According to the World Health Organization (WHO), multidrug-resistant pathogens caused over 1.27 million deaths worldwide in 2020. And figures are rising, with projections pointing to antimicrobial resistance surpassing cancer as the leading cause of death by 2050. Now, researchers at the HUN-REN Biological Research Center have unveiled the role of pre-existing genetic variabilities and specific cross-resistance patterns among several antibiotics designed to combat gram-positive bacteria.

The PD-1 receptor, a major immune checkpoint inhibitor whose signaling is the target of multiple blockbuster anticancer drugs, differs functionally between rodents and humans in previously unknown ways. Researchers from the University of California, San Diego, and co-authors at the Chinese Academy of Sciences and the National Cancer Institute reported these findings in the Jan. 3, 2025, online issue of Science Immunology.

2024 saw the completion of several cellular-resolution brain maps, including the entire fly brain and a comprehensive connections map of a cubic centimeter of human brain. 2025 began with the addition of another important map. In the Jan. 1, 2025, issue of Nature, researchers from the Allen Institute presented a map of areas and cell types where aging most affected the mouse brain.

Among the most profound results presented at the 2024 European Society for Medical Oncology Congress were the 10-year data from the Checkmate-067 and Keynote-006 trials of Opdivo and Keytruda as first-line agents in advanced or metastatic melanoma in which 10-year overall survival topped 40%. The success of checkpoint blockade, however, has not extended to all tumor types, but in 2024, molecular studies have led to advances in gene therapies and a multitude of approaches that have opened the door to hope.

In the 1970s, scientists from several countries proposed to reconstruct, one by one, all the neurons in the brain as they appear under an electron microscope. They started with a small worm. Caenorhabditis elegans has only 302 neurons. It took 16 years. How much time would be required to repeat this arduous task for the 100 billion neurons in the human brain?

Researchers at the University of Leipzig and ETH Zurich have used single-cell sequencing to identify differences between fat tissue of obese individuals who are metabolically unhealthy, and those who were in good metabolic health. The findings, which were published online Dec. 17, 2024, in Cell Metabolism, identify measurements that can be used to decouple obesity from metabolic disease.

Investigators at the Helmholtz Institute have shown that inceptor, an inhibitor of the insulin signaling pathway, acted by binding insulin and targeting it for degradation. “Insulin was discovered 100 years ago, and the insulin receptor was discovered 50 years ago,” Heiko Lickert told BioWorld. “Now we have a new insulin receptor, which degrades insulin.” Lickert is the senior author of the paper reporting the new insights into how inceptor works, which were published online in Nature Metabolism.

Researchers from the University of California San Francisco (UCSF) have successfully replicated the design of regulatory T cells, achieving local targeted immune suppression and protection from CAR T-cell cytotoxicity. Many of the treatments used so far in the context of inflammatory and autoimmune disorders lead to systemic immunosuppression. In this sense, limiting immunosuppression locally to targeted tissues may help overcome systemic toxicity.

Although it does not generally infect humans, a single mutation of the H5N1 virus in the highly pathogenic avian and bovine clade 2.3.4.4b could overcome this barrier and possibly trigger a pandemic. Scientists at The Scripps Research Institute have warned of this possibility after studying the three-dimensional structure of the viral hemagglutinin and seeing how a change in one amino acid would make it more suitable for the human cell receptor. The researchers stress the need to monitor new mutations of this virus in order to act quickly in case the global jump to our species occurs.

A ketone body, a molecule derived from the metabolism of acids to obtain energy when glucose is not available, could become an effective ally in treating Alzheimer’s or preventing the effects of aging on the brain. A group of scientists at the Buck Institute for Research on Aging have studied the role of β-hydroxybutyrate as a signaling metabolite of misfolded proteins by interacting with them and altering their solubility, a mechanism that allows their elimination, as observed in preclinical models.