Several related substances were detected at trace level in (2R)-2,3-dihydro-2-methyl-6-nitro-2-[[4-[4-[4-(trifluoromethoxy)phenoxy]-1-piperidinyl] phenoxy] methyl]imidazo[2, 1-b]oxazole drug substance by a newly devel...Several related substances were detected at trace level in (2R)-2,3-dihydro-2-methyl-6-nitro-2-[[4-[4-[4-(trifluoromethoxy)phenoxy]-1-piperidinyl] phenoxy] methyl]imidazo[2, 1-b]oxazole drug substance by a newly developed high-performance liquid chromatography method. All related substances were characterized rapidly but some impurities were found to be intermediates. Proposed structures were further confirmed by characterization using NMR, FT-IR, and HRMS techniques. Based on the spectroscopic data;unknown related sub-stances were characterized as 1-(Methylsulfonyl)-4-[4-(trifluoromethoxy) phenoxy]piperidine;4-{4-[4-(Tri-fluoromethoxy)-phenoxy]piperidin-1-yl}phenol and 4-{4-[4-(trifluoromethoxy)phenoxy]piperidin-1-yl}phenyl methane sulfonate;4-Bromophenyl methane sulfonate, Ethyl 3,6-dihydro-1(2H)-pyridine carboxylate, (2S)-3-(4-Bromophenoxy)-2-hydroxy-2-methylpropyl methane sulfonate, (2S)-3-(4-Bromophenoxy)-2-methylpropane-1,2-diyldimethane-sulfonate, (2S)-2-Methyl-3-(4-{4-[4-(trifluoromethoxy) phenoxy]-piperidin-1-yl} phenoxy)-propane-1,2-diyldimethane sulfonate, (S)-3-(4-Bromophenoxy)-2-methyl-propane-1,2-diol and corresponding Enantiomer, (2R)-2-[(4-Bromo-phenoxy)methyl]-2-methyloxirane and (2R)-2-[(4-bromophenoxy)methyl]-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole. A possible mechanism for the formation of these related substances is also proposed.展开更多
A brief review of the works of the author and his co-authors on the application of nonlinear analysis, numerical and analytical methods for solving the nonlinear inverse problems (synthesis problems) for optimizing th...A brief review of the works of the author and his co-authors on the application of nonlinear analysis, numerical and analytical methods for solving the nonlinear inverse problems (synthesis problems) for optimizing the different types of radiating systems, is presented in the paper. The synthesis problems are formulated in variational statements and further they are reduced to research and numerical solution of nonlinear integral equations of Hammerstein type. The existence theorems are proof, the investigation methods of nonuniqueness problem of solutions and numerical algorithms of finding the optimal solutions are proved.展开更多
Nitrogenous compounds(i.e.,amines,amides,nitriles,oximes,amino acids and nitrogen-heterocycles derivatives)are important building blocks for synthetic chemistry,pharmaceuticals,and functional materials.Conventional sy...Nitrogenous compounds(i.e.,amines,amides,nitriles,oximes,amino acids and nitrogen-heterocycles derivatives)are important building blocks for synthetic chemistry,pharmaceuticals,and functional materials.Conventional synthetic strategies involve the use of toxic organic nitrogenous precursors or expensive heterogeneous catalysts under elevated temperatures and pressurized oxygen.Heterogeneous electrocatalysis can initiate the activation of inorganic N sources(i.e.,NH_(3)and NO^(-)_(x))under ambient reactions in liquid phase by applying a small bias,thus allowing the synthesis of value?added nitrogenous compounds from carbonyls,alkenes,keto acids,and even carbon dioxide in a sustainable manner without the use of oxidants/reductants.This review outlines recent de-velopments in electrosynthesis of nitrogenous compounds using inorganic N sources,focusing on reaction mechanisms understanding,the design and optimization of efficient electrocatalysts,and the advances in cell configurations for various C‒N coupling reactions.The limitations and challenges in applications are also discussed.展开更多
For decades,the central dogma of oncology has been that a cancer’s identity is inextricably linked to its anatomical origin.This principle underpins the entire diagnostic and therapeutic framework,from histology-base...For decades,the central dogma of oncology has been that a cancer’s identity is inextricably linked to its anatomical origin.This principle underpins the entire diagnostic and therapeutic framework,from histology-based classification to site-specific treatment guidelines.Yet,this framework catastrophically fails for a substantial population of patients diagnosed with cancer of unknown primary(CUP).These patients present metastatic disease,yet their primary tumors remain elusive despite exhaustive clinical workup1.CUP,accounting for 1%-3%of all cancer diagnoses,is an enigma with devastating consequences;the median overall survival is only 2-12 months2-4.The inability to pinpoint an origin forces clinicians to rely on broad-spectrum empirical chemotherapy,such as taxane-carboplatin regimens,which have limited efficacy and exclude patients from the promise of targeted therapies and clinical trials5.CUP is not only a diagnostic challenge but also an indictment of the siloed approach to understanding malignancy:this cancer highlights the limitations of origin-based diagnostic frameworks.However,the confluence of high-dimensional biological data and advanced artificial intelligence(AI)is now poised to address this long-standing diagnostic limitation and to herald a new era for not only CUP but also oncology as a whole(Figure 1).展开更多
Pseudomonas aeruginosa is an opportunistic pathogen responsible for severe nosocomial infections.This multidrug-resistant bacterium can cause pneumonia and cystic fibrosis,both of which are associated with high morbid...Pseudomonas aeruginosa is an opportunistic pathogen responsible for severe nosocomial infections.This multidrug-resistant bacterium can cause pneumonia and cystic fibrosis,both of which are associated with high morbidity and mortality rates.The lipopolysaccharide of P.aeruginosa serves as an attractive target for the development of effective glycoconjugate vaccines.In this article,we report the first chemical synthesis of the highly challenging tetrasaccharide repeating unit of the P.aeruginosa serotype O3 O-antigen using a two-directional[1+(2+1)]glycosylation strategy.The synthesis is particularly challenging due to the poor nucleophilicity of the axial C4 hydroxyl group of l-galactose and the steric hindrance imposed by the 3S-hydroxybutyryl(Hb)chain.Furthermore,the presence of an acetyl group at the ortho position relative to the glycosylation site on l-galactose can lead to undesirable acetyl migration.Additionally,it is noteworthy that the selective removal of a 2-naphthylmethyl ether(Nap)during the late stages of synthesis,particularly in the presence of multiple benzyl groups,can be somewhat challenging to predict.Through the careful selection of synthetic strategies,building blocks,and optimized reaction conditions,we achieved the stereoselective glycosylations,selective oxidation of primary alcohols,remarkable enhancement of acceptor activity,and efficient introduction of the 3S-Hb group.The synthetic methodology presented in this work serves as a valuable reference for the preparation of structurally related oligosaccharides.By incorporating an aminopropyl linker,the target tetrasaccharide facilitates glycan microarray preparation and in vivo immunological assessments,thereby accelerating progress toward a synthetic glycoconjugate vaccine for P.aeruginosa.展开更多
The formaidehyde-free finishing agent 4,5-di-hydroxy-1,3-dimethy1-2-imidazolidinone(DMeDHEU)was prepared by the reaction of 1,3-dimethylurea and glyoxal.The reaction rate and equilib-rium conversion in relation to pH ...The formaidehyde-free finishing agent 4,5-di-hydroxy-1,3-dimethy1-2-imidazolidinone(DMeDHEU)was prepared by the reaction of 1,3-dimethylurea and glyoxal.The reaction rate and equilib-rium conversion in relation to pH value,molar ratio,temperature and catalyst were studied.The conversionto DMeDHEU,catalyzed with citric acid/anhydrousNaAc,reached 95% in 6 hours at 40℃, pH 5.5 andmolar ratio 1.2.展开更多
We report an immobilized enzyme-catalyzed batch and continuous-flow synthesis of optically pure ethyl(R)-pantothenate((R)-PaOEt),the direct precursor of d-pantothenic acid.Firstly,a ketoreductase mutant designated as ...We report an immobilized enzyme-catalyzed batch and continuous-flow synthesis of optically pure ethyl(R)-pantothenate((R)-PaOEt),the direct precursor of d-pantothenic acid.Firstly,a ketoreductase mutant designated as M2,carrying two-point mutations of F97L and M242F relative to the wild-type SSCR,was constructed by site-directed mutagenesis,exhibited simultaneously improved activity toward ethyl 2′-ketopantothenate(K-PaOEt)and isopropanol,and could effectively catalyze the stereoselective reduction of K-PaOEt to(R)-PaOEt by using isopropanol as the sacrificial co-substrate to regenerate NADPH.After screening six commercially available carriers,an amino resin LXTE-700 was identified as the best solid support for the immobilization of M2 via the glutaraldehyde activation method.Upon optimization of the immobilization process and reaction conditions,the fabricated immobilized enzyme M2@amino resin demonstrated excellent recyclability and reusability,with the complete conversion of K-PaOEt to(R)-PaOEt being still realized after 12 cycles of reuse.Finally,M2@amino resin-catalyzed synthesis of(R)-PaOEt was successfully implemented in continuous-flow,accomplishing a 6.3 times higher space-time yield than that with the batch synthesis(529.2 versus 84 g L^(-1) d^(-1)).Our developed flow biocatalysis system also features an outstanding operational stability,as evidenced by the 100%conversion rate achieved after 15 consecutive days of operation.展开更多
This report provides for the first time rapid novel environment friendly cell surface based synthesis of stable gold nanoprisms at room temperature using Penicillium citrinum MTCC9999 biomass. The UV-Visible spectral ...This report provides for the first time rapid novel environment friendly cell surface based synthesis of stable gold nanoprisms at room temperature using Penicillium citrinum MTCC9999 biomass. The UV-Visible spectral scan of dispersed gold nanoparticles (GNPs) solution showed absorption maxima at 540 nm due to surface plasma resonance (SPR) of gold nanoparticles. Typical Transmission Electron Microscopic (TEM) images showed that most of them were prism (55%) shaped with a diameter ranging from 20 - 40 nm. These results obtained from TEM correlated well with the data obtained from Dynamic Light Scattering (DLS) experiment. Average zeta potential of GNPs was -20 mV suggesting some biomolecules capped the nanoparticles imparting a net negative charge over it. FTIR analysis also showed that protein molecules were involved in stabilization.展开更多
The deuterium labeling has garnered significant interest in drug discovery due to its critical role on improving pharmacokinetic and metabolic properties.However,despite its pharmaceutical value,the general and rapid ...The deuterium labeling has garnered significant interest in drug discovery due to its critical role on improving pharmacokinetic and metabolic properties.However,despite its pharmaceutical value,the general and rapid syntheses of aromatic scaffolds that contains deuterium remain an important yet elusive task.State-of-the-art approaches mainly relied on the transition metal-catalyzed C-H deuteration via the assistance of directing groups(DGs),which often suffered from over-deuteration and lengthy step counts required for installation and/or removal of DG.Herein,we report a generalizable synthetic linchpin strategy for the facile preparation of the ortho-deuterated aromatic core.Through capture of aryne-derived 1,3-zwitterion with heavy water,we synthesized an array of ortho-deuterated aryl sulfonium salts.These novel linchpins not only participated the transition metal catalyzed cross-coupling reaction as nucleophiles,but also served as aryl radical reservoirs under photochemical or electrochemical conditions,enabling facile and precise access to structurally diverse deuterated aromatics.Moreover,we have disclosed a novel EDA complex enabled direct arylation of phosphines under visible-light irradiation,further expanding the utility of our platform approach.展开更多
The nucleus-initiated augmentation of ER membrane is reflected in a coordinated synthesis and intercalation of the explicit proteins and lipids required for the replacement, repair and function of the cell and its org...The nucleus-initiated augmentation of ER membrane is reflected in a coordinated synthesis and intercalation of the explicit proteins and lipids required for the replacement, repair and function of the cell and its organelles. The direct connection between nucleus and the membranes containing labeled sphingosine (SphN) and ceramide (Cer) was affirmed by determining synthetic activity of serine palmitoyltransferase (SPT). The SPT and the newly synthesized serine-labeled lipid products were identified in the Outer- and Inner-Nuclear Membrane (ONM, INM) and ER. The pulse-chase experiments disclosed that the incorporation of radiolabeled lipids into both nuclear membranes declined upon their simultaneous increase in Endoplasmic Reticulum (ER). These results, and prior findings regarding metabolic transfer of nuclear membrane phosphoinositides to the outer leaflet of ER [Slomiany and Slomiany, Health, 2011, 3, 187-199], allowed us to reason that INM and ONM are not distinct entities, but uninterrupted continuum facing nucleosol and then cytosol when protracted into segment known as ER. Consequently, the identification of SPT and its products in the inner leaflet of nuclear and ER microsomes lent credence to the luminal presence of Cer in Golgi, luminal synthesis of glycosphingolipids (GSphLs), sphingomyelin (SM), and their delivery to the outer leaflet of apical and basolateral cell membrane, respectively. The findings presented in this communication provide further support to our concept that the factual intercalation of proteins and lipids into the cell membranes can only take place during their simultaneous synthesis that is guided by the nuclear and cytosolic processes enacted in nuclear-ER membrane continuum. At the nuclear stage, the signal-specific genes expression promotes active synthesis and intercalation of lipids into the organelles’ customized membrane that is protracted and articulated in ER in form of transport vesicles.展开更多
This paper realizes a sign language-to-speech conversion system to solve the communication problem between healthy people and speech disorders. 30 kinds of different static sign languages are firstly recognized by com...This paper realizes a sign language-to-speech conversion system to solve the communication problem between healthy people and speech disorders. 30 kinds of different static sign languages are firstly recognized by combining the support vector machine (SVM) with a restricted Boltzmann machine (RBM) based regulation and a feedback fine-tuning of the deep model. The text of sign language is then obtained from the recognition results. A context-dependent label is generated from the recognized text of sign language by a text analyzer. Meanwhile,a hiddenMarkov model (HMM) basedMandarin-Tibetan bilingual speech synthesis system is developed by using speaker adaptive training.The Mandarin speech or Tibetan speech is then naturally synthesized by using context-dependent label generated from the recognized sign language. Tests show that the static sign language recognition rate of the designed system achieves 93.6%. Subjective evaluation demonstrates that synthesized speech can get 4.0 of the mean opinion score (MOS).展开更多
Among various architectures of polymers,end-group-free rings have attracted growing interests due to their distinct physicochemical performances over the linear counterparts which are exemplified by reduced hydrodynam...Among various architectures of polymers,end-group-free rings have attracted growing interests due to their distinct physicochemical performances over the linear counterparts which are exemplified by reduced hydrodynamic size and slower degradation.It is key to develop facile methods to large-scale synthesis of polymer rings with tunable compositions and microstructures.Recent progresses in large-scale synthesis of polymer rings against single-chain dynamic nanoparticles,and the example applications in synchronous enhancing toughness and strength of polymer nanocomposites are summarized.Once there is the breakthrough in rational design and effective large-scale synthesis of polymer rings and their functional derivatives,a family of cyclic functional hybrids would be available,thus providing a new paradigm in developing polymer science and engineering.展开更多
To solve the problem of robust servo performance of Flight Environment Testbed(FET)of Altitude Ground Test Facilities(AGTF) over the whole operational envelope, a two-degree-offreedom μ synthesis method based on Line...To solve the problem of robust servo performance of Flight Environment Testbed(FET)of Altitude Ground Test Facilities(AGTF) over the whole operational envelope, a two-degree-offreedom μ synthesis method based on Linear Parameter Varying(LPV) schematic is proposed, and meanwhile a new structure frame of μ synthesis control on two degrees of freedom with double integral and weighting functions is presented, which constitutes a core support part of the paper. Aimed at the problem of reference command's rapid change, one freedom feed forward is adopted, while another freedom output feedback is used to meet good servo tracking as well as disturbance and noise rejection; furthermore, to overcome the overshoot problem and acquire dynamic tuning,the integral is introduced in inner loop, and another integral controller is used in outer loop in order to guarantee steady errors; additionally, two performance weighting functions are designed to achieve robust specialty and control energy limit considering the uncertainties in system. As the schedule parameters change over large flight envelope, the stability of closed-loop LPV system is proved using Lyapunov inequalities. The simulation results show that the relative tracking errors of temperature and pressure are less than 0.5% with LPV μ synthesis controller. Meanwhile, compared with non-LPV μ synthesis controller in large uncertainty range, the proposed approach in this research can ensure robust servo performance of FET over the whole operational envelope.展开更多
ADPr-ATP is a natural nucleotide with three sugar rings and five pentavalent phosphorus,and can be produced through TIR-catalyzed ADP-ribosylation reactions for plant immunity.Here,we report the first total synthesis ...ADPr-ATP is a natural nucleotide with three sugar rings and five pentavalent phosphorus,and can be produced through TIR-catalyzed ADP-ribosylation reactions for plant immunity.Here,we report the first total synthesis of ADPr-ATP(1)with a total yield of 6.4%through 14 steps,featuring late-stage P(V)−N activation reaction of pyrophosphate(4)and 5′-phosphoromorpholidate(25).The protected adenosine 5′-phosphoromorpholidate(24)was prepared on the basis of a scalable to adenosine 5′′-monophosphate(2).The construction of P(V)−N bond in phosphoramidate is esteemed as a critical step as they are sufficiently stable in deprotection reactions.The chemical synthesis of ADPr-ATP can offer an appealing alternative to traditional enzymatic synthesis and fractionation methods.Furthermore,the pRib-AMP and its prodrug are also synthesized to evaluate cytotoxicity and anti-influenza activity in vitro.展开更多
Conjugated microporous polymers(CMPs)are a unique class of organic porous materials characterized byπ-conjugated structures and permanent micropores,distinguishing them from non-porous polymers and conventionalπ-con...Conjugated microporous polymers(CMPs)are a unique class of organic porous materials characterized byπ-conjugated structures and permanent micropores,distinguishing them from non-porous polymers and conventionalπ-conjugated polymers.CMPs offer extensive versatility in synthetic approaches,enabling the synthesis of cross-linked and mesoporous structures.Advances in chemical processes,structural design,and synthesis methodologies have been developed,resulting in a diverse range of CMPs with unique configurations and properties,contributing to the fast expansion of the field.CMPs are particularly notable for their ability to enable the competitive utilization ofπ-conjugated structures within mesoporous configurations,making them valuable for investigations across various domains.They have shown considerable promise in addressing fuel and environmental challenges,demonstrated by their exceptional performance in applications such as vapor adsorption,heterogeneous catalysis,light emission,light harvesting,and energy generation.This review examines the chemical engineering principles underlying CMPs,including synthesis approaches,systemic research advancements,multifunctional investigations boundaries,potential applications,and progress in synthesis,dimensionality,and morphology studies.Specifically,it offers a comparative analysis of CMPs and linear polymeric materials,aiding in the development of functional polymers.Furthermore,this review explores the primary fundamental limitations of CMPs in fuel-related domains and discusses alternative strategies,including novel synthesis methods incorporating interactions and morphologies,to address these challenges.Ultimately,this assessment aims to provide a valuable and inspiring resource for professionals in the field of fuel management,guiding future research and development efforts.展开更多
α-Chiral amides are common in pharmaceuticals,agrochemicals,natural products,and peptides,prompting the need for new synthetic methods.Here,we introduce a nickel-catalyzed asymmetric reductive amidation method to syn...α-Chiral amides are common in pharmaceuticals,agrochemicals,natural products,and peptides,prompting the need for new synthetic methods.Here,we introduce a nickel-catalyzed asymmetric reductive amidation method to synthesizeα-chiral amides from benzyl ammonium salts and isocyanates.The key to success is using a chiral 2,2-bipyridine ligand(-)-Ph-SBpy,enabling high yield(up to 95%)and enantiomeric ratio(up to 98:2 er)under mild conditions.Addition of phenol prevents isocyanate polymerization by reversibly forming a carbamate intermediate,enhancing selectivity and efficiency.The synthetic utility is showcased through transformations of the enantioenriched amides,and the mechanism and enantioselectivity are supported by experimental and computational studies.展开更多
Structural engineering of Pt-based nanoalloys is crucial for the rational design and manufacturing of high-performance and low-cost electrocatalysts for hydrogen evolution reaction(HER).Here,we reported PtNi nanoparti...Structural engineering of Pt-based nanoalloys is crucial for the rational design and manufacturing of high-performance and low-cost electrocatalysts for hydrogen evolution reaction(HER).Here,we reported PtNi nanoparticles with a refined size of 2.71 nm and regular strains loaded on carbon black,synthesized using the high-temperature liquid shock(HTLS)method.This approach offers significant advantages over conventional synthesis methods,including high scalability,rapid reaction rates,and precise control over the size and shape of nanocrystals.Importantly,the synthesized PtNi electrocatalysts demonstrate outstanding catalytic activity and long-term stability for HER,achieving low overpotentials of 19 and 203 mV at current densities of 10 and 1000 mA/cm^(2),respectively.The superior performance can be attributed to the combination of a refined particle size,lattice strains,and synergistic effects between Pt and Ni.This rapid liquid-state synthesis demonstrated here holds great potential for scalable and industrial manufacturing of micro-/nano-catalysts.展开更多
High temperature stress (HT) significantly reduces maize yield by impairing starch accumulation in kernels.However,the mechanism by which HT affects starch synthesis remains controversial-whether through reduced assim...High temperature stress (HT) significantly reduces maize yield by impairing starch accumulation in kernels.However,the mechanism by which HT affects starch synthesis remains controversial-whether through reduced assimilate supply or direct inhibition on kernel metabolism.To clarify these mechanisms,a heat-sensitive maize hybrid,Xianyu 335 (XY),was exposed to 30℃/20℃ (maximum/minimum temperature,control) and 40℃/30℃ for seven consecutive days during the seed setting stage.Synchronous pollination (SP),apical pollination (AP),and shading treatments were applied to manipulate the inherent source–sink ratio in maize plants.Results showed that apical kernel weight decreased by 11.9%under 40℃ in the SP treatment.The ^(13)C content,starch accumulation,and cell-wall invertase (CWIN) activity also declined by 15.9,36.7,and 16.4%,respectively,under HT.In the shading treatment,40℃/30℃ caused even greater reductions in^(13)C content,starch accumulation,and CWIN activity due to diminished assimilate supply.Conversely,in the AP treatment,starch content and CWIN activity increased by 22.0 and 18.5%,respectively,under 40℃/30℃,resulting in kernel weight and ^(13)C content similar to those in SP and shading treatments regardless of temperature.Consistent with apical kernels under AP,HT did not negatively affect middle kernels in either SP or shading treatments,as kernel weight and starch content remained unchanged under HT.Although all kernels were exposed to the same HT or control environment,their responses varied a lot.The impaired starch synthesis in apical kernels under HT was rescued by increasing carbon supply via AP treatment.The contrasting performance among middle kernels,apical kernels under AP,and apical kernels under SP or shading indicates that reduced carbon supply is a critical factor underlying inhibited starch accumulation.Our findings provide a theoretical basis for further understanding kernel abortion under HT.展开更多
The two-electron electrochemical oxygen reduction reaction(ORR)affords an appealing alternative for on-site production of hydrogen peroxide(H_(2)O_(2)),which can fulfill the demands of various applications even at low...The two-electron electrochemical oxygen reduction reaction(ORR)affords an appealing alternative for on-site production of hydrogen peroxide(H_(2)O_(2)),which can fulfill the demands of various applications even at low concentrations.Under neutral or near-neutral conditions,the electrolyte environment capable of electrochemically synthesizing H_(2)O_(2) exhibits diversity and holds vast potential for practical applications;however,the electrocatalytic performance is limited without desirable electrode materials.In this contribution,methoxylated nickel hydroxides were proposed for high-performance on-site H_(2)O_(2) electrosynthesis in different potassium fertilizer solutions.The methoxylation compared to pristine Ni(OH)_(2) was demonstrated to optimize the electronic structure with favorable adsorption of reaction intermediates,obviously enhancing the activity and selectivity.In 0.10 M K_(2)SO_(4) solution,H_(2)O_(2) production ranged from 28.1 to 153.6 mg h^(-1) cm^(-2) at current densities of-50 to-250 mA cm^(-2),accompanied by Faradaic efficiency values exceeding 88.0%.An integrated system was devised by combining fertilization,disinfection,and irrigation through the coupling of two-electron ORR with agricultural irrigation,utilizing nutrient solutions as the electrolyte for on-site H_(2)O_(2) electrosynthesis.These findings afford a promising avenue for the practical application of 2e-ORR in neutral environments.展开更多
文摘Several related substances were detected at trace level in (2R)-2,3-dihydro-2-methyl-6-nitro-2-[[4-[4-[4-(trifluoromethoxy)phenoxy]-1-piperidinyl] phenoxy] methyl]imidazo[2, 1-b]oxazole drug substance by a newly developed high-performance liquid chromatography method. All related substances were characterized rapidly but some impurities were found to be intermediates. Proposed structures were further confirmed by characterization using NMR, FT-IR, and HRMS techniques. Based on the spectroscopic data;unknown related sub-stances were characterized as 1-(Methylsulfonyl)-4-[4-(trifluoromethoxy) phenoxy]piperidine;4-{4-[4-(Tri-fluoromethoxy)-phenoxy]piperidin-1-yl}phenol and 4-{4-[4-(trifluoromethoxy)phenoxy]piperidin-1-yl}phenyl methane sulfonate;4-Bromophenyl methane sulfonate, Ethyl 3,6-dihydro-1(2H)-pyridine carboxylate, (2S)-3-(4-Bromophenoxy)-2-hydroxy-2-methylpropyl methane sulfonate, (2S)-3-(4-Bromophenoxy)-2-methylpropane-1,2-diyldimethane-sulfonate, (2S)-2-Methyl-3-(4-{4-[4-(trifluoromethoxy) phenoxy]-piperidin-1-yl} phenoxy)-propane-1,2-diyldimethane sulfonate, (S)-3-(4-Bromophenoxy)-2-methyl-propane-1,2-diol and corresponding Enantiomer, (2R)-2-[(4-Bromo-phenoxy)methyl]-2-methyloxirane and (2R)-2-[(4-bromophenoxy)methyl]-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole. A possible mechanism for the formation of these related substances is also proposed.
文摘A brief review of the works of the author and his co-authors on the application of nonlinear analysis, numerical and analytical methods for solving the nonlinear inverse problems (synthesis problems) for optimizing the different types of radiating systems, is presented in the paper. The synthesis problems are formulated in variational statements and further they are reduced to research and numerical solution of nonlinear integral equations of Hammerstein type. The existence theorems are proof, the investigation methods of nonuniqueness problem of solutions and numerical algorithms of finding the optimal solutions are proved.
基金the NSFC(No.22472112)the Suzhou Foreign Academician Workstation(No.SWY2022001)for financial supportsthe Soochow Municipal Laboratory for Low Carbon Technologies and Industries.
文摘Nitrogenous compounds(i.e.,amines,amides,nitriles,oximes,amino acids and nitrogen-heterocycles derivatives)are important building blocks for synthetic chemistry,pharmaceuticals,and functional materials.Conventional synthetic strategies involve the use of toxic organic nitrogenous precursors or expensive heterogeneous catalysts under elevated temperatures and pressurized oxygen.Heterogeneous electrocatalysis can initiate the activation of inorganic N sources(i.e.,NH_(3)and NO^(-)_(x))under ambient reactions in liquid phase by applying a small bias,thus allowing the synthesis of value?added nitrogenous compounds from carbonyls,alkenes,keto acids,and even carbon dioxide in a sustainable manner without the use of oxidants/reductants.This review outlines recent de-velopments in electrosynthesis of nitrogenous compounds using inorganic N sources,focusing on reaction mechanisms understanding,the design and optimization of efficient electrocatalysts,and the advances in cell configurations for various C‒N coupling reactions.The limitations and challenges in applications are also discussed.
基金supported by the National Natural Science Foundation of China(Grant Nos.32270688,31801117,and 82430107 to X.L.,and 32500589 to H.S.)the China Postdoctoral Science Foundation(Grant Nos.BX20240253 and 2024M762384 to H.S.)+1 种基金the Natural Science Foundation of Tianjin(Grant No.24JCQNJC01280 to H.S.)Tianjin Key Medical Discipline(Specialty)Construction Project(Grant No.TJYXZDXK-3-003A).
文摘For decades,the central dogma of oncology has been that a cancer’s identity is inextricably linked to its anatomical origin.This principle underpins the entire diagnostic and therapeutic framework,from histology-based classification to site-specific treatment guidelines.Yet,this framework catastrophically fails for a substantial population of patients diagnosed with cancer of unknown primary(CUP).These patients present metastatic disease,yet their primary tumors remain elusive despite exhaustive clinical workup1.CUP,accounting for 1%-3%of all cancer diagnoses,is an enigma with devastating consequences;the median overall survival is only 2-12 months2-4.The inability to pinpoint an origin forces clinicians to rely on broad-spectrum empirical chemotherapy,such as taxane-carboplatin regimens,which have limited efficacy and exclude patients from the promise of targeted therapies and clinical trials5.CUP is not only a diagnostic challenge but also an indictment of the siloed approach to understanding malignancy:this cancer highlights the limitations of origin-based diagnostic frameworks.However,the confluence of high-dimensional biological data and advanced artificial intelligence(AI)is now poised to address this long-standing diagnostic limitation and to herald a new era for not only CUP but also oncology as a whole(Figure 1).
基金the National Key R&D Program of China(No.2023YFC2308000)the National Natural Science Foundation of China(Nos.22478153,22477046,22177041)+3 种基金the Max Planck Society International Partner Group Programthe China Scholarship Council(CSC)the Fundamental Research Funds for the Central Universities for fundingthe Max-Planck Society for generous financial support.
文摘Pseudomonas aeruginosa is an opportunistic pathogen responsible for severe nosocomial infections.This multidrug-resistant bacterium can cause pneumonia and cystic fibrosis,both of which are associated with high morbidity and mortality rates.The lipopolysaccharide of P.aeruginosa serves as an attractive target for the development of effective glycoconjugate vaccines.In this article,we report the first chemical synthesis of the highly challenging tetrasaccharide repeating unit of the P.aeruginosa serotype O3 O-antigen using a two-directional[1+(2+1)]glycosylation strategy.The synthesis is particularly challenging due to the poor nucleophilicity of the axial C4 hydroxyl group of l-galactose and the steric hindrance imposed by the 3S-hydroxybutyryl(Hb)chain.Furthermore,the presence of an acetyl group at the ortho position relative to the glycosylation site on l-galactose can lead to undesirable acetyl migration.Additionally,it is noteworthy that the selective removal of a 2-naphthylmethyl ether(Nap)during the late stages of synthesis,particularly in the presence of multiple benzyl groups,can be somewhat challenging to predict.Through the careful selection of synthetic strategies,building blocks,and optimized reaction conditions,we achieved the stereoselective glycosylations,selective oxidation of primary alcohols,remarkable enhancement of acceptor activity,and efficient introduction of the 3S-Hb group.The synthetic methodology presented in this work serves as a valuable reference for the preparation of structurally related oligosaccharides.By incorporating an aminopropyl linker,the target tetrasaccharide facilitates glycan microarray preparation and in vivo immunological assessments,thereby accelerating progress toward a synthetic glycoconjugate vaccine for P.aeruginosa.
文摘The formaidehyde-free finishing agent 4,5-di-hydroxy-1,3-dimethy1-2-imidazolidinone(DMeDHEU)was prepared by the reaction of 1,3-dimethylurea and glyoxal.The reaction rate and equilib-rium conversion in relation to pH value,molar ratio,temperature and catalyst were studied.The conversionto DMeDHEU,catalyzed with citric acid/anhydrousNaAc,reached 95% in 6 hours at 40℃, pH 5.5 andmolar ratio 1.2.
基金the Science and Technology R&D Major Project of Jiangxi Province(No.20244AFI92001)the National Natural Science Foundation of China(Nos.22071033 and 21801047)for the financial supports.
文摘We report an immobilized enzyme-catalyzed batch and continuous-flow synthesis of optically pure ethyl(R)-pantothenate((R)-PaOEt),the direct precursor of d-pantothenic acid.Firstly,a ketoreductase mutant designated as M2,carrying two-point mutations of F97L and M242F relative to the wild-type SSCR,was constructed by site-directed mutagenesis,exhibited simultaneously improved activity toward ethyl 2′-ketopantothenate(K-PaOEt)and isopropanol,and could effectively catalyze the stereoselective reduction of K-PaOEt to(R)-PaOEt by using isopropanol as the sacrificial co-substrate to regenerate NADPH.After screening six commercially available carriers,an amino resin LXTE-700 was identified as the best solid support for the immobilization of M2 via the glutaraldehyde activation method.Upon optimization of the immobilization process and reaction conditions,the fabricated immobilized enzyme M2@amino resin demonstrated excellent recyclability and reusability,with the complete conversion of K-PaOEt to(R)-PaOEt being still realized after 12 cycles of reuse.Finally,M2@amino resin-catalyzed synthesis of(R)-PaOEt was successfully implemented in continuous-flow,accomplishing a 6.3 times higher space-time yield than that with the batch synthesis(529.2 versus 84 g L^(-1) d^(-1)).Our developed flow biocatalysis system also features an outstanding operational stability,as evidenced by the 100%conversion rate achieved after 15 consecutive days of operation.
文摘This report provides for the first time rapid novel environment friendly cell surface based synthesis of stable gold nanoprisms at room temperature using Penicillium citrinum MTCC9999 biomass. The UV-Visible spectral scan of dispersed gold nanoparticles (GNPs) solution showed absorption maxima at 540 nm due to surface plasma resonance (SPR) of gold nanoparticles. Typical Transmission Electron Microscopic (TEM) images showed that most of them were prism (55%) shaped with a diameter ranging from 20 - 40 nm. These results obtained from TEM correlated well with the data obtained from Dynamic Light Scattering (DLS) experiment. Average zeta potential of GNPs was -20 mV suggesting some biomolecules capped the nanoparticles imparting a net negative charge over it. FTIR analysis also showed that protein molecules were involved in stabilization.
基金supported by the National Natural Science Foundation of China (Nos.22271010 and 21702013)。
文摘The deuterium labeling has garnered significant interest in drug discovery due to its critical role on improving pharmacokinetic and metabolic properties.However,despite its pharmaceutical value,the general and rapid syntheses of aromatic scaffolds that contains deuterium remain an important yet elusive task.State-of-the-art approaches mainly relied on the transition metal-catalyzed C-H deuteration via the assistance of directing groups(DGs),which often suffered from over-deuteration and lengthy step counts required for installation and/or removal of DG.Herein,we report a generalizable synthetic linchpin strategy for the facile preparation of the ortho-deuterated aromatic core.Through capture of aryne-derived 1,3-zwitterion with heavy water,we synthesized an array of ortho-deuterated aryl sulfonium salts.These novel linchpins not only participated the transition metal catalyzed cross-coupling reaction as nucleophiles,but also served as aryl radical reservoirs under photochemical or electrochemical conditions,enabling facile and precise access to structurally diverse deuterated aromatics.Moreover,we have disclosed a novel EDA complex enabled direct arylation of phosphines under visible-light irradiation,further expanding the utility of our platform approach.
文摘The nucleus-initiated augmentation of ER membrane is reflected in a coordinated synthesis and intercalation of the explicit proteins and lipids required for the replacement, repair and function of the cell and its organelles. The direct connection between nucleus and the membranes containing labeled sphingosine (SphN) and ceramide (Cer) was affirmed by determining synthetic activity of serine palmitoyltransferase (SPT). The SPT and the newly synthesized serine-labeled lipid products were identified in the Outer- and Inner-Nuclear Membrane (ONM, INM) and ER. The pulse-chase experiments disclosed that the incorporation of radiolabeled lipids into both nuclear membranes declined upon their simultaneous increase in Endoplasmic Reticulum (ER). These results, and prior findings regarding metabolic transfer of nuclear membrane phosphoinositides to the outer leaflet of ER [Slomiany and Slomiany, Health, 2011, 3, 187-199], allowed us to reason that INM and ONM are not distinct entities, but uninterrupted continuum facing nucleosol and then cytosol when protracted into segment known as ER. Consequently, the identification of SPT and its products in the inner leaflet of nuclear and ER microsomes lent credence to the luminal presence of Cer in Golgi, luminal synthesis of glycosphingolipids (GSphLs), sphingomyelin (SM), and their delivery to the outer leaflet of apical and basolateral cell membrane, respectively. The findings presented in this communication provide further support to our concept that the factual intercalation of proteins and lipids into the cell membranes can only take place during their simultaneous synthesis that is guided by the nuclear and cytosolic processes enacted in nuclear-ER membrane continuum. At the nuclear stage, the signal-specific genes expression promotes active synthesis and intercalation of lipids into the organelles’ customized membrane that is protracted and articulated in ER in form of transport vesicles.
基金The research leading to these results was partly funded by the National Natural Science Foundation of China (Grant No. 61263036, 61262055), Gansu Science Fund for Distinguished Young Scholars (Grant No. 1210RJDA007) and Natural Science Foundation of Gansu (Grant No. 1506RJYA126).
文摘This paper realizes a sign language-to-speech conversion system to solve the communication problem between healthy people and speech disorders. 30 kinds of different static sign languages are firstly recognized by combining the support vector machine (SVM) with a restricted Boltzmann machine (RBM) based regulation and a feedback fine-tuning of the deep model. The text of sign language is then obtained from the recognition results. A context-dependent label is generated from the recognized text of sign language by a text analyzer. Meanwhile,a hiddenMarkov model (HMM) basedMandarin-Tibetan bilingual speech synthesis system is developed by using speaker adaptive training.The Mandarin speech or Tibetan speech is then naturally synthesized by using context-dependent label generated from the recognized sign language. Tests show that the static sign language recognition rate of the designed system achieves 93.6%. Subjective evaluation demonstrates that synthesized speech can get 4.0 of the mean opinion score (MOS).
基金Supported by the National Natural Science Foundation of China(Nos.52293472,22473096 and 22471164)。
文摘Among various architectures of polymers,end-group-free rings have attracted growing interests due to their distinct physicochemical performances over the linear counterparts which are exemplified by reduced hydrodynamic size and slower degradation.It is key to develop facile methods to large-scale synthesis of polymer rings with tunable compositions and microstructures.Recent progresses in large-scale synthesis of polymer rings against single-chain dynamic nanoparticles,and the example applications in synchronous enhancing toughness and strength of polymer nanocomposites are summarized.Once there is the breakthrough in rational design and effective large-scale synthesis of polymer rings and their functional derivatives,a family of cyclic functional hybrids would be available,thus providing a new paradigm in developing polymer science and engineering.
文摘To solve the problem of robust servo performance of Flight Environment Testbed(FET)of Altitude Ground Test Facilities(AGTF) over the whole operational envelope, a two-degree-offreedom μ synthesis method based on Linear Parameter Varying(LPV) schematic is proposed, and meanwhile a new structure frame of μ synthesis control on two degrees of freedom with double integral and weighting functions is presented, which constitutes a core support part of the paper. Aimed at the problem of reference command's rapid change, one freedom feed forward is adopted, while another freedom output feedback is used to meet good servo tracking as well as disturbance and noise rejection; furthermore, to overcome the overshoot problem and acquire dynamic tuning,the integral is introduced in inner loop, and another integral controller is used in outer loop in order to guarantee steady errors; additionally, two performance weighting functions are designed to achieve robust specialty and control energy limit considering the uncertainties in system. As the schedule parameters change over large flight envelope, the stability of closed-loop LPV system is proved using Lyapunov inequalities. The simulation results show that the relative tracking errors of temperature and pressure are less than 0.5% with LPV μ synthesis controller. Meanwhile, compared with non-LPV μ synthesis controller in large uncertainty range, the proposed approach in this research can ensure robust servo performance of FET over the whole operational envelope.
基金supported by the National Natural Science Foundation of China(Nos.82204209 and 82130103)Natural Science Foundation of Henna Province(No.242300421084).
文摘ADPr-ATP is a natural nucleotide with three sugar rings and five pentavalent phosphorus,and can be produced through TIR-catalyzed ADP-ribosylation reactions for plant immunity.Here,we report the first total synthesis of ADPr-ATP(1)with a total yield of 6.4%through 14 steps,featuring late-stage P(V)−N activation reaction of pyrophosphate(4)and 5′-phosphoromorpholidate(25).The protected adenosine 5′-phosphoromorpholidate(24)was prepared on the basis of a scalable to adenosine 5′′-monophosphate(2).The construction of P(V)−N bond in phosphoramidate is esteemed as a critical step as they are sufficiently stable in deprotection reactions.The chemical synthesis of ADPr-ATP can offer an appealing alternative to traditional enzymatic synthesis and fractionation methods.Furthermore,the pRib-AMP and its prodrug are also synthesized to evaluate cytotoxicity and anti-influenza activity in vitro.
基金supported by the King Khalid University,Abha,Saudi Arabiathe Deanship of Scientific Research at King Khalid University for funding this work through Large Groups Project under grant number(R.G.P.2/335/46)the Guangdong Office of Research Projects at the Provincial University(No.2024KCXTD064)。
文摘Conjugated microporous polymers(CMPs)are a unique class of organic porous materials characterized byπ-conjugated structures and permanent micropores,distinguishing them from non-porous polymers and conventionalπ-conjugated polymers.CMPs offer extensive versatility in synthetic approaches,enabling the synthesis of cross-linked and mesoporous structures.Advances in chemical processes,structural design,and synthesis methodologies have been developed,resulting in a diverse range of CMPs with unique configurations and properties,contributing to the fast expansion of the field.CMPs are particularly notable for their ability to enable the competitive utilization ofπ-conjugated structures within mesoporous configurations,making them valuable for investigations across various domains.They have shown considerable promise in addressing fuel and environmental challenges,demonstrated by their exceptional performance in applications such as vapor adsorption,heterogeneous catalysis,light emission,light harvesting,and energy generation.This review examines the chemical engineering principles underlying CMPs,including synthesis approaches,systemic research advancements,multifunctional investigations boundaries,potential applications,and progress in synthesis,dimensionality,and morphology studies.Specifically,it offers a comparative analysis of CMPs and linear polymeric materials,aiding in the development of functional polymers.Furthermore,this review explores the primary fundamental limitations of CMPs in fuel-related domains and discusses alternative strategies,including novel synthesis methods incorporating interactions and morphologies,to address these challenges.Ultimately,this assessment aims to provide a valuable and inspiring resource for professionals in the field of fuel management,guiding future research and development efforts.
基金the National Natural Science Foundation of China(Nos.22150410339,W2432012,22301233 and 22171218)the Ministry of Science and Technology China(No.wgxz2022188)。
文摘α-Chiral amides are common in pharmaceuticals,agrochemicals,natural products,and peptides,prompting the need for new synthetic methods.Here,we introduce a nickel-catalyzed asymmetric reductive amidation method to synthesizeα-chiral amides from benzyl ammonium salts and isocyanates.The key to success is using a chiral 2,2-bipyridine ligand(-)-Ph-SBpy,enabling high yield(up to 95%)and enantiomeric ratio(up to 98:2 er)under mild conditions.Addition of phenol prevents isocyanate polymerization by reversibly forming a carbamate intermediate,enhancing selectivity and efficiency.The synthetic utility is showcased through transformations of the enantioenriched amides,and the mechanism and enantioselectivity are supported by experimental and computational studies.
基金the staff of beamline BL13SSW at Shanghai Synchrotron Radiation Facility for experiments supports. This study was financially supported by the National Natural Science Foundation of China (No. 12205165)Hebei Province Innovation Ability Improvement Plan Project (No. 225676111H).
文摘Structural engineering of Pt-based nanoalloys is crucial for the rational design and manufacturing of high-performance and low-cost electrocatalysts for hydrogen evolution reaction(HER).Here,we reported PtNi nanoparticles with a refined size of 2.71 nm and regular strains loaded on carbon black,synthesized using the high-temperature liquid shock(HTLS)method.This approach offers significant advantages over conventional synthesis methods,including high scalability,rapid reaction rates,and precise control over the size and shape of nanocrystals.Importantly,the synthesized PtNi electrocatalysts demonstrate outstanding catalytic activity and long-term stability for HER,achieving low overpotentials of 19 and 203 mV at current densities of 10 and 1000 mA/cm^(2),respectively.The superior performance can be attributed to the combination of a refined particle size,lattice strains,and synergistic effects between Pt and Ni.This rapid liquid-state synthesis demonstrated here holds great potential for scalable and industrial manufacturing of micro-/nano-catalysts.
基金financially supported by the National Natural Science Foundation of China (32071978)the National Key Research and Development Program of China (2022YFD2300901 and 2022YFD2300905)。
文摘High temperature stress (HT) significantly reduces maize yield by impairing starch accumulation in kernels.However,the mechanism by which HT affects starch synthesis remains controversial-whether through reduced assimilate supply or direct inhibition on kernel metabolism.To clarify these mechanisms,a heat-sensitive maize hybrid,Xianyu 335 (XY),was exposed to 30℃/20℃ (maximum/minimum temperature,control) and 40℃/30℃ for seven consecutive days during the seed setting stage.Synchronous pollination (SP),apical pollination (AP),and shading treatments were applied to manipulate the inherent source–sink ratio in maize plants.Results showed that apical kernel weight decreased by 11.9%under 40℃ in the SP treatment.The ^(13)C content,starch accumulation,and cell-wall invertase (CWIN) activity also declined by 15.9,36.7,and 16.4%,respectively,under HT.In the shading treatment,40℃/30℃ caused even greater reductions in^(13)C content,starch accumulation,and CWIN activity due to diminished assimilate supply.Conversely,in the AP treatment,starch content and CWIN activity increased by 22.0 and 18.5%,respectively,under 40℃/30℃,resulting in kernel weight and ^(13)C content similar to those in SP and shading treatments regardless of temperature.Consistent with apical kernels under AP,HT did not negatively affect middle kernels in either SP or shading treatments,as kernel weight and starch content remained unchanged under HT.Although all kernels were exposed to the same HT or control environment,their responses varied a lot.The impaired starch synthesis in apical kernels under HT was rescued by increasing carbon supply via AP treatment.The contrasting performance among middle kernels,apical kernels under AP,and apical kernels under SP or shading indicates that reduced carbon supply is a critical factor underlying inhibited starch accumulation.Our findings provide a theoretical basis for further understanding kernel abortion under HT.
基金the support from the National Natural Science Foundation of China(22478221)China Postdoctoral Science Foundation(2023M741920 and GZC20231259)+1 种基金Huaneng Group Science and Technology Research Project(HNKJ23-H71)Department of Chemical Engineering-iBHE Cooperation Joint Fund Project(DCE-iBHE-2025-3)。
文摘The two-electron electrochemical oxygen reduction reaction(ORR)affords an appealing alternative for on-site production of hydrogen peroxide(H_(2)O_(2)),which can fulfill the demands of various applications even at low concentrations.Under neutral or near-neutral conditions,the electrolyte environment capable of electrochemically synthesizing H_(2)O_(2) exhibits diversity and holds vast potential for practical applications;however,the electrocatalytic performance is limited without desirable electrode materials.In this contribution,methoxylated nickel hydroxides were proposed for high-performance on-site H_(2)O_(2) electrosynthesis in different potassium fertilizer solutions.The methoxylation compared to pristine Ni(OH)_(2) was demonstrated to optimize the electronic structure with favorable adsorption of reaction intermediates,obviously enhancing the activity and selectivity.In 0.10 M K_(2)SO_(4) solution,H_(2)O_(2) production ranged from 28.1 to 153.6 mg h^(-1) cm^(-2) at current densities of-50 to-250 mA cm^(-2),accompanied by Faradaic efficiency values exceeding 88.0%.An integrated system was devised by combining fertilization,disinfection,and irrigation through the coupling of two-electron ORR with agricultural irrigation,utilizing nutrient solutions as the electrolyte for on-site H_(2)O_(2) electrosynthesis.These findings afford a promising avenue for the practical application of 2e-ORR in neutral environments.
