In response to the 'cages in courts' issue in criminal trials,after reviewing a series of cases such as 'Svinarenko and Slyadnev v.Russia',the European Court of Human Rights has gradually clarified tha...In response to the 'cages in courts' issue in criminal trials,after reviewing a series of cases such as 'Svinarenko and Slyadnev v.Russia',the European Court of Human Rights has gradually clarified that the 'human dignity of the accused and his right to a fair trial are higher than the value of court security',thus found that putting the accused in a cage dock or improper use of a glass cabin dock are in breach of Article 3 and Article 6 of the European Convention on Human Rights,constitutes degrading treatment and violates the right to a fair trial.This position is in line with the international overall trend,which is of significance as a reference for China’s courts.Domestic courts should take the initiative to change the current use of the 'low fence dock' to further enhance China’s judicial civilization.展开更多
Compounds that selectively modulate multiple targets can provide clinical benefits and are an alternative to traditional highly selective agents for unique targets.High-throughput screening(HTS)for multitarget-directe...Compounds that selectively modulate multiple targets can provide clinical benefits and are an alternative to traditional highly selective agents for unique targets.High-throughput screening(HTS)for multitarget-directed ligands(MTDLs)using approved drugs,and fragment-based drug design has become a regular strategy to achieve an ideal multitarget combination.However,the unexpected presence of panassay interference compounds(PAINS)suspects in the development of MTDLs frequently results in nonspecific interactions or other undesirable effects leading to artefacts or false-positive data of biological assays.Publicly available filters can help to identify PAINS suspects;however,these filters cannot comprehensively conclude whether these suspects are"bad"or innocent.Additionally,these in silico approaches may inappropriately label a ligand as PAINS.More than 80% of the initial hits can be identified as PAINS by the filters if appropriate biochemical tests are not used resulting in false positive data that are unacceptable for medicinal chemists in manuscript peer review and future studies.Therefore,extensive offline experiments should be used after online filtering to discriminate"bad"PAINS and avoid incorrect evaluation of good scaffolds.We suggest that the use of"Fair Trial Strategy"to identify interesting molecules in PAINS suspects to provide certain structure-function insight in MTDL development.展开更多
文摘In response to the 'cages in courts' issue in criminal trials,after reviewing a series of cases such as 'Svinarenko and Slyadnev v.Russia',the European Court of Human Rights has gradually clarified that the 'human dignity of the accused and his right to a fair trial are higher than the value of court security',thus found that putting the accused in a cage dock or improper use of a glass cabin dock are in breach of Article 3 and Article 6 of the European Convention on Human Rights,constitutes degrading treatment and violates the right to a fair trial.This position is in line with the international overall trend,which is of significance as a reference for China’s courts.Domestic courts should take the initiative to change the current use of the 'low fence dock' to further enhance China’s judicial civilization.
基金financially supported by National Natural Science Foundation of China(31870325)Key Laboratory for Tumor Precision Medicine of Shanxi Province Research Fund(KLTPMSX2022-B3,China)+1 种基金Innovation and Entrepreneurship Training Program for Undergraduate(202010316043S,China)“Double First Class”Subject Innovation Team Construction Project of China Pharmaceutical University(CPU2018GY12,China)。
文摘Compounds that selectively modulate multiple targets can provide clinical benefits and are an alternative to traditional highly selective agents for unique targets.High-throughput screening(HTS)for multitarget-directed ligands(MTDLs)using approved drugs,and fragment-based drug design has become a regular strategy to achieve an ideal multitarget combination.However,the unexpected presence of panassay interference compounds(PAINS)suspects in the development of MTDLs frequently results in nonspecific interactions or other undesirable effects leading to artefacts or false-positive data of biological assays.Publicly available filters can help to identify PAINS suspects;however,these filters cannot comprehensively conclude whether these suspects are"bad"or innocent.Additionally,these in silico approaches may inappropriately label a ligand as PAINS.More than 80% of the initial hits can be identified as PAINS by the filters if appropriate biochemical tests are not used resulting in false positive data that are unacceptable for medicinal chemists in manuscript peer review and future studies.Therefore,extensive offline experiments should be used after online filtering to discriminate"bad"PAINS and avoid incorrect evaluation of good scaffolds.We suggest that the use of"Fair Trial Strategy"to identify interesting molecules in PAINS suspects to provide certain structure-function insight in MTDL development.
