Publisher Health

A blood test could potentially be used to assess a patient’s risk of type 2 diabetes, a new study from Edith Cowan University (ECU) has found.
The most commonly used inflammatory biomarker currently used to predict the risk of type 2 diabetes is high-sensitivity C-reactive protein (CRP). However, emerging research has suggested that the joint assessment of biomarkers, rather than assessing each individually, would improve the chances of predicting diabetes risk and diabetic complications.
A study by ECU researcher Dan Wu investigated the connection between systematic inflammation, assessed by joint cumulative high-sensitivity CRP and another biomarker called monocyte to high-density lipoprotein ratio (MHR), and incident type 2 diabetes.
The study followed more than 40,800 non-diabetic participants over a near ten-year period, with more than 4,800 of the participants developing diabetes over this period. Wu said that of those patients presenting with type 2 diabetes, significant interaction between MHR and CRP was observed.
“Specifically, increases in the MHR in each CRP stratum increased the risk of type 2 diabetes; concomitant increases in MHR and CRP presented significantly higher incidence rates and risks of diabetes.
“Furthermore, the association between chronic inflammation (reflected by the joint cumulative MHR and CRP exposure) and incident diabetes was highly age- and sex-specific and influenced by hypertension, high cholesterol, or prediabetes. The addition of the MHR and CRP to the clinical risk model significantly improved the prediction of incident diabetes,” said Wu.
Females most at risk
The study found that females had a greater risk of type 2 diabetes conferred by joint increases in CRP and MHR, with Wu stating that sex hormones could account for these differences.

Wu said that the research findings corroborated the involvement of chronic inflammation in causing early-onset diabetes and merited specific attention.
“Epidemiological evidence indicates a consistent increase in early-onset diabetes, especially in developing countries. Leveraging this age-specific association between chronic inflammation and type 2 diabetes may be a promising method for achieving early identification of at-risk young adults and developing personalised interventions,” she added.
Wu noted that the chronic progressive nature of diabetes and the enormous burden of subsequent comorbidities further highlighted the urgent need to address this critical health issue.
Although aging and genetics are non-modifiable risk factors, other risk factors could be modified through lifestyle changes. Inflammation is strongly influenced by life activities and metabolic conditions such as diet, sleep disruptions, chronic stress, and glucose and cholesterol dysregulation, thereby indicating the potential benefits of monitoring risk-related metabolic conditions.
Wu said that the dual advantages of cost effectiveness and the wide availability of cumulative MHR and CRP in current clinical settings, potentiated the widespread use of these measures as a convenient tool for predicting the risk of diabetes.

Osteoporosis can be detected and prevented more effectively thanks to a new diagnostic tool created by a team made up of researchers from the UPF BCN MedTech unit, the companies 3D-Shaper Medical and CETIR Medical Group, and Hospital de la Santa Creu i Sant Pau.
This public-private collaboration has given rise to the design of a new tool to calculate the risk of fracture due to femoral osteoporosis, from a biomechanics approach -which studies the mechanical structures of living beings such as those that account for the movement of the body-, with implementation costs that make its application feasible in clinical practice.
This tool fuses statistical methods to generate three-dimensional images of the femur, developed by 3D-Shaper Medical, with biomechanical simulations developed with BCN MedTech (UPF). As a starting point for applying statistical methods, the new tool uses 2D images obtained from the most widespread method for the clinical diagnosis of osteoporosis today (DXA). It should be borne in mind that currently, the most widespread diagnostic tools are based on two-dimensional images, which do not adequately capture the density of the trabecular and cortical compartments of the bone. This is essential to assess bone strength and prevent possible fractures.
The research behind the new diagnostic method has recently been disclosed in a scientific article published in Journal of Clinical Densitometry. Its authors are Muhammad Qasim, Mirella Lopez Picazo and Ludovic Humbert, of 3D-ShaperMedical; Carlos Ruiz Wills and Jérôme Noailly from the BCN MedTech unit, linked to the UPF Department of Information and Communication Technologies (DTIC); Silvana Di Gregorio and Luis Miguel del Río Barquero, from CETIR Medical Group; and Jorge Malouf Sierra, from Hospital de la Santa Creu i Sant Pau. The research was supported financially by the Spanish Ministry of Science, Innovation and Universities, the State Research Agency, the Agency for Business Competitiveness of the Government of Catalonia (ACCIÓ) and the EU’s Horizon 2020 Marie Sklodowska-Curie Programme.
Why is there a need to improve current methods?
Today, the most widespread method used to diagnose femoral osteoporosis is so-called dual-energy X-ray absorptiometry (DXA). This technique enables determining the mineral density of bone tissue, based on the amount of radiation it can absorb. Indeed, osteoporosis is linked to a loss of bone density, which decreases bone strength and increases the risk of fracture. This method, which yields two-dimensional images, has limitations for determining the volumetric distribution of mineral density -which must be three-dimensional-, which is essential to carefully examine bone strength and improve fracture prevention.
Another, more advanced method that is scarcely implemented in clinical diagnosis due to the fact that it exposes patients to higher levels of radiation, is quantitative computed tomography (QCT). Tomography scans yield detailed images of different internal regions of the body including bone tissue, also using X-rays, but with 3D reconstructions of bone volume. Previous studies have shown that this 3D capability of QCT makes it a better-prepared technique for estimating bone strength and fracture risk than the conventional 2D-DXA method. In addition, it allows translating volumetric information on bone morphology and quality into mechanical information on bone strength. However, its use has not been extended to clinical practice, not only because it exposes patients to higher doses of radiation, but also due to its high cost and because the it takes longer to process images obtained by QCT than 2D-DXA images.

The research proposes an effective and feasible method for clinical practice
The new method is based on 3D dual-energy X-ray absorptiometry (3D-DXA), a technique developed by the team at 3D-Shaper Medical based on the research initiated at UPF before the creation of the technology-based company. Essentially, “the new methodology complements and improves DXA with computational and statistical systems that allow estimating the mineral density of the entire bone volume, as well as obtaining detailed three-dimensional images of its shape. It also opens up the possibility of converting this volumetric information into quantitative information on bone strength, based on biomechanical simulations with the finite element method, one of the specialities of the BCN MedTech team,” explains Jérôme Noailly, principal investigator in biomechanics and mechanobiology of this UPF research unit.
3D-DXA uses two-dimensional DXA images onto which an added three-dimensional biomechanical simulation is applied. In this way, results equivalent to those of computed tomography can be obtained, since volumetric and geometric measurements are translated into femur resistance capacity results of the scanned subject. The new tool has the potential to improve current diagnoses that are commonly performed using the conventional DXA method, which are not capacitated to detect up to 50% of patients at high risk of femur fracture.
In fact, the research team as a whole has already tested the effectiveness of 3D-DXA to quantify bone resistance, with a study carried out on 157 patients. Their results improve the prospects of achieving the next step: predicting fracture risk based on DXA images.

In the first comprehensive evidence-based guideline on the use of fecal microbiota-based therapies for gastrointestinal disease, the American Gastroenterological Association recommends fecal microbiota transplant (FMT) for most patients with recurrent Clostridioides difficile (C. diff) infection.
“Using fecal microbiota transplant, we take stool from a healthy donor and transfer it to the colon of the person with recurrent C. diff, restoring balance to their gut microbiome,” explains guideline author Dr. Anne Peery. “FMT is a safe and effective treatment with enough scientific evidence to offered to most patients with two or more C. diff recurrences.”
In the U.S., nearly half a million people each year experience C. diff. One in six of those people will deal with a C. diff recurrence within two to eight weeks.
For patients with recurrent C. diff infection at a high risk of recurrence:For hospitalized patients with severe C. diff infection:

FMT therapies are not recommended as a treatment for inflammatory bowel diseases (IBD) or irritable bowel syndrome (IBS). AGA encourages patients interested in FMT for conditions other than C. diff to participate in a clinical trial.
Key takeaways FMT offers hope to patients suffering from recurrent C. diff infection, as a safe and effective treatment. The majority of patients with recurrent C. diff are candidates and can consider an FMT therapy to prevent recurrence. “C. diff is debilitating. Thanks to this new American Gastroenterological Association guideline, patients will suffer for shorter periods of time and be able to get back to leading happy and healthy lives,” concluded Amanda Kabage, MS, FMT researcher and FMT recipient who contributed to the development of this guideline.
This guideline covers the use of conventional FMT, performed most commonly using donor stool delivered via colonoscopy, as well as recently FDA-approved therapies such as fecal microbiota live-jslm (REBYOTA) delivered via enema and fecal microbiota spores live-brpk (VOWST) delivered in an oral capsule.

Queensland researchers have discovered that a mutation allows some E. coli bacteria to cause severe disease in people while other bacteria are harmless, a finding that could help to combat antibiotic resistance.
Professor Mark Schembri and Dr Nhu Nguyen from The University of Queensland’s Institute for Molecular Bioscience and Associate Professor Sumaira Hasnain from Mater Research found the mutation in the cellulose making machinery of E. coli bacteria.
Professor Schembri said the mutation gives the affected E. coli bacteria the green light to spread further into the body and infect more organs, such as the liver, spleen and brain.
“Our discovery explains why some E. coli bacteria can cause life-threatening sepsis, neonatal meningitis and urinary tract infections (UTIs), while other E. coli bacteria can live in our bodies without causing harm,” Professor Schembri said.
“The ‘good’ bacteria make cellulose and ‘bad’ bacteria can’t.”
Bacteria produce many substances on their cell surfaces that can stimulate or dampen the immune system of the host.
“The mutations we identified stopped the E. coli making the cell-surface carbohydrate cellulose and this led to increased inflammation in the intestinal tract of the host,” Professor Schembri said.

“The result was a breakdown of the intestinal barrier, so the bacteria could spread through the body.”
In models that replicate human disease, the team showed that the inability to produce cellulose made the bacteria more virulent, so it caused more severe disease, including infection of the brain in meningitis and the bladder in UTIs.
Associate Professor Hasnain said understanding how bacteria spread from intestinal reservoirs to the rest of the body was important in preventing infections.
“Our finding helps explain why certain types of E. coli become more dangerous and provides an explanation for the emergence of different types of highly virulent and invasive bacteria,” she said.
Professor Schembri said E. coli was the most dominant pathogen associated with bacterial antibiotic resistance.
“In 2019 alone, almost 5 million deaths worldwide were associated with bacterial antibiotic resistance, with E. coli causing more than 800,000 of these deaths,” he said.
“As the threat of superbugs that are resistant to all available antibiotics increases worldwide, finding new ways to prevent this infection pathway is critical to reduce the number of human infections.”
The collaboration included teams from UQ’s School of Biomedical Sciences led by Associate Professor Jana Vukovic and from Griffith University’s School of Pharmacy and Medical Sciences led by Professor Glen Ulett.
Video explainer: https://youtu.be/_vmXaHRbmEI

With ever-increasing life expectancy comes the challenge of treating age-related disorders such as osteoporosis. Although there are effective drugs for treating this metabolic bone disease, they can be expensive and have side effects, limiting their availability to some people. In the search for alternative drug candidates, researchers reporting in ACS Central Science have discovered and fully replicated a compound from a botanical source, female ginseng, that had potent anti-osteoporotic activity in cellular tests.
Osteoporosis and low bone mass impact 54 million American adults over the age of 50, according to the International Osteoporosis Foundation. The disease can progress to significant disability, such as hip and spine fractures, and financial burdens, such as lost wages and hospitalization. Several drugs have proven effective in either preventing bone loss or promoting bone formation, but each comes with potential side effects, including injury to jaw and leg bones. Searching for alternative treatments, Hao Gao, Xin-Luan Wang and colleagues turned to female ginseng (Angelica sinensis), which has long been used in traditional Chinese medicine to treat osteoporosis.
The researchers performed chemical extraction on the medicinal plant and identified two new compounds, calling them falcarinphthalide A and B, that were structurally unlike anything previously discovered in female ginseng. They also determined potential biosynthetic precursors and metabolic pathways that the plants use to form these compounds. Then, with these mechanisms as starting points, the team devised lab synthesis methods and produced the compounds at quantities sufficient for biological testing. Inspired by the traditional efficacy of female ginseng, the team tested the compounds for their impact on the formation of cells called osteoclasts, which facilitate bone loss. They observed that only falcarinphthalide A and its precursors showed osteoclast inhibitory activity and an anti-osteoporotic effect. Further analysis showed that falcarinphthalide A blocked key molecular pathways involved in osteoclast generation. The researchers say that this study opens up the possibilities for new osteoporosis treatments based on the female ginseng compound, whether in its current form or as a structural template for further drug development.

Texas A&M School of Veterinary Medicine & Biomedical Sciences (VMBS), Baylor College of Medicine and Texas Children’s Hospital researchers have discovered that meningiomas — the most common type of brain tumor in humans and dogs — are extremely similar genetically.
These newly discovered similarities will allow doctors to use a classification system that identifies aggressive tumors in both humans and dogs, while also opening the door for new and exciting collaborations between human and animal medicine.
Until now, the lack of reliable and viable experimental models has been a barrier to understanding the biology of and developing effective treatments for these brain tumors.
“The discovery that naturally occurring canine tumors closely resemble their human counterparts opens numerous avenues for exploring the biology of these challenging tumors,” said Dr. Akash Patel, an associate professor of neurosurgery at Baylor College of Medicine and principal investigator at the Jan and Dan Duncan Neurological Research Institute (Duncan NRI) at Texas Children’s Hospital. “It also provides opportunities for developing and studying novel treatments applicable to both humans and dogs.”
The study, published Feb. 20 in the scientific journal Acta Neuropathologica, was led by Patel; Dr. Jonathan Levine, a VMBS professor and head of the Department of Small Animal Clinical Sciences (VSCS); and Dr. Tiemo Klisch, assistant professor at Baylor College of Medicine and principal investigator at Duncan NRI. VSCS assistant professor Dr. Beth Boudreau was a key collaborator.
For the project, the team analyzed 62 canine meningiomas from 27 dog breeds and discovered that the tumors shared remarkable similarities to the same kinds of tumors when they occur in humans. This is the largest study to date of the gene expression profiles of canine meningiomas.
Watching The Signs
The new discovery was made possible by building on recent work conducted by Patel’s team, as well as previous work by Levine and Boudreau that explored gliomas, another type of brain tumor.

In 2019, Patel and others at Baylor College of Medicine and Texas Children’s Hospital found that they could classify meningiomas in humans into three biologically distinct subtypes — MenG A, B, and C — by analyzing their RNA. The new classification system can predict patient outcomes with greater accuracy than the standard tissue sample analysis.
“Because RNA shows how a tumor’s genes activate, it allows researchers to accurately predict how a tumor will behave — whether it will be aggressive or if it’s going to respond to certain therapies,” Levine said.
In 2020, Levine, Boudreau, and colleagues at the VMBS and the Jackson Laboratory for Genetic Medicine found genetic similarities between gliomas — the second most common type of brain tumors — in humans and dogs.
Armed with a new way of detecting aggressive tumors and the knowledge that dogs and humans share some brain tumor traits, Patel reached out to Levine about applying the findings to study meningiomas.
“We ended up agreeing to provide Patel with canine tumor samples we had worked years and years to archive, to see if he could isolate the RNA, which is not always easy to do,” Levine said. “He was able to produce this very robust dataset that showed a similar pattern structure to human tumors. Our team also provided Dr. Patel with key clinical outcome data, including responses to certain treatments.”
Moving To Clinical Trials
Now that the researchers have established a connection between tumors across the two species, they can begin preparations for clinical trials, which can take several years to plan and fund.

“We’re really interested in creating wins for both human and animal medicine,” Levine said. “For example, we hope to give dog owners access to therapy that’s not available anywhere else in the world through clinical trials. At the same time, that information will also inform the next step of human trials.”
Incidentally, a separate group of researchers from the University of California, Davis, conducted a similar study with matching conclusions about meningiomas in dogs and people and published its work in the same journal. The two research groups look forward to collaborating in the future to develop tumor treatments for both species.
“I think there is a terrific opportunity for the teams at Baylor, Texas A&M, Texas Children’s and University of California to collaborate to create a clinical trial,” Levine said.
“If we do one trial, we’d be able to enroll patients a lot more quickly, which would make it easier to get larger datasets, resulting in stronger findings. So, we have a lot of interest in doing a collaborative trial,” he said. “We really see the team out in California as potential partners.”
For now, the next step is looking through the data from both studies to see if there are clues that will lead to new therapies.
“One of the benefits of this project is that we already have all this genetic data that we can use to decide what might make a good treatment,” Levine said. “Part one has set us up very well to work on part two.”

Baleen whales are the largest animals to have ever roamed our planet and as top predators play a vital role in marine ecosystems. To communicate across vast distances and find each other, baleen whales depend critically on the production of sounds that travels far in murky and dark oceans.
However, since whale songs were first discovered more than 50 years ago, it remained unknown how baleen whales produce their complex vocalizations — until now.
A new study in the journal Nature reports that baleen whales evolved unique structures in their larynx that enable their low-frequency vocalizations, but also limit their communication range.
The study was led by voice scientists Professor Coen Elemans, at the Department of Biology, University of Southern Denmark and Professor Tecumseh Fitch at the Department of Behavioral and Cognitive Biology, University of Vienna in Austria.
“The toothed and baleen whales evolved from land mammals that had a larynx serving two functions: protecting the airways and sound production. However, their transition to aquatic life placed new and strict demands on the larynx to prevent choking underwater,” says Tecumseh Fitch.
The study shows that baleen whales nevertheless can still produce sound with their larynx, but they have evolved novel structures to do so, that only exists in baleen whales. First, the tiny cartilages in the human larynx — called the arytenoids — that change the position of our vocal folds, have changed dramatically in whales.
“The arytenoids changed into large, long cylinders fused at the base to form a large U-shaped rigid structure that extends nearly the full length of the larynx,” Elemans says.

“This is probably to keep a rigid open airway when they have to move huge amounts of air in and out during explosive surface breathing,” states Fitch.
“We found that this U-shaped structure pushes against a big fatty cushion on the inside of the larynx. When the whales push air from their lungs past this cushion, it starts to vibrate and this generates very low frequency underwater sounds,” says Elemans.
Trying to work on the biology and particularly physiology of whales is very challenging.
“Even though humans hunted whales close to the brink of extinction, they made very little effort in trying to learn about their physiology,” says Magnus Wahlberg, whale expert at University of Southern Denmark and co-author on the study.
“Strandings are unique and rare opportunities to learn about these amazing animals, but even then, it is very hard to study physiology, because the tissue decays so fast. Whales are known to explode on the beach,” adds Wahlberg.
Thanks to Danish and Scottish Marine Mammal Stranding Networks, the researchers could quickly extract the larynx of a sei, minke and humpback whale for close investigation in the lab.

“Our experiments showed for the first time how the whales make their very low frequency vocalizations,” says Elemans.
To understand how muscle activity could change the calls, the researchers built a computational model of the entire whale larynx.
“Our model includes accurate 3D shapes of the larynx and its muscles, which made it possible to simulate, for example, how the frequency is controlled through muscle modulation,” say Qian Xue and Xudong Zheng, professors at the Mechanical Engineering Department at Rochester Institute of Technology, USA, co-authors on the study.
“Our model accurately predicted the results of our experiments, but we could also calculate acoustic features we could not measure in the lab, such as the frequency range,” says Weili Jiang, postdoc at Rochester Institute of Technology, USA, co-author on the study.
The models predicted the natural vocalizations of the whales very well.
However, these newly discovered anatomical features that allowed whales to successfully communicate in the vast oceans also poses unsurmountable physiological limits for many baleen whales.
Combining experiments and models, the researchers provide the first evidence that baleen whales are physiologically incapable of escaping anthropogenic noise, because it masks their voices, and thus limits their communication range.
“Regrettably, the frequency range and maximum communication depth of 100 meters we predict, overlaps completely with the dominant frequency range and depth of human-made noise caused by shipping traffic,” Elemans says.
“The first acoustic recordings of humpback whale song by Roger and Katy Payne in 1970 resonated with humanity profoundly, started the flourishing field of marine bioacoustics, and sparked global interest in marine conservation efforts.” says Coen Elemans.
“These recordings were so politically important then that they are aboard the Voyager space missions,” he continues.
The Payne’s made people aware how quiet the seas were before humans started the widespread use of propeller ships and continuously running shipboard generators. Those were the seas whales evolved in.
Elemans adds: “Compared to the seventies, our oceans are now even more filled with human-made noise from shipping lanes, drilling activity and seismic guns. We need strict regulations for such noise, because these whales are dependent on sound for communication. Now we show that despite their amazing physiology they literally cannot escape the noise humans make in the oceans.”

Scientists have gained new insights into how neurons in the brain communicate during a decision, and how the connections between neurons may help reinforce a choice.
The study — conducted in mice and led by neuroscientists at Harvard Medical School — is the first to combine structural, functional, and behavioral analyses to explore how neuron-to-neuron connections support decision-making.
Findings appear Feb. 21 in Nature.
“How the brain is organized to help make decisions is a big, fundamental question, and the neural circuitry — how neurons are connected to one another — in brain areas that are important for decision-making isn’t well understood,” said Wei-Chung Allen Lee, associate professor of neurobiology in the Blavatnik Institute at HMS and professor of neurology at Boston Children’s Hospital. Lee is co-senior author on the paper with Christopher Harvey, professor of neurobiology at HMS, and Stefano Panzeri, professor at University Medical Center Hamburg-Eppendorf.
In the research, mice were tasked with choosing which way to go in a maze to find a reward. The researchers found that a mouse’s decision to go left or right activated sequential groups of neurons, culminating in the suppression of neurons linked to the opposite choice.
These specific connections between groups of neurons may help sculpt decisions by shutting down neural pathways for alternative options, Lee said.
A fruitful collaboration is born
It was a chance meeting on a bench outside their building during a fire drill that led Harvey and Lee to realize the complementary nature of their work. On that day, they forged a collaboration that propelled the new work.

The Harvey lab uses mice to study behavioral and functional aspects of decision-making. Typical experiments involve placing a mouse in a virtual reality maze and recording neural activity as it makes decisions. Such experiments have shown that distinct, but intermingled, sets of neurons fire when an animal chooses left versus right.
Lee works in a new field of neuroscience called connectomics, which aims to comprehensively map connections between neurons in the brain. The goal, he said, is to figure out “which neurons are talking to each other, and how neurons are organized into networks.”
By combining their expertise, Harvey and Lee were able to delve deeper into the different types of neurons involved in decision-making and how these neurons are connected.
Choosing a direction
The new study focused on a region of the brain called the posterior parietal cortex — what Lee describes as an “integrative hub” that receives and processes information gathered by multiple senses to help animals make decisions.
“We were interested in understanding how neural dynamics arise in this brain area that is important for navigational decision-making,” Lee said. “We’re looking for rules of connectivity — simple principles that provide a foundation for the brain’s computations as it makes decisions.”
The Harvey lab recorded neural activity as mice ran a T-shaped maze in virtual reality. A cue, which happened several seconds beforehand, indicated to the mice whether a reward would be in the left or right arm of the T. The Lee lab used powerful microscopes to map the structural connections between the same neurons recorded during the maze task.

By combining modalities, the researchers distinguished excitatory neurons — those that activate other cells — from inhibitory neurons, which suppress other cells. They found that a specific set of excitatory neurons fired when a mouse decided to turn right, and these “right-turn” neurons activated a set of inhibitory neurons that curbed activity in “left-turn” neurons. The opposite was true when a mouse decided to turn left.
“As the animal is expressing one choice, the wiring of the neuronal circuit may help stabilize that choice by suppressing other choices,” Lee said. “This could be a mechanism that helps an animal maintain a decision and prevents ‘changes of mind’.”
The findings need to be confirmed in humans, although Lee expects that there is some conservation across species.
The researchers see many directions for future research. One is exploring the connections between neurons involved in decision-making in other brain regions.
We used these combined experimental techniques to find one rule of connectivity, and now we want to find others,” Lee said.
Harvard University filed a patent application for GridTape (WO2017184621A1) on behalf of Lee, Hildebrand, and Graham as inventors and negotiated licensing agreements with interested partners.

Sometimes our bodies need a boost. Millions of Americans rely on pacemakers — small devices that regulate the electrical impulses of the heart in order to keep it beating smoothly. But to reduce complications, researchers would like to make these devices even smaller and less intrusive.
A team of researchers with the University of Chicago has developed a wireless device, powered by light, that can be implanted to regulate cardiovascular or neural activity in the body. The featherlight membranes, thinner than a human hair, can be inserted with minimally invasive surgery and contain no moving parts.
Published Feb. 21 in Nature, the results could help reduce complications in heart surgery and offer new horizons for future devices.
“The early experiments have been very successful, and we’re really hopeful about the future for this translational technology,” said Pengju Li, a graduate student at the University of Chicago and first author on the paper.
‘A new frontier’
The laboratory of Prof. Bozhi Tian has been developing devices for years that can use technology similar to solar cells to stimulate the body. Photovoltaics are attractive for this purpose because they do not have moving parts or wires that can break down or become intrusive — especially useful in delicate tissues like the heart. And instead of a battery, researchers simply implant a tiny optic fiber alongside to provide power.
But for the best results, the scientists had to tweak the system to work for biological purposes, rather than how solar cells are usually designed.

“In a solar cell, you want to collect as much sunlight as possible and move that energy along the cell no matter what part of the panel is struck,” explained Li. “But for this application, you want to be able to shine a light at a very localized area and activate only that one area.”
For example, a common heart therapy is known as cardiac resynchronization therapy, where different parts of the heart are brought back into sync with precisely timed charges. In current therapies, that’s achieved with wires, which can have their own complications.
Li and the team set out to create a photovoltaic material that would only activate exactly where the light struck.
The eventual design they settled on has two layers of a silicon material known as P-type, which respond to light by creating electrical charge. The top layer has many tiny holes — a condition known as nanoporosity — which boost the electrical performance and concentrate electricity without allowing it to spread.
The result is a miniscule, flexible membrane, which can be inserted into the body via a tiny tube along with an optic fiber — a minimally invasive surgery. The optic fiber lights up in a precise pattern, which the membrane picks up and turns into electrical impulses.
The membrane is just a single micrometer thin — about 100 times smaller than the finest human hair — and a few centimeters square. It weighs less than one fiftieth of a gram; significantly less than current state-of-the-art pacemakers, which weigh at least five grams. “The more lightweight a device is, the more comfortable it typically is for patients,” said Li.

This particular version of the device is meant for temporary use. Instead of another invasive surgery to remove the pacemaker, it simply dissolves over time into a nontoxic compound known as silicic acid. However, the researchers said that the devices could be engineered to last to different desired lifespans, depending on how long the heart stimulation is desired.
“This advancement is a game-changer in cardiac resynchronization therapy,” said Narutoshi Hibino, professor of surgery at the University of Chicago Medicine and co-corresponding author on the study. “We’re at the cusp of a new frontier where bioelectronics can seamlessly integrate with the body’s natural functions.”
Light use
Though the first trials were conducted with heart tissue, the team said the approach could be used for neuromodulation as well — stimulating nerves in movement disorders like Parkinson’s, for example, or to treat chronic pain or other disorders. Li coined the term ‘photoelectroceuticals’ for the field.
Tian said the day when they first tried the pacemaker in trials with pig hearts, which are very similar to those of humans, remains vivid in his memory. “I remember that day because it worked in the very first trial,” he said. “It’s both a miraculous achievement and a reward for our extensive efforts.”
A screening method developed by Li to map the photoelectrochemical output of various silicon-based materials could also have uses elsewhere, Tian pointed out, such as in fields like new battery technologies, catalysts, or photovoltaic cells.

Researchers have revealed the mechanism of a drug shown to be effective in treating certain types of cancer, which targets a protein modification silencing the expression of multiple tumor suppressor genes. They also demonstrated in clinical trials the efficacy of the drug in reducing tumor growth in blood cancer. The findings could lead to longer-term treatments for the disease and therapies for other types of cancer with similar underlying causes.
A team of researchers from the University of Tokyo and their collaborators focused on therapies targeting H3K27me3, a modification on a DNA-packaging histone protein, which plays a large role in regulating gene expression. The modification occurs when methyl groups, each consisting of three hydrogen atoms bonded to a single carbon atom (CH3), are added to the protein in a process called methylation.
The modification, also referred to as being epigenetic (a heritable change in gene function that occurs without altering the sequence of the DNA), has been tied to the repression, or reducing the expression, of tumor suppressor genes, with the accumulation of the methylated histones around the genes.
Because of its effects on repressing genes, H3K27me3 is being targeted by therapies to correct some of the disordered gene expression observed in cancer cells. While this therapy is effective for some cancers, the mechanism of H3K27me3 therapies on tumor cells was not yet known.
The research team conducted a study characterizing the effects of H3K27me3 on cancer cells by treating patients who have adult T-cell leukemia/lymphoma (ATL), a rare type of blood cancer, with valemetostat. The drug prevents the methylation of histone H3 by inhibiting the histone-modifying enzymes EZH1 and EZH2, which increase H3K27 and have been found to be abnormal in cancers. Treating patients with valemetostat decreased H3K27me3 and the condensation of DNA, opening up several tumor-suppressor genes for expression in cancer cells.
“Before H3K27me3-inhibitor therapies were developed, no effective treatments for blood cancers with accumulated genetic abnormalities existed, and new treatments needed to be developed,” said Makoto Yamagishi, first author of the paper and associate professor at the Graduate School of Frontier Sciences at the University of Tokyo. “Once we established that these therapies were effective against some types of cancer, understanding the therapeutic mechanisms of these drugs became extremely important.”
The team established that valemetostat treatment decreased tumor size and produced a durable clinical response to therapy in the clinical trial of patients with ATL, an aggressive cancer with many genetic mutations. The patients were able to safely remain on valemetostat treatment for more than two years.
“In blood cancers with poor prognosis due to genetic abnormalities, epigenetic mechanisms mediated by methylated histones can be targeted therapeutically,” said Professor Kaoru Uchimaru, also of the Graduate School of Frontier Sciences and last author of the study. “Valemetostat can restore expression of many tumor suppressor genes and sustainably inhibit tumor cell growth.”
Characterizing the mechanism of valemetostat therapy in patients with ATL is a huge step forward for epigenetic cancer treatments that target the expression of genes in cancer cells. The team recognizes, however, that many challenges remain. Cancers can become resistant to H3K27me3-inhibitor therapies if patients are treated for long periods of time, allowing cancer to recur. In some cases, cancer cells had acquired new mutations that interfered with valemetostat’s effectiveness over time and reduced long-term patient response to the drug.
“EZH1/2 inhibitors are effective treatments, but a mechanism of resistance to long-term treatment has also been identified,” said Yamagishi. “Based on this mechanism of resistance, it is important to continue to improve treatment methods and develop combination therapies that provide longer-term therapeutic effects.”