Recently,diffusion models have emerged as a promising paradigm for molecular design and optimization.However,most diffusion-based molecular generative models focus on modeling 2D graphs or 3D geom-etries,with limited research on molecular sequence diffusion models.The International Union of Pure and Applied Chemistry(IUPAC)names are more akin to chemical natural language than the simplified molecular input line entry system(SMILES)for organic compounds.In this work,we apply an IUPAC-guided conditional diffusion model to facilitate molecular editing from chemical natural language to chemical language(SMILES)and explore whether the pre-trained generative performance of diffusion models can be transferred to chemical natural language.We propose DiffIUPAC,a controllable molecular editing diffusion model that converts IUPAC names to SMILES strings.Evaluation results demonstrate that our model out-performs existing methods and successfully captures the semantic rules of both chemical languages.Chemical space and scaffold analysis show that the model can generate similar compounds with diverse scaffolds within the specified constraints.Additionally,to illustrate the model's applicability in drug design,we conducted case studies in functional group editing,analogue design and linker design.

BACKGROUND:Paraspinal muscle degeneration is one of the main causative factors of low back pain,and the changes in the paraspinal muscles are closely related to its occurrence and development.At present,clinical practitioners focus on the changes of paraspinal muscles in degenerative lumbar diseases to prevent and treat lumbar diseases,but ignore the connection and related mechanisms between lumbar intervertebral disc degeneration and paraspinal muscles.OBJECTIVE:To comprehensively summarize the interaction between paraspinal muscles and lumbar intervertebral discs,and to review the relationship and mechanisms between lumbar intervertebral disc degeneration and paraspinal muscles,in order to provide a reference for clinical prevention and treatment.METHODS:Chinese keywords"lumbar intervertebral disc,paraspinal muscle,multifidus muscle,low back pain,degeneration,imaging,magnetic resonance imaging"were used to search the relevant literature in Chinese databases such as CNKI,VIP,and WanFang.English keywords"lumbar disc,paraspinal muscle,multifidus muscle,low back pain,degeneration,imaging,MRI"were used to search the relevant literature in databases such as Medline,PubMed,and Web of Science.After preliminary screening of titles and abstracts,68 articles were finally selected for result analysis according to the inclusion and exclusion criteria.RESULTS AND CONCLUSION:(1)Researchers have used various methods to evaluate the degree of paraspinal muscle degeneration,and at the same time evaluated the degree of lumbar intervertebral disc degeneration according to the Pfirrmann grading system.It is found that clinical diagnosis and treatment should pay attention to gender differences,and the influence of factors such as obesity on the degeneration of intervertebral discs and muscles,in order to develop more individualized treatment plans.(2)There is a certain correlation between lumbar intervertebral disc degeneration and paraspinal muscle fat infiltration,but the research results are controversial.Most studies have found that fat infiltration of the paraspinal muscles(especially the multifidus muscle)is positively correlated with the degree of lumbar intervertebral disc degeneration.(3)It is currently believed that the three mechanisms of disuse atrophy,denervation,and inflammatory factors may interact with each other to jointly lead to structural and functional changes in the paraspinal muscles,which are closely related to the occurrence of lumbar intervertebral disc degeneration and low back pain.(4)Clinically,attention should be paid to the changes of the muscles at the level below the affected nerve root segment,which is helpful for the diagnosis and localization of lumbar radiculopathy.At the same time,inhibition of inflammatory factors may become a potential target for treatment.(5)Clinically,the first step is to correct nerve root compression through appropriate medication or surgery to control inflammatory reactions and nerve root pain,and then carry out targeted muscle rehabilitation training.If necessary,consider using new treatment methods such as interferential current electrical stimulation to improve the patient's symptoms and prognosis.

Recently, diffusion models have emerged as a promising paradigm for molecular design and optimization. However, most diffusion-based molecular generative models focus on modeling 2D graphs or 3D geometries, with limited research on molecular sequence diffusion models. The International Union of Pure and Applied Chemistry (IUPAC) names are more akin to chemical natural language than the Simplified Molecular Input Line Entry System (SMILES) for organic compounds. In this work, we apply an IUPAC-guided conditional diffusion model to facilitate molecular editing from chemical natural language to chemical language (SMILES) and explore whether the pre-trained generative performance of diffusion models can be transferred to chemical natural language. We propose DiffIUPAC, a controllable molecular editing diffusion model that converts IUPAC names to SMILES strings. Evaluation results demonstrate that our model outperforms existing methods and successfully captures the semantic rules of both chemical languages. Chemical space and scaffold analysis show that the model can generate similar compounds with diverse scaffolds within the specified constraints. Additionally, to illustrate the model's applicability in drug design, we conducted case studies in functional group editing, analogue design and linker design.

BACKGROUND:Paraspinal muscle degeneration is one of the main causative factors of low back pain,and the changes in the paraspinal muscles are closely related to its occurrence and development.At present,clinical practitioners focus on the changes of paraspinal muscles in degenerative lumbar diseases to prevent and treat lumbar diseases,but ignore the connection and related mechanisms between lumbar intervertebral disc degeneration and paraspinal muscles.OBJECTIVE:To comprehensively summarize the interaction between paraspinal muscles and lumbar intervertebral discs,and to review the relationship and mechanisms between lumbar intervertebral disc degeneration and paraspinal muscles,in order to provide a reference for clinical prevention and treatment.METHODS:Chinese keywords"lumbar intervertebral disc,paraspinal muscle,multifidus muscle,low back pain,degeneration,imaging,magnetic resonance imaging"were used to search the relevant literature in Chinese databases such as CNKI,VIP,and WanFang.English keywords"lumbar disc,paraspinal muscle,multifidus muscle,low back pain,degeneration,imaging,MRI"were used to search the relevant literature in databases such as Medline,PubMed,and Web of Science.After preliminary screening of titles and abstracts,68 articles were finally selected for result analysis according to the inclusion and exclusion criteria.RESULTS AND CONCLUSION:(1)Researchers have used various methods to evaluate the degree of paraspinal muscle degeneration,and at the same time evaluated the degree of lumbar intervertebral disc degeneration according to the Pfirrmann grading system.It is found that clinical diagnosis and treatment should pay attention to gender differences,and the influence of factors such as obesity on the degeneration of intervertebral discs and muscles,in order to develop more individualized treatment plans.(2)There is a certain correlation between lumbar intervertebral disc degeneration and paraspinal muscle fat infiltration,but the research results are controversial.Most studies have found that fat infiltration of the paraspinal muscles(especially the multifidus muscle)is positively correlated with the degree of lumbar intervertebral disc degeneration.(3)It is currently believed that the three mechanisms of disuse atrophy,denervation,and inflammatory factors may interact with each other to jointly lead to structural and functional changes in the paraspinal muscles,which are closely related to the occurrence of lumbar intervertebral disc degeneration and low back pain.(4)Clinically,attention should be paid to the changes of the muscles at the level below the affected nerve root segment,which is helpful for the diagnosis and localization of lumbar radiculopathy.At the same time,inhibition of inflammatory factors may become a potential target for treatment.(5)Clinically,the first step is to correct nerve root compression through appropriate medication or surgery to control inflammatory reactions and nerve root pain,and then carry out targeted muscle rehabilitation training.If necessary,consider using new treatment methods such as interferential current electrical stimulation to improve the patient's symptoms and prognosis.