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Lipolysis supports bone formation by providing osteoblasts with endogenous fatty acid substrates to maintain bioenergetic status

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Bone Research 2023年第4期11卷 876-894页

作者： Ananya Nandy Ron C.M.Helderman Santosh Thapa Shobana Jayapalan Alison Richards Nikita Narayani michael P.Czech Clifford J.Rosen Elizabeth Rendina-Ruedy Department of Medicine Division of Clinical PharmacologyVanderbilt University Medical CenterNashvilleTN 37232USA Program in Molecular Medicine University of Massachusetts Chan Medical SchoolWorcesterMA 01605USA maine Medical Center Research Institute ScarboroughMEUSA Molecular Physiology and Biophysics Vanderbilt UniversityNashvilleTN 37232USA

Bone formation is a highly energy-demanding process that can be impacted by metabolic *** has been considered the principal substrate for osteoblasts,although fatty acids are also important for osteoblast ***,we report that osteoblasts can derive energy from endogenous fatty acids stored in lipid droplets via lipolysis and that this process is critical for bone *** such,we demonstrate that osteoblasts accumulate lipid droplets that are highly dynamic and provide the molecular mechanism by which they serve as a fuel source for energy generation during osteoblast *** cytoplasmic lipolysis leads to both an increase in lipid droplet size in osteoblasts and an impairment in osteoblast *** fatty acids released by lipolysis from these lipid droplets become critical for cellular energy production as cellular energetics shifts towards oxidative phosphorylation during nutrient-depleted *** vivo,conditional deletion of the ATGL-encoding gene Pnpla2 in osteoblast progenitor cells reduces cortical and trabecular bone parameters and alters skeletal lipid ***,our data demonstrate that osteoblasts store fatty acids in the form of lipid droplets,which are released via lipolysis to support cellular bioenergetic status when nutrients are *** in this process result in impairment of bone formation,specifically reducing ATP production and overall osteoblast function.

关键词： endogenous maintain osteoblast

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machine learning for the discovery of molecular recognition based on single-walled carbon nanotube corona-phases

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npj Computational materials 2022年第1期8卷 1265-1277页

作者： Xun Gong Nicholas Renegar Retsef Levi michael S.Strano massachusetts Institute of Technology Department of Chemical EngineeringCambridgeMAUSA massachusetts Institute of Technology Operations Research CenterCambridgeMAUSA massachusetts Institute of Technology Sloan School of ManagementCambridgeMAUSA

Nanoparticle corona phase(CP)design offers a unique approach toward molecular recognition(MR)for sensing ***-walled carbon nanotube(SWCNT)CPs can additionally transduce MR through its band-gap photoluminescence(PL).While DNA oligonucleotides have been used as SWCNT CPs,no generalized scheme exists for MR prediction de novo due to their sequence-dependent three-dimensional *** work generated the largest DNA-SWCNT PL response library of 1408 elements and leveraged machine learning(ML)techniques to understand MR and DNA sequence dependence through local(LFs)and high-level features(HLFs).Out-of-sample analysis of our ML model showed significant correlations between model predictions and actual sensor responses for 6 out of 8 experimental *** HLF combinations were found to be uniquely correlated with different ***,models utilizing both LFs and HLFs show improvement over that with HLFs alone,demonstrating that DNA-SWCNT CP engineering is more complex than simply specifying molecular properties.

关键词： walled carbon utilizing

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Broadband 200-nm second-harmonic generation in silicon in the telecom band

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Light(Science & Applications) 2020年第1期9卷 1844-1850页

作者： Neetesh Singh manan Raval Alfonso Ruocco michael R.Watts Research Laboratory of Electronics Massachusetts Institute of Technology77 Massachusetts AvenueCambridgeMA 02139USA

Silicon is well known for its strong third-order optical nonlinearity,exhibiting efficient supercontinuum and four-wave mixing processes.A strong second-order effect that is naturally inhibited in silicon can also be observed,for example,by electrically breaking the inversion symmetry and quasi-phase matching the pump and the *** generate an efficient broadband second-harmonic signal,however,the most promising technique requires matching the group velocities of the pump and the *** this work,we utilize dispersion engineering of a silicon waveguide to achieve group velocity matching between the pump and the signal,along with an additional degree of freedom to broaden the second harmonic through the strong third-order *** demonstrate that the strong self-phase modulation and cross-phase modulation in silicon help broaden the second harmonic by 200 nm in the ***,we show a waveguide design that can be used to generate a second-harmonic signal in the entire nearinfrared *** work paves the way for various applications,such as efficient and broadband complementarymetal oxide semiconductor based on-chip frequency synthesizers,entangled photon pair generators,and optical parametric oscillators.

关键词： waveguide synthesizer harmonic

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Overexpression of an ABA biosynthesis gene using a stress-inducible promoter enhances drought resistance in petunia

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Horticulture Research 2015年第1期2卷 255-263页

作者： Alejandro C Estrada-Melo Chao ma michael S Reid Cai-Zhong Jiang Department of Plant Sciences University of California DavisDavisCAUSA United States Department of Agriculture Crops Pathology and Genetic Research UnitAgricultural Research ServiceDavisCAUSA

The response of plants to drought stress includes reduced transpiration as stomates close in response to increased abscisic acid(ABA)*** overexpression of 9-cis-epoxycarotenoid dioxygenase(NCED),a key enzyme in ABA biosynthesis,increases drought resistance,but causes negative pleiotropic effects on plant growth and *** overexpressed the tomato NCED(LeNCED1)in petunia plants under the control of a stress-inducible promoter,*** water stress,the transgenic plants had increased transcripts of NCED mRNA,elevated leaf ABA concentrations,increased concentrations of proline,and a significant increase in drought *** transgenic plants also displayed the expected decreases in stomatal conductance,transpiration,and *** 14 days without water,the control plants were dead,but the transgenic plants,though wilted,recovered fully when ***-watered transgenic plants grew like non-transformed control plants and there was no effect of the transgene on seed dormancy.

关键词： inducible pet drought

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Cell atlas of CCl_(4)-induced progressive liver fibrosis reveals stage-specific responses

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Zoological Research 2023年第3期44卷 451-466页

作者： Peng-Cheng Guo Jing Zuo Ke-Ke Huang Guang-Yao Lai Xiao Zhang Juan An Jin-Xiu Li Li Li Liang Wu Yi-Ting Lin Dong-Ye Wang Jiang-Shan Xu Shi-Jie Hao Yang Wang Rong-Hai Li Wen ma Yu-Mo Song Chang Liu Chuan-Yu Liu Zhen Dai Yan Xu Amar Deep Sharma michael Ott Qing Ou-Yang Feng Huo Rong Fan Yong-Yin Li Jin-Lin Hou Giacomo Volpe Long-Qi Liu Miguel A.Esteban Yi-Wei Lai State Key Laboratory for Zoonotic Diseases Key Laboratory for Zoonosis Research of Ministry of EducationInstitute of ZoonosisCollege of Veterinary MedicineJilin UniversityChangchunJilin 130062China BGI-Hangzhou HangzhouZhejiang 310012China BGI-Shenzhen ShenzhenGuangdong 518083China Key Laboratory of Biological Targeting Diagnosis Therapy and Rehabilitation of Guangdong Higher Education InstitutesFifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong 510799China Laboratory of Integrative Biology Guangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouGuangdong 510530China Joint School of Life Sciences Guangzhou Institutes of Biomedicine and Health and Guangzhou Medical UniversityGuangzhouGuangdong 510530China School of Life Sciences Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230026China College of Life Sciences University of Chinese Academy of SciencesBeijing 100049China Guangzhou Institutes of Biomedicine and Health Chinese Academy of SciencesGuangzhouGuangdong 510530China Biotherapy Centre Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China Department of Gastroenterology Hepatology and EndocrinologyHannover Medical SchoolHannover 30625Germany Department of Hepatobiliary Surgery and Liver Transplant Center General Hospital of Southern Theater CommandGuangzhouGuangdong 510010China Department of Infectious Diseases Nanfang HospitalSouthern Medical UniversityGuangdong Provincial Key Laboratory of Viral Hepatitis ResearchGuangzhouGuangdong 510515China Hematology and Cell Therapy Unit IRCCS-Istituto Tumori‘Giovanni Paolo II’Bari 70124Italy Institute of Experimental Hematology Hannover Medical SchoolHannover 30625Germany

Chronic liver injury leads to progressive liver fibrosis and ultimately cirrhosis,a major cause of morbidity and mortality ***,there are currently no effective anti-fibrotic therapies available,especially for latestage patients,which is partly attributed to the major knowledge gap regarding liver cell heterogeneity and cellspecific responses in different fibrosis *** reveal the multicellular networks regulating mammalian liver fibrosis from mild to severe phenotypes,we generated a single-nucleus transcriptomic atlas encompassing 49919nuclei corresponding to all main liver cell types at different stages of murine carbon tetrachloride(CCl_(4))-induced progressive liver *** analysis distinguished the sequential responses to injury of hepatocytes,hepatic stellate cells and endothelial ***,we reconstructed the cell-cell interactions and gene regulatory networks implicated in these *** integrative analyses uncovered previously overlooked aspects of hepatocyte proliferation exhaustion and disrupted pericentral metabolic functions,dysfunction for clearance by apoptosis of activated hepatic stellate cells,accumulation of pro-fibrotic signals,and the switch from an anti-angiogenic to a pro-angiogenic program during CCl_(4)-induced progressive liver *** dataset thus constitutes a useful resource for understanding the molecular basis of progressive liver fibrosis using a relevant animal model.

关键词： Liver fibrosis Toxicity Single-cell and single-nucleus RNA-sequencing Hepatocytes Hepatic stellate cells Angiogenesis Cell-cell interactions Gene regulatory networks

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Synthesis of trifluoromethyl-/cyclopropyl-substituted 2-isoxazolines by DBU-promoted domino reaction

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Chinese Chemical Letters 2017年第8期28卷 1780-1783页

作者： Xiao-Dong Liu Hai-Yan ma Chun-Hui Xing Long Lu School of Chemistry and Molecular Engineering East China University of Science and Technology Key Laboratory of Organofluorine Chemistry Shanghai Institute of Organic Chemistry Chinese Academy of Sciences

NTrifluoromethyl and cyclopropyl substituted 2-isoxazolines were synthesized via a DBU-promoted domino reaction of β-trifluoromethyl-/β-cyclopropyl-substituted enones with hydroxylamine. The domino reaction consists of a michael addition and the followed cyclization. A wide range of 3-substituted 5-cyclopropyl-5-trifluoromethyl-2-isoxazolines were obtained in good to excellent yields under mild reaction conditions. The method could also apply to other trifluoromethyl-substituted enones.

关键词： Isoxazoline Enone michael addition Cyclization Domino reaction

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In situ assembly of fibrinogen/hyaluronic acid hydrogel via knob-hole interaction for 3D cellular engineering

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Bioactive materials 2017年第4期2卷 253-259页

作者： Shengjie Huang Chunfen Wang Jingwei Xu Lie ma Changyou Gao MOE Key Laboratory of macromolecular Synthesis and Functionalization Department of Polymer Science and EngineeringZhejiang UniversityHangzhou310027China

Hyaluronic acid(HA)-based hydrogels have applied widely for biomedical applications due to its biocompatibility and ***,the use of initiators or crosslinkers during the hydrogel formation may cause cytotoxicity and thereby impair the *** by the crosslinking mechanism of fibrin gel,a novel HA-based hydrogel was developed via the in situ supramolecular assembly based on knob-hole interactions between fibrinogen and knob-grafted HA(knob-g-HA)in this *** knob-grafted HA was synthesized by coupling knob peptides(GPRPAAC,a mimic peptide of fibrin knob A)to HA via michael *** the translucent fibrinogen/knob-g-HA hydrogels were prepared by simply mixing the solutions of knob-g-HA and fibrinogen at the knob/hole ratio of *** rheological behaviors of the fibrinogen/knob-g-HA hydrogels with the fibrinogen concentrations of 50,100 and 200 mg/mL were evaluated,and it was found that the dynamic storage moduli(G0)were higher than the loss moduli(G00)over the whole frequency range for all the *** SEM results showed that fibrinogen/knob-g-HA hydrogels presented the heterogeneous mesh-like structures which were different from the honeycomb-like structures of fibrinogen/ma-HA ***,a higher swelling ratio was obtained in the groups of fibrinogen/knob-g-HA ***,the cytocompatibility of fibrinogen/knob-g-HA hydrogels was proved by live/dead stainings and MTT assays in the 293T cells encapsulation *** these results highlight the biological potential of the fibrinogen/knob-g-HA hydrogels for 3D cellular engineering.

关键词： Fibrinogen Knob-hole interactions Hyaluronic acid In situ assembly Cell encapsulation

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In-hospital outcomes and readmission in older adults treated with percutaneous coronary intervention for stable ischemic heart disease

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Journal of Geriatric Cardiology 2022年第9期19卷 631-642页

作者： Dae Yong Park Jonathan M.Hanna Sumeet Kadian mannat Kadian WSchuyler Jones Abdulla Al Damluji Ajar Kochar Jeptha P.Curtis michael G.Nanna Department of Medicine Cook County HealthChicagoILUSA Department of Internal Medicine Yale School of MedicineNew HavenCTUSA University of Connecticut StorrsCTUSA East Lyme High School East LymeCTUSA Section of Interventional Cardiology Duke University Health SystemDurhamNCUSA Section of Interventional Cardiology Johns Hopkins UniversityBaltimoreMDUSA Section of Interventional Cardiology Brigham and Women’s HospitalBostonMAUSA Section of Cardiovascular Medicine Yale School of MedicineNew HavenCTUSA

Background Percutaneous coronary intervention(PCI)for stable ischemic heart disease(SIHD)in older adults requires a metic-ulous assessment of procedural risks and benefits,but contemporary data on outcomes in this population is ***,we examined the risk of near-term readmission,bleeding,and mortality in high-risk cohort of older adults undergoing inpatient PCI for *** We analyzed the National Readmissions Database from 2017 to 2018 to identify index hospitalizations in which PCI was performed for *** were stratified into those≥75 years old(older adults)and thosemary outcome was 90-day *** outcomes included in-hospital mortality,hospital length of stay(LOS),and total hospital *** A total of 74,516 patients underwent inpatient PCI for SIHD,of whom 24,075 were older *** adult patients had higher odds of in-hospital mortality(OR=2.00,95%CI:1.68-2.38),intracranial hemorrhage(OR=2.03,95%CI:1.24-3.34),and gastrointestinal hemorrhage(OR=1.72,95%CI:1.43-2.07)during index hospitalization,with longer LOS and in-hospital *** adults also experienced a higher hazard of 90-day readmission for any cause(HR=1.61,95%CI:1.57-1.66)and car-diovascular causes(HR=1.84,95%CI:1.77-1.91).CONCLUSION Older adults undergoing inpatient PCI for SIHD were at increased risk for in-hospital mortality,periprocedural morbidities,higher cost,and readmissions compared with younger *** these differences may improve shared decision-making for patients with SIHD being considered for PCI.

关键词： mortality coronary younger

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The Case in the Vase： What Can a Ming Novel Tell Us about Traditional Chinese Legal Culture？

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Frontiers of History in China 2017年第4期12卷 621-625页

作者： michael Szonyi Fairbank Center for Chinese Studies Harvard University Cambridge MA 02138 USA

The more than thirty legal disputes and cases mentioned in The Plum in the Golden Vase （Jinpingmei） make this late Ming novel an invaluable source for the study of law and legal culture in premodern China. This lecture illustrates that the cases in the novel describe in considerable detail each of the formal steps in the Ming process of legal adjudication. But the work also conveys the message that despite the formal process, the legal system does not deliver justice. However, an alternative system of justice that is mostly implicit in the text, the justice of a disinterested and moral Heaven, ultimately prevails. Finally, the contemporary implications of this traditional understanding of law and justice are explored.

关键词： Jinpingrnei Ming dynasty, legal history, legal process, corruption, gong'an (case) literature

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Full-spin-wave-scaled stochastic micromagnetism for mesh-independent simulations of ferromagnetic resonance and reversal

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npj Computational materials 2022年第1期8卷 315-323页

作者： Harald Oezelt Luman Qu Alexander Kovacs Johann Fischbacher markus Gusenbauer Roman Beigelbeck Dirk Praetorius masao Yano Tetsuya Shoji Akira Kato Roy Chantrell michael Winklhofer Gergely T.Zimanyi Thomas Schrefl Department for Integrated Sensor Systems Danube University Krems2700Wiener NeustadtAustria Department of Physics University of CaliforniaDavisCA95616USA Christian Doppler Laboratory for magnet design through physics informed machine learning 2700Wiener NeustadtAustria Institute for Analysis and Scientific Computing Vienna University of Technology1040WienAustria Toyota Motor Corp. Toyota City471-8572Japan Department of Physics University of YorkYorkYO105DDUK Institute for Biology and Environmental Sciences IBU Carl von Ossietzky University of Oldenburg26129OldenburgGermany

In this paper,we address the problem that standard stochastic Landau-Lifshitz-Gilbert(sLLG)simulations typically produce results that show unphysical mesh-size *** root cause of this problem is that the effects of spin-wave fluctuations are ignored in *** propose to represent the effect of these fluctuations by a full-spin-wave-scaled stochastic LLG,or FUSSS LLG *** FUSSS LLG,the intrinsic parameters of the sLLG simulations are first scaled by scaling factors that integrate out the spin-wave fluctuations up to the mesh size,and the sLLG simulation is then performed with these scaled *** developed FUSSS LLG by studying the Ferromagnetic Resonance(FMR)in Nd_(2)Fe_(14)B *** nominal scaling greatly reduced the mesh size dependence relative to *** then performed three tests and validations of our FUSSS LLG with this modified scaling.(1)We studied the same FMR but with magnetostatic fields included.(2)We simulated the total magnetization of the Nd_(2)Fe_(14)B cube.(3)We studied the effective,temperature-and sweeping rate-dependent coercive field of the *** all three cases,we found that FUSSS LLG delivered essentially mesh-size-independent results,which tracked the theoretical expectations better than unscaled *** by these successful validations,we propose that FUSSS LLG provides marked,qualitative progress towards accurate,high precision modeling of micromagnetics in hard,permanent magnets.

关键词： stochastic wave scaling

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