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A selective, brain-penetrant GalR1 antagonist restores cholinergic signaling in vitro and rescues cholinergic cognitive deficits in mice

In this study, we characterized PAC-832, a small-molecule GalR1 antagonist with sub-micromolar potency (IC50 = 0.28 μM), 30-fold selectivity over GalR2 and GalR3, and excellent brain penetration and drug-like properties. In functional cell-based assays, PAC-832 reversed galanin-mediated suppression of acetylcholine release. In a scopolamine challenge model, PAC-832 attenuated cognitive deficits in the Y-maze and NOR tasks, with effect sizes comparable to donepezil.

The scopolamine model is widely used in behavioral mouse research to evaluate compounds for procognitive activity. However, because scopolamine impairs cognition by blocking muscarinic receptors rather than by reducing acetylcholine release, our behavioral results do not directly assess whether PAC-832 acts by restoring cholinergic signaling in vivo, or whether it acts through an alternative downstream mechanism. Establishing the former will require direct measurement of acetylcholine release in the CNS (e.g. using microdialysis or biosensor-based approaches) and/or GalR1-dependent in vivo validation (e.g. using transgenic GalR1-knockout mice).

Nonetheless, our work addresses a longstanding pharmacological gap in the galanin field. Despite decades of work implicating galanin signaling in CNS function and disease, translational progress has been limited by a lack of subtype-selective, brain-penetrant small molecule galanin modulators. Recent therapeutic development within the galanin field has largely focused on GalR2 agonism, while GalR1-targeting approaches have remained dependent on peptide tools unable to pass the blood-brain barrier. PAC-832 is, to our knowledge, the first GalR1-selective small molecule antagonist with sufficient brain exposure to test the effects of GalR1 antagonism following peripheral administration.

Chemical impurities make carbon surfaces superslippery, researchers find

Engineers often treat impurities as a problem to eliminate to improve material performance. But new research from Osaka Metropolitan University and Fraunhofer Institute for Mechanics of Materials IWM suggests that in some cases, a little chemical messiness is exactly what helps materials slide more smoothly. The findings were published in Advanced Science.

When two surfaces slide or rub against each other, friction occurs. While friction is essential for many everyday applications, it also wears down machines, wastes energy and limits the lifespan of moving parts. Therefore, research has focused on achieving superlow friction, or superlubricity, in which surfaces can slide past one another with exceptionally low resistance.

“While graphene-or graphite-like structures are known to enable nearly frictionless sliding, creating and maintaining such structures in practical systems remains challenging,” said Takuya Kuwahara, lecturer at Osaka Metropolitan University’s Graduate School of Engineering and lead author of the study.

A species of gut bacteria could ease anxiety and diarrhea-predominant IBS

Irritable bowel syndrome (IBS) is a condition characterized by abdominal pain, bloating and changes in bowel movements, estimated to affect between 10% and 15% of people worldwide. Past studies suggest that in many cases this condition is accompanied by anxiety, an emotional state marked by worry, fear and/or overthinking about specific life events.

While IBS and anxiety are known to often occur together, the biological processes linking the two have not yet been fully elucidated. One possibility is that bacteria and other microorganisms living in the digestive tract, broadly referred to as gut microbiota, contribute to these biological processes.

Researchers at Wuhan University of Science and Technology and Huazhong University of Science and Technology carried out a study aimed at shedding more light on the biological mechanisms linking a type of IBS called diarrhea-predominant IBS (IBS-D), which is associated with frequent loose stools, with anxiety.

Single-cell dissection of plasma cell clonal evolution to smoldering multiple myeloma after CD19 CAR-T cell therapy in B-cell acute lymphoblastic leukemia

Chimeric antigen receptor T (CAR-T) cell therapy has revolutionized the treatment of B-cell malignancies, achieving deep and durable remissions in patients with B-cell acute lymphoblastic leukemia (B-ALL).1 Despite remarkable therapeutic successes, rare but clinically significant secondary hematologic malignancies have been reported during CAR-T cell therapy, often driven by lineage switching or clonal selection.2 Moreover, CAR-T cell therapy drives profound remodeling of the immune microenvironment, and the sustained inflammatory signaling may promote clonal evolution and influence disease progression.3 High-resolution approaches, such as single-cell RNA sequencing (scRNA-seq) and single-cell B-cell receptor sequencing (scBCR-seq), enable characterization of transcriptional programs, clonal identity, and temporal dynamics to dissect CAR-T cell therapy-induced clonal evolution and immune remodeling.4

Here, we report a case of B-ALL with B-cell receptor (BCR) heterogeneity at diagnosis that evolved into smoldering multiple myeloma (SMM) following CD19-targeted CAR-T therapy. The co-occurrence of B-ALL and SMM is exceptionally rare, as it requires malignant clones at distinct stages of B-cell development. This case provides a unique opportunity to dissect how CAR-T cell therapy drives B-lineage clonal evolution and reshapes the immune microenvironment. To this end, bone marrow mononuclear cells (BMMNC) were collected at multiple time points and subjected to longitudinal scRNA-seq and scBCR-seq to track dynamic changes in malignant and immune cell populations, thereby elucidating the mechanisms of clonal evolution and immune remodeling following CAR-T cell therapy. The patient gave informed consent and was enrolled in a clinical trial registered at clinicaltrials.gov (Identifier: NCT00123456).

A 13-second eye test may help predict recovery of consciousness after severe brain injury

A simple bedside eye test may help predict recovery of consciousness in patients with severe brain injuries, according to new research presented at the European Academy of Neurology (EAN) Congress 2026.

The study found that a previously overlooked phase of the pupil response to light, known as the late light-off response (LOR), predicted improvements in consciousness seven days later in patients with acute brain injury. In contrast, standard pupil measurements already widely used in intensive care units (ICUs), including the Neurological Pupil Index (NPi) and pupillary light reflex (PLR) latency, did not predict later gains in consciousness.

Newly identified fossil sheds light on evolutionary history of saber-toothed cats

Fossils tucked away in a museum drawer and identified merely as “feline” are actually from a very ancient and enigmatic saber-toothed cat that inhabited North America more than 5 million years ago. Newly identified by a UC Berkeley paleontologist, the nearly complete skull helps clarify how these large-fanged felines evolved over millennia before going extinct about 10,000 years ago.

One clear takeaway is that these cats started out with smaller fangs—the upper canines—but evolved increasingly longer ones that may have led to their ultimate demise. California’s state fossil, Smilodon fatalis (originally called S. californicus), was the culmination of that trend. It had some of the largest upper canines of any saber-toothed animal—up to 7 inches (18 centimeters) long—but was the last saber-toothed animal to survive.

According to Berkeley postdoctoral fellow Narimane Chatar, the cranium, teeth and lower jaw (or mandible) she stumbled upon in the American Museum of Natural History in New York are from the species Adelphailurus kansensis, originally discovered in Kansas and known only from jaw fragments and teeth. Now, with the first complete skull of the cat, she has been able to tentatively place the animal within the family tree of saber-toothed carnivores and contrast it with the most recognizable saber-toothed cat, Smilodon, which ranged throughout the Americas.

Scratching that bug bite might feel good at first but science explains why it’s a bad idea

You’ve likely heard it since childhood: Don’t scratch that bug bite or rash, you’ll make it worse. But why would something that feels so good be bad?

A lot of things can cause itchiness, sometimes serious diseases. Whatever the cause, doctors have long warned that scratching too much can damage the skin. Now researchers better understand why even a mildly annoying itch could put you on an itch-and-scratch cycle if you give in.

How did they find out? In part by putting tiny “cones of shame” onto mice to uncover what happens on a cellular level when an itch gets scratched—or left alone.

When a pool or pond turns green with algae, don’t reach for chemicals—nature has better solutions

When the Lincoln Memorial Reflecting Pool turned green with algae just days after a US$15 million renovation, the U.S. government scrambled for chemicals and expensive technical solutions to fix the iconic landmark.

Trying to kill algae with chemicals is a common response when community ponds or other water features go green. But as a scientist who studies freshwater ecology, I can tell you there are better solutions that cost far less, last longer and carry less risk of harm to pets and wildlife.

Rather than battling against nature, these alternatives work with nature for long-term solutions.

Hospital AI tool predicts low blood sugar in patients up to 24 hours in advance

Cedars-Sinai Health Sciences University investigators developed an AI-based model that can identify hospitalized patients at risk of low blood sugar up to 24 hours before the condition occurs. The long short-term memory (LSTM) model, described in npj Digital Medicine, could help clinicians intervene earlier and prevent complications, including, in severe cases, seizures, coma and long-term heart arrhythmias.

The model addresses a longstanding challenge in hospital care. Low blood sugar, also called hypoglycemia, is a common and potentially life-threatening complication among hospitalized patients, including those receiving diabetes treatment, those who are fasting before procedures or those in critical care. However, there are no widely used tools for predicting which hospitalized patients may develop hypoglycemia.

“Today, most hospital care for hypoglycemia is reactive, and we respond after a patient’s blood sugar drops,” said Roma Gianchandani, MD, senior author of the study and vice chair of quality and innovation in the Department of Medicine and program director for diabetes.

AI can be an ally in rooting out ransomware threats

AI can be used to prevent cybersecurity threats linked to ransomware, says University of Cincinnati researcher Nelly Elsayed.

“We are in a hype era of AI,” says Elsayed, associate professor in the UC School of Information Technology. “Some people support it, others fear it, but in general people who design technology are trying to use it for good.”

Elsayed, founder and leader of the Applied Machine Learning and Intelligence Lab at UC, recently published research in the Journal of Information Security and Applications, arguing that generative AI may be an ally in strengthening ransomware defense.

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