First-generation EGFR tyrosine kinase inhibitors (TKIs) such as erlotinib have significant activity in NSCLC patients with activating EGFR mutations. However, EGFR-TKI resistance inevitably occurs ...after approximately 12 months of treatment. Acquired mechanisms of resistance, other than secondary mutations in EGFR (T790 M) which account for 50–60%, are less well understood. Here, we identified lncRNA H19 as a significantly downregulated lncRNA in vitro models and clinical specimens with acquired EGFR-TKI resistance, H19 knockdown or overexpression conferred resistance or sensitivity, respectively, both in vitro and in vivo models. H19 downregulation contributed to erlotinib resistance through interaction and upregulation of PKM2, which enhanced the phosphorylation of AKT. AKT inhibitors restored the sensitivity of erlotinib-resistant cells to erlotinib. In EGFR-mutant patients treated with EGFR-TKIs, low H19 levels were associated with a shorter progression-free survival (PFS) (P = 0.021). These findings revealed a novel mechanism of low-level H19 in the regulation of erlotinib resistance in EGFR-mutant lung cancers. Combination of AKT inhibitors and EGFR-TKIs could be a rational therapeutic approach for some subgroups of EGFR-mutant lung cancer patients.
•LncRNA H19 is downregulated in vitro models and clinical specimens with acquired EGFR-TKI resistance.•H19 knockdown or overexpression confers resistance or sensitivity, respectively, both in vitro and in vivo models.•H19 regulates EGFR-TKI resistance by interacting with PKM2, which mediates AKT activation.•AKT inhibitors restore the sensitivity of erlotinib-resistant cells to erlotinib.
Lithium, as the green energy, its application and exploitation attract much attention. The lithium extraction kinetics with N,N-bis(2-ethylhexyl) acetamide(N523) in sulfonated kerosene has been ...investigated experimentally using Lewis Cell. The effects of diffusion resistance area, interfacial area, temperature and the concentration of reagents were studied. The results showed that the diffusion resistance mainly existed in aqueous phase, the extraction process was a diffusion-controlled kinetics process with an interfacial reaction and the extraction kinetic equation was obtained.
•Lithium extraction kinetics with N523 was investigated using a Lewis Cell.•The diffusion resistance mainly existed in aqueous phase.•The extraction kinetics was diffusion-controlled.•The extraction rate equation could be expressed by R = 2.63 × 10−7Li+FeCl4−N523.
The perovskite CH3NH3PbI3 was prepared on a mesoscopic TiO2 film, starting from electrodepositing PbO, to iodination to PbI2, and then interdiffusion reaction with CH3NH3I. The as-prepared film was ...used as a light absorber for the perovskite solar cells, exhibiting a high PCE of 12.5% under standard AM 1.5 conditions.
Double kissing (DK) crush approach for patients with coronary bifurcation lesions, particularly localized at distal left main or lesions with increased complexity, is associated with significant ...reduction in clinical events when compared with provisional stenting. Recently, randomized clinical trial has demonstrated the net clinical benefits by intravascular ultrasound (IVUS)-guided implantation of drug-eluting stent in all-comers. However, the improvement in clinical outcome after DK crush treatment guided by IVUS over angiography guidance for patients with complex bifurcation lesions have never been studied in a randomized fashion.
DKCRUSH VIII study is a prospective, multicenter, randomized controlled trial designed to assess superiority of IVUS-guided vs angiography-guided DK crush stenting in patients with complex bifurcation lesions according to DEFINITION criteria. A total of 556 patients with complex bifurcation lesions will be randomly (1:1 of ratio) assigned to IVUS-guided or angiography-guided DK crush stenting group. The primary end point is the rate of 12-month target vessel failure, including cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization. The secondary end points consist of the individual component of primary end point, all-cause death, myocardial infarction, and in-stent restenosis. The safety end point is the incidence of definite or probable stent thrombosis. An angiographic follow-up will be performed for all patients at 13 months and clinical follow-up will be continued annually until 3 years after the index procedure.
DKCRUSH VIII trial is the first study designed to evaluate the differences in efficacy and safety between IVUS-guided and angiography-guided DK crush stenting in patients with complex true bifurcation lesions. This study will also provide IVUS-derived criteria to define optimal DK crush stenting for bifurcation lesions at higher complexity.
Dietary n-3 polyunsaturated fatty acids (PUFA) exert anti-inflammatory and immunoregulatory effects through down-regulating the innate and adoptive immune response. However, the effect of dietary n-3 ...PUFA on CD4+CD25+ regulatory T cells (Tregs) is unclear.
The current study was to examine the relationship between n-3 PUFA and Tregs as well as their immunoregulatory effect in immune-mediated liver injury.
The mice model feeding with n-3 PUFA-enriched diet was established and Tregs were analyzed. Effect of docosahexaenoic acid (DHA) on Tregs proliferation and induction was determined in vitro. The potential immunotherapeutic effect of dietary n-3 PUFA was investigated through Con A-induced hepatitis model.
Long-term administration of dietary n-3 PUFA significantly increased hepatic Tregs and modulated their phenotype. n-3 PUFA or DHA directly increased natural Tregs (nTreg) proliferation but didn't increase inducible Tregs (iTreg). In addition, the expression of peroxisome proliferator activated receptor gamma (PPAR-γ), transforming growth factor β (TGF-β) and interleukin (IL)-10 were significantly up-regulated in n-3 PUFA-enriched diet-fed mice. Finally, n-3 PUFA-enriched diet alleviated liver injury induced by Con A and down-regulated pro-inflammatory cytokines expression, accompanied by increased PPAR-γ expression.
Dietary n-3 PUFA enhanced Tregs generation through up-regulating PPAR-γ and TGF-β expression, and protected mice from Con A-induced liver injury. This finding provides a promising potential therapeutic method in treating inflammatory and autoimmune disease.
5α-reductase inhibitors (5-ARI) are widely employed for the treatment of benign prostatic hyperplasia. It has been noted that 5-ARI exhibit the potential to attenuate the risk of prostate cancer, but ...consistent agreement has not been achieved. Moreover, the effect of 5-ARI on cancer-specific mortality and progression of prostate cancer remains unclear. Therefore, the goal of the current meta-analysis was to elucidate the impact of 5-ARI on the incidence and progression of prostate cancer. We searched for all studies assessing the effect of 5-ARI on risk of prostate cancer in PubMed, Embase, Medline, and Cochrane Library databases. Pooled relative risk (RR) and corresponding 95% confidence intervals (CIs) were accepted to evaluate the association between 5-ARI and the risk of prostate cancer. Synthetic results implied that subjects who accepted 5-ARI compared with the placebo group experienced a distinctly weakened overall incidence of prostate cancer (RR = 0.74; 95% CI: 0.66-0.82; P < 0.001). Subgroup analyses further revealed that 5-ARI reduction of the incidence of prostate cancer was limited to low-grade (Gleason score 2-6; RR = 0.68; 95% CI: 0.57-0.81; P < 0.001) and intermediate-grade tumors (Gleason score 7; RR = 0.81; 95% CI: 0.67-0.97; P = 0.023), but not high-grade tumors (Gleason score >7; RR = 1.19; 95% CI: 0.98-1.43; P = 0.069). The results also showed that 5-ARI treatment did not significantly alter prostate cancer-specific mortality (RR = 1.0; 95% CI: 0.95-1.05; P = 0.916). In addition, it was worth noting that 5-ARI treatment acted in a protective role that presented a dramatic benefit to delay the progression of low-risk tumors (RR = 0.58; 95% CI: 0.43-0.78; P < 0.001).
Objective We assessed the efficacy and safety of a weekly pegylated human growth hormone (PEG-rhGH) (Jintrolong) vs daily rhGH for children with growth hormone deficiency (GHD). Design Phase II and ...III, multicenter, open-label, randomized controlled trials. Methods 108 and 343 children with treatment-naive GHD from 6 hospitals in China were enrolled in the phase II and III studies respectively. Patients in the phase II study were randomized 1:1:1 to weekly Jintrolong (0.1 mg/kg/week PEG-rhGH complex), weekly Jintrolong (0.2 mg/kg/week PEG-rhGH complex) or daily rhGH (0.25 mg/kg/week) for 25 weeks. Patients in the phase III study were randomized in a 2:1 ratio to weekly Jintrolong (0.2 mg/kg/week) or daily rhGH (0.25 mg/kg/week) for 25 weeks. The primary endpoint for both studies was height velocity (HV) increase at the end of treatment. Other growth-related parameters, safety and compliance were also monitored. Results The phase II study established the preliminary efficacy, safety and recommended dose of Jintrolong PEG-rhGH. In the phase III study, we demonstrated significantly greater HV increases in patients receiving Jintrolong treatment (from 2.26 ± 0.87 cm/year to 13.41 ± 3.72 cm/year) vs daily rhGH (from 2.25 ± 0.82 cm/year to 12.55 ± 2.99 cm/year) at the end of treatment (P < 0.05). Additionally, significantly greater improvement in the height standard deviation scores was associated with Jintrolong throughout the treatment (P < 0.05). Adverse event rates and treatment compliance were comparable between the two groups. Conclusion Jintrolong PEG-rhGH at a dose of 0.2 mg/kg/week for 25 weeks is effective and safe for GHD treatment and is non-inferior to daily rhGH.
An Sb2S3 absorber layer is coated on mesoporous TiO2 films through a sequential deposition method: SbCl3 aqueous solution is first deposited, followed by reaction with H2S gas and further thermal ...annealing. Under our conditions, the Sb2S3-based solid-state heterojunction solar cells yield efficiencies of up to 6.27% at 100 mW cm-2 AM 1.5 G.
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•The control mode of the extraction reaction was a mixed control mode which occurred at the interfacial area.•The lithium extraction rate equation by TBP-FeCl3 extraction system from ...salt lake brine could be expressed as follows:•The results of thermodynamic functions suggested the extraction lithium reaction was exothermic, spontaneous and the lower temperature was favorable for extraction.
The extraction kinetics of lithium from brine by tri-n-butyl phosphate had been researched experimentally using Lewis cell technique. Different parameters such as interfacial area, temperature, agitation speed, the concentration of Li+, Fe3+ and TBP were studied separately to identify the reaction location and the extraction reaction regime. The experimental results demonstrated the control mode of the extraction reaction was a mixed control mode which occurred at the interfacial area. Further analysis suggested the extraction rate equation can be expressed as follows: R=3.145×10-3Li+FeCl4-TBP2
The results of thermodynamic functions suggested the extraction reaction was an entropy increase process and extraction reaction was spontaneous.
Multiwalled carbon nanotubes (MWCNTs) have been widely used as reinforcement fillers in past decades. However, the reinforcement effect has been greatly hindered by the limited available interface ...area (AIA) with polymer matrices for polymer composites. Successively, the method of oxidative unzipping MWCNTs into graphene nanoribbons (GNRs) was demonstrated to be the effective way for addressing the inherent drawback of MWCNTs. However, the GNRs are easy to agglomerate in polymer matrix even at relatively low loading amount. In this paper, we found that the functionalization of GNRs with Kevlar® can significantly improve the dispersion state of GNRs in polymer matrix. Consequently, Kevlar®-functionalized graphene nanoribbons (KGNRs) were successfully prepared through non-covalent functionalization of π–π stacking interaction between the aromatic area of Kevlar® and the graphitic surface of GNRs. As-prepared KGNRs were characterized by FT-IR, TGA, XRD and TEM measurements. Poly(vinyl chloride) (PVC) and poly(methyl methacrylate) (PMMA) were selected as model polymers to investigate the reinforcement effect of KGNRs. The KGNRs could be well dispersed in PVC and PMMA matrices at relatively high loading level. Meantime, the ultimate tensile strengths and Young's modulus of KGNRs/PVC and KGNRs/PMMA composite films were significantly improved. Based on the observations above, KGNRs hold great promise in many potential applications in the future.
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