Objective To investigate the role and the underlying mechanisms of N6-methyladenosine(m6A)reader YTHDF3 in macrophages activation.Methods shRNA-mediated Ythdf3 knockdown in RAW264.7 cells was performed and these RAW264.7 cells were stimulated with LPS.Then,changes in the pro-inflammatory and anti-tumor functions,including cytokine production,phagocytosis,and tumoricidal ability were evaluated.The effect of Ythdf3 knockdown on the activation of the Toll-like receptor 4(TLR4)downstream MAPK and NF-κB pathways was assessed by immunoblotting.After Ythdf3 knockdown,the expression levels and mRNA stability of key junction proteins and signaling molecules of the TLR4 signaling pathway were analyzed to identify YTHDF3 target genes and investigate the underlying regulatory mechanism.Results After LPS stimulation of wild-type RAW264.7 cells,the level of pro-inflammatory factors increased and then decreased.However,the level of YTHDF3 showed the opposite trend to that of pro-inflammatory factors,suggesting that YTHDF3 might play a role in the negative regulation of macrophage activation.shRNA-mediated Ythdf3 knockdown in RAW264.7 cells significantly increased the expression of pro-inflammatory factors,nitric oxide(NO)production,and phagocytosis.In addition,Ythdf3 knocked-down RAW264.7 cells co-cultured with tumor cells exhibited enhanced tumor killing ability.The findings suggested that YTHDF3 deletion could promote LPS-induced activation of RAW264.7 cells and enhance their production of pro-inflammatory factors and tumor killing function.further investigation into the underlying mechanisms revealed that Ythdf3 knockdown inhibited the degradation of Cd36,Irak1,Tab1/2,and Tirap mRNAs,which were key junction proteins and signaling molecules in the TLR4 pathway,which in turn,enhanced the phosphorylation of p38,a downstream key kinase and the activation of macrophages.Conclusion By targeting the mRNA of the key junction proteins and signaling molecules of the TLR4 pathway,YTHDF3 accelerates their rapid degradation and suppresses macrophage activation.Ythdf3 knockdown significantly promotes macrophage activation and enhances the tumor killing activities of macrophages.

Objective:To measure the retinal structural and functional parameters of adult Macaca fascicularis, and explore the similarity of the retinal structural and functional parameters between non-human primates and normal human retinas.Methods:Six eyes of 3 5-year-old adult Macaca fascicularis were examined by in vivo detection including color fundus photography, retinal optical coherence tomography (OCT) and electroretinogram (ERG) to determine the thickness of the inner/outer retina at the fovea and 1 000/2 000 μm away from the nasal, temporal, superior and inferior regions of the fovea, the thickness of the retinal nerve fiber layer (RNFL), the area of optic disc, the area of optic cup, the area ratio of cup to disc and the biological parameters of flash ERG.Differences in the above parameters between left and right eyes were analyzed.The similarity of parameters between Macaca fascicularis and human was compared with reference to published literature.The use and care of animals complied with the Regulation on the Management of Experimental Animals.The study protocol was approved by the Institutional Animal Care and Use Committee of Hubei Topgene Biotechnology (NO.IACUC-2019-012). Results:The foveal thickness, optic disc area, cup-disc area ratio, and average RNFL thickness in normal adult Macaca fascicularis were (252.31±4.79)μm, (1.89±0.05)mm 2, 0.14±0.01, and (103.53±0.58)μm, respectively.The b-wave amplitude of dark-adapted 0.01 ERG was (66.75±7.29)μV.The a- and b-wave amplitudes of dark-adapted 3.0 ERG response were (57.15±15.01) and (122.10±25.51)μV, respectively.The a- and b-wave amplitudes, the amplitude of oscillation potentials, and the latency of dark-adapted 10.0 ERG response were (72.98±20.14)μV, (131.67±13.78)μV, (49.98±10.08)μV, and (30.02±5.76)ms, respectively.The a- and b-wave amplitudes of light-adapted 3.0 ERG were (9.16±2.75) and (40.43±5.57)μV, respectively.The latency and the amplitude of the light-adapted 30 Hz flicker was (26.61±1.19)ms and (24.72±5.10)μV, respectively.There was no significant difference in the parameters between left and right eyes (all at P>0.05). The retinal thickness in central fovea, mean RNFL thickness, waveform and amplitude of ERG of Macaca fascicularis were similar to normal human. Conclusions:The structure and function of the retina of adult Macaca fascicularis are similar to those of normal humans.As a laboratory animal for preclinical drug research, in vivo studies of Macaca fascicularis can refer to normal human retinal parameters.

Ionizing radiation has been widely used for diagnosis and treatment of diseases. Nevertheless, radiation exposure may increase the risk of skin, cardiovascular system, hematological system, and metabolic disorders, and even the risk of cancers. Rational use of ionizing radiation improves prognosis and facilitates biomedical research, while misuse or overuse may result in serious consequences. Scientific and objective assessment of health hazards of medical radiation and establishment of effective protective interventions are of great importance to control the risk of radiation exposure. This article reviews the health hazards and protective measures of medical radiation.

Objective:To explore the association between sibling violence experience and emotional and behavioral problems.Methods:A Multistage stratified cluster sampling was used in Hunan province, 1735 participants from multiple-child family were recruited to survey the prevalence of sibling violence and the occurrence of emotional and behavioral problems with the Strength and Difficulties Questionnaires (SDQ).Results:According to SDQ total score, the rate of abnormal emotion and behavior in children and adolescents involved in sibling violence was higher than that in students who were not experienced sibling violence [45.6％ (236/518) vs.26.8％ (326/1217) ], the rate in bully-victim was higher than that in pure-victim and pure-bully [52.8％ (132/250) vs.37.9％ (74/195) vs.41.1％ (30/73) ].The rates in children and adolescents who were bullied and perpetrated more than 4 sub-types of sibling violence were 63.4％ (53/93) and 76.9％ (60/78).Conclusion:There is an association between sibling violence experience and emotional and behavioral problems among children and adolescents in rural areas.