G protein coupled receptor kinase 2 (GRK2) is a kinase that regulates cardiac signaling activity. Inhibiting GRK2 is a promising mechanism for the treatment of heart failure (HF). Further development and optimization ...G protein coupled receptor kinase 2 (GRK2) is a kinase that regulates cardiac signaling activity. Inhibiting GRK2 is a promising mechanism for the treatment of heart failure (HF). Further development and optimization of inhibitors targeting GRK2 are highly meaningful. Therefore, in order to design GRK2 inhibitors with better performance, the most active molecule was selected as a reference compound from a data set containing 4-pyridylhydrazone derivatives and triazole derivatives, and its scaffold was extracted as the initial scaffold. Then, a powerful optimization-based framework for de novo drug design, guided by binding affinity, was used to generate a virtual molecular library targeting GRK2. The binding affinity of each virtual compound in this dataset was predicted by our developed deep learning model, and the designed potential compound with high binding affinity was selected for molecular docking and molecular dynamics simulation. It was found that the designed potential molecule binds to the ATP site of GRK2, which consists of key amino acids including Arg199, Gly200, Phe202, Val205, Lys220, Met274 and Asp335. The scaffold of the molecule is stabilized mainly by H-bonding and hydrophobic contacts. Concurrently, the reference compound in the dataset was also simulated by docking. It was found that this molecule also binds to the ATP site of GRK2. In addition, its scaffold is stabilized mainly by H-bonding and π-cation stacking interactions with Lys220, as well as hydrophobic contacts. The above results show that the designed potential molecule has similar binding modes to the reference compound, supporting the effectiveness of our framework for activity-focused molecular design. Finally, we summarized the interaction characteristics of general GRK2 inhibitors and gained insight into their molecule-target binding mechanisms, thereby facilitating the expansion of lead to hit compound.展开更多
The selection of chemical reactions is directly related to the quality of synthesis pathways,so a reasonable reaction evaluation metric plays a crucial role in the design and planning of synthesis pathways.Since react...The selection of chemical reactions is directly related to the quality of synthesis pathways,so a reasonable reaction evaluation metric plays a crucial role in the design and planning of synthesis pathways.Since reaction conditions also need to be considered in synthesis pathway design,a reaction metric that combines reaction time,temperature,and yield is required for chemical reactions of different reaction agents.In this study,a chemical reaction graph descriptor which includes the atom-atom mapping relationship is proposed to effectively describe reactions.Then,through pre-training using graph contrastive learning and fine-tuning through supervised learning,we establish a model for generating the probability of reaction superiority(RSscore).Finally,to validate the effectiveness of the current evaluation index,RSscore is applied in two applications,namely reaction evaluation and synthesis routes analysis,which proves that the RSscore provides an important agents-considered evaluation criterion for computer-aided synthesis planning(CASP).展开更多
Small-molecule drugs are essential for maintaining human health. The objective of this study is to identify a molecule that can inhibit the Factor Xa protein and be easily procured. An optimization-based de novo drug ...Small-molecule drugs are essential for maintaining human health. The objective of this study is to identify a molecule that can inhibit the Factor Xa protein and be easily procured. An optimization-based de novo drug design framework, Drug CAMD, that integrates a deep learning model with a mixed-integer nonlinear programming model is used for designing drug candidates. Within this framework, a virtual chemical library is specifically tailored to inhibit Factor Xa. To further filter and narrow down the lead compounds from the designed compounds, comprehensive approaches involving molecular docking,binding pose metadynamics(BPMD), binding free energy calculations, and enzyme activity inhibition analysis are utilized. To maximize efficiency in terms of time and resources, molecules for in vitro activity testing are initially selected from commercially available portions of customized virtual chemical libraries. In vitro studies assessing inhibitor activities have confirmed that the compound EN300-331859shows potential Factor Xa inhibition, with an IC_(50)value of 34.57 μmol·L^(-1). Through in silico molecular docking and BPMD, the most plausible binding pose for the EN300-331859-Factor Xa complex are identified. The estimated binding free energy values correlate well with the results obtained from biological assays. Consequently, EN300-331859 is identified as a novel and effective sub-micromolar inhibitor of Factor Xa.展开更多
Over the last three decades,flexibility and controllability considerations for heat exchanger networks(HENs)have received great attention,respectively.However,they should be simultaneously incorporated in HEN synthesi...Over the last three decades,flexibility and controllability considerations for heat exchanger networks(HENs)have received great attention,respectively.However,they should be simultaneously incorporated in HEN synthesis to allow the economic performance to be achievable in a practical operating environment.This paper proposes a method for simultaneous synthesis of flexible and controllable HEN by considering their coupling.The key idea is to add the bypasses with optimized initial fractions and positions to explore such coupling,and consequently enabling HENs to be operated successfully over a range of disturbance variations.These are implemented by identifying and quantifying disturbance propagations,and then examining the sensitivity of bypasses to the entire HEN.In this way,the superstructurebased mixed integer non-linear programming(MINLP)with objective function of minimizing the total annual cost is formulated.A case study is used to demonstrate the application of the proposed method.Quantitative measures and dynamic simulation show the ability to provide the satisfactory flexibility and controllability of the obtained HEN.展开更多
In this paper, an efficient methodology for synthesizing the indirect work exchange networks(WEN) considering isothermal process and adiabatic process respectively based on transshipment model is first proposed. In co...In this paper, an efficient methodology for synthesizing the indirect work exchange networks(WEN) considering isothermal process and adiabatic process respectively based on transshipment model is first proposed. In contrast with superstructure method, the transshipment model is easier to obtain the minimum utility consumption taken as the objective function and more convenient for us to attain the optimal network configuration for further minimizing the number of units. Different from division of temperature intervals in heat exchange networks,different pressure intervals are gained according to the maximum compression/expansion ratio in consideration of operating principles of indirect work exchangers and the characteristics of no pressure constraints for stream matches. The presented approach for WEN synthesis is a linear programming model applied to the isothermal process, but for indirect work exchange networks with adiabatic process, a nonlinear programming model needs establishing. Additionally, temperatures should be regarded as decision variables limited to the range between inlet and outlet temperatures in each sub-network. The constructed transshipment model can be solved first to get the minimum utility consumption and further to determine the minimum number of units by merging the adjacent pressure intervals on the basis of the proposed merging methods, which is proved to be effective through exergy analysis at the level of units structures. Finally, two cases are calculated to confirm it is dramatically feasible and effective that the optimal WEN configuration can be gained by the proposed method.展开更多
As part of efforts to reduce anthropogenic CO_(2) emissions by the steelmaking industry,this study investigated the direct reduction of industrially produced hematite pellets with H_(2) using the Doehlert experimental...As part of efforts to reduce anthropogenic CO_(2) emissions by the steelmaking industry,this study investigated the direct reduction of industrially produced hematite pellets with H_(2) using the Doehlert experimental design to evaluate the effect of pellet diameter(10.5-16.5 mm),porosity(0.36-0.44),and temperature(600-1200℃).A strong interactive effect between temperature and pellet size was observed,indicating that these variables cannot be considered independently.The increase in temperature and decrease in pellet size considerably favor the reduction rate,while porosity did not show a relevant effect.The change in pellet size during the reduction was negligible,except at elevated temperatures due to crack formation.A considerable decrease in mechanical strength at high temperatures suggests a maximum process operating temperature of 900℃.Good predictive capacity was achieved using the modified grain model to simulate the three consecutive non-catalytic gas-solid reactions,considering different pellet sizes and porosities,changes during the reaction from 800 to 900℃.However,for other temperatures,different mechanisms of structural modifications must be considered in the modeling.These results represent significant contributions to the development of ore pellets for CO_(2)-free steelmaking technology.展开更多
Due to the deterioration of serious energy dilemma,energy-conservation and emission–reduction have been the strategic target in the past decades,thus people have identified the vital importance of higher energy effic...Due to the deterioration of serious energy dilemma,energy-conservation and emission–reduction have been the strategic target in the past decades,thus people have identified the vital importance of higher energy efficiency and the influence of lower carbon development.Since work exchange network is a significant part of energy recovery system,its optima design will have dramatically significant effect on energy consumption reduction in chemical process system.With an extension of the developed transshipment model in isothermal process,a novel step-wise methodology for synthesis of direct work exchange network(WEN)in adiabatic process involving heat integration is first proposed in this paper,where a nonlinear programming(NLP)model is formulated by regarding the minimum utility consumption as objective function and optimizing the initial WEN in accordance with the presented matching rules to get the optimized WEN configuration at first.Furthermore,we focus on the work exchange network synthesis with heat integration to attain the minimal total annual cost(TAC)with the introduction of heat-exchange equipment that is achieved by the following strategies in sequence:introducing heat-exchange equipment directly,adjusting the work quantity of the adjacent utility compressors or expanders,and approximating upper/lower pressure limits consequently to obtain considerable cost savings of expanders or compressors and work utility.Finally,a case taken from the literature is studied to illustrate the feasibility and effectiveness of the proposed method.展开更多
Integrating multiple systems into one has become an important trend in Process Systems Engineering research field since there is strong demand from the modern industries. In this study, a stage-wise superstructurebase...Integrating multiple systems into one has become an important trend in Process Systems Engineering research field since there is strong demand from the modern industries. In this study, a stage-wise superstructurebased method is proposed to synthesize a combined mass and heat exchange network(CM&HEN) which has two parts as the mass exchange network(MEN) and heat exchange network(HEN) involved. To express the possible heat exchange requirements resulted from mass exchange operations, a so called "indistinct HEN superstructure(IHS)", which can contain the all potential matches between streams, is constructed at first. Then, a non-linear programming(NLP) mathematical model is established for the simultaneous synthesis and optimization of networks. Therein, the interaction between mass exchange and heat exchange is modeling formulated.The NLP model has later been examined using an example from literature, and the effectiveness of the proposed method has been demonstrated with the results.展开更多
Because of its paramount importance in the successful industrial control strategy of a given heat exchanger network(HEN),the control structure designs for providing appropriate manipulated variable(MV)and controlled v...Because of its paramount importance in the successful industrial control strategy of a given heat exchanger network(HEN),the control structure designs for providing appropriate manipulated variable(MV)and controlled variable pairings have received considerable attention.However,quite frequently HENs with such control structures face the problem of hard constraints,typically holding the HENs at less controlled operating space.So both the MV pairings and the above control pairings should be considered to design a control structure.This paper investigates the systematic incorporation of the two pairings,and presents a methodology for designing such two-tier control structure.This is developed based on the sequential strategy,coupling an indirect-tier with direct-tier control structure design,wherein the intention is realized in the former stage and the latter is implemented for further optimization.The MV identification and pairing are achieved through variations in heat load of heat exchangers to design the indirect-tier control structure.Then the direct-tier control structure is followed the relative gain array pairing rules.With the proposed methodology,on the one hand,it generates an explicit connection between the MV pairings and the HEN configuration,and the quantitative interaction measure is improved to avoid the multiple solutions to break the relationship among all the control pairings into individuals;on the other hand,a two-tier control structure reveals control potentials and control system design requirements,this may avoid complex and economically unfavourable control and HEN structures.The application of proposed framework is illustrated with two cases involving the dynamic simulation analysis,the quantitative assessment and the random test.展开更多
Thermal degradation of a FR-4 type printed circuit board, PCB, containing brominated flame retardant has been studied both in inert and oxidative atmosphere for the emission control of harmful brominated compounds. Th...Thermal degradation of a FR-4 type printed circuit board, PCB, containing brominated flame retardant has been studied both in inert and oxidative atmosphere for the emission control of harmful brominated compounds. The presence of oxygen in atmosphere resulted in the reduction of the yield of hydrogen bromide, one of the major brominated compounds in thermal treatment, and in the enhancement of the formation of bromine and hypobromous acid. The intentional addition of zinc oxide to the PCB powder sample gave rise to the fixation of Br as zinc bromide. It also resulted in the promotion of the release of brominated compounds in comparison to the case of pure PCB. Thus, the addition of the oxide can be a benefit with respect to the bromine fixation and the kinetics of thermal treatment of PCB as well as metal recovery.展开更多
Heteroatom doped porous carbon materials have emerged as essential cathode material for metal-air battery systems in the context of soaring demands for clean energy conversion and storage.Herein,a three-dimensional ni...Heteroatom doped porous carbon materials have emerged as essential cathode material for metal-air battery systems in the context of soaring demands for clean energy conversion and storage.Herein,a three-dimensional nitrogen-doped carbon self-supported electrode(TNCSE)is fabricated through thermal treatment and acid activation of raw wood.The resulting TNCSE retains the hierarchical porous architecture of parent raw lumber and holds substantial defect sites and doped N sites in the carbon skeleton.Assembled as a cathode in the rechargeable zinc-air battery,the TNCSE exhibits a superior peak power density of 134.02 m W/cm^(2)and an energy density of 835.92 m Ah/g,significantly exceeding the ones reference commercial 20%Pt/C does.More strikingly,a limited performance decay of 1.47%after an ultra long-period(500 h)cycle is also achieved on the TNCSE.This work could offer a green and cost-save approach for rationally converting biomass into a robust self-supporting cathode material for a rechargeable zinc-air battery.展开更多
We report herein that a commercially available CeO2 is an active and reusable catalyst for the C3-selective alkenylation of oxindole with aldehydes under solvent-free conditions. This catalytic method is generally app...We report herein that a commercially available CeO2 is an active and reusable catalyst for the C3-selective alkenylation of oxindole with aldehydes under solvent-free conditions. This catalytic method is generally applicable to different aromatic and aliphatic aldehydes, giving 3-alkyledene-oxindoles in high yields(87%–99%) and high stereoselectivities(79%–93% to E-isomers). This is the first example of the catalytic synthesis of 3-alkenyl-oxindoles from oxindole and various aliphatic aldehydes. The Lewis acid-base interaction between Lewis acid sites on CeO2 and benzaldehyde was studied by in situ IR. The structure-activity relationship study using CeO2 catalysts with different sizes suggests that defect-free CeO2 surface is the active site for this reaction.展开更多
Binding kinetic properties of protein–ligand complexes are crucial factors affecting the drug potency.Nevertheless,the current in silico techniques are insufficient in providing accurate and robust predictions for bi...Binding kinetic properties of protein–ligand complexes are crucial factors affecting the drug potency.Nevertheless,the current in silico techniques are insufficient in providing accurate and robust predictions for binding kinetic properties.To this end,this work develops a variety of binding kinetic models for predicting a critical binding kinetic property,dissociation rate constant,using eight machine learning(ML)methods(Bayesian Neural Network(BNN),partial least squares regression,Bayesian ridge,Gaussian process regression,principal component regression,random forest,support vector machine,extreme gradient boosting)and the descriptors of the van der Waals/electrostatic interaction energies.These eight models are applied to two case studies involving the HSP90 and RIP1 kinase inhibitors.Both regression results of two case studies indicate that the BNN model has the state-of-the-art prediction accuracy(HSP90:R^(2)_(test)=0:947,MAE_(test)=0.184,rtest=0.976,RMSE_(test)=0.220;RIP1 kinase:R^(2)_(test)=0:745,MAE_(test)=0.188,rtest=0.961,RMSE_(test)=0.290)in comparison with other seven ML models.展开更多
The potential of mesenchymal stem cells(MSCs)in regenerative medicine has been largely known due to their capability to induce tissue regeneration in vivo with minimum inflammation during implantation.This adult stem ...The potential of mesenchymal stem cells(MSCs)in regenerative medicine has been largely known due to their capability to induce tissue regeneration in vivo with minimum inflammation during implantation.This adult stem cell type exhibit unique features of tissue repair mechanism and immune modulation mediated by their secreted factors,called secretome.Recently,the utilization of secretome as a therapeutic agent provided new insight into cell-free therapy.Nevertheless,a sufficient amount of secretome is necessary to realize their applications for translational medicine which required a proper biomanufacturing process.Several factors related to their production need to be considered to produce a clinical-grade secretome as a biological therapeutic agent.This viewpoint highlights the current challenges and considerations during the biomanufacturing process of MSCs secretome.展开更多
Cold energy generation systems must be improved to prevent catastrophic climate change. In this study, we focused on an absorption chiller cycle with HFC-134a and an ionic liquid pair as the refrigerant and absorbent,...Cold energy generation systems must be improved to prevent catastrophic climate change. In this study, we focused on an absorption chiller cycle with HFC-134a and an ionic liquid pair as the refrigerant and absorbent, respectively. It was expected that this absorption chiller cycle could generate cold heat below 0°C. Two liquids were selected and their absorption equilibrium with this pair was evaluated for the absorption chiller cycle. We measured the adsorbed amount at equilibrium with 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide [BMIM][Tf2N] and N-trimethyl-N-butylammonium bis(trifluoromethanesulfonyl)imide [N1113][Tf2N]. The experimental results were reproduced using the non-random two liquid (NRTL) model. This analysis model corresponded well in terms of the amount of adsorption at equilibrium with the experimental results. A Duhring diagram was also generated the NRTL model, and the absorption cycle characteristics as a function of temperature were determined. The absorption chiller cycle obtained cold heat at 10°C with a regeneration temperature of 70°C in addition to generating cold heat below 0°C.展开更多
Bacillus subtilis was investigated as production of biosurfactant using a combination based on waste of candy industry and glycerol from biodiesel production process as only substrate. The experimental design chosen f...Bacillus subtilis was investigated as production of biosurfactant using a combination based on waste of candy industry and glycerol from biodiesel production process as only substrate. The experimental design chosen for optimization by response surface methodology was a central composite rotatable design (CCRD) and dry weight (DW) and crude biosurfactant (CB) concentrations were selected as responses in analysis. Two techniques were implemented response surface methodology (RSM) and artificial neural network (ANN). First challenge of study was to assess the effects of the interactions between variables and reach optimum values. With the CCRD results, RSM and ANN models were developed, optimizing the production of biosurfactant. The correlation coefficients (R2) of RSM models explained 88% for DW and 73% for CB of the interactions among substrate concentrations, while ANN models explained 99% for DW and 98% for CB, demonstrating that developed ANN models were more accurate and consistent in predicting optimized conditions than RSM model. The maximum DW and CB produced in the optimum conditions were 25.60 ± 5.0 g/L and 668 ± 40 mg/L, respectively. The crude biosurfactant also showed applications in cases of oil spreading in water due to clear zone produced in Petri dishes assays.展开更多
This study focused on CO<sub>2</sub> separation technology with adsorption. This paper describes the analysis carried out by a CO<sub>2</sub> pressure swing adsorption simulation to scale up th...This study focused on CO<sub>2</sub> separation technology with adsorption. This paper describes the analysis carried out by a CO<sub>2</sub> pressure swing adsorption simulation to scale up the absorber. An unsteady one-dimensional balance model was constructed by considering the material, energy, and momentum. In the CO<sub>2</sub> breakthrough test, the beginning time and CO<sub>2</sub> concentration at outlet of CO<sub>2</sub> breakthrough in the calculation were almost equivalent to that of experiment results. The correlation consistency of the calculation results with the analysis model and the experimental results obtained by a bench scale experiment was evaluated. The transport phenomena in the adsorber were investigated at the adsorption, rinse, and desorption steps according to the calculation results. The starting time of CO<sub>2</sub> breakthrough obtained by the analysis is equal to that obtained by the adsorption breakthrough experiment. This confirms that the CO<sub>2</sub> adsorption, and the temperature and velocity distribution in the adsorber, change as a function of the adsorption, rinse, and desorption steps, respectively. Additionally, the CO<sub>2</sub> concentration of the captured gas and the amount of CO<sub>2</sub> quantity were 93.4% per day and 2.9 ton/day, respectively. These values are equal to those obtained by the bench scale experiment.展开更多
Ammonia synthesis reactors operate in conditions of high pressure and high temperature. Consequently, the flow inside these reactors always presents interaction between components in the feed mixture. A modeling accou...Ammonia synthesis reactors operate in conditions of high pressure and high temperature. Consequently, the flow inside these reactors always presents interaction between components in the feed mixture. A modeling accounts these interactions with pressure, temperature and the molar fraction is essential to converter simulation more realistic. The compositional approach based on cubic equations of state provides the influences of the component of a gas mixture using mixing rules and binary interaction parameters. This multicomponent description makes the model more robust and reliable for properties mixture prediction. In this work, two models of ammonia synthesis reactors were simulated: adiabatic and autothermal. The fitted expression of Singh and Saraf was used. The adiabatic reactor model presented a maximum relative error of 1.6% in temperature and 11.4% in conversion while the autothermal reactor model presents a maximum error of 2.7% in temperature, when compared to plant data. Furthermore, a sensitivity analysis in input variables of both converter models was performed to predict operational limits and performance of the Models for Ammonia Reactor Simulation (MARS).展开更多
Even with rigorous environmental regulations, phenol still is a major contaminant. One possible solution is the use of heterogeneous photocatalysis due to low chemical addition, feasibility and reliability to be impla...Even with rigorous environmental regulations, phenol still is a major contaminant. One possible solution is the use of heterogeneous photocatalysis due to low chemical addition, feasibility and reliability to be implanted on cost-effective industrial process. TiO2 is the most employed photocatalyst because of its favorable (photo) chemical properties and ZnO is considered one of the best alternative for that. Other oxides were tested in lesser proportions, like CuO and Ga2O3. When the photocatalyst is dispersed as slurry, higher degradation rates are achieved due to high solid to liquid contact area when compared with supported form. The aim of this work was to develop a batch recirculating photocatalytic reactor and evaluate its efficiency when assisted by the photocatalysts TiO2 P25, ZnO, CuO and β-Ga2O3. TiO2 achieved 95% mineralization after 200 min reaction in an average degradation rate of 0.68 mg·L﹣1·min﹣1 and ZnO was less efficient (0.41 mg·L﹣1·min﹣1). Ga2O3 and CuO presented poor performance, mainly due to low surface area for the CuO syntesized and the absorption of the UV radiation by the reactor walls, decreasing Ga2O3 activity. Degradation intermediates were detected in diverse concentrations and at different operational times for each oxide tested, which indicate different degradation mechanisms.展开更多
The concentration of the major greenhouse gas CO_(2)is rapidly increasing in the atmosphere,leading to global warming and a range of environmental issues.An efficient circulation and utilization of CO_(2)is critical i...The concentration of the major greenhouse gas CO_(2)is rapidly increasing in the atmosphere,leading to global warming and a range of environmental issues.An efficient circulation and utilization of CO_(2)is critical in the current environmental context.Methanation,an exothermic process,emerges as a critical strategy for effective CO_(2)utilization.On this front,there is a significant demand for rational design of catalysts that maintain high activity and methane selectivity over a wide temperature range(250-550℃).The catalyst that can promise a consistent reaction even at 500℃under an atmospheric pressure is thus obliged.The present study investigated bimetallic catalysts with SiC,which is known for its exceptional thermal conductivity,and CeO_(2),which is characterized by its CO_(2)affinity,as base materials.We incorporated Ni-M and Ru-M(M=Co and Mn)as the active metals,each loaded at 2%.Impressively,with merely 20 mg,the Ni-Co/SiC catalyst achieved a CO_(2)conversion rate of 77%and CH_(4)selectivity of 88%at 500℃,in a fixed-bed tubular reactor system with conditions of H_(2)/CO_(2)=4,a total flow rate of 70 ml min^(-1),and a steady GHSV of 12,000 h^(-1).Moreover,2Ni-2Co/CeO_(2)catalyst demonstrated exceptional performance with a 76%conversion of CO_(2)and a 83%selectivity for CH_(4),all under identical conditions.The catalyst’s durability was confirmed by a subsequent 40-hour stability test,which showed only a 3-5%degradation.The developed catalysts were comprehensively characterized by BET/BJH,CO pulse chemisorption,H_(2)-TPR,HAADF-STEM-EDS,SEM-EDS and XRD etc.to unveil their physicochemical and surface traits.It was found that Co and Mn,when integrated,effectively restrained the agglomeration of Ni and Ru particles,ensuring optimal metal dispersion on the support.In conclusion,our synthesized bimetallic catalysts shown a sustained catalytic capability,even in the high-temperature environment.展开更多
基金supported by the National Natural Science Foundation of China Excellent Young Scientist Fund(22422801)the National Natural Science Foundation of China General Project(22278053)+1 种基金the National Natural Science Foundation of China General Project(22078041)Dalian High-level Talents Innovation Support Program(2023RQ059).
文摘G protein coupled receptor kinase 2 (GRK2) is a kinase that regulates cardiac signaling activity. Inhibiting GRK2 is a promising mechanism for the treatment of heart failure (HF). Further development and optimization of inhibitors targeting GRK2 are highly meaningful. Therefore, in order to design GRK2 inhibitors with better performance, the most active molecule was selected as a reference compound from a data set containing 4-pyridylhydrazone derivatives and triazole derivatives, and its scaffold was extracted as the initial scaffold. Then, a powerful optimization-based framework for de novo drug design, guided by binding affinity, was used to generate a virtual molecular library targeting GRK2. The binding affinity of each virtual compound in this dataset was predicted by our developed deep learning model, and the designed potential compound with high binding affinity was selected for molecular docking and molecular dynamics simulation. It was found that the designed potential molecule binds to the ATP site of GRK2, which consists of key amino acids including Arg199, Gly200, Phe202, Val205, Lys220, Met274 and Asp335. The scaffold of the molecule is stabilized mainly by H-bonding and hydrophobic contacts. Concurrently, the reference compound in the dataset was also simulated by docking. It was found that this molecule also binds to the ATP site of GRK2. In addition, its scaffold is stabilized mainly by H-bonding and π-cation stacking interactions with Lys220, as well as hydrophobic contacts. The above results show that the designed potential molecule has similar binding modes to the reference compound, supporting the effectiveness of our framework for activity-focused molecular design. Finally, we summarized the interaction characteristics of general GRK2 inhibitors and gained insight into their molecule-target binding mechanisms, thereby facilitating the expansion of lead to hit compound.
基金the financial support of the National Natural Science Foundation of China(22078041,22278053)Dalian High-level Talents Innovation Support Program(2021RQ105)the Fundamental Research Funds for China Central Universities(DUT22QN209,DUT22LAB608).
文摘The selection of chemical reactions is directly related to the quality of synthesis pathways,so a reasonable reaction evaluation metric plays a crucial role in the design and planning of synthesis pathways.Since reaction conditions also need to be considered in synthesis pathway design,a reaction metric that combines reaction time,temperature,and yield is required for chemical reactions of different reaction agents.In this study,a chemical reaction graph descriptor which includes the atom-atom mapping relationship is proposed to effectively describe reactions.Then,through pre-training using graph contrastive learning and fine-tuning through supervised learning,we establish a model for generating the probability of reaction superiority(RSscore).Finally,to validate the effectiveness of the current evaluation index,RSscore is applied in two applications,namely reaction evaluation and synthesis routes analysis,which proves that the RSscore provides an important agents-considered evaluation criterion for computer-aided synthesis planning(CASP).
基金financial supports of the National Natural Science Foundation of China (22078041, 22278053,22208042)Dalian High-level Talents Innovation Support Program (2023RQ059)“the Fundamental Research Funds for the Central Universities (DUT20JC41, DUT22YG218)”。
文摘Small-molecule drugs are essential for maintaining human health. The objective of this study is to identify a molecule that can inhibit the Factor Xa protein and be easily procured. An optimization-based de novo drug design framework, Drug CAMD, that integrates a deep learning model with a mixed-integer nonlinear programming model is used for designing drug candidates. Within this framework, a virtual chemical library is specifically tailored to inhibit Factor Xa. To further filter and narrow down the lead compounds from the designed compounds, comprehensive approaches involving molecular docking,binding pose metadynamics(BPMD), binding free energy calculations, and enzyme activity inhibition analysis are utilized. To maximize efficiency in terms of time and resources, molecules for in vitro activity testing are initially selected from commercially available portions of customized virtual chemical libraries. In vitro studies assessing inhibitor activities have confirmed that the compound EN300-331859shows potential Factor Xa inhibition, with an IC_(50)value of 34.57 μmol·L^(-1). Through in silico molecular docking and BPMD, the most plausible binding pose for the EN300-331859-Factor Xa complex are identified. The estimated binding free energy values correlate well with the results obtained from biological assays. Consequently, EN300-331859 is identified as a novel and effective sub-micromolar inhibitor of Factor Xa.
基金Supported by the National Natural Science Foundation of China(21576036,21776035)
文摘Over the last three decades,flexibility and controllability considerations for heat exchanger networks(HENs)have received great attention,respectively.However,they should be simultaneously incorporated in HEN synthesis to allow the economic performance to be achievable in a practical operating environment.This paper proposes a method for simultaneous synthesis of flexible and controllable HEN by considering their coupling.The key idea is to add the bypasses with optimized initial fractions and positions to explore such coupling,and consequently enabling HENs to be operated successfully over a range of disturbance variations.These are implemented by identifying and quantifying disturbance propagations,and then examining the sensitivity of bypasses to the entire HEN.In this way,the superstructurebased mixed integer non-linear programming(MINLP)with objective function of minimizing the total annual cost is formulated.A case study is used to demonstrate the application of the proposed method.Quantitative measures and dynamic simulation show the ability to provide the satisfactory flexibility and controllability of the obtained HEN.
基金Supported by the National Natural Science Foundation of China(21576036 and 21776035)
文摘In this paper, an efficient methodology for synthesizing the indirect work exchange networks(WEN) considering isothermal process and adiabatic process respectively based on transshipment model is first proposed. In contrast with superstructure method, the transshipment model is easier to obtain the minimum utility consumption taken as the objective function and more convenient for us to attain the optimal network configuration for further minimizing the number of units. Different from division of temperature intervals in heat exchange networks,different pressure intervals are gained according to the maximum compression/expansion ratio in consideration of operating principles of indirect work exchangers and the characteristics of no pressure constraints for stream matches. The presented approach for WEN synthesis is a linear programming model applied to the isothermal process, but for indirect work exchange networks with adiabatic process, a nonlinear programming model needs establishing. Additionally, temperatures should be regarded as decision variables limited to the range between inlet and outlet temperatures in each sub-network. The constructed transshipment model can be solved first to get the minimum utility consumption and further to determine the minimum number of units by merging the adjacent pressure intervals on the basis of the proposed merging methods, which is proved to be effective through exergy analysis at the level of units structures. Finally, two cases are calculated to confirm it is dramatically feasible and effective that the optimal WEN configuration can be gained by the proposed method.
基金Institute of Technological Research–IPT,Fundcao de AmparoàPesquisa do Estado de Sao PauloBrazil[Process 2019/05840-3]+1 种基金Conselho Nacional de Desenvolvimento Científico e TecnológicoBrazil[Process 167470/2018-3]。
文摘As part of efforts to reduce anthropogenic CO_(2) emissions by the steelmaking industry,this study investigated the direct reduction of industrially produced hematite pellets with H_(2) using the Doehlert experimental design to evaluate the effect of pellet diameter(10.5-16.5 mm),porosity(0.36-0.44),and temperature(600-1200℃).A strong interactive effect between temperature and pellet size was observed,indicating that these variables cannot be considered independently.The increase in temperature and decrease in pellet size considerably favor the reduction rate,while porosity did not show a relevant effect.The change in pellet size during the reduction was negligible,except at elevated temperatures due to crack formation.A considerable decrease in mechanical strength at high temperatures suggests a maximum process operating temperature of 900℃.Good predictive capacity was achieved using the modified grain model to simulate the three consecutive non-catalytic gas-solid reactions,considering different pellet sizes and porosities,changes during the reaction from 800 to 900℃.However,for other temperatures,different mechanisms of structural modifications must be considered in the modeling.These results represent significant contributions to the development of ore pellets for CO_(2)-free steelmaking technology.
基金Supported by the National Natural Science Foundation of China(21576036,21406026)
文摘Due to the deterioration of serious energy dilemma,energy-conservation and emission–reduction have been the strategic target in the past decades,thus people have identified the vital importance of higher energy efficiency and the influence of lower carbon development.Since work exchange network is a significant part of energy recovery system,its optima design will have dramatically significant effect on energy consumption reduction in chemical process system.With an extension of the developed transshipment model in isothermal process,a novel step-wise methodology for synthesis of direct work exchange network(WEN)in adiabatic process involving heat integration is first proposed in this paper,where a nonlinear programming(NLP)model is formulated by regarding the minimum utility consumption as objective function and optimizing the initial WEN in accordance with the presented matching rules to get the optimized WEN configuration at first.Furthermore,we focus on the work exchange network synthesis with heat integration to attain the minimal total annual cost(TAC)with the introduction of heat-exchange equipment that is achieved by the following strategies in sequence:introducing heat-exchange equipment directly,adjusting the work quantity of the adjacent utility compressors or expanders,and approximating upper/lower pressure limits consequently to obtain considerable cost savings of expanders or compressors and work utility.Finally,a case taken from the literature is studied to illustrate the feasibility and effectiveness of the proposed method.
基金Supported by the Fundamental Research Funds for the Central Universities of China(DUT14RC(3)046)China Postdoctoral Science Foundation(2014M551091)the National Natural Science Foundation of China(21406026)
文摘Integrating multiple systems into one has become an important trend in Process Systems Engineering research field since there is strong demand from the modern industries. In this study, a stage-wise superstructurebased method is proposed to synthesize a combined mass and heat exchange network(CM&HEN) which has two parts as the mass exchange network(MEN) and heat exchange network(HEN) involved. To express the possible heat exchange requirements resulted from mass exchange operations, a so called "indistinct HEN superstructure(IHS)", which can contain the all potential matches between streams, is constructed at first. Then, a non-linear programming(NLP) mathematical model is established for the simultaneous synthesis and optimization of networks. Therein, the interaction between mass exchange and heat exchange is modeling formulated.The NLP model has later been examined using an example from literature, and the effectiveness of the proposed method has been demonstrated with the results.
基金financial support from Jiangsu Collaborative Innovation Center for Cultural Creativity (XYN1911)the National Natural Science Foundation of China (22008023+1 种基金21776035)Natural Science Foundation of Jiangsu Education Department (20KJB510041)
文摘Because of its paramount importance in the successful industrial control strategy of a given heat exchanger network(HEN),the control structure designs for providing appropriate manipulated variable(MV)and controlled variable pairings have received considerable attention.However,quite frequently HENs with such control structures face the problem of hard constraints,typically holding the HENs at less controlled operating space.So both the MV pairings and the above control pairings should be considered to design a control structure.This paper investigates the systematic incorporation of the two pairings,and presents a methodology for designing such two-tier control structure.This is developed based on the sequential strategy,coupling an indirect-tier with direct-tier control structure design,wherein the intention is realized in the former stage and the latter is implemented for further optimization.The MV identification and pairing are achieved through variations in heat load of heat exchangers to design the indirect-tier control structure.Then the direct-tier control structure is followed the relative gain array pairing rules.With the proposed methodology,on the one hand,it generates an explicit connection between the MV pairings and the HEN configuration,and the quantitative interaction measure is improved to avoid the multiple solutions to break the relationship among all the control pairings into individuals;on the other hand,a two-tier control structure reveals control potentials and control system design requirements,this may avoid complex and economically unfavourable control and HEN structures.The application of proposed framework is illustrated with two cases involving the dynamic simulation analysis,the quantitative assessment and the random test.
文摘Thermal degradation of a FR-4 type printed circuit board, PCB, containing brominated flame retardant has been studied both in inert and oxidative atmosphere for the emission control of harmful brominated compounds. The presence of oxygen in atmosphere resulted in the reduction of the yield of hydrogen bromide, one of the major brominated compounds in thermal treatment, and in the enhancement of the formation of bromine and hypobromous acid. The intentional addition of zinc oxide to the PCB powder sample gave rise to the fixation of Br as zinc bromide. It also resulted in the promotion of the release of brominated compounds in comparison to the case of pure PCB. Thus, the addition of the oxide can be a benefit with respect to the bromine fixation and the kinetics of thermal treatment of PCB as well as metal recovery.
基金the financial support from the National Natural Science Foundation of China(No.21905055)the start-up funding of Guangdong University of Technology(Nos.220413207 and 220418129)support from Research Fund Program of Key Laboratory of Fuel Cell Technology of Guangdong Province。
文摘Heteroatom doped porous carbon materials have emerged as essential cathode material for metal-air battery systems in the context of soaring demands for clean energy conversion and storage.Herein,a three-dimensional nitrogen-doped carbon self-supported electrode(TNCSE)is fabricated through thermal treatment and acid activation of raw wood.The resulting TNCSE retains the hierarchical porous architecture of parent raw lumber and holds substantial defect sites and doped N sites in the carbon skeleton.Assembled as a cathode in the rechargeable zinc-air battery,the TNCSE exhibits a superior peak power density of 134.02 m W/cm^(2)and an energy density of 835.92 m Ah/g,significantly exceeding the ones reference commercial 20%Pt/C does.More strikingly,a limited performance decay of 1.47%after an ultra long-period(500 h)cycle is also achieved on the TNCSE.This work could offer a green and cost-save approach for rationally converting biomass into a robust self-supporting cathode material for a rechargeable zinc-air battery.
基金supported financially by a series of JSPS KAKENHI grants:17H01341,18K14051,18K14057,and 19K05556 from the Japan Society for the Promotion of Science(JSPS)by the Japanese Ministry of Education,Culture,Sports,Science,and Technology(MEXT)within the projects"Integrated Research Consortium on Chemical Sciences(IRCCS)"and"Elements Strategy Initiative to Form Core Research Center"by the JST-CREST project JPMJCR17J3。
文摘We report herein that a commercially available CeO2 is an active and reusable catalyst for the C3-selective alkenylation of oxindole with aldehydes under solvent-free conditions. This catalytic method is generally applicable to different aromatic and aliphatic aldehydes, giving 3-alkyledene-oxindoles in high yields(87%–99%) and high stereoselectivities(79%–93% to E-isomers). This is the first example of the catalytic synthesis of 3-alkenyl-oxindoles from oxindole and various aliphatic aldehydes. The Lewis acid-base interaction between Lewis acid sites on CeO2 and benzaldehyde was studied by in situ IR. The structure-activity relationship study using CeO2 catalysts with different sizes suggests that defect-free CeO2 surface is the active site for this reaction.
基金financial supports of“the Fundamental Research Funds for the Central Universities”(DUT22YG218),NSFC(22278053,22078041)China Postdoctoral Science Foundation(2022M710578)“the Dalian High-level Talents Innovation Support Program”(2021RQ105).
文摘Binding kinetic properties of protein–ligand complexes are crucial factors affecting the drug potency.Nevertheless,the current in silico techniques are insufficient in providing accurate and robust predictions for binding kinetic properties.To this end,this work develops a variety of binding kinetic models for predicting a critical binding kinetic property,dissociation rate constant,using eight machine learning(ML)methods(Bayesian Neural Network(BNN),partial least squares regression,Bayesian ridge,Gaussian process regression,principal component regression,random forest,support vector machine,extreme gradient boosting)and the descriptors of the van der Waals/electrostatic interaction energies.These eight models are applied to two case studies involving the HSP90 and RIP1 kinase inhibitors.Both regression results of two case studies indicate that the BNN model has the state-of-the-art prediction accuracy(HSP90:R^(2)_(test)=0:947,MAE_(test)=0.184,rtest=0.976,RMSE_(test)=0.220;RIP1 kinase:R^(2)_(test)=0:745,MAE_(test)=0.188,rtest=0.961,RMSE_(test)=0.290)in comparison with other seven ML models.
基金This study is supported by Universitas Aisyiyah Yogyakarta as a part of the Collaborative Biotechnology Research Advancement Project 2021.
文摘The potential of mesenchymal stem cells(MSCs)in regenerative medicine has been largely known due to their capability to induce tissue regeneration in vivo with minimum inflammation during implantation.This adult stem cell type exhibit unique features of tissue repair mechanism and immune modulation mediated by their secreted factors,called secretome.Recently,the utilization of secretome as a therapeutic agent provided new insight into cell-free therapy.Nevertheless,a sufficient amount of secretome is necessary to realize their applications for translational medicine which required a proper biomanufacturing process.Several factors related to their production need to be considered to produce a clinical-grade secretome as a biological therapeutic agent.This viewpoint highlights the current challenges and considerations during the biomanufacturing process of MSCs secretome.
文摘Cold energy generation systems must be improved to prevent catastrophic climate change. In this study, we focused on an absorption chiller cycle with HFC-134a and an ionic liquid pair as the refrigerant and absorbent, respectively. It was expected that this absorption chiller cycle could generate cold heat below 0°C. Two liquids were selected and their absorption equilibrium with this pair was evaluated for the absorption chiller cycle. We measured the adsorbed amount at equilibrium with 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide [BMIM][Tf2N] and N-trimethyl-N-butylammonium bis(trifluoromethanesulfonyl)imide [N1113][Tf2N]. The experimental results were reproduced using the non-random two liquid (NRTL) model. This analysis model corresponded well in terms of the amount of adsorption at equilibrium with the experimental results. A Duhring diagram was also generated the NRTL model, and the absorption cycle characteristics as a function of temperature were determined. The absorption chiller cycle obtained cold heat at 10°C with a regeneration temperature of 70°C in addition to generating cold heat below 0°C.
文摘Bacillus subtilis was investigated as production of biosurfactant using a combination based on waste of candy industry and glycerol from biodiesel production process as only substrate. The experimental design chosen for optimization by response surface methodology was a central composite rotatable design (CCRD) and dry weight (DW) and crude biosurfactant (CB) concentrations were selected as responses in analysis. Two techniques were implemented response surface methodology (RSM) and artificial neural network (ANN). First challenge of study was to assess the effects of the interactions between variables and reach optimum values. With the CCRD results, RSM and ANN models were developed, optimizing the production of biosurfactant. The correlation coefficients (R2) of RSM models explained 88% for DW and 73% for CB of the interactions among substrate concentrations, while ANN models explained 99% for DW and 98% for CB, demonstrating that developed ANN models were more accurate and consistent in predicting optimized conditions than RSM model. The maximum DW and CB produced in the optimum conditions were 25.60 ± 5.0 g/L and 668 ± 40 mg/L, respectively. The crude biosurfactant also showed applications in cases of oil spreading in water due to clear zone produced in Petri dishes assays.
文摘This study focused on CO<sub>2</sub> separation technology with adsorption. This paper describes the analysis carried out by a CO<sub>2</sub> pressure swing adsorption simulation to scale up the absorber. An unsteady one-dimensional balance model was constructed by considering the material, energy, and momentum. In the CO<sub>2</sub> breakthrough test, the beginning time and CO<sub>2</sub> concentration at outlet of CO<sub>2</sub> breakthrough in the calculation were almost equivalent to that of experiment results. The correlation consistency of the calculation results with the analysis model and the experimental results obtained by a bench scale experiment was evaluated. The transport phenomena in the adsorber were investigated at the adsorption, rinse, and desorption steps according to the calculation results. The starting time of CO<sub>2</sub> breakthrough obtained by the analysis is equal to that obtained by the adsorption breakthrough experiment. This confirms that the CO<sub>2</sub> adsorption, and the temperature and velocity distribution in the adsorber, change as a function of the adsorption, rinse, and desorption steps, respectively. Additionally, the CO<sub>2</sub> concentration of the captured gas and the amount of CO<sub>2</sub> quantity were 93.4% per day and 2.9 ton/day, respectively. These values are equal to those obtained by the bench scale experiment.
文摘Ammonia synthesis reactors operate in conditions of high pressure and high temperature. Consequently, the flow inside these reactors always presents interaction between components in the feed mixture. A modeling accounts these interactions with pressure, temperature and the molar fraction is essential to converter simulation more realistic. The compositional approach based on cubic equations of state provides the influences of the component of a gas mixture using mixing rules and binary interaction parameters. This multicomponent description makes the model more robust and reliable for properties mixture prediction. In this work, two models of ammonia synthesis reactors were simulated: adiabatic and autothermal. The fitted expression of Singh and Saraf was used. The adiabatic reactor model presented a maximum relative error of 1.6% in temperature and 11.4% in conversion while the autothermal reactor model presents a maximum error of 2.7% in temperature, when compared to plant data. Furthermore, a sensitivity analysis in input variables of both converter models was performed to predict operational limits and performance of the Models for Ammonia Reactor Simulation (MARS).
基金This project was financially supported by National Council for Scientific and Technological Development(CNPq)National Council for the Improvement of Higher Education(CAPES).
文摘Even with rigorous environmental regulations, phenol still is a major contaminant. One possible solution is the use of heterogeneous photocatalysis due to low chemical addition, feasibility and reliability to be implanted on cost-effective industrial process. TiO2 is the most employed photocatalyst because of its favorable (photo) chemical properties and ZnO is considered one of the best alternative for that. Other oxides were tested in lesser proportions, like CuO and Ga2O3. When the photocatalyst is dispersed as slurry, higher degradation rates are achieved due to high solid to liquid contact area when compared with supported form. The aim of this work was to develop a batch recirculating photocatalytic reactor and evaluate its efficiency when assisted by the photocatalysts TiO2 P25, ZnO, CuO and β-Ga2O3. TiO2 achieved 95% mineralization after 200 min reaction in an average degradation rate of 0.68 mg·L﹣1·min﹣1 and ZnO was less efficient (0.41 mg·L﹣1·min﹣1). Ga2O3 and CuO presented poor performance, mainly due to low surface area for the CuO syntesized and the absorption of the UV radiation by the reactor walls, decreasing Ga2O3 activity. Degradation intermediates were detected in diverse concentrations and at different operational times for each oxide tested, which indicate different degradation mechanisms.
基金support made this research possible.Additionally,Chopendra G.Wasnik(D2001369)support provided by JICA(Japan International Cooperation Agency,Japan)through the IITH-JICA FRIENDSHIP scholarship during the study。
文摘The concentration of the major greenhouse gas CO_(2)is rapidly increasing in the atmosphere,leading to global warming and a range of environmental issues.An efficient circulation and utilization of CO_(2)is critical in the current environmental context.Methanation,an exothermic process,emerges as a critical strategy for effective CO_(2)utilization.On this front,there is a significant demand for rational design of catalysts that maintain high activity and methane selectivity over a wide temperature range(250-550℃).The catalyst that can promise a consistent reaction even at 500℃under an atmospheric pressure is thus obliged.The present study investigated bimetallic catalysts with SiC,which is known for its exceptional thermal conductivity,and CeO_(2),which is characterized by its CO_(2)affinity,as base materials.We incorporated Ni-M and Ru-M(M=Co and Mn)as the active metals,each loaded at 2%.Impressively,with merely 20 mg,the Ni-Co/SiC catalyst achieved a CO_(2)conversion rate of 77%and CH_(4)selectivity of 88%at 500℃,in a fixed-bed tubular reactor system with conditions of H_(2)/CO_(2)=4,a total flow rate of 70 ml min^(-1),and a steady GHSV of 12,000 h^(-1).Moreover,2Ni-2Co/CeO_(2)catalyst demonstrated exceptional performance with a 76%conversion of CO_(2)and a 83%selectivity for CH_(4),all under identical conditions.The catalyst’s durability was confirmed by a subsequent 40-hour stability test,which showed only a 3-5%degradation.The developed catalysts were comprehensively characterized by BET/BJH,CO pulse chemisorption,H_(2)-TPR,HAADF-STEM-EDS,SEM-EDS and XRD etc.to unveil their physicochemical and surface traits.It was found that Co and Mn,when integrated,effectively restrained the agglomeration of Ni and Ru particles,ensuring optimal metal dispersion on the support.In conclusion,our synthesized bimetallic catalysts shown a sustained catalytic capability,even in the high-temperature environment.
