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The biosynthetic pathway of the hallucinogen mescaline and its heterologous reconstruction

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Molecular Plant 2024年第7期17卷 1129-1150页

作者： Paula Berman Luis Alejandro de Haro Ana-Rita Cavaco Sayantan Panda Younghui Dong Nikolay Kuzmich Gabriel Lichtenstein Yoav Peleg Hila Harat Adam Jozwiaki Jianghua Cai Uwe Heinig Sagit Meir Ilana Rogachev Asaph Aharoni Department of Plant and Environmental sciences Weizmann Institute of ScienceRehovot 7610001Israel Life sciences Core Facilities Weizmann Institute of ScienceRehovot 7610001Israel The Maurice and Vivienne Wohl institute for Drug Discovery Weizmann Institute of ScienceRehovot 7610001Israel Present address:Department of Cell and Metabolic Biology Leibniz Institute of Plant BiochemistryWeinberg 306120 Halle(Saale)Germany Department of Molecular&Cellular Pharmacology University of Miami Miler School of MedicineMiamiFL 33136USA Department of Botany and Plant sciences University of California RiversideRiversideCA 92521USA Laboratory of Plant Hormones and Development Regulation of Chongqing School of Life SciencesChongqing UniversityChongqing 401331China

Mescaline,among the earliest identified natural hallucinogens,holds great potential in psychotherapy ***,despite the existence of a postulated biosynthetic pathway for more than half a century,the specific enzymes involved in this process are yet to be *** this study,we investigated the cactus Lophophora williamsii(Peyote),the largest known natural producer of the phenethylamine *** employed a multi-faceted approach,combining de novo whole-genome and transcriptome sequencing with comprehensive chemical profiling,enzymatic assays,molecular modeling,and pathway engineering for pathway *** identified four groups of enzymes responsible for the six catalytic steps in the mescaline biosynthetic pathway,and an N-methyltransferase enzyme that N-methylates all phenethylamine intermediates,likely modulating mescaline levels in ***,we reconstructed the mescaline biosynthetic pathway in both Nicotiana benthamiana plants and yeast cells,providing novel insights into several challenges hindering complete heterologous mescaline *** together,our study opens up avenues for exploration of sustainable production approaches and responsible utilization of mescaline,safeguarding this valuable natural resource for future generations.

关键词： mescaline Lophophora williamsi Peyote biosynthetic pathway de novo genome sequencing mo-lecular modeling

Gastroesophageal reflux following peroral endoscopic myotomy for achalasia:Bumps in the road to success

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World Journal of Gastroenterology 2024年第29期30卷 3461-3464页

作者： David Itskoviz Stephen David Howard Malnick Kaplan Medical Center Institute of Gastroenterology and HepatologyHebrew University Medical School of JerusalemRehovot 76100Israel Kaplan Medical Center Department of Internal Medicine CHebrew University Medical School of JerusalemRehovot 76100Israel

Achalasia can significantly impair the quality of *** clinical presentation typically includes dysphagia to both solids and liquids,chest pain,and *** can be delayed in patients with atypical presentations,and they might receive a wrong diagnosis,such as gastroesophageal reflux disease(GERD),owing to overlapping symptoms of both *** the cause of achalasia is poorly understood,its impact on the motility of the esophagus and gastroesophageal junction is well *** treatment modalities have been utilized,with the most common being surgical Heller myotomy with concomitant fundoplication and pneumatic balloon ***,peroral endoscopic myotomy(POEM)has gained popularity as an effective treatment for achalasia,despite a relatively high incidence of GERD occurring after treatment compared to other *** magnitude of post-POEM GERD depends on its definition and is influenced by patient and procedure-related *** longterm sequelae of post-POEM GERD are yet to be determined,but it appears to have a benign course and is usually manageable with clinically available *** risk factors for post-POEM GERD and modifying the POEM procedure in selected patients may improve the overall success of this technique.

关键词： Achalasia Per-oral endoscopic myotomy Gastroesophageal reflux Pneumatic dilatation Heller myotomy Proton pump inhibitor Acidic fermentation

Cerebral and muscle tissue oxygenation during exercise in healthy adults: A systematic review

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Journal of Sport and Health science 2024年第4期13卷 459-471,F0003页

作者： Diego Orcioli-Silva Victor Spiandor Beretta Paulo Cezar Rocha Santos Felipe Marroni Rasteiro Anita Brum Marostegan Rodrigo Vitorio Claudio Alexandre Gobatto Fulvia Barros Manchado-Gobatto Laboratory of Applied Sport Physiology(LAFAE) School of Applied Sciences(FCA)University of Campinas(UNICAMP)Limeira 13484-350Brazil Posture and Gait Studies Laboratory(LEPLO) Institute of BiosciencesSao Paulo State University(UNESP)Rio Claro 13506-900Brazil Physical Education Department School of Technology and SciencesSao Paulo State University(UNESP)Presidente Prudente 19060-900Brazil Department of Computer science&Applied Mathematics Weizmann Institute of ScienceRehovot 7610001Israel Center of Advanced Technologies in Rehabilitation Sheba Medical CenterRamat Gan 5265601Israel Department of Sport Exercise and RehabilitationNorthumbria UniversityNewcastle upon Tyne NE18STUK

Background:Near-infrared spectroscopy(NIRS)technology has allowed for the measurement of cerebral and skeletal muscle oxygenation simultaneously during *** this technology has been growing and is now successfully used in laboratory and sports settings,this systematic review aimed to synthesize the evidence and enhance an integrative understanding of bloodﬂow adjustments and oxygen(O_(2))changes(i.e.,the balance between O_(2) delivery and O_(2) consumption)within the cerebral and muscle systems during ***:A systematic review was conducted using PubMed,Embase,Scopus,and Web of science databases to search for relevant studies that simultaneously investigated cerebral and muscle hemodynamic changes using the near-infrared spectroscopy system during *** review considered manuscripts written in English and available before February 9,*** step of screening involved evaluation by 2 inde-pendent authors,with disagreements resolved by a third *** Joanna Briggs institute Critical Appraisal Checklist was used to assess the methodological quality of the ***:Twenty studies were included,of which 80%had good methodological quality,and involved 290 young or middle-aged *** types of exercises were used to assess cerebral and muscle hemodynamic changes,such as cycling(n=11),treadmill(n=1),knee extension(n=5),isometric contraction of biceps brachii(n=3),and duet swim routines(n=1).The cerebral hemodynamics anal-ysis was focused on the frontal cortex(n=20),while in the muscle,the analysis involved vastus lateralis(n=18),gastrocnemius(n=3),biceps brachii(n=5),deltoid(n=1),and intercostal muscle(n=1).Overall,muscle deoxygenation increases during exercise,reaching a plateau in voluntary exhaustion,while in the brain,oxyhemoglobin concentration increases with exercise intensity,reaching a plateau or declining at the exhaustion ***:Muscle and cerebral oxygenation respond differently to exercise,with muscle

关键词： Near-infrared spectroscopy Hemodynamic Blood flow Brain Muscle metabolism

探索Bi_(2)SeO_(5)的高介电性能:从块体到双层和单层

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science China Materials 2024年第3期67卷 906-913页

作者：董欣月何育彧管乐祝元昊吴金雄付会霞颜丙海 Tianjin Key Lab for Rare Earth Materials and Applications Center for Rare Earth and Inorganic Functional MaterialsSmart Sensor Interdisciplinary Science CenterSchool of Materials Science and EngineeringNankai UniversityTianjin 300350China Center of Quantum Materials and Devices College of PhysicsChongqing UniversityChongqing 401331China Chongqing Key Laboratory for Strongly Coupled Physics Chongqing UniversityChongqing 401331China Department of Condensed Matter Physics Weizmann Institute of ScienceRehovot 7610001Israel

Bi_(2)SeO_(5)是一种具有优异电绝缘性能的范德华(vdW)层状介电材料,引起了极大关注.然而,目前关于Bi_(2)SeO_(5)的研究主要停留在实验层面,仍然缺乏对其原子级薄膜的介电性能的相关理论认识.本文通过第一性原理计算确定了Bi_(2)SeO_(5... 详细信息

Bi_(2)SeO_(5)是一种具有优异电绝缘性能的范德华(vdW)层状介电材料,引起了极大关注.然而,目前关于Bi_(2)SeO_(5)的研究主要停留在实验层面,仍然缺乏对其原子级薄膜的介电性能的相关理论认识.本文通过第一性原理计算确定了Bi_(2)SeO_(5)的介电性能,发现其块体、双层和单层均具有超高平均介电常数(εr>20).研究表明,单层Bi_(2)SeO_(5)与双层Bi_(2)O_(2)Se之间的导带和价带能量偏移量均大于1 eV,表明单层Bi_(2)SeO_(5)依然可作为原子薄Bi_(2)O_(2)Se的良好介电层.此外,不同于h-BN或其他2D vdW绝缘体,Bi_(2)SeO_(5)的εr由其离子部分主导,且随着厚度的减小几乎保持不变.计算发现,单层Bi_(2)SeO_(5)的等效氧化层厚度可薄至0.3 n m,且单层Bi_(2)SeO_(5)在拉伸或压缩应变达到6%时均能保持高介电常数,这极大地促进了它与各种二维半导体的集成.本工作证明单层Bi_(2)SeO_(5)可以作为高性能二维电子器件良好的封装和介电层.

关键词： Bi_(2)SeO_(5) high-κ equivalent oxide thickness dielectric constant van der Waals first-principles calculations

From non-alcoholic fatty liver disease to metabolic-associated steatotic liver disease:Rationale and implications for the new terminology

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World Journal of Hepatology 2024年第6期16卷 863-866页

作者： Stephen David Howard Malnick Doron Zamir Department of Internal Medicine C Kaplan Medical CenterRehovot 76100Israel Department of Internal Medicine D Barzilai Medical CenterAshkelon 7830604Israel

Non-alcoholic fatty liver disease(NAFLD)was the term first used to describe hepatic steatosis in patients with the metabolic syndrome who did not consume excess amounts of *** liver disease(ALD)has many similarities to NAFLD in both pathogenesis and *** entity is now the most prevalent chronic liver disease worldwide as a consequence of the epidemic of *** to incorporate the importance of the metabolic syndrome in the development of steatosis resulted in the renaming of NAFLD as metabolic-associated fatty liver *** new term,however,has the disadvantage of the use of terms that may be perceived as *** terms fatty and non-alcoholic have negative connotations in many *** addition,non-alcoholic is not usually a term applicable to pediatric cases of hepatic ***,an international collaborative effort,with participants from 56 countries,after a global consultation process,recommended to change the nomenclature to steatotic liver disease-including metabolic dysfunction-associated steatotic liver disease,metabolic-associated steatohepatitis and metabolic dysfunction-associated *** new terminology is consistent with most of the previously published epidemiological studies and will have a major impact on research into diagnosis,prognosis and treatment.

关键词： Non-alcoholic fatty liver disease Steatosis metabolic-associated steatotic liver disease Nomenclature

Control of electron beam current,charge,and energy spread using density downramp injection in laser wakefield accelerators

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Matter and Radiation at Extremes 2023年第2期8卷 14-24页

作者： Céline S.Hue Yang Wan Eitan Y.Levine Victor Malka Department of Physics of Complex Systems Weizmann Institute of ScienceRehovotIsrael

Density downramp injection has been demonstrated to be an elegant and efficient approach for generating high-quality electron beams in laser wakefield *** studies have demonstrated the possibilities of generating electron beams with charges ranging from tens to hundreds of picocoulombs while maintaining good beam ***,the plasma and laser parameters in these studies have been limited to specific ranges or attention has been focused on separate physical processes such as beam loading,which affects the uniformity of the accelerating field and thus the energy spread of the trapped electrons,the repulsive force from the rear spike of the bubble,which reduces the transverse momentum P⊥of the trapped electrons and results in small beam emittance,and the laser evolution when traveling in the *** this work,we present a comprehensive numerical study of downramp injection in the laser wakefield,and we demonstrate that the current profile of the injected electron beam is directly correlated with the density transition parameters,which further affects the beam charge and energy *** fine-tuning the plasma density parameters,electron beams with high charge(up to several hundreds of picocoulombs)and low energy spread(around 1%FWHM)can be *** these results are supported by large-scale quasi-threedimensional particle-in-cell *** anticipate that the electron beams with tunable beam properties generated using this approach will be suitable for a wide range of applications.

关键词： tuning beam injection

Hydration Lubrication in Biomedical Applications:From Cartilage to Hydrogels

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Accounts of Materials Research 2022年第2期3卷 213-223页

作者： Weifeng Lin Jacob Klein Department of Molecular Chemistry and Materials science Weizmann Institute of ScienceRehovot 76100Israel

CONSPECTUS:In the course of evolution,nature has achieved remarkably lubricated surfaces,with healthy articular cartilage in the major(synovial)joints being the prime example,that can last a lifetime as they slide past each other with ultralow friction(friction coefficientμ=the force to slide surfaces past each other/load compressing the surfaces<0.01)under physiological pressures(up to 10 MPa or more)).Such properties are unmatched by any man-made *** precise mechanism of low friction between such sliding cartilage tissues,which is closely related to osteoarthritis(OA),the most widespread joint disease,affecting hundreds of millions worldwide,has been studied for nearly a century,but is still not fully ***,the roles of load bearing by interstitial fluid within the cartilage bulk and that of thin exuded fluid films at the interface between the sliding cartilage surfaces have been proposed as the main lubrication *** recent work,however,suggests that molecular boundary layers at the surfaces of articular cartilage and other tissues play a major role in their *** particular,in recent years hydration lubrication has emerged as a new paradigm for boundary lubrication in aqueous media based on subnanometer hydration shells which massively reduce frictional *** vectors of hydration lubrication include trapped hydrated ions,hydrated surfactants,biological macromolecules,biomimetic polymers,polyelectrolytes and polyzwitterionic brushes,and close-packed layers of phosphatidylcholine(PC)vesicles,all having in common the exposure of highly hydrated groups at the slip *** them,vesicles(or bilayers)of PC lipids,which are the most widespread lipid class in mammals,are exceptionally efficient lubricating elements as a result of the high hydration of the phosphocholine headgroups they *** lipids are ubiquitous in joints,leading to the proposal that macromolecular surface complexes exposing PC bilayers

关键词： hydration frictional exceptional

多带笼目超导体CsV_(3)Sb_(5)衍生体系的可调磁通涡旋束缚态

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science Bulletin 2024年第7期69卷 885-892页

作者：黄子豪韩相和赵振刘锦锦李鹏飞谭恒心王秩伟姚裕贵杨海涛颜丙海蒋坤胡江平汪自强陈辉高鸿钧 Beijing National Center for Condensed Matter Physics Institute of PhysicsChinese Academy of SciencesBeijing 100190China School of Physical sciences University of Chinese Academy of SciencesBeijing 100190China Centre for Quantum Physics Key Laboratory of Advanced Optoelectronic Quantum Architecture and Measurement(MOE)School of PhysicsBeijing Institute of TechnologyBeijing 100081China Beijing Key Lab of Nanophotonics and Ultrafine Optoelectronic Systems Beijing Institute of TechnologyBeijing 100081China Department of Condensed Matter Physics Weizmann Institute of ScienceRehovot 7610001Israel Hefei National Laboratory Hefei 230088China Department of Physics Boston CollegeChestnut Hill MA 02467USA

Vortices and bound states offer an effective means of comprehending the electronic properties of ***,surface-dependent vortex core states have been observed in the newly discovered kagome superconductors CsV_(3)Sb_(5).Although the spatial distribution of the sharp zero energy conductance peak appears similar to Majorana bound states arising from the superconducting Dirac surface states,its origin remains *** this study,we present observations of tunable vortex bound states(VBSs)in two chemically-doped kagome superconductors Cs(V_(1-x)Tr_(x))_(3)Sb_(5)(Tr=Ta or Ti),using low-temperature scanning tunneling microscopy/*** CsV_(3)Sb_(5)-derived kagome superconductors exhibit full-gap-pairing superconductivity accompanied by the absence of long-range charge orders,in contrast to pristine CsV_(3)Sb_(5).Zero-energy conductance maps demonstrate a field-driven continuous reorientation transition of the vortex lattice,suggesting multiband *** Ta-doped CsV_(3)Sb_(5)displays the conventional cross-shaped spatial evolution of Caroli-de Gennes-Matricon bound states,while the Tidoped CsV_(3)Sb_(5)exhibits a sharp,non-split zero-bias conductance peak(ZBCP)that persists over a long distance across the *** spatial evolution of the non-split ZBCP is robust against surface effects and external magnetic field but is related to the doping *** study reveals the tunable VBSs in multiband chemically-doped CsV_(3)Sb_(5)system and offers fresh insights into previously reported Y-shaped ZBCP in a non-quantum-limit condition at the surface of kagome superconductor.

关键词： Kagome superconductor Chemical doping Vortex lattice transition Vortex bound states Majorana bound states

Fast UV-vis-NIR photoresponse of self-oriented F_(16)CuPc nanoribbons

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Nano Research 2023年第7期16卷 9561-9568页

作者： Lingyu Zhang Xingyu Wang Wei Zhou Hao Wang Jiaxun Song Zihao Zhao Jihui Liao Jian Song Yajun Li Jinyou Xu institute of Electronic Paper Displays South China Academy of Advanced OptoelectronicsSouth China Normal UniversityGuangzhou 510006China Department of Materials and Interfaces Weizmann Institute of ScienceRehovot 76100Israel

Controlling the vapor-deposited nanoribbons to grow along a consistent orientation will enable the desired in situ integration of functional devices,representing a major technological advance compared to post-growth processing *** this work,ntype F_(16)CuPc molecules are self-assembled into horizontally-oriented nanoribbons with a consistent growth axis after creating periodic hydrophobic nanogrooves on a sapphire ***,electrodes are deposited directly on the growth substrate to enable in situ fabrication of *** on the deposited electrodes,these horizontally-oriented nanoribbons are connected to form a monolithic photodetector with a large sensing area or an on-chip array of photodetectors with multiple detector *** in situ integration strategy avoids potential structural damage and contamination from impurities associated with post-growth processing ***,the vapor-deposited nanoribbons can retain their high quality during the device manufacturing process,which contributes to performance *** a result,the in-situ integrated F_(16)CuPc photodetectors exhibit a sensitive response in the ultraviolet-visible-near-infrared(UV-vis-NIR)*** response time is on the order of tens of milliseconds,the fastest record ever for the F_(16)CuPc-based ***,statistics from an array of 6×6 photodetectors show little variation in their sensitivity and response time,and hence this in situ fabrication scheme will contribute to the implementation of on-chip integrated photodetectors with consistent performance based on bottom-up ***,this self-oriented growth provides a versatile option to achieve desired in-situ integrated functional devices based on bottom-up nanoribbons.

关键词： fluorinated copper phthalocyanine nanoribbon planar array photodetector in situ integration