1.Brain Aperiodic Dynamics
Zhi-Cai HU ; Zhen ZHANG ; Jiang WANG ; Gui-Ping LI ; Shan LIU ; Hai-Tao YU
Progress in Biochemistry and Biophysics 2025;52(1):99-118
Brain’s neural activities encompass both periodic rhythmic oscillations and aperiodic neural fluctuations. Rhythmic oscillations manifest as spectral peaks of neural signals, directly reflecting the synchronized activities of neural populations and closely tied to cognitive and behavioral states. In contrast, aperiodic fluctuations exhibit a power-law decaying spectral trend, revealing the multiscale dynamics of brain neural activity. In recent years, researchers have made notable progress in studying brain aperiodic dynamics. These studies demonstrate that aperiodic activity holds significant physiological relevance, correlating with various physiological states such as external stimuli, drug induction, sleep states, and aging. Aperiodic activity serves as a reflection of the brain’s sensory capacity, consciousness level, and cognitive ability. In clinical research, the aperiodic exponent has emerged as a significant potential biomarker, capable of reflecting the progression and trends of brain diseases while being intricately intertwined with the excitation-inhibition balance of neural system. The physiological mechanisms underlying aperiodic dynamics span multiple neural scales, with activities at the levels of individual neurons, neuronal ensembles, and neural networks collectively influencing the frequency, oscillatory patterns, and spatiotemporal characteristics of aperiodic signals. Aperiodic dynamics currently boasts broad application prospects. It not only provides a novel perspective for investigating brain neural dynamics but also holds immense potential as a neural marker in neuromodulation or brain-computer interface technologies. This paper summarizes methods for extracting characteristic parameters of aperiodic activity, analyzes its physiological relevance and potential as a biomarker in brain diseases, summarizes its physiological mechanisms, and based on these findings, elaborates on the research prospects of aperiodic dynamics.
2.Cross-sectional survey of healthcare-associated infection in 5 736 medical institutions across China in 2024
Cui ZENG ; Wuqiang GAO ; Fu QIAO ; Hui ZHAO ; Xu FANG ; Linping LI ; Xiuwen CHEN ; Jiansen CHEN ; Dan LI ; Yuan ZHOU ; Lingli YU ; Qinglan MENG ; Xia MOU ; Lijuan XIONG ; Weiguang LI ; Ding LIU ; Jiaqing XIAO ; Limei OU ; Baozhen LI ; Jun YIN ; Haojun ZHANG ; Qiang FU ; Qun LU ; Biao WU ; Ya-wei XING ; Shumei SUN ; Shuncai WANG ; Longmin DU ; Jingping ZHANG ; Wen-ying HE ; Gui CHENG ; Nan REN ; Xun HUANG ; Anhua WU
Chinese Journal of Infection Control 2025;24(11):1572-1583
Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27%.The number of HAI episodes was 38 032,and case prevalence rate was 1.38%.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66%to 2.35%.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65%.The most common infection site was the lower respiratory tract(44.66%),followed by the urinary tract(12.94%),surgical site(9.32%),upper respiratory tract(7.02%),and bloodstream infection(5.78%).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02%),department of neurosurgery(5.51%),and department(group)of hematology(5.34%).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10%)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76%),Pseudomonas aeruginosa(13.33%),Escherichia coli(12.79%),Acinetobacter baumannii(9.23%),and Staphylococcus aureus(7.88%).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71%.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18%.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46%.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.
3.Screening Results of Thalassemia and Analysis of Rare Genotypes
Gui-Xiang WANG ; Yang YU ; Xing HE ; Xiao-Hua LIU
Journal of Experimental Hematology 2025;33(6):1714-1719
Objective:To analyze the genotypes and distribution of thalassemia in Xindu District of Chengdu,in order to provide reference for the prevention and treatment of thalassemia in this area.Methods:A total of 3 679 samples screened for thalassemia gene in Xindu District People's Hospital of Chengdu from June 2021 to April 2024 were selected as the study objects.Blood related parameters were detected by blood analyzer,hemoglobin composition was analyzed by capillary electrophoresis,and routine thalassemia gene detection was performed by PCR+flow-through hybridization.For the samples whose hematologic characteristics did not match the conventional results of thalassemia genes,the genotypes were determined by gene sequencing technology and the results were analyzed.Results:Among 3 679 samples,540 carriers were detected,the total detection rate was 14.68%.Among them,329 cases were α-thalassemia,with a total of 8 genotypes.The top 3 genotype in frequency were--SEA/αα(45.29%,149/329),-α3.7/αα(38.91%,128/329),and-α4.2/αα(6.08%,20/329).There were 197 cases of β-thalassemia,with a total of 10 genotypes,and the top 3 genotype in frequency were βCD41-42(-TCTT)/βN(29.95%,59/197),βCD17(A>T)/βN(27.92%,55/197),and βIVSII-654(C>T)/βN(24.87%,49/197).There were 14 cases of αβ-thalassemia,with a total of 12 genotypes,and the main were-α3.7/αα,βIVSII-654(C>T)/βN and-α3.7/αα,βCD41-42(-TCTT)/βN.There was a rare thalassemia genotype(--SEA/HKαα).In addition,three rare abnormal hemoglobin mutations and one unreported abnormal hemoglobin mutation(HBA1:c.300+13C>G site heterozygous mutation)were also found.Conclusion:The detection rate of thalassemia gene in this area is high and the genotype is complex.In gene diagnosis,we should pay attention to the combination of multi-technology detection to avoid missing rare genotypes.
4.Correlation Analysis of Northwest Dryness Syndrome with Pulmonary Tuberculosis in Moyu County,Hetian Prefecture,Xinjiang
Xiu-mei WANG ; Huan LIU ; Yu-cun ZHANG ; GULISHALA·TURSUN ; Hua-gui LI
Progress in Modern Biomedicine 2025;25(11):1788-1798
Objective:To explore the incidence characteristics and correlation analysis of Western dryness syndrome in pulmonary tuberculosis patients in Moyu County,Hetian Prefecture,Xinjiang,and to provide a basis for the prevention and treatment strategies and effectiveness evaluation of pulmonary tuberculosis in Xinjiang.Methods:89 confirmed cases of pulmonary tuberculosis in Moyu County,Hotian Prefecture,Xinjiang from October 2023 to October 2024 were selected as the case group,and 117 healthy individuals matched with the case group in terms of gender,age,and education level in Moyu County,Hotian Prefecture,Xinjiang during the same period were selected as the control group.The general information and incidence of Northwest dryness syndrome between two groups were compared.The incidence and severity of Northwest dryness syndrome in tuberculosis patients,as well as the main and secondary syndrome scores of Northwest dryness syndrome were analyzed.The influencing factors of pulmonary tuberculosis were analyzed.The scores of the main syndrome of Northwest dryness syndrome(lung wei kong pi dryness syndrome)and the concurrent syndrome of Northwest dryness syndrome(heart kidney yin deficiency syndrome,lung heart spleen wind fire dryness syndrome,liver kidney essence blood deficiency syndrome,spleen stomach dampness syndrome,spleen stomach yin deficiency syndrome)between the control group and the case group were compared.The correlation between pulmonary tuberculosis and the on set of Northwest dryness syndrome were analyzed by Spearman rank sum test.Results:There was no significant difference between the control group and the case group in terms of body mass index(BMI),age,education level,gender,etc.(P>0.05).The incidence of Northwest dryness syndrome in the case group was significantly higher than that in the control group(P<0.05).The Northwest Dry Syndrome Scale score in the severe group was higher than that in the mild and moderate groups,and the Northwest Dry Syndrome Scale score in the moderate group was higher than that in the mild group(P<0.05).Among 89 patients with pulmonary tuberculosis,the main syndrome of lung wei kong pi dryness syndrome had the highest number of cases,totaling 42 cases(47.19%).The highest number of concurrent syndromes were heart kidney yin deficiency syndrome,totaling 36 cases(40.45%),followed by spleen stomach yin deficiency syndrome,totaling 35 cases(39.33%).The results showed that suffering from Northwest dryness syndrome was a risk factor for pulmonary tuberculosis(P<0.05).There were significant differences in the scores of the main syndrome of Northwest dryness(Lung Wei Kong Pi dryness syndrome),the concurrent syndrome of Northwest dryness(Lung Heart Spleen Wind Fire dryness syndrome),and the concurrent syndrome of Northwest dryness(Spleen Stomach Yin Deficiency syndrome)between the control group and the case group(P<0.05).There was no significant difference in the scores of Northwest dryness syndrome(liver and kidney essence and blood deficiency syndrome),Northwest dryness syndrome(heart and kidney yin deficiency syndrome),and Northwest dryness syndrome(spleen and stomach dampness syndrome)between the control group and the case group(P>0.05).The score of pulmonary tuberculosis syndrome was positively correlated with various types of Northwest dryness syndrome(P<0.05),and there was a significant correlation at the 0.001 level between pulmonary Wei Kong Pi dryness syndrome,pulmonary heart spleen wind fire dryness syndrome,and spleen stomach dampness syndrome(P<0.05).The correlation between liver and kidney essence and blood deficiency syndrome and spleen and stomach yin deficiency syndrome is significant at the 0.01 level(P<0.05).The correlation between heart and kidney yin deficiency syndrome is significant at the 0.05 level(P<0.05).Conclusion:The northwest dryness syndrome is related to the occurrence of pulmonary tuberculosis in Moyu County,Hotan Prefecture,Xinjiang,and is a risk factor for the occurrence of pulmonary tuberculosis.There is a significant positive correlation between the pulmonary tuberculosis syndrome score and various types of northwest dryness syndrome,among which the lung wei kong pi dryness syndrome,lung heart spleen wind fire dryness syndrome,and spleen stomach dampness syndrome have the most significant impact on the pulmonary nucleus syndrome score.
5.Technical action analysis of the female table tennis player with shoulder impingement syndrome executing forehand topspin
Mengli WEI ; Yaping ZHONG ; Huixian GUI ; Tingting YU ; Shaohua YU ; Guangying WANG
Chinese Journal of Sports Medicine 2025;44(6):442-450
Objective To analyze the technical movement characteristics of female table tennis play-ers with shoulder impingement syndrome when hitting a forehand topspin loop ball,in order to explore the reasons for shoulder impingement syndrome.Methods Thirteen female table tennis athletes with shoulder impingement syndrome were recruited for the shoulder impingement group(age 20.31±2.56 years,height 165.69±4.00 cm,weight 56.62±6.00 kg)and 13 healthy female table tennis athletes(age 21.54±2.78 years,height 165.54±4.45 cm,weight 60.08±8.02 kg)were selected for the healthy group.Kinematic and electromyographic data of the upper limbs were collected during six tri-als of forehand topspin strokes using a three-dimensional motion capture system and a wireless surface electromyographic system.The data were then averaged and compared between the groups.Results The shoulder impingement group had a greater shoulder flexion angular velocity at the end of the forward swing compared to the healthy group(t=-3.689,P=0.001).In addition,the shoulder impingement group showed significantly smaller trunk torsion angular amplitude(t=2.614,P=0.015)and average an-gular velocity of trunk torsion(t=3.958,P=0.001).Furthermore,the peak activation level of the anteri-or serratus muscle was smaller in the shoulder impingement group compared to the healthy group(t=2.363,P=0.027).Finally,the deactivation duration of both the triceps brachii and brachioradialis mus-cles was shorter in the shoulder impingement group compared to the latter(t=3.705,P=0.002;t=3.29,P=0.004).Conclusion Female table tennis players with shoulder impingement syndrome exhibit the fol-lowing characteristics in their forehand topspin:1)insufficient trunk rotation and premature deactiva-tion of the brachioradialis muscle,which lead to excessive loading on the shoulder during flexion;2)inadequate activation of the serratus anterior muscle,resulting in compromised scapular stability;3)premature deactivation of the triceps brachii muscle,which negatively affects the control of eccentric contraction velocity at the shoulder joint.
6.Survey on the current situation of breast reconstruction after breast cancer surgery in 203 hospitals
Yan WANG ; Yuanyuan GUI ; Mo LI ; Jianxin WANG ; Ailing YANG ; Jinbiao YU ; Jianghong ZHOU
Chinese Journal of Plastic Surgery 2025;41(6):599-606
Objective:To investigate the current status of breast reconstruction after breast cancer surgery in hospitals in China.Methods:This study was a cross-sectional study using convenience sampling. A self-designed survey questionnaire was used to investigate nurses of department of breast diseases in China from May to August 2023. The content of the questionnaire included four aspects: identification information, basic hospital information, the implementation situation of breast reconstruction after breast cancer surgery, and the situation of medical and nursing human resources for breast reconstruction, with a total of 39 items. Statistical analysis was performed using SPSS 26.0 software. The non-normally distributed measurement data were expressed as M( Q1, Q3), and the Mann-Whitney U test was used for comparison between groups. Numeric data were expressed as frequency and percentage, and comparisons between groups were made using the χ2-test or Fisher’s exact probability method. P<0.05 indicated that the difference was statistically significant. Results:A total of 212 public hospitals from 31 provinces, autonomous regions and municipalities participated in the survey. Two hundred and three hospitals (95.8%) returned valid data, including 155 Grade Ⅲ Level A hospitals, 19 Grade Ⅲ Level B and C hospitals, and 29 Grade Ⅱ hospitals. There were 157 general hospitals, 32 specialized cancer hospitals, and 14 other hospitals. Thirty-nine hospitals did not perform breast reconstruction surgery. A total of 164 hospitals (80.8%) had already carried out breast reconstruction surgery, among which the proportion of breast reconstruction in Grade Ⅲ Level A hospitals [90.3% (140/155)] was significantly higher than that in Grade Ⅲ Level B and C hospitals [52.6% (10/19)] and Grade Ⅱ hospitals [48.3% (14/29)] ( P<0.01). The proportion of breast reconstruction in specialized cancer hospitals [96.9% (31/32)] was significantly higher than that in general hospitals [79.0% (124/157)] and other types of hospitals [64.3% (9/14)] ( P<0.05). Among the 164 hospitals, 310 (150, 637.5) patients underwent breast cancer surgery and 30 (10, 100) patients underwent breast reconstruction in 2022. The proportion of patients undergoing breast reconstruction surgery among breast cancer surgery patients was 13.3% (4.0%, 20.0%). The number of patients receiving immediate breast reconstruction was 11 (2.5, 46.5) cases, and the number of those receiving delayed breast reconstruction was 5 (0, 18.5) cases. Among 203 hospitals, the median proportions of breast oncoplastic surgeons and specialized nurses among healthcare providers in breast surgery departments were 28.6% (2/7) and 75.0% (12/16), respectively. In comparison of the 164 hospitals offering breast reconstruction surgery and 39 hospitals not, the median numbers of breast oncoplastic surgeons were 3 (1, 8) versus 1 (0, 3), and qualified breast reconstruction nurses were 12 (6, 16) versus 1 (0, 8), respectively. All differences were statistically significant (all P<0.01). Conclusion:About 80% of hospitals in China have offered breast reconstruction procedures after breast cancer surgery, and the proportion of Grade Ⅲ Level A hospitals and specialized cancer hospitals is higher than that of other types of hospitals. The proportion of patients undergoing breast reconstruction after breast cancer surgery is relatively low, and there is a considerable potential of improvements. Breast oncoplastic surgeons and nurses are insufficient, so it is necessary to strengthen the training of specialized medical staff and improve surgical techniques and the level of nursing services simultaneously, so as to improve the quality of life of breast cancer patients.
7.Cation Channel TMEM63A Autonomously Facilitates Oligodendrocyte Differentiation at an Early Stage.
Yue-Ying WANG ; Dan WU ; Yongkun ZHAN ; Fei LI ; Yan-Yu ZANG ; Xiao-Yu TENG ; Linlin ZHANG ; Gui-Fang DUAN ; He WANG ; Rong XU ; Guiquan CHEN ; Yun XU ; Jian-Jun YANG ; Yongguo YU ; Yun Stone SHI
Neuroscience Bulletin 2025;41(4):615-632
Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca2+ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a-/- OPCs in vitro and myelination in Tmem63a-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca2+ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals
;
Cell Differentiation/physiology*
;
Oligodendroglia/metabolism*
;
Mice, Knockout
;
Mice
;
Male
;
Myelin Sheath/metabolism*
;
Humans
;
Child
;
Cells, Cultured
;
Oligodendrocyte Precursor Cells/metabolism*
8.Analysis of The Characteristics of Brain Functional Activity in Gross Motor Tasks in Children With Autism Based on Functional Near-infrared Spectroscopy Technology
Wen-Hao ZONG ; Qi LIANG ; Shi-Yu YANG ; Feng-Jiao WANG ; Meng-Zhao WEI ; Hong LEI ; Gui-Jun DONG ; Ke-Feng LI
Progress in Biochemistry and Biophysics 2025;52(8):2146-2162
ObjectiveBased on functional near-infrared spectroscopy (fNIRS), we investigated the brain activity characteristics of gross motor tasks in children with autism spectrum disorder (ASD) and motor dysfunctions (MDs) to provide a theoretical basis for further understanding the mechanism of MDs in children with ASD and designing targeted intervention programs from a central perspective. MethodsAccording to the inclusion and exclusion criteria, 48 children with ASD accompanied by MDs were recruited into the ASD group and 40 children with typically developing (TD) into the TD group. The fNIRS device was used to collect the information of blood oxygen changes in the cortical motor-related brain regions during single-handed bag throwing and tiptoe walking, and the differences in brain activation and functional connectivity between the two groups of children were analyzed from the perspective of brain activation and functional connectivity. ResultsCompared to the TD group, in the object manipulative motor task (one-handed bag throwing), the ASD group showed significantly reduced activation in both left sensorimotor cortex (SMC) and right secondary visual cortex (V2) (P<0.05), whereas the right pre-motor and supplementary motor cortex (PMC&SMA) had significantly higher activation (P<0.01) and showed bilateral brain region activity; in terms of brain functional integration, there was a significant decrease in the strength of brain functional connectivity (P<0.05) and was mainly associated with dorsolateral prefrontal cortex (DLPFC) and V2. In the body stability motor task (tiptoe walking), the ASD group had significantly higher activation in motor-related brain regions such as the DLPFC, SMC, and PMC&SMA (P<0.05) and showed bilateral brain region activity; in terms of brain functional integration, the ASD group had lower strength of brain functional connectivity (P<0.05) and was mainly associated with PMC&SMA and V2. ConclusionChildren with ASD exhibit abnormal brain functional activity characteristics specific to different gross motor tasks in object manipulative and body stability, reflecting insufficient or excessive compensatory activation of local brain regions and impaired cross-regions integration, which may be a potential reason for the poorer gross motor performance of children with ASD, and meanwhile provides data support for further unraveling the mechanisms underlying the occurrence of MDs in the context of ASD and designing targeted intervention programs from a central perspective.
9.Optimization strategy for anesthesia in modified radical mastectomy for breast cancer:Paravertebral nerve block combined with opioid-free gen-eral anesthesia
Yong-zhi CHEN ; Yu-jiao ZHANG ; Bin SHI ; Gui-juan WANG ; Yuan LI ; Ren-yi CHEN
Chinese Journal of Current Advances in General Surgery 2025;28(2):114-118
Objective:This study aimed to evaluate the application effect of opioid-free anesthesia(OFA)in modified radical mastectomy for breast cancer.Methods:80 patients undergoing unilateral modified radical mastec-tomy were randomly divided into two groups:general anesthesia group(G group)and OFA group(O group).The G group received general anesthesia with opioid drugs and a laryngeal mask,while the O group received general anes-thesia with intravenous lidocaine combined with thoracic paravertebral nerve block and a laryngeal mask.The average arterial pressure(MAP)and heart rate(HR)of the patients were recorded at the time of admission(T0),induction(T1),start of surgery(T2),gland resection(T3),and admission to the recovery room(T4).The surgical time,awakening time,ex-tubation time,and getting out of bed time were recorded.The VAS score at 2 hours(T5),6 hours(T6),and 12 hours(T7)after surgery,as well as the systemic immune-inflammatory index(SII)before surgery(T8),6 hours after surgery(T9),and 12 hours after surgery(T10)were recorded.The occurrence of postoperative nausea and vomiting(PONV)and post-mastectomy pain syndrome(PMPS)were recorded.The occurrence of adverse events such as poor nerve block effect,pneumothorax,hematoma,and local anesthetic toxicity were also recorded.Results:The MAP and HR of the O group were more stable than those of the G group during surgery(P<0.05).The awakening time,extubation time,and getting out of bed time in the O group were earlier than those in the G group(P<0.05).The VAS and SII values after surgery were significantly lower in the O group than in the G group(P<0.05).The incidence of PONV was also signifi-cantly decreased(P<0.05).In addition,no adverse events such as pneumothorax,hematoma,or local anesthetic toxic-ity occurred in the O group.Conclusion:Pioid-free anesthesia is safe and effective in modified radical mastectomy for breast cancer,shortening recovery time,time to first flatus,and time to ambulation,while alleviating postoperative pain,systemic inflammatory response,perioperative hemodynamic fluctuations,and the incidence of postoperative nau-sea and vomiting.
10.Optimizing blood-brain barrier permeability in KRAS inhibitors:A structure-constrained molecular generation approach
Xia SHENG ; Yike GUI ; Jie YU ; Yitian WANG ; Zhenghao LI ; Xiaoya ZHANG ; Yuxin XING ; Yuqing WANG ; Zhaojun LI ; Mingyue ZHENG ; Liquan YANG ; Xutong LI
Journal of Pharmaceutical Analysis 2025;15(8):1848-1859
Kirsten rat sarcoma viral oncogene homolog(KRAS)protein inhibitors are a promising class of thera-peutics,but research on molecules that effectively penetrate the blood-brain barrier(BBB)remains limited,which is crucial for treating central nervous system(CNS)malignancies.Although molecular generation models have recently advanced drug discovery,they often overlook the complexity of bio-logical and chemical factors,leaving room for improvement.In this study,we present a structure-constrained molecular generation workflow designed to optimize lead compounds for both drug effi-cacy and drug absorption properties.Our approach utilizes a variational autoencoder(VAE)generative model integrated with reinforcement learning for multi-objective optimization.This method specifically aims to enhance BBB permeability(BBBp)while maintaining high-affinity substructures of KRAS in-hibitors.To support this,we incorporate a specialized KRAS BBB predictor based on active learning and an affinity predictor employing comparative learning models.Additionally,we introduce two novel metrics,the knowledge-integrated reproduction score(KIRS)and the composite diversity score(CDS),to assess structural performance and biological relevance.Retrospective validation with KRAS inhibitors,AMG510 and MRTX849,demonstrates the framework's effectiveness in optimizing BBBp and highlights its potential for real-world drug development applications.This study provides a robust framework for accelerating the structural enhancement of lead compounds,advancing the drug development process across diverse targets.

Result Analysis
Print
Save
E-mail