Bin Liu

Sep 16, 2024 | nature.com | Bin Liu |Xin Gao |Honglan Zhou |Baoshan Gao |Faping Li |Haolin Teng

Chronic Kidney Disease (CKD) stands as a substantial challenge within the global health landscape. The elevated metabolic demands essential for sustaining normal kidney function have propelled an increasing interest in unraveling the intricate relationship between mitochondrial dysfunction and CKD. However, the authentic causal relationship between these two factors remains to be conclusively elucidated. This study endeavors to address this knowledge gap through the Mendelian Randomization (MR) method. We utilized large-scale QTL datasets (including 31,684 eQTLs samples, 1980 mQTLs samples, and 35,559 pQTLs samples) to precisely identify key genes related to mitochondrial function as exposure factors. Subsequently, we employed GWAS datasets (comprising 480,698 CKD samples and 1,004,040 eGFRcrea samples) as outcome factors. Through a comprehensive multi-level analysis (encompassing expression, methylation, and protein quantification loci), we evaluated the causal impact of these genes on CKD and estimated glomerular filtration rate (eGFR). The integration and validation of diverse genetic data, complemented by the application of co-localization analysis, bi-directional MR analysis, and various MR methods, notably including inverse variance weighted, have collectively strengthened our confidence in the robustness of these findings. Lastly, we validate the outcomes through examination in human RNA sequencing datasets encompassing various subtypes of CKD. This study unveils significant associations between the glycine amidinotransferase (GATM) and CKD, as well as eGFR. Notably, an augmentation in GATM gene and protein expression corresponds to a diminished risk of CKD, whereas distinct methylation patterns imply an increased risk. Furthermore, a discernible reduction in GATM expression is observed across diverse pathological subtypes of CKD, exhibiting a noteworthy positive correlation with GFR. These findings establish a causal relationship between GATM and CKD, thereby highlighting its potential as a therapeutic target. This insight lays the foundation for the development of potential therapeutic interventions for CKD, presenting substantial clinical promise.

Mar 21, 2024 | nature.com | Quli Fan |Wentao Song |Yufu Tang |Bin Liu |Wei Huang |Jianwu Tian | +3 more

Photodynamic therapy (PDT) is a promising cancer treatment but has limitations due to its dependence on oxygen and high-power-density photoexcitation. Here, we report polymer-based organic photosensitizers (PSs) through rational PS skeleton design and precise side-chain engineering to generate •O2− and •OH under oxygen-free conditions using ultralow-power 808 nm photoexcitation for tumor-specific photodynamic ablation. The designed organic PS skeletons can generate electron-hole pairs to sensitize H2O into •O2− and •OH under oxygen-free conditions with 808 nm photoexcitation, achieving NIR-photoexcited and oxygen-independent •O2− and •OH production. Further, compared with commonly used alkyl side chains, glycol oligomer as the PS side chain mitigates electron-hole recombination and offers more H2O molecules around the electron-hole pairs generated from the hydrophobic PS skeletons, which can yield 4-fold stronger •O2− and •OH production, thus allowing an ultralow-power photoexcitation to yield high PDT effect. Finally, the feasibility of developing activatable PSs for tumor-specific photodynamic therapy in female mice is further demonstrated under 808 nm irradiation with an ultralow-power of 15 mW cm−2. The study not only provides further insights into the PDT mechanism but also offers a general design guideline to develop an oxygen-independent organic PS using ultralow-power NIR photoexcitation for tumor-specific PDT. Conventional photodynamic therapy (PDT) is hindered by oxygen-dependent photosensitization pathways and high-power-density photoexcitation. Here, the authors develop polymer-based organic photosensitizers (PSs) through PS skeleton design and side-chain engineering to allow tumor-specific PDT under oxygen-free conditions using ultralow-power 808 nm photoexcitation.