Publisher Health

Northwestern University engineers have developed a new sponge that can remove metals — including toxic heavy metals like lead and critical metals like cobalt — from contaminated water, leaving safe, drinkable water behind.
In proof-of-concept experiments, the researchers tested their new sponge on a highly contaminated sample of tap water, containing more than 1 part per million of lead. With one use, the sponge filtered lead to below detectable levels.
After using the sponge, researchers also were able to successfully recover metals and reuse the sponge for multiple cycles. The new sponge shows promise for future use as an inexpensive, easy-to-use tool in home water filters or large-scale environmental remediation efforts.
The study was published late yesterday (May 10) in the journal ACS ES&T Water. The paper outlines the new research and sets design rules for optimizing similar platforms for removing — and recovering — other heavy-metal toxins, including cadmium, arsenic, cobalt and chromium.
“The presence of heavy metals in the water supply is an enormous public health challenge for the entire globe,” said Northwestern’s Vinayak Dravid, senior author of the study. “It is a gigaton problem that requires solutions that can be deployed easily, effectively and inexpensively. That’s where our sponge comes in. It can remove the pollution and then be used again and again.”
Dravid is the Abraham Harris Professor of Materials Science and Engineering at Northwestern’s McCormick School of Engineering and director of global initiatives at the International Institute for Nanotechnology.

Sopping up spills
The project builds on Dravid’s previous work to develop highly porous sponges for various aspects of environmental remediation. In May 2020, his team unveiled a new sponge designed to clean up oil spills. The nanoparticle-coated sponge, which is now being commercialized by Northwestern spinoff MFNS Tech, offers a more efficient, economic, ecofriendly and reusable alternative to current approaches to oil spills.
But Dravid knew it wasn’t enough.
“When there is an oil spill, you can remove the oil,” he said. “But there also are toxic heavy metals — like mercury, cadmium, sulfur and lead — in those spills. So, even when you remove the oil, some of the other toxins might remain.
Rinse and repeat
To tackle this aspect of the issue, Dravid’s team, again, turned to sponges coated with an ultrathin layer of nanoparticles. After testing many different types of nanoparticles, the team found that a manganese-doped goethite coating worked best. Not only are manganese-doped goethite nanoparticles inexpensive to make, easily available and nontoxic to human, they also have the properties necessary to selectively remediate heavy metals.

“You want a material with a high surface area, so there’s more room for the lead ions to stick to it,” said Benjamin Shindel, a Ph.D. student in Dravid’s lab and the paper’s first author. “These nanoparticles have high-surface areas and abundant reactive surface sites for adsorption and are stable, so they can be reused many times.”
The team synthesized slurries of manganese-doped goethite nanoparticles, as well as several other compositions of nanoparticles, and coated commercially available cellulose sponges with these slurries. Then, they rinsed the coated sponges with water in order to wash away any loose particles. The final coatings measured just tens of nanometers in thickness.
When submerged into contaminated water, the nanoparticle-coated sponge effectively sequested lead ions. The U.S. Food and Drug Administration requires that bottled drinking water is below 5 parts per billion of lead. In filtration trials, the sponge lowered the amount of lead to approximately 2 parts per billion, making it safe to drink.
“We’re really happy with that,” Shindel said. “Of course, this performance can vary based on several factors. For instance, if you have a large sponge in a tiny volume of water, it will perform better than a tiny sponge in a huge lake.”
Recovery bypasses mining
From there, the team rinsed the sponge with mildly acidified water, which Shindel likened to “having the same acidity of lemonade.” The acidic solution caused the sponge to release the lead ions and be ready for another use. Although the sponge’s performance declined after the first use, it still recovered more than 90% of the ions during subsequent use cycles.
This ability to gather and then recover heavy metals is particularly valuable for removing rare, critical metals, such as cobalt, from water sources. A common ingredient in lithium-ion batteries, cobalt is energetically expensive to mine and accompanied by a laundry list of environmental and human costs.
If researchers could develop a sponge that selectively removes rare metals, including cobalt, from water, then those metals could be recycled into products like batteries.
“For renewable energy technologies, like batteries and fuel cells, there is a need for metal recovery,” Dravid said. “Otherwise, there is not enough cobalt in the world for the growing number of batteries. We must find ways to recover metals from very dilute solutions. Otherwise, it becomes poisonous and toxic, just sitting there in the water. We might as well make something valuable with it.”
Standardized scale
As a part of the study, Dravid and his team set new design rules to help others develop tools to target particular metals, including cobalt. Specifically, they pinpointed which low-cost and nontoxic nanoparticles also have high-surface areas and affinities for sticking to metal ions. They studied the performance of coatings of manganese, iron, aluminum and zinc oxides on lead adsorption. Then, they established relationships between the structures of these nanoparticles and their adsorptive properties.
Called Nanomaterial Sponge Coatings for Heavy Metals (or “Nano-SCHeMe”), the environmental remediation platform can help other researchers differentiate which nanomaterials are best suited for particular applications.
“I’ve read a lot of literature that compares different coatings and adsorbents,” said Caroline Harms, an undergraduate student in Dravid’s lab and paper co-author. “There really is a lack of standardization in the field. By analyzing different types of nanoparticles, we developed a comparative scale that actually works for all of them. It could have a lot of implications in moving the field forward.”
Dravid and his team imagine that their sponge could be used in commercial water filters, for environmental clean-up or as an added step in water reclamation and treatment facilities.
“This work may be pertinent to water quality issues both locally and globally,” Shindel said. “We want to see this out in the world, where it can make a real impact.”
Dravid and Northwestern have financial interests (equities, royalties) in MFNS Tech.

It often was thought that the speed of information transmitted among regions of the brain stabilized during early adolescence. A study in Nature Neuroscience by Mayo Clinic researchers and colleagues from the Netherlands found transmission speeds continue to increase into early adulthood.
Because problems such asanxiety, depression and bipolar disorders can emerge in late adolescence and early adulthood, a better understanding of brain development may help clinicians offer therapies to treat these disorders.
“A fundamental understanding of the developmental trajectory of brain circuitry may help identify sensitive periods of development when doctors could offer therapies to their patients,” says Dora Hermes, Ph.D., a Mayo Clinic biomedical engineer and senior author of the study.
Called the human connectome, the structural system of neural pathways in the brain or nervous system develops as people age. But how structural changes affect the speed of neuronal signaling has not been well described.
“Just as transit time for a truck would depend on the structure of the road, so does the transmission speed of signals among brain areas depend on the structure of neural pathways,” Dr. Hermes explains. “The human connectome matures during development and aging, and can be affected by disease. All these processes may affect the speed of information flow in the brain. “In the study, Dr. Hermes and colleagues stimulated pairs of electrodes with a brief electrical pulse to measure the time it took signals to travel among brain regions in 74 research participants between the ages of 4 and 51. The intracranial measurements were done in a small population of patients who had electrodes implanted for epilepsy monitoring at University Medical Center Utrecht, Netherlands.
The response delays in connected brain regions showed that transmission speeds in the human brain increase throughout childhood and even into early adulthood. They plateau around 30 to 40 years of age.
The team’s data indicate that adult transmission speeds were about two times faster compared to those typically found in children. Transmission speeds also were typically faster in 30- or 40-year-old subjects compared to teenagers.
Brain transmission speed is measured in milliseconds, a unit of time equal to one-thousandth of a second. For example, the researchers measured the neuronal speed of a 4-year-old patient at 45 milliseconds for a signal to travel from the frontal to parietal regions of the brain. In a 38-year-old patient, the same pathway was measured at 20 milliseconds. For comparison, the blink of an eye takes about 100 to 400 milliseconds.
The researchers are working to characterize electrical stimulation-driven connectivity in the human brain. One of the next steps is to better understand how transmission speeds change with neurological diseases. They are collaborating with pediatric neurosurgeons and neurologists to understand how diseases change transmission speeds compared to what would be considered within the normal range for a certain age group.
The research is supported by the National Institute of Mental Health of the National Institutes of Health (R01MH122258).

Improved cookstoves, which are widely used for cooking in developing countries, produce twice as many harmful ultrafine air pollution particles (PM0.1) as conventional stoves, according to a new study from the University of Surrey.
Researchers from Surrey’s Global Centre for Clean Air Research (GCARE) found that while improved cookstoves can reduce fine particles (PM2.5) by up to 65%, they can actually increase the emission of ultrafine particles.
The GCARE team also found that ultrafine particles’ large surface areas allow them to absorb a significant amount of hazardous metals and chemicals, such as arsenic, lead, nitrate, sulphate and polycyclic aromatic hydrocarbons.
Professor Prashant Kumar, co-author of the study and Director of GCARE at the University of Surrey, said:
“The global cost-of-living crisis has led to many turning to wood, coal, peat and other biomass fuels for domestic fuel combustion to cook or heat their homes. Unfortunately, our research suggests that there may be an even higher health cost to pay in the near future.
“These tiny particles can easily infiltrate the nasal passages, leading to potential health risks, and our most vulnerable will pick up that bill.”
Improved cookstoves are designed to reduce fuel consumption, smoke and harmful emissions during cooking. In addition, they are often designed to be more efficient and to burn fuel more thoroughly than traditional stoves.

Despite the known health impacts of domestic burning, it is thought that 2.8 billion people globally use solid fuels for heating their homes. Around 20% of households in Ireland use wood for fuel. According to the Environment Protection Agency, approximately 12.7 million people in America use wood as a major heat source.
Professor Kumar added:
“One bright spot that needs to be investigated further is the development of DEFRA-approved heat stoves that are designed to improve combustion efficiency and reduce pollutant emission. The use of eco-fuel pellets that emit fewer toxic fumes should also be considered as part of the package for improving the status quo.
“This is clearly a global issue impacting developing countries and superpowers alike, and so we all need to come together to ensure that clean air is available to all of society and not just the fortunate few.”
The research has been published by Science of the Total Environment, and it builds upon GCARE’s recently released kitchen guidance.
The University of Surrey is a world-leading centre for excellence in sustainability — where our multidisciplinary research connects society and technology to equip humanity with the tools to tackle climate change, clean our air, reduce the impacts of pollution on health and help us live better, more sustainable lives. The University is committed to improving its own resource efficiency on its estate and being a sector leader, aiming to be carbon neutral by 2030. A focus on research that makes a difference to the world has contributed to Surrey being ranked 55th in the world in the Times Higher Education (THE) University Impact Rankings 2022, which assesses more than 1,400 universities’ performance against the United Nations’ Sustainable Development Goals (SDGs).

Researchers have used a common disinfectant and antiseptic to create a new antimicrobial coating material that effectively kills bacteria and viruses, including MRSA and SARS-COV-2.
Scientists at the University of Nottingham’s School of Pharmacy took chlorhexidine, often used by dentists to treat mouth infections and for pre-surgical cleaning, and used it to coat the polymer, acrylonitrile butadiene styrene (ABS). The new study published in Nano Select shows that this new material was found to be effective in killing the microbes responsible for a range of infections and illnesses and could be used as an effective antimicrobial coating on a range of plastic products.
Plastics are widely used in medical settings, from intravenous bags and implantable devices to hospital beds and toilet seats. Some microbial species can survive in a hospital setting despite enhanced cleaning regimes, leading to an increased risk of patients getting infections whilst in hospital which then need antibiotic treatment. These microorganisms can survive and remain infectious on abiotic surfaces, including plastic surfaces, for extended periods, sometimes up to several months.
Dr Felicity de Cogan, Assistant Professor in Pharmaceutical Science of Biological Medicines led this study, she said: “As plastic is such a widely used material that we know can harbour infectious microorganisms we wanted to investigate a way to use this material to destroy the bacteria. We achieved this by bonding a disinfectant with the polymer to create a new coating material and discovered not only does it act very quickly, killing bacteria within 30 minutes, it also doesn’t spread into the environment or leach from the surface when touched. Making plastic items using this material could really help tackle the issue of antibiotic resistance and reduce hospital acquired infections.”
The researchers used a special imaging technique called Time-of-Flight Secondary Ion Mass Spectrometry (TOF-SIMS) to examine the material at molecular level. This revealed the material was antimicrobial and rapidly killed microbes and after 45 minutes the surfaces were still clear of these microbes. It was also effective against SARS-COV-2, with no viable virions found after 30 minutes. Additionally, the surfaces were also effective in killing chlorhexidine-resistant strains of bacteria.
The COVID-19 pandemic has drawn increased attention to hospital-acquired infections, as it has been estimated that 20% of all patients hospitalized with COVID-19 contracted the virus while already in hospital. It has been estimated that in 2016/17, 4.7% of adult hospital inpatients contracted an infection whilst in hospital, with 22,800 patients dying due to these infections despite these deaths being preventable. The most common pathogens that cause hospital-acquired infections are Escherichia coli, Staphylococcus aureus, and Clostridium difficile. Outbreaks of infection in the clinic are frequently caused by strains resistant to antimicrobial drugs.
Dr de Cogan continues: “Research has shown that contaminated surfaces, including plastic surfaces, can act as a reservoir of antimicrobial resistance genes, encouraging the spread of antimicrobial resistance across bacterial species through horizontal gene transfer despite deep cleaning practices. It is paramount that new technologies are developed to prevent the spread of pathogenic microorganisms to vulnerable patients and address the ever-increasing threat of antimicrobial resistance.
“This research offers an effective way to do this and the material could be added to plastic materials during manufacture, it could also potentially be used as a spray.”

In the future, artificial intelligence will play an important role in medicine. In diagnostics, successful tests have already been performed: for example, the computer can learn to categorise images with great accuracy according to whether they show pathological changes or not. However, it is more difficult to train an artificial intelligence to examine the time-varying conditions of patients and to calculate treatment suggestions — this is precisely what has now been achieved at TU Wien in cooperation with the Medical University of Vienna.
With the help of extensive data from intensive care units of various hospitals, an artificial intelligence was developed that provides suggestions for the treatment of people who require intensive care due to sepsis. Analyses show that artificial intelligence already surpasses the quality of human decisions. However, it is now important to also discuss the legal aspects of such methods.
Making optimal use of existing data
“In an intensive care unit, a lot of different data is collected around the clock. The patients are constantly monitored medically. We wanted to investigate whether these data could be used even better than before,” says Prof. Clemens Heitzinger from the Institute for Analysis and Scientific Computing at TU Wien (Vienna). He is also Co-Director of the cross-faculty “Center for Artificial Intelligence and Machine Learning” (CAIML) at TU Wien.
Medical staff make their decisions on the basis of well-founded rules. Most of the time, they know very well which parameters they have to take into account in order to provide the best care. However, the computer can easily take many more parameters than a human into account — and in some cases this can lead to even better decisions.
The computer as planning agent
“In our project, we used a form of machine learning called reinforcement learning,” says Clemens Heitzinger. “This is not just about simple categorisation — for example, separating a large number of images into those that show a tumour and those that do not — but about a temporally changing progression, about the development that a certain patient is likely to go through. Mathematically, this is something quite different. There has been little research in this regard in the medical field.”

The computer becomes an agent that makes its own decisions: if the patient is well, the computer is “rewarded.” If the condition deteriorates or death occurs, the computer is “punished.” The computer programme has the task of maximising its virtual “reward” by taking actions. In this way, extensive medical data can be used to automatically determine a strategy which achieves a particularly high probability of success.
Already better than a human
“Sepsis is one of the most common causes of death in intensive care medicine and poses an enormous challenge for doctors and hospitals, as early detection and treatment is crucial for patient survival,” says Prof. Oliver Kimberger from the Medical University of Vienna. “So far, there have been few medical breakthroughs in this field, which makes the search for new treatments and approaches all the more urgent. For this reason, it is particularly interesting to investigate the extent to which artificial intelligence can contribute to improve medical care here. Using machine learning models and other AI technologies are an opportunity to improve the diagnosis and treatment of sepsis, ultimately increasing the chances of patient survival.”
Analysis shows that AI capabilities are already outperforming humans: “Cure rates are now higher with an AI strategy than with purely human decisions. In one of our studies, the cure rate in terms of 90-day mortality was increased by about 3% to about 88%,” says Clemens Heitzinger.
Of course, this does not mean that one should leave medical decisions in an intensive care unit to the computer alone. But the artificial intelligence may run along as an additional device at the bedside — and the medical staff can consult it and compare their own assessment with the artificial intelligence’s suggestions. Such artificial intelligences can also be highly useful in education.
Discussion about legal issues is necessary
“However, this raises important questions, especially legal ones,” says Clemens Heitzinger. “One probably thinks of the question who will be held liable for any mistakes made by the artificial intelligence first. But there is also the converse problem: what if the artificial intelligence had made the right decision, but the human chose a different treatment option and the patient suffered harm as a result?” Does the doctor then face the accusation that it would have been better to trust the artificial intelligence because it comes with a huge wealth of experience? Or should it be the human’s right to ignore the computer’s advice at all times?
“The research project shows: artificial intelligence can already be used successfully in clinical practice with today’s technology — but a discussion about the social framework and clear legal rules are still urgently needed,” Clemens Heitzinger is convinced.

Much of what is now considered modern medicine originated as folk remedies or traditional, Indigenous practices. These customs are still alive today, and they could help address a variety of conditions. Now reporting in ACS Omega, a team of researchers have identified compounds in the leaves of a particular medicinal Labrador tea plant used throughout the First Nations of Nunavik, Canada, and demonstrated that one of them has activity against the parasite responsible for malaria.
“Labrador tea” refers to multiple, closely related plants — all members of the genus Rhododendron. These are small, evergreen shrubs with fuzzy leaves that, as their name suggests, are steeped to make herbal teas commonly used by the Inuit and Indigenous nations in the U.S. and Canada. Reportedly, drinks made from the leaves or roots can aid in treating colds or the flu, headaches or stomach aches, nasal congestion and many other ailments. Past studies have shown that essential oils extracted from the plants have antimicrobial properties, which could help fight antibiotic-resistant microbes. Dwarf Labrador tea, or Rhododendron subarcticum, produces a particularly aromatic brew and grows in the harsher conditions of the subarctic, found from Alaska to Siberia just south of the Arctic Circle. Despite its common use as a traditional medicine, its chemical composition and potential antimicrobial applications remain relatively unstudied. So, Normand Voyer and colleagues wanted to characterize the makeup of R. subarcticum for the first time and test its antiparasitic activity.
The team gathered R. subarcticum leaves from Nunavik, a region in northern Quebec. The researchers extracted the essential oil from the leaves and analyzed it with gas chromatography, mass spectrometry and flame ionization detection, to identify 53 compounds. It turns out that 64.7% of the oil was comprised of ascaridole, followed by p-cymene at 21.1%. This combination of compounds has not previously been reported in closely related North American Labrador tea varieties, though it has been found in subspecies originating in Europe and Asia.
To see whether this essential oil had antimalarial properties, the team exposed two strains of Plasmodium falciparum, a malaria-causing parasite, to the oil or to just ascaridole. In the experiment, one of the strains was resistant to known antimalaria drugs. The data showed that ascaridole was the primarily component that acted against both strains of the parasite, which is consistent with other, antiparasitic traditional medicines also rich in the compound. The researchers say that this work bolsters the importance of investigating and protecting plants used in traditional medicines, especially those from harsher climates impacted by climate change.
The authors thank the Whapmagoostui Cree Nation Council and Kuujjuarapik Inuit Community Council for sharing their knowledge, and acknowledge funding from the Natural Science and Engineering Research Council of Canada, Fonds de Recherche du Québec — Nature et Technologies, Sentinel North and IDEX UCAjedi.

Researchers at the University of East Anglia have used cutting-edge imaging technology to measure acute pressure changes inside the heart.
The state-of-the-art technology uses magnetic resonance imaging (MRI) to create detailed images of the heart.
Using the new technology, the team discovered that pressure inside the heart goes up when given a specific medication for testing the heart’s blood flow.
They also found out why this medication called adenosine, makes patients breathless during the test.
The team say their findings could help doctors better diagnose and monitor patients with heart disease and heart failure.
Lead researcher Dr Pankaj Garg, from UEA’s Norwich Medical School, said: “When patients present with symptoms of heart disease, doctors use a special test called heart MRI to take detailed pictures of the heart and see how well it is working.

“Sometimes, patients are given a special medication called adenosine during the heart MRI test to see how blood flows through the heart, and it can cause breathlessness.
“We wanted to better understand the way that the heart functions, and why patients become breathless when given adenosine.”
The UEA team worked with researchers at the University of Leeds and studied 33 patients referred for a stress cardiac MRI.
This test is performed to help evaluate the blood flow in the heart arteries, looking for blockages.
The research team took pictures of the patient’s heart when it was resting and when it was working hard after being given adenosine.

“Adenosine mimics the effect of exercise on the heart while the patient is lying down on the scanner,” said Dr Garg, “And we discovered why it makes patients get out of breath.
Postgraduate researcher Hosamadin Assadi, also from UEA’s Norwich Medical School, said: “We looked at the top chamber of the heart, called the left atrium, and also looked at the lower part of the heart, called the left ventricle.
“We used advanced software to measure and study the heart, and we also estimated the pressures inside the heart before and after giving the medication.
“Our study shows that after giving patients adenosine, the heart’s left atrium got bigger really fast — just before the blood flowed out.
“This is important as it shows that the previously published heart MRI pressure model is adaptable to acute changes in the heart and can be more broadly used to diagnose and monitor heart disease — in particular heart failure.
“We also found that a measure called LVFP, which tells us about the pressure inside the heart, went up when the heart was working hard.”
Dr Garg’s previous work showed that a 4D heart MRI scan can create detailed flow images of the heart, and how this non-invasive imaging technique can measure the peak velocity of blood flow in the heart accurately and precisely.
The scan takes just six to eight minutes and can provide precise imaging of the heart valves and the flow inside the heart in three-dimensions, helping doctors determine the best course of treatment for patients.
“This work strengthens the notion of using heart MRI to measure pressures inside the heart,” added Dr Garg.
‘An acute increase in Left Atrial Volume and Left Ventricular Filling Pressure During Adenosine administered Myocardial Hyperaemia: CMR First-Pass Perfusion Study’ is published in the journal BMC Cardiovascular Disorders.

Bacteria can rapidly evolve resistance to antibiotics by adapting special pumps to flush them out of their cells, according to new research from the Quadram Institute and University of East Anglia.
Antimicrobial resistance is a growing problem of global significance. The rise of resistant “superbugs” threatens our ability to use antimicrobials like antibiotics to treat and prevent the spread of infections caused by microorganisms.
It is hoped that the findings will improve how antibiotics are used to help prevent further spread of antimicrobial resistance.
Prof Mark Webber UEA’s Norwich Medical School, and the Quadram Institute, said: “Knowing the details of the mechanisms bacteria develop to become resistant is a key step to understanding antimicrobial resistance. We hope that this kind of work to understand when and how resistance emerges can help us use antibiotics better to minimise selection of resistance.”
The team studied how exposure to antimicrobials leads to the emergence of resistance.
Broadly, superbugs’ defences against antibiotics involve inactivating or evading drugs, stop them getting into their cells, or getting them out of their cells before they can have any effect. But exactly how they do this is still being worked out.

In this new study Dr Eleftheria Trampari from QI, Prof Webber, and colleagues recreated the evolutionary stresses that lead to antimicrobial resistance by exposing Salmonella bacteria to two different antibiotics.
The bacteria were allowed to grow and reproduce in two different states that mimic how they live in the environment.
Some were planktonic — floating in a liquid broth — but others were in biofilms. Bacteria form biofilms on surfaces, as a way of protecting themselves against stresses and most bacteria in the real world exist in a biofilm.
Hundreds of generations of bacteria were grown and exposed to the antibiotics, and in this evolution simulation, survival of the fittest selected those bacteria best adapted to cope with the presence of the antibiotics.
To identify how these ‘winners’ had become resistant, the researchers sequenced the genomes of the resistant bacteria, to identify which genes had changed compared to their non-resistant ancestors.

They found that both antibiotics selected different mutations in a molecular pump that Salmonella uses to get rid of toxic compounds from inside its cells. With colleagues from the University of Essex and University of Cagliari, they found that these two different changes altered how the pump worked in totally different ways. One made it easier for the pumps to catch drugs, the other made it easier for drugs to slide through the pump.
A search of a databases of genomes of Salmonella isolates found that one of these mutations has also arisen multiple times in the real world, in Salmonella from patients, livestock and food in the UK, US and EU, as far back as 2003.
The findings confirm a primary role for these pumps as the first line of defence against antimicrobials.
“This work simulates what happens in the real world where bacteria are constantly exposed to varying concentrations of antimicrobials” said Dr Eleftheria Trampari from the Quadram Institute and first author on the study. “Studying how resistant strains emerge and predict which drugs they will not respond to can be helpful in developing diagnostics and treatment strategies.”
The study was supported by the Biotechnology and Biological Sciences Research Council, part of UKRI.

Scripps Research chemists have solved a long-standing problem in the field of pharmaceutical chemistry with a relatively simple and controllable method for making benzocyclobutenes (BCBs) — a class of reactive compounds that are highly valued as building blocks for drug molecules, but have been relatively hard to access.
The new method, described in a paper in Science on May 12, uses designer ligand molecules with palladium-atom catalysts to break pairs of adjacent methylene-type C-H bonds in relatively cheap and abundant carboxylic acids. Breaking these bonds enables the making of BCBs with unprecedented ease through a process called a formal [2+2] cycloaddition.
The researchers demonstrated the new method with relatively easy syntheses of several BCBs found in traditional medicines and in experimental and approved drug molecules
“Our new method requires only a saturated aliphatic chain and aryl halides as coupling partners for a formal cycloaddition yielding a four-membered ring,” says study senior author Jin-Quan Yu, PhD, the Bristol Myers Squibb Endowed Chair in Chemistry and Frank and Bertha Hupp Professor in the Department of Chemistry at Scripps Research. “By contrast, the traditional method for making BCBs requires more steps and yields a mix of products that are hard to separate.”
BCBs have a unique core structure consisting of a relatively rigid, strained and reactive ring of four carbon atoms fused to a benzene ring. They are present in some natural medicinal compounds and in the heart-failure drug ivabradine. In general, their propensity for biological activity makes them potentially very useful building blocks for drugs. They are also key ingredients in photosensitive polymers, polymer dielectrics and other advanced materials.
The synthesis of BCBs has been challenging, however. The limitations of the various methods that have been published include an inability to control the order in which individual reactions occur, so that the reaction products include not only the desired product but also unwanted ones. Yu’s new method for the first time enables this control — a property called regioselectivity.
Last year, the Yu lab developed a method for the palladium-catalyzed, β- and γ-methylene C-H functionalization of free aliphatic acids, to make structurally diverse γ- and δ-lactones — also highly valued as potential pharmaceutical building blocks. Inspired by that method and using it as a starting point, they pursued a similar approach to surmount the challenge of BCB regioselective synthesis.
For the new method, they employed bidentate amide-pyridone ligands bearing palladium catalysts to activate the C-H bonds of two adjacent methylene units in a carboxylic acid.
“In the presence of a dihaloheteroarene, two C-H bonds and two aryl-halogen bonds are stitched together almost miraculously to form a bicyclic BCB scaffold,” Yu says. “Regioselectivity is achieved through the differentiation between the aryl iodide and bromide sites.”
The chemists showed that the method can be used with a wide range of cyclic and acyclic aliphatic acids to generate diverse BCBs and hetero-BCBs — a dream come true for many pharmaceutical chemists.
“The ability to make direct use of abundant and structurally varied acyclic and cyclic acids as substrates, without pre-functionalization, substantially expands chemists’ access to diverse BCB scaffolds — including heterocyclic BCBs that can be very useful in drug molecules,” Yu says.

From low-carb to intermittent fasting, surgery to Ozempic — people turn to a seemingly never-ending array of diets, procedures and drugs to lose weight. While it has been long understood that limiting the amount of food eaten can promote healthy aging in a wide range of animals, including humans, a new study from University of Michigan has revealed that the feeling of hunger itself may be enough to slow aging.
Previous research has demonstrated that even the taste and smell of food can reverse the beneficial, life-extending effects of diet restriction, even without its consumption.
These intriguing findings drove first author Kristy Weaver, Ph.D., principal investigator Scott Pletcher, Ph.D., and their colleagues to examine whether changes in the brain that prompt the drive to seek food could be behind longer life.
“We’ve sort of divorced [the life extending effects of diet restriction] from all of the nutritional manipulations of the diet that researchers had worked on for many years to say they’re not required,” said Pletcher. “The perception of not enough food is sufficient.”
To do this, they induced hunger in flies in several ways. The first was to alter the amount of branched-chain amino acids, or BCAAs, in a test snack food and later allow the flies to freely feed on a buffet of yeast or sugar food. Flies fed the low-BCAA snack consumed more yeast than sugar in the buffet than did the flies fed the high-BCAA snack. This kind of preference for yeast over sugar is one indicator of need-based hunger.
The researchers noted that this behavior wasn’t due to the calorie content of the low-BCAA snack; in fact, these flies consumed more food and more total calories. When flies ate a low-BCAA diet for life, they also lived significantly longer than flies fed high-BCAA diets.
To look at hunger apart from dietary composition, they used a unique technique, activating neurons associated with the hunger drive in flies using exposure to red light, using a technique called optogenetics. These flies consumed twice as much food than did flies who were not exposed to the light stimulus. The red-light activated flies also lived significantly longer than flies used as a control.
“We think we’ve created a type of insatiable hunger in flies,” said Weaver. “And by doing so, the flies lived longer.”
What’s more, the team was able to map the molecular mechanics of hunger to changes in the epigenome of the neurons involved — and to identify that neurons responded to the presence or absence of a specific amino acid in the diet. These changes can affect how much of specific genes are expressed in the brains of flies and, consequently, their feeding behavior and aging.
The authors note that caution should be used before applying the findings to people, but “there’s every reason to expect that the mechanisms discovered are likely to modulate hunger drives in other species.”
They next plan to examine how the drive to eat for pleasure, present in both flies and people, may also be linked to lifespan.