1.SITA:Predicting site-specific immunogenicity for therapeutic antibodies
Yewei CUN ; Hao DING ; Tiantian MAO ; Yuan WANG ; Caicui WANG ; Jiajun LI ; Zihao LI ; Mengdie HU ; Zhiwei CAO ; Tianyi QIU
Journal of Pharmaceutical Analysis 2025;15(6):1378-1389
Antibody humanization is critical to reduce immunogenicity and enhance efficacy in the preclinical phase of the development of therapeutic antibodies originated from animal models.Computational suggestions have long been desired,but available tools focused on immunogenicity calculation of whole antibody sequences and sequence segments,missing the individual residue sites.This study introduces Site-specific Immunogenicity for Therapeutic Antibody(SITA),a novel computational framework that predicts B-cell immunogenicity score for not only the overall antibody,but also individual residues,based on a comprehensive set of amino acid descriptors characterizing physicochemical and spatial features for antibody structures.A transfer-learning-inspired framework was purposely adopted to overcome the scarcity of Antibody-Antibody structural complexes.On an independent testing dataset derived from 13 Antibody-Antibody structural complexes,SITA successfully predicted the epitope sites for Antibody-Antibody structures with a receiver operating characteristic(ROC)-area unver the ROC curve(AUC)of 0.85 and a precision-recall(PR)-AUC of 0.305 at the residue level.Furthermore,the SITA score can significantly distinguish immunogenicity levels of whole human antibodies,therapeutic antibodies and non-human-derived antibodies.More importantly,analysis of an additional 25 thera-peutic antibodies revealed that over 70%of them were detected with decreased immunogenicity after modification compared to their parent variants.Among these,nearly 66%antibodies successfully iden-tified actual modification sites from the top five sites with the highest SITA scores,suggesting the ability of SITA scores for guide the humanization of antibody.Overall,these findings highlight the potential of SITA in optimizing immunogenicity assessments during the process of therapeutic antibody design.
2.Sleep disorders in patients with brain tumors
Qiang LIANG ; Tianyi HU ; Tong YANG ; Qiang LI
Chinese Journal of Nervous and Mental Diseases 2025;51(5):314-320,封3
Patients with brain tumors frequently experience comorbid sleep disorders,which can impair daytime functioning and significantly impact patient quality of life and prognosis.The clinical manifestations of sleep disorders in brain tumor patients are primarily characterized by insomnia and excessive daytime sleepiness.The underlying mechanisms remain unclear and are likely influenced by multiple factors,including tumor location and type,neurotransmitter abnormalities,and emotional disorders.Both non-pharmacological interventions such as cognitive behavioral therapy and individualized pharmacological treatments can effectively alleviate sleep disorders in brain tumor patients.Moderate exercise may further improve sleep symptoms and long-term outcomes.The current review summarizes and discuss advanced findings regarding clinical manifestations,risk factors,assessment tools,and intervention strategies for sleep disorders comorbid with brain tumors,aiming to enhance clinical understanding and provide references for early identification and management of this comorbidity.
3.Rho/ROCK signaling pathway and its regulatory effects on viral replication and cell tight junctions
Shiqi SHAN ; Simin WANG ; Yuheng LI ; Qian WENG ; Tianyi YIN ; Zhihua PEI ; Kai WANG ; Guixue HU
Chinese Journal of Veterinary Science 2025;45(6):1322-1328
Rho proteins and the Rho-associated protein kinase(ROCK)signaling pathway are cruci-al components of intracellular signaling cascades.Rho proteins,which belong to the small GTPase family,play a pivotal role in regulating essential elements of the cytoskeleton within cells.ROCK functions as a downstream effector protein kinase of Rho,modulating various biological processes,including cell morphology,migration,and proliferation.Recent studies have underscored the signifi-cance of the ROCK signaling pathway in the replication of a diverse group of viruses.Furthermore,it has been discovered that some viruses disrupt cellular contraction,adhesion,and migration through the Rho/ROCK pathway,subsequently influencing the immune response triggered by vi-ral infections and affecting the tight junctions between cells.This article primarily reviews the re-search progress regarding the Rho/ROCK signaling pathway and its key signaling molecules,Rho and ROCK,in terms of their activation and regulation of viral replication and tight junction pro-teins between cells.
4.SITA: Predicting site-specific immunogenicity for therapeutic antibodies.
Yewei CUN ; Hao DING ; Tiantian MAO ; Yuan WANG ; Caicui WANG ; Jiajun LI ; Zihao LI ; Mengdie HU ; Zhiwei CAO ; Tianyi QIU
Journal of Pharmaceutical Analysis 2025;15(6):101316-101316
Antibody (Ab) humanization is critical to reduce immunogenicity and enhance efficacy in the preclinical phase of the development of therapeutic Abs originated from animal models. Computational suggestions have long been desired, but available tools focused on immunogenicity calculation of whole Ab sequences and sequence segments, missing the individual residue sites. This study introduces Site-specific Immunogenicity for Therapeutic Antibody (SITA), a novel computational framework that predicts B-cell immunogenicity score for not only the overall antibody, but also individual residues, based on a comprehensive set of amino acid descriptors characterizing physicochemical and spatial features for antibody structures. A transfer-learning-inspired framework was purposely adopted to overcome the scarcity of Ab-Ab structural complexes. On an independent testing dataset derived from 13 Ab-Ab structural complexes, SITA successfully predicted the epitope sites for Ab-Ab structures with a receiver operating characteristic (ROC)-area unver the ROC curve (AUC) of 0.85 and a precision-recall (PR)-AUC of 0.305 at the residue level. Furthermore, the SITA score can significantly distinguish immunogenicity levels of whole human Abs, therapeutic Abs and non-human-derived Abs. More importantly, analysis of an additional 25 therapeutic Abs revealed that over 70% of them were detected with decreased immunogenicity after modification compared to their parent variants. Among these, nearly 66% Abs successfully identified actual modification sites from the top five sites with the highest SITA scores, suggesting the ability of SITA scores for guide the humanization of antibody. Overall, these findings highlight the potential of SITA in optimizing immunogenicity assessments during the process of therapeutic antibody design.
5.The chain mediating role of rejection sensitivity and adaptability between maternal rejection and internet addiction in college students
Mianli ZHAO ; Yuecui KAN ; Tianyi BU ; Jiawei ZHOU ; Xiaomeng HU ; Kexin QIAO ; Xuan LIU ; Yanjie YANG
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(5):459-464
Objective:To explore the relationship between maternal rejection and internet addiction in college students, as well as the chain mediating role of rejection sensitivity and adaptability.Methods:From March to May 2024, a total of 1 119 college students were surveyed using the short-form Egna Minnen av Barndoms Uppforstran for Chinese(s-EMBU-C), internet addiction test(IAT), rejection sensitivity questionnaire(RSQ), and the China college student adjustment scale(CCSAS).SPSS 26.0 statistical software was used for independent sample t-test, one-way ANOVA, Pearson product moment correlation, and multiple linear regression analysis, and PROCESS 4.0 macro program was used for chain mediation analysis. Results:(1)Maternal rejection (11.19±2.97) was positively correlated with internet addiction (44.89±9.74)( r=0.60, P<0.01) and rejection sensitivity (102.93±55.63)( r=0.63, P<0.01), while negatively correlated with adaptability (200.19±14.18)( r=-0.56, P<0.01) among college students. Rejection sensitivity was positively correlated with internet addiction ( r=0.75, P<0.01) and negatively correlated with adaptability ( r=-0.76, P<0.01). Adaptability was negatively correlated with internet addiction ( r=-0.68, P<0.01). (2)Maternal rejection had a significant direct effect on internet addiction among college students (effect value=0.193, 95% CI=0.145-0.241), accounting for 32.06%(0.193/0.602) of the total effect. Rejection sensitivity mediated the relationship between maternal rejection and internet addiction (effect value=0.290, 95% CI=0.232-0.357), accounting for 48.17%(0.290/0.602) of the total effect. Adaptability also mediated this relationship (effect value=0.028, 95% CI=0.009-0.053), accounting for 4.65%(0.028/0.602) of the total effect. Additionally, there was a chain mediation effect of rejection sensitivity and adaptability on the relationship between maternal rejection and internet addiction (effect value=0.091, 95% CI=0.052-0.130), accounting for 15.12%(0.091/0.602) of the total effect. Conclusion:Maternal rejection can directly influence internet addiction in college students, and it can also indirectly influence internet addiction through the independent mediating effects of rejection sensitivity and adaptability, as well as through the chain mediating effects of both rejection sensitivity and adaptability.
6.Perceived stress and ego depletion of college students: the mediating role of emotional eating and the moderating role of peer relationship
Siyu WEI ; Yuecui KAN ; Tianyi BU ; Xiaomeng HU ; Kexin QIAO ; Xuan LIU ; Zirui LI ; Yanjie YANG
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(4):357-362
Objective:To explore the effects of perceived stress on ego depletion of college students, as well as the mediating role of emotional eating and the moderating role of peer relationship.Methods:A cross-sectional survey of 1 088 college students was conducted using the perceived stress scale, the Dutch eating behavior questionnaire, the self-control resource depletion scale, and the peer relationship measurement from December 2023 to April 2024.PROCESS Macro program in SPSS 25.0 software was used to test the mediating effect of emotional eating and the moderating effect of peer relationship.Results:(1)The score of perceived stress, emotional eating, peer relationship and ego depletion were 39.26±8.35, 39.19±12.15, 2.00(1.00), and 18.19±7.15, respectively.(2)Perceived stress was positively correlated with emotional eating, ego depletion, and peer relationship( r=0.36, 0.61, 0.25, all P<0.01). Emotional eating was positively correlated with ego depletion and peer relationship( r=0.40, 0.19, both P<0.01). And ego depletion was positively correlated with peer relationship( r=0.23, P<0.01).(3)Emotional eating played a partial mediating role in the effect of perceived stress on ego depletion( β=0.077, 95% CI=0.053-0.104), and the mediating effect accounted for 12.38%(0.077/0.622) of the total effect.(4)Peer relationship played a moderating role between perceived stress and emotional eating. Under low peer relationship, perceived stress had a significant positive predictive effect on emotional eating( βsimple=0.46, P<0.01), and under high peer relationship, the predictive effect of perceived stress on emotional eating was significantly weaker( βsimple=0.26, P<0.01). Conclusions:Perceived stress not only directly affects ego depletion, but also indirectly affects ego depletion through emotional eating in college students.High levels of peer relationship can weaken the impact of perceived stress and high emotional eating on ego depletion.
7.A hemolytic protection method for extracting DNA from Plasmodium dried blood spots
Jiahuan HU ; Tianyi HUANG ; Yuting HUANG
Chinese Journal of Endemiology 2025;44(1):61-65
Objective:To study and evaluate the efficacy of hemolytic protection method for extracting DNA from Plasmodium dried blood spots (DBS). Methods:Centrifugal column method, resin method, and hemolytic protection method were used, respectively, to extract DNA from the same batch of DBS (1.0, 10.0, 100.0, 1 000.0, 10 000.0 parasites/μl blood) that were prepared and preserved according to unified standards. Dilute DNA extracted from 1.0 parasites/μl blood DBS by 10 times to prepare 0.1 parasites/μl blood template DNA. Nested PCR was used to detect templates prepared by the three different methods (with template DNA of ≥1.0 parasites/μl blood DBS repeated 3 times). The limit of detection (LOD) and detection rate were compared by repeating the detection of 0.1 parasites/μl blood template DNA for 30 times. The ultra-micro ultraviolet spectrophotometer was used to measure the concentration and purity of DNA extracted from DBS (10.0, 100.0, and 1 000.0 parasites/μl blood), three times each, and the DNA recovery amount was calculated. Meanwhile, the applicability and cost of different methods were analyzed.Results:The nested PCR detection rate of the template DNA of ≥1.0 parasite/μl blood DBS extracted by the three methods was all 3/3. For the 0.1 parasite/μl blood template DNA, the nested PCR detection rates were 0 (0/30), 73.33% (22/30), and 100% (30/30), respectively, and there was a significant difference (χ 2 = 65.95, P < 0.001). The LOD was 1.0, 0.1, 0.1 parasite/μl blood, respectively. When comparing the DNA concentration, purity, and recovery amount extracted by the 3 methods, all showed significant differences ( H = 23.25, 17.50, 23.25, P < 0.001). The centrifugal column method has 9 steps, an extraction time of 2.5 h, and the cost for each sample was 33.32 yuan. The resin method has 7 steps, an extraction time of 20.0 h, and the cost for each sample was 7.11 yuan. The hemolytic protection method has 4 steps, an extraction time of 1.0 h, and the cost for each sample was 1.96 yuan. Conclusion:Hemolytic protection method is an efficient, sensitive, rapid, and economical method for extracting DNA from Plasmodium DBS.
8.The chain mediating role of rejection sensitivity and adaptability between maternal rejection and internet addiction in college students
Mianli ZHAO ; Yuecui KAN ; Tianyi BU ; Jiawei ZHOU ; Xiaomeng HU ; Kexin QIAO ; Xuan LIU ; Yanjie YANG
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(5):459-464
Objective:To explore the relationship between maternal rejection and internet addiction in college students, as well as the chain mediating role of rejection sensitivity and adaptability.Methods:From March to May 2024, a total of 1 119 college students were surveyed using the short-form Egna Minnen av Barndoms Uppforstran for Chinese(s-EMBU-C), internet addiction test(IAT), rejection sensitivity questionnaire(RSQ), and the China college student adjustment scale(CCSAS).SPSS 26.0 statistical software was used for independent sample t-test, one-way ANOVA, Pearson product moment correlation, and multiple linear regression analysis, and PROCESS 4.0 macro program was used for chain mediation analysis. Results:(1)Maternal rejection (11.19±2.97) was positively correlated with internet addiction (44.89±9.74)( r=0.60, P<0.01) and rejection sensitivity (102.93±55.63)( r=0.63, P<0.01), while negatively correlated with adaptability (200.19±14.18)( r=-0.56, P<0.01) among college students. Rejection sensitivity was positively correlated with internet addiction ( r=0.75, P<0.01) and negatively correlated with adaptability ( r=-0.76, P<0.01). Adaptability was negatively correlated with internet addiction ( r=-0.68, P<0.01). (2)Maternal rejection had a significant direct effect on internet addiction among college students (effect value=0.193, 95% CI=0.145-0.241), accounting for 32.06%(0.193/0.602) of the total effect. Rejection sensitivity mediated the relationship between maternal rejection and internet addiction (effect value=0.290, 95% CI=0.232-0.357), accounting for 48.17%(0.290/0.602) of the total effect. Adaptability also mediated this relationship (effect value=0.028, 95% CI=0.009-0.053), accounting for 4.65%(0.028/0.602) of the total effect. Additionally, there was a chain mediation effect of rejection sensitivity and adaptability on the relationship between maternal rejection and internet addiction (effect value=0.091, 95% CI=0.052-0.130), accounting for 15.12%(0.091/0.602) of the total effect. Conclusion:Maternal rejection can directly influence internet addiction in college students, and it can also indirectly influence internet addiction through the independent mediating effects of rejection sensitivity and adaptability, as well as through the chain mediating effects of both rejection sensitivity and adaptability.
9.Perceived stress and ego depletion of college students: the mediating role of emotional eating and the moderating role of peer relationship
Siyu WEI ; Yuecui KAN ; Tianyi BU ; Xiaomeng HU ; Kexin QIAO ; Xuan LIU ; Zirui LI ; Yanjie YANG
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(4):357-362
Objective:To explore the effects of perceived stress on ego depletion of college students, as well as the mediating role of emotional eating and the moderating role of peer relationship.Methods:A cross-sectional survey of 1 088 college students was conducted using the perceived stress scale, the Dutch eating behavior questionnaire, the self-control resource depletion scale, and the peer relationship measurement from December 2023 to April 2024.PROCESS Macro program in SPSS 25.0 software was used to test the mediating effect of emotional eating and the moderating effect of peer relationship.Results:(1)The score of perceived stress, emotional eating, peer relationship and ego depletion were 39.26±8.35, 39.19±12.15, 2.00(1.00), and 18.19±7.15, respectively.(2)Perceived stress was positively correlated with emotional eating, ego depletion, and peer relationship( r=0.36, 0.61, 0.25, all P<0.01). Emotional eating was positively correlated with ego depletion and peer relationship( r=0.40, 0.19, both P<0.01). And ego depletion was positively correlated with peer relationship( r=0.23, P<0.01).(3)Emotional eating played a partial mediating role in the effect of perceived stress on ego depletion( β=0.077, 95% CI=0.053-0.104), and the mediating effect accounted for 12.38%(0.077/0.622) of the total effect.(4)Peer relationship played a moderating role between perceived stress and emotional eating. Under low peer relationship, perceived stress had a significant positive predictive effect on emotional eating( βsimple=0.46, P<0.01), and under high peer relationship, the predictive effect of perceived stress on emotional eating was significantly weaker( βsimple=0.26, P<0.01). Conclusions:Perceived stress not only directly affects ego depletion, but also indirectly affects ego depletion through emotional eating in college students.High levels of peer relationship can weaken the impact of perceived stress and high emotional eating on ego depletion.
10.Rho/ROCK signaling pathway and its regulatory effects on viral replication and cell tight junctions
Shiqi SHAN ; Simin WANG ; Yuheng LI ; Qian WENG ; Tianyi YIN ; Zhihua PEI ; Kai WANG ; Guixue HU
Chinese Journal of Veterinary Science 2025;45(6):1322-1328
Rho proteins and the Rho-associated protein kinase(ROCK)signaling pathway are cruci-al components of intracellular signaling cascades.Rho proteins,which belong to the small GTPase family,play a pivotal role in regulating essential elements of the cytoskeleton within cells.ROCK functions as a downstream effector protein kinase of Rho,modulating various biological processes,including cell morphology,migration,and proliferation.Recent studies have underscored the signifi-cance of the ROCK signaling pathway in the replication of a diverse group of viruses.Furthermore,it has been discovered that some viruses disrupt cellular contraction,adhesion,and migration through the Rho/ROCK pathway,subsequently influencing the immune response triggered by vi-ral infections and affecting the tight junctions between cells.This article primarily reviews the re-search progress regarding the Rho/ROCK signaling pathway and its key signaling molecules,Rho and ROCK,in terms of their activation and regulation of viral replication and tight junction pro-teins between cells.

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