Two hypotheses have been proposed to explain how the brain perceives pain. One is the Estimate Hypothesis, where the brain estimates the intensity of pain based on predictions. The other is the Surprise Hypothesis, where the brain perceives pain as the difference between prediction and reality, otherwise known as the prediction error. In this study, the mechanism underlying the perception of pain were investigated. In the experiment, healthy participants received painful thermal stimuli and reported felt pain intensity while observing painful or non-painful visual stimuli in the virtual reality. The researchers found that the participants strongly perceived pain when the prediction error was large, demonstrating that the Surprise Hypothesis more adequately explains the pain perception mechanism in the brain. The study further confirmed that pain was amplified when unexpected events occurred.

People with chronic pain often experience vague pain-related fears and anxieties. Possibly, this uncertain gap between expectation and reality further increases the perceived intensity of pain. Therefore, reducing the gap between pain expectation and reality or “surprise” is important in reducing pain. A better understanding of pain perception would facilitate the development of new treatments that would enhance recovery from chronic pain and trauma.

This work was supported by JSPS KAKENHI (grant numbers 19H05729 and 23KJ0261).

Thermoelectric coolers, also called solid-state refrigerators, can induce localized cooling by using an electric current to transfer heat from one side of the device to another. Their long lifetimes, invulnerability to leaks, size and shape tunability, and the lack of moving parts (such as circulating liquids) make these devices ideal for diverse cooling applications, such as electronics. However, manufacturing them out of ingots is associated with high costs and generates lots of material waste. In addition, the devices’ performance remains limited.

Now, a team at the Institute of Science and Technology Austria (ISTA), led by Verbund Professor for Energy Sciences and Head of the Werner Siemens Thermoelectric Laboratory Maria Ibáñez, with first author and ISTA postdoc Shengduo Xu, developed high-performance thermoelectric materials out of the 3D printer and used them to build a thermoelectric cooler. “Our innovative integration of 3D printing into thermoelectric cooler fabrication greatly improves manufacturing efficiency and reduces costs,” says Xu. Also, in contrast to previous attempts at 3D printing thermoelectric materials, the present method yields materials with considerably higher performance. ISTA Professor Ibáñez adds, “With commercial-level performance, our work has the potential to extend beyond academia, holding practical relevance and attracting interest from industries seeking real-world applications.”

Pushing the boundaries of thermoelectric technologies

While all materials demonstrate some thermoelectric effect, it is often too negligible to be useful. Materials exhibiting a high enough thermoelectric effect are usually so-called “degenerate semiconductors,” i.e., “doped” semiconductors, to which impurities are introduced intentionally so they behave like conductors. Current state-of-the-art thermoelectric coolers are produced using ingot-based manufacturing techniques — expensive and power-hungry procedures requiring extensive machining processes after production, where a lot of material is wasted. “With our present work, we can 3D print exactly the needed shape of thermoelectric materials. In addition, the resulting devices exhibit a net cooling effect of 50 degrees in the air. This means that our 3D-printed materials perform similarly to ones that are significantly more expensive to manufacture,” says Xu. Thus, the team of ISTA material scientists proposes a scalable and cost-effective production method for thermoelectric materials, circumventing energy-intensive and time-consuming steps.

Printed materials with optimized particle bonding

Beyond applying 3D printing techniques to produce thermoelectric materials, the team designed the inks so that, as the carrier solvent evaporates, effective and robust atomic bonds are formed between grains, creating an atomically connected material network. As a result, the interfacial chemical bonds improve the charge transfer between grains. This explains how the team managed to enhance the thermoelectric performance of their 3D-printed materials while also shedding new light on the transport properties of porous materials. “We employed an extrusion-based 3D printing technique and designed the ink formulation to ensure the integrity of the printed structure and boost particle bonding. This allowed us to produce the first thermoelectric coolers from printed materials with comparable performance to ingot-based devices while saving material and energy,” says Ibáñez.

Medical applications, energy harvesting, and sustainability

Beyond rapid heat management in electronics and wearable devices, thermoelectric coolers could have medical applications, including burn treatment and muscle strain relief. In addition, the ink formulation method developed by the team of ISTA scientists can be adapted for other materials to be used in high-temperature thermoelectric generators — devices that can generate electrical voltage from a temperature difference. According to the team, such an approach could broaden the applicability of thermoelectric generators across various waste energy harvesting systems.

“We successfully executed a full-cycle approach, from optimizing the raw materials’ thermoelectric performance to fabricating a stable, high-performance end-product,” says Ibáñez. Xu adds, “Our work offers a transformative solution for thermoelectric device production and heralds a new era of efficient and sustainable thermoelectric technologies.”

A study into the vaccine’s effectiveness, published in eBioMedicine, was led by experts from the Sydney Infectious Diseases Institute at University of Sydney, the Centenary Institute and the Monash Institute of Pharmaceutical Science (MIPS) at Monash University.

Currently the only approved vaccine for TB is the century-old Bacillus Calmette-Guerin (BCG) vaccine, which is widely used despite its effectiveness in adults being inconsistent.

The study found that the new mRNA vaccine was successful in triggering an immune defence response that helped to reduce TB numbers in infected mice. In addition, the researchers discovered that for mice that had received the BCG vaccine, a booster dose of the new mRNA vaccine significantly improved their long-term protection.

The vaccine used mRNA technology, which is where genetic instructions are used to trigger an immune response in the body, as opposed to using a weakened or deadened version of a virus.

Senior author Professor Jamie Triccas, Deputy Director of the Sydney Infectious Diseases Institute, said: “Our findings demonstrate that an mRNA vaccine can induce potent, pathogen-specific immune responses that target TB, a disease that has long evaded effective vaccine development. This represents a major advance in TB vaccine research and provides a strong rationale for further clinical development.”

TB is the leading cause of infectious mortality worldwide, responsible for approximately 1.3 million deaths annually, with a particular prevalence in countries such as India, Indonesia, Vietnam and Pakistan.

The researchers hope that the mRNA vaccine will ultimately be more effective and consistent than the BCG when used in humans. This is because, unlike protein-based or live-attenuated vaccines (those that contain a weakened version of a pathogen), mRNA vaccines allow for rapid adaptation, making them an attractive option for global TB control efforts.

Dr Claudio Counoupas, co-lead author from the Centenary Institute’s Centre for Infection & Immunity, highlighted the vaccine’s potential impact: “mRNA vaccines offer a scalable, cost-effective, and adaptable platform that can be rapidly deployed against infectious diseases. This study is an important step in demonstrating that mRNA technology is not just for COVID-19 but could be a game-changer for bacterial diseases like TB.”

Professor Colin Pouton from Monash University, a key contributor to the study, explained: “The success of mRNA vaccines in the COVID-19 pandemic underscored their ability to generate strong immune responses. Our study provides the evidence that this platform can be harnessed for TB, potentially improving protection and durability of immunity in a way that traditional vaccines cannot.”

Following the study’s promising results, the research team is now looking to advance the vaccine to clinical trials.

“Our next goal is to refine the formulation and assess its efficacy in larger models before moving to human studies,” said Professor Triccas. “Given the global burden of TB and the limitations of current vaccines, we believe this platform could provide a new pathway toward eradicating this disease.”

Phosphorus and nitrogen, which are essential for plant growth, are often supplemented by chemical fertilizers to assure proper balance and output of produce. However, the amount of these nutrients on the planet is increasing due to excessive use, which in turn is causing various environmental problems. For this reason, there is a growing movement to promote sustainable agriculture through the recycling of phosphorus and nitrogen. In Japan, a target has been set to reduce the use of chemical fertilizers by 30% by 2050.

With this in mind, a research group led by Ryosuke Endo, a lecturer, and graduate student Satoru Sakuma at Osaka Metropolitan University’s Graduate School of Agriculture conducted an experiment on producing recycled liquid fertilizer from organic waste as a replacement for chemical fertilizers. Using food waste, manure, and sewer sludge, the researchers filled nitrification reactors with organic waste and tap water, then extracted nitrified biogas digestate (f-NBD) to use as seed culture. The phosphorus and nitrogen outputs from each type of organic waste were compared. This experimental method produced nutrient solutions capable of replacing unsustainable chemical phosphorus and nitrogen.

Additionally, the researchers have established an improved method that increases phosphorus solubility, as phosphorus often fails to dissolve during traditional fertilizer production methods. By lowering the pH of the waste-derived liquid fertilizer, the phosphorus will dissolve and produce high phosphorus content, before the pH is restored to its original level.

“This research suggests that it is possible to replace up to 100% of the nitrogen and up to 77% of the phosphorus in liquid chemical fertilizers with the solution produced in this study,” stated graduate student Sakuma.

“Reducing the use of chemical fertilizers has become a global trend,” Dr. Endo added, “but hydroponic agricultural systems are highly dependent on them. By applying the results of this research and reusing the phosphorus contained in organic waste as liquid fertilizer, we hope that this will lead to the development of recycling-oriented agriculture.”

The study, published Jan. 30 in the Journal of Antimicrobial Chemotherapy, adds to growing evidence that lenacapavir may be a powerful new tool in the global anti-HIV drug arsenal. Approximately, 1.5 million people are living with HIV in Uganda.

“Our data shows that only 1.6% of the individuals studied are living with HIV strains that have any known lenacapavir-associated resistance mutations,” said senior author Dr. Guinevere Lee, assistant professor of virology in medicine at Weill Cornell Medicine. “That’s important because it shows lenacapavir is likely to be effective against strains of HIV circulating in East Africa.”

Since the 1990s, HIV drug combinations targeting different steps in the virus’ life cycle have been able to reduce virus load in patients to nearly undetectable levels. But drug resistance is a growing concern as the virus has evolved ways to thwart existing therapies. Lenacapavir, however, is the first drug to disrupt the protective capsid layer surrounding HIV’s genetic material (RNA), blocking the virus’s ability to reproduce and be transmitted from person to person.

Treatment twice a year with lenacapavir has been effective in patients who have never been treated and those with HIV strains that are resistant to other drugs. Last year, clinical trials showed that lenacapavir injections were 100% effective in preventing HIV infection among women in sub-Saharan Africa, who were HIV-negative.

However, little information was available about pre-existing resistance to lenacapavir in less well-studied HIV-1 strains like subtype A1 and D, which are more common in Eastern and Southern Africa. HIV-1 subtype B strains, which predominantly affect Europe and the United States, rarely have pre-existing mutations that would cause lenacapavir drug resistance.

Dr. Lee and her colleagues at Mbarara University of Science and Technology in Uganda and Massachusetts General Hospital in Boston helped fill that gap. They sequenced the capsid proteins from HIV-1 subtypes A1 and D from 546 Ugandan patients, who had never used antiretroviral therapy before. This approach allowed the investigators to examine naturally circulating viral variants.

They found that none of the patients had genetic mutations that would lead to major lenacapavir resistance. Only nine participants had minor lenacapavir resistance mutations that could partially reduce the effectiveness, but not enough to cause full resistance to the drug.

“Our study supports lenacapavir’s potential efficacy in this region. As lenacapavir is rolled out in East Africa, further studies will need to monitor for the emergence of drug-resistant strains,” Dr. Lee said. “It is important that we ensure HIV research reaches understudied communities where unique viral strains circulate.”