Osteoporosis weakens bones, making them fragile and more likely to break. As Japan’s population continues to age, the number of people affected is projected to surpass 15 million. Among the various types of fractures caused by osteoporosis, compression fractures of the spine, known as osteoporotic vertebral fractures, are the most common. These injuries can result in long-term disability and severely reduce quality of life, highlighting the need for safer and more effective treatments.

How Fat-Derived Stem Cells Help Rebuild Bone

Stem cells derived from adipose tissue (ADSCs) show strong potential for repairing bone damage. These multipotent cells can develop into various types of tissue, including bone. When ADSCs are cultivated into three-dimensional spherical groups called spheroids, their ability to promote tissue repair increases. Pre-differentiating these spheroids toward bone-forming cells further enhances their effectiveness in stimulating bone regeneration.

Led by Graduate School of Medicine student Yuta Sawada and Dr. Shinji Takahashi, the Osaka research team used ADSCs to create bone-differentiated spheroids and combined them with β-tricalcium phosphate, a material commonly used in bone reconstruction. The mixture was applied to rats with spinal fractures, resulting in significant improvements in bone healing and strength.

The researchers also observed that genes responsible for bone formation and regeneration became more active after the treatment, suggesting that the approach stimulates the body’s natural healing processes.

Promising Outlook for Future Treatments

“This study has revealed the potential of bone differentiation spheroids using ADSCs for the development of new treatments for spinal fractures,” said Sawada. “Since the cells are obtained from fat, there is little burden on the body, ensuring patient safety.”

Dr. Takahashi added, “This simple and effective method can treat even difficult fractures and may accelerate healing. This technique is expected to become a new treatment that helps extend the healthy life of patients.”

The findings were published in Bone & Joint Research.

How organisms grow in response to changing nutrient conditions has long been one of biology’s central questions. Across all forms of life — from microbes to plants and animals — growth depends on access to nutrients, energy, and the internal machinery of cells. Although scientists have studied how these factors affect growth, most research has focused on individual nutrients or specific biochemical pathways. What has remained unclear is how all these interconnected processes within a cell work together to control growth when resources are limited.

A Global Principle That Unites Living Systems

To explore this mystery, ELSI’s Specially Appointed Associate Professor Tetsuhiro S. Hatakeyama and RIKEN Special Postdoctoral Researcher Jumpei F. Yamagishi discovered a new unifying concept that describes how all living cells manage growth under resource constraints. Their work introduces what they call the global constraint principle for microbial growth — a framework that could reshape how scientists understand biological systems.

Since the 1940s, microbiologists have relied on the “Monod equation” to describe how microbes grow. This model shows that growth rates increase with added nutrients until they level off. However, the Monod equation assumes that only one nutrient or biochemical reaction limits growth at a time. In reality, cells perform thousands of simultaneous chemical processes that must share finite resources.

A Network of Constraints Inside Every Cell

According to Hatakeyama and Yamagishi, the traditional model captures only a small part of what’s happening. Instead of a single bottleneck, cellular growth is shaped by a complex network of limitations that interact to slow growth as nutrients accumulate. The global constraint principle explains that when one limiting factor — such as a nutrient — is alleviated, other constraints like enzyme production, cell volume, or membrane space begin to take over.

Using a technique known as “constraint-based modeling,” the team simulated how cells distribute and manage internal resources. Their results showed that while each additional nutrient helps microbes grow, its benefit gradually decreases — each one contributes less than the last.

“The shape of growth curves emerges directly from the physics of resource allocation inside cells, rather than depending on any particular biochemical reaction,” explains Hatakeyama.

Uniting Classic Laws of Biology

This new principle brings together two of biology’s foundational growth laws: the Monod equation and Liebig’s law of the minimum. Liebig’s law states that a plant’s growth is limited by whichever nutrient is scarcest (for example, nitrogen or phosphorus). Even if all other nutrients are plentiful, the plant can only grow as much as the least available one allows.

By merging these two concepts, the researchers created what they call a “terraced barrel” model. In this model, new limiting factors appear in stages as nutrient availability increases. This explains why organisms — from single-celled microbes to complex plants — experience diminishing growth returns even when conditions seem ideal, as each new stage reveals a fresh constraint.

Hatakeyama compares this to an updated version of Liebig’s famous barrel analogy, in which a plant’s growth is limited by its shortest stave, representing the scarcest resource. “In our model, the barrel staves spread out in steps,” he says, “each step representing a new limiting factor that becomes active as the cell grows faster.”

To test their hypothesis, the researchers built large-scale computer models of Escherichia coli bacteria. These models incorporated details about how cells use proteins, how crowded they are inside, and the physical limits of their membranes. The simulations accurately predicted the observed slowing of growth as nutrients were added and showed how oxygen and nitrogen levels affected the results. Laboratory experiments confirmed that the model’s predictions matched real biological behavior.

Toward Universal Laws of Life’s Growth

The discovery offers a new way to understand how life grows, without the need to model every molecule or reaction in detail. The global constraint principle provides a framework that unifies many aspects of biology. “Our work lays the groundwork for universal laws of growth,” says Yamagishi. “By understanding the limits that apply to all living systems, we can better predict how cells, ecosystems, and even entire biospheres respond to changing environments.”

This principle could have far-reaching applications. It may lead to more efficient microbial production in biotechnology, improved crop yields through better nutrient management, and stronger models for predicting how ecosystems respond to climate change. Future research may explore how this principle applies to different types of organisms and how multiple nutrients interact to influence growth. By bridging cellular biology with ecological theory, this study moves science closer to a universal framework for understanding life’s growth limits.

Earth-Life Science Institute (ELSI) is one of Japan’s prominent World Premiere International (WPI) research centers. It aims to drive breakthroughs in interdisciplinary science by attracting top researchers from around the world to collaborate on challenging scientific problems. ELSI’s mission focuses on studying the origin and co-evolution of Earth and life.

The Institute of Science Tokyo (Science Tokyo) was established on October 1, 2024, through the merger of Tokyo Medical and Dental University (TMDU) and Tokyo Institute of Technology (Tokyo Tech). Its mission is “Advancing science and human wellbeing to create value for and with society.”

Japan’s World Premier International Research Center Initiative (WPI), launched in 2007 by the Ministry of Education, Culture, Sports, Science and Technology (MEXT), supports a network of elite research centers that operate with a high degree of independence and global collaboration. The program is managed by the Japan Society for the Promotion of Science (JSPS).

RIKEN, Japan’s largest research institute for basic and applied science, produces over 2,500 papers each year in leading journals across physics, chemistry, biology, engineering, and medicine. Known for its interdisciplinary and international approach, RIKEN has earned a worldwide reputation for scientific excellence.

A new study led by Professor Jan de Jonge, a work and sports psychologist at Eindhoven University of Technology in the Netherlands (and Adjunct Professor at the University of South Australia), found that insufficient and poor-quality sleep significantly increases the chance of getting hurt while running.

In a survey of 425 recreational runners, the researchers discovered that participants who reported shorter sleep duration, lower sleep quality, or frequent sleep problems were almost twice as likely to experience an injury compared to those who slept well.

The results, published in Applied Sciences, provide what Prof de Jonge calls “compelling evidence that sleep is a critical yet often overlooked component of injury prevention.”

“While runners specifically focus on mileage, nutrition and recovery strategies, sleep tends to fall to the bottom of the list,” he explains. “Our research shows that poor sleepers were 1.78 times more likely to report injuries than those with stable, good quality sleep, with a 68% likelihood of sustaining an injury over a 12-month period. That’s a strong reminder that how well you rest is just as important as how hard you train.”

Sleep: The Missing Element in Runner Recovery

Recreational running remains one of the most popular sports worldwide, yet it carries a substantial risk of injury. Studies estimate that up to 90% of runners will be injured at some point, resulting in millions of dollars lost each year in medical bills and missed work.

Prof de Jonge’s team took a comprehensive approach, examining sleep not only in terms of duration but also quality and disorders. This broader view helped identify how different aspects of sleep contribute to physical vulnerability.

“Sleep is a vital biological process that allows the body and mind to recover and adapt to the physical and mental demands of training,” says Prof de Jonge. “When sleep is disrupted or insufficient, the body’s ability to repair tissues, regulate hormones and maintain focus diminishes, all of which can increase injury risk.”

The study revealed that runners who struggled with falling asleep, woke up frequently during the night, or rarely felt rested were the most prone to injury. In contrast, those who maintained consistent sleep schedules and felt well-rested reported significantly fewer injuries.

Rethinking Training: Why Sleep Deserves Equal Priority

Prof de Jonge emphasizes that the research carries important lessons for both recreational and competitive runners, as well as for coaches and health professionals.

“We often assume that more training equals better performance, but that’s not necessarily the case,” he notes. “Runners (especially those balancing training with work, family and social commitments) may actually need more sleep than average adults to recover properly. Sleep should be treated as a performance priority, not an afterthought.”

Experts generally recommend seven to nine hours of sleep per night, though athletes often benefit from additional rest, including short naps, to enhance both physical and mental recovery.

To improve sleep quality, consistent bedtimes, limiting screen use before sleep, reducing caffeine and alcohol, and maintaining a quiet, cool environment are all advised.

“Sleep quality and sleep duration are both important, but quantity often provides the bed-rock,” Prof de Jonge concludes. “Sleep should be recognized not only as a recovery tool, but also as a potential predictor of injury vulnerability in recreational sports.”

The study, “Sleep Matters: Profiling Sleep Patterns to Predict Sports Injuries in Recreational Runners,” was published in Applied Sciences.

In a large randomized clinical trial, researchers found that managing patients’ vitamin D levels through a “target-to-treat” approach — where blood levels were monitored and dosages were adjusted to reach an optimal range — cut the likelihood of a second heart attack by 50%.

The findings were presented on Nov. 9 at the 2025 American Heart Association Scientific Sessions in New Orleans.

Encouraging Early Results from Intermountain Researchers

These results are very encouraging, said Heidi May, PhD, cardiovascular epidemiologist at Intermountain Health and the study’s principal investigator. “We observed no adverse outcomes when giving patients higher doses of vitamin D₃ supplementation, and to significantly reduce the risk of another heart attack, which are exciting results,” said Dr. May. “We’re excited with these results but know we have further work to do to validate these findings.”

According to researchers, the results carry global importance, as between one-half and two-thirds of people worldwide have low levels of vitamin D.

In the past, most individuals received sufficient vitamin D through sunlight exposure. Today, with lifestyle changes and medical advice aimed at reducing skin cancer risk, people spend less time in the sun and must rely more on dietary supplements such as vitamin D₃ to maintain healthy levels.

From Observation to Precision Treatment

Low vitamin D levels have long been linked to poor cardiovascular outcomes in observational studies. However, earlier clinical trials that provided standard supplementation doses failed to show measurable reductions in heart disease risk. Intermountain scientists wanted to test a different idea: rather than giving everyone the same dose, what if supplementation was adjusted to reach a specific, healthy vitamin D level?

“Previous studies just gave patients supplementation without regularly checking blood levels of vitamin D to determine what supplementation achieved,” said Dr. May. “With more targeted treatment, when we checked exactly how supplementation was working and made adjustments, we found that patients had their risk of another heart attack cut in half.”

Inside the TARGET-D Clinical Trial

The Intermountain study, called the TARGET-D trial, ran from April 2017 to May 2023 and included 630 patients who had suffered a heart attack within a month of enrolling. Participants were followed until March 2025 to monitor cardiovascular outcomes.

Patients were randomly assigned to one of two groups: one received no vitamin D management, and the other underwent active, targeted vitamin D₃ treatment.

The goal for the treatment group was to raise blood vitamin D levels to above 40 nanograms per milliliter (ng/mL). At the start, 85% of participants had vitamin D₃ levels below that threshold (<40 ng/mL).

Dosing, Monitoring, and Results

More than half of the patients receiving targeted therapy required an initial dose of 5,000 international units (IU) of vitamin D₃, compared to typical supplement recommendations of 600-800 IU.

Vitamin D blood levels were checked annually for those maintaining healthy levels. Patients with lower levels were tested every three months and had their dosage adjusted until reaching the 40 ng/mL target. Afterward, their levels were monitored once a year.

Researchers tracked major cardiac events (MACE), including heart attacks, strokes, heart failure hospitalizations, or deaths. Out of 630 participants, 107 experienced such events. While there was no significant difference in the overall risk of MACE between the two groups, the chance of having a second heart attack was cut in half among those receiving targeted vitamin D treatment.

Next Steps for Heart and Vitamin D Research

Researchers plan to expand their work with a larger clinical trial to confirm and build upon these findings.

A larger study group will allow us to more fully evaluate whether targeted vitamin D management can reduce not only repeat heart attacks but also other forms of cardiovascular disease, said Dr. May.

On February 25, 2024, XRISM used its Resolve instrument to observe the neutron star GX13+1, the compact remnant of a once larger star. GX13+1 shines brightly in X-rays that come from an accretion disk of superheated material spiraling inward and striking the star’s surface.

These inward flows can also launch powerful outflows that alter the space around them. How these outflows arise is still under investigation, which is why the team targeted GX13+1.

Resolve can precisely measure the energy of individual X-ray photons, so the scientists anticipated seeing fine-grained details that had never been captured before.

“When we first saw the wealth of details in the data, we felt we were witnessing a game-changing result,” says Matteo Guainazzi, ESA XRISM project scientist. “For many of us, it was the realization of a dream that we had chased for decades.”

Why cosmic winds matter

These winds are not just curiosities. They drive large-scale change in the universe.

Similar winds also blow from systems with supermassive black holes at galaxy centers. They can compress giant molecular clouds to trigger star birth or heat and disperse those clouds to halt star formation. Astronomers refer to this push and pull as feedback, and in extreme cases the wind from a central black hole can regulate the growth of its entire host galaxy.

Because the processes around supermassive black holes might mirror those near GX13+1, the team chose this neutron star system as a closer, brighter target that could reveal the underlying physics in sharper detail.

A timely surge to the Eddington limit

Just before the planned observations, GX13+1 unexpectedly brightened and reached or even surpassed the Eddington limit.

This limit describes what happens as matter falls onto a compact object such as a black hole or a neutron star. More infalling matter releases more energy. As the energy output rises, the radiation exerts pressure on the incoming material and pushes it outward. At the Eddington limit, the high-energy light being produced can drive almost all of the infalling matter back into space as a wind.

Resolve recorded GX13+1 during this dramatic phase.

“We could not have scheduled this if we had tried,” said Chris Done, Durham University, UK, the lead researcher on the study. “The system went from about half its maximum radiation output to something much more intense, creating a wind that was thicker than we’d ever seen before.”

A slow, dense wind defies expectations

Despite the intense outburst, the wind’s speed remained near 1 million km/h. That is swift on Earth but slow compared with winds near the Eddington limit around supermassive black holes, where outflows can reach 20 to 30 percent of light speed, more than 200 million km/h.

“It is still a surprise to me how ‘slow’ this wind is,” says Chris, “as well as how thick it is. It’s like looking at the Sun through a bank of fog rolling towards us. Everything goes dimmer when the fog is thick.”

Neutron star vs black hole winds

This was not the only contrast. Earlier XRISM observations of a supermassive black hole at the Eddington limit revealed an ultrafast, clumpy wind. By comparison, the outflow from GX13+1 appears slow and smooth.

“The winds were utterly different but they’re from systems which are about the same in terms of the Eddington limit. So if these winds really are just powered by radiation pressure, why are they different?” asks Chris.

Accretion disk temperature as the key

The team suggests the answer lies in the temperature of the accretion disk around the central object. Counterintuitively, disks around supermassive black holes tend to be cooler than those in stellar-mass systems with neutron stars or black holes.

Disks around supermassive black holes are much larger. They can be extremely luminous, yet that power is spread over a vast area, so the typical radiation they emit peaks in ultraviolet light. Stellar-mass systems radiate more strongly in X-rays.

Ultraviolet light interacts with matter more readily than X-rays. Chris and colleagues propose that this difference allows ultraviolet radiation to push material more efficiently, generating the much faster winds seen near supermassive black holes.

What this means for galaxy evolution

If this explanation holds, it will refine how scientists think about the exchange of energy and matter in extreme environments. It could also clarify how these processes influence the growth of galaxies and the broader evolution of the cosmos.

“The unprecedented resolution of XRISM allows us to investigate these objects — and many more -in far greater detail, paving the way for the next-generation, high-resolution X-ray telescope such as NewAthena,” says Camille Diez, ESA Research fellow.

XRISM mission at a glance

XRISM (pronounced krizz-em) launched on September 7, 2023. The mission is led by the Japan Aerospace Exploration Agency (JAXA) in partnership with NASA and ESA. It flies with two instruments: Resolve, an X-ray calorimeter that measures the energy of individual X-ray photons to deliver an unprecedented level of energy resolution (the capability of an instrument to distinguish the X-ray ‘colors’), and Xtend, a wide-field X-ray CCD camera that images the surrounding region.

Dr. Mir Faizal, an Adjunct Professor at UBC Okanagan’s Irving K. Barber Faculty of Science, and his collaborators, Drs. Lawrence M. Krauss, Arshid Shabir, and Francesco Marino, have shown that the underlying fabric of reality operates in a way no computer could ever replicate.

Their study, published in the Journal of Holography Applications in Physics, doesn’t just dispute the idea of a simulated universe like The Matrix. It goes further, demonstrating that the cosmos itself is built upon a kind of understanding that lies outside the reach of any algorithm.

The Simulation Hypothesis Meets Mathematics

“It has been suggested that the universe could be simulated. If such a simulation were possible, the simulated universe could itself give rise to life, which in turn might create its own simulation. This recursive possibility makes it seem highly unlikely that our universe is the original one, rather than a simulation nested within another simulation,” says Dr. Faizal. “This idea was once thought to lie beyond the reach of scientific inquiry. However, our recent research has demonstrated that it can, in fact, be scientifically addressed.”

The team’s findings rest on the evolving understanding of what reality truly is. Physics has moved far beyond Isaac Newton’s view of solid objects moving through space. Einstein’s theory of relativity replaced that classical model, and quantum mechanics transformed it yet again. Now, at the forefront of theoretical physics, quantum gravity proposes that even space and time are not fundamental elements. Instead, they arise from something deeper — pure information.

The Hidden Realm Beneath Reality

Physicists describe this informational layer as a “Platonic realm,” a mathematical foundation more real than the physical world we perceive. According to the new research, it is from this realm that space and time themselves emerge.

However, the scientists demonstrated that even this information-based structure cannot fully describe reality through computation alone. By applying advanced mathematical principles, including Gödel’s incompleteness theorem, they proved that any consistent and complete model of existence requires what they call “non-algorithmic understanding.”

To grasp this idea, imagine how a computer works — it follows a set of defined instructions step by step. Yet, some truths exist that cannot be reached by following any sequence of logical operations. These are known as “Gödelian truths,” and while they are real, they cannot be proven using computation.

Where Computation Fails

Consider the statement, “This true statement is not provable.” If it were provable, it would be false, contradicting logic. If it cannot be proven, then it is true, which means any logical system attempting to prove it is incomplete. In either case, computation alone falls short.

“We have demonstrated that it is impossible to describe all aspects of physical reality using a computational theory of quantum gravity,” says Dr. Faizal. “Therefore, no physically complete and consistent theory of everything can be derived from computation alone. Rather, it requires a non-algorithmic understanding, which is more fundamental than the computational laws of quantum gravity and therefore more fundamental than spacetime itself.”

Why the Universe Cannot Be Simulated

If the underlying rules of the Platonic realm seem similar to those governing a computer simulation, could that realm itself be simulated? The answer, according to the researchers, is no.

“Drawing on mathematical theorems related to incompleteness and indefinability, we demonstrate that a fully consistent and complete description of reality cannot be achieved through computation alone,” explains Dr. Faizal. “It requires non-algorithmic understanding, which by definition is beyond algorithmic computation and therefore cannot be simulated. Hence, this universe cannot be a simulation.”

Co-author Dr. Lawrence M. Krauss notes that the implications of this finding extend deep into the foundations of physics. “The fundamental laws of physics cannot be contained within space and time, because they generate them. It has long been hoped, however, that a truly fundamental theory of everything could eventually describe all physical phenomena through computations grounded in these laws. Yet we have demonstrated that this is not possible. A complete and consistent description of reality requires something deeper — a form of understanding known as non-algorithmic understanding.”

Reality Beyond Algorithms

As Dr. Faizal summarizes, “Any simulation is inherently algorithmic — it must follow programmed rules. But since the fundamental level of reality is based on non-algorithmic understanding, the universe cannot be, and could never be, a simulation.”

For years, the simulation hypothesis was regarded as untestable, confined to the realms of philosophy and speculative fiction. This new research, however, anchors it firmly in mathematical and physical theory — delivering what may be the final, definitive answer to one of science’s most intriguing questions.