Tuesday, September 30, 2025

PARACELSUSIAN ALCHEMY

New insight into the response mechanism of arsenic in treating acute promyelocytic leukemia




Science China Press
Abstract of Single-cell omics analysis reveals tumor microenvironment rewiring after arsenic trioxide therapy in acute promyelocytic leukemia 

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Abstract of Single-cell omics analysis reveals tumor microenvironment rewiring after arsenic trioxide therapy in acute promyelocytic leukemia

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Credit: ©Science China Press






In this study, researchers from Harbin Medical University conducted a comprehensive characterization of the tumor microenvironment in APL patients undergoing arsenic trioxide (ATO) therapy using single-cell sequencing. Initially, APL cells were classified into distinct subpopulations, revealing several groups with diverse characteristics. Notably, one LSC-like subpopulation, marked by high expression of stemness-related genes and a pronounced LSC signature, was identified as the root of differentiation arrest in APL. This subpopulation was largely eradicated following treatment, offering novel insights into how ATO affects APL cells.

As is well known, lymphocytes, including T cells, NK cells, and B cells, are key components of antitumor immunity. The researchers subsequently analyzed other immune components, with a particular focus on lymphocytes. They found that ATO treatment induced the enrichment of a CD8 T cell subpopulation, termed the CD8 ISG subtype, characterized by elevated expression of interferon-stimulated genes. Further analyses indicated that ATO treatment significantly enhanced both the effector functions and TCR clonotype expansion of this subtype. Additionally, through a constructed co-expression network, they revealed further functional characteristics of this CD8 subpopulation. For example, beyond its association with ISG genes, this subpopulation also exhibited signatures related to myeloid differentiation, arsenic response, and immune activation.

Subsequently, the researchers observed that NK cells in APL patients exhibited a dysfunctional state, which was largely reversed following ATO therapy. Notably, an activated NK cell subpopulation associated with the ATO response was identified, characterized by pronounced NFκB signaling and inflammatory activation. In addition, ATO treatment was found to remodel the distribution of immunoglobulin proteins, as revealed by integrated scRNA-seq and scBCR-seq analyses. Finally, the study elucidated the complex cellular communication network and identified the LT pathway as a key signaling axis mediating interactions between the CD8 ISG subtype and NK NFκB subtype with APL cells, contributing to myeloid differentiation and immune activation.

In conclusion, this study mapped the rewired hematopoietic lineage and notably identified two lymphocyte subpopulations associated with the response to ATO treatment: the CD8 ISG T cells and the NK NFκB cells, which provides a deeper insight into the underlying mechanisms in the context of ATO therapy for APL patients.

The authors acknowledge funding from the National Key Research and Development Program of China; the National Natural Science Foundation of China; the Natural Science Foundation of Heilongjiang Province (Key Program) and the project of scientific research business expenses of provincial research institutes.

 

Building better batteries with amorphous materials and machine learning




Indian Institute of Science (IISc)
Making ions move faster by making structures amorphous 

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Making ions move faster by making structures amorphous

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Credit: Vijay Choyal





Lithium-ion batteries power most electronics, but they have limited energy density – they can store only a certain amount of energy per mass or volume of the battery. “In order to store even more energy with the same mass or volume, you will have to explore alternative energy storage technologies,” says Sai Gautam Gopalakrishnan, Assistant Professor at the Department of Materials Engineering, IISc.

Gopalakrishnan and his team have studied how to boost the movement of ions in magnesium batteries, which can have a higher energy density. In a new study, using a machine learning model, they show that using amorphous materials as positive electrodes to build these batteries can significantly increase their rate of energy transfer.

Lithium ion or magnesium batteries contain a positive (cathode) and a negative (anode) electrode, separated by a liquid electrolyte. Each time a lithium or magnesium ion goes from the cathode to the anode or vice versa, energy is exchanged with the device. “In magnesium batteries, each magnesium atom can actually exchange two electrons, whereas each lithium atom can only exchange one electron with the external circuit. So, you can get close to twice the amount of energy per atom moved,” explains Gopalakrishnan. 

The cathodes need to act like a sponge – upon applying an external potential, they should absorb and release magnesium ions into the electrolyte. But the main bottleneck in commercialising magnesium batteries is the lack of good materials that can act as cathodes, Gopalakrishnan says. So far, scientists have largely been looking at crystalline materials, which have a periodically ordered arrangement of atoms. However, because magnesium moves very slowly within these materials, they are unable to absorb and release magnesium ions at a fast enough rate. 

”If we break the crystallinity and create something that is amorphous, haphazard, and chaotic, that may actually help magnesium to move fairly well within the structure,” Gopalakrishnan explains. 

The team built a computational model of an amorphous vanadium pentoxide material and calculated how fast magnesium ions can move within it. To build such models, scientists typically use a method called density functional theory (DFT), which accurately models systems at an electronic level. But it takes a long time to simulate amorphous systems using this method. Molecular dynamics (MD) simulations – in which one studies interactions between atoms – are faster but less accurate. “Modelling amorphous systems accurately is very difficult,” says Vijay Choyal, first author of the study and a former postdoctoral scholar at IISc.

To combine speed and accuracy, the team used a machine learning framework. They first used DFT to generate data on how the amorphous cathode would function at a small scale. After training their machine learning model on this data, they used the model to perform MD simulations. With MD, they were able to model the material at a larger scale – to get a better picture of how far the magnesium moves within the amorphous material and how long it takes. Compared to state-of-the-art crystalline magnesium materials, the team observed about five orders of magnitude improvement in the rate of magnesium movement in the amorphous form.

“Our work offers a completely different pathway to identify electrode materials for batteries and takes us a step closer to commercialisation of magnesium batteries,” says Gopalakrishnan. 

The team hopes that experimentalists can now work on this amorphous material and test its effectiveness in the lab. “One disadvantage is that we don't know how stable the amorphous materials can be when used in a practical battery,” says Debsundar Dey, co-author of the study and former MTech student at IISc. “The key takeaway is that using amorphous materials increases the mobility of ions, but we also need to experimentally validate our observations.” 

Future mRNA vaccines may prevent food and seasonal allergies




Early research increases potential of more mRNA vaccine breakthroughs.




University of Pennsylvania School of Medicine




A new mRNA vaccine stopped allergens from causing dangerous immune reactions and life-threatening inflammation in mice, according to researchers from the Perelman School of Medicine at the University of Pennsylvania and Cincinnati Children’s. The vaccine, outlined in the Journal of Clinical Investigation, may one day be tested and tailored to a variety of seasonal and food allergies.

“This is a potential breakthrough for millions of people worldwide who suffer from life-threatening allergies,” said Nobel laureate Drew Weissman, MD, PhD, the Roberts Family Professor in Vaccine Research at Penn and co-lead of the study with Cincinnati Children’s Marc E. Rothenberg, MD, PhD,

Weissman, Penn colleagues Jilian Melamed, PhD, an assistant professor of Infectious Diseases, Mohamad-Gabriel Alameh, PhD, an assistant professor of Pathology and Laboratory Medicine, and the Cincinnati Children’s researchers led by Marc E. Rothenberg, MD, PhD, director of the division of Allergy and Immunology, modeled this new vaccine on the design of the COVID-19 mRNA lipid nanoparticle (LNP) vaccines.

This time, however, scientists tweaked the mRNA to instruct cells to produce proteins that resemble certain allergens. By presenting these proteins in a controlled way, the vaccine didn’t cause allergic reactions but did instruct the immune system to respond more appropriately in the future. And, when mice were later exposed to the respective allergens, the vaccines worked.

When mice with specific allergies were exposed to the allergens, none of the mice vaccinated with the respective allergy vaccine had an allergic reaction. Vaccinated mice had fewer allergy-related white blood cells, made fewer inflammation-causing proteins, and their lungs produced less mucus. Their airways were also protected against narrowing, which often happens during asthma, and they made special antibodies that protected against allergic reactions.

A platform with broad potential

Unlike traditional allergy shots, which involve repeated administration of purified allergens over months or years, the mRNA-based approach offers a more flexible solution. Because the mRNA can be tailored to encode proteins from different allergens, the platform could be adapted to treat a wide range of allergic conditions—from seasonal pollen allergies to food sensitivities and asthma. Additionally, many severe food allergies do not have vaccines to protect against severe allergic reactions.

“People with food allergies that can cause anaphylactic shock are rightfully fearful in social situations, eating out in public, sharing food, and engaging in other fun activities where there are food and allergens around,” said Weissman. “Allowing people to partake in foods they were never able to eat would be incredibly rewarding, but I’ll even be happy if we can one day introduce a vaccine that allows parents to breathe just a little easier when sending their kids to class birthday parties.”

The study represents a proof-of-concept that mRNA vaccines can be used not only to prevent infectious diseases but also to adjust immune responses in chronic conditions like allergies and even celiac disease. Researchers say the next steps include testing the vaccine’s safety in humans, determining how many allergens can be included in a single dose, and evaluating how long protection lasts.

“We saw mRNA vaccines save lives during the pandemic, and as the most-tested type of vaccine in history, we know it’s the safest and most effective vaccine ever created,” said Weissman. “We are deeply committed to continuing to uncover the potential of this technology.”

This research was supported by the Food Allergy Fund and a grant from the National Institute of Health’s National Institute of Diabetes and Digestive and Kidney Diseases (P30 DK078392).

 

Zoom fatigue is a thing of the past



Recent study undertaken by JGU has revealed that online meetings are not more exhausting than face-to-face meetings



Johannes Gutenberg Universitaet Mainz

Junior Professor Dr. Hadar Nesher Shoshan 

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Junior Professor Dr. Hadar Nesher Shoshan

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Credit: Photo/©: Miriam Diaz





Online meetings are exhausting – this phenomenon, dubbed "zoom fatigue", was widely reported in the media during the COVID-19 pandemic. "And this was certainly what happened during lockdown," points out Junior Professor Hadar Nesher Shoshan of Johannes Gutenberg University Mainz (JGU). "But we have found out by means of a recent study that this is no longer the case under the conditions that prevail today. In fact, it seems that video meetings are not more exhausting than face-to-face meetings." The results of the study have been just published in the Journal of Occupational Health Psychology.

No longer evidence of zoom fatigue

With the help of a collective of 125 subjects, Nesher Shoshan together with Assistant Professor Wilken Wehrt from Maastricht University investigated how exhausting online meetings are in comparison with other forms of meeting. They asked the subjects to report over a period of 10 days on the following aspects: If they had taken part in a meeting, whether that meeting was online or face-to-face and whether they were dealing with other things during the meeting. They were also asked if there had been the opportunity to take a break or stretch their legs and how exhausted the meeting had made them feel. This enabled the researchers to collect information on 945 meetings, of which 62 percent were video meetings. "Our initial hypothesis was that zoom fatigue still existed. After all, all previous studies had come to this conclusion, so there was no reason to doubt that this result was correct," adds Nesher Shoshan. "However, we found no evidence of the phenomenon! According to our findings, online meetings are not more fatiguing than in-person meetings." In fact, the researchers report that video meetings shorter than 44 minutes are actually less exhausting than other meetings.

Previous studies based on data collected during the pandemic

The question is how this discrepancy in results of the new and the former studies came about. Nesher Shoshan postulates that this is because the study she undertook with her colleague uses data collected recently, while the other studies employed data collated during the COVID-19 pandemic. She goes on to explain: "It is more likely that the cause of zoom fatigue was the pandemic situation itself rather than the online meeting conditions. Projected onto zoom meetings, linked as they were closely with lockdown, were all the negative aspects associated with the circumstances. People were missing their old way of life, their social contacts and were no longer enjoying their work. Our results highlight the importance in the social sciences of replicating research findings in the appropriate historical setting." Nesher Shoshan believes that their new findings have important practical implications with regard to the working world, particularly when it comes to the assumed 'disadvantages' of working from home. "We have been able, at least to some extent, to undermine the argument that online meetings while working from home can still cause burn-out among personnel even though the pandemic is over."