Deep Learning-Based State-of-Health Estimation of Proton-Exchange Membrane Fuel Cells under Dynamic Operation Conditions.

Proton-exchange membrane fuel cells (PEMFCs) play a crucial role in the transition to sustainable energy systems. Accurately estimating the state of health (SOH) of PEMFCs under dynamic operating conditions is essential for ensuring their reliability and longevity. This study designed dynamic operating conditions for fuel cells and conducted durability tests using both crack-free fuel cells and fuel cells with uniform cracks. Utilizing deep learning methods, we estimated the SOH of PEMFCs under dynamic operating conditions and investigated the performance of long short-term memory networks (LSTM), gated recurrent units (GRU), temporal convolutional networks (TCN), and transformer models for SOH estimation tasks. We also explored the impact of different sampling intervals and training set proportions on the predictive performance of these models. The results indicated that shorter sampling intervals and higher training set proportions significantly improve prediction accuracy. The study also highlighted the challenges posed by the presence of cracks. Cracks cause more frequent and intense voltage fluctuations, making it more difficult for the models to accurately capture the dynamic behavior of PEMFCs, thereby increasing prediction errors. However, under crack-free conditions, due to more stable voltage output, all models showed improved predictive performance. Finally, this study underscores the effectiveness of deep learning models in estimating the SOH of PEMFCs and provides insights into optimizing sampling and training strategies to enhance prediction accuracy. The findings make a significant contribution to the development of more reliable and efficient PEMFC systems for sustainable energy applications.

Structural Basis and Mechanism of Chiral Benzedrine Molecules Interacting With Third Dopamine Receptor.

In order to investigate the chiral benzedrine molecules corresponding to their different characteristics in biochemical systems, we studied their interaction with D3 R using the docking method, molecular dynamic simulation, and quantum chemistry. The obtained results indicate that the active residues for R-benzedrine (RAT) bound with D3 R are Ala132, Asp133, and Tyr55, while Asn57, Asp133, Asp168, Cys172, Gly54, Trp24, and Vall136 act as the active residues for S-benzedrine (SAT). The different active pockets are observed for ART or SAT because they possess different active residues. The binding energies between RAT and SAT with D3 R were determined to be -44.0 kJ.mol(-1) and -71.2 kJ.mol(-1) , respectively. These results demonstrate that SAT within the studied pocket of D3 R has a stronger capability of binding with D3 R, while it is more feasible for RAT to leave from the interior positions of D3 R. In addition, the results suggest that the D3 R protein can recognize chiral benzedrine molecules and influence their different addictive and pharmacological effects in biochemical systems. Chirality 28:674-685, 2016. © 2016 Wiley Periodicals, Inc.

4-(2-Fluoro-benzo-yl)-1-[2-(4-hy-droxy-phen-yl)-2-oxoeth-yl]piperazin-1-ium trifluoro-acetate.

In the crystal structure of the title compound, C(19)H(20)FN(2)O(3) (+)·C(2)F(3)O(2) (-), N-H⋯O and O-H⋯O hydrogen bonds link two cations and two anions into a 22-atom ring. These rings are further linked into a three dimensional network by weak C-H⋯O contacts.

[X-ray fluorescence spectrum studies on bioorganic carbon in cereals and carbon chemical circulation].

The bioorganic carbon contents and chemical element compositions in six kinds of cereals: paddy (rice), wheat (flour), soybean, millet, sorghum and corn were determined by X-ray fluorescence (XRF) spectrum, meanwhile a new method was established to probe their protein contents. In the cereals, the average bioorganic carbon content is about 440%. The highest protein content is 42.74% from soybean, and other protein content is 28.56% in millet, 27.57% in wheat, 24.99% in corn, 22.21% in sorghum, but only 20.31% in rice. Based on our new definition of carbon chemical circulation presented in the current work, the authors have found that in 2009 humankind used bioorganic carbon to discharge CO2 into the earth's atmosphere that accounts for one percent of the total CO2 discharge, and consumed organic carbon to release CO2 into the earth's atmosphere, accounting for 10.73% of the total CO2 discharge. The clear definition of carbon chemical circulation and the discharged CO2 content from the distinct types of carbon compounds would advance the study on carbon chemical circulation and the atmospheric CO2 greenhouse effect. Our work further found that it takes eight years to circulate the total earth's atmospheric CO2. The short period shows the sensitivity for CO2 to keep its dynamical equilibrium in the earth's atmosphere. However, no experimental data has been reported to prove a heavy destructive greenhouse effect of CO2 existing in the earth's atmosphere.

Analysis of Fuel Cell Stack Performance Attenuation and Individual Cell Voltage Uniformity Based on the Durability Cycle Condition.

Based on the dynamic cycle condition test of a 4.5 kW fuel cell stack, the performance attenuation and individual cell voltage uniformity of the proton exchange membrane fuel cell (PEMFC) stack was evaluated synthetically. The performance decay period of the fuel cell stack was 180-600 h, the decrease of voltage and power was evaluated by rate and amplitude. The results show that the performance of the fuel cell stack decreased with the increase of test time and current density. When the test was carried out to 600 h, under rated operating conditions, the voltage attenuation rate was 130 µV/h, and the voltage reduced by 71 mV, with a decrease of 10.41%. The power attenuation rate was 0.8 W/h, with a decrease of 10.42%. The statistical parameter variation coefficient was used to characterize the voltage consistency of individual cells. It was found that the voltage uniformity is worse at the high current density point and with a long-running process. The variation coefficient was 3.1% in the worst performance.

[X-ray fluorescence spectrum analysis of chemical element for spider and silkworm silk and its applications].

Elemental compositions in spider and silkworm silks were determined by X-ray fluorescence (XRF) spectrum to probe the silk-forming mechanisms and an elemental basis for spider silk with excellent characteristics. XRF analysis demonstrates that in the silkworm silk, the elemental content is 47.10% for C, 29.92% for O and 16. 52% for N, including metal elemental contents: 0.166 2% for Ca, 0.104 0% for Mg and 0.039 5% for K, while Na, Zn, Ni, Fe and Cr show less micro quantity. Due to relative high quantity for Ca and Mg, they both play an important role in the silk-forming mechanism by silkworm. In the spider silk, the determined main nonmetal elemental contents are 44.09% for C, 26.64% for O and 22.34% for N. The high content of nitrogen may be an elemental basis for spider silk with excellent characteristic. The main metal elemental contents are 0.268 0% for Na, 0.081 4% for K and 0.011 6% for Mg, while Ca, Zn, Ni, Cu and Cr possess less micro quantity in the spider silk. Because of relative high quantity for Na and K, they both play an important role in the silk-forming mechanism by spider. The elemental compositions investigated by using mathematic statistic method are quite in agreement with those demonstrated by using XRF spectrum, which validates the experimentally determined elemental compositions in the spider and silkworm silks.

Double-sides sticking mechanism of vinblastine interacting with α,ß-tubulin to get activity against cancer cells.

Vinblastine (VLB) and its derivatives have been used for clinical first-line drugs to treat various cancers. Due to the resistance and serious side effects from using VLB and its derivatives, there is a need to discover and develop novel VLB derivatives with high activity against cancer cells. In order to better discover and develop new VLB derivatives, we need to study the structural basis of VLB's anti-cancer cytotoxicity and the mechanism of its interaction with α,ß-tubulins. Based on the crystal structure of α,ß-microtubule complex protein, the molecular dynamics method including the sampling PMF method was used to study the variation of dissociation free energy (ΔG) of α,ß-tubulins under different system conditions, and then from which to study the mechanism of the interaction between VLB and α,ß-tubulins. The obtained results show that the dissociation of pure α,ß-tubulins requires 197.8 kJ·mol-1 for ΔG. When the VLB molecule exists between the interface of α,ß-tubulins, the dissociation ΔG of α,ß-tubulins reaches 220.5 kJ·mol-1, which is greater than that of pure α,ß-tubulin. The VLB molecule is formed by connecting a vindoline moiety (VM) molecule with a catharanthine moiety (CM) molecule through a carbon-carbon bond, which is a larger molecule. When the CM molecule exists in the middle of α,ß-tubulin interface, the dissociation ΔG of α,ß-tubulins is 46.2 kJ·mol-1, during which the CM moves with ß-tubulin. When the VM molecule exists between the middle of α,ß-tubulin interface, the dissociation ΔG of α,ß-tubulins is 86.7 kJ·mol-1, during which it moves with α-tubulin. Therefore, the VLB molecule is like a double-sides tape to stick α-tubulin and ß-tubulin together. The VLB molecule intervenes the dynamic equilibrium between dissociation and aggregation of α-tubulin and ß-tubulin by a double-sides sticking mechanism to exert high activity with toxicity against cancer cell. Besides, our results demonstrate that VLB has its structural basis for anticancer cytotoxicity due to its two compositions composed of a CM molecule and a VM molecule although they have little toxicity against cancer cell alone.

Structural Basis and Mechanism for Vindoline Dimers Interacting with α,ß-Tubulin.

Vinblastine and its derivatives used in clinics as antitumor drugs often cause drug resistance and some serious side effects; thus, it is necessary to study new vinblastine analogues with strong anticancer cytotoxicity and low toxicity. We designed a dimer molecule using two vindoline-bonded dimer vindoline (DVB) and studied its interaction with α,ß-tubulin through the double-sided adhesive mechanism to explore its anticancer cytotoxicity. In our work, DVB was docked into the interface between α-tubulin and ß-tubulin to construct a complex protein structure, and then it was simulated for 100 ns using the molecular dynamics technology to become a stable and refined complex protein structure. Based on such a refined structure, the quantum chemistry at the level of the MP2/6-31G(d,p) method was used to calculate the binding energies for DVB interacting with respective residues. By the obtained binding energies, the active site residues for interaction with DVB were found. Up to 20 active sites of residues within α,ß-tubulin interacting with DVB are labeled in ß-Asp179, ß-Glu207, ß-Tyr210, ß-Asp211, ß-Phe214, ß-Pro222, ß-Tyr224, and ß-Leu227 and α-Asn249, α-Arg308, α-Lys326, α-Asn329, α-Ala333, α-Thr334, α-Lys336, α-Lys338, α-Arg339, α-Ser340, α-Thr349, and α-Phe351. The total binding energy between DVB and α,ß-tubulin is about -251.0 kJ·mol-1. The sampling average force potential (PMF) method was further used to study the dissociation free energy (ΔG) along the separation trajectory of α,ß-tubulin under the presence of DVB based on the refined structure of DVB with α,ß-tubulin. Because of the presence of DVB within the interface between α- and ß-tubulin, ΔG is 252.3 kJ·mol-1. In contrast to the absence of DVB, the separation of pure ß-tubulin needs a free energy of 196.9 kJ·mol-1. The data show that the presence of DVB adds more 55.4 kJ·mol-1 of ΔG to hinder the normal separation of α,ß-tubulin. Compared to vinblastine existing, the free energy required for the separation of α,ß-tubulin is 220.5 kJ·mol-1. Vinblastine and DVB can both be considered through the same double-sided adhesive mechanism to give anticancer cytotoxicity. Because of the presence of DVB, a larger free energy is needed for the separation of α,ß-tubulin, which suggests that DVB should have stronger anticancer cytotoxicity than vinblastine and shows that DVB has a broad application prospect.

Molecular dynamics simulation of d-Benzedrine transmitting through molecular channels within D3R.

Dex-Benzedrine (known as d-Benzedrine or SAT) acts in dopamine receptors of central nerve cell system. In clinic, SAT is used to treat a variety of diseases; meanwhile, it has dependence and addiction. In order to investigate the pharmacology and addiction mechanisms of SAT as a medicine, in this paper, we have studied the structure of D3R complex protein with SAT, and based on which, using potential mean force with umbrella samplings and the simulated phospholipid bilayer membrane (or POPC bilayer membrane), the molecular dynamics simulation was performed to obtain free energy changes upon the trajectories for SAT moving along the molecular channels within D3R. The free energy change for SAT transmitting toward the outside of cell along the functional molecular channel within D3R is 83.5 kJ mol-1. The change of free energy for SAT to permeate into the POPC bilayer membrane along the protective molecular channel within D3R is 87.7 kJ mol-1. Our previous work gave that the free energy for Levo-Benzedrine (RAT) transmitting toward the outside of cell along the functional molecular channel within D3R is 91.4 kJ mol-1, while it is 117.7 kJ mol-1 for RAT to permeate into the POPC bilayer membrane along the protective molecular channel within D3R. The values of free energy suggest that SAT relatively prefers likely to pass through the functional molecular channel within D3R for increasing the release of dopamine molecules resulting in a variety of functional effects for SAT. The obtained results show that the pharmacology and addiction mechanisms of SAT as a drug are closely related to the molecular dynamics and mechanism for SAT transmitting along molecular channels within D3R.

Theoretical insight into the structural mechanism for the binding of vinblastine with tubulin.

Vinblastine (VLB) is one of vinca alkaloids with high cytotoxicity toward cancer cells approved for clinical use. However, because of drug resistance, toxicity, and other side effects caused from the use of VLB, new vinca alkaloids with higher cytotoxicity toward cancer cells and other good qualities need to develop. One strategy is to further study and better understand the essence why VLB possesses the high cytotoxicity toward cancer cells. In present work, by using molecular simulation, molecular docking, density functional calculation, and the crystal structure of α,ß-tubulin complex, we find two modes labeled in catharanthine moiety (CM) and vindoline moiety (VM) modes of VLB bound with the interface of α,ß-tubulin to probe the essence why VLB has the high cytotoxicity toward cancer cells. In the CM mode, nine key residues B-Ser178, B-Asp179, B-Glu183, B-Tyr210, B-Asp226, C-Lys326, C-Asp327, C-Lys336, and C-Lys352 from the α,ß-tubulin complex are determined as the active sites for the interaction of VLB with α,ß-tubulin. Some of them such as B-Ser178, B-Glu183, B-Tyr210, B-Asp226, C-Lys326, C-Asp327, and C-Lys336 are newly identified as the active sites in present work. The affinity between VLB and the active pocket within the interface of α,ß-tubulin is -60.8 kJ mol(-1) in the CM mode. In the VM mode, that is a new mode established in present paper, nine similar key residues B-Lys176, B-Ser178, B-Asp179, B-Glu183, B-Tyr210, B-Asp226, C-Lys326, C-Asp327, and C-Lys336 from the α,ß-tubulin complex are found as the active sites for the interaction with VLB. The difference is from one key residue C-Lys352 in the CM mode changed to the key residue B-Lys176 in the VM mode. The affinity between VLB and the active pocket within the interface of α,ß-tubulin is -96.3 kJ mol(-1) in the VM mode. Based on the results obtained in present work, and because VLB looks like two faces, composed of CM and VM both to have similar polar active groups, to interact with the active sites, we suggest double-faces sticking mechanism for the binding of VLB to the interface of α,ß-tubulin. The double-faces sticking mechanism can be used to qualitatively explain high cytotoxicity toward cancer cells of vinca alkaloids including vinblastine, vincristine, vindestine, and vinorelbine approved for clinical use and vinflunine still in a phase III clinical trial. Furthermore, this mechanism will be applied to develop novel vinca alkaloids with much higher cytotoxicity toward cancer cells.

Nucleobase-functionalized conjugated polymer for detection of copper(II).

In recent years, supramolecular organization of thiophene derivatives, oligo- and polythiophene, have been developed with various designs to achieve complex functions. Here, we describe the synthesis and characterization of a conjugated polymer with thymidine side chain bases and polythiophene backbones (PTT) instead of phosphate bonds in DNA, and the PTT exhibits exceptional fluorescence quenching efficiency upon binding of Cu(2+) ions in aqueous medium, which is suggested to be electron transfer from the π* orbit at the excited state of PTT to the 3d orbit of Cu(2+) ions and subsequent Cu(2+)-mediated interpolymer π-stacking aggregation. Furthermore, Cu(2+) ions can be selectively and easily monitored by the fluorescence quenching of PTT, which can be used for detection of Cu(2+) ions with good selectivity and high sensitivity in aqueous medium. Both experimental and theoretical methods have been devoted to demonstrate the strong affinity and steric interaction of PTT toward Cu(2+). These findings will illustrate new directions for the design of nucleobase-functionalized materials with transition metals responsive activity.

Molecular dynamics simulation and density functional theory studies on the active pocket for the binding of paclitaxel to tubulin.

Paclitaxel (PTX) is used to treat various cancers, but it also causes serious side effects and resistance. To better design similar compounds with less toxicity and more activity against drug-resistant tumors, it is important to clearly understand the PTX-binding pocket formed by the key residues of active sites on ß-tubulin. Using a docking method, molecular dynamics (MD) simulation and density functional theory (DFT), we identified some residues (such as Arg278, Asp26, Asp226, Glu22, Glu27, His229, Arg369, Lys218, Ser277 and Thr276) on ß-tubulin that are the active sites responsible for interaction with PTX. Another two residues, Leu371 and Gly279, also likely serve as active sites. Most of these sites contact with the "southern hemisphere" of PTX; only one key residue interacts with the "northern hemisphere" of PTX. These key residues can be divided into four groups, which serve as active compositions in the formation of an active pocket for PTX binding to ß-tubulin. This active binding pocket enables a very strong interaction (the strength is predicted to be in the range of -327.8 to -365.7 kJ mol(-1)) between ß-tubulin and PTX, with various orientated conformations. This strong interaction means that PTX possesses a high level of activity against cancer cells, a result that is in good agreement with the clinical mechanism of PTX. The described PTX pocket and key active residues will be applied to probe the mechanism of tumor cells resistant to PTX, and to design novel analogs with superior properties.

Structural insight into the mechanism of epothilone A bound to beta-tubulin and its mutants at Arg282Gln and Thr274Ile.

Epothilone A (EpoA) is under investigation as an antitumor agent. To provide better understanding of the activity of EpoA against cancers, by theoretical studies such as using docking method, molecular dynamics simulation and density functional theory calculations, we identify several key residues located on ß-tubulin as the active sites to establish an active pocket responsible for interaction with EpoA. Eight residues (Arg276, Asp224, Asp26, His227, Glu27, Glu22, Thr274, and Met363) are identified as the active sites to form the active pocket on ß-tubulin. The interaction energy is predicted to be -121.3 kJ/mol between EpoA and ß-tubulin. In the mutant of ß-tubulin at Thr274Ile, three residues (Arg359, Glu27, and His227) are identified as the active sites for the binding of EpoA. In the mutant of ß-tubulin at Arg282Gln, three residues (Arg276, Lys19, and His227) serve as the active sites. The interaction energy is reduced to -77.2 kJ/mol between EpoA and Arg282Gln mutant and to -50.2 kJ/mol between EpoA and Thr274Ile mutant. The strong interaction with ß-tubulin is significant to EpoA's activity against cancer cells. When ß-tubulin is mutated either at Arg282Gln or at Thr274Ile, the decreased strength of interaction explains the activity reduced for EpoA. Therefore, this work shows that the structural basis of the active pocket plays an important role in regulating the activity for EpoA with a Taxol-like mechanism of action to be promoted as an antitumor agent.

The key residues of active sites on the catalytic fragment for paclitaxel interacting with poly (ADP-ribose) polymerase.

Poly(ADP-ribose) polymerase (PARP) is regarded as a target protein for paclitaxel (PTX) to bind. An important issue is to identify the key residues as active sites for PTX interacting with PARP, which will help to understand the potential drug activity of PTX against cancer cells. Using docking method and MD simulation, we have constructed a refined structure of PTX docked on the catalytic function domain of PARP (PDB code: 1A26). The residues Glu327(988), Tyr246(907), Lys242(903), His165(826), Asp105(766), Gln102(763) and Gln98(759) in PARP are identified as potential sites involved in interaction with PTX according to binding energy (E(b)) between PTX and single residue calculated with B3LYP/6-31G(d,p). These residues form an active binding pocket located on the surface of the catalytic fragment, possibly interacting with the required groups of PTX leading to its activity against cancer cells. It is noted that most of the active sites make conatct with the "southern hemisphere" of PTX except for one residue, Tyr246(907), which interacts with the "northern hemisphere" of PTX. The conformation of PTX in complex with the catalytic fragment is observed as being T-shaped, similar to that complexed with ß-tubulin. The total Eb of -269.9 kJ/mol represents the potent interaction between PTX and the catalytic fragment, implying that PTX can readily bind to the active pocket. The tight association of PTX with the catalytic fragment would inhibit PARP activation, suggesting a potential application of PTX as an effective antineoplastic agent.