In the pharmaceutical field,machine learning can play an important role in drug development,production and treatment.Co-crystallization techniques have shown promising potential to enhance the properties of active pha...In the pharmaceutical field,machine learning can play an important role in drug development,production and treatment.Co-crystallization techniques have shown promising potential to enhance the properties of active pharmaceutical ingredients(APIs)such as solubility,permeability,and bioavailability,all without altering their chemical structure.This approach opens new avenues for developing natural products into effective drugs,especially those previously challenging in formulation.Emodin,an anthraquinone-based natural product,is a notable example due to its diverse biological activities;however,its physicochemical limitations,such as poor solubility and easy sublimation,restricted its clinical application.While various methods have improved emodin's physicochemical properties,research on its bioavailability remains limited.In our study,we summarize cocrystals and salts produced through co-crystallization technology and identify piperazine as a favorable coformer.Conflicting conclusions from computational chemistry and molecular modeling method and machine learning method regarding the formation of an emodin-piperazine cocrystal or salt led us to experimentally validate these possibilities.Ultimately,we successfully obtained the emodin-piperazine cocrystal,which were characterized and evaluated by several in vitro methods and pharmacokinetic studies.In addition,experiments have shown that emodin has a certain therapeutic effect on sepsis,so we also evaluated emodin-piperazine biological activity in a sepsis model.The results demonstrate that co-crystallization significantly enhances emodin's solubility,permeability,and bioavailability.Pharmacodynamic studies indicate that the emodin-piperazine cocrystal improves sepsis symptoms and provides protective effects against liver and kidney damage associated with sepsis.This study offers renewed hope for natural products with broad biological activities yet hindered by physicochemical limitations by advancing co-crystallization as a viable development approach.展开更多
The electric catfish(Malapterurus electricus),belonging to the family Malapteruridae,order Siluriformes(Actinopterygii:Ostariophysi),is one of the six branches that has independently evolved electrical organs.We assem...The electric catfish(Malapterurus electricus),belonging to the family Malapteruridae,order Siluriformes(Actinopterygii:Ostariophysi),is one of the six branches that has independently evolved electrical organs.We assembled a 796.75 Mb M.electricus genome and anchored 88.72%sequences into 28 chromosomes.Gene family analysis revealed 295 expanded gene families that were enriched on functions related to glutamate receptors.Convergent evolutionary analyses of electric organs among different lineage of electric fishes further revealed that the coding gene of rho guanine nucleotide exchange factor 4-like(arhgef4),which is associated with G-protein coupled receptor(GPCR)signaling pathway,underwent adaptive parallel evolution.Gene identification suggests visual degradation in catfishes,and an important role for taste in environmental adaptation.Our findings fill in the genomic data for a branch of electric fish and provide a relevant genetic basis for the adaptive evolution of Siluriformes.展开更多
The remarkable morphological diversity and species abundance of teleost fishes offer a valuable resource for understanding vertebrate evolution.In phase I of the Fish10K project,genomes of 110 teleost species were seq...The remarkable morphological diversity and species abundance of teleost fishes offer a valuable resource for understanding vertebrate evolution.In phase I of the Fish10K project,genomes of 110 teleost species were sequenced and assembled,filling gaps in 3 previously unrepresented orders,and integrated with existing data to generate a 464 species wholegenome alignment spanning all teleost orders-the largest such resource beyond mammals and birds.展开更多
基金funded by the National Natural Science Foundation of China(No.22278443)CAMS Innovation Fund for Medical Sciences(No.2022-I2M-1-015)+3 种基金the Key R&D Program of Shandong Province(No.2021ZDSYS26)Xinjiang Uygur Autonomous Region Innovation Environment Construction Special Fund and Technology Innovation Base Construction Key Laboratory Open Project(No.2023D04065)2023 Xinjiang Uygur Autonomous Region Innovation Tianchi Talent Introduction Program for financial supportthe Key Project of Natural Science of Bengbu Medical University(No.2024byzd138).
文摘In the pharmaceutical field,machine learning can play an important role in drug development,production and treatment.Co-crystallization techniques have shown promising potential to enhance the properties of active pharmaceutical ingredients(APIs)such as solubility,permeability,and bioavailability,all without altering their chemical structure.This approach opens new avenues for developing natural products into effective drugs,especially those previously challenging in formulation.Emodin,an anthraquinone-based natural product,is a notable example due to its diverse biological activities;however,its physicochemical limitations,such as poor solubility and easy sublimation,restricted its clinical application.While various methods have improved emodin's physicochemical properties,research on its bioavailability remains limited.In our study,we summarize cocrystals and salts produced through co-crystallization technology and identify piperazine as a favorable coformer.Conflicting conclusions from computational chemistry and molecular modeling method and machine learning method regarding the formation of an emodin-piperazine cocrystal or salt led us to experimentally validate these possibilities.Ultimately,we successfully obtained the emodin-piperazine cocrystal,which were characterized and evaluated by several in vitro methods and pharmacokinetic studies.In addition,experiments have shown that emodin has a certain therapeutic effect on sepsis,so we also evaluated emodin-piperazine biological activity in a sepsis model.The results demonstrate that co-crystallization significantly enhances emodin's solubility,permeability,and bioavailability.Pharmacodynamic studies indicate that the emodin-piperazine cocrystal improves sepsis symptoms and provides protective effects against liver and kidney damage associated with sepsis.This study offers renewed hope for natural products with broad biological activities yet hindered by physicochemical limitations by advancing co-crystallization as a viable development approach.
基金supported by the major scientific and technological projects of Hainan Province(ZDKJ2019011)the special funding of“Blue granary”scientific and technological innovation of China(2018YFD0900301-05).
文摘The electric catfish(Malapterurus electricus),belonging to the family Malapteruridae,order Siluriformes(Actinopterygii:Ostariophysi),is one of the six branches that has independently evolved electrical organs.We assembled a 796.75 Mb M.electricus genome and anchored 88.72%sequences into 28 chromosomes.Gene family analysis revealed 295 expanded gene families that were enriched on functions related to glutamate receptors.Convergent evolutionary analyses of electric organs among different lineage of electric fishes further revealed that the coding gene of rho guanine nucleotide exchange factor 4-like(arhgef4),which is associated with G-protein coupled receptor(GPCR)signaling pathway,underwent adaptive parallel evolution.Gene identification suggests visual degradation in catfishes,and an important role for taste in environmental adaptation.Our findings fill in the genomic data for a branch of electric fish and provide a relevant genetic basis for the adaptive evolution of Siluriformes.
基金supported by The General Program(Key Program,Major Research Plan)of National Natural Science Foundation of China nos.32170439(to G.Y.F.),32122021(to K.W.),32293252,and 32170438(to C.C.F.)the Thousands Marine Species Genome Sequencing Project of Qingdao Free Trade Zone Management Committee(to G.Y.F.)+3 种基金Shandong Province Key Research and Development Plan no.2023CXPT057(to G.Y.F.)the Specially appointed Professor Program of Jiangsu Province,the Jiangsu Foreign Expert Bureau,and the Jiangsu Provincial Department of Technology grant JSSCTD202142(to I.S.)received technical support from the China National Gene Banksupported by the High-performance Computing Platform of YZBSTCACC.
文摘The remarkable morphological diversity and species abundance of teleost fishes offer a valuable resource for understanding vertebrate evolution.In phase I of the Fish10K project,genomes of 110 teleost species were sequenced and assembled,filling gaps in 3 previously unrepresented orders,and integrated with existing data to generate a 464 species wholegenome alignment spanning all teleost orders-the largest such resource beyond mammals and birds.
