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【Foreword】 【Invited Article】 Jiunn-rong Yeh, “Constitutional Dialogism for Basic Rights: Beyond Constitutional Interpretation”

This issue has a total of three research articles. The authors and titles of these articles are as follows:

Please see the table of contents below:

The newest issue of Academia Economic Papers has just been published by the Institute of Economics. Articles in this issue (Vol. 52, No. 1) include:

The latest issue of Taiwan Economic Forecast and Policy has been published. Articles in this issue include:

The use of protein stabilizers or pharmacological chaperones to protect specific enzymes and impart a therapeutic benefit is an emerging strategy in drug discovery. However, designing molecules that can bind optimally to their targets at physiological pH remains a major challenge. The research, led by Dr. Wei-Chieh Cheng at Genomics Research Center, Academia Sinica, found that a dibasic polyhydroxylated pyrrolidine ACK170 (US 10995067 B2) exhibited superior pH-selective inhibitory activity and chaperoning activity for human α-galactosidase A (α-Gal A) through the Natural Product-Inspired Combinatorial Chemistry (NPICC) strategy. To further investigate the role of different C-1 moieties on the pH-selectivity and protecting effects of these compounds, researchers designed and synthesized a library of monobasic and dibasic iminosugars, screened them for α-Gal A stabilizing activity using thermal shift and heat-induced denaturation assays, and characterized the mechanistic basis for this stabilization using X-ray crystallography and binding assays. It was noted that the dibasic iminosugar ACK170 protect α-Gal A from denaturation and inactivation at lower concentrations than monobasic or other N-substituted derivatives; a finding attributed to the nitrogen on the C-1 methylene of ACK170 which forms the bifurcated salt bridges with two carboxyl residues, E203 and D231, and is responsible for their pH-selective binding to α-Gal A. Moreover, ACK170 demonstrated promising results to improve enzyme replacement therapy and exhibited significant chaperoning effects in Fabry cells. These findings suggest that amino-iminosugar ACK170 is a useful model to demonstrate how an additional exocyclic amino group can improve their pH-selectivity and protecting effects. This research has been published on February 23, 2024 in JACS Au, providing new insights into the design of pH-selective small molecules for the treatment of lysosomal storage diseases.

Earth’s long-term, stable magnetic field is critical for being a habitable planet. Mars had a global magnetic field at ~4.3 billion years ago, which, however, only lasted for ~0.7 billion years. To decipher the origin of such short-lived dynamo, an international research team led by Dr. Wen-Pin Hsieh at the Institute of Earth Sciences, Academia Sinica, has precisely measured the thermal conductivity of iron-sulfur alloys at Martian core’s high pressure-temperature conditions. Research team demonstrated that Martian core is much more thermally conductive than previously inferred. Combined with numerical modeling on Martian core’s thermal evolution, they further found that such high thermal conduction with efficient cooling diminishes thermal convection, significantly contributing to the cessation of Martian dynamo. As the seismic data from Insight mission showed important advances in the internal structure of Mars, the research findings further provide crucial insights to the thermal and magnetic evolution, energy budget, and dynamics of Mars. The international team includes Drs. Wen-Pin Hsieh and Frédéric Deschamps of IES, etc. The results have been published in Science Advances on March 20, 2024.

UFMylation is an emerging ubiquitin-like post-translational modification that regulates various biological processes. Dysregulation of the UFMylation pathway leads to human diseases including cancers. However, the physiological role of UFMylation in T cells remains unclear. A research team led by Dr. Yu-Ru Lee at the Institute of Biomedical Sciences, Academia Sinica, reported that mice with conditional knockout (cKO) Ufl1, a UFMylation E3 ligase, in T cells exhibit effective tumor control. Single-cell RNA sequencing analysis shows that tumor-infiltrating cytotoxic CD8+ T cells are increased in Ufl1 cKO mice. Moreover, UFL1 promotes PD-1 UFMylation to antagonize PD-1 ubiquitination and degradation. Furthermore, AMPK phosphorylates UFL1 at Thr536, disrupting PD-1 UFMylation to trigger its degradation. Of note, UFL1 ablation in T cells reduces PD-1 UFMylation, subsequently destabilizing PD-1 and enhancing CD8+ T cell activation. Thus, Ufl1 cKO mice bearing tumors have a better response to anti-CTLA-4 immunotherapy. Collectively, This research findings uncover a crucial role of UFMylation in T cells and highlight UFL1 as a potential target for cancer treatment. This research has been published on February 19, 2024 in Molecular Cell.

The goal of this edited volume is to introduce the roles that popular customs and culture have played in Wenzhou’s social and cultural history.

Cellular surface proteins are often coated with camouflaging glycans. Quantitative descriptions of the structures and dynamics of protein surface glycans are challenging, not least because of their intrinsic compositional and conformational heterogeneity. An international research team led by Dr. Shang-Te Danny Hsu at the Institute of Biological Chemistry, Academia Sinica, Dr. Mateusz Sikora (Max Planck Institute for Biophysics) and Dr. Cyril Hanus (Université Paris-Cité) present a computationally effective algorithm, GlycoSHIELD, for generating atomic glycoprotein models in minutes using personal computers that can reproduce structural features observed by cryo-EM, mass spectrometry and small-angle X-ray scattering. GlycoSHIELD enables quantitative analysis of the shielding effects, structural modulation and function implications of protein glycosylation. Dr Hsu is responsible for all the experimental work generated to validate and improve the computational algorithms jointly developed by Dr. Sikora and Dr Hanus. This research has been published on February 29, 2024 in Cell.

The latest issue of《Bulletin of the Institute of Mathematics Academia Sinica New Series》has been published. Articles in this issue include:

A research team led by Dr. Yi-Ying Chen at the Research Center for Environmental Changes, Academia Sinica, collaborated with National Chung Hsing University and Utah State University, focusing on studying Taiwan’s recent drought. The study, which meticulously combines in-situ data, advanced satellite observations, and ecological data analysis, reveals the drastic effects of severe drought on wildfire and the carbon sequestration capacity of Taiwan's subtropical forests. Drought events have the potential to disrupt the functionality of forest ecosystems, shifting them from carbon sinks to carbon sources. Satellite monitoring of ground water levels can offer a predictive lead-time of 1 to 2 months to anticipate emissions. It is recommended to choose drought-resistant tree species for future forest management strategies, plan firebreaks, and simultaneously monitor forest net ecosystem exchanges as action plans to adapt climate warming. The results have been published in the February issue of Environmental Research Letters in 2024.