The current method for assessing medication-related liver injury is not providing an accurate picture of some medications’toxicity—or lack thereof—to the liver,according to anew study led by researchers from the Perelman School of Medicine.Classification of amedication’s potential to damage the liver,termed“hepatotoxicity,”has been historically determined by counting individual reported cases of acute liver injury(ALI).Instead,the researchers used real-world health care data to measure rates of ALI within apopulation and uncovered that some medications’levels of danger to the liver are being misclassified,in apaper published in JAMA Internal Medicine.“Incidence rates of severe ALI can be avaluable tool for determining amedication’s toxicity to the liver and when patients should be monitored,since incidence rates provide atruer,real-world look at this toxicity.Case reports did not accurately reflect observed rates of ALI because they do not consider the number of persons exposed to amedication,and cases of drug-induced liver injury are often underreported,”says senior author Vincent Lo Re.Within the study,17 different medications had rates that exceeded five severe ALI events per 10,000“person-years,”a measure that reflects both the amount of people in agroup and how long the study observes them.The team determined that 11 of these medications were in lower categories of hepatoxicity by case counts that were likely not reflective of their true risk,since their incidence rates revealed higher levels of toxicity.To determine incidence rates,Lo Re and his team,including lead author Jessie Torgersen,an assistant professor of medicine,examined electronic medical record data on almost 8million people.Each person did not have pre-existing liver or biliary disease when they began taking any of the 194 medications that were studied.Each of those medications were analyzed due to suspicion that they could cause harm to the liver,since each had more than four published reports of liver toxicity associated with their use.On the other side of the hepatotoxicity coin,the researchers found eight medications that were classified as the most hepatotoxic based on the number of published case reports,but should actually be in the least liver-toxic group,with incidence rates of less than one severe ALI event per 10,000 person-years.With these findings,the researchers hope that there might soon be mechanisms established within electronic medical records to alert clinicians to closely monitor the liver-related laboratory tests of patients who start amedication with ahigh observed rate of severe ALI. 查看详细>>

Artificial intelligence models often play arole in medical diagnoses,especially when it comes to analyzing images such as X-rays.However,studies have found that these models don’t always perform well across all demographic groups,usually faring worse on women and people of color.These models have also been shown to develop some surprising abilities.In 2022,MIT researchers reported that AI models can make accurate predictions about apatient’s race from their chest X-rays—something that the most skilled radiologists can’t do.That research team has now found that the models that are most accurate at making demographic predictions also show the biggest“fairness gaps”—that is,discrepancies in their ability to accurately diagnose images of people of different races or genders.The findings suggest that these models may be using“demographic shortcuts”when making their diagnostic evaluations,which lead to incorrect results for women,Black people,and other groups,the researchers say.“It’s well-established that high-capacity machine-learning models are good predictors of human demographics such as self-reported race or sex or age.This paper re-demonstrates that capacity,and then links that capacity to the lack of performance across different groups,which has never been done,”says Marzyeh Ghassemi,an MIT associate professor of electrical engineering and computer science,a member of MIT’s Institute for Medical Engineering and Science,and the senior author of the study.The researchers also found that they could retrain the models in away that improves their fairness.However,their approached to“debiasing”worked best when the models were tested on the same types of patients they were trained on,such as patients from the same hospital.When these models were applied to patients from different hospitals,the fairness gaps reappeared.“I think the main takeaways are,first,you should thoroughly evaluate any external models on your own data because any fairness guarantees that model developers provide on their training data may not transfer to your population.Second,whenever sufficient data is available,you should train models on your own data,”says Haoran Zhang,an MIT graduate student and one of the lead authors of the new paper.MIT graduate student Yuzhe Yang is also alead author of the paper,which appears today in Nature Medicine.Judy Gichoya,an associate professor of radiology and imaging sciences at Emory University School of Medicine,and Dina Katabi,the Thuan and Nicole Pham Professor of Electrical Engineering and Computer Science at MIT,are also authors of the paper. 查看详细>>

Cassini observations of Saturn provide the most extensive dataset available to characterize the atmosphere of any giant planet.I will celebrate the 20th anniversary of Cassini orbit insertion at Saturn(July 1)by presenting results based on the analysis of observations of the middle and upper atmosphere obtained by the UVIS and CIRS instruments during the last two years of the Cassini mission in 2016-2017.These results provide asnapshot of the middle and upper atmosphere around the northern summer solstice,including apole-to-pole map of temperatures as well as the distribution of methane and its photochemical products.They provide evidence that the seasonal circulation pattern in the stratosphere penetrates to the thermosphere and allow us,for the first time,infer neutral wind speeds in the upper atmosphere.The retrieved temperatures and winds also demonstrate the importance auroral electrodynamics and heating in controlling both the dynamics and energy balance of the thermosphere.They indicate that polar auroral heating followed by redistribution of energy to lower latitudes(stirring),enabled by momentum deposition by gravity waves and other sources of drag(shaking),is afeasible mechanism to explain the higher than expected temperatures in the thermosphere and therefore to solve the long-standing“energy crisis”on Saturn.Given the similarity of the subsequently observed temperatures on Jupiter,the same mechanism may also explain the temperatures observed in Jupiter’s thermosphere.Finally,we conclude by providing preliminary estimates of what is required to explain the observed temperatures in the upper atmosphere of Uranus,as afirst step towards apossible common mechanism to explain the higher than expected upper atmosphere temperatures on the giant planets. 查看详细>>

Drug development is typically slow:The pipeline from basic research discoveries that provide the basis for anew drug to clinical trials and then production of awidely available medicine can take decades.But decades can feel impossibly far off to someone who currently has afatal disease.Broad Institute of MIT and Harvard Senior Group Leader Sonia Vallabh is acutely aware of that race against time,because the topic of her research is aneurodegenerative and ultimately fatal disease—fatal familial insomnia,a type of prion disease—that she will almost certainly develop as she ages.Vallabh and her husband,Eric Minikel,switched careers and became researchers after they learned that Vallabh carries adisease-causing version of the prion protein gene and that there is no effective therapy for fatal prion diseases.The two now run alab at the Broad Institute,where they are working to develop drugs that can prevent and treat these diseases,and their deadline for success is not based on grant cycles or academic expectations but on the ticking time bomb in Vallabh’s genetic code.That is why Vallabh was excited to discover,when she entered into acollaboration with Whitehead Institute for Biomedical Research member Jonathan Weissman,that Weissman’s group likes to work at full throttle.In less than two years,Weissman,Vallabh,and their collaborators have developed aset of molecular tools called CHARMs that can turn off disease-causing genes such as the prion protein gene—as well as,potentially,genes coding for many other proteins implicated in neurodegenerative and other diseases—and they are refining those tools to be good candidates for use in human patients.Although the tools still have many hurdles to pass before the researchers will know if they work as therapeutics,the team is encouraged by the speed with which they have developed the technology thus far.“The spirit of the collaboration since the beginning has been that there was no waiting on formality,”Vallabh says.“As soon as we realized our mutual excitement to do this,everything was off to the races.”Co-corresponding authors Weissman and Vallabh and co-first authors Edwin Neumann,a graduate student in Weissman’s lab,and Tessa Bertozzi,a postdoc in Weissman’s lab,describe CHARM—which stands for Coupled Histone tail for Autoinhibition Release of Methyltransferase—in apaper published today in the journal Science.“With the Whitehead and Broad Institutes right next door to each other,I don’t think there’s any better place than this for agroup of motivated people to move quickly and flexibly in the pursuit of academic science and medical technology,”says Weissman,who is also aprofessor of biology at MIT and aHoward Hughes Medical Institute Investigator.“CHARMs are an elegant solution to the problem of silencing disease genes,and they have the potential to have an important position in the future of genetic medicines.” 查看详细>>

If there’s one thing we humans are good at,it’s producing heat.Significant amounts,and in many cases most of the energy we generate and put into our systems we lose as heat,whether it be our appliances,our transportation,our factories,even our electrical grid.“Waste heat is everywhere,”said UC Santa Barbara mechanical engineering professor Bolin Liao,who specializes in thermal science and renewable energy.“Our power plants,our car exhaust pipes—there are so many places where we create excess heat waste.”For the moment,we’re fairly limited as to how we can make the most out of this dissipating heat.But Liao and UCSB colleagues,alongside collaborators from Ohio State University and University of Hong Kong are making headway toward putting that heat to use,with afirst-time comprehensive characterization of the thermoelectric properties of high-quality cadmium arsenide thin films.“If we could harvest that waste heat then that would be fantastic,”he said.“That would really increase our energy efficiency and it’s also areally sustainable energy source.”The team’s research is published in the journal Advanced Materials.A better thermoelectric material“To obtain high efficiency,we need the material to conduct electricity well,conduct heat poorly and generate ahigh voltage for agiven temperature difference,”Liao said.Poor heat conduction minimizes heat dissipation while maintaining atemperature difference across the material,resulting in an electric current enhanced by the material’s high-performing electric conductivity.The voltage resulting from atemperature gradient is known as the Seebeck effect.This combination of electrical and thermal transport properties is ideal but,according to Liao,“very hard to achieve in practice.”Enter cadmium arsenide(Cd3As2),a Dirac semimetal with promising transport properties,in particular,a low thermal conductivity and high electron mobility.“We were pretty excited about this material,and we thought‘okay,this is really acombination of these two great properties,”Liao said.“But there is only one problem.“This problem was that in addition to good electric conduction and poor thermal conduction,you also need this material to be able to generate enough voltage under atemperature gradient.”As asemimetal,cadmium arsenide is excellent at conducting electricity very rapidly,but it only generates avery small Seebeck voltage.To create auseful voltage,Liao explained,one would need to open up aband gap.“You want this material to have acertain energy range where the electrons cannot conduct.That’s called aband gap,”he said.Because of the gap,which essentially blocks the free flow of electrons,enough electrical“pressure”(a.k.a.voltage)can build up as aresponse to atemperature difference across the material.In bulk cadmium arsenide crystals,there is no band gap. 查看详细>>

An Engineering research team led by Professor Yue Chen from the Department of Mechanical Engineering at the University of Hong Kong(HKU)has achieved aremarkable milestone in the realm of thermal transport in crystals.The research highlights the potential of simple crystal structures to achieve low thermal conductivity.This discovery not only underscores the importance of exploring new materials for applications in thermal insulation and thermoelectrics but also calls for further experimental investigations to expand the repertoire of materials with ultralow thermal conductivity.Traditionally,efforts to lower the lattice thermal conductivity of materials have focused on complex material systems,where lower thermal conductivity is typically observed.However,the pursuit of simple crystals with ultralow thermal conductivity has proven to be achallenging task.In their research,the team identified an exceptional candidate,AgTlI2,which defies conventional expectations by exhibiting an extraordinarily low thermal conductivity of 0.25 W/mK at room temperature—a rarity among simple crystals.Through acombination of state-of-the-art experimental techniques,including X-ray diffraction experiments and ab initio molecular dynamics simulations,coupled with advanced anharmonic lattice dynamics,the team gained comprehensive insights into the complex thermal transport mechanisms of AgTlI2 at room temperature.Their findings revealed acoexistence of ultralow particle-like and wavelike phonon thermal transports in AgTlI2,elucidating the underlying nature of its ultralow thermal conductivity.Moreover,leveraging their understanding of thermal transport in AgTlI2,the team proposed an effective alternative approach for identifying other simple materials with ultralow thermal conductivity,promising to expand the repertoire of materials with strongly suppressed thermal transport.This interdisciplinary study was conducted in collaboration with Professor Emmanuel Guilmeau‘s team from CRISMAT at Normandie University in France,Professor Zheyong Fan‘s team from Bohai University,China,and Professor Pierric Lemoine from Institute Jean Lamour,France.The collaborative effort allowed for the integration of expertise from multiple research groups,including sample preparation,synchrotron X-ray scattering,low-temperature thermal conductivity measurement,and ab initio simulations.“The discovery of the ultralow thermal conductivity of AgTlI2 is aresult of acombined effort of both theorists and experimentalists.”the first author of the paper,Dr Zezhu Zeng,expressed.He is currently aPost-doctoral Fellow in Professor Geoff Thornton‘s group at University College London and Professor Bingqing Cheng‘s group at University of California,Berkeley and Institute of Science and Technology,Austria.Dr Xingchen Shen from CRISMAT at French National Center for Scientific Research(CNRS)also contributed as aco-first author.“This work implies the important role of simple crystals on thermal insulation,paving the way for new research directions.”said Professor Chen.The findings have been published in the scientific journal Nature Communications with the title“Pushing thermal conductivity to its lower limit in crystals with simple structures”. 查看详细>>

DALLAS–June 25,2024–Patients with moderate to severe treatment-resistant depression(TRD)might have better symptom relief from ketamine infusions than from electroconvulsive therapy(ECT),but those with severe TRD could benefit more from ECT early in treatment,an analysis led by aUT Southwestern Medical Center researcher shows.The findings,published in JAMA Network Open,are the first to identify characteristics that distinguish which treatments might benefit TRD patients more.“Patients with TRD and their physicians can incorporate these findings in their shared decision-making process when selecting between ketamine and ECT,”said first author Manish Jha,M.D.,Associate Professor of Psychiatry and an O’Donnell Clinical Neuroscience Scholar at UT Southwestern.Dr.Jha is also an Investigator in the Peter O’Donnell Jr.Brain Institute.Previous studies have suggested that up to athird of adults with major depressive disorder have TRD,meaning they haven’t experienced adequate improvement with two or more courses of antidepressants.For decades,doctors have treated TRD patients with ECT,which delivers ajolt of electricity to the brain.More recently,ketamine–a drug historically used as an anesthetic–has also been used to treat TRD.In astudy known as the ELEKT-D clinical trial that published last year in the New England Journal of Medicine and was led by Amit Anand,M.D.,Professor of Psychiatry at Harvard Medical School,Dr.Jha and his colleagues showed that ECT and ketamine produced comparable results in agroup of 403 patients with TRD at five U.S.medical centers.However,it was unclear whether patients’baseline characteristics could predict which would be more beneficial.So Dr.Jha and research colleagues across the U.S.analyzed ELEKT-D’s results in asubgroup of 365 patients–195 had received up to six ketamine infusions over three weeks,and 170 had received up to nine ECT treatments over three weeks.Twice weekly during the treatment phase and at one follow-up after their treatments ended,these patients filled out aquestionnaire designed to assess their depression symptoms.The questionnaire was developed by former UTSW physician-researcher A.John Rush,M.D.,Professor Emeritus at the Duke-NUS Medical School at the National University of Singapore,and Madhukar Trivedi,M.D.,Professor of Psychiatry,Chief of the Division of Mood Disorders,and founding Director of the Center for Depression Research and Clinical Care at UT Southwestern.The patients also were assessed with aclinician-administered diagnostic tool.In addition,they underwent evaluations assessing various demographic and clinical characteristics,such as age,sex,concurrent use of other treatments,cognitive function,and whether they were being treated for their depression as an inpatient or outpatient.When the researchers compared the patients’symptom assessments over three weeks with their demographic and clinical characteristics,they found that patients were most likely to benefit from ketamine if they had moderate to severe overall depression at baseline or were receiving treatments as outpatients.Patients with very severe depression or who received their treatments as inpatients had more benefit early in their treatment course from ECT.However,by their last appointment,patients with these characteristics who received ketamine had similar outcomes. 查看详细>>

Cyclodextrins(CDs),a class of cyclic oligosaccharides that were“born”in 1891,have opened up endless research and commercial opportunities in numerous fields that span carbohydrate,supramolecular(host-guest)and analytical chemistry all the way from research laboratories in academia to the mass production of products—e.g.,skin care enablers to drug delivery systems—in industry.Although they have been known for over 130 years,the most accessible cyclic homologues areα-,β-,andγ-CDs,which contain six,seven,and eight D-glucopyranosyl units,respectively.The odyssey of naturally occurring CDs suggests that despite the number of CDs is rather limited,their reach has been limitless.For along time,scientists(chemists,biologists,medical scientists,etc)have been exploring novel methods to synthesise—both chemically and enzymatically—CD homologues.These efforts include the syntheses of unusual smaller analogues with only 3,4,and 5D-glucose units and the making of rare larger CDs with 9to 12 D-glucose units.All the currently available CDs are composed solely of D-glucopyranosyl units as the monomers,while the syntheses of mirror-image CDs have remained an untouched goal of the CD community,limiting the realisation of their full potential,such as in the development of new supramolecular sensors and catalysts,chiral materials,as well as innovative drug delivery systems and active pharmaceutical ingredients.In order to fulfil this fundamental research niche,a collaborative research team led by Professor Sir Fraser STODDART in the Department of Chemistry of The University of Hong Kong(HKU)and Professor Daniel ARMSTRONG in the Department of Chemistry and Biochemistry of The University of Texas at Arlington,recently developed aconcise approach to link L-glucopyranosyl monosaccharides together in ahighly diastereoselective and scalable manner,resulting in the production of circa half-gram quantities ofα-,β-,andγ-L-CDs.The availability of L-CDs for the first time—ever since the serendipitous discovery of their natural counterparts back in 1891—has enabled the elucidation of an unprecedented chiral self-sorting of aracemic modification ofβ-CDs in the solid state and an investigation of the chiral recognition of enantiomeric guests byα-L-CD in water.The research work was recently published and featured on the Cover in aleading scientific journal–Nature Synthesis.A corresponding News&Views Article written by Professor Sophie BEEREN,a cyclodextrin expert working at Technical University of Denmark,was also published in the same Journal(https://www.nature.com/articles/s44160-024-00512-w). 查看详细>>

近日，南方科技大学理学院化学系副教授刘柳团队在双亲性主族元素多重键化学领域取得重要进展。研究成果以“一例晶态的锡炔（A Crystalline Stannyne）”为题，发表在《自然化学》（Nature Chemistry）杂志上。该成果通过取代基的π供电子效应和空间保护，合成了一种双亲性锡炔分子（R1−C≡Sn−R2↔R1−C(:)−Sn(:)−R2）。这类分子的分离表征扩展了人们对元素化学的认知，推动了双亲性（ambiphilicity；既亲核也亲电）主族元素化学的发展。新型主族元素结构基元的创制对合成化学、药物化学以及材料科学等多个领域的发展至关重要。大多数过渡金属具有部分占据的d电子，价层轨道既亲核也亲电，和小分子发生较强的相互作用。不同于过渡金属元素，主族元素的非价层电子是完全填充的，这一特点使得主族元素化合物的化学活性直接与其价层电子的能级和分布有关，同时也受到原子半径和元素电负性的显著影响。然而，近期的研究揭示，低价态下的配位不饱和主族元素化合物展现出与过渡金属相似的前线轨道特性和化学行为。这些具有“类过渡金属”行为的主族元素化合物，其化学特性主要体现为双亲性。双亲性的主族分子不仅能够活化惰性小分子，还在催化和材料科学等领域展现了巨大的潜力。炔烃分子（R1−C≡C−R2）无法共振成两个双亲的卡宾中心（图1a）。然而，炔烃的重元素类似物与炔烃有着显著不同的电子结构。由于重元素中心孤对电子惰性以及最外层轨道半径匹配差等原因，削弱了其形成多重键，因此炔烃的重元素类似物具有邻位双亲性质（R1−E≡E−R2↔R1−E(:)−E(:)−R2;E=Si,Ge,Sn,Pb）。值得注意的是，自从1836年首次发现乙炔，异核的炔烃重元素类似物（R1−C≡E−R2↔R1−C(:)−E(:)−R2;E=Si,Ge,Sn,Pb）一直未被科学家突破（图1）。近期，课题组利用π电子“推拉”策略和大位阻取代基，稳定了双亲性锡炔分子（R1−C≡Sn−R2↔R1−C(:)−Sn(:)−R2）（图2），首次实现了相邻异核双亲元素中心的构建（图3a），解决了主族元素化学领域内的重要难题。核磁共振和理论计算均支持锡炔3为单线态化合物。其中锡炔最主要的共振式为3A联烯结构（图3b）。基于理论计算，作者发现锡炔的碳原子具有反电子态卡宾的性质。通过实验研究，作者探索了锡炔的反应化学。所有化合物均经过了核磁、晶体结构、高分辨质谱等表征（图4）。该研究填补了异核炔烃重元素类似物的空白，扩展了人们对重元素化学的认知。鉴于独特的电子性质，锡炔分子有望革新双亲性主族元素的发展。近年来，刘柳课题组一直致力于双亲性主族元素化学的研究。瞄准主族结构基元“0到1”的原始创新，就“如何稳定（多重）双亲性结构基元”这一核心科学问题，通过合理的设计，成功分离表征或原位构建了一系列双亲性主族化合物，深度探讨了这些新颖结构基元的化学性质以及潜在的应用前景。截至目前，课题组以南科大为通讯单位发表Science 1篇、Nat.Chem.1篇、Nat.Synth.1篇、Chem.1篇、CCS Chem.1篇、J.Am.Chem.Soc.7篇、Angew.Chem.Int.Ed.8篇。这些研究工作先后多次被ChemistryViews、Nat.Synth.、Chem.、Synfacts以Highlight或Preview进行介绍。 查看详细>>

Chemotherapy and other treatments that take down cancer cells can also destroy patients’immune cells.Every year,that leads tens of thousands of cancer patients with weakened immune systems to contract infections that can turn deadly if unmanaged.Doctors must strike abalance between giving enough chemotherapy to eradicate cancer while not giving so much that the patient’s white blood cell count gets dangerously low,a condition known as neutropenia.It can also leave patients socially isolated in between rounds of chemotherapy.Currently,the only way for doctors to monitor their patients’white blood cells is through blood tests.Now Leuko is developing an at-home white blood cell monitor to give doctors amore complete view of their patients’health remotely.Rather than drawing blood,the device uses light to look through the skin at the top of the fingernail,and artificial intelligence to analyze and detect when white blood cells reach dangerously low levels.The technology was first conceived of by researchers at MIT in 2015.Over the next few years,they developed aprototype and conducted asmall study to validate their approach.Today,Leuko’s devices have accurately detected low white blood cell counts in hundreds of cancer patients,all without drawing asingle drop of blood.“We expect this to bring aclear improvement in the way that patients are monitored and cared for in the outpatient setting,”says Leuko co-founder and CTO Ian Butterworth,a former research engineer in MIT’s Research Laboratory of Electronics.“I also think there’s amore personal side of this for patients.These people can feel vulnerable around other people,and they don‘t currently have much they can do.That means that if they want to see their grandkids or see family,they’re constantly wondering,‘Am Iat high risk?’”The company has been working with the Food and Drug Administration(FDA)over the last four years to design studies confirming their device is accurate and easy to use by untrained patients.Later this year,they expect to begin apivotal study that will be used to register for FDA approval.Once the device becomes an established tool for patient monitoring,Leuko’s team believes it could also give doctors anew way to optimize cancer treatment.“Some of the physicians that we have talked to are very excited because they think future versions of our product could be used to personalize the dose of chemotherapy given to each patient,”says Leuko co-founder and CEO Carlos Castro-Gonzalez,a former postdoc at MIT.“If apatient is not becoming neutropenic,that could be asign that you could increase the dose.Then every treatment could be based on how each patient is individually reacting.” 查看详细>>