Objective To investigate the role of poly(rC)-binding protein 1(PCBP1)in cadmium(Cd)-induced ferroptosis in mouse neuroblastoma Neuro-2a(N2A)cells.Methods N2A cells were exposed to a concentration gradient of CdCl?(0,1,2,4 μmol/L)for 72 h.Cell viability was assessed by trypan blue staining.Western blotting was employed to detect the expression of ferroptosis-related proteins(GPX4,HMOX1,ACSL4)and PCBP1.Intracellular Fe2? level and lipid peroxidation were detected using FerroOrange and BODIPY581/591 C11 probes,respectively.Ferrostatin-1(Fer-1),a ferroptosis inhibitor,was applied to confirm the critical role of ferroptosis in Cd-induced cytotoxicity.Molecular docking was performed to elucidate the interaction between PCBP1 and ferritin,as well as the binding sites of Cd2?.PCBP1 overexpression plasmid was further constructed for functional validation.Results Cd exposure suppressed cell viability in N2A cells in a dose-dependent manner(P<0.01),significantly down-regulated GPX4 expression(P<0.05),up-regulated HMOX1 expression(P<0.01),and induced Fe2? overload and lipid peroxidation(P<0.01).Molecular docking revealed that Cd2? directly bound to the KH2 domain of PCBP1 and then co-localized on the outer surface of ferritin heavy chain.Overexpression of PCBP1 markedly reversed Cd-induced Fe2? accumulation,GPX4 down-regulation,lipid peroxidation,and cell death.Conclusion Cd exposure disrupts PCBP1-mediated iron homeostasis via transcriptional suppression and competitive displacement of metal ions,and then synergistically drives Fe2? overload-triggered ferroptosis cascades,ultimately leading to neurotoxicity.Targeting PCBP1-mediated iron homeostasis can effectively mitigate Cd-induced neurotoxicity,and may serve as a novel therapeutic strategy.

Objective To evaluate the safety and efficacy of the combined treatment with an optimized intense pulsed light (IPL) and a non-ablative fractional laser (NAFL) for facial rejuvenation.Methods A prospective,split-face,randomized,controlled study was conducted.A total of 22 testees with facial photoaging,who aged from 35 to 55 years,were enrolled into this study from the Department of Dermatology of Peking University First Hospital between March and June in 2017.By a random number table,the two sides of each testee's face were randomized to receive combined treatment with optimized IPL immediately followed by non-ablative 1 565 nm Erbium:Glass fractional laser (combined treatment group) or non-ablative 1 565 nm Erbium:Glass fractional laser alone (NAFL group) once every month for 3 sessions.Before the treatment,60 and 90 days after the treatment (1 month after the second and third treatment respectively),photos of the treatment regions were taken,skin physiology parameters (including skin melanin,erythema indices,water content of the stratum corneum,transepidermal water loss [TEWL],skin flexibility and glossiness) were measured,and subjective and objective clinical evaluation was carried out.After each treatment,adverse reactions were assessed by two dermatologists independently,including facial erythema,swelling and crusting,desquamation,pigmentation and pains.Results During the treatment course,1 testee dropped out due to pains,another 1 testee dropped out for personal reasons,and 20 testees completed the treatment and follow-up.The combined treatment group showed significantly decreased melanin indices on days 60 and 90 (152.9 ± 36.9 and 155.0 ± 38.1,respectively) compared with that before the treatment (168.4 ± 41.3,F =5.321,P ＜ 0.05).On day 60,the melanin index was significantly lower in the combined treatment group than in the NAFL group (159.4 ± 35.3,P ＜ 0.05).However,the melanin indices on days 60 and 90 in the NAFL group (159.4 ± 35.3,156.7 ± 36.3) did not significantly differ from that before the treatment (165.9 ± 35.4,P ＞ 0.05).No significant difference was observed between the pre-and post-treatment erythema indices in either of the two groups (both P ＞ 0.05).The water content of the stratum corneum on days 60 and 90 significantly increased compared with that before the treatment in both the combined treatment group (F =21.795,P ＜ 0.001) and NAFL group (F =21.798,P ＜ 0.001),while the TEWL on days 60 and 90 significantly decreased compared with that before the treatment in both the combined treatment group (F =8.848,P =0.001) and NAFL group (F =5.833,P ＜ 0.05).However,there were no significant differences in either of the water content of the stratum corneum or TEWL on days 60 and 90 between the two groups (P ＞ 0.05).On days 60 and 90,the combined treatment group and NAFL group both showed significantly increased skin flexibility (P＜ 0.05,0.001,respectively) and glossiness (both P ＜ 0.001) compared with those before the treatment.On day 90,the skin glossiness in the combined treatment group was higher than that in the NAFL group (P ＜ 0.05).The short-term adverse reactions included transient pain,erythema and swelling which lasted 2-3 days,and slight desquamation.The main adverse reaction was mild local pigmentation,which lasted 2-3 months and then subsided gradually.Conclusion The 3 sessions of treatment with an optimized IPL immediately followed by a 1 565 nm NAFL is clinically superior to those with the NAFL alone for improving the facial pigmentation and skin glossiness,and the adverse reactions are usually transient and mild.