How A Simple Blood Test can Identify Women At Risk For Preterm Birth (Medicine)

One in ten babies is born prematurely in the United States, but a blood test during a routine prenatal visit could reveal if a woman is at risk of a preterm delivery, according to a Michigan State University researcher.

“Preterm births are common,” said Hanne Hoffmann, an assistant professor in the Department of Animal Science in the College of Agriculture and Natural Resources. “If we know the mother is at risk for a preterm birth, her doctor can monitor her more closely.”

Hoffmann’s research was published online June 18 in the Journal Biology of Reproduction.  Hoffmann and her colleagues studied 157 healthy mothers with no history of preterm births, among them 51 who subsequently gave birth preterm. Researchers looked at second trimester data for evidence of biomarkers that could signal preterm delivery.

“How often do you find the needle in the haystack?” Hoffmann said. “We were excited to discover lower mRNA levels in the CRY2 and CLOCK genes.”

The CRY2 and CLOCK genes belong to a family of genes responsible for cell circadian rhythms. Hoffmann said that each human cell has its own 24-hour clock that keeps track of time inside the cell. Low levels of mRNA, or messenger DNA, in those two genes is associated with a higher risk of preterm birth, suggesting these genes provide information as to when labor should start.

Decreased levels of mRNA in the mother’s blood become present during the second trimester of pregnancy when most women have an important 20-week prenatal appointment to screen for Down syndrome. This presents the ideal time to also test for the risk of preterm delivery.

The next step is to determine if the CRY2 and CLOCK genes are coming from the mother, placenta or fetus. The researchers also want to see how the mRNA levels in healthy women compare with levels in women with underlying conditions or a history of preterm births to determine if this blood test could be helpful for these at-risk mothers, too.

“If we could measure women’s mRNA levels and tell them for their second or third pregnancies, that they aren’t at risk for a preterm birth because their levels are higher (in a normal/healthy range), that would be such a comfort to the mothers who previously had a preterm birth,” Hoffmann said.The researchers are also interested in looking at other genes such as another circadian clock gene, called PER3, that in combination with CRY2 and CLOCK levels could indicate other pregnancy complications such a preeclampsia and gestational diabetes. 

“If I can help one baby make it to full term who wasn’t supposed to, that would make my day,” said Hoffmann.

Preterm birth graphic
© Emilie Lorditch

Reference: Guoli Zhou et al, Low CLOCK and CRY2 in 2nd trimester human maternal blood and risk of preterm birth: a nested case-control study†, Biology of Reproduction (2021). DOI: 10.1093/biolre/ioab119


Provided by MSU

Scientists Explore The Latent Regenerative Potential Of The Inner Ear (Medicine)

Scientists from the USC Stem Cell laboratory of Neil Segil have identified a natural barrier to the regeneration of the inner ear’s sensory cells, which are lost in hearing and balance disorders. Overcoming this barrier may be a first step in returning inner ear cells to a newborn-like state that’s primed for regeneration, as described in a new study published in Developmental Cell.

“Permanent hearing loss affects more than 60 percent of the population that reaches retirement age,” said Segil, who is a Professor in the Department of Stem Cell Biology and Regenerative Medicine, and the USC Tina and Rick Caruso Department of Otolaryngology – Head and Neck Surgery. “Our study suggests new gene engineering approaches that could be used to channel some of the same regenerative capability present in embryonic inner ear cells.”

In the inner ear, the hearing organ, which is the cochlea, contains two major types of sensory cells: “hair cells” that have hair-like cellular projections that receive sound vibrations; and so-called “supporting cells” that play important structural and functional roles.

When the delicate hair cells incur damage from loud noises, certain prescription drugs, or other harmful agents, the resulting hearing loss is permanent in older mammals. However, for the first few days of life, lab mice retain an ability for supporting cells to transform into hair cells through a process known as “transdifferentiation”, allowing recovery from hearing loss. By one week of age, mice lose this regenerative capacity—also lost in humans, probably before birth.

Based on these observations, postdoctoral scholar Litao Tao, PhD, graduate student Haoze (Vincent) Yu, and their colleagues took a closer look at neonatal changes that cause supporting cells to lose their potential for transdifferentiation.

In supporting cells, the hundreds of genes that instruct transdifferentiation into hair cells are normally turned off. To turn genes on and off, the body relies on activating and repressive molecules that decorate the proteins known as histones.  In response to these decorations known as “epigenetic modifications,” the histone proteins wrap the DNA into each cell nucleus, controlling which genes are turned “on” by being loosely wrapped and accessible, and which are turned “off” by being tightly wrapped and inaccessible. In this way, epigenetic modifications regulate gene activity and control the emergent properties of the genome.

In the supporting cells of the newborn mouse cochlea, the scientists found that hair cell genes were suppressed by both the lack of an activating molecule, H3K27ac, and the presence of the repressive molecule, H3K27me3.  However, at the same time, in the newborn mouse supporting cells, the hair cell genes were kept “primed” to activate by the presence of yet a different histone decoration, H3K4me1.  During transdifferentiation of a supporting cell to a hair cell, the presence of H3K4me1 is crucial to activate the correct genes for hair cell development.

Unfortunately with age, the supporting cells of the cochlea gradually lost H3K4me1, causing them to exit the primed state. However, if the scientists added a drug to prevent the loss of H3K4me1, the supporting cells remained temporarily primed for transdifferentiation. Likewise, supporting cells from the vestibular system, which naturally maintained H3K4me1, were still primed for transdifferentiation into adulthood.

“Our study raises the possibility of using therapeutic drugs, gene editing, or other strategies to make epigenetic modifications that tap into the latent regenerative capacity of inner ear cells as a way to restore hearing,” said Segil. “Similar epigenetic modifications may also prove useful in other non-regenerating tissues, such as the retina, kidney, lung, and heart.”

Additional co-authors of the study include Juan Llamas, Talon Trecek, Xizi Wang, and Zlatka Stojanova in the Segil Lab at USC, and Andrew K. Groves at Baylor College of Medicine.

Sixty percent of this project was supported by federal funding from the National Institute on Deafness and Other Communication Disorders (R01DC015829, R01DC014832, T32DC009975, F31DC017376). Additional funding came from the Hearing Restoration Project at Hearing Health Foundation.

Featured image: The organ of Corti, the hearing organ of the inner ear, contains rows of sensory hearing cells (green) surrounded by supporting cells (blue). (Image by Yassan Abdolazimi/Segil Lab/USC Stem Cell)


Reference: Enhancer decommissioning imposes an epigenetic barrier to sensory hair cell regeneration, Developmental Cell (2021). DOI: 10.1016/j.devcel.2021.07.003


Provided by Keck School of Medicine of USC

Dual-Drug Therapy Shows Promise for Treating Alcohol Use Disorder (Medicine)

UC San Francisco researchers have leveraged two new molecules, one of which is currently in clinical oncology trials, to devise a dual-drug therapy for alcohol use disorder (AUD), without the side effects or complications associated with current treatment regimens. The approach had highly successful results in mice and may be applicable to other drugs that are often abused.

At the root of the team’s thinking is the idea that AUD and other substance abuse disorders are the result of reinforced pathways in the brain, and that those pathways can be blocked or redirected, ending cravings and habitual behavior.

“Alcohol use disorder is really a process of maladapted learning and memory,” said Dorit Ron, PhD, a professor of neurology and senior author on the study, published July 17 in Nature Communications. “Alcohol is rewarding, and we learn to associate alcohol, and even the environment in which we drink the alcohol, with that reward.”

Current pharmaceutical options for AUD attempt to change behavior by making alcohol consumption an unpleasant experience and some require patients to abstain for several days before beginning treatment.

Since 2010, Ron, who is also faculty in the Weill Institute for Neurosciences, has taken a different approach, studying the role of the enzyme mTORC1 in the creation of those memories and associations, with the goal of creating an effective drug that can treat the neurological causes of AUD.

Ordinarily, mTORC1 is involved in brain plasticity, helping to create connections between neurons that reinforce memory. In previous work, Ron showed that consuming alcohol activates the enzyme in the brain.

Ron has also shown that blocking the activity of mTORC1 with the FDA-approved compound rapamycin, used to treat some types of cancer and suppress immune response in transplant patients, can halt cravings in mice engineered for alcohol use disorder. But mTORC1 contributes to a bevy of other bodily tasks related to metabolism and liver function, and people taking it for an extended period often develop liver toxicity, glucose intolerance, and other side effects.

For some of her previous work, Ron had teamed up with Kevan Shokat, PhD, a professor of cellular molecular pharmacology, who had created RapaLink-1, a molecule similar to rapamycin, which he designed specifically to keep a tight grip on mTORC1 and completely subdue it. A version of the drug is now being tested in oncology clinical trials.

Shokat’s thought was that, since Ron is concerned only with the activity of mTORC1 in the brain, that’s the only place where RapaLink-1 or rapamycin needs to be effective. So Ziyang Zhang, PhD, a postdoctoral researcher in Shokat’s lab, designed a second molecule that would latch onto RapaLink-1 or rapamycin—essentially negating its effect—while at the same time being too big to cross the blood-brain barrier.

In other words, Shokat reasoned that RapaLink-1 or rapamycin could administered and allowed to circulate throughout the body. Once it had a chance to reach the brain, Rapablock could be given, halting the activity of Rapalink-1 everywhere except in that targeted area.

The tactic worked like a charm when it was tested on the mice by Yann Ehinger, PhD, a postdoctoral researcher in Ron’s lab. “We could see these side effects in mice who are taking rapamycin or RapaLink-1, and then when you give Rapablock, it’s like magic, the side effects are gone,” said Ron.

Shokat said a similar strategy is being explored in treating other conditions, such as Parkinson’s disease. Those trials involve different drugs, but the underlying principle is the same: one drug results in the desired effect in the brain, while its activity is blocked by a molecule that isn’t able to cross the blood-brain barrier.

Ron believes that tackling addiction from this neurological perspective has potential for broad applications. She notes that while we see addiction with a wide chemical array of molecules—alcohol, nicotine, cocaine, opiates, and the like—the addictive behavior that results from each is the same.

“It’s really quite striking,” she said, adding that a whole body of study points to the possibility of mTORC1 being a kind of supermolecule that is activated by all misused drugs. “If that’s true,” Ron said, “It suggests that this approach can be applied to other drugs of abuse as well, essentially solving the problem of addiction.”

Funding: This research was supported by the National Institute of Alcohol Abuse and Alcoholism, R01 AA027474, and the National Cancer Institute, R01CA221969. For additional funding information, please see the paper.


Reference: Yann Ehinger et al, Brain-specific inhibition of mTORC1 eliminates side effects resulting from mTORC1 blockade in the periphery and reduces alcohol intake in mice, Nature Communications (2021). DOI: 10.1038/s41467-021-24567-x


Provided by UCSF

UT Southwestern Finds Crucial New Molecular Mechanisms and Biomarkers in Ovarian Cancer (Medicine)

UT Southwestern faculty have discovered what appears to be an Achilles’ heel in ovarian cancers, as well as new biomarkers that could point to which patients are the best candidates for possible new treatments.

The finding, published in the journal Cell, was made in part using a research tool invented in a UT Southwestern lab in the Cecil H. and Ida Green Center for Reproductive Biology Sciences.

W. Lee Kraus, Ph.D. © UT Southwestern Medical Center

The research was led by W. Lee Kraus, Ph.D., Professor of Obstetrics and Gynecology and Pharmacology and a member of the Harold C. Simmons Comprehensive Cancer Center.

“Many researchers are trying to find dependencies in cancers by asking why a cancer cell amplifies a gene, increases the levels of a protein, or upregulates a critical cellular pathway. These changes give that cancer a selective advantage, but at the same time they can become an Achilles’ heel – something that, if the alteration was blocked, would kill the cancer or stop its growth,” he said.

Dr. Kraus and his team, including lead author Sridevi Challa, Ph.D., a postdoctoral researcher in the lab, found that ovarian cancers massively amplify an enzyme, NMNAT-2, that makes NAD+. NAD+ is the substrate for a family of enzymes called PARPs, which chemically modify proteins with ADP-ribose from NAD+. In this study, the team found that one PARP family member, PARP-16, uses NAD+ to modify ribosomes, the protein synthesizing machines of the cell.

A challenge for this work was that a single ADP-ribose group attached to a protein is difficult to detect. Dr. Kraus and his team overcame this problem by developing a synthetic mono(ADP-ribose) detection reagent made up of natural protein domains fused together, which can be used to detect ADP-ribosylated proteins in cells and patient samples.

In collaboration with UT Southwestern clinicians, led by Jayanthi Lea, M.D., Professor of Obstetrics and Gynecology and member of the Simmons Cancer Center, Dr. Kraus and his team screened human ovarian cancer patient samples using the mono(ADP-ribose) detection reagent to identify those with low or high levels of mono(ADP-ribose).

“We were able to show that when ribosomes are mono(ADP-ribosyl)ated in ovarian cancer cells, the modification changes the way they translate mRNAs into proteins,” Dr. Kraus said. “The ovarian cancers amplify NMNAT-2 to increase the levels of NAD+ available for PARP-16 to mono(ADP-ribosyl)ate ribosomes, giving them a selective advantage by allowing them to fine-tune the levels of translation and prevent toxic protein aggregation. But that selective advantage also becomes their Achilles’ heel. They’re addicted to NMNAT-2, so inhibition or reduction of NMNAT-2 inhibits the growth of the cancer cells.”

This study identified mono(ADP-ribose) and NMNAT-2 as potential biomarkers for ovarian cancers, which may allow clinicians to determine which ovarian cancer patients may respond well and which will not. Even more ovarian cancer patients might do well if an inhibitor is developed for PARP-16, which blocks ribosome mono(ADP-ribosyl)ation.

Dr. Kraus, an expert in PARPs, said medical science has had great success in developing FDA-approved PARP-1 inhibitors, and an inhibitor for PARP-16 is likely.

“No PARP-16 inhibitors are currently in clinical trials, but labs in academia and the pharmaceutical industry are developing specific and potent inhibitors of PARP-16. Such a drug could be an effective therapeutic for treating ovarian cancers,” he said.

Dr. Kraus is a founder and consultant for Ribon Therapeutics Inc., and ARase Therapeutics Inc. He is also co-holder of U.S. patent 9,599,606 covering the mono(ADP-ribose) detection reagent, which has been licensed to and is sold by EMD Millipore.

“Dr. Kraus’ research is not just a great advance in basic science. It has real promise for clinician investigators and cancer care practitioners because it shows a biomarker and a pathway a future drug could target. The fact that technology developed in his laboratory helped make these findings shows how our faculty builds on their findings to break new ground,” said Carlos L. Arteaga, M.D., Director of the Simmons Cancer Center.

Other researchers who contributed to this study include Beman R. Khulpateea, Tulip Nandu, Cristel V. Camacho, Keun W. Ryu, Hao Chen, and Yan Peng. 

The research work was supported by a grant from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK069710) as well as funds from the Cecil H. and Ida Green Center for Reproductive Biology Sciences Endowment to Kraus, and a postdoctoral fellowship from the Ovarian Cancer Research Alliance (GAA202103-0003) to Challa.

Dr. Arteaga holds the The Lisa K. Simmons Distinguished Chair in Comprehensive Oncology. Kraus holds the Cecil H. and Ida Green Distinguished Chair in Reproductive Biology Sciences. Dr. Lea holds the Patricia Duniven Fletcher Distinguished Professorship in Gynecological Oncology.


Reference: Sridevi Challa et al, Ribosome ADP-ribosylation inhibits translation and maintains proteostasis in cancers, Cell (2021). DOI: 10.1016/j.cell.2021.07.005


Provided by UT Southwestern Medical Center

Gene Mutation Weakens Virus-Fighting Protein in the Gut Causing Rare Inflammatory Bowel Disease (Biology)

International research collaboration finds that a genetic mutation causes rare disease, very early onset inflammatory bowel disease.

Johns Hopkins Medicine researchers, in collaboration with national and international researchers, have identified a genetic mutation in a small number of children with a rare type of inflammatory bowel disease. The discovery of the mutation, which weakens the activity of a protein linked to how the immune system fights viruses in the gut, may help researchers pinpoint the cause of more common bowel diseases, investigators say.

The study, published June 29, 2021 in Human Genetics, may also suggest new ways to target the immune system’s role in gut diseases. 

“We aimed to see if children have a greater genetic susceptibility for this type of inflammatory bowel disease because they develop it so young,” says Anthony Guerreiro Jr., M.D, Ph.D., M.S., director of the Very Early Onset Inflammatory Bowel Disease Clinic and assistant professor of pediatrics at the Johns Hopkins University School of Medicine.

Unlike other inflammatory bowel diseases, very early onset inflammatory bowel disease is diagnosed in patients before the age of 6, occurring in four out of every 100,000 births worldwide. In such young patients, the disease does not often respond to anti-inflammatory medications, and sometimes requires surgery to remove all or parts of the colon.

Inflammatory bowel diseases are chronic, inflammatory conditions — including Crohn’s disease and ulcerative colitis — that occur when immune cells in the intestines are over-activated and cause sustained inflammation in the gut. These diseases are thought to be caused by multiple genetic mutations and environmental factors, such as diet and pollution as well as disruptions to the makeup of gut bacteria. Treatments usually include prescription drugs that curb inflammation.

Since the most common characteristic of bowel diseases is inflammation, scientists have long suspected genetic ties between the immune system and bowel disease. Inflammation is the immune system’s response to damaged tissue. 

For the current study, the scientists collected tissue samples from 24 patients with very early onset inflammatory bowel disease seen at The Johns Hopkins Hospital and Johns Hopkins Children’s Center and performed whole exome sequencing, a method that looks at the protein-producing areas of a gene to identify mutations.

Among the 24 patients, the scientists found mutations in four patients in parts of a gene called IFIH1, which produces a protein involved in the virus-fighting branch of the immune system. Other genetic sequencing studies have also linked the IFIH1 gene to inflammatory bowel diseases, and the current research provides new evidence for its involvement in very early onset inflammatory bowel disease.

Because of the small number of patients in the first round of sequencing, the researchers turned to a Johns Hopkins-developed online database called GeneMatcher, which contains genetic variations from people worldwide. Guerrerio and GeneMatcher co-founder Nara Sobreira, M.D, Ph.D, assistant professor of genetics and pediatrics at the Johns Hopkins University of Medicine, found an additional 18 patients with very early onset inflammatory bowel disease being studied at both the NIH and in Padova, Italy.

The combined research teams found IFIH1 mutations in four of the 18 new patients, bringing the total of IFIH1 mutations found to 8 out of the 42 patients. Among the IFIH1 mutations, the researchers discovered nine mutations which resulted in abnormal production of a protein called MDA5. In the eight patients with the mutations, MDA5 function was much lower than normal.

When functioning properly, MDA5 is a part of the inborn immune system that helps fight off viruses in the gut. Using protein assays that mimicked the activity of normal and abnormal MDA5, the researchers found that in each patient with the IFIH1 mutation, the MDA5 proteins only partially worked, but not enough to do their job of battling viruses. The researchers suspect this loss of function in the protein causes the improper activation of the immune system, triggering the inflammation that leads to very early onset inflammatory bowel disease.

The researchers also believe that the partially functioning MDA5 proteins protect patients from more severe and rare immune diseases, such as Singleton-Merton syndrome and Aicardi-Goutières syndrome, that are associated with no MDA5 production.

“When you look at the physical changes associated with IFIH1 mutations, there are a wide range and they are really very different,” says Sobreira. “It’s crucial to know that these different variations in the same gene can cause these different characteristics.”

Guerrerio and Sobreira hope their findings will help other clinicians and patients pinpoint the genetic cause of their disease and inform treatment options. They also believe the research provides additional evidence of the link between inflammatory bowel diseases and the virus-fighting part of the body’s immune response.

The work was supported by grant HG006542 from the National Human Genome Research Institute and funding from the Intramural Research Program of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.

Other scientists who conducted the research include Elizabeth Wohler, Jing You, Renan Martin, Maria Oliva-Hemker and David Valle from Johns Hopkins; Mara Cananzi, Antonio Marzollo, Paola Gaio, Claudia Mescoli, Luca Bosa, Maria Gabelli, Giorgio Perilongo and Alessandra Biffi from the University Hospital of Padova, Italy; Silvia Bresolin, Maurizio Dalle Carbonare and Alberta Leon from Istituto di Ricerca Pediatrica in Padova, Italy; Huie Jing, Sangeeta Bade, Wesley Tung and Helen C. Su from the National Institute of Allergy and Infectious Diseases, National Institutes of Health; Jennifer E. Posey, Shalini N. Jhangiani, Richard Kellermayer and James R. Lupski from the Baylor College of Medicine; Joselito Sobreira Filho from Universidade Federal de Sao Paulo in Sao Paulo, Brazil; and Howard A. Kader from University of Maryland School of Medicine.

This news story was researched and written by Johns Hopkins Medicine science writing intern Haley Wasserman.

Featured image credit: Getty Images


Reference: Mara Cananzi et al, IFIH1 loss-of-function variants contribute to very early-onset inflammatory bowel disease, Human Genetics (2021). DOI: 10.1007/s00439-021-02300-4


Provided by Johns Hopkins University School of Medicine

UVA Scientists Upturn Understanding of How Key Hormones Act in Cells (Biology)

Researchers at the University of Virginia School of Medicine have overturned conventional wisdom on the workings of vital hormone receptors within cells, a finding that could boost drug development for diabetes and related metabolic disorders, cancer and other diseases.

The scientists in UVA’s Department of Pharmacology outline an entirely new paradigm to explain the activation of a type of hormone receptor, known as Type II receptors, found inside our cells’ nuclei. These receptors play important roles in our body’s use of cholesterol and glucose, among other critical processes.

“Nuclear receptors are the only class of DNA-binding proteins that are druggable. Drug development has been focused exclusively on designing artificial hormones that would replace the natural ones and activate the receptor because everyone believed that binding of the receptor to DNA was constant,” senior researcher Irina M. Bochkis said. “To everyone’s surprise, we find that DNA needs to be opened for the receptor to bind. For different artificial hormones, distinct parts of DNA become accessible, some leading to beneficial and others to detrimental effects.

“If we can target the places in DNA that lead to favorable effects and avoid accessing sites that would lead to adverse ones, the efficacy of the drugs would be greatly improved.”

Understanding Hormone Action

Scientists have thought that two important hormone receptors, known as FXR & LXRα, were permanently bound to DNA inside the nuclei of our cells. But Bochkis and her team found that this wasn’t the case. Instead, a complex cascade of events is required to activate the hormone receptors, they determined.

A key player in these proceedings is a protein called Foxa2. Our DNA is locked up inside our chromosomes in a form known as chromatin; Foxa2 turns the key in that lock. This causes the chromatin to open temporarily. Once this occurs, hormone binding can occur, the UVA scientists determined.

Senior researcher Irina M. Bochkis is an assistant professor of pharmacology in the UVA School of Medicine. (Photo by Dan Addison, University of Virginia)

Foxa2 plays other important roles as well, they found. After it opens the chromatin, it ensures the activation of the proper receptor and suppresses a competing receptor. Computational analysis by researcher Nihal Reddy, an undergraduate student, was crucial to prove this point. 

Based on their findings, the researchers have dubbed Foxa2 a “gatekeeper” in the hormone-binding process. And it may act as the gatekeeper for other Type II receptors in the nucleus as well, the researchers conclude. 

“People did not believe us because they had a different model they relied on for so long. Our initial findings described only LXRα. We decided to include FXR to show Foxa2 opens DNA for multiple receptors in a common mechanism,” said researcher Xiaolong Wei, the co-first author of a new scientific paper outlining the findings. “That involved doubling the amount of numerous genomic experiments we performed, which took me a while to complete. But it is worth it.” 

Researcher Xiaolong Wei served as the co-first author of a new scientific paper outlining the findings. (Contributed photo)

Another surprising finding: Previously, scientists had thought that ligand (or artificial hormone) binding leads only to activation of genes by the receptor. But the new work from Bochkis and her collaborators turns that belief on its ear. Ligand binding forces Foxa2 and the nuclear receptor to interact; this leads to opening of DNA by Foxa2 and subsequent receptor binding and gene activation. Foxa2 and the nuclear receptor do not interact without the ligand, they found.

“Now when I teach endocrinology, I can finally show the correct model of receptor activation instead of saying that the textbook has not kept up with research,” Bochkis said. “Our findings will change the way people approach drug design and hopefully lead to formulations that lack harmful side effects.”

Findings Published

The researchers have published their findings in the scientific journal Molecular Metabolism. The research team consisted of Jessica Kain, Xiaolong Wei, Nihal A. Reddy, Andrew J. Price, Claire Woods and Irina Bochkis. 

The research was supported by the National Institutes of Health’s National Diabetes and Digestive and Kidney Diseases Institute, R01 award DK121059.


Provided by University of Virginia

Oxygen-vacancy-mediated Catalysis Boosts Direct Methanation of Biomass (Chemistry)

Biomethane (CH4) can be used as feedstock for modern chemical industry or burned directly as a fuel.

Currently, CH4 is mainly produced via a multi-step process in which biomass is first gasified into biogas, followed by the methanation of the latter. This method requires high temperature and pressure and shows low selectivity for chemical or biological processes.

Recently, a research group led by Prof. WANG Feng from the Dalian Institute of Chemical Physics of the Chinese Academy of Sciences, in collaboration with Prof. WANG Min’s group from Dalian University of Technology, proposed interfacial oxygen-vacancy (Vo)-mediated catalysis over Ru/TiO2 for the direct methanation of lignocellulosic biomass at temperatures below 200°C and with a selectivity above 95%.

The results were published in Joule on July 27.

“We proposed the Vo-mediated catalysis process to couple the oxidation of biomass into CO2 with the hydrogenation of CO2 into CH4, leading to the direct methanation of biomass under mild conditions,” said Prof. WANG Min.

The researchers found that the biomass substrate molecule was oxidized by the lattice oxygen of Ru/P25 into CO2, and Vo formed on Ru/P25. Subsequently, the dissociated oxygen atoms derived from CO2 could restore the Vo during the CO2 hydrogenation process.

Moreover, they found that the Vo-mediated catalysis process could stably catalyze the production of CH4 from aqueous glycerol at temperatures as low as 120 °C and with a selectivity above 99%.

“This direct methanation process is simpler and more efficient than the traditional two-step process of biogas production and methanation,” said Prof. WANG Feng. “It opens up a new route for the utilization of biomass resources.”

This work was supported by the National Natural Science Foundation of China, the Ministry of Science and Technology of the People’s Republic of China, and the Strategic Priority Research Program of the Chinese Academy of Sciences.

Featured image: Graphical abstract © Zhou et al.


Reference: Hongru Zhou, “Oxygen-vacancy-mediated catalytic methanation of lignocellulose at temperatures below 200°C”, Joule, 2021. DOI: https://doi.org/10.1016/j.joule.2021.07.001


Provided by Chinese Academy of Sciences

Researchers Construct Lab-made ‘Cells’ with Organelles to Mimic Cellular Signaling (Chemistry)

Cells are compartmentalized microreactors that integrate spatially organized organelles in a confined space to afford biochemical reaction networks.

Hierarchical lab-made ‘cells’ with compartmentalized organelles can serve as a model of cellular organization for the study of metabolic reaction network and the design of biological computation.

In a study published in Science Advances, the research group led by Prof. QIAO Yan at the Institute of Chemistry of the Chinese Academy of Sciences, and Prof. LIN Yiyang at Beijing University of Chemical Technology, developed a complex protocell model made of proteins and stuffed with tiny liquid coacervate droplets resembling cellular substructures can respond to changes in their environment, similar to living cells.

This light and pH-sensitive microdroplets are prototype of membraneless organelles formed by short, light-sensitive molecules and long, pH-sensitive polymers via liquid-liquid phase separation. The tiered protocells are capable of harvesting biomacromolecules (e.g., DNA and proteins) by condensing them into liquid droplets, and recruiting small molecules from surroundings, which allows for active control of enzyme-catalyzed reactions.

These subcompartments of protocells can sense a variety of extracellular signals (e.g., light, pH and chemical species), take actions and adapt their physicochemical behaviours, which can be utilized to design Boolean logic gates (NOR and NAND) using biochemical signals as inputs.

The information-processing ability could allow researchers to program the protocells as if they were computer chips, to control chemical reactions.

This study was highlighted in Nature.

Featured image: AzoGlu2/DEAE-dextran coacervate microdroplets. (A) Schematic of active AzoGlu2/DEAE-dextran complexation to produce microdroplet condensation via LLPS. The process is responsive to wavelength-dependent light irradiation, or subtle pH changes triggered disassembly-assembly of coacervates. (B) Phase diagram showing the presence of microdroplets (orange region) at different trans-AzoGlu2/DEAE-dextran molar ratio and trans-AzoGlu2 concentrations. (C) Optical microscopy image and (D) 3D confocal fluorescence microscopy image (loaded with HPTS) showing the formation of coacervate microdroplets in a mixture of trans-AzoGlu2 (10 mM) and DEAE-dextran (10 mM monomer). (E) Optical microscopy image showing disassembly of microdroplets after UV light irradiation for 7 min. (F) Count number of coacervates in the mixture of trans-AzoGlu2 (10 mM) and DEAE-dextran (10 mM monomer) as detected by flow cytometry with different durations of UV light irradiation. Error bars represent the SDs of three independent measurements. (G) Reversible diameter changes of trans-AzoGlu2/DEAE-dextran microdroplets with UV/blue light irradiation for 10 cycles. (H) Transmittance of trans-AzoGlu2/DEAE-dextran mixtures and (I) their coacervate counts suggesting the existence of coacervate microdroplets at a narrow pH window. Scale bars, 10 μm. Credit: DOI: 10.1126/sciadv.abf9000


Reference: Wenjing Mu et al, Membrane-confined liquid-liquid phase separation toward artificial organelles, Science Advances (2021). DOI: 10.1126/sciadv.abf9000


Provided by Chinese Academy of Sciences

New Solid-state Thermal Diode Developed with Better Rectification Performance (Physics)

The effective control of heat transfer is of great significance to improve energy efficiency. Thermal diode is one of the key elements for heat flow controlling. Similar to the current rectification effect of electronic diodes, heat flow is easily directed through one direction in a thermal diode, while obstructed in the opposite direction. Sizable heat rectification can be obtained using a junction of two solid materials with opposite trends in thermal conductivity as a function of temperature. This type of thermal diodes is attractive due to their scalability and analogy to electrical diode design.

A team led by Prof. TONG Peng from the Hefei Institutes of Physical Science (HFIPS) of the Chinese Academy of Sciences (CAS) had reported that they’ve found sulfides Ni1-xFexS, a series of materials that may unlock new ways to better thermal rectification.

Recently, the same team announced that they constructed a novel thermal diode with a combined material of Ni0.85Fe0.15S and alumina, which displayed excellent performance over solid-state thermal diodes ever reported. Their up-to-date result was published on Journal Physical Review Applied.

In their previous study, they discovered the abrupt jump of thermal conductivity in the vicinity of the first-order phase transition (FOPT) in Ni1-xFexS. The change of thermal conductivity reaches as large as 200%, which suggests the sulfides are promising materials for designing solid-state thermal diodes.

On this base, they constructed a thermal diode with Ni0.85Fe0.15S (bonded by 10wt.%Ag) and Al2O3 as two segments. The thermal diode exhibits excellent thermal rectification performance. When the cold end of the thermal diode is set at 250 K, at a temperature bias of 97 K, the maximum thermal rectification coefficient γmax reaches 1.51.

The Ni0.85Fe0.15S/Al2O3 thermal diode shows advantages over other solid-state thermal diodes ever reported. Namely, its γmax is the largest among the reported values, meanwhile the requested temperature bias for driving γmax is at least 100 K less than that of reported thermal diodes having comparable γmax values. 

The outstanding thermal rectification effect of the current thermal diode may have potential applications in thermal management systems, for example, caloric refrigeration and energy conversion.

Moreover, on the base of systematical experimental and theoretical analysis, the team clarified how the thermal rectification factor is affected by the cold terminal temperature, the length ratio of Ni0.85Fe0.15S and Al2O3 segments, and the sharpness of the FOPT of Ni0.85Fe0.15S.

These new results provide guides for designing new solid-state thermal diodes in the future.

This work was supported by the National Natural Science Foundation of China, the Key Research Program of Frontier Sciences and the Users with Excellence Program of Hefei Science Center of CAS.

Featured image: (a) and (b) represent for the schematic geometry of the thermal diode consisting of Ni0.85Fe0.15S and Al2O3 for forward and reverse direction. (c) Thermal rectification factor (γ) as a function of temperature bias (ΔT) along with those reported. (Image by ZHANG Xuekai)  


Reference: Xuekai Zhang, Peng Tong, Jianchao Lin, Kun Tao, Xuelian Wang, Lulu Xie, Wenhai Song, and Yuping Sun, “Large Thermal Rectification in a Solid-State Thermal Diode Constructed of Iron-Doped Nickel Sulfide and Alumina”, Phys. Rev. Applied 16, 014031 – Published 13 July 2021. DOI: https://doi.org/10.1103/PhysRevApplied.16.014031


Provided by Chinese Academy of Sciences