An estimated 100 million people in the U.S. have metabolic dysfunction-associated steatotic liver disease (MASLD), formerly called nonalcoholic fatty liver disease, according to the American Liver Foundation. Roughly 20% to 25% of those affected go on to develop metabolic dysfunction-associated steatohepatitis (MASH), a more serious form of the condition in which excess liver fat is accompanied by inflammation, cell injury and scarring.

Why MASH Is Difficult to Treat

Current care mainly centers on lifestyle changes and efforts to limit additional liver damage. Although medications are available, treatment options are still limited, and there is currently no cure for MASH.

Earlier research has suggested that damaged mitochondria, the structures that produce energy for cells, may contribute to the development and progression of MASH. In the new multicenter study, Cedars-Sinai researchers found that levels of an enzyme called UBE2N decline in liver cells as the disease becomes more advanced.

“The UBE2N enzyme appears to protect the liver from the inflammation and damage associated with MASH by helping remove damaged mitochondria and supporting the breakdown of fat,” said Ekihiro Seki, MD, PhD, professor of Medicine and Biomedical Sciences at Cedars-Sinai and co-corresponding author of the study. “When levels of the enzyme fell, we saw more damaged cells and injury to the liver.”

Restoring UBE2N Reduced Liver Damage in Mice

The researchers then restored UBE2N to normal levels in the livers of laboratory mice. After doing so, they observed reductions in fat accumulation, inflammation and scarring.

Those results suggest that UBE2N could become a potential treatment target for preventing MASLD from advancing to MASH.

“The identification of this enzyme’s role in regulating mitochondria in the liver is an important advance in understanding steatotic liver disease,” said Shelly Lu, MD, the Women’s Guild Chair in Gastroenterology and director of the Karsh Division of Gastroenterology and Hepatology at Cedars-Sinai. “Future studies can test whether enhancing this protective pathway can complement existing treatments, identify patients most likely to benefit and lead to new therapeutic approaches for preventing advanced disease.”

Additional Cedars-Sinai authors include Michitaka Matsuda, So Yeon Kim, Takashi Tsuchiya and Yoon Seok Roh.

Additional authors include: Feng Wang, Jin Lee, Jeong-Su Park, Meizhou Huang, Hwan Ma, Guoyan Sui, Zixiong Zhou, Xufeng Wu, Haram Lee, Soohwan Oh, Hanseul Park, Key-Hwan Lim, Chun-Woong Park, Sang-Bae Han, Jin Tae Hong and Michael Karin.

Funding: This work was supported by the National Research Foundation of Korea (grant nos. RS-2025-02273102 and RS-2025-02603096), Regional Innovation System & Education (RISE) programme of Chungbuk (grant no. 2025-RISE-11-014-03), the Pinnacle Research Award of American Association for the Study of Liver Diseases (AASLD, to J.L.), the San Diego Digestive Diseases Research Center (SDDRC) Pilot/Feasibility Grant (NIDDK P30 DK120515, to J.L.), the National Institutes of Health (grant nos. R01DK085252, R01DK138591 and R01CA301632) and the National Natural Science Foundation of China (grant no. 82404726).

The carefully planned gravity assist changed Juice’s direction by 20° relative to its previous trajectory and increased its speed by 3.5 km/s. During the four weeks leading up to the encounter, mission controllers needed to make only one small course correction (out of six opportunities set aside) to place the spacecraft on the precise approach needed to take full advantage of Earth’s gravity.

Controllers began monitoring Juice particularly closely on August 17 and will continue that intensive tracking through October 10.

Juice Makes a Close Pass Over Earth

Juice reached its closest point to Earth at 13:45 CEST (11:45 UTC) on September 28. At that moment, the spacecraft passed just 8640 km above the Indian Ocean while taking a sequence of images with its onboard monitoring cameras.

“The flyby required ultra-precise navigation in real time. Thanks to our very careful planning, we used only a small amount of the propellant reserved for this flyby,” says Angela Dietz, Juice’s Spacecraft Operations Manager. “This gives us more to use at Jupiter to carry out observations of the planet’s icy moons.”

Preserving that fuel is especially valuable because Juice will eventually need it while carrying out its ambitious scientific campaign around Jupiter and its moons.

Earth Becomes a Test Site for Juice

Changing the spacecraft’s trajectory was the primary purpose of the flyby, but the encounter also gave the mission team a valuable chance to test Juice’s science instruments using a real planetary target.

This was the third such opportunity during the mission. The first came during Juice’s 2024 lunar-Earth gravity assist, followed by the spacecraft’s 2025 observations of Comet 3I/ATLAS.

Teams from ESA’s spacecraft operations, science operations and technical centers spent months coordinating with the outside groups responsible for Juice’s 10 scientific instruments. Their goal was to carefully schedule when each instrument could operate and extract as much science and calibration time as possible from the spacecraft’s limited resources.

“Juice’s journey to Jupiter provides only a few opportunities to calibrate and validate the instruments under well-understood environmental conditions,” explains Juice project scientist Claire Vallat, who led the effort.

“Given the limited time available and operational constraints, instrument activities sometimes have to be prioritized, for example when Juice was in Earth’s shadow this morning, and relying on battery power alone. During this flyby, calibration activities were prioritized based on their relevance to preparing the instruments for their work at Jupiter, while also considering whether an opportunity is unique or can be scheduled later in the journey.”

Preparing for Jupiter’s Icy Moons

Although the Earth encounter required extensive preparation, it is relatively simple compared with what awaits Juice at Jupiter. The spacecraft is scheduled to carry out 35 flybys of the giant planet’s large moons Ganymede, Callisto and Europa.

Planning for those encounters began years in advance. For the Europa flybys, discussions about how the instruments will operate began about 10 years ago and will continue until Juice finally passes the moon in the early 2030s.

Earth therefore serves as an important rehearsal. Scientists can use the flyby to calibrate the instruments, learn how they behave once they are operating in space (where they always work a little differently to on Earth!), and refine the tools that will later be used to analyze the data.

The encounters with Jupiter’s icy moons will be much more scientifically demanding. By then, Juice will need to be ready to capture as much high-quality information as possible during each precious flyby.

Juice Explores Earth’s Magnetic Tail

The spacecraft also spent several days traveling through Earth’s magnetotail, the long extension of Earth’s magnetic field that stretches away from the Sun.

That gave Juice an opportunity to measure magnetic fields and electrically charged particles far from Earth. At the same time, the European-Chinese Smile mission has been observing the northern lights while measuring magnetic fields and particles much closer to the planet.

Combining measurements from Juice and Smile could give scientists a rare way to link activity deep in Earth’s magnetotail with events occurring around the planet’s polar regions.

Scientists expect to release images and spectra from some of Juice’s instruments in the coming weeks, once the data have reached Earth and instrument teams have had time to evaluate them. Among the anticipated results are high-resolution images of Earth and the Moon taken by JANUS, Juice’s scientific camera.

Juice Will Return to Earth One More Time

Juice is not finished with Earth yet.

In January 2029, the spacecraft will return for a third and final flyby of our planet. That encounter will place Juice on the final trajectory needed to reach Jupiter in 2031.

About Juice

ESA’s Jupiter Icy Moons Explorer, ‘Juice’, is humankind’s next bold mission to the outer Solar System. It will make detailed observations of gas giant Jupiter and its three large ocean-bearing moons – Ganymede, Callisto and Europa. This ambitious mission will characterise these moons with a powerful suite of remote sensing, geophysical and in situ instruments to discover more about these compelling destinations as potential habitats for past or present life.

Juice will monitor Jupiter’s complex magnetic, radiation and plasma environment in depth and its interplay with the moons, studying the Jupiter system as an archetype for gas giant systems across the Universe.

Juice launched on an Ariane 5 from Europe’s Spaceport in Kourou in April 2023. It has an eight-year cruise with flybys of Earth and Venus to slingshot it to Jupiter. It will make 35 flybys of the three large moons while orbiting Jupiter, before changing orbits to Ganymede.