Biomanufacturing,which uses renewable resources as raw materials and uses biological processes to produce energy and chemicals,has long been regarded as a production model that replaces the unsustainable fossil econom...Biomanufacturing,which uses renewable resources as raw materials and uses biological processes to produce energy and chemicals,has long been regarded as a production model that replaces the unsustainable fossil economy.The construction of non-natural and efficient biosynthesis routes of chemicals is an important goal of green biomanufacturing.Traditional methods that rely on experience are difficult to support the realization of this goal.However,with the rapid development of information technology,the intelligence of biomanufacturing has brought hope to achieve this goal.Retrobiosynthesis and computational enzyme design,as two of the main technologies in intelligent biomanufacturing,have developed rapidly in recent years and have made great achievements and some representative works have demonstrated the great value that the integration of the two fields may bring.To achieve the final integration of the two fields,it is necessary to examine the information,methods and tools from a bird’s-eye view,and to find a feasible idea and solution for establishing a connection point.For this purpose,this article briefly reviewed the main ideas,methods and tools of the two fields,and put forward views on how to achieve the integration of the two fields.展开更多
Cross polarization(CP)is a widely used solid-state nuclear magnetic resonance(NMR)technique for enhancing the polarization of dilute S spins from much larger polarization of abundant I spins such as 1 H.To achieve suc...Cross polarization(CP)is a widely used solid-state nuclear magnetic resonance(NMR)technique for enhancing the polarization of dilute S spins from much larger polarization of abundant I spins such as 1 H.To achieve such a polarization transfer,the I spin should either be spin-locked or be converted to the dipolar ordered state through adiabatic demagnetization in the rotating frame.In this work,we analyze the spin dynamics of the Hartmann-Hahn CP(HHCP)utilizing the 1 H spin-locking,and the dipolar-order CP(DOCP)having the 1 H adiabatic demagnetization.We further propose an adiabatic demagnetization CP(ADCP)where a constant radio-frequency pulse is applied on the S spin while 1 H is adiabatically demagnetized.Our analyses indicate that ADCP utilizes the adiabatic passage to effectively achieve the polarization transfer from the 1 H to S spins.In addition,the dipolar ordered state generated during the 1 H demagnetization process could also be converted into the observable S polarization through DOCP,further enhancing the polarized signals.It is shown by both static and magic-angle-spinning(MAS)NMR experiments that ADCP has dramatically broadened the CP matching condition over the other CP schemes.Various samples have been used to demonstrate the polarization transfer efficiency of this newly proposed ADCP scheme.展开更多
As a valid tool for solving ground state problems,imaginary time evolution(ITE)is widely used in physical and chemical simulations.Different ITE-based algorithms in their quantum counterpart have recently been propose...As a valid tool for solving ground state problems,imaginary time evolution(ITE)is widely used in physical and chemical simulations.Different ITE-based algorithms in their quantum counterpart have recently been proposed and applied to some real systems.We experimentally realize the variational-based quantum imaginary time evolution(QITE)algorithm to simulate the ground state energy of hydrogen(H_2)and lithium hydride(Li H)molecules in a superconducting qubit system.The H_2 molecule is directly simulated using the 3-qubit circuit with unitary-coupled clusters(UCC)ansatz.We also combine QITE with the cluster mean-field(CMF)method to obtain an effective Hamiltonian.The Li H molecule is correspondingly simulated using the 3-qubit circuit with hardware-efficient ansatz.For comparison,the Li H molecule is also directly simulated using the 4-qubit circuit with UCC ansatz at the equilibrium point.All the experimental results show a convergence within 4 iterations,with high-fidelity ground state energy obtained.For a more complex system in the future,the CMF may allow further grouping of interactions to obtain an effective Hamiltonian,then the hybrid QITE algorithm can possibly simulate a relatively large-scale system with fewer qubits.展开更多
Acid-base dissociation constant(pK_(a)) is a key physicochemical parameter in chemical science, especially in organic synthesis and drug discovery. Current methodologies for pK_(a) prediction still suffer from limited...Acid-base dissociation constant(pK_(a)) is a key physicochemical parameter in chemical science, especially in organic synthesis and drug discovery. Current methodologies for pK_(a) prediction still suffer from limited applicability domain and lack of chemical insight. Here we present MF-SuP-pK_(a)(multi-fidelity modeling with subgraph pooling for pK_(a) prediction), a novel pK_(a) prediction model that utilizes subgraph pooling, multi-fidelity learning and data augmentation. In our model, a knowledgeaware subgraph pooling strategy was designed to capture the local and global environments around the ionization sites for micro-pK_(a) prediction. To overcome the scarcity of accurate pK_(a) data, lowfidelity data(computational pK_(a)) was used to fit the high-fidelity data(experimental pK_(a)) through transfer learning. The final MF-SuP-pK_(a) model was constructed by pre-training on the augmented ChEMBL data set and fine-tuning on the DataWarrior data set. Extensive evaluation on the DataWarrior data set and three benchmark data sets shows that MF-SuP-pK_(a) achieves superior performances to the state-of-theart pK_(a) prediction models while requires much less high-fidelity training data. Compared with Attentive FP, MF-SuP-pK_(a) achieves 23.83% and 20.12% improvement in terms of mean absolute error(MAE) on the acidic and basic sets, respectively.展开更多
Background: Endoscopic biopsy can underestimate gastric malignancies as low-grade intraepithelial neoplasia (LGIN). Definitively diagnosed LGIN would progress. This study aimed to evaluate predictive factors to identi...Background: Endoscopic biopsy can underestimate gastric malignancies as low-grade intraepithelial neoplasia (LGIN). Definitively diagnosed LGIN would progress. This study aimed to evaluate predictive factors to identify malignancies misdiagnosed as LGIN by biopsy and LGIN at high risk of progression.Methods: The clinical records of patients diagnosed with gastric LGIN by endoscopic biopsy who underwent at least two endoscopies during the first year of follow-up between 2007 and 2017 were retrospectively collected. Three endoscopists reviewed photographs of the initial endoscopy, described lesion characteristics, and made endoscopic diagnoses. Logistic regression was used to analyze predictors to identify malignancies underestimated as LGIN. A receiver operating characteristic curve was used to evaluate the diagnostic accuracy of these predictors. Patient clinical outcomes of follow-up >1 year were collected. Kaplan-Meier estimates with log-rank tests and Cox proportional hazards regression were used to analyze predictors of progression.Results: Overall, 48 of 182 (26.4%) patients were proven to have malignancies. A single lesion, a large lesion size, and marked intestinal metaplasia (IM) were independent predictors of initially misdiagnosed malignancies. The area under the curve of these predictors was 0.871, with a sensitivity of 68.7% and specificity of 92.5%. Twelve of 98 patients (12.2%) progressed during the 33-month median follow-up period. A whitish appearance, irregular margins, marked IM, and histological diagnosis of LGIN more than twice within the first year were predictors for progression.Conclusions: Lesions diagnosed as LGIN by biopsy with marked IM and other predictors above should be prudently treated for high potential to be malignancies or progress. Endoscopic follow-up with repeated biopsies within the first year is recommended.展开更多
This work is aimed to study the effects of component size and solubility on the surface composition of spray dried(SD)uniform two-component particles fabricated by micro-fluidic spray dryer.Various precursor liquid co...This work is aimed to study the effects of component size and solubility on the surface composition of spray dried(SD)uniform two-component particles fabricated by micro-fluidic spray dryer.Various precursor liquid consisting of small molecular of methionine(Met,33 g/L)or lysine(Lys,739 g/L)and large-sized silica(12 nm)were prepared by adjusting the mass ratio of components.X-ray energy disper-sive results showed that the respective enrichment degree(De)of Met and Lys on the surface of SD-M1S9 and-L1S9 prepared at 150 C were 182±9% and 125±14%.The De of hydrophobic Met for SD-M1S1 and-M9S1 were 46±9% and 4±2%,respectively,whereas relative hydrophilic Lys mainly distributed internal of the particle meanwhile the De of silica on the surface for SD-L1S1 and-L9S1 were 17±4%and 12±1%,respectively.Drying temperature(120 and 180℃)showed more apparent effect on the De of amino acid for the particles of less amino acid.The possible formation mechanism of surface composition and the surface composition impact on the wettability of particles were explored.These results provide new guidance for manufacturing functional SD powders with various components.展开更多
Functional near-infrared spectroscopy(fNIRS)is a technique of detecting cerebral cortical function by using near-infrared light,which is a multifunctional neuroimaging technique and provides a convenient and efficient...Functional near-infrared spectroscopy(fNIRS)is a technique of detecting cerebral cortical function by using near-infrared light,which is a multifunctional neuroimaging technique and provides a convenient and efficient detection method in neuroscience.In consideration of acceptability,safety,high spatial and temporal resolutions compared with electroencephalogram(EEG)and functional magnetic resonance imaging(fMRI),fNIRS is widely used to study different psychiatric disorders,most prominently affective disorders,schizophrenic illnesses,brain organic mental disorders and neurodevelopmental disorders,etc.The article focuses on the latest research progress and practical application of fNIRS in psychiatric disorders,especially traumatic brain,including studies on the characterization of phenomenology,treatment effects and descriptions of neuroimaging data.展开更多
Background:Type 1 autoimmune pancreatitis(AIP)is the pancreatic manifestation of IgG4-related disease.However,this benign disease can result in the peripancreatic vascular involvement(PVI)on occasion,which increases t...Background:Type 1 autoimmune pancreatitis(AIP)is the pancreatic manifestation of IgG4-related disease.However,this benign disease can result in the peripancreatic vascular involvement(PVI)on occasion,which increases the difficulty of diagnosis and treatment of this clinical entity as well as for differentiating it from pancreatic malignancies.Methods:We retrospectively reviewed the information on demographics,clinical presentation,laboratory,imaging and endoscopic findings of 101 hospitalized patients with type 1 AIP treated in our department.All the patients were divided into non-PVI and PVI groups according to the first hospitalized medical data.Univariate and multivariate analyses were performed to analyse the potential predictive parameter(s)of PVI in AIP patients.Results:Among the 101 type 1 AIP patients,52(51.5%)exhibited PVI,with a male/female ratio 5.5:1.Their average age was 58.37±8.68 years old.Univariate analysis revealed that the location of pancreatitis lesions,including the pancreatic tail(P=0.010),the presence of splenomegaly(P=0.001)and the white blood cell(WBC)number in peripheral blood(P=0.020),were significantly associated with PVI.The location of pancreatitis lesions,including the pancreatic tail(P=0.023),and the presence of splenomegaly(P=0.010)were found to be independent predictors of the development of PVI by a multivariable regression analysis.A total of 18 out of 25 patients in PVI group who underwent corticosteroid treatment and no less than 6 months radiological follow-up showed improvement in vascular lesions,and no case exhibited exacerbation of PVI lesions during follow-up.Of 36 patients in non-PVI group who were followed up for no less than 6 months,only one case exhibited PVI.Conclusions:This retrospective study demonstrated that type 1 AIP was associated with a high proportion of PVI.Pancreatic tail involvement and splenomegaly may predict the PVI in type 1 AIP.PVI lesions are reversible in a subset of patients.展开更多
基金financially supported by Shanghai Clinical Center for Mental Disorders(2014)the Medical Guidance Program of Shanghai Science and Technology Committee(No.15411961400)
基金support from the National Nat-ural Science Foundation of China(U1663227,21861132017,21811530003,21878170).
文摘Biomanufacturing,which uses renewable resources as raw materials and uses biological processes to produce energy and chemicals,has long been regarded as a production model that replaces the unsustainable fossil economy.The construction of non-natural and efficient biosynthesis routes of chemicals is an important goal of green biomanufacturing.Traditional methods that rely on experience are difficult to support the realization of this goal.However,with the rapid development of information technology,the intelligence of biomanufacturing has brought hope to achieve this goal.Retrobiosynthesis and computational enzyme design,as two of the main technologies in intelligent biomanufacturing,have developed rapidly in recent years and have made great achievements and some representative works have demonstrated the great value that the integration of the two fields may bring.To achieve the final integration of the two fields,it is necessary to examine the information,methods and tools from a bird’s-eye view,and to find a feasible idea and solution for establishing a connection point.For this purpose,this article briefly reviewed the main ideas,methods and tools of the two fields,and put forward views on how to achieve the integration of the two fields.
基金supported by the NSF Cooperative Agreement DMR-1644779the State of Florida.X.H.P.acknowledges the supports from the National Key R&D Program of China(Grants No.2018YFA0306600)+1 种基金the National Science Foundation of China(Grants No.11927811,12150014)Anhui Initiative in Quantum Information Technologies(Grant No.AHY050000).
文摘Cross polarization(CP)is a widely used solid-state nuclear magnetic resonance(NMR)technique for enhancing the polarization of dilute S spins from much larger polarization of abundant I spins such as 1 H.To achieve such a polarization transfer,the I spin should either be spin-locked or be converted to the dipolar ordered state through adiabatic demagnetization in the rotating frame.In this work,we analyze the spin dynamics of the Hartmann-Hahn CP(HHCP)utilizing the 1 H spin-locking,and the dipolar-order CP(DOCP)having the 1 H adiabatic demagnetization.We further propose an adiabatic demagnetization CP(ADCP)where a constant radio-frequency pulse is applied on the S spin while 1 H is adiabatically demagnetized.Our analyses indicate that ADCP utilizes the adiabatic passage to effectively achieve the polarization transfer from the 1 H to S spins.In addition,the dipolar ordered state generated during the 1 H demagnetization process could also be converted into the observable S polarization through DOCP,further enhancing the polarized signals.It is shown by both static and magic-angle-spinning(MAS)NMR experiments that ADCP has dramatically broadened the CP matching condition over the other CP schemes.Various samples have been used to demonstrate the polarization transfer efficiency of this newly proposed ADCP scheme.
基金supported by the National Natural Science Foundation of China(Grant Nos.12074336,and 11934010)the National Key Research and Development Program of China(Grant No.2019YFA0308602)+1 种基金the Fundamental Research Funds for the Central Universities in China(Grant No.2020XZZX002-01)the funding support from Tencent Corporation。
文摘As a valid tool for solving ground state problems,imaginary time evolution(ITE)is widely used in physical and chemical simulations.Different ITE-based algorithms in their quantum counterpart have recently been proposed and applied to some real systems.We experimentally realize the variational-based quantum imaginary time evolution(QITE)algorithm to simulate the ground state energy of hydrogen(H_2)and lithium hydride(Li H)molecules in a superconducting qubit system.The H_2 molecule is directly simulated using the 3-qubit circuit with unitary-coupled clusters(UCC)ansatz.We also combine QITE with the cluster mean-field(CMF)method to obtain an effective Hamiltonian.The Li H molecule is correspondingly simulated using the 3-qubit circuit with hardware-efficient ansatz.For comparison,the Li H molecule is also directly simulated using the 4-qubit circuit with UCC ansatz at the equilibrium point.All the experimental results show a convergence within 4 iterations,with high-fidelity ground state energy obtained.For a more complex system in the future,the CMF may allow further grouping of interactions to obtain an effective Hamiltonian,then the hybrid QITE algorithm can possibly simulate a relatively large-scale system with fewer qubits.
基金financially supported by National Key Research and Development Program of China (2021YFF1201400)National Natural Science Foundation of China (22220102001)Natural Science Foundation of Zhejiang Province (LZ19H300001, LD22H300001, China)。
文摘Acid-base dissociation constant(pK_(a)) is a key physicochemical parameter in chemical science, especially in organic synthesis and drug discovery. Current methodologies for pK_(a) prediction still suffer from limited applicability domain and lack of chemical insight. Here we present MF-SuP-pK_(a)(multi-fidelity modeling with subgraph pooling for pK_(a) prediction), a novel pK_(a) prediction model that utilizes subgraph pooling, multi-fidelity learning and data augmentation. In our model, a knowledgeaware subgraph pooling strategy was designed to capture the local and global environments around the ionization sites for micro-pK_(a) prediction. To overcome the scarcity of accurate pK_(a) data, lowfidelity data(computational pK_(a)) was used to fit the high-fidelity data(experimental pK_(a)) through transfer learning. The final MF-SuP-pK_(a) model was constructed by pre-training on the augmented ChEMBL data set and fine-tuning on the DataWarrior data set. Extensive evaluation on the DataWarrior data set and three benchmark data sets shows that MF-SuP-pK_(a) achieves superior performances to the state-of-theart pK_(a) prediction models while requires much less high-fidelity training data. Compared with Attentive FP, MF-SuP-pK_(a) achieves 23.83% and 20.12% improvement in terms of mean absolute error(MAE) on the acidic and basic sets, respectively.
基金This work was supported by grants from the Beijing Municipal Science and Technology Program(No.Z181100001618013)the National Key Research and Development Program of China(No.2016YFC1302802)。
文摘Background: Endoscopic biopsy can underestimate gastric malignancies as low-grade intraepithelial neoplasia (LGIN). Definitively diagnosed LGIN would progress. This study aimed to evaluate predictive factors to identify malignancies misdiagnosed as LGIN by biopsy and LGIN at high risk of progression.Methods: The clinical records of patients diagnosed with gastric LGIN by endoscopic biopsy who underwent at least two endoscopies during the first year of follow-up between 2007 and 2017 were retrospectively collected. Three endoscopists reviewed photographs of the initial endoscopy, described lesion characteristics, and made endoscopic diagnoses. Logistic regression was used to analyze predictors to identify malignancies underestimated as LGIN. A receiver operating characteristic curve was used to evaluate the diagnostic accuracy of these predictors. Patient clinical outcomes of follow-up >1 year were collected. Kaplan-Meier estimates with log-rank tests and Cox proportional hazards regression were used to analyze predictors of progression.Results: Overall, 48 of 182 (26.4%) patients were proven to have malignancies. A single lesion, a large lesion size, and marked intestinal metaplasia (IM) were independent predictors of initially misdiagnosed malignancies. The area under the curve of these predictors was 0.871, with a sensitivity of 68.7% and specificity of 92.5%. Twelve of 98 patients (12.2%) progressed during the 33-month median follow-up period. A whitish appearance, irregular margins, marked IM, and histological diagnosis of LGIN more than twice within the first year were predictors for progression.Conclusions: Lesions diagnosed as LGIN by biopsy with marked IM and other predictors above should be prudently treated for high potential to be malignancies or progress. Endoscopic follow-up with repeated biopsies within the first year is recommended.
基金supported by the National Natural Science Foundation of China(No.21878197)the Natural Science Foundation of Jjiangsu Province(No.BK20180096)+2 种基金Jiangsu Higher Education Iinstitutions(No.18KJA530004)the Suzhou Municipal Science and Technology Bureau(No.SYG201810)the Post-Doctoral Science Foundation ofjangsu(2021K356C)。
文摘This work is aimed to study the effects of component size and solubility on the surface composition of spray dried(SD)uniform two-component particles fabricated by micro-fluidic spray dryer.Various precursor liquid consisting of small molecular of methionine(Met,33 g/L)or lysine(Lys,739 g/L)and large-sized silica(12 nm)were prepared by adjusting the mass ratio of components.X-ray energy disper-sive results showed that the respective enrichment degree(De)of Met and Lys on the surface of SD-M1S9 and-L1S9 prepared at 150 C were 182±9% and 125±14%.The De of hydrophobic Met for SD-M1S1 and-M9S1 were 46±9% and 4±2%,respectively,whereas relative hydrophilic Lys mainly distributed internal of the particle meanwhile the De of silica on the surface for SD-L1S1 and-L9S1 were 17±4%and 12±1%,respectively.Drying temperature(120 and 180℃)showed more apparent effect on the De of amino acid for the particles of less amino acid.The possible formation mechanism of surface composition and the surface composition impact on the wettability of particles were explored.These results provide new guidance for manufacturing functional SD powders with various components.
文摘Functional near-infrared spectroscopy(fNIRS)is a technique of detecting cerebral cortical function by using near-infrared light,which is a multifunctional neuroimaging technique and provides a convenient and efficient detection method in neuroscience.In consideration of acceptability,safety,high spatial and temporal resolutions compared with electroencephalogram(EEG)and functional magnetic resonance imaging(fMRI),fNIRS is widely used to study different psychiatric disorders,most prominently affective disorders,schizophrenic illnesses,brain organic mental disorders and neurodevelopmental disorders,etc.The article focuses on the latest research progress and practical application of fNIRS in psychiatric disorders,especially traumatic brain,including studies on the characterization of phenomenology,treatment effects and descriptions of neuroimaging data.
基金National Natural Science Foundation of China,Joint Fund Project(grant No.U20A600)National Key R&D Program of China(grant No.2020YFC2002702)+1 种基金National Key Technology Research and Development Program(grant No.2016YFC1302802)Beijing Municipal Science and Technology Project(grant No.Z181100001618013).
文摘Background:Type 1 autoimmune pancreatitis(AIP)is the pancreatic manifestation of IgG4-related disease.However,this benign disease can result in the peripancreatic vascular involvement(PVI)on occasion,which increases the difficulty of diagnosis and treatment of this clinical entity as well as for differentiating it from pancreatic malignancies.Methods:We retrospectively reviewed the information on demographics,clinical presentation,laboratory,imaging and endoscopic findings of 101 hospitalized patients with type 1 AIP treated in our department.All the patients were divided into non-PVI and PVI groups according to the first hospitalized medical data.Univariate and multivariate analyses were performed to analyse the potential predictive parameter(s)of PVI in AIP patients.Results:Among the 101 type 1 AIP patients,52(51.5%)exhibited PVI,with a male/female ratio 5.5:1.Their average age was 58.37±8.68 years old.Univariate analysis revealed that the location of pancreatitis lesions,including the pancreatic tail(P=0.010),the presence of splenomegaly(P=0.001)and the white blood cell(WBC)number in peripheral blood(P=0.020),were significantly associated with PVI.The location of pancreatitis lesions,including the pancreatic tail(P=0.023),and the presence of splenomegaly(P=0.010)were found to be independent predictors of the development of PVI by a multivariable regression analysis.A total of 18 out of 25 patients in PVI group who underwent corticosteroid treatment and no less than 6 months radiological follow-up showed improvement in vascular lesions,and no case exhibited exacerbation of PVI lesions during follow-up.Of 36 patients in non-PVI group who were followed up for no less than 6 months,only one case exhibited PVI.Conclusions:This retrospective study demonstrated that type 1 AIP was associated with a high proportion of PVI.Pancreatic tail involvement and splenomegaly may predict the PVI in type 1 AIP.PVI lesions are reversible in a subset of patients.
