Hydrogen sulfide(H_(2)S)is a gas signaling molecule with versatile bioactivities;however,its exploitation for disease treatment appears challenging.This study describes the design and characteriza-tion of a novel type...Hydrogen sulfide(H_(2)S)is a gas signaling molecule with versatile bioactivities;however,its exploitation for disease treatment appears challenging.This study describes the design and characteriza-tion of a novel type of H_(2)S donoredrug conjugate(DDC)based on the thio-ProTide scaffold,an evolu-tion of the ProTide strategy successfully used in drug discovery.The new H_(2)S DDCs achieved hepatic co-delivery of H_(2)S and an anti-fibrotic drug candidate named hydronidone,which synergistically attenuated liver injury and resulted in more sufficient intracellular drug exposure.The potent hepatoprotective ef-fects were also attributed to the H_(2)S-mediated multipronged intervention in lipid peroxidation both at the whole cellular and lysosomal levels.Lysosomal H_(2)S accumulation and H_(2)S DDC activation were facilitated by the hydrolysis through the specific lysosomal hydrolase,representing a distinct mechanism for lysosomal targeting independent of the classical basic moieties.These findings provided a novel pattern for the design of optimally therapeutic H_(2)S DDC and organelle-targeting functional molecules.展开更多
Recent advance in large-scale genome se-quencing has generated a huge volume of pro-tein sequences. In order to timely utilize the in-formation hidden in these newly discovered sequences, it is highly desired to devel...Recent advance in large-scale genome se-quencing has generated a huge volume of pro-tein sequences. In order to timely utilize the in-formation hidden in these newly discovered sequences, it is highly desired to develop com- putational methods for efficiently identifying their various attributes because the information thus obtained will be very useful for both basic research and drug development. Particularly, it would be even more useful and welcome if a user-friendly web-server could be provided for each of these methods. In this minireview, a sy- stematic introduction is presented to highlight the development of these web-servers by our group during the last three years.展开更多
This article focuses on a profile of personnel who work with retired volunteers. The data was sourced by using two standardised measuring instrument, interviews, focus groups and observation. The Leadership Qualities ...This article focuses on a profile of personnel who work with retired volunteers. The data was sourced by using two standardised measuring instrument, interviews, focus groups and observation. The Leadership Qualities Inventory (LQI-S) was used as one standardised measuring instrument. The following elements were measured namely leadership, people-oriented, task-oriented and self-oriented qualities. The Neethling Brain Instrument (NBI) was used as a second standardised instrument. This instru- ment measured the subconscious’ preferences in four quadrants namely analytical (L1), systematic (L2), emotional (R2) and holistic (R1). From the data an empowerment programme was developed for personnel involved at service centres for elderly persons.展开更多
基金supported by the National Natural Science Foundation of China(grant No.82173686)CAMS Innovation Fund for Medical Sciences(CIFMS)(2021-I2M-5-011,China)+1 种基金Leading Technology Foundation Research Project of Jiangsu Province(BK20192005,China)Outstanding Youth Foundation of Jiangsu Province(No.BK20200081,China).
文摘Hydrogen sulfide(H_(2)S)is a gas signaling molecule with versatile bioactivities;however,its exploitation for disease treatment appears challenging.This study describes the design and characteriza-tion of a novel type of H_(2)S donoredrug conjugate(DDC)based on the thio-ProTide scaffold,an evolu-tion of the ProTide strategy successfully used in drug discovery.The new H_(2)S DDCs achieved hepatic co-delivery of H_(2)S and an anti-fibrotic drug candidate named hydronidone,which synergistically attenuated liver injury and resulted in more sufficient intracellular drug exposure.The potent hepatoprotective ef-fects were also attributed to the H_(2)S-mediated multipronged intervention in lipid peroxidation both at the whole cellular and lysosomal levels.Lysosomal H_(2)S accumulation and H_(2)S DDC activation were facilitated by the hydrolysis through the specific lysosomal hydrolase,representing a distinct mechanism for lysosomal targeting independent of the classical basic moieties.These findings provided a novel pattern for the design of optimally therapeutic H_(2)S DDC and organelle-targeting functional molecules.
文摘Recent advance in large-scale genome se-quencing has generated a huge volume of pro-tein sequences. In order to timely utilize the in-formation hidden in these newly discovered sequences, it is highly desired to develop com- putational methods for efficiently identifying their various attributes because the information thus obtained will be very useful for both basic research and drug development. Particularly, it would be even more useful and welcome if a user-friendly web-server could be provided for each of these methods. In this minireview, a sy- stematic introduction is presented to highlight the development of these web-servers by our group during the last three years.
文摘This article focuses on a profile of personnel who work with retired volunteers. The data was sourced by using two standardised measuring instrument, interviews, focus groups and observation. The Leadership Qualities Inventory (LQI-S) was used as one standardised measuring instrument. The following elements were measured namely leadership, people-oriented, task-oriented and self-oriented qualities. The Neethling Brain Instrument (NBI) was used as a second standardised instrument. This instru- ment measured the subconscious’ preferences in four quadrants namely analytical (L1), systematic (L2), emotional (R2) and holistic (R1). From the data an empowerment programme was developed for personnel involved at service centres for elderly persons.
