Scientists discover oral compound that helps “reset” the body clock forward

A potential breakthrough for jet lag and shift work-related sleep disorders

Kanazawa University

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(Upper left) Jet lag from international travel; (Upper right) Mic-628-induced phase advances in behavioral, central, and peripheral circadian clocks; (bottom) Mic-628-CRY recruits CLOCK-BMAL1 dimer to dual E-boxes, inducing Period1.

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Credit: Kanazawa University

Key findings

A collaborative team including Emeritus Professor Tei H. (Kanazawa University), Associate Professor Takahata Y. (Osaka University), Professor Numano R. (Toyohashi University of Technology), and Associate Professor Uriu K. (Institute of Science Tokyo) discovered that Mic-628 selectively induces the mammalian clock gene Per1.
Mic-628 works by binding to the repressor protein CRY1, promoting the formation of a CLOCK–BMAL1–CRY1–Mic-628 complex that activates Per1 transcription through a “dual E-box” DNA element. As a result, both the central clock in the brain’s suprachiasmatic nucleus (SCN) and peripheral clocks in tissues such as the lungs were advanced—in tandem and independent of dosing time.

In a simulated jet lag mouse model (6-hour light-dark phase advance), a single oral dose of Mic-628 shortened re-entrainment time from seven days to four. Mathematical modeling revealed that the compound’s stable and unidirectional phase-advancing effect is mediated by a negative auto-regulatory feedback of the PER1 protein itself.

 

Background and significance

Adapting to eastward travel, such as west-to-east transmeridian flights, or to night-shift work requires advancing the internal clock, a process that normally takes longer and is physiologically harder than delaying it. Existing methods, such as light therapy or melatonin, are heavily constrained by timing and often yield inconsistent results. Mic-628’s consistent phase-advance effect, regardless of when it is administered, represents a new pharmacological strategy for resetting the circadian clock.

 

What’s next?

The researchers plan to investigate the safety and efficacy of Mic-628 in further animal and human studies. Because it reproducibly advances the body clock through a well-defined molecular mechanism, Mic-628 may serve as a prototype “smart drug” for managing jet lag, shift work-related sleep problems, and other circadian misalignment disorders.

These results will be published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) in 2026.

 

About Kanazawa University

- Contributing to Society through "Future Oriented Intelligence", Built on an "All Kanazawa University" Approach. Kanazawa University (KU), founded in 1862, is a research university dedicated to education, while opening up its doors to both local and global society. Guided by our vision, "Kokorozashi," we contribute to society through "Future-oriented Intelligence," addressing current challenges and anticipating future ones from both local and global perspectives. KU includes 4 colleges, 20 schools, 7 graduate schools, a hospital, and specialized research centers such as the Cancer Research Institute, a leading hub for research on cancer metastasis and drug development. Over 1,000 researchers drive innovation and international collaboration across diverse fields. KU is advancing research through WPI (World Premier International Research Center Initiative) and J-PEAKS (Program for Forming Japan's Peak Research Universities), accelerating interdisciplinary and international collaborations and innovations. Learn more here: https://www.kanazawa-u.ac.jp/en/

 

About The University of Osaka

The University of Osaka was founded in 1931 as one of the seven imperial universities of Japan and is now one of Japan's leading comprehensive universities with a broad disciplinary spectrum. This strength is coupled with a singular drive for innovation that extends throughout the scientific process, from fundamental research to the creation of applied technology with positive economic impacts. Its commitment to innovation has been recognized in Japan and around the world. Now, The University of Osaka is leveraging its role as a Designated National University Corporation selected by the Ministry of Education, Culture, Sports, Science and Technology to contribute to innovation for human welfare, sustainable development of society, and social transformation.

Learn more here:
https://resou.osaka-u.ac.jp/en

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Journal

Proceedings of the National Academy of Sciences

DOI

10.1073/pnas.2509943123 

Article Title

A Period1 inducer specifically advances circadian clock in mice

 

Why are some animal and human signals honest, while others are deceptive?

Hun-Ren Ökológiai Kutatóközpont

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An in-depth analysis reveals that signals, like the ornate train of the peacock need not be exaggerated, costly, or wasteful to be honest. More fit individuals can invest more into signalling (reproduction) and survival and they can do it along a different trade-off (teal curve) than less fit individuals (red curve). This also means that fitter males may get more long-term reward (e.g. offspring) than weaker ones, independent of the actual energetic cost of the signal.

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Credit: Credit: István Zachar 2026

For decades, scientists have tried to answer a simple question: why be honest when deception is possible? Whether it is a peacock’s tail, a stag’s roar, or a human’s résumé, signals are means to influence others by transmitting information and advantages can be gained by cheating, for example by exaggeration. But if lying pays, why does communication not collapse?

The dominant theory for honest signals has long been the handicap principle, which claims that signals are honest because they are costly to produce. It argues that a peacock’s tail, for example, is an honest signal of a male’s condition or quality to potential mates because it is so costly to produce. Only high-quality birds could afford such a handicap, wasting resources growing it, demonstrating their superb quality to females, whereas poor quality males cannot afford such ornaments.

A new synthesis by Szabolcs Számadó, Dustin J. Penn and István Zachar (from the Budapest University of Technology and Economics, University of Veterinary Medicine Vienna and HUN-REN Centre for Ecological Research, respectively) challenges that logic. They argue that honesty does not depend on how costly or wasteful a signal is, but rather on the trade-offs between investments and benefits, faced by signalers.

They explain that signals are not honest because they are costly, instead, honesty evolves when it is beneficial and deception is costly. Previous studies inspired by the handicap principle (refuted by the authors in the paper) misleadingly focused on only the costs of signalling. Yet biological functions, like signalling, cannot be understood in the evolutionary context without their benefits, often realized in the long run.

The new theory, called Signalling Trade-Off Theory, shifts the focus from absolute cost to choice in what to invest. In biology, every organism faces competing demands: investing more in one thing means having less for another. Time spent courting cannot be spent feeding; energy put into bright feathers cannot be used for immune defence. These are trade-offs. And these are also present in economic choices for humans. Crucially, they differ between individuals. A healthy, well-fed animal can afford different choices than a weak or starving one. According to several theoretical studies, signalling trade-offs and not absolute costs define whether deception or honesty evolves.

“Signals, in theory, can be absolutely cost free in terms of immediate energy investment.” – István Zachar, one of the authors explains – “Honesty does not come from how much a signal harms you but from what kind of cost-benefit ratio you can realize with it.” And this trade-off between investments and benefits is defined by the condition of the individual.

According to theory, honest signals arise when these trade-offs respect the true quality of the individual, i.e. are condition-dependent. High-quality individuals get more return from the same investment than low-quality ones. As a result, the best strategy for a strong individual is to signal more, while the best strategy for a weak individual is to signal less. “Both are behaving optimally,” the author says, “but because their trade-offs are different, their signals end up revealing who they are.” This is how honesty is defined.

This perspective helps clear up a long-standing puzzle. An increasing number of studies show that honest signals are sometimes cheap, cost-free, or even beneficial to produce. Under the handicap view, this was baffling because honesty was supposed to require wasteful costs. Under the trade-off view, it is what one would expect. What matters is not whether a signal costs something in absolute terms, but whether pretending to be better than you are would push you into a worse overall outcome. Trade-offs apply to cheaters as well, and while they can increase their reproductive success by a fake message, this may severely affect their survival.

The trade-off theory also explains why deception is common. If different quality individuals face the same trade-offs, then nothing stops them from using the same signal. In those cases, mimics, bluffers, and cheats can thrive. “Dishonesty is absolutely not a failure of nature,” – Zachar notes. “It is what you get when the trade-offs that normally separate the different quality individuals disappear or become identical.”

This idea helps make sense of cases ranging from harmless butterflies mimicking poisonous ones to animals that increase their sexual displays when they are near death. In such “terminal investment,” there is little future to protect, so the usual balance between today and tomorrow is gone, and exaggerated signalling becomes worthwhile.

Why does this matter beyond biology? Because the same logic applies to human communication, from advertising to cooperation based on reputation. We all operate under trade-offs (inherited or learnt) between short-term gains and long-term consequences. Signals are reliable when those trade-offs differ across people in ways that make bluffing unprofitable.

“The real question is not ‘how costly is this signal?’” – Zachar says – “It is ‘what would it cost this person, in terms of what else they could have done, to fake it?’”

By reframing honesty in terms of trade-offs rather than waste, the new theory brings signalling back in line with a broader understanding of evolution: organisms are not rewarded for squandering resources, but for allocating them efficiently under constraints. In that light, honest communication is not a miracle. It is a natural outcome of living in a non-quantum biological world where every choice closes off another.

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Journal

Journal of Evolutionary Biology

DOI

10.1093/jeb/voaf144 

Method of Research

Literature review

Subject of Research

Animals

Article Title

A general signalling theory: why honest signals are explained by trade-offs rather than costs or handicaps

 

Comparison and selection of support schemes for deep buried soft broken section of Xinjin expressway spiral tunnel—a case study of Hankou tunnel

ELSP

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The analysis findings from this study on tunnel excavation support could be applied to deep-buried sections with Grade V surrounding rock and to tunnels under similar engineering contexts.

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Credit: Dechun Lu, Xiaoyu Liu, Caixia Guo, Xiuli Du/ Beijing University of Technology, Haining Xu/China Construction Road and Bridge Group Fourth Engineering Co., Ltd.

The research focused on the Hankou Tunnel, a deep-lying section of the challenging Xinjin Expressway spiral tunnel group. To find the best way to support the tunnel walls, the research team turned to advanced computer simulation technology (using the ABAQUS platform). Researchers created detailed digital models to simulate the entire construction process from start to finish. Published in Smart Construction, the findings offer crucial reference for designing more effective support systems for other deep mountain tunnels built in similar rock formations.

Nowadays mountain tunnels are playing an increasingly critical role in modern transportation systems, leading to the continuous emergence of numerous long, deep-buried mountain tunnel projects. However, there remains ongoing debate about how effectively standard ground anchors work in tunnels and their true supporting role. Meanwhile, although pre-support pipes are commonly used for advance reinforcement, there has been little research into how they perform when combined with ground anchors.

To address this gap, a research team led by Professor Dechun Lu from Beijing University of Technology developed highly accurate computer simulations that replicate the entire tunnel excavation process. Using these models, the team compared the effectiveness of ground anchors and pre-support pipes, both individually and in combination, offering new evidence to help optimize support strategies in challenging ground conditions.

Professor Lu explained: "Our model was carefully validated by comparing its results with actual data from the construction site, ensuring that it reliably reflects real-world engineering conditions."

After validating the model against real-world field measurements, the research team closely examined multiple indicators of deformation and mechanical response. These included the settlement of the tunnel crown, the inward horizontal movement of the surrounding rock and primary support, the development of stress fields in the rock mass, and the identification of potential plastic failure zones.

Graduate researcher Xiaoyu Liu explained: "We conducted a thorough and detailed analysis of the simulation results. This not only focused on the final stresses and deformations after tunnel excavation was complete but also investigated how these values changed throughout the construction process and at each major step."

Integrating engineering cost calculations with their simulation findings, the researchers conducted a detailed comparative analysis of how well ground anchors and pre-support pipes performed in this deep section of the Hankou Tunnel.

The study concluded that, for the geological conditions examined, a support system combining primary lining, secondary lining, and ground anchors was sufficient to effectively control rock stress and deformation. Pre-support pipes can serve as a valuable extra step in particularly weak or fractured zones, helping to pre-stabilize the ground before the main excavation passes through.

This approach provides engineers with a flexible strategy: use the combined lining and anchor system as the standard, and add pre-support pipes specifically where the ground conditions are poorest.

While the team acknowledges that certain details in the simulation models could be further refined, this research represents an important step toward safer and more reliable reinforcement methods for mountain tunnels.

This paper “Comparison and selection of support schemes for deep buried soft broken section of Xinjin expressway spiral tunnel—a case study of Hankou tunnel” was published in Smart Construction (ISSN: 2960-2033), a peer-reviewed open access journal dedicated to original research articles, communications, reviews, perspectives, reports, and commentaries across all areas of intelligent construction, operation, and maintenance, covering both fundamental research and engineering applications. The journal is now indexed in Scopus, and article submission is completely free of charge until 2026.

Lu D, Liu X, Xu H, Guo C, Du . Comparison and selection of support schemes for deep buried soft broken section of Xinjin expressway spiral tunnel—a case study of Hankou tunnel. Smart Constr. 2026(1):0002, https://doi.org/10.55092/sc20260002.

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Journal

Smart Construction

DOI

10.55092/sc20260002 

Method of Research

Computational simulation/modeling

Subject of Research

Not applicable

Article Title

Comparison and selection of support schemes for deep buried soft broken section of Xinjin expressway spiral tunnel—a case study of Hankou tunnel