Serine/arginine-rich splicing factor 7 (SRSF7), a known splicing factor, has been revealed to play oncogenic roles in multiple cancers. However, the mechanisms underlying its oncogenic roles have not been well addressed. Here, based on N⁶-methyladenosine (m⁶A) co-methylation network analysis across diverse cell lines, we find that the gene expression of SRSF7 is positively correlated with glioblastoma (GBM) cell-specific m⁶A methylation. We then indicate that SRSF7 is a novel m⁶A regulator, which specifically facilitates the m⁶A methylation near its binding sites on the mRNAs involved in cell proliferation and migration, through recruiting the methyltransferase complex. Moreover, SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m⁶A methyltransferase. The two m⁶A sites on the mRNA for PDZ-binding kinase (PBK) are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Together, our discovery reveals a novel role of SRSF7 in regulating m⁶A and validates the presence and functional importance of temporal- and spatial-specific regulation of m⁶A mediated by RNA-binding proteins (RBPs).
Humans ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glioblastoma/genetics* ; Methyltransferases/metabolism* ; RNA Splicing Factors/metabolism* ; RNA, Messenger/genetics* ; RNA-Binding Proteins/metabolism* ; Serine-Arginine Splicing Factors/metabolism* ; RNA Methylation/genetics*

Objective To investigate the association between bicuspid aortic valve ( BAV ) morphologic findings ( raphe vs nonraphe) ,the degree of valve dysfunction and prognosis . Methods Clinical and echocardiographic data in 317 BAV patients were analyzed retrospectively . According to the Sievers classification ,the morphologic BAV findings were categorized into no raphe ( type 0) ,one raphe ( type 1) and two raphes ( type 2 ) . T he patients with type 1 were further divided into three subtypes ,including R‐L subtype ( fusion of the left and right coronary cusps ) ,R‐N subtype ( fusion of the right and noncoronary cusps) and L‐N subtype ( fusion of the left and noncoronary cusps ) . Results Of the 317 patients ,there were 83 ( 26 .2% ) of type 0 ,232 ( 73 .2% ) of type 1 and 2 ( 0 .6% ) of type 2 .Among the 232 patients of type 1 ,there were 126 ( 54 .3% ) of R‐L subtype ,88 ( 37 .9% ) of R‐N subtype and 18 ( 7 .8% ) of L‐N subtype . BAV with raphe had a significantly higher prevalence of aortic valve calcification [ 120 ( 51 .3% ) vs 19 ( 22 .9% ) , P ＜ 0 .001 ] ,with significantly higher frequencies of aortic stenosis [ 164 ( 70 .1% ) vs 6 ( 7 .2% ) , P＜ 0 .001 ] ,aortic regurgitation [ 168 ( 71 .8% ) vs 40 ( 48 .2% ) , P ＝ 0 .001 ] ,increased left ventricular mass[ ( 253 .4 ± 113 .7) g vs ( 176 .4 ± 69 .3) g , P ＜0 .001] and left heart failure [ 34 ( 14 .5% ) vs 3 ( 3 .6% ) , P ＝0 .009] . Furthermore ,the dilation of aortic root and ascending aorta in BAV patients with raphe were significantly higher than those without raphe ( P ＜0 .01 ) ,however ,ascending aortic aneurysm rates were not significant between BAV with and without raphe[ 23( 9 .8% ) vs 4( 4 .8% ) , P ＝0 .251] . T he patients in R‐N subtype had a significantly higher proportion of aortic valve calcification than those in R‐L and L‐N subtype [ 55 ( 62 .5% ) vs 57 ( 45 .2% ) vs 6 ( 33 .3% ) , P ＝ 0 .01 ] ,with a significantly higher frequency of severe aortic stenosis [ 50 ( 56 .8% ) vs 21 ( 16 .7% ) vs 3 ( 16 .7% ) , P ＜0 .001 ] . However , there was no significant difference among different subtypes in other complications( P ＞0 .05).Conclusions T he presence of raphe is associated with a higher frequency of significant aortic valve calcification ,aortic valve dysfunction ,and increases left ventricular mass and left heart failure .T he R‐N type is also associated with aortic valve calcification and severe aortic stenosis .

Objective To evaluate the accuracy and value of automatically assessing left ventricular systolic function in rats with myocardial infarction ( MI) by myocardial contrast echocardiography ( MCE) based on neutrosophic similarity score( NSS) algorithm. Methods According to different infarction size (IS),SD rats were divided into large MI (MI-L,IS≥15% ) and small MI (MI-S,IS＜15% ) groups. MCE was performed before MI and at 7,28 days after MI. In vitro study:the automatic segmentation of the endocardial contour based on neutrosophic similarity score algorithm was compared with the manual segmentation boundary. In vivo study:the left ventricular ejection fraction( LVEF) were calculated using the NSS system,biplane Simpson and PV-loop,respectively,and then NSS-LVEF,Simpson-LVEF and PV-LVEF were acquired,respectively. The IS was calculated by Masson and HE staining. The consistency between the two LVEFs was evaluated by Bland-Altman. The intraclass correlation coefficient ( ICC) was calculated to evaluate the reproducibility of MCE analysis system. Results ① The endocardial contour obtained by automatic segmentation had good agreement with the boundary of artificial tracing. ② There was no significant difference among the three LVEFs in same group ( F ＝0.028, P ＝ 0.973),but there was significant difference in different group ( F ＝78.61, P ＜0.01). NSS-LVEF was well consistent with both Simpson-LVEF and PV-LVEF. ③ The ICC of NSS algorithm for inter-observer and intra-observer were 0.96 and 0.98,respectively. ④Compared with before MI and at 7 days after MI,the LVEF in MI-L and MI-S groups at 28 days after MI decreased significantly ( P ＜0.05),especially in MI-L group ( P ＜0.01). There was significantly negative correlation between LVEF and IS ( r ＝ －0.917, P ＜ 0.01). Conclusions Left ventricular endocardium can be identificated automatically and LVEF can be calculated rapidly and accurately by MCE based on neutrosophic similarity score algorithm in rats with myocardial infarction.

Objective: To investigate the methods for qualitative pathological assessment of dynamic changes in liver fibrosis/cirrhosis after antiviral therapy in patients with chronic hepatitis B (CHB), since antiviral therapy can partially reverse liver fibrosis and cirrhosis caused by hepatitis B and semi-quantitative, rather than qualitative, pathological assessment is often used for the research on liver fibrosis regression. Methods: Previously untreated CHB patients with liver fibrosis and cirrhosis were enrolled, and liver biopsy was performed before treatment and at 78 weeks after the antiviral therapy based on entecavir. The follow-up assessment was performed once every half a year. Based on the proportion of different types of fibrous septum, we put forward the new qualitative criteria called P-I-R classification (predominantly progressive, predominantly regressive, and indeterminate) for evaluating dynamic changes in liver fibrosis. This classification or Ishak fibrosis stage was used to evaluate the change in liver fibrosis after treatment and Ishak liver inflammation score was used to evaluate the change in liver inflammation after treatment. Results: A total of 112 CHB patients who underwent liver biopsy before and after treatment were enrolled, and among these patients, 71 with an Ishak stage of ≥3 and qualified results of live biopsy were included in the final analysis. Based on the P-I-R classification, 58% (41/71) were classified as predominantly progressive, 29% (21/71) were classified as indeterminate, and 13% (9/71) were classified as predominantly regressive; there were no significant differences between the three groups in alanine aminotransferase, aspartate aminotransferase, albumin, HBeAg positive rate, HBV DNA, and liver stiffness (P < 0.05). After treatment, the proportion of predominantly progressive, indeterminate, or predominantly regressive patients changed to 11% (8/71), 11% (8/71), and 78% (55/71), respectively. Among the 35 patients who had no change in Ishak stage after treatment, 72% (25/35) were classified as predominantly regressive and had certain reductions in the Laennec score, percentage of collagen area, and liver stiffness. Conclusion This new P-I-R classification can be used to assess the dynamic changes in liver fibrosis after antiviral therapy in CHB patients.

Objective To explore the application value of quantitative analysis of tissue diffusion by ultrasound elastography in evaluating the evolution of achilles tendinopathy and indirectly reflecting the feature of tendon biomechanics.Methods Rabbits underwent 0.1 ml (group M) or 0.3 ml (group S)collagenase or 0.2 ml saline (group C) injection.The percentage of area displaying blue (％AREA) in the area of interest was measured by the diffusion quantitative technique of ultrasound elastography at baseline and 1,3,7 and 14 days after model.The achilles tendon was obtained for pathological examination to observe the changes of collagen fibers and tested to measure the maximum tensile load by the universal testing machine.Results (1) The ％AREAs in group M and S at 1,3,7 and 14 days after model were smaller than those in group C (P ＜0.05),and reached its lowest value at 3 days after model.％ AREA in groupSwas significant lower than that in group M at 3 or 7 days after model (P ＜0.05).(2) The maximum tensile loads in group M at 1,3 and 7 days after model were smaller than those in group C (P ＜0.05),but there was no significant difference between group M and C at 14 days after model (P ＞0.05).The maximum tensile load in group S was significant lower than those in group M and C after model (P ＜0.05),and arrived its lowest point at 3 days after model.(3) The ％AREA was positively associated with the maximum tensile load of achilles tendon (r =0.87,P ＜0.001).Conclusions Ultrasound elastography can dynamically monitor the evolution of achilles tendinopathy and reflect the biomechanical state of achilles tendon.

Myasthenia gravis is autoimmune diseases which mediated with acetylcholine receptor antibody.Based on the studies in rencent years,treatment of MG has made great progress.Thisreview will discuss several aspects,such as immune tolerance induced by dendritic cells,blocking monoclonal antibodies,hematopoietic stem cell transplantion,and provide new ideas and methods for the treatment of myasthenia gravis.