Head and neck squamous cell carcinomas (HNSCCs) are a type of cancer originating in the mucosal epithelium of the mouth, pharynx, and larynx, the sixth most common cancer in the world. However, there is no effective treatment for HNSCCs. More than 90% of HNSCCs overexpress epidermal growth factor receptors (EGFRs). Although small molecule inhibitors and monoclonal antibodies have been developed to target EGFRs, few EGFR-targeted therapeutics are approved for clinical use. Ferroptosis is a new kind of programmed death induced by the iron catalyzed excessive peroxidation of polyunsaturated fatty acids. A growing body of evidence suggests that ferroptosis plays a pivotal role in inhibiting the tumor process. However, whether and how ferroptosis-inducers (FINs) play roles in hindering HNSCCs are unclear. In this study, we analyzed the sensitivity of different HNSCCs to ferroptosis-inducers. We found that only tongue squamous cell carcinoma cells and laryngeal squamous cell carcinoma cells, but not nasopharyngeal carcinoma cells, actively respond to ferroptosis-inducers. The different sensitivities of HNSCC cells to ferroptosis induction may be attributed to the expression of KRAS and ferritin heavy chain (FTH1) since a high level of FTH1 is associated with the poor prognostic survival of HNSCCs, but knocked down FTH1 can promote HNSCC cell death. Excitingly, the ferroptosis-inducer RSL3 plays a synthetic role with EGFR monoclonal antibody Cetuximab to inhibit the survival of nasopharyngeal carcinoma cells (CNE-2), which are insensitive to both ferroptosis induction and EGFR inhibition due to a high level of FTH1 and a low level of EGFR, respectively. Our findings prove that FTH1 plays a vital role in ferroptosis resistance in HNSCCs and also provide clues to target HNSCCs resistant to ferroptosis induction and/or EGFR inhibition.
BackgroundExisting guidelines recommend endoscopic treatment within 12 h or 12–24 h for patients with esophagogastric variceal bleeding (EGVB) in cirrhosis. In addition, research findings on the optimal time for endoscopy are inconsistent.AimThe aim of this study was to investigate the relationship between the timing of endoscopy and clinical outcomes in cirrhotic patients with EGVB and to analyze the risk factors for the composite outcomes after endoscopic treatment.MethodsFrom January 2019 to June 2020, 456 patients with cirrhotic EGVB who underwent endoscopy were matched by a 1:1 propensity score. Finally, 266 patients were divided into two groups, including 133 patients within 12 h (urgent endoscopy group) of admission and after 12 h (non-urgent endoscopy group). Baseline data and clinical outcomes were compared. Logistic regression model analysis was used to determine risk factors for 30 days rebleeding and mortality.ResultsIn 266 patients, the overall 30 days rebleeding rate and mortality were 10.9% (n = 29) and 3.4% (n = 9), respectively. Patients who underwent endoscopic treatment within 12 h had significantly higher 30 days rebleeding outcomes than those who underwent treatment beyond 12 h (15 vs. 6.8%, p = 0.003). However, 30 days mortality did not differ significantly between the two groups (3 vs. 3.8%, p = 0.736). Logistic regression analysis showed that age and shock on admission were independent risk factors for the composite outcome of 30 days rebleeding and mortality in patients with EGVB.ConclusionThe 30 days rebleeding rate in patients with cirrhotic EGVB treated with urgent endoscopy was significantly higher than that in patients treated with non-urgent endoscopy, but there was no significant difference in 30 days mortality.
Silicon anode materials have the absolute predominance of high theoretical specific capacity, but its conductivity is low. What is more, the huge volume expansion (∼300%) of silicon during cycling causes rapid capacity fading. Herein, high-performance Si@void@C nanoparticles are synthesized by a unique ZnO template and mild strategy for the first time. Compared with the traditional synthesis method, a milder and environmentally friendly synthesis strategy provides a new feasible scheme for the large-scale commercialization of silicon anodes. The carbon layer blocks the silicon from the electrolyte and improves the conductivity of materials, and the yolk–void–shell structure accommodates the volume expansion of silicon during cycling. Si@void@C nanoparticles prepared with the ZnO template show excellent cycle and rate performances compared with the traditional synthetic strategy. After 500 cycles, the specific capacity of Si@void@C still maintains 934 mA h g–1 at 1 A g–1, and the average specific capacity is as high as 1125.4 mA h g–1 at a high current density of 4 A g–1. To sum up, the potential of Si@void@C anode for lithium-ion batteries cannot be underestimated.
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