Novel Wound Dressing Seals, Protects, and Prevents Scar Formation with ‘Significant’ Advantages (Medicine)

University of Chicago researcher Xiaoyang Wu has developed a novel wound dressing that can stop bleeding while preventing infection and scarring using a single material, which has potential applications in drug delivery, among other areas.

“Scarring is one of the worst consequences of severe wounds,” said Wu, an associate professor in the Ben May Department of Cancer Research at the University of Chicago, noting that human skin is particularly prone to develop scars.

Taking a materials science approach, the researchers developed a new method to overcome scarring by inhibiting collagen synthesis by blocking transforming growth factor beta (TGF-β) – a cytokine that plays an important role in cell signaling, both in skin wound repair and tissue fibrosis.

“Increasing evidence suggests TGF-β is important in early phase wound repair for wound closure. But, later on, the signal may promote and enhance scarring,” Wu said. This makes timing key. “We cannot simply block the signal, because that would slow down wound healing and would be dangerous for the patient,” he explained.

To overcome this, the researchers designed a timed-release system that combines a sutureless wound closure hydrogel material with a biodegradable microcapsule system, which enables them to control when the TGF-β inhibitor is released. “In this way, we can enhance skin wound repair and after 7-14 days can release the inhibitor that blocks the skin scaring process at the same time by using one material,” Wu added.

The study results were recently published in Nature Communications.

(The wounds in skin grafts were treated with PLGA capsules with or without TGFβ inhibitor in HA-NB hydrogel, or alginate hydrogel as control at different time points) © University of Chicago

Beyond cosmetic surgery, current treatment for scarring is not ideal and there is no reliable way to prevent scars from forming if a patient experiences a deep or messy wound. “The system we developed is very convenient for application,” said Wu, adding that the system could also be used in different applications, such as drug delivery, in the future.

“We believe the novel system will have potential clinical importance in the future,” he said. To pursue these additional applications the next steps include filing an investigational new drug (IND) application with the US Food and Drug Administration (FDA). The researchers also need to ensure consistent manufacturing of the material and are exploring collaborations with pharmaceutical companies to move the research forward.

Additionally, because the whole system was developed using a very biocompatible material with adhesive properties, Wu said it has applications inside the body as well, adhering to and closing bleeding arteries and cardiac walls after UV light irradiation. The researchers demonstrated the ability to do this in animal models, suggesting significant advantages as a traumatic wound sealant.

“Normal wound binding material does work well,” said Wu, noting that currently, the most reliable material is fibers, which like surgical glue, is less biocompatible. “Biocompatibility is a significant advantage of our system,” he explained, “It is superior compared to current existing materials.”

Featured image: The inventors have developed a method to enhance skin wound repair and prevent scarring after wounding and surgery. (Image credit: iStock.com/allanswart)


Reference: Jian Zhang et al, A pulsatile release platform based on photo-induced imine-crosslinking hydrogel promotes scarless wound healing, Nature Communications (2021). DOI: 10.1038/s41467-021-21964-0


Provided by University of Chicago

Chemists Produced An Unusual Organic Pigment, Which is “Switched On” By An Electrical Charge (Chemistry)

In photosynthesis and organic photovoltaics, pigment molecules convert light into electrical charge. A team of chemists have now produced an unusual organic pigment, which is “switched on” by an electrical charge to become a potent dye that absorbs light in the near-infrared range. The team’s study, published in the journal Angewandte Chemie, suggests potential applications in systems for electrophysical materials research, photovoltaics, and sensor technology.

Charged pigments with intense colors have been predominantly metal based. One well-known example is iron-based Berlin blue or Prussian blue, which is a rich, deep blue. In terms of their chemistry, dyes and pigments of this kind are symmetrical molecules, with one side having a higher charge than the other. The sides exchange electrons, and the molecule absorbs light that is at the same wavelength as this energy exchange.

Purely organic pigments with similarly intense colors are rare. Nonetheless, Francis D’Souza’s team from the University of North Texas, and colleagues, have now developed a modular organic molecular system precisely to meet this brief. Compared to metals, organic materials have the advantage of being easy to modify. The team chose to target modular construction of the dye molecules, to give customizable molecules that could potentially be given a wide variety of different properties.

The core of the new molecule was made of a red fluorescent dye molecule. The researchers then attached a two-part “push–pull”, or “donor–acceptor”, molecular system to both sides of this core. These systems were able to stabilize electrical charges under specific conditions.

In the uncharged state, the pigment was just a blue-colored dye molecule. But when an electronic charge was applied, it demonstrated its full capabilities. The team observed a new, intense absorption band, but not in the visible-light range. The new dye absorbed in the near-infrared range, i.e., in the transitional region between visible light and heat radiation on the electromagnetic spectrum.

It was only when the two donor–acceptor units resonated with each other that absorption became possible: “The additional, free electron shuffles between the two chemically equivalent entities revealing a new charge-transfer peak in the near-infrared region,” state the authors. The molecule had become a mixed valence compound, with similar properties to metal-based dye compounds.

These electronically switchable organic pigments could be excellent model substances for basic research, says D’Souza. They could be used to help better understand electron transfer, as found in photosynthesis, for example. In addition to their potential as research aids, they could be used as efficient electron-transporting material in photonic devices and are also suitable as markers for analyzing electron transitions.


Reference: Faizal Khan et al, Photoinduced Charge Separation Prompted Intervalence Charge Transfer in a Bis(thienyl)diketopyrrolopyrrole Bridged Donor‐TCBD Push‐Pull System, Angewandte Chemie International Edition (2021). DOI: 10.1002/anie.202108293


Provided by Wiley

New Way To Probe Exotic Matter Aids In The Study of Atomic and Particle Physics (Physics)

Physicists have created a new way to observe details about the structure and composition of materials that improves upon previous methods. Conventional spectroscopy changes the frequency of light shining on a sample over time to reveal details about them. The new technique, Rabi-oscillation spectroscopy, does not need to explore a wide frequency range, so can operate much more quickly. This method could be used to interrogate our best theories of matter in order to form a better understanding of the material universe.

Though we cannot see them with the naked eye, we are all familiar with the atoms that make up matter. Collections of positive protons, neutral neutrons and negative electrons give rise to all the matter we interact with. However, there are more exotic forms of matter, including exotic atoms, which are not made from these three basic components. Muonium, for example, is like hydrogen, which typically has one electron in orbit around one proton, but has a positively charged muon particle in place of the proton.

Muons are important in cutting-edge physics as they allow physicists to test our best theories about matter such as quantum electrodynamics or the Standard Model, with extremely high accuracy. This in itself is important, as only when a robust theory is pushed to its extremes may cracks start to form that could indicate where new, more complete theories are needed and even what they might be. This is why the study of muonium is of great interest to the physics community, but up until now, it has evaded detailed observation.

“Muonium is a very short-lived atom, so it is important to make quick observations with as much power as possible in order to obtain the best signal from the limited observation time,” said Associate Professor Hiroyuki A.Torii from the Graduate School of Science at the University of Tokyo. “Conventional spectroscopic methods require repeated observations across a range of frequencies to find the particular key frequency we are looking for, known as the resonance frequency, and this takes time.”

So, Torii and his team devised a new kind of spectroscopic method that makes use of a well-understood physical effect known as Rabi oscillation. Rabi-oscillation spectroscopy does not need to search for frequency signals in order to convey information about an atom. Instead, it looks at the raw sensor, or time-domain, data over a shorter amount of time and delivers information based on that. This new method offers vast improvements in precision.

“The study of exotic atoms requires knowledge of low-energy atomic physics and high-energy particle physics. This combination of disciplines within physics suggests we’re on a path to a more complete understanding of our material universe,” said Torii. “I’m eager to see physicists use Rabi-oscillation spectroscopy to peer ever deeper into the world of exotic atoms containing unusual particles and isotopes, and other kinds of matter created at particle accelerators around the world.”

Featured image: (Top) The outside of the apparatus installed in a particle accelerator at the J-PARC facility in Tokai, Ibaraki Prefecture, north of Tokyo. (Lower left) The electronic components including a high-precision sensor. (Lower right) A detailed microscopic image of the silicon sensor that makes the observations. Credit: Torii et al.


Reference: S. Nishimura et al, Rabi-Oscillation Spectroscopy of the Hyperfine Structure of Muonium Atoms, Physical Review Letters (2021). arXiv:2007.12386 [hep-ex] arxiv.org/abs/2007.12386


Provided by University of Tokyo

New CRISPR/Cas9 Technique Corrects Cystic Fibrosis in Cultured Human Stem Cells (Medicine)

Researchers from the group of Hans Clevers (Hubrecht Institute) corrected mutations that cause cystic fibrosis in cultured human stem cells. In collaboration with the UMC Utrecht and Oncode Institute, they used a technique called prime editing to replace the ‘faulty’ piece of DNA with a healthy piece. The study, published in Life Science Alliance on August 9th, shows that prime editing is safer than the conventional CRISPR/Cas9 technique. “We have for the first time demonstrated that this technique really works and can be safely applied in human stem cells to correct cystic fibrosis.”

Cystic fibrosis (CF) is one of the most prevalent genetic diseases worldwide and has grave consequences for the patient. The mucus in the lungs, throat and intestines is sticky and thick, which causes blockages in organs. Although treatments are available to dilute the mucus and prevent inflammations, CF is not yet curable. However, a new study from the group of Hans Clevers (Hubrecht Institute) in collaboration with the UMC Utrecht and Oncode Institute offers new hope.

Correcting CF mutations

The researchers succeeded in correcting the mutations that cause CF in human intestinal organoids. These organoids, also called mini-organs, are tiny 3D structures that mimic the intestinal function of patients with CF. They were previously developed by the same research group from stem cells of patients with CF and stored in a biobank in Utrecht. For the study, published in Life Science Alliance, a technique named prime editing was used to replace the piece of mutated DNA that causes CF with a healthy piece of DNA in these organoids.

Image of organoids
Cystic Fibrosis patient derived organoids do not show a swelling response. The swelling response is regained after prime-editing mediated repair of the CFTR channel. Credit: Eyleen de Poel and Maarten Geurts, copyright: UMC Utrecht and Hubrecht Institute.
Safer than CRISPR/Cas9

Prime editing is a newer version of the better-known gene editing technique CRISPR/Cas9. CRISPR/Cas9 cuts the DNA before correcting it. Although this corrects the mutated piece of DNA, it also causes damage in other regions in the genome. “In our study, prime editing proves to be a safer technique than the conventional CRISPR/Cas9. It can build in a new piece of DNA without causing damage elsewhere in the DNA. That makes the technique promising for application in patients,” says Maarten Geurts, first author on the publication.

Swelling

The mutations that cause CF are localized in the CFTR channel, which is present in the cells of various organs including the lungs. Due to the mutations, the channel does not function properly, leaving the layer of mucus that covers the cells with too little water: the mucus becomes sticky. The addition of a substance called forskolin causes healthy organoids to swell, but this does not happen in organoids with mutations in the CFTR channel. “We applied prime editing to the mutations, after which the treated organoids demonstrated the same response as the healthy organoids: they became swollen. That provided us with proof that our technique worked and replaced the mutated DNA,” Geurts explains.Cystic Fibrosis patient derived organoids do not show a swelling response. The swelling response is regained after prime-editing mediated repair of the CFTR channel. Credit: Eyleen de Poel and Maarten Geurts, copyright: UMC Utrecht and Hubrecht Institute.

Curing genetic diseases

Now that the researchers showed that the mutations that cause CF can be safely corrected, applications in the clinic come one step closer. “New variants of CRISPR/Cas9, such as prime editing, can safely correct mutations without causing damage in other regions of the DNA. This will hopefully enable us to cure or even prevent genetic diseases in the future.” But before that, some challenges still lie ahead for the researchers. The technique for example still needs to be adapted for safe use in humans. “But this is a great step towards successfully applying prime editing in the clinic,” Geurts concludes.

Featured image: Swelling response of patient derived mini-guts. Collapsed organoids (left) show active swelling response that is mediated by the CFTR ion channel after one hour incubation with forskolin (right). Green staining shows complete cells (Calcein green) and DNA is shown in Blue. Credit: Eyleen de Poel, copyright: UMC Utrecht.


Publication

“Evaluating CRISPR-based Prime Editing for cancer modeling and CFTR repair in organoids”. Maarten Geurts, Eyleen de Poel, Cayetano Pleguezuelos-Manzano, Rurika Oka, Léo Carrillo, Amanda Andersson-Rolf, Matteo Boretto, Jesse Brunsveld, Ruben van Boxtel, Jeffrey Beekman, and Hans Clevers. Life Science Alliance (2021).


Provided by Hubrecht Institute

Geologists Discover That The NASA Rover Has Been Exploring Surface Sediments, Not Lake Deposits For Last Eight Years (Planetary Science)

In 2012, NASA landed the rover Curiosity in the Gale crater on Mars because the crater was thought by many scientists to be the site of an ancient lake on Mars more than 3 billion years ago. Since that time, the rover has been driving along, carrying out geological analyses with its suite of instruments for over 3,190 sols (martian days, equivalent to 3278 earth days). After analysing the data, researchers from Department of Earth Sciences, the Faculty of Science at HKU, have proposed that the sediments measured by the rover during most of the mission did not actually form in a lake.

The researcher team suggested that the large mound of sedimentary rocks explored and analysed for the last eight years actually represent sand and silt deposited as air-fall from the atmosphere and reworked by the wind. The alteration minerals formed by the interaction between water and the sand did not occur in a lake setting. The “wet” environment, they propose, actually represents weathering similar to soil formation under rainfall in an ancient atmosphere that was very different from the present one.

The discovery was published recently in Science Advances in a paper led by research postgraduate student Jiacheng LIU, his advisor Associate Professor Dr Joe MICHALSKI, and co-author Professor Mei Fu ZHOU, all of whom are affiliated with the Department of Earth Sciences. The researchers used chemistry measurements and x-ray diffraction (XRD) measurements, in addition to images of rock textures, to reveal how compositional trends in the rocks relate to geological processes.

“Jiacheng has demonstrated some very important chemical patterns in the rocks, which cannot be explained in the context of a lake environment,” said Dr Michalski. “The key point is that some elements are mobile, or easy to dissolve in water, and some elements are immobile, or in other words, they stay in the rocks. Whether an element is mobile or immobile depends not only on the type of element but also on the properties of the fluid. Was the fluid acidic, saline, oxidising etc. Jiacheng’s results show that immobile elements are correlated with each other, and strongly enriched at higher elevations in the rock profile. This points toward top-down weathering as you see in soils. Further, he shows that iron is depleted as weathering increases, which means that the atmosphere at the time was reducing on ancient Mars, not oxidising like it is on the modern day, rusted planet.”

These images show Gale crater in High Resolution Stereo Camera (HRSC) images, with elevation colorised in blue. The image on the left shows the standard model where Gale crater is generally assumed to have been a large lake (flooded to at least an elevation of ~4,000m). The image at the right is the model proposed by Liu et al., in which only very small, shallow lakes existed on the floor of Gale crater (with the crater flooded only to an elevation of approximately ~4,500m). Most of the sediments were deposited from the atmosphere as air-fall deposits and later weathered from precipitation or ice-melt. A star marks the rover’s landing site. Credit: ESA/HRSC/DLR

Understanding how the Martian atmosphere, and the surface environment as a whole, evolved is important for the exploration for possible life on Mars, as well as our understanding of how Earth may have changed during its early history. “Obviously, studying Mars is extremely difficult, and the integration of creative and technologically advanced methodologies are necessary. Liu and co-authors have made intriguing observations via the utilisation of remote sensing techniques to understand the chemical composition of ancient sediments that inform on their early development. Their data present challenges to existing hypotheses for both the depositional environment of these unique rock formations and the atmospheric conditions that they formed under – specifically, the authors show evidence for weathering processes under a reducing atmosphere in a subareal environment similar to a desert, rather than formation in an aqueous lake environment. Indeed, this work will inspire new and exciting directions for future research.” Assistant Professor from Department of Earth Science Dr Ryan McKenzie added.

China successfully landed its first lander, Zhurong, on Mars in May this year. Zhurong is currently roving the plains of Utopia Planitia, exploring mineralogical and chemical clues to recent climate change. China is also planning a sample return mission likely to occur at the end of this decade.

Featured image: An image taken by the Curiosity Rover MastCam  instrument shows layered sedimentary rocks composing Mount Sharp. The rover has been driving from the floor of Gale crater up through the rocks within these hills in order to understand how the rocks change from lower in the section (older) to higher in the section (younger). The rover have traversed rocks over >400 meters of elevation from the beginning of the mission. Credit: NASA’s Mars Curiosity Rover


Reference: Jiacheng Liu et al, Intense subaerial weathering of eolian sediments in Gale crater, Mars, Science Advances (2021). DOI: 10.1126/sciadv.abh2687


Provided by The University of Hong Kong

‘Cool’ Kids In The Cosmos May Not Be So Unique (Planetary Science)

Rice models infer small stars share similar dynamics to our sun, key to planet habitability

Stars scattered throughout the cosmos look different, but they may be more alike than once thought, according to Rice University researchers.

Alison Farrish
Alison Farrish (Photo courtesy of Rice University)

New modeling work by Rice scientists shows that “cool” stars like the sun share the dynamic surface behaviors that influence their energetic and magnetic environments. This stellar magnetic activity is key to whether a given star hosts planets that could support life.

The work by Rice postdoctoral researcher Alison Farrish and astrophysicists David Alexander and Christopher Johns-Krull appears in a published study in The Astrophysical Journal. The research links the rotation of cool stars with the behavior of their surface magnetic flux, which in turn drives the star’s coronal X-ray luminosity, in a way that could help predict how magnetic activity affects any exoplanets in their systems.

The study follows another led by Farrish and Alexander that showed a star’s space “weather” may make planets in their “Goldilocks zone” uninhabitable.

“All stars spin down over their lifetimes as they shed angular momentum, and they get less active as a result,” Farrish said. “We think the sun in the past was more active and that might have affected the early atmospheric chemistry of Earth. So thinking about how the higher energy emissions from stars change over long timescales is pretty important to exoplanet studies.”

“More broadly, we’re taking models that were developed for the sun and seeing how well they adapt to stars,” said Johns-Krull.

The researchers set out to model what far-flung stars are like based on the limited data available. The spin and flux of some stars have been determined, along with their classification — types FGK and M — which gave information about their sizes and temperatures.

They compared the properties of the sun, a G-type star, through its Rossby number, a measure of stellar activity that combines its speed of rotation with its subsurface fluid flows that influence the distribution of magnetic flux on a star’s surface, with what they knew of other cool stars. Their models suggest that each star’s “space weather” works in much the same way, influencing conditions on their respective planets.

“The study suggests that stars — at least cool stars — are not too dissimilar from each other,” Alexander said. “From our perspective, Alison’s model can be applied without fear or favor when we look at exoplanets around M or F or K stars, as well, of course, as other G stars.

“It also suggests something much more interesting for established stellar physics, that the process by which a magnetic field is generated may be quite similar in all cool stars. That’s a bit of a surprise,” he said. This could include stars that, unlike the sun, are convective down to their cores.

Christopher Johns-Krull
Christopher Johns-Krull © Rice University

“All stars like the sun fuse hydrogen and helium in their cores and that energy is first carried in the radiation of photons toward the surface,” Johns-Krull said. “But it hits a zone about 60% to 70% of the way that’s just too opaque, so it starts to undergo convection. Hot matter moves from below, the energy radiates away, and the cooler matter falls back down.

“But stars with less than a third of the mass of the sun don’t have a radiative zone; they’re convective everywhere,” he said. “A lot of ideas about how stars generate a magnetic field rely on there being a boundary between the radiative and the convection zones, so you would expect stars that don’t have that boundary to behave differently. This paper shows that in many ways, they behave just like the sun, once you adjust for their own peculiarities.”

Farrish, who recently earned her doctorate at Rice and begins a postdoctoral research assignment at NASA’s Goddard Space Flight Center soon, noted the model applies only to unsaturated stars.

“Conversely, the sun is in the unsaturated regime, where we do see a correlation between magnetic activity and energetic emission,” she said. “That happens at a more moderate activity level, and those stars are of interest because they might provide more hospitable environments for planets.”

David Alexander
David Alexander © Rice University

“The bottom line is the observations, which span four spectral types including both fully and partially convective stars, can be reasonably well represented by a model generated from the sun,” Alexander said. “It also reinforces the idea that even though a star that is 30 times more active than the sun may not be a G-class star, it’s still captured by the analysis that Alison has done”.

“We do have to be clear that we’re not simulating any specific star or system,” he said. “We are saying that statistically, the magnetic behavior of a typical M star with a typical Rossby number behaves in a similar fashion to that of the sun which allows us to assess its potential impact on its planets.”

A critical wild card is a star’s activity cycle, which can’t be incorporated into the models without years of observation. (The sun’s cycle is 11 years, evidenced by sunspot activity when its magnetic field lines are most distorted.)

Johns-Krull said the model will still be useful in many ways. “One of my areas of interest is studying very young stars, many of which are, like low-mass stars, fully convective,” he said. “Many of these have disc material around them and are still forming planets. How they interact is mediated, we think, by the stellar magnetic field.

“So, Alison’s modeling work can be used to learn about the large-scale structure of very magnetically active stars, and that can then allow us to test some ideas about how these young stars and their disks interact.”

Minjing Li, a visiting undergraduate from the University of Science and Technology of China, is a co-author of the paper. Alexander is a professor of physics and astronomy and director of the Rice Space Institute. Johns-Krull is a professor of physics and astronomy.

A National Science Foundation INSPIRE grant supported the research.

Featured image: Rice University scientists have shown that “cool” stars like the sun share dynamic surface behaviors that influence their energetic and magnetic environments. Stellar magnetic activity is key to whether a given star can host planets that support life. (Credit: NASA)


Reference: Alison O. Farrish et al, Modeling Stellar Activity-rotation Relations in Unsaturated Cool Stars, The Astrophysical Journal (2021). DOI: 10.3847/1538-4357/ac05c7


Provided by Rice University

X-ray Study Reveals How Lead Sulphide Particles Self-organise in Real Time (Material Science)

The structure adopted by lead sulphide nanoparticles changes surprisingly often as they assemble to form ordered superlattices. This is revealed by an experimental study that has been conducted at DESY’s X-ray source PETRA III. A team led by the DESY scientists Irina Lokteva and Felix Lehmkühler, from the Coherent X-ray Scattering group headed by Gerhard Grübel, has observed the self-organisation of these semiconductor nanoparticles in real time. The results have been published in the journal Chemistry of Materials. The study helps to better understand the self-assembly of nanoparticles, which can lead to significantly different structures.

Among other things, lead sulphide nanoparticles are used in photovoltaic cells, light-emitting diodes and other electronic devices. In the study, the team investigated the way in which the particles self-organise to form a highly ordered film. They did so by placing a drop of liquid (25 millionths of a litre) containing the nanoparticles inside a small cell and allowing the solvent to evaporate slowly over the course of two hours. The scientists then used an X-ray beam at the P10 beamline to observe in real time what structure the particles formed during the assembly.

To their surprise, the structure adopted by the particles changed several times during the process. “First we see the nanoparticles forming a hexagonal symmetry, which leads to a nanoparticle solid having a hexagonal lattice structure,” Lokteva reports. “But then the superlattice suddenly changes, and displays a cubic symmetry. As it continues to dry, the structure makes two more transitions, becoming a superlattice with tetragonal symmetry and finally one with a different cubic symmetry.” This sequence has been never revealed before in such detail.

The team suggests that the hexagonal structure (hexagonal close-packed, HCP) persists for as long as the surface of the particles is swollen by the solvent. Once the film dries a little bit, its internal structure changes to a cubic symmetry (body-centred cubic, BCC). However, residues of the solvent still remain between the individual nanoparticles inside the film. As this evaporates, the structure changes two more times (body-centred tetragonal BCT and face-centred cubic FCC).

The superlattice of lead sulphide nanoparticles takes on six different internal structures during the drying process. Illustration: Lokteva et al.; Chemistry of Materials, 2021.

The final structure of the film depends on a number of different factors, as Lokteva explains. They include the type of solvent and how quickly it evaporates, size and concentration of the nanoparticles, but also the nature of the so-called ligands that surround the particles and their density. Scientists use the term ligand to describe certain molecules that bind to the nanoparticle surface and prevent them from agglomeration. In the study, the team used oleic acid for this purpose; its molecules cover the particles, much like the wax that prevents gummy bears from sticking to each other in a bag. This is a well-established process in nanotechnology.

“Our research indicates that the final structure of the superlattice also depends on whether the individual nanoparticles are surrounded by many or few oleic acid molecules,” reports Lokteva. “In an earlier study, we obtained films with a BCC/BCT crystal structure when the ligand density was high. Here, we specifically looked at nanoparticles with a low ligand density, and this led to an FCC structure. So when using nanoparticles, the ligand density ought to be determined, which is not a standard practice at the moment,” explains the DESY scientist.

These observations are also important when it comes to other materials, the team points out. “Lead sulphide is an interesting model system that helps us to better understand the general mechanisms by which nanoparticles self-assemble,” Lokteva explains. “Nature can provide nanostructures with various interesting properties via the phenomenon of self-assembly, and we now have the tools to look over nature’s shoulder as it constructs these structures.”

Featured image:The lead sulphide nanoparticles, which are about eight nanometres (millionths of a millimetre) in size, initially arrange themselves into a layer with hexagonal symmetry. Credit: University of Hamburg, Stefan Werner.


Reference:Real-Time X-ray Scattering Discovers Rich Phase Behavior in PbS Nanocrystal Superlattices during In Situ Assembly; Irina Lokteva, Michael Dartsch, Francesco Dallari, Fabian Westermeier, Michael Walther, Gerhard Grübel, and Felix Lehmkühler; Chemistry of Materials, 2021.


Provided by Deutsches Elektronen-Synchrotron DESY
A Research Centre of the Helmholtz Association

Spotting And Hearing Heart Attacks Before They Strike (Medicine)

If heart attacks blared a warning signal, patients would have a better chance of avoiding them. That’s the idea behind a new imaging technique developed by a Spartan-led team of researchers.

“We shine light into an artery where we’ve delivered certain types of particles that can absorb that light,” said Bryan Smith, an associate professor in Michigan State University’s College of Engineering. “As a product of the release of that energy, they can literally shout back at us in ways that we can detect and use to create 3D images.”

To be clear, the sound signal isn’t audible to human ears, but it’s easily captured by an ultrasound’s transducer. Thanks to Smith and his colleagues, this technique can now be used to directly image atherosclerotic plaques, the medical term for fatty clumps that accumulate in arteries that can lead to strokes and heart attacks.

The researchers showcased the new technique in mice, the first step towards advancing the technology for use in humans. The team published its results in an article that’s now available online in the journal Advanced Functional Materials. The journal will also feature the work as an inside cover story in a September issue.

“The power of our new technique is in its selectivity,” said Smith, who is the director of the Translational NanoImmunoEngineering Lab located at MSU’s Institute for Quantitative Health Science and Engineering, or IQ.

“There are certainly other methods to image plaques, but what distinguishes this strategy is that it’s cellular,” Smith said. “We’re specifically looking at the cells—called macrophages and monocytes—that are most responsible for making a plaque vulnerable in the first place.”

Although it’s difficult to prove whether a particular plaque is responsible for a stroke or heart attack in a patient, the prevailing idea is that vulnerable plaques are the most dangerous, Smith said. These are inflammatory plaques that can rupture and consequently block blood vessels.

In addition to fatty deposits, vulnerable plaques also contain lots of immune cells, including many macrophages and monocytes. Smith and his colleague have developed nanoparticles—tiny tubules made of carbon atoms—that naturally and specifically seek out these cells.null

In injecting the particles into mice, researchers send the tubes searching for specific immune cells that congregate in plaques. The researchers can then shine laser light into the arteries. If there is a plaque present, the particles will absorb the light and emit sound waves. The researchers then use this acoustic signal to locate and visualize the plaque.

“If you look at a normal blood vessel versus one with a plaque, there’re a lot more macrophages and monocytes in the one with the plaque,” Smith said. “And our method is really looking at the monocytes and macrophages. Virtually no other cell type takes up the nanoparticles.”

The idea behind coupling light and sound, known as the photoacoustic effect, dates back to Alexander Graham Bell in the late 1800s, Smith said. Still, to go from that idea to a medical diagnostic, it required the development of crucial technologies such as lasers and ultrasounds. The technique is now coming of age with the Food and Drug Administration approving a photoacoustic imaging machine for detecting breast cancer earlier this year.

In the future, doctors may image arterial plaques in a precise and noninvasive way through Smith and his team’s innovations with nanoparticles. Joining Smith on the project were researchers from Stanford and Emory universities.

“This exciting progress in nanomedicine was only possible because of our multi-disciplinary team of experts,” said Eliver Ghosn, a collaborator on the project and an assistant professor at the Emory University School of Medicine and its Lowance Center for Human Immunology.

“Currently, there is no effective way to accurately locate and treat vulnerable plaques before they lead to a heart attack or stroke,” Ghosn said. “We hope our studies will help change that.”

From a treatment standpoint, Smith’s lab has also already shown that it can pack their nanoparticles with a drug used to fight plaques. Moving forward, the team will explore using these particles to aid with imaging and delivering a therapeutic.

“So you might ask, can you connect those ideas, develop a combination of a therapy and a diagnostic? I think the answer is absolutely yes,” Smith said. “There is a lot of potential in that realm. It’s in the pipeline.”

Featured image: A new imaging technique uses nanoparticles to help reveal vulnerable plaques in arteries that can lead to strokes and heart attacks. Immune cells in the plaque attract the nanoparticles, which can then emit a signal that’s seen in red in the image on the right, taken from a mouse artery. That signal is absent—meaning a plaque goes undetected—in the artery shown on the left, which shows a mouse that did not receive the nanoparticles. Credit: Adv. Funct. Mater.


Reference: Mahsa Gifani et al, Ultraselective Carbon Nanotubes for Photoacoustic Imaging of Inflamed Atherosclerotic Plaques, Advanced Functional Materials (2021). DOI: 10.1002/adfm.202101005


Provided by Michigan State University

Immunotherapy May Be Effective for a Subgroup Metastatic Colorectal Cancer Patients, Study Finds (Medicine)

Researchers at City of Hope, a world-renowned research and treatment center for cancer, diabetes and other life-threatening diseases, looked at the most common type of metastatic colorectal cancer and discovered that these patients are more responsive to checkpoint blockade immunotherapy, an innovative treatment that helps the immune system recognize and attack cancerous cells, if tumors have not spread to the liver.

Colorectal cancer is the third most common cancer and the leading cause of cancer-related deaths in the United States, according to the Centers for Disease Control and Prevention. City of Hope’s findings, published in JAMA Network Open today, are important because immunotherapy traditionally has been seen as ineffective against microsatellite stable (MSS) colorectal cancer, which represents 95% of all metastatic colorectal cancer cases. These patients have few treatment options once they become resistant to chemotherapy.

The retrospective study included 95 City of Hope patients with MSS metastatic colorectal cancer who received immune checkpoint inhibitor PD-1/PD-L1 targeted therapy once their disease became resistant to chemotherapy. The median time of disease progression for patients who did not have liver metastases was four months compared to one and a half months for those whose cancer had spread to the liver.

“When we stratified the patients by the presence or absence of liver metastases, we noted that about 20% of patients without liver metastases had a major response to anti-PD-1 or anti-PD-L1 therapy, while none of the patients with liver metastases experienced a positive response,” said Marwan Fakih, M.D., co-director of the Gastrointestinal Cancer Program and the Judy & Bernard Briskin Distinguished Director of Clinical Research at City of Hope. “Colorectal cancer patients without liver metastases could benefit from immunotherapy considerably more than patients with liver metastases.”

When colorectal cancer spreads to the liver, some patients can undergo surgery to remove all tumors; however, sometimes these tumors cannot be removed surgically. That’s when chemotherapy is used, but “chemotherapy is destined to stop working, and we have to look into additional treatment options,” Fakih said, adding, “To our knowledge, this is the largest study to evaluate the impact of PD-1/PD-L1 targeting on patient response as stratified by site of metastatic disease.”

The clinical significance, Fakih said, is that advanced colorectal cancer patients with liver metastases should not be considered for PD-1/PD-L1-based therapy. Instead, other novel investigational strategies are recommended.

“For patients without liver metastatic disease, PD-1/PD-L1-based therapies, particularly those combining these agents with tyrosine kinase inhibitors (TKI), hold significant promise,” he said, noting that TKIs that target the tumor vasculature modify the tumor environment and make it more responsive to PD-1/PD-L1 therapy.

Featured image: Cancer — Histopathologic image of colonic carcinoid. Credit: Wikipedia/CC BY-SA 3.0


Reference: Clinical Response to Immunotherapy Targeting PD-1/PD-L1 in Patients with Treatment Resistant Microsatellite Stable Colorectal Cancer with and without Liver Metastases, JAMA Network Open (2021).


Provided by City of Hope National Medical Center