The safety and durability of lithium-ion batteries under mechanical constraints depend significantly on electrochemical,thermal,and mechanical fields in applications.Characterizing and quantifying the multi-field coup...The safety and durability of lithium-ion batteries under mechanical constraints depend significantly on electrochemical,thermal,and mechanical fields in applications.Characterizing and quantifying the multi-field coupling behaviors requires interdisciplinary efforts.Here,we design experiments under mechanical constraints and introduce an in-situ analytical framework to clarify the complex interaction mechanisms and coupling degrees among multi-physics fields.The proposed analytical framework integrates the parameterization of equivalent models,in-situ mechanical analysis,and quantitative assessment of coupling behavior.The results indicate that the significant impact of pressure on impedance at low temperatures results from the diffusion-controlled step,enhancing kinetics when external pressure,like 180 to 240 k Pa at 10℃,is applied.The diversity in control steps for the electrochemical reaction accounts for the varying impact of pressure on battery performance across different temperatures.The thermal expansion rate suggests that the swelling force varies by less than 1.60%per unit of elevated temperature during the lithiation process.By introducing a composite metric,we quantify the coupling correlation and intensity between characteristic parameters and physical fields,uncovering the highest coupling degree in electrochemical-thermal fields.These results underscore the potential of analytical approaches in revealing the mechanisms of interaction among multi-fields,with the goal of enhancing battery performance and advancing battery management.展开更多
An aerogel electrode composed of conductive active materials based on nanocellulose aerogels can absorb more electrolytes,as well as enhance electron transport and ion diffusion channels.In the present study,aerogels ...An aerogel electrode composed of conductive active materials based on nanocellulose aerogels can absorb more electrolytes,as well as enhance electron transport and ion diffusion channels.In the present study,aerogels with high strength were successfully prepared using 2,2,6,6-tetramethyl-1-piperidinyloxy free radical(TEMPO)-oxidized cellulose nanofibrils(CNF)as a raw material and polyethyleneimine(PEI)as a crosslinking agent.Simultaneously,functional electrode materials were prepared via self-assembly.Based on our findings,PEI can significantly improve the water and solvent solubility and enhance the wet strength and shape recovery ability of CNF aerogels.Meanwhile,the minimum density of the aerogel reached 0.0160 g/cm3,the maximum porosity was approximately 98.5%,and the maximum stress approximated 0.02 MPa.Furthermore,electrochemical tests revealed that after self-assembly of reduced graphene oxide(RGO)and polyaniline(PANI)solution,the mass specific capacitance of the functional composite aerogel was approximately 92 F/g and exhibited good chargedischarge performance.展开更多
With the use of acrylic acid(AA)as a monomer,humic acid(HA)and starch as raw materials,potassium persulfate(KPS)as initiator,and N,Ndimethylacrylamide(MBA)as a cross-linking agent,AA/HA/Starch graft copolymer was prep...With the use of acrylic acid(AA)as a monomer,humic acid(HA)and starch as raw materials,potassium persulfate(KPS)as initiator,and N,Ndimethylacrylamide(MBA)as a cross-linking agent,AA/HA/Starch graft copolymer was prepared and characterized by SEM and FT-IR.The effects of temperature,adsorption time,adsorbent dosage,pH value and Cu^(2+)initial concentration of the solution on the adsorption performance of the crosslinked graft copolymer were also investigated.The results showed that the Cu^(2+)adsorption capacity of the AA/HA/Starch graft copolymer increased firstly and then decreased with increasing adsorbent dosage and the initial pH value of Cu^(2+)solution.With the increase of Cu^(2+)initial concentration and the extension of adsorption time,the adsorption amount of Cu^(2+)increased rapidly and then stabilized.And it decreased slightly with the increase of temperature.At pH value of 5.5,temperature of 298 K,adsorbent dosage of 50 mg,adsorption time of 125 min,and 100 mL Cu^(2+)solution with Cu^(2+)initial concentration of 100 mg/L,the Cu^(2+)adsorption capacity of the crosslinked graft copolymer was 238 mg/g.The adsorption of Cu^(2+)by the adsorbent followed the pseudo-second-order kinetic equation and Langmuir isothermal adsorption model,and the adsorption was attached to monolayer chemical adsorption.This study proved that AA/HA/Starch graft copolymer could be used as an efficient adsorbent for the removal of harmful and toxic metal cations such as Cu^(2+)from industrial wastewater.展开更多
Lipase-catalyzed stereoselective resolution of cis-(±)-dimethyl 1-acetylpiperidine-2,3-dicarboxylate(cis-(±)-1)is an attractive route for the synthesis of(S,S)-2,8-diazobicyclo[4.3.0]nonane,an important chir...Lipase-catalyzed stereoselective resolution of cis-(±)-dimethyl 1-acetylpiperidine-2,3-dicarboxylate(cis-(±)-1)is an attractive route for the synthesis of(S,S)-2,8-diazobicyclo[4.3.0]nonane,an important chiral intermediate of the fluoroquinolone antibiotic,moxifloxacin.In our previous study,a lipase from Sporisorium reilianum(SRL)was identified to possess excellent thermostability and pH stability.However,the low enzymatic activity of the SRL is a challenge that must be addressed.A rational design was initially employed for SRL tailoring according to the engineered Candida antarctica lipase B(CALB),resulting in a beneficial variant called SRL-I194N/V195L.Subsequently,two key amino acid residues in loop 6,L145 and L154,which might modulate the lid conformation between open and closed,were identified.A tetra-site variant,SRL-I194N/V195L/L145V/L154G(V13),with a significantly enhanced activity of 87.8 U∙mg^(−1) was obtained;this value was 2195-fold higher than that of wild-type SRL.Variant V13 was used to prepare optically pure(2S,3R)-dimethyl 1-acetylpiperidine-2,3-dicarboxylate((2S,3R)-1),resolving 1 mol∙L^(−1) cis-(±)-1 with a conversion of 49.9%in 2 h and absolute stereoselectivity(E>200).Excellent stability with a half-life of 92.5 h was also observed at 50℃.Overall,the study findings reveal a lipase with high activity toward cis-(±)-1 at an industrial level and may offer a general strategy for enhancing the enzyme activity of other lipases and other classes of enzymes with a lid moiety.展开更多
5G has pushed the use of radio spectrum to a new level,and cognitive clustering network can effectively improve the utilization of radio spectrum,which is a feasible way to solve the growing demand for wireless commun...5G has pushed the use of radio spectrum to a new level,and cognitive clustering network can effectively improve the utilization of radio spectrum,which is a feasible way to solve the growing demand for wireless communications.However,cognitive clustering network is vulnerable to PUEA attack,which will lead to the degradation of system detection performance,thereby reducing the energy efficiency.Aiming at these problems,this paper investigates the optimal energy efficiency resource allocation scheme for cognitive clustering network under PUEA attack.A cooperative user selection algorithm based on selection factor is proposed to effectively resist PUEA user attack and improve detection performance.We construct the energy efficiency optimization problem under multi-constraint conditions and transform the nonlinear programming problem into parametric programming problem,which is solved by Lagrangian function and Karush-Kuhn-Tucker condition.Then the sub-gradient iterative algorithm based on optimal energy efficiency under PUEA attack is proposed and its complexity is analyzed.Simulation results indicate that proposed method is effective when subjected to PUEA attacks,and the impact of different parameters on energy efficiency is analyzed.展开更多
Amyloid-b,tau pathology,and biomarkers of neurodegeneration make up the core diagnostic biomarkers of Alzheimer disease(AD).However,these proteins represent only a fraction of the complex biological processes underlyi...Amyloid-b,tau pathology,and biomarkers of neurodegeneration make up the core diagnostic biomarkers of Alzheimer disease(AD).However,these proteins represent only a fraction of the complex biological processes underlying AD,and individuals with other brain diseases in which AD pathology is a comorbidity also test positive for these diagnostic biomarkers.More ADspecific early diagnostic and disease staging biomarkers are needed.In this study,we performed tandem mass tag proteomic analysis of paired cerebrospinal fluid(CSF)and serum samples in a discovery cohort comprising 98 participants.Candidate biomarkers were validated by parallel reaction monitoring–based targeted proteomic assays in an independent multicenter cohort comprising 288 participants.We quantified 3,238 CSF and 1,702 serum proteins in the discovery cohort,identifying 171 and 860 CSF proteins and 37 and 323 serum proteins as potential early diagnostic and staging biomarkers,respectively.In the validation cohort,58 and 21 CSF proteins,as well as 12 and 18 serum proteins,were verified as early diagnostic and staging biomarkers,respectively.Separate 19-protein CSF and an 8-protein serum biomarker panels were built by machine learning to accurately classify mild cognitive impairment(MCI)due to AD from normal cognition with areas under the curve of 0.984 and 0.881,respectively.The 19-protein CSF biomarker panel also effectively discriminated patients with MCI due to AD from patients with other neurodegenerative diseases.Moreover,we identified 21 CSF and 18 serum stage-associated proteins re-flecting AD stages.Our findings provide a foundation for developing bloodbased tests for AD screening and staging in clinical practice.展开更多
To address the increasing need for detecting and validating protein biomarkers in clinical specimens,mass spectrometry(MS)-based targeted proteomic techniques,including the selected reaction monitoring(SRM),parallel r...To address the increasing need for detecting and validating protein biomarkers in clinical specimens,mass spectrometry(MS)-based targeted proteomic techniques,including the selected reaction monitoring(SRM),parallel reaction monitoring(PRM),and massively parallel dataindependent acquisition(DIA),have been developed.For optimal performance,they require the fragment ion spectra of targeted peptides as prior knowledge.In this report,we describe a MS pipeline and spectral resource to support targeted proteomics studies for human tissue samples.To build the spectral resource,we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker.We then applied the workflow to generate DPHL,a comprehensive DIA pan-human library,from 1096 data-dependent acquisition(DDA)MS raw files for 16 types of cancer samples.This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer(PCa)patients.Thereafter,PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated.As a second application,the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma(DLBCL)patients and 18 healthy control subjects.Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM.These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery.DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.展开更多
Physical and chemical technologies have been continuously progressing advances in neuroscience research.The development of research tools for closed-loop control and monitoring neural activities in behaving animals is...Physical and chemical technologies have been continuously progressing advances in neuroscience research.The development of research tools for closed-loop control and monitoring neural activities in behaving animals is highly desirable.In this paper,we introduce a wirelessly operated,miniaturized microprobe system for optical interrogation and neurochemical sensing in the deep brain.Via epitaxial liftoff and transfer printing,microscale light-emitting diodes(micro-LEDs)as light sources and poly(3,4-ethylenedioxythiophene)polystyrene sulfonate(PEDOT:PSS)-coated diamond films as electrochemical sensors are vertically assembled to form implantable optoelectrochemical probes for real-time optogenetic stimulation and dopamine detection capabilities.A customized,lightweight circuit module is employed for untethered,remote signal control,and data acquisition.After the probe is injected into the ventral tegmental area(VTA)of freely behaving mice,in vivo experiments clearly demonstrate the utilities of the multifunctional optoelectrochemical microprobe system for optogenetic interference of place preferences and detection of dopamine release.The presented options for material and device integrations provide a practical route to simultaneous optical control and electrochemical sensing of complex nervous systems.展开更多
Gut microbial dysbiosis has been linked to many noncommunicable diseases.However,little is known about specific gut microbiota composition and its correlated metabolites associated with molecular signatures underlying...Gut microbial dysbiosis has been linked to many noncommunicable diseases.However,little is known about specific gut microbiota composition and its correlated metabolites associated with molecular signatures underlying host response to infection.Here,we describe the construction of a proteomic risk score based on 20 blood proteomic biomarkers,which have recently been identified as molecular signatures predicting the progression of the COVID-19.We demonstrate that in our cohort of 990 healthy individuals without infection,this proteomic risk score is positively associated with proinflammatory cytokines mainly among older,but not younger,individuals.We further discover that a core set of gut microbiota can accurately predict the above proteomic biomarkers among 301 individuals using a machine learning model and that these gut microbiota features are highly correlated with proinflammatory cytokines in another independent set of 366 individuals.Fecal metabolomics analysis suggests potential amino acid-related pathways linking gut microbiota to host metabolism and inflammation.Overall,our multi-omics analyses suggest that gut microbiota composition and function are closely related to inflammation and molecular signatures of host response to infection among healthy individuals.These results may provide novel insights into the cross-talk between gut microbiota and host immune system.展开更多
A lipase from Sporisorium reilianum SRZ2(SRL)with 73%amino acid sequence identity to Candida antarctica lipase B(CALB)was cloned and overexpressed in Pichia pastoris.The recombinant SRL showed a preference for short-c...A lipase from Sporisorium reilianum SRZ2(SRL)with 73%amino acid sequence identity to Candida antarctica lipase B(CALB)was cloned and overexpressed in Pichia pastoris.The recombinant SRL showed a preference for short-chain p-nitrophenyl esters.It achieved maximum activity at pH 8.0 and 65°C for p-nitrophenyl hexanoate(C6)with Km and kcar/Km values of 0.14 mmol·L-1 and 1712 min 1.mmol·L-1 at 30℃,respec-tively.SRL displayed excellent thermostability and pH stability,retaining more than 79%of its initial activity after incubation at 60℃ for 72h and 75%atpH 3to 11 for 72 h.It also maintained most of its activity in the presence of inhibitors and detergents except sodium dodecyl sulfate,and it tolerated organic solvents.SRL was covalently immobilized and successfully used for ethyl hexanoate synthesis in cyclohexane or in a solvent-free system with a high conversion yield(>95%).Furthermore,high con-version yield was also achieved for the synthesis of various short-chain flavor esters when high substrate concentra-tions of2 mol.LI were applied.This study indicated that a.CALB-type lipase from S.reiliamum SRZ2 showed great potential in organic ester synthesis.展开更多
Thermometric detectors are crucial in evaluating the condition of target objects spanning from environments to the human body.Optical-based thermal sensing tools have received extensive attention,in which the photon u...Thermometric detectors are crucial in evaluating the condition of target objects spanning from environments to the human body.Optical-based thermal sensing tools have received extensive attention,in which the photon upconversion process with low autofluorescence and high tissue penetration depth is considered as a competent method for temperature monitoring,particularly in biomedical fields.Here,we present an optoelectronic thermometer via infrared-to-visible upconversion,accomplished by integrated light receiving and emission devices.Fully fabricated thin-film,microscale devices present temperature-dependent light emission with an intensity change of 1.5%℃^(-1) and a spectral shift of 0.18 nm℃^(-1).The sensing mechanism is systematically characterized and ascribed to temperature dependent optoelectronic properties of the semiconductor band structure and the circuit operation condition.Patterned device arrays showcase the capability for spatially resolved temperature mapping.Finally,in vitro and in vivo experiments implemented with integrated fiber-optic sensors demonstrate real-time thermal detection of dynamic human activity and in the deep brain of animals,respectively.展开更多
Dear editors,Colorectal cancer(CRC)is the second leading cause of cancer deaths in developed countries[1].The malignant transformation from small clumps to cancer takes about 10 years[2].This study aimed to characteri...Dear editors,Colorectal cancer(CRC)is the second leading cause of cancer deaths in developed countries[1].The malignant transformation from small clumps to cancer takes about 10 years[2].This study aimed to characterize proteomic dynamics associated with CRC development and progres-sion,and identify novel therapeutic targets for intercepting the underlying oncogenic processes.We have optimized pressure cycling technology(PCT)coupled with data-independent acquisition mass spectrometry(DIA-MS)for robust and reproducible proteomic analysis of biopsy-level formalin-fixed paraffin-embedded(FFPE)tissues[3].展开更多
基金supported by the National Science Fund for Excellent Youth Scholars of China(52222708)the National Natural Science Foundation of China(51977007)。
文摘The safety and durability of lithium-ion batteries under mechanical constraints depend significantly on electrochemical,thermal,and mechanical fields in applications.Characterizing and quantifying the multi-field coupling behaviors requires interdisciplinary efforts.Here,we design experiments under mechanical constraints and introduce an in-situ analytical framework to clarify the complex interaction mechanisms and coupling degrees among multi-physics fields.The proposed analytical framework integrates the parameterization of equivalent models,in-situ mechanical analysis,and quantitative assessment of coupling behavior.The results indicate that the significant impact of pressure on impedance at low temperatures results from the diffusion-controlled step,enhancing kinetics when external pressure,like 180 to 240 k Pa at 10℃,is applied.The diversity in control steps for the electrochemical reaction accounts for the varying impact of pressure on battery performance across different temperatures.The thermal expansion rate suggests that the swelling force varies by less than 1.60%per unit of elevated temperature during the lithiation process.By introducing a composite metric,we quantify the coupling correlation and intensity between characteristic parameters and physical fields,uncovering the highest coupling degree in electrochemical-thermal fields.These results underscore the potential of analytical approaches in revealing the mechanisms of interaction among multi-fields,with the goal of enhancing battery performance and advancing battery management.
文摘An aerogel electrode composed of conductive active materials based on nanocellulose aerogels can absorb more electrolytes,as well as enhance electron transport and ion diffusion channels.In the present study,aerogels with high strength were successfully prepared using 2,2,6,6-tetramethyl-1-piperidinyloxy free radical(TEMPO)-oxidized cellulose nanofibrils(CNF)as a raw material and polyethyleneimine(PEI)as a crosslinking agent.Simultaneously,functional electrode materials were prepared via self-assembly.Based on our findings,PEI can significantly improve the water and solvent solubility and enhance the wet strength and shape recovery ability of CNF aerogels.Meanwhile,the minimum density of the aerogel reached 0.0160 g/cm3,the maximum porosity was approximately 98.5%,and the maximum stress approximated 0.02 MPa.Furthermore,electrochemical tests revealed that after self-assembly of reduced graphene oxide(RGO)and polyaniline(PANI)solution,the mass specific capacitance of the functional composite aerogel was approximately 92 F/g and exhibited good chargedischarge performance.
文摘With the use of acrylic acid(AA)as a monomer,humic acid(HA)and starch as raw materials,potassium persulfate(KPS)as initiator,and N,Ndimethylacrylamide(MBA)as a cross-linking agent,AA/HA/Starch graft copolymer was prepared and characterized by SEM and FT-IR.The effects of temperature,adsorption time,adsorbent dosage,pH value and Cu^(2+)initial concentration of the solution on the adsorption performance of the crosslinked graft copolymer were also investigated.The results showed that the Cu^(2+)adsorption capacity of the AA/HA/Starch graft copolymer increased firstly and then decreased with increasing adsorbent dosage and the initial pH value of Cu^(2+)solution.With the increase of Cu^(2+)initial concentration and the extension of adsorption time,the adsorption amount of Cu^(2+)increased rapidly and then stabilized.And it decreased slightly with the increase of temperature.At pH value of 5.5,temperature of 298 K,adsorbent dosage of 50 mg,adsorption time of 125 min,and 100 mL Cu^(2+)solution with Cu^(2+)initial concentration of 100 mg/L,the Cu^(2+)adsorption capacity of the crosslinked graft copolymer was 238 mg/g.The adsorption of Cu^(2+)by the adsorbent followed the pseudo-second-order kinetic equation and Langmuir isothermal adsorption model,and the adsorption was attached to monolayer chemical adsorption.This study proved that AA/HA/Starch graft copolymer could be used as an efficient adsorbent for the removal of harmful and toxic metal cations such as Cu^(2+)from industrial wastewater.
基金This work was financially supported by the National Key Research and Development Program of China(2021YFC2102100 and 2018YFA0901400)the Fundamental Research Funds for the Provincial Universities of Zhejiang(RF-C2019005)+1 种基金the National Natural Science Foundation of China(32000898)the Natural Science Foundation of Zhejiang Province(LQ21B060006).
文摘Lipase-catalyzed stereoselective resolution of cis-(±)-dimethyl 1-acetylpiperidine-2,3-dicarboxylate(cis-(±)-1)is an attractive route for the synthesis of(S,S)-2,8-diazobicyclo[4.3.0]nonane,an important chiral intermediate of the fluoroquinolone antibiotic,moxifloxacin.In our previous study,a lipase from Sporisorium reilianum(SRL)was identified to possess excellent thermostability and pH stability.However,the low enzymatic activity of the SRL is a challenge that must be addressed.A rational design was initially employed for SRL tailoring according to the engineered Candida antarctica lipase B(CALB),resulting in a beneficial variant called SRL-I194N/V195L.Subsequently,two key amino acid residues in loop 6,L145 and L154,which might modulate the lid conformation between open and closed,were identified.A tetra-site variant,SRL-I194N/V195L/L145V/L154G(V13),with a significantly enhanced activity of 87.8 U∙mg^(−1) was obtained;this value was 2195-fold higher than that of wild-type SRL.Variant V13 was used to prepare optically pure(2S,3R)-dimethyl 1-acetylpiperidine-2,3-dicarboxylate((2S,3R)-1),resolving 1 mol∙L^(−1) cis-(±)-1 with a conversion of 49.9%in 2 h and absolute stereoselectivity(E>200).Excellent stability with a half-life of 92.5 h was also observed at 50℃.Overall,the study findings reveal a lipase with high activity toward cis-(±)-1 at an industrial level and may offer a general strategy for enhancing the enzyme activity of other lipases and other classes of enzymes with a lid moiety.
基金by the National Natural Science Foundation of China for Young Scholars under Grant No.61701167.
文摘5G has pushed the use of radio spectrum to a new level,and cognitive clustering network can effectively improve the utilization of radio spectrum,which is a feasible way to solve the growing demand for wireless communications.However,cognitive clustering network is vulnerable to PUEA attack,which will lead to the degradation of system detection performance,thereby reducing the energy efficiency.Aiming at these problems,this paper investigates the optimal energy efficiency resource allocation scheme for cognitive clustering network under PUEA attack.A cooperative user selection algorithm based on selection factor is proposed to effectively resist PUEA user attack and improve detection performance.We construct the energy efficiency optimization problem under multi-constraint conditions and transform the nonlinear programming problem into parametric programming problem,which is solved by Lagrangian function and Karush-Kuhn-Tucker condition.Then the sub-gradient iterative algorithm based on optimal energy efficiency under PUEA attack is proposed and its complexity is analyzed.Simulation results indicate that proposed method is effective when subjected to PUEA attacks,and the impact of different parameters on energy efficiency is analyzed.
基金This work was supported by grants from the Key Research and Development project of Zhejiang Province(2019C03039)the National Natural Science Foundation of China(81970998)+1 种基金the Science Innovation 2030-Brain Science and Brain-Inspired Intelligence Technology Major Projects(nos.2021ZD0201103 and 2021ZD0201803)the Integrative Traditional Chinese and Western Medicine Innovation Team for Neurodegenerative Diseases of Zhejiang Province.
文摘Amyloid-b,tau pathology,and biomarkers of neurodegeneration make up the core diagnostic biomarkers of Alzheimer disease(AD).However,these proteins represent only a fraction of the complex biological processes underlying AD,and individuals with other brain diseases in which AD pathology is a comorbidity also test positive for these diagnostic biomarkers.More ADspecific early diagnostic and disease staging biomarkers are needed.In this study,we performed tandem mass tag proteomic analysis of paired cerebrospinal fluid(CSF)and serum samples in a discovery cohort comprising 98 participants.Candidate biomarkers were validated by parallel reaction monitoring–based targeted proteomic assays in an independent multicenter cohort comprising 288 participants.We quantified 3,238 CSF and 1,702 serum proteins in the discovery cohort,identifying 171 and 860 CSF proteins and 37 and 323 serum proteins as potential early diagnostic and staging biomarkers,respectively.In the validation cohort,58 and 21 CSF proteins,as well as 12 and 18 serum proteins,were verified as early diagnostic and staging biomarkers,respectively.Separate 19-protein CSF and an 8-protein serum biomarker panels were built by machine learning to accurately classify mild cognitive impairment(MCI)due to AD from normal cognition with areas under the curve of 0.984 and 0.881,respectively.The 19-protein CSF biomarker panel also effectively discriminated patients with MCI due to AD from patients with other neurodegenerative diseases.Moreover,we identified 21 CSF and 18 serum stage-associated proteins re-flecting AD stages.Our findings provide a foundation for developing bloodbased tests for AD screening and staging in clinical practice.
基金supported by the National Natural Science Foundation of China(Grant No.81972492)National Science Fund for Young Scholars(Grant No.21904107)+7 种基金Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholars(Grant No.LR19C050001)Hangzhou Agriculture and Society Advancement Program(Grant No.20190101A04)Westlake Startup Grantresearch funds from the National Cancer Centre Singapore and Singapore General Hospital,Singaporethe National Key R&D Program of China(Grant No.2016YFC0901704)Zhejiang Innovation Discipline Project of Laboratory Animal Genetic Engineering(Grant No.201510)the Netherlands Cancer Society(Grant No.NKI 2014-6651)The Netherlands Organization for Scientific Research(NWO)-Middelgroot(Grant No.91116017)
文摘To address the increasing need for detecting and validating protein biomarkers in clinical specimens,mass spectrometry(MS)-based targeted proteomic techniques,including the selected reaction monitoring(SRM),parallel reaction monitoring(PRM),and massively parallel dataindependent acquisition(DIA),have been developed.For optimal performance,they require the fragment ion spectra of targeted peptides as prior knowledge.In this report,we describe a MS pipeline and spectral resource to support targeted proteomics studies for human tissue samples.To build the spectral resource,we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker.We then applied the workflow to generate DPHL,a comprehensive DIA pan-human library,from 1096 data-dependent acquisition(DDA)MS raw files for 16 types of cancer samples.This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer(PCa)patients.Thereafter,PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated.As a second application,the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma(DLBCL)patients and 18 healthy control subjects.Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM.These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery.DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.
基金This research is supported by the National Natural Science Foundation of China(NSFC)(61874064)the Beijing Innovation Center for Future Chips,Tsinghua University,and the Beijing National Research Center for Information Science and Technology(BNR2019ZS01005)。
文摘Physical and chemical technologies have been continuously progressing advances in neuroscience research.The development of research tools for closed-loop control and monitoring neural activities in behaving animals is highly desirable.In this paper,we introduce a wirelessly operated,miniaturized microprobe system for optical interrogation and neurochemical sensing in the deep brain.Via epitaxial liftoff and transfer printing,microscale light-emitting diodes(micro-LEDs)as light sources and poly(3,4-ethylenedioxythiophene)polystyrene sulfonate(PEDOT:PSS)-coated diamond films as electrochemical sensors are vertically assembled to form implantable optoelectrochemical probes for real-time optogenetic stimulation and dopamine detection capabilities.A customized,lightweight circuit module is employed for untethered,remote signal control,and data acquisition.After the probe is injected into the ventral tegmental area(VTA)of freely behaving mice,in vivo experiments clearly demonstrate the utilities of the multifunctional optoelectrochemical microprobe system for optogenetic interference of place preferences and detection of dopamine release.The presented options for material and device integrations provide a practical route to simultaneous optical control and electrochemical sensing of complex nervous systems.
基金supported by the National Natural Science Foundation of China(82073529,81903316,81773416,81972492,21904107,81672086)Zhejiang Ten-thousand Talents Program(2019R52039)+3 种基金Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholars(LR19C050001)the 5010 Program for Clinical Researches(2007032)the Sun Yat-sen University,Hangzhou Agriculture and Society Advancement Program(20190101A04)Tencent foundation(2020)。
文摘Gut microbial dysbiosis has been linked to many noncommunicable diseases.However,little is known about specific gut microbiota composition and its correlated metabolites associated with molecular signatures underlying host response to infection.Here,we describe the construction of a proteomic risk score based on 20 blood proteomic biomarkers,which have recently been identified as molecular signatures predicting the progression of the COVID-19.We demonstrate that in our cohort of 990 healthy individuals without infection,this proteomic risk score is positively associated with proinflammatory cytokines mainly among older,but not younger,individuals.We further discover that a core set of gut microbiota can accurately predict the above proteomic biomarkers among 301 individuals using a machine learning model and that these gut microbiota features are highly correlated with proinflammatory cytokines in another independent set of 366 individuals.Fecal metabolomics analysis suggests potential amino acid-related pathways linking gut microbiota to host metabolism and inflammation.Overall,our multi-omics analyses suggest that gut microbiota composition and function are closely related to inflammation and molecular signatures of host response to infection among healthy individuals.These results may provide novel insights into the cross-talk between gut microbiota and host immune system.
文摘A lipase from Sporisorium reilianum SRZ2(SRL)with 73%amino acid sequence identity to Candida antarctica lipase B(CALB)was cloned and overexpressed in Pichia pastoris.The recombinant SRL showed a preference for short-chain p-nitrophenyl esters.It achieved maximum activity at pH 8.0 and 65°C for p-nitrophenyl hexanoate(C6)with Km and kcar/Km values of 0.14 mmol·L-1 and 1712 min 1.mmol·L-1 at 30℃,respec-tively.SRL displayed excellent thermostability and pH stability,retaining more than 79%of its initial activity after incubation at 60℃ for 72h and 75%atpH 3to 11 for 72 h.It also maintained most of its activity in the presence of inhibitors and detergents except sodium dodecyl sulfate,and it tolerated organic solvents.SRL was covalently immobilized and successfully used for ethyl hexanoate synthesis in cyclohexane or in a solvent-free system with a high conversion yield(>95%).Furthermore,high con-version yield was also achieved for the synthesis of various short-chain flavor esters when high substrate concentra-tions of2 mol.LI were applied.This study indicated that a.CALB-type lipase from S.reiliamum SRZ2 showed great potential in organic ester synthesis.
基金National Natural Science Foundation of China(NSFC)(62005016,61874064)Tsinghua University Initiative Scientifc Research Program+1 种基金Bejing Municipal Natural Science Foundation(4202032)EnSan Frontier Innovation Foundation(2022003).
文摘Thermometric detectors are crucial in evaluating the condition of target objects spanning from environments to the human body.Optical-based thermal sensing tools have received extensive attention,in which the photon upconversion process with low autofluorescence and high tissue penetration depth is considered as a competent method for temperature monitoring,particularly in biomedical fields.Here,we present an optoelectronic thermometer via infrared-to-visible upconversion,accomplished by integrated light receiving and emission devices.Fully fabricated thin-film,microscale devices present temperature-dependent light emission with an intensity change of 1.5%℃^(-1) and a spectral shift of 0.18 nm℃^(-1).The sensing mechanism is systematically characterized and ascribed to temperature dependent optoelectronic properties of the semiconductor band structure and the circuit operation condition.Patterned device arrays showcase the capability for spatially resolved temperature mapping.Finally,in vitro and in vivo experiments implemented with integrated fiber-optic sensors demonstrate real-time thermal detection of dynamic human activity and in the deep brain of animals,respectively.
基金supported by the National Key Research and Development Program of China(Grant No.2017YFC0908200),National Natural Science Founda-tion of China(Grant No.81972270,81972492,32027801,21904107),the Zhejiang Provincial Science Foundation for Distinguished Young Scholars(Grant No.LR19C050001),Hangzhou Agriculture and Society Advancement Program(Grant No.20190101A04)and 2019 Zhejiang University Academic Award for Outstanding Doctoral Candidates to YK.S(Grant No.2019071).
文摘Dear editors,Colorectal cancer(CRC)is the second leading cause of cancer deaths in developed countries[1].The malignant transformation from small clumps to cancer takes about 10 years[2].This study aimed to characterize proteomic dynamics associated with CRC development and progres-sion,and identify novel therapeutic targets for intercepting the underlying oncogenic processes.We have optimized pressure cycling technology(PCT)coupled with data-independent acquisition mass spectrometry(DIA-MS)for robust and reproducible proteomic analysis of biopsy-level formalin-fixed paraffin-embedded(FFPE)tissues[3].