As total life expectancy increases, the prevalence of age-related diseases such as diabetes and Alzheimer's disease is also increasing. Many hypotheses about Alzheimer's disease have been developed, including ...As total life expectancy increases, the prevalence of age-related diseases such as diabetes and Alzheimer's disease is also increasing. Many hypotheses about Alzheimer's disease have been developed, including cholinergic neuron damage, oxidative stress, and inflammation. Acetylcholine is a major neurotransmitter in the brain and cholinergic deficits leads to cognitive dysfunction and decline. Recent studies have linked diabetes as a risk factor in developing Alzheimer's disease and other types of dementia. The incidence of patients with type II diabetes and increased levels and activity of α-amylase is higher in patients with dementia. It has been shown that aromatherapy with essential oils from the mint family can improve cognitive performance in Alzheimer's disease patients. Selected monoterpenoids from these essential oils are reported to inhibit acetylcholinesterase, both in vitro and in vivo. Terpenoids are small, fat-soluble organic molecules that can transfer across nasal mucosa if inhaled, or penetrate through the skin after topical application, enter into the blood and cross the blood-brain barrier. Recent evidence supports the idea that the common constituents of essential oils also inhibit α-amylase, a starch digestive enzyme that plays an important role in the control of diabetes. The mint family is a fragrant plant family that contains most of the culinary herbs found in the Mediterranean diet. The Mediterranean diet is considered to be one of the healthiest diets in the world, and is found to be beneficial not only for the heart but also for the brain. Herbs used in this diet are rich in antioxidants that can prevent oxidative damage caused by free radicals. However, our study shows that they also contain biologically active compounds with potent α-amylase and acetylcholinesterase inhibitory activities. Consumption of fresh herbs can help boost memory and reduce sugar levels in the body. The use of herbs as a functional food could lead to significant improvements in health. Cognitive stimulation with medical food and medical herbs could delay development of cognitive decline, and improve the quality of life of Alzheimer's disease patients. This effect can be enhanced if combined with aromatherapy, topically or by inhalation, and/or by ingestion. Terpenes and terpenoids, the primary constituents of these essential oils are small, lipid soluble organic molecules that can be absorbed through the skin or across nasal mucosa into the systemic blood circulation. Many terpenes can also cross the blood-brain barrier. Therefore, topical application or inhalation of essential oils will also produce a systemic effect.展开更多
Redox homeostasis refers to the balance between the production of reactive oxygen species(ROS)as well as reactive nitrogen species(RNS),and their elimination by antioxidants.It is linked to all important cellular acti...Redox homeostasis refers to the balance between the production of reactive oxygen species(ROS)as well as reactive nitrogen species(RNS),and their elimination by antioxidants.It is linked to all important cellular activities and oxidative stress is a result of imbalance between pro-oxidants and antioxidant species.Oxidative stress perturbs many cellular activities,including processes that maintain the integrity of DNA.Nucleic acids are highly reactive and therefore particularly susceptible to damage.The DNA damage response detects and repairs these DNA lesions.Efficient DNA repair processes are therefore essential for maintaining cellular viability,but they decline considerably during aging.DNA damage and deficiencies in DNA repair are increasingly described in age-related neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis and Huntington’s disease.Furthermore,oxidative stress has long been associated with these conditions.Moreover,both redox dysregulation and DNA damage increase significantly during aging,which is the biggest risk factor for neurodegenerative diseases.However,the links between redox dysfunction and DNA damage,and their joint contributions to pathophysiology in these conditions,are only just emerging.This review will discuss these associations and address the increasing evidence for redox dysregulation as an important and major source of DNA damage in neurodegenerative disorders.Understanding these connections may facilitate a better understanding of disease mechanisms,and ultimately lead to the design of better therapeutic strategies based on preventing both redox dysregulation and DNA damage.展开更多
The Fourier transform(FT),a cornerstone of optical processing,enables rapid evaluation of fundamental mathematical operations,such as derivatives and integrals.Conventionally,a converging lens performs an optical FT i...The Fourier transform(FT),a cornerstone of optical processing,enables rapid evaluation of fundamental mathematical operations,such as derivatives and integrals.Conventionally,a converging lens performs an optical FT in free space when light passes through it.The speed of the transformation is limited by the thickness and the focal length of the lens.By using the wave nature of surface plasmon polaritons(SPPs),here we demonstrate that the FT can be implemented in a planar configuration with a minimal propagation distance of around 10 mm,resulting in an increase of speed by four to five orders of magnitude.The photonic FT was tested by synthesizing intricate SPP waves with their Fourier components.The reduced dimensionality in the minuscule device allows the future development of an ultrafast on-chip photonic information processing platform for large-scale optical computing.展开更多
The development of rapid,selective,and sensitivefluorescent sensors is essential for visualizing and quantifying biological molecules and processes in vitro,ex vitro,and in vivo,which is important for not only fundame...The development of rapid,selective,and sensitivefluorescent sensors is essential for visualizing and quantifying biological molecules and processes in vitro,ex vitro,and in vivo,which is important for not only fundamental biological studies but the accurate diagnosis of diseases.The emergingfield of activity-based sensing(ABS),a sensing method that utilizes molecular reactivity for analyte detection possesses many advantages including high specificity,sensitivity and accuracy.The aggrega-tion caused quenching phenomenon which occurs in most conventionalfluorophores results in reduced labeling efficiency of the target analytes and low photobleaching resistance,therefore limiting the applications of the ABS strategy.In contrast,aggre-gation induced emission(AIE)active luminogens(AIEgens)provide exceptional molecular frameworks for ABS.Of the many reaction classes utilized in the AIEgen ABS approach,click chemistry has become increasing popular.In this review,the sensing concepts of the ABS approach with AIEgens and the principles of click chemistry are discussed,followed by a systematic summary of the application of specific click chemistry reactions in AIEgen ABS protocols for the detection of an array of target analytes.Furthermore,the utility of click chemistry in the construction of AIEgens for bioimaging will also be showcased throughout the review.展开更多
Obesity has been linked to a range of pathologies,including dementia.In contrast,regular physical activity is associated with the prevention or reduced progression of neurodegeneration.Specifically,physical activity c...Obesity has been linked to a range of pathologies,including dementia.In contrast,regular physical activity is associated with the prevention or reduced progression of neurodegeneration.Specifically,physical activity can improve memory and spatial cognition,reduce age-related cognitive decline,and preserve brain volume,but the mechanisms are not fully understood.Accordingly,we investigated whether any detrimental effects of high-fat diet(HFD)-induced obesity on cognition,motor behavior,adult hippocampal neurogenesis,and brain-derived neurotrophic factor(BDNF)could be mitigated by voluntary exercise training in male C57Bl/6 mice.HFD-induced impairment of motor function was not reversed by exercise.Importantly,voluntary wheel running improved long-term memory and increased hippocampal neurogenesis,suggesting that regular physical activity may prevent cognitive decline in obesity.展开更多
The idea of using ultrashort X-ray pulses to obtain images of single proteins frozen in time has fascinated and inspired many.It was one of the arguments for building X-ray free-electron lasers.According to theory,the...The idea of using ultrashort X-ray pulses to obtain images of single proteins frozen in time has fascinated and inspired many.It was one of the arguments for building X-ray free-electron lasers.According to theory,the extremely intense pulses provide sufficient signal to dispense with using crystals as an amplifier,and the ultrashort pulse duration permits capturing the diffraction data before the sample inevitably explodes.This was first demonstrated on biological samples a decade ago on the giant mimivirus.Since then,a large collaboration has been pushing the limit of the smallest sample that can be imaged.The ability to capture snapshots on the timescale of atomic vibrations,while keeping the sample at room temperature,may allow probing the entire conformational phase space of macromolecules.Here we show the first observation of an X-ray diffraction pattern from a single protein,that of Escherichia coli GroEL which at 14 nm in diameter is the smallest biological sample ever imaged by X-rays,and demonstrate that the concept of diffraction before destruction extends to single proteins.From the pattern,it is possible to determine the approximate orientation of the protein.Our experiment demonstrates the feasibility of ultrafast imaging of single proteins,opening the way to single-molecule time-resolved studies on the femtosecond timescale.展开更多
The orbital angular momentum(OAM)of light has been shown to be useful in diverse fields ranging from astronomy and optical trapping to optical communications and data storage.However,one of the primary impediments pre...The orbital angular momentum(OAM)of light has been shown to be useful in diverse fields ranging from astronomy and optical trapping to optical communications and data storage.However,one of the primary impediments preventing such applications from widespread adoption is the lack of a straightforward and dynamic method to sort incident OAM states without altering the states.Here,we report a technique that can dynamically filter individual OAM states and preserve the incident OAM states for subsequent processing.Although the working principle of this technique is based on resonance,the device operation is not limited to a particular wavelength.OAM states with different wavelengths can resonate in the resonator without any additional modulation other than changing the length of the cavity.Consequently,we are able to demonstrate a reconfigurable OAM sorter that is constructed by cascading such optical resonators.This approach does not require specially designed components and is readily amenable to integration into potential applications.展开更多
Organic photovoltaic(OPV)materials are promising candidates for cheap,printable solar cells.However,there are a very large number of potential donors and acceptors,making selection of the best materials difficult.Here...Organic photovoltaic(OPV)materials are promising candidates for cheap,printable solar cells.However,there are a very large number of potential donors and acceptors,making selection of the best materials difficult.Here,we show that machine-learning approaches can leverage computationally expensive DFT calculations to estimate important OPV materials properties quickly and accurately.We generate quantitative relationships between simple and interpretable chemical signature and one-hot descriptors and OPV power conversion efficiency(PCE),open circuit potential(Voc),short circuit density(Jsc),highest occupied molecular orbital(HOMO)energy,lowest unoccupied molecular orbital(LUMO)energy,and the HOMO–LUMO gap.The most robust and predictive models could predict PCE(computed by DFT)with a standard error of±0.5 for percentage PCE for both the training and test set.This model is useful for pre-screening potential donor and acceptor materials for OPV applications,accelerating design of these devices for green energy applications.展开更多
Aim:Neuroblastoma is a pediatric cancer of the sympathetic nervous system.Using various parameters including stage of the disease,amplification status of N-Myc,DNA index and histopathology,neuroblastoma can be stratif...Aim:Neuroblastoma is a pediatric cancer of the sympathetic nervous system.Using various parameters including stage of the disease,amplification status of N-Myc,DNA index and histopathology,neuroblastoma can be stratified into low-and high-risk groups.Recent advances in treatment have significantly improved the survival rate of lowrisk neuroblastoma patients.However,the overall survival rate of high-risk neuroblastoma group,especially N-Myc amplified patients,is poor.Moreover,the survivors of both low-and high-risk neuroblastoma manifest adverse side effects to chemotherapy and thus their quality of life is impaired.Considering all these factors,there is an urgent need to develop therapeutic strategies with natural compounds to improve the survival rate and to reduce the side effects.In this study,we hypothesised that the mesenchymal nature of neuroblastoma cells is a reason,at least in part,for the aggressive and treatment resistant phenotype.Method:In order to validate our hypothesis,we used publicaly available RNA-Seq data,in vitro assays and xenograft mouse models.Results:Using a combinatorial treatment of mesenchymal-to-epithelial inducers(curcumin or silibinin)with doxorubicin significantly increased the cell death in a panel of neuroblastoma cells in vitro.Follow up analysis in vivo,confirmed the therapeutic benefit of utilising the combination of curcumin with doxorubicin.The combinatorial therapy significantly reduced the tumor burden and increased the survival of mice implanted with high-risk neuroblastoma cells.Conclusion:Taken together,this study shows the efficacy of using curcumin in combination with doxorubicin to improve the survival rate and has the potential to enhance the quality of life of neuroblastoma patients.展开更多
Biothiols are important species in physiological processes such as regulating protein structures, redox homeostasis and cell signalling. Alternation in the biothiol levels is associated with various pathological proce...Biothiols are important species in physiological processes such as regulating protein structures, redox homeostasis and cell signalling. Alternation in the biothiol levels is associated with various pathological processes, therefore non-invasive fluorescent probes with high specificity to biothiols are highly desirable research utilities. Meanwhile, fluorescent probes with aggregationinduced emission properties(AIEgens) possess unique photophysical properties that allow modulation of the sensing process through controlling the aggregation-disaggregation or the intramolecular rotational motions of the fluorophores. Herein we review the recent progress in the development of biothiol-specific AIEgens. In particular, the molecular design principles to target different types of biothiols and the corresponding sensing mechanisms are discussed, along with the potential of the future design and development of multi-functional bioprobes.展开更多
The misalignment of optical vortex(OV) beams, including transversal displacement and tilt, occurs in many situations, including on reflection or refraction at an interface between two different media and in propagatio...The misalignment of optical vortex(OV) beams, including transversal displacement and tilt, occurs in many situations, including on reflection or refraction at an interface between two different media and in propagation and tracking systems for optical communications. We propose a reliable method to determine and subsequently eliminate tilt and transversal displacement in an OV beam. An experimental setup was established to verify the proposed method, and the experimental results showed good agreement with those of the numerical simulations.Using the measured misalignments, the initial orbital angular momentum spectrum can be recovered in free space.展开更多
We report a dual-contrast method of simultaneously measuring and visualizing the volumetric structural information in live biological samples in three-dimensional(3D) space. By introducing a direct way of deriving the...We report a dual-contrast method of simultaneously measuring and visualizing the volumetric structural information in live biological samples in three-dimensional(3D) space. By introducing a direct way of deriving the 3D scattering potential of the object from the synthesized angular spectra, we obtain the quantitative subcellular morphology in refractive indices(RIs) side-by-side with its fluorescence signals. The additional contrast in RI complements the fluorescent signal, providing additional information of the targeted zones. The simultaneous dual-contrast 3D mechanism unveiled interesting information inaccessible with previous methods, as we demonstrated in the human immune cell(T cell) experiment. Further validation has been demonstrated using a Monte Carlo model.展开更多
The in situ physicochemical analysis of nanostructured functional materials is crucial for advances in their design and production. X-ray coherent diffraction imaging (CDI) methods have recently demonstrated impress...The in situ physicochemical analysis of nanostructured functional materials is crucial for advances in their design and production. X-ray coherent diffraction imaging (CDI) methods have recently demonstrated impressive potential for characterizing such materials with a high spatial resolution and elemental sensitivity; however, moving from the current ex situ static regime to the in situ dynamic one remains a challenge. By combining soft X-ray ptychography and single-shot keyhole CDI, we performed the first in situ spatiotemporal study on an electrodeposition process in a sealed wet environment, employed for the fabrication of oxygen-reduction catalysts, which are key components for alkaline fuel cells and metal-air batteries. The results provide the first experimental demonstration of theoretically predicted Turing-Hopf electrochemical pattern formation resulting from morphochemical coupling, adding a new dimension for the in-depth in situ characterization of electrodeposition processes in space and time.展开更多
As a frontier imaging technique for biomedical applications,photoacoustic(PA)imaging has been developed rapidly.The development of new design strategies and excellent PA imaging reagents to boost PA conversion is eage...As a frontier imaging technique for biomedical applications,photoacoustic(PA)imaging has been developed rapidly.The development of new design strategies and excellent PA imaging reagents to boost PA conversion is eagerly desirable for high quality PA imaging but complicated to realize.Herein,we develop a new strategy in which PA imaging reagents with better properties can be easily optimized by polymerization.A series of new PA imaging reagents were designed and synthesized.The polymerization strategy can effectively promote the PA signal by specifically increasing the thermal-to-acoustic conversion efficiency.As these materials shared the same building units,the optimized effectiveness of polymerization strategy in terms of near-infrared light-harvesting capacity and thermal-to-acoustic conversion efficiency are discussed,rationally.The polymers with intense intramolecular motion exhibit an amplified PA signal by elevating thermal-to-acoustic conversion and its higher light-harvesting capability at redshifted region.The simultaneously strong PA signal and photothermal conversion efficiency of p-TTmB NPs enable precise PA imaging and effective photothermal therapy.This work highlights a simple and available design guideline of polymerization for amplifying the PA effect and optimizing existing materials.展开更多
文摘As total life expectancy increases, the prevalence of age-related diseases such as diabetes and Alzheimer's disease is also increasing. Many hypotheses about Alzheimer's disease have been developed, including cholinergic neuron damage, oxidative stress, and inflammation. Acetylcholine is a major neurotransmitter in the brain and cholinergic deficits leads to cognitive dysfunction and decline. Recent studies have linked diabetes as a risk factor in developing Alzheimer's disease and other types of dementia. The incidence of patients with type II diabetes and increased levels and activity of α-amylase is higher in patients with dementia. It has been shown that aromatherapy with essential oils from the mint family can improve cognitive performance in Alzheimer's disease patients. Selected monoterpenoids from these essential oils are reported to inhibit acetylcholinesterase, both in vitro and in vivo. Terpenoids are small, fat-soluble organic molecules that can transfer across nasal mucosa if inhaled, or penetrate through the skin after topical application, enter into the blood and cross the blood-brain barrier. Recent evidence supports the idea that the common constituents of essential oils also inhibit α-amylase, a starch digestive enzyme that plays an important role in the control of diabetes. The mint family is a fragrant plant family that contains most of the culinary herbs found in the Mediterranean diet. The Mediterranean diet is considered to be one of the healthiest diets in the world, and is found to be beneficial not only for the heart but also for the brain. Herbs used in this diet are rich in antioxidants that can prevent oxidative damage caused by free radicals. However, our study shows that they also contain biologically active compounds with potent α-amylase and acetylcholinesterase inhibitory activities. Consumption of fresh herbs can help boost memory and reduce sugar levels in the body. The use of herbs as a functional food could lead to significant improvements in health. Cognitive stimulation with medical food and medical herbs could delay development of cognitive decline, and improve the quality of life of Alzheimer's disease patients. This effect can be enhanced if combined with aromatherapy, topically or by inhalation, and/or by ingestion. Terpenes and terpenoids, the primary constituents of these essential oils are small, lipid soluble organic molecules that can be absorbed through the skin or across nasal mucosa into the systemic blood circulation. Many terpenes can also cross the blood-brain barrier. Therefore, topical application or inhalation of essential oils will also produce a systemic effect.
基金supported by an Australian National Health and Medical Research Council(NHMRC)Dementia Teams Research Grant(1095215)Macquarie University MQCRF fellowship,Fight MND Foundation,and Motor Neuron Disease Research Australia.
文摘Redox homeostasis refers to the balance between the production of reactive oxygen species(ROS)as well as reactive nitrogen species(RNS),and their elimination by antioxidants.It is linked to all important cellular activities and oxidative stress is a result of imbalance between pro-oxidants and antioxidant species.Oxidative stress perturbs many cellular activities,including processes that maintain the integrity of DNA.Nucleic acids are highly reactive and therefore particularly susceptible to damage.The DNA damage response detects and repairs these DNA lesions.Efficient DNA repair processes are therefore essential for maintaining cellular viability,but they decline considerably during aging.DNA damage and deficiencies in DNA repair are increasingly described in age-related neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis and Huntington’s disease.Furthermore,oxidative stress has long been associated with these conditions.Moreover,both redox dysregulation and DNA damage increase significantly during aging,which is the biggest risk factor for neurodegenerative diseases.However,the links between redox dysfunction and DNA damage,and their joint contributions to pathophysiology in these conditions,are only just emerging.This review will discuss these associations and address the increasing evidence for redox dysregulation as an important and major source of DNA damage in neurodegenerative disorders.Understanding these connections may facilitate a better understanding of disease mechanisms,and ultimately lead to the design of better therapeutic strategies based on preventing both redox dysregulation and DNA damage.
基金supported by the National Natural Science Foundation of China 61427819the Ministry of Science and Technology of China under National Basic Research Program of China(973)grant(No.2015CB352004)+4 种基金the Discovery Early Career Researcher Award funded by the Australian Research Council under projects DE120102352 and DE130100954,respectivelysupport from the La Trobe Research Focus Area(RFA)of Understanding Diseases,theMelbourne Collaboration Grant and the Interdisciplinary Seed Fund through theMelbourne Materials Institute(MMI)support from the Defence Science Institute,Australiathe Advanced Optics in Engineering Programme with Grant number 122-360-0009 from the Agency for Science,Technology and Research(A*STAR)and Singapore Ministry of Education Academic Research Fund Tier 3 with Grant number MOE2011-T3-1-005the fellowship support from the A*STAR.
文摘The Fourier transform(FT),a cornerstone of optical processing,enables rapid evaluation of fundamental mathematical operations,such as derivatives and integrals.Conventionally,a converging lens performs an optical FT in free space when light passes through it.The speed of the transformation is limited by the thickness and the focal length of the lens.By using the wave nature of surface plasmon polaritons(SPPs),here we demonstrate that the FT can be implemented in a planar configuration with a minimal propagation distance of around 10 mm,resulting in an increase of speed by four to five orders of magnitude.The photonic FT was tested by synthesizing intricate SPP waves with their Fourier components.The reduced dimensionality in the minuscule device allows the future development of an ultrafast on-chip photonic information processing platform for large-scale optical computing.
基金Australian Research Council,Grant/Award Number:FT210100271Australia-China Science and Research Fund-Joint Research Centre on Personal Health Technologies,Grant/Award Number:ACSRF65777。
文摘The development of rapid,selective,and sensitivefluorescent sensors is essential for visualizing and quantifying biological molecules and processes in vitro,ex vitro,and in vivo,which is important for not only fundamental biological studies but the accurate diagnosis of diseases.The emergingfield of activity-based sensing(ABS),a sensing method that utilizes molecular reactivity for analyte detection possesses many advantages including high specificity,sensitivity and accuracy.The aggrega-tion caused quenching phenomenon which occurs in most conventionalfluorophores results in reduced labeling efficiency of the target analytes and low photobleaching resistance,therefore limiting the applications of the ABS strategy.In contrast,aggre-gation induced emission(AIE)active luminogens(AIEgens)provide exceptional molecular frameworks for ABS.Of the many reaction classes utilized in the AIEgen ABS approach,click chemistry has become increasing popular.In this review,the sensing concepts of the ABS approach with AIEgens and the principles of click chemistry are discussed,followed by a systematic summary of the application of specific click chemistry reactions in AIEgen ABS protocols for the detection of an array of target analytes.Furthermore,the utility of click chemistry in the construction of AIEgens for bioimaging will also be showcased throughout the review.
基金supported by an NHMRC Investigator Grant(APP1194141)supported by project grants from the NHMRC(APP1042465,APP1041760,and APP1156511).
文摘Obesity has been linked to a range of pathologies,including dementia.In contrast,regular physical activity is associated with the prevention or reduced progression of neurodegeneration.Specifically,physical activity can improve memory and spatial cognition,reduce age-related cognitive decline,and preserve brain volume,but the mechanisms are not fully understood.Accordingly,we investigated whether any detrimental effects of high-fat diet(HFD)-induced obesity on cognition,motor behavior,adult hippocampal neurogenesis,and brain-derived neurotrophic factor(BDNF)could be mitigated by voluntary exercise training in male C57Bl/6 mice.HFD-induced impairment of motor function was not reversed by exercise.Importantly,voluntary wheel running improved long-term memory and increased hippocampal neurogenesis,suggesting that regular physical activity may prevent cognitive decline in obesity.
基金supported by the Universität Hamburg and DFG grant numbers(INST 152/772-1|152/774-1|152/775-1|152/776-1|152/777-1 FUGG)We acknowledge the support of funding from:Cluster of Excellence‘CUI:Advanced Imaging of Matter’of the Deutsche Forschungsgemeinschaft(DFG)-EXC 2056-project ID 390715994+7 种基金ERC-2013-CoG COMOTION 614507NFR 240770Fellowship from the Joachim Herz Stiftung(P.L.X.)P.L.X.and H.N.C.acknowledge support from the Human Frontiers Science Program(RGP0010/2017)J.H.acknowledges support from the European Development Fund:Structural dynamics of biomolecular systems(ELIBIO)(CZ.02.1.01/0.0/0.0/15_003/0000447)EMBO long-term fellowship(ALTF 356-2018)awarded to L.E.F.the Röntgen-Ångström Cluster(2015-06107 and 2019-06092)the Swedish Research Council(2017-05336,2018-00234 and 2019-03935)the Swedish Foundation for Strategic Research(ITM17-0455).
文摘The idea of using ultrashort X-ray pulses to obtain images of single proteins frozen in time has fascinated and inspired many.It was one of the arguments for building X-ray free-electron lasers.According to theory,the extremely intense pulses provide sufficient signal to dispense with using crystals as an amplifier,and the ultrashort pulse duration permits capturing the diffraction data before the sample inevitably explodes.This was first demonstrated on biological samples a decade ago on the giant mimivirus.Since then,a large collaboration has been pushing the limit of the smallest sample that can be imaged.The ability to capture snapshots on the timescale of atomic vibrations,while keeping the sample at room temperature,may allow probing the entire conformational phase space of macromolecules.Here we show the first observation of an X-ray diffraction pattern from a single protein,that of Escherichia coli GroEL which at 14 nm in diameter is the smallest biological sample ever imaged by X-rays,and demonstrate that the concept of diffraction before destruction extends to single proteins.From the pattern,it is possible to determine the approximate orientation of the protein.Our experiment demonstrates the feasibility of ultrafast imaging of single proteins,opening the way to single-molecule time-resolved studies on the femtosecond timescale.
基金partially supported the National Natural Science Foundation of China under grant Nos.U1701661/61935013/61427819/11604219/61675136The National Key R&D Program of China under grant No.2018YFB1801801+3 种基金the Leading Talents Program of Guangdong Province under grant No.00201505the Natural Science Foundation of Guangdong Province under grant No.2016A030312010the Shenzhen Science and Technology Innovation Commission under grant No.KQJSCX20170727100838364/KQTD2015071016560101/KQTD20180412181324255the support of the Endeavour Australia Cheung Kong Research Fellowship funded by the Department of Education and Training,Australia.
文摘The orbital angular momentum(OAM)of light has been shown to be useful in diverse fields ranging from astronomy and optical trapping to optical communications and data storage.However,one of the primary impediments preventing such applications from widespread adoption is the lack of a straightforward and dynamic method to sort incident OAM states without altering the states.Here,we report a technique that can dynamically filter individual OAM states and preserve the incident OAM states for subsequent processing.Although the working principle of this technique is based on resonance,the device operation is not limited to a particular wavelength.OAM states with different wavelengths can resonate in the resonator without any additional modulation other than changing the length of the cavity.Consequently,we are able to demonstrate a reconfigurable OAM sorter that is constructed by cascading such optical resonators.This approach does not require specially designed components and is readily amenable to integration into potential applications.
基金This work was supported by the Australian Government through the Australian Research Council(ARC)under the Centre of Excellence scheme(project number CE170100026)This work was also supported by computational resources provided by the Australian Government through the National Computational Infrastructure National Facility and the Pawsey Supercomputer Centre.
文摘Organic photovoltaic(OPV)materials are promising candidates for cheap,printable solar cells.However,there are a very large number of potential donors and acceptors,making selection of the best materials difficult.Here,we show that machine-learning approaches can leverage computationally expensive DFT calculations to estimate important OPV materials properties quickly and accurately.We generate quantitative relationships between simple and interpretable chemical signature and one-hot descriptors and OPV power conversion efficiency(PCE),open circuit potential(Voc),short circuit density(Jsc),highest occupied molecular orbital(HOMO)energy,lowest unoccupied molecular orbital(LUMO)energy,and the HOMO–LUMO gap.The most robust and predictive models could predict PCE(computed by DFT)with a standard error of±0.5 for percentage PCE for both the training and test set.This model is useful for pre-screening potential donor and acceptor materials for OPV applications,accelerating design of these devices for green energy applications.
基金Suresh Mathivanan is supported by Australian Research Council Future Fellowship(FT180100333)the project was not funded by the basic science fellowship.Angela Di Giannatale is supported by a Grant from the Italian Ministry of Health(GR-2016-02364088).
文摘Aim:Neuroblastoma is a pediatric cancer of the sympathetic nervous system.Using various parameters including stage of the disease,amplification status of N-Myc,DNA index and histopathology,neuroblastoma can be stratified into low-and high-risk groups.Recent advances in treatment have significantly improved the survival rate of lowrisk neuroblastoma patients.However,the overall survival rate of high-risk neuroblastoma group,especially N-Myc amplified patients,is poor.Moreover,the survivors of both low-and high-risk neuroblastoma manifest adverse side effects to chemotherapy and thus their quality of life is impaired.Considering all these factors,there is an urgent need to develop therapeutic strategies with natural compounds to improve the survival rate and to reduce the side effects.In this study,we hypothesised that the mesenchymal nature of neuroblastoma cells is a reason,at least in part,for the aggressive and treatment resistant phenotype.Method:In order to validate our hypothesis,we used publicaly available RNA-Seq data,in vitro assays and xenograft mouse models.Results:Using a combinatorial treatment of mesenchymal-to-epithelial inducers(curcumin or silibinin)with doxorubicin significantly increased the cell death in a panel of neuroblastoma cells in vitro.Follow up analysis in vivo,confirmed the therapeutic benefit of utilising the combination of curcumin with doxorubicin.The combinatorial therapy significantly reduced the tumor burden and increased the survival of mice implanted with high-risk neuroblastoma cells.Conclusion:Taken together,this study shows the efficacy of using curcumin in combination with doxorubicin to improve the survival rate and has the potential to enhance the quality of life of neuroblastoma patients.
基金supported by Australian Research Council (DE170100058)Rebecca L. Cooper Medical Research Foundation
文摘Biothiols are important species in physiological processes such as regulating protein structures, redox homeostasis and cell signalling. Alternation in the biothiol levels is associated with various pathological processes, therefore non-invasive fluorescent probes with high specificity to biothiols are highly desirable research utilities. Meanwhile, fluorescent probes with aggregationinduced emission properties(AIEgens) possess unique photophysical properties that allow modulation of the sensing process through controlling the aggregation-disaggregation or the intramolecular rotational motions of the fluorophores. Herein we review the recent progress in the development of biothiol-specific AIEgens. In particular, the molecular design principles to target different types of biothiols and the corresponding sensing mechanisms are discussed, along with the potential of the future design and development of multi-functional bioprobes.
基金supported by the National Natural Science Foundation of China (Nos. 61571377, 61771412, and 61871336)the Fundamental Research Funds for the Central Universities (No. 20720180068)
文摘The misalignment of optical vortex(OV) beams, including transversal displacement and tilt, occurs in many situations, including on reflection or refraction at an interface between two different media and in propagation and tracking systems for optical communications. We propose a reliable method to determine and subsequently eliminate tilt and transversal displacement in an OV beam. An experimental setup was established to verify the proposed method, and the experimental results showed good agreement with those of the numerical simulations.Using the measured misalignments, the initial orbital angular momentum spectrum can be recovered in free space.
基金Australian Research Council(ARC)(DE120102352)National Natural Science Foundation of China(NSFC)(61427819)+2 种基金Shenzhen Science and Technology Innovation Commission(KQCS2015032416183980)Government of Guangdong Province(00201505)Schweizerischer Nationalfonds zur Forderung der Wissenschaftlichen Forschung(SNF)(149652)
文摘We report a dual-contrast method of simultaneously measuring and visualizing the volumetric structural information in live biological samples in three-dimensional(3D) space. By introducing a direct way of deriving the 3D scattering potential of the object from the synthesized angular spectra, we obtain the quantitative subcellular morphology in refractive indices(RIs) side-by-side with its fluorescence signals. The additional contrast in RI complements the fluorescent signal, providing additional information of the targeted zones. The simultaneous dual-contrast 3D mechanism unveiled interesting information inaccessible with previous methods, as we demonstrated in the human immune cell(T cell) experiment. Further validation has been demonstrated using a Monte Carlo model.
文摘The in situ physicochemical analysis of nanostructured functional materials is crucial for advances in their design and production. X-ray coherent diffraction imaging (CDI) methods have recently demonstrated impressive potential for characterizing such materials with a high spatial resolution and elemental sensitivity; however, moving from the current ex situ static regime to the in situ dynamic one remains a challenge. By combining soft X-ray ptychography and single-shot keyhole CDI, we performed the first in situ spatiotemporal study on an electrodeposition process in a sealed wet environment, employed for the fabrication of oxygen-reduction catalysts, which are key components for alkaline fuel cells and metal-air batteries. The results provide the first experimental demonstration of theoretically predicted Turing-Hopf electrochemical pattern formation resulting from morphochemical coupling, adding a new dimension for the in-depth in situ characterization of electrodeposition processes in space and time.
基金supported by the National Key R&D Program of China (Intergovernmental Cooperation Project, 2017YFE0132200)the National Natural Science of Fundation of China (Nos.51961160730, 51873092, and 81921004)+1 种基金the Fundamental Research Funds for the Central Universitiesthe Tianjin Science Fund for Distinguished Young Scholars (19JCJQJC61200)
文摘As a frontier imaging technique for biomedical applications,photoacoustic(PA)imaging has been developed rapidly.The development of new design strategies and excellent PA imaging reagents to boost PA conversion is eagerly desirable for high quality PA imaging but complicated to realize.Herein,we develop a new strategy in which PA imaging reagents with better properties can be easily optimized by polymerization.A series of new PA imaging reagents were designed and synthesized.The polymerization strategy can effectively promote the PA signal by specifically increasing the thermal-to-acoustic conversion efficiency.As these materials shared the same building units,the optimized effectiveness of polymerization strategy in terms of near-infrared light-harvesting capacity and thermal-to-acoustic conversion efficiency are discussed,rationally.The polymers with intense intramolecular motion exhibit an amplified PA signal by elevating thermal-to-acoustic conversion and its higher light-harvesting capability at redshifted region.The simultaneously strong PA signal and photothermal conversion efficiency of p-TTmB NPs enable precise PA imaging and effective photothermal therapy.This work highlights a simple and available design guideline of polymerization for amplifying the PA effect and optimizing existing materials.