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Microscopy & Microtechniques by Gwyneth Astles Microscopy uncovers ‘hidden record’ of blood sugar history
Scientists at National Taiwan University (NTU) have developed a pioneering optical microscopy method that can reconstruct a person’s long-term blood glucose history from a simple blood sample, opening new frontiers for diabetes and cancer research.
The interdisciplinary team, led by Professors Chi-Kuang Sun and Tzung-Dau Wang, developed colour-resolved third-harmonic- generation microscopy (cTHGM) - a label-free imaging technique capable of distinguishing glycated haemoglobin (HbA1c) from normal haemoglobin inside individual red blood cells.
Unlike current monitoring systems, which capture only short- term glucose levels, the new approach allows researchers to trace blood sugar fl uctuations over the 120-day lifespan of red blood cells. This effectively provides a ‘molecular time-lapse’ of a person’s metabolic history.
To achieve this, the NTU team built a broadband, femtosecond- laser-based microscope that detects nanometre-scale wavelength shifts caused by chemical differences in haemoglobin molecules.
The result is a non-invasive, high-resolution chemical map showing how much glucose each red blood cell has encountered during its lifetime.
“If continuous glucose monitoring gives you a short clip of daily sugar changes, our imaging method offers the full 120-day documentary,” explained Professor Sun.
The researchers believe cTHGM could enhance precision diabetes management and help identify early signs of metabolic disorders linked to cancer. Beyond clinical use, the technique opens possibilities for real-time, colour-sensitive molecular imaging in living tissues.
The study [1], published in Science Advances, demonstrates how advanced microscopy can turn invisible biochemical traces into powerful diagnostic information.
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1. Color-resolved third harmonic generation microscopy for single-RBC HbA1c measurement and glycemic history assessment published in Science Advances
The new imaging technology noninvasively measures glycated hemoglobin in individual red blood cells. This breakthrough enables retrospective reconstruction of a person’s blood sugar history, opening new possibilities for diabetes management and early cancer risk assessment. Credit: National Taiwan University
66024pr@reply-direct.com TRAT1 protein revealed as molecular switch in T helper cells
Researchers at the Medical University of Vienna have uncovered how a little-studied protein, TRAT1 (T Cell Receptor Associated Transmembrane Adaptor 1), acts as a molecular switch in the immune system. By controlling the activity of T helper cells, TRAT1 balances immune attack and restraint - a mechanism critical for preventing excessive infl ammation and autoimmune disease. The fi ndings were published in Cell Communication and Signaling [1].
T helper cells are the ‘conductors’ of the immune system, directing other immune cells and tailoring responses to specifi c threats. They are divided into effector T cells, which actively attack invaders, and regulatory T cells (Treg), which restrain immune activity. Until now, the precise molecular signals controlling this balance were poorly understood.
The Vienna team, led by Ralf Schmidt and Klaus Schmetterer, applied a combination of advanced
cellular and molecular techniques to study TRAT1 function. Primary human CD4⁺ T cells -
including thymus-derived and induced Treg cells - were genetically modifi ed using CRISPR/Cas9-mediated deletion or retro-/lentiviral overexpression of TRAT1. Functional assays, fl ow cytometry, cytokine quantifi cation, and RNA sequencing revealed how TRAT1 modulates T cell activity. Mechanistic studies included pathway inhibition with small molecules and phospho-protein analysis, while the effect of TRAT1 on Treg function was further assessed in a CAR- Treg context using an immune organoid model of allo-rejection.
The results show that TRAT1 acts differently depending on the T cell subtype. In effector T cells, TRAT1 ensures controlled activation: deleting it boosts activity but reduces production of infl ammatory messengers such as interleukin-17. In Treg cells, TRAT1 supports targeted suppressive functions, enhancing inhibition of some immune cell types more than others.
“TRAT1 acts like a molecular switch, controlling both immune attack and suppression,” explained study leader Klaus Schmetterer.
Ultra-fast imaging captures nanosecond droplet dynamics
Researchers at the University of Michigan have gained
unprecedented insight into the behaviour of microscopic droplets used in drug delivery - capturing events that last only billionths of a second. Using a combination of ultra-fast framing and streak imaging, the team was able to visualise the rapid release of fl uids at a level of detail impossible with conventional techniques.
“These droplets burst and release their contents in nanoseconds, a timescale far too fast for traditional imaging methods,” explained Mr Wai Chan of Specialised Imaging. “By combining framing and streak images, we can simultaneously see both the 2D spatial structure and the temporal evolution of the event.”
The approach relies on an optical system that allows multiple imaging instruments to share the same fi eld of view. This makes it possible to correlate high-resolution spatial snapshots from the framing camera with continuous temporal data from the streak
camera - effectively creating a molecular time-lapse of ultrafast processes.
The study provides a new window into how ultrasonic fl uid release can be controlled and optimised for biomedical applications, including drug delivery systems. Beyond medicine, the techniques demonstrate how combining different high-speed
modalities can reveal previously invisible phenomena in fl uid dynamics, material science, and beyond.
By capturing events at up to a billion frames per second, this dual imaging strategy opens exciting possibilities for scientists seeking to understand and control ultrafast, transient processes - from microscopic droplets to high-speed material deformations.
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Framing and streak camera images taken before, during and after the ultrasound arrival.
imaging
“Understanding this dual role could help us design targeted therapies for autoimmune diseases and transplant rejection.”
Importantly, altered TRAT1 expression was observed in patients with graft-versus-host disease (GvHD) and systemic lupus erythematosus, indicating disrupted T helper cell signalling in these conditions. These insights could guide the development of cell-based immunotherapies, such as tailor-made CAR-Treg cells to prevent unwanted immune reactions. Proof-of-concept work has already been demonstrated in a novel 3D cell culture model for transplant rejection, according to fi rst author Tobias Frey.
More information online:
ilmt.co/PL/YeJw
1. T cell receptor associated transmembrane adaptor 1 (TRAT1) modulates human Th17 published in Cell Communication and Signaling
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