Publisher Health

A team of UCF College of Medicine researchers has created a digital topographical map of the cardiac sympathetic neural network, the region that controls the body’s heart rate and its “fight-or-flight” response. They hope this map will eventually serve as a guide to treat cardiovascular conditions using bioelectronic devices.
The study, led by Dr. Zixi Jack Cheng, a neuro-cardiovascular scientist, was published in the Scientific Reports journal and was the project of an interdisciplinary team of researchers from UCF along with several other institutions as well as industry partners MBF Bioscience and SPARC Data and Resource Center. The project has been supported by the NIH Common Fund’s Stimulating Peripheral Activity to Relieve Conditions (SPARC) program, and funding from National Institute on Neural Disorders and Stroke and National Heart, Lung and Blood Institute.
“This mapping goes beyond what you can find in a textbook,” Dr. Cheng said. “This is a digitized brain-heart atlas that will be interactive. We hope it will serve as a guide not only for scientists and physicians, but also for students as they learn the neuroanatomy of the heart.”
The map may serve as a guide for treatments such as neuromodulation therapy — electronically stimulating nerves to treat cardiovascular conditions.
Dr. Cheng’s team and his SPARC collaborators previously created a comprehensive 3D map of a rodent heart’s intrinsic nervous system. The system, known as the “little heart brain,” contains thousands of neurons around the heart that regulate heartbeat and blood circulation. Their latest project extended that study and mapped topographical network of the nerves in the sympathetic nervous system and its connection to the heart. The team hopes the advanced blueprint will help scientists and physicians to study the brain-heart connection and navigate more precise control of different heart regions including those that control the heartbeat.
The sympathetic nervous system plays a pivotal role in regulating cardiac functions through an intricate network of nerves. It can help the body respond to dangerous or stressful situations, by speeding up the body’s heart rate to deliver more blood to areas that need more oxygen. The system also controls the heart rate, blood pressure, digestion and other vital functions.
To create the map, the team used a combination of state-of-the-art techniques to image, trace, digitize and quantitatively map the distribution of the sympathetic nervous system including the heart’s whole atria and ventricles.
“The groundbreaking part of this project is the precision at which the mapping is completed at the microscopic level which allows us to see the single cells and single nerve axons,” said Dr. Cheng. This is the first time that scientists will see the whole organ at such an intricate level.”
Dr. Yuanyuan Zhang, the postdoctoral fellow in Dr. Cheng’s lab, explained that this map will help researchers further test the functional role of a specific of nerve by activating or deactivating it and observing its impact on the body. He said the mapping can also serve as a guide for treatments such as neuromodulation therapy — electronically stimulating nerves to treat cardiovascular conditions such as hypertension, sleep apnea and heart failure.
“Utilizing our map as a sympathetic-cardiac atlas opens the door for innovative therapies for several cardiovascular diseases, nerve-related disorders and avoids side effects associated with many pharmaceuticals,” added Ariege Bizanti, a Ph.D. candidate in Dr. Cheng’s lab.
Heart disease is the leading cause of death for men and women in the United States, accounting for 697,000 deaths in 2020 according to statistics from the Centers for Disease Control. One person dies every 34 seconds in the United States from cardiovascular disease.
“The cardiac-sympathetic nerve system is very complex and remains poorly understood,” said Dr. Jin Chen, another UCF collaborator on the project. “So having this detailed mapping in the heart could give us important insights into the architecture of cardiac-sympathetic nerve and provide the foundation for future functional and molecular studies of sympathetic control of the heart.”

Many disease-causing bacteria like Streptococcus pneumoniae (S. pneumoniae) are encased in a sugar layer called the capsular polysaccharide (CPS). This layer is often essential for infections. In a ground-breaking discovery by scientists from the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine), features of the CPS that help the bacteria to colonise the human respiratory tract were identified. The research showed that the structures of the CPS capsule and its types of linkages and combinations matter greatly in allowing the bacteria to better attach and survive on the lining of the upper and lower human respiratory tracts.
To challenge the widely-held notion that structurally diverse CPS capsules in S. pneumoniae perform the same function in promoting bacterial colonisation, the team, led by Assistant Professor Chris Lok-To Sham and graduate student, Jade Chun Ye-Yu, from the Infectious Diseases Translational Research Programme at NUS Medicine, constructed bacterial mutants displaying one of the 84 types of CPS found in S. pneumoniae. The mutants were then introduced to respiratory cells to investigate their abilities to bind to the respiratory tracts. Using a molecular barcode to distinguish the strains, the team examined whether varying CPS in these mutants would affect binding on the nasal and bronchial cells.
The results showed that the CPS with rhamnose sugar residues bound poorly to the airway cells, while CPS with glycan motifs bound strongly. The experiment demonstrated that the structural configurations and the types of CPS play important roles in the strength of attachment and survival on the human airway.
“In the past, scientists recognised that the proteins found in bacteria are not by chance, and they do serve a purpose. Bacteria have shown a preference for certain types of sugars on their capsules, and a specific linkage of sugars. Our research proves that some of these combinations benefit the bacteria because they aid in colonising the human respiratory tract. This finding will shed more light on the range of CPS types to be included in future vaccines, as current vaccines against S. pneumoniae do not cover the many types of CPS produced by the bacteria,” added Jade Chun, who is also from the Department of Microbiology and Immunology at NUS Medicine.
S. pneumoniae is a major driver of pneumonia, septicaemia, and meningitis. Collectively, these infections are among the leading causes of morbidity and mortality in the elderly and young children. To fight against these deadly infections, pneumococcal vaccines are administered to stimulate antibody production to the CPS. However, the bacteria can manipulate their CPS structure to evade these antibodies. This biochemical warfare results in more than a hundred types of CPSs produced by S. pneumoniae, which increases the challenge of producing effective vaccines. While the diversity of CPS is well appreciated, what actually makes the CPS a lethal weapon for the bacteria remains unclear.

Discovery of a gene in multiple mammalian species could pave the way for a highly effective, reversible and non-hormonal male contraceptive for humans and animals.
Washington State University researchers identified expression of the gene, Arrdc5, in the testicular tissue of mice, pigs, cattle and humans. When they knocked out the gene in mice, it created infertility only in the males, impacting their sperm count, movement and shape. The researchers detailed their findings in the journal Nature Communications.
“The study identifies this gene for the first time as being expressed only in testicular tissue, nowhere else in the body, and it’s expressed by multiple mammalian species,” said Jon Oatley, senior author and professor in WSU’s School of Molecular Biosciences. “When this gene is inactivated or inhibited in males, they make sperm that cannot fertilize an egg, and that’s a prime target for male contraceptive development.”
While other molecular targets have been identified for potential male contraceptive development, the Arrdc5 gene is specific to the male testes and found in multiple species. Importantly, lack of the gene also causes significant infertility creating a condition called oligoasthenoteratospermia or OAT. This condition, the most common diagnosis for human male infertility, shows a decrease in the amount of sperm produced, slowed mobility and distorted shape so that the sperm are unable to fuse with an egg.
In the WSU study, the male mice lacking this gene produced 28% less sperm that moved 2.8 times slower than in normal mice – and about 98% of their sperm had abnormal heads and mid-pieces.
The study indicates that the protein encoded by this gene is required for normal sperm production. Oatley’s team will next work on designing a drug that would inhibit production or function of that protein.

Disrupting this protein wouldn’t require any hormonal interference, a key hurdle in male contraception since testosterone plays other roles beyond sperm production in men including building bone mass and muscle strength as well as red blood cell production. Designing a drug to target this protein would also make it easily reversible as a contraceptive.
“You don’t want to wipe out the ability to ever make sperm – just stop the sperm that are being made from being made correctly,” he said. “Then, in theory, you could remove the drug and the sperm would start being built normally again.”
Oatley and study first author Mariana Giassetti have filed a provisional patent for the development of a male contraceptive based on this gene and the protein it encodes.
Because the gene is found across mammalian species, this knowledge also holds promise for use in animals, Oatley said. The team analyzed available biological data on DNA and protein sequences in mammals and found the gene in almost every known mammal species. This opens the potential to develop male contraception for use in livestock, perhaps replacing castration in some instances as a way to control reproduction, and in wildlife when managers seek to limit overpopulation of a species.
The initial focus, however, is on giving humans more control over their own reproduction. While there are many forms of birth control for women, they are not always effective or widely available, and more than half of pregnancies worldwide are still unintended, according to the United Nations.
“Developing a way to curb population growth and stop unwanted pregnancies is really important for the future of the human race,” said Oatley. “Right now, we don’t really have anything on the male side for contraception other than surgery and only a small percentage of men choose vasectomies. If we can develop this discovery into a solution for contraception, it could have far-ranging impacts.”
This study received support from the National Institutes of Health and WSU’s Functional Genomics Initiative, a multi-year university investment to support development of genetic technology research.

Wireless wearable biosensors have been a game changer in personalized health monitoring and healthcare digitization because they can efficiently detect, record, and monitor medically significant biological signals. Chipless resonant antennae are highly promising components of wearable biosensors, as they are affordable and tractable. However, their practical applications are limited by low sensitivity (inability to detect small biological signals) caused by low quality (Q) factor of the system.
To overcome this hurdle, researchers led by Professor Takeo Miyake from Waseda University, Professor Yin Sijie from Beijing Institute of Technology, and Taiki Takamatsu from Japan Aerospace Exploration Agency, have developed a wireless bioresonator using “parity-time (PT) symmetry” that can detect minute biological signals. Their work has been published in Advanced Materials Technologies.
In this study, the researchers designed a bioresonator consisting of a magnetically coupled reader and sensor with high Q factor, and thus, increased sensitivity to biochemical changes. The reader and sensor both comprise an inductor (L) and capacitor (C) that are parallel-connected to a resistor (R). In the sensor, the resistor is a chemical sensor called a “chemiresistor” that converts biochemical signals into changes in resistance. The chemiresistor contains an enzymatic electrode with an immobilized enzyme. Minute biochemical changes at the enzymatic electrode (in response to changes in the levels of biomolecules such as blood sugar or lactate) are thus converted into electrical signals by the sensor, and then amplified at the reader.
Explaining the technical concept behind their novel biosensor, Miyake says, “We modeled the characteristics of the PT-symmetric wireless sensing system by using an eigenvalue solution and input impedance, and experimentally demonstrated the sensitivity enhancement at/near the exceptional point by using parallel inductance-capacitance-resistance (LCR) resonators.The developed amplitude modulation-based PT-symmetric bioresonator can detect small biological signals that have been difficult to measure wirelessly until now. Moreover, our PT-symmetric system provides two types of readout modes: threshold-based switching and enhanced linear detection. Different readout modes can be used for different sensing ranges.”
The researchers tested the system (here containing a glucose-specific enzyme) on human tear fluids and found that it could detect glucose concentrations ranging from 0.1 to 0.6 mM. They also tested it with a lactate-specific enzyme and commercially available human skin and found that it could measure lactate levels in the range of 0.0 to 4.0 mM through human skin tissue, without any loss of sensitivity. This result further indicates that the biosensor can be used as an implantable device. Compared to a conventional chipless resonant antenna-based system, the PT-symmetric system achieved a 2000-fold higher sensitivity in linear and a 78% relative change in threshold-based detection respectively.
Sharing his vision for the future, Miyake concludes, “The present telemetry system is robust and tunable. It can enhance the sensitivity of sensors to small biological signals. We envision that this technology can be used for developing smart contact lenses to detect tear glucose and/or implantable medical devices to detect lactate for efficient monitoring of diabetes and blood poisoning.”

A species of ordinary gut bacteria that we all carry flourishes when the intestinal flora is knocked out by a course of antibiotics. Since the bacteria is naturally resistant to many antibiotics, it causes problems, particularly in healthcare settings. A study led from Lund University in Sweden now shows how two molecular mechanisms can work together make the bacterium extra resistant. “Using this knowledge, we hope to be able to design even better medicines,” says Vasili Hauryliuk, senior lecturer at Lund University, who led the study.
The threat from antibiotic resistant bacteria is as well-known as it is grave. Last year, The Lancet reported that an estimated 1.27 million people died in 2019 as a result of bacterial infection that could not be treated with existing medicines. To tackle this threat is it is essential to understand the underpinning molecular mechanisms.
During antibiotic treatment, the normal intestinal flora is disturbed, which provides an opportunity for antibiotic resistant bacterial pathogens that are otherwise suppressed though competition with the “good” gut bacteria. One of the most problematic bacterial species is Clostridioides difficile, C. diff. It is found in our intestines, is resistant to antibiotic treatments and can cause serious diarrheal infections. The bacteria’s ability to create spores means it is easily spread and therefore causes problems in healthcare settings, resulting both in increased mortality and extended treatment times.
“Instead of the antibiotic saving you, in this case it promotes a secondary bacterial infection,” says Vasili Hauryliuk.
“The risk of infection with C. diff is known to increase after treatment with an antibiotic called clindamycin, but the reason for this was unknown. Our research showed a novel protein conveys resistance to the class of antibiotics to which clindamycin belong,” says Obana Nozomu, assistant professor at the University of Tsukuba and one of the researchers behind the study.
The mechanism of C. diff resistance has been investigated in an international collaboration between researchers in Sweden, Japan, the United Kingdom, USA, Estonia and Germany, and the results of this study have been published in Nucleic Acids Research. When researchers have identified a novel protein that is responsible for the resistance. The protein works on the ribosome — the molecular factory that produces the proteins in the bacteria, and that gives the bacteria its abilities. The ribosome is one of the primary antibiotic targets: if proteins cannot be synthesised, the bacteria will not grow, replicate and cause the infection.
“This newly discovered protein kicks the antibiotic molecule out of the ribosome. We also saw that it combines with another resistance factor. The second chemically modifies the ribosome so that the antibiotic molecules to bind less tightly to it. The extra-potent resistance is the result of two mechanisms, two factors, which combine and in so doing give the bacteria its ‘superpowers’ against antibiotics,” says Gemma C. Atkinson, senior lecturer at Lund University and co-author of the article.
The researchers used cryogenic electron microscopy in order to study the resistance mechanisms against antibiotics on a molecular level. This knowledge opens the way for new treatment strategies against resistance and the infections that the bacteria cause.
“A couple of years ago, Andrew G. Myers lab at Harvard University has developed a new generation of ribosome-binding antibiotics, known as iboxamycin. It is a very potent medicine that knocks out ‘ordinary’ C. diff bacteria. The results of this study, however, show that C. diff strains that have both resistance factors are, unfortunately, resistant to this antibiotic as well. This means that it is necessary to design antibiotic molecules that bind even tighter in order to overpower this kind of resistance. We now collaborate with the Myers group on this direction.” says Vasili Hauryliuk.
This study also found that certain antibiotics that target the ribosome induce the production of the resistance factor. This may also provide clues for designing new antibiotic molecules, since resistance cannot be induced if resistance factors are not synthesized.

A team of engineering and health researchers has developed a tool that improves the ability of electronic devices to detect when a human patient is coughing, which has applications in health monitoring. The new tool relies on an advanced artificial intelligence (AI) algorithm that helps the AI better identify uncertainty when faced with unexpected data in real-world situations.
“When AI is being trained to identify the sound of coughing, this is usually done with ‘clean’ data — there is not a lot of background noise or confusing sounds,” says Edgar Lobaton, corresponding author of a paper on the work and an associate professor of electrical and computer engineering at North Carolina State University. “But the real world is full of background noise and confusing sounds. So previous cough detection technologies often struggled with ‘false positives’ — they would say that someone was coughing even if nobody was coughing.
“We’ve developed an algorithm that helps us address this problem by allowing an AI to express uncertainty. Rather than having to decide ‘Yes, that was a cough’ or ‘No, that wasn’t a cough,’ the AI can also report that it has detected a sound it’s not familiar with. In other words, the AI is given a third option: ‘I don’t know what that was.'”
Cough detection technology is of interest for several potential health monitoring applications.
“For example, there is interest in using wearable health monitoring devices that would detect coughs in people who have asthma, which could trigger a notification about increased risk of an asthma attack,” Lobaton says. “There is also interest in using cough detection for COVID monitoring, and so on.”
However, previous cough detection technologies had high rates of false positives, with the relevant AI reporting many unfamiliar sounds as coughing. These false positives significantly limited their utility.

“In the near term, our work limits the reporting of false positives by allowing the AI to note when it hears sounds that it can’t identify,” Lobaton says. “In the longer term, our algorithm should allow us to continually train the AI, by telling it whether the unfamiliar sounds it is hearing are coughs or are unrelated noises. This should allow for much more precise detection over time.”
In addition, the researchers tested the new algorithm in computational models and found that the modified cough detection AI can operate effectively using far fewer sound samples per second than previous technologies. For example, previous cough detection tools used approximately 16,000 sound samples per second, while the new AI tool makes use of 750 sound samples per second, with similar sensitivity and fewer false positives.
“Using fewer sound samples is a significant advantage for two reasons,” Lobaton says. “First, it means that the electronic device requires less computing power — which allows us to make it smaller and more energy efficient. Second, using fewer sound samples means that the technology will not be recording understandable speech, which addresses privacy concerns.”
The researchers are currently in the process of incorporating the new algorithm into a wearable health monitoring device that can be used in real-world testing.
What’s more, the researchers say the approach they’ve taken here could be used to address a range of AI applications in which the AI is likely to encounter unexpected input that it was not trained to understand.
“We’re looking for research partners who can help us explore other health monitoring challenges that this AI modification could help address in a meaningful way,” Lobaton says.
The work was done with support from the National Science Foundation (NSF) under grant number 1915599, and from NC State’s NSF-funded Advanced Self-Powered Systems of Integrated Sensors and Technologies (ASSIST) Center under grant 1160483. The mission of the ASSIST Center is to create self-powered wearables capable of long-term multi-modal sensing without having to replace or charge batteries.

Scientists at the U.S. Department of Energy’s (DOE) Brookhaven National Laboratory have discovered new details about the electrons in a nickel-based family of superconducting materials. The research, described in two papers published in Physical Review X, reveals that these nickel-based materials have certain similarities with — and key differences from — copper-based superconductors. Comparing the two kinds of “high-temperature” superconductors may help scientists zero in on key features essential for these materials’ remarkable ability to carry electrical current without losing energy as heat.
“The quest to understand high-temperature superconductors is a decades-old challenge,” said Mark Dean of Brookhaven Lab’s Condensed Matter Physics & Materials Science Department, who led the research described in both papers. Ever since copper-based, or cuprate, superconductors were discovered in the 1980s, scientists have been trying to understand what makes them tick.
The interest is driven in large part by their potential for energy-saving applications. Picture power lines that deliver electricity to homes far from wind and solar farms without losing a speck of energy, and computers and other devices that function flawlessly without the need for expensive and energy-intensive cooling.
Trouble is, despite their “high-temperature” moniker, cuprate superconductors themselves must be kept extremely cold to operate — well below zero degrees Fahrenheit. Discovering what allows electrons in these materials to overcome their normal “like-charge” repulsion and flow with no resistance could perhaps point the way to superconductors that operate in closer to real-world conditions.
“These materials are also a testbed for efforts to understand other quantum materials where electrons interact very strongly,” said Steven Johnston, a theorist at the University of Tennessee and a coauthor of the paper. “You could make a reasonable argument that this is the most important open problem in the physics of materials.”
Nickel analogs
As part of the quest to crack the case on cuprates, scientists have looked for analogs — similar superconducting compounds they could study and compare to give them clues for improving properties.

“Maybe, if you just tweak something, you can make a property such as the temperature of the transition to superconductivity higher, or you can make materials with cheaper elements for applications,” said Yao Shen, a postdoctoral researcher at Brookhaven and first author of the publications.
Nickel was a logical choice. Its proximity to copper on the periodic table implies that compounds made from these next-door-neighbor transition metals might operate in similar ways but with enough differences to point out what is essential to superconductivity.
But even before scientists at Stanford University successfully created a nickel-based superconductor in 2019, others wondered whether the nickel compounds could be considered true analogs to cuprates. Once the nickelates were synthesized, the quest to find out began.
“Seeing” electronic behavior
These studies used x-rays at Brookhaven Lab’s National Synchrotron Light Source II (NSLS-II), a DOE Office of Science user facility that enables research on the microscopic structure, chemistry, and other properties of all sorts of materials. The team used the Soft Inelastic X-Ray (SIX) beamline, run by study collaborators Valentina Bisogni and Jonathan Pelliciari, to compare the electronic properties of a layered nickelate superconductor (La4Ni3O8) with those of a well-known cuprate (La2?xSrxCuO4).

They wanted to know which electrons (from which elements) in each compound contribute to superconductivity and other electronic properties, including the presence of a “charge-density wave.” This ordered pattern of electrons might play a role in generating the material’s superconductivity.
“Scientists have evidence that superconductivity in cuprates is associated with very strong magnetic interactions between the copper ions,” said Michael Norman, a collaborating scientist from Argonne National Laboratory. “So, in addition to comparing the electrons involved in superconductivity in these two materials, we also wanted to look for evidence of magnetic interactions between the nickel ions in these nickelates and understand which elements contribute electrons that form both the charge and magnetic density waves in these materials.”
The SIX beamline, with its world-leading energy resolution, allows the scientists to “see” these subatomic scale details by tuning the x-ray energy precisely to the individual elements in the sample using a technique called resonant inelastic x-ray scattering (RIXS).
“We can tune our x-ray energy to resonate with either the oxygen or nickel or other elements and then we can see the electronic properties of those specific elements,” Dean said. “We used that alongside theory calculations to get a detailed picture of how these materials work electronically.”
Key similarities and differences
The findings indicate substantial similarities between the nickelate and cuprate superconductors — and some differences.
For example, the scientists found that in both sets of materials, the transition metal (copper or nickel) and oxygen both contribute to the materials’ electronic properties, but the magnetic interactions among nickel atoms, mediated by intervening oxygens, are slightly weaker than the oxygen-mediated magnetic interactions among copper atoms in the cuprates.
“Cuprates have this very nice well-aligned energy between the copper and the oxygen, and that’s why they are very strongly magnetic,” Shen said. “A similar thing happens in the nickel compounds just to a slightly less perfect extent.”
The scientists found some key differences in the electronic properties that contribute to the generation of charge order — the charge density wave — in the two classes of superconductors. It turns out that the charge density wave in the nickelate is much more complex than that of the cuprate, coming from the combined interactions of all the different elements in the material.
“These findings indicate that the nickel compounds are promising to learn more about how the cuprates work, and they indicate the different ways you might want to change the nickel compounds to make them more like the cuprates — to have stronger magnetism or stronger superconductivity,” said Jennifer Sears, a postdoctoral researcher at Brookhaven.
“X-rays are really showing their power in probing these types of problems. The capabilities at NSLS-II have made it possible for us to work out this physics quite quickly in a way that wouldn’t have been the case without this new generation of RIXS instruments,” noted collaborator Matteo Mitrano of Harvard University.
Next steps include exploring the contributions of the rare-earth elements — lanthanum, strontium, and others — to the properties of these materials.
“The rare earth layer is not thought to be electronically active in the cuprates, but that’s an open question in the nickel-based materials,” Dean said.
The tools at NSLS-II will make it possible to explore that question, too.
Additional co-authors on this work included John Mitchell of Argonne National Laboratory, who together with Junjie Zhang provided the material samples that were prepared using unique high pressure crystal growth techniques, and x-ray spectroscopy specialist Gilberto Fabbris, who is also based at Argonne. The research and the facilities used were funded by the DOE Office of Science (BES).

A research model of dietary intake in 184 countries, developed by researchers at the Friedman School of Nutrition Science and Policy at Tufts University, estimates that poor diet contributed to over 14.1 million cases of type 2 diabetes in 2018, representing over 70% of new diagnoses globally. The analysis, which looked at data from 1990 and 2018, provides valuable insight into which dietary factors are driving type 2 diabetes burden by world region. The study was published April 17 in the journal Nature Medicine.
Of the 11 dietary factors considered, three had an outsized contribution to the rising global incidence of type 2 diabetes: Insufficient intake of whole grains, excesses of refined rice and wheat, and the overconsumption of processed meat. Factors such as drinking too much fruit juice and not eating enough non-starchy vegetables, nuts, or seeds, had less of an impact on new cases of the disease.
“Our study suggests poor carbohydrate quality is a leading driver of diet-attributable type 2 diabetes globally, and with important variation by nation and over time,” says senior author Dariush Mozaffarian, Jean Mayer Professor of Nutrition and dean for policy at the Friedman School. “These new findings reveal critical areas for national and global focus to improve nutrition and reduce devastating burdens of diabetes.”
Type 2 diabetes is characterized by the resistance of the body’s cells to insulin. Of the 184 countries included in the Nature Medicine study, all saw an increase in type 2 diabetes cases between 1990 and 2018, representing a growing burden on individuals, families, and healthcare systems.
The research team based their model on information from the Global Dietary Database, along with population demographics from multiple sources, global type 2 diabetes incidence estimates, and data on how food choices impact people living with obesity and type 2 diabetes from multiple published papers.
The analysis revealed that poor diet is causing a larger proportion of total type 2 diabetes incidence in men versus women, in younger versus older adults, and in urban versus rural residents at the global level.
Regionally, Central and Eastern Europe and Central Asia — particularly in Poland and Russia, where diets tend to be rich in red meat, processed meat, and potatoes — had the greatest number of type 2 diabetes cases linked to diet. Incidence was also high in Latin America and the Caribbean, especially in Colombia and Mexico, which was credited to high consumption of sugary drinks, processed meat, and low intake of whole grains.
Regions where diet had less of an impact on type 2 diabetes cases included South Asia and Sub-Sharan Africa — though the largest increases in type 2 diabetes due to poor diet between 1990 and 2018 were observed in Sub-Saharan Africa. Of the 30 most populated countries studied, India, Nigeria, and Ethiopia had the fewest case of type 2 diabetes related to unhealthy eating.
“Left unchecked and with incidence only projected to rise, type 2 diabetes will continue to impact population health, economic productivity, health care system capacity, and drive heath inequities worldwide,” says first author Meghan O’Hearn. She conducted this research while a PhD candidate at the Friedman School and currently works as Impact Director for Food Systems for the Future, a non-profit institute and for-profit fund that enables innovative food and agriculture enterprises to measurably improve nutrition outcomes for underserved and low-income communities. “These findings can help inform nutritional priorities for clinicians, policymakers, and private sector actors as they encourage healthier dietary choices that address this global epidemic.”
Other recent studies have estimated that 40% of type 2 diabetes cases globally are attributed to suboptimal diet, lower than the 70% reported in the Nature Medicine paper. The research team attributes this to the new information in their analysis, such as the first ever inclusion of refined grains, which was one of the top contributors to diabetes burdens; and updated data on dietary habits based on national individual-level dietary surveys, rather than agricultural estimates. The investigators also note that they presented the uncertainty of these new estimates, which can continue to be refined as new data emerges.

To get therapies into the brain after a stroke, researchers are increasingly making use of the blood-brain barrier, which allows only certain molecules to pass from the blood into the brain. In a study published earlier this year in Molecular Therapy, Japanese researchers have found that antisense oligonucleotides — specialized molecules that can modulate RNA and alter protein production — are preferentially taken up from the blood into areas of stroke damage when they’re linked to a specific kind of lipid known as ?-tocopherol (TOC).
Current stroke therapies are only effective if they are delivered within a short window of time, which limits their effectiveness in many patients. Many new therapies are being investigated that can be applied outside this short window of opportunity. One such therapy involves the use of antisense oligonucleotides, which can be targeted to increase the production of beneficial proteins after a stroke, for example, or to decrease the production of harmful proteins. However, getting these molecules into the right area at the right time can be difficult, something that the researchers at Tokyo Medical and Dental University wanted to address.
“We’ve recently developed an antisense oligonucleotide known as a DNA/RNA heteroduplex oligonucleotide, or HDO,” says senior author of the study Takanori Yokota. “To see how different lipids affect the uptake of HDO in the brain, we linked it to either cholesterol or TOC and then injected it into the blood of mice who had been given an experimentally induced stroke in just one side of the brain.”
Unexpectedly, the TOC-linked molecules were observed at very high levels in the stroke-lesioned side of the brain only, whereas the cholesterol-linked molecules were high in both sides of the brain. This suggests that TOC specifically increases HDO uptake after stroke, while cholesterol does not. Furthermore, because HDO can be tailored to target different genes, it was used to silence a gene known to be beneficial in stroke. As expected, the researchers observed greater areas of stroke-related damage in the mice treated with this TOC-linked HDO.
“Together, our findings suggest that TOC-linked HDO is safe to use and is preferentially taken up and incorporated into cells in areas of stroke damage,” says Yokota. “This delivery method is potentially very useful for the targeted up- or down-regulation of protein expression after stroke.”
Given the relative lack of stroke therapies targeting the pathological processes that happen after a stroke, the current findings are very important. Increasing anti-inflammatory proteins and/or lowering inflammatory proteins in the stroke-lesioned brain is a promising way to avoid secondary damage to the brain after a stroke has occurred, and will lead to reductions in stroke-related disabilities.

Sickle cell disease (SCD) is a serious blood disorder affecting millions of people, primarily those of African descent. A mutation in the gene that encodes a subunit of the oxygen-carrying molecule, hemoglobin, causes the disease. Scientists at St. Jude Children’s Research Hospital and the Broad Institute of MIT and Harvard showed a precise genome editing approach, prime editing, can change mutated hemoglobin genes back to their normal form in SCD patient cells, which restores normal blood parameters after transplantation into mice. The findings were published today in Nature Biomedical Engineering.
Scientists have rapidly developed technologies to edit DNA, including Cas9 nucleases and base editors, to treat genetic diseases. The study’s researchers demonstrated how a “third-generation” programmable gene editing technology called prime editing could convert the mutation that causes SCD into the normal DNA sequence, thereby rescuing the disease.
“Prime editing is a promising approach because, in theory, we can directly correct disease mutations to specific healthy DNA sequences of our choosing,” said co-corresponding authorJonathan Yen, Ph.D., St. JudeDepartment of Hematology. “We optimized prime editing in long-term blood stem cells and showed that the prime editing cells maintain full engraftment efficiency in an animal with a clinically relevant system.”
“These results show efficient prime editing of blood stem cells and that the prime-edited cells maintain their full ability to engraft and repopulate the bone marrow of an animal,” said senior and co-corresponding author David Liu, Ph.D., Richard Merkin, Professor at Broad Institute of MIT and Harvard, whose lab invented prime editing in 2019. “Bringing the ‘search-and-replace’ versatility of prime editing to blood stem cells raises the possibility of applying this technology to treat a wide range of diseases involving blood cells.”
Fixing the mutation that causes sickle cell disease
The researchers showed that the prime editing system could find the disease-causing mutation in the adult hemoglobin gene with high specificity and replace it efficiently with the healthy DNA sequence variant carried by most humans. Prime editing successfully corrected this mutation with up to 41% conversion in blood stem cells from SCD patients. Previous research has shown that editing over 20% of cells likely translates to therapeutic benefit.

Adding to the approach’s therapeutic promise is the observation that when the researchers transplanted prime-edited cells from four SCD patients into mice, normal hemoglobin production was present in about 45% of circulating red blood cells, even up to 17 weeks later. After the transplant, when placed in low-oxygen environments, the red blood cells isolated from the mouse bone marrow reduced sickling by half, from about 67% to 37%.
Improving precision gene editing
“We have identified what might be the next wave of therapies for genetic anemias,” said co-author Mitchell Weiss, M.D., Ph.D., St. Jude Department of Hematology chair. “We took the newest cutting-edge genetic engineering technology and showed that we could make meaningful gene edits for future therapies.”
While the scientists conducted the research in SCD patient cells transplanted into mice, the approach may have advantages over current genome editing methods used in clinical trials, such as Cas9 nucleases, which make double-stranded breaks in DNA that prime editing largely avoids. The collaborators had previously shown base editing, an alternative genome editing technology, could turn the sickle cell mutation into a benign variant, but not the original healthy sequence, in a 2021 Nature publication. The current study showed prime editing could turn the disease mutation into the original normal gene variant through a T-to-A conversion, which base editing cannot make.
Though the study showed the potential benefits of using prime editing to cure genetic anemias, it also showed limitations. Prime editing requires a time-consuming process to adapt and optimize each step of the protocol, such as designing the prime editing guide RNAs (pegRNAs) that target the prime editing system to the right DNA region and specify the desired edit.

Safety first
Safety remains a concern for all genomic editing technologies, especially novel approaches. While the current study, consistent with other labs’ reports on prime editing, showed virtually no off-target prime editing, it could have unforeseen safety issues as a newer gene editing technology.
“We are doing our best to predict toxicity, but we won’t know the true extent of the risks of this therapy until it is used in patients,” said Weiss.
Even with these challenges, the scientists are optimistic about the future of prime editing.
“Because of its unique versatility, prime editing has the potential to cure many more genetic diseases,” Yen said. “It will be a challenge to get to the clinic. It will require extensive manufacturing development, process optimization and safety assessment. But the proof of concept is there. Our work now opens the door to developing cures for many hematological diseases.”