the effects of hypertension and diabetes themselves. The results may support the rationality and value of simultaneous tight control of hypertension and hyperhomocysteinemia to prevent CKD.

13.
Int J Mol Sci ; 20(16)2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31409031

RESUMO

Little information is available regarding the effect of melatonin on the quality and fertilization capability of sex-sorted bull sperm, and even less about the associated mechanism. Sex-sorted sperm from three individual bulls were washed twice in wash medium and incubated in a fertilization medium for 1.5 h, and each was supplemented with melatonin (0, 10-3 M, 10-5 M, 10-7 M, and 10-9 M). The reactive oxygen species (ROS) and endogenous antioxidant activity (glutathione peroxidase (GPx); superoxide dismutase (SOD); catalase (CAT)), apoptosis (phosphatidylserine [PS] externalization; mitochondrial membrane potential (Δψm)), acrosomal integrity events (malondialdehyde (MDA) level; acrosomal integrity), capacitation (calcium ion [Ca2+]i level; cyclic adenosine monophosphate (cAMP); capacitation level), and fertilization ability of the sperm were assessed. Melatonin receptor 1 (MT1) and 2 (MT2) expression were examined to investigate the involvement of melatonin receptors on sex-sorted bull sperm capacitation. Our results show that treatment with 10-5 M melatonin significantly decreased the ROS level and increased the GPx, SOD, and CAT activities of sex-sorted bull sperm, which inhibited PS externalization and MDA levels, and improved Δψm, acrosomal integrity, and fertilization ability. Further experiments showed that melatonin regulates sperm capacitation via MT1. These findings contribute to improving the fertilization capacity of sex-sorted bull sperm and exploring the associated mechanism.

14.
Sci Total Environ ; 695: 133694, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31421331

RESUMO

A novel photocatalytic carbon nanotube sponge with three-dimensional Bombax-structure was fabricated by a facile chemical vapor deposition followed by in situ ion-exchange approach. The as-prepared sponge achieved both high-efficiency adsorption and photocatalysis towards antibiotics, which can remove up to 90% of tetracycline within an hour. The morphology and mechanism of the photocatalytic CNT sponge were explored by multiple measures. Results show the functional groups and high specific surface area of CNT sponge play vital roles in preparing this Bombax-structured Ag3PO4/CNT sponge, the band gap of which can be tuned by varying the ration between Ag3PO4 and CNT. The photodegradation experiments of tetracycline with the assistance of ultrasound irradiation were performed, Ag3PO4/CNT sponge exhibits preferable photocatalytic activity, which can be attributed to both the enhancement of specific surface area of Ag3PO4 and the cavitation effect on CNT surface. The efficiency contributed by ultrasound could account for more than half of the degradation efficiency when the ultrasound power was 100 W. The improvement in transfer efficiency and the delay in charge recombination of Ag3PO4/CNT sponge were further verified by Electrochemical impedance spectra (EIS) and Photoluminescence tests (PL). Reactive free-radical species were detected by the Electron Spin Resonance (ESR). The intermediates and possible pathway were analyzed by gas chromatography-mass spectrometer (GC-MS) technique.

15.
Dalton Trans ; 48(35): 13248-13259, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31414090

RESUMO

Cobalt has been extensively studied as an effective catalyst for the electrooxidation of sodium borohydride. However, there is still the problem of the low catalytic activity of cobalt catalysts. The improvement in the catalytic activity of cobalt for the electrooxidation of sodium borohydride has become a challenge. In this paper, a novel catalyst Co-P alloy was supported on a copper foam (CF) substrate by a one-step electrodeposition method. In the electrodeposition process, a Co-P/CF electrode with a three-dimensional (3D) porous structure was successfully prepared using hydrogen bubbles as a dynamic template. Through the physical characterization of Co-P/CF, it was proven that the doping of P element produced more Co clusters on the surface of the electrode, which resulted in more active sites. These characteristics were very beneficial for NaBH4 electrooxidation. The electrochemical characterization confirmed that the electrocatalytic activity of Co-P/CF for NaBH4 was better than that of Co/CF. At room temperature, for the Co-P/CF in 2.0 mol dm-3 NaOH + 0.20 mol dm-3 NaBH4 solution, the oxidation current density reached 1795 mA cm-2 at -0.20 V (vs. Ag/AgCl), which was higher than that previously reported the literature.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31312874

RESUMO

PURPOSE: The purpose of this study was to evaluate and compare the clinical outcomes of two different fixation techniques for anatomic medial patellofemoral ligament (MPFL) reconstruction. METHODS: A retrospective study was undertaken between 2012 and 2018 of 60 cases of patellar dislocation who underwent surgical reconstruction between 2007 and 2010: 30 patients were treated with modified semi-tunnel bone bridge fixation (group A) and 30 patients with suture anchor fixation (group B). All patients had computed tomography scans available to review the patellar tilt angle and lateral patellar angle (LPA). In addition, a physical examination was performed, and the patellar apprehension sign and patellar stability were evaluated. Knee function was also evaluated using the Kujala score and Lysholm score. RESULTS: At a minimum 5-year follow-up, the patellar tilt angle and LPA were restored to the normal range, and a significant difference was observed between the groups. There was a significant improvement in knee function in the Kujala and Lysholm scores after surgery in both groups. At the final follow-up, the mean Kujala and Lysholm scores in groups A and B were significantly different. CONCLUSION: Both the semi-tunnel bone bridge and suture anchor fixation for double-bundle anatomic reconstruction of the MPFL can effectively restore patellar stability and improve knee function. The semi-tunnel bone bridge technique achieved statistically better knee function than the suture anchor technique at a minimum 5-year follow-up. LEVEL OF EVIDENCE: III.

17.
Biomaterials ; 218: 119328, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31299457

RESUMO

Bioavailable persistent luminescence material is an ideal internal light source for long-term photodynamic therapy, but inevitably suffers from low utilization efficiency and weak persistent luminescence due to corrosion and screening processes. Herein, we show a facile and smart "turning solid into gel" strategy to fabricate persistent luminescence hydrogel for high-efficient persistent luminescence-sensitized photodynamic therapy. The homogeneous persistent luminescence hydrogel was synthesized via dispersing high-temperature calcined persistent luminescence material without corrosion and screening into a biocompatible alginate-Ca2+ hydrogel. The simple synthesis strategy allows 100% of utilization efficiency and intact persistent luminescence of persistent luminescence material. The persistent luminescence hydrogel possesses favorable biocompatibility, bright persistent luminescence, red light renewability, good syringeability, and strong fixing ability in tumors. The persistent luminescence hydrogel can be easily injected in vivo as a powerful localized light source for superior persistent luminescence-sensitized photodynamic therapy of tumors. The "turning solid into gel" strategy enables taking full advantages of persistent luminescence for biological applications, and shows great potential in utilizing diverse theranostic agents regardless of hydrophilicity and hydrophobicity.

18.
J Pharmacol Exp Ther ; 370(2): 278-287, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31167814

RESUMO

Glecaprevir and pibrentasvir are oral direct-acting antiviral agents approved in combination for treatment of chronic hepatitis C viral infection. In vitro studies identified the combination as potentially clinically relevant inhibitors of the efflux transporters P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and the hepatic uptake transporters organic anion transporting polypeptide (OATP) 1B1 and OATP1B3. Glecaprevir inhibited P-gp, BCRP, OATP1B1, and OATP1B3 with IC50 values of 0.33, 2.3, 0.017, and 0.064 µM, respectively. Pibrentasvir inhibited P-gp, BCRP, and OATP1B1 with IC50 values of 0.036, 14, and 1.3 µM, respectively. Neither agent inhibited organic cation transporter (OCT) 1, OCT2, organic anion transporter (OAT) 1, OAT3, multidrug and toxin extrusion (MATE) 1, or MATE2K. Open-label phase 1 clinical drug-drug interaction studies were conducted in healthy subjects to evaluate interaction potential of glecaprevir/pibrentasvir and coadministered selective substrates for P-gp (digoxin, dabigatran etexilate, and sofosbuvir), BCRP (rosuvastatin and sofosbuvir), and OATP1B1/3 (pravastatin and rosuvastatin). The pharmacokinetic maximum plasma concentration (C max) and area under the concentration-time curve (AUC) parameters were evaluated for probe substrates alone and in combination with glecaprevir/pibrentasvir. The C max central values increased by 72%, 105%, 123%, 462%, and 66% for digoxin, dabigatran, pravastatin, rosuvastatin, and sofosbuvir, respectively, and the AUC central values increased by 48%, 138%, 130%, 115%, and 125% for digoxin, dabigatran, pravastatin, rosuvastatin, and sofosbuvir, respectively. Exposure of sofosbuvir metabolite GS-331007 (nucleoside analog) was similar with or without glecaprevir/pibrentasvir. The outcomes of the clinical drug-drug interaction studies confirmed clinically relevant inhibition of P-gp, BCRP, and OATP1B1/3, and were used to provide dosing guidance for the concomitant use of glecaprevir/pibrentasvir with relevant transporter substrates.

19.
Biomark Med ; 13(9): 773-783, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31157544

RESUMO

Aim: To investigate whether monocyte to HDL cholesterol ratio (MHR) can improve the risk stratification of reduced renal function by estimating atherosclerosis. Patients & methods: The cross-sectional study included 8159 subjects (males: 45.73%, mean age: 54.12 years) from Northeast China in 2013. Results: Each standard deviation increase of MHR brought 42.9% additional risk of reduced renal function in males. In females, MHR strongly correlated with reduced renal function before it reached a breakpoint (MHR = 0.25). Additionally, net reclassification improvement identified the value of MHR (0.199; 95% CI: 0.030-0.369; p = 0.021) to improve the risk classification of renal function reduction. Conclusion: This study implicates that MHR is independently associated with reduced renal function and can refine the risk stratification of renal function reduction.

20.
Molecules ; 24(12)2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31242597

RESUMO

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. Isoxazoline and isoxazole derivatives represent an important class of five-membered heterocycles, which play a pivotal role in drug discovery. In our previous study, we developed a series of isoxazole derivatives with an efficient method. In this study, we evaluated their effects on tumor cell growth. HCT116 cells were treated with isoxazole derivatives; an cholecystokinin octapeptide (CCK-8) assay was used to calculate the IC50 (half maximal inhibitory concentration) of each derivative. Compound SHU00238, which was obtained by the copper nitrate-mediated [2+2+1] cycloaddition reaction of olefinic azlactone with naphthalene-1,4-dione, has a lower IC50; we analyzed its inhibitory activity in further assays. Cell apoptosis was estimated by flow cytometry analysis in vitro. SHU00238 injection was used to treat tumor-bearing mice. We found that SHU00238 suppressed cell viability and promoted cell apoptosis in vitro. SHU00238 treatment significantly inhibited colonic tumor growth in vivo. Furthermore, we compared the miRNAs expression changes in HCT116 cells before and after SHU00238 treatment. MiRNA profiling revealed that SHU00238 treatment affected cell fate by regulating a set of miRNAs. In conclusion, SHU00238 impedes CRC tumor cell proliferation and promotes cell apoptosis by miRNAs regulation.

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