Application of artificial intelligence combined with near infrared spectroscopy in the continuous counter-current extraction process of Angelica dahurica formula granules.

The establishment of near infrared (NIR) spectroscopy model mostly relies on chemometrics, and spectral analysis combined with artificial intelligence (AI) provides a new way of thinking for pharmaceutical quality inspection, new algorithms such as back propagation artificial neural networks (BP-ANN) and swarm intelligence optimization algorithms such as sparrow search algorithm (SSA) provide core technical support. In order to explore the application of AI in the pharmaceutical field, in this study, Angelica dahurica formula granules with a relatively complex system were selected as the research object. Quantitative analysis models were established by using partial least squares regression (PLSR) with a micro-NIR spectrometer, and BP-ANN modeling results were compared. For the best PLSR models of six characteristic components in the continuous counter-current extract of Angelica dahurica, R2v of imperatorin was lower than 0.90, and the RPD values of imperatorin, phellopterin, and isoimperatorin were even lower than 1. When the prediction model established by SSA-BP-ANN was used for quantitative analysis, R2v of six components were all higher than 0.92, and the RPD values all higher than 1.5, which proved that the BP-ANN method was better than PLSR. This study confirmed that in the continuous counter-current extraction progress of Angelica dahurica formula granules, the use of micro-NIR spectrometer combined with AI could realize the rapid prediction of the contents of six characteristic components. The comparison results provided a scientific reference for the process analysis and on-line monitoring in the production process of traditional Chinese medicine by micro-NIR spectrometer combined with AI.

Implementation of near-infrared spectroscopy and convolutional neural networks for predicting particle size distribution in fluidized bed granulation.

Monitoring the particle size distribution (PSD) is crucial for controlling product quality during fluidized bed granulation. This paper proposed a rapid analytical method that quantifies the D10, D50, and D90 values using a Convolutional Block Attention Module-Convolutional Neural Network (CBAM-CNN) framework tailored for deep learning with near-infrared (NIR) spectroscopy. This innovative framework, which fuses CBAM with CNN, excels at extracting intricate features while prioritizing crucial ones, thereby facilitating the creation of a robust multi-output regression model. To expand the training dataset, we incorporated the C-Mixup algorithm, ensuring that the deep learning model was trained comprehensively. Additionally, the Bayesian optimization algorithm was introduced to optimize the hyperparameters, improving the prediction performance of the deep learning model. Compared with the commonly used Partial Least Squares (PLS), Support Vector Machine (SVM), and Artificial Neural Network (ANN) models, the CBAM-CNN model yielded higher prediction accuracy. Furthermore, the CBAM-CNN model avoided spectral preprocessing, preserved the spectral information to the maximum extent, and returned multiple predicted values at one time without degrading the prediction accuracy. Therefore, the CBAM-CNN model showed better prediction performance and modeling convenience for analyzing PSD values in fluidized bed granulation.

Three Stages of Dynamic Assembly Process of Dipeptide-Based Supramolecular Gel Revealed by In Situ Infrared Spectroscopy.

The exploration of short peptide-based assembly is vital for understanding protein-misfolding-associated diseases and seeking strategies to attenuate aggregate formation. While, the molecular mechanism of their structural evolution remains poorly studied in view of the dynamic and unpredictable assembly process. Herein, infrared (IR) spectroscopy, which serves as an in situ and real-time analytical technique, was intelligently employed to investigate the mechanism of phase transition and aggregate formation during the dynamic assembly process of diphenylalanine. Combined with other spectroscopy and electron microscopy technologies, three stages of gel formation and the main driving forces in different stages were revealed. A variety of stoichiometric methods such as continuous wavelet transform, principal component analysis, and two-dimensional correlation spectroscopy techniques were conducted to analyze the original time-dependent IR spectra to obtain detailed information on the changes in the amide bands and hydration layer. The microenvironment of hydrogen bonding among amide bands was significantly changed with the addition of pyridine derivatives, resulting in great differences in the properties of co-assembled gels. This work not only provides a universal analytical way to reveal the dynamic assembly process of dipeptide-based supramolecular gel but also expands their applications in supramolecular regulation and high-throughput screens in situ.

Identification and determination of different processed products and their extracts of Crataegi Fructus by infrared spectroscopy combined with two-dimensional correlation analysis.

The fruit of Crataegus sp. is known as "Shanzha (SZ)" in China and is widely used in the food, beverage, and traditional Chinese medicine (TCM) industries. SZ usually requires thermal processing to reduce the irritation of its acidity to the gastric mucosa. Different processed products of SZ resulting from thermal processing have different or even opposite functions in clinical applications. In addition, 5-hydroxymethylfurfural (5-HMF) intermediates produced during thermal processing are carcinogenic to humans. Therefore, the aim of this study was to explore a rapid and accurate method by Fourier transform infrared spectroscopy (FT-IR) for the identification of different processed products and the determination of 5-HMF in extracts. In qualitative identification, a three-stage infrared spectroscopy identification method (raw spectra, the second derivative spectra, and two-dimensional correlation (2DCOS) spectra) was developed to distinguish different processed products of SZ step by step. In quantitative determination, partial least squares regression combined with different variable selection methods, especially the 2DCOS method, was applied to determine the 5-HMF content. The results show that temperature-induced 2DCOS synchronous spectra can effectively identify different processed products of SZ by shape, intensity, and position of auto-peaks or cross-peaks, and the variables selected by power spectra from concentration-induced 2DCOS synchronous spectra have better prediction ability for 5-HMF compared to full variables. The above results demonstrate that 2D-COS analysis is a potential tool in qualitative and quantitative analysis, which can improve sample identification accuracy and determination capabilities. This study not only establishes a rapid and accurate method for the identification of different processed products but also provides a practical reference for food safety and the efficient use of TCM.

Tunable Chirality of Self-Assembled Dipeptides Mediated by Bipyridine Derivative.

Supramolecular peptide assemblies have been widely used for the development of biomedical, catalytical, and optical materials with chiral nanostructures in view of the intrinsic chirality of peptides. However, the assembly pathway and chiral transformation behavior of various peptides remain largely elusive especially for the transient assemblies under out-of-equilibrium conditions. Herein, the N-fluorenylmethoxycarbonyl-protected phenylalanine-tyrosine dipeptide (Fmoc-FY) was used as a peptide assembly platform, which showed that the assembly proceeds multistep evolution. The original spheres caused by liquid-liquid phase separation (LLPS) can nucleate and elongate into the formation of right-handed helices which were metastable and easily converted into microribbons. Interestingly, a bipyridine derivative can be introduced to effectively control the assembly pathway and induce the formation of thermodynamically stable right-handed or left-handed helices at different stoichiometric ratios. In addition, the chiral assembly can also be regulated by ultrasound or enzyme catalysis. This minimalistic system not only broadens the nucleation-elongation mechanisms of protein aggregates but also promotes the controllable design and development of chiral biomaterials.

A Novel Variable Selection Method Based on Binning-Normalized Mutual Information for Multivariate Calibration.

Variable (wavelength) selection is essential in the multivariate analysis of near-infrared spectra to improve model performance and provide a more straightforward interpretation. This paper proposed a new variable selection method named binning-normalized mutual information (B-NMI) based on information entropy theory. "Data binning" was applied to reduce the effects of minor measurement errors and increase the features of near-infrared spectra. "Normalized mutual information" was employed to calculate the correlation between each wavelength and the reference values. The performance of B-NMI was evaluated by two experimental datasets (ideal ternary solvent mixture dataset, fluidized bed granulation dataset) and two public datasets (gasoline octane dataset, corn protein dataset). Compared with classic methods of backward and interval PLS (BIPLS), variable importance projection (VIP), correlation coefficient (CC), uninformative variables elimination (UVE), and competitive adaptive reweighted sampling (CARS), B-NMI not only selected the most featured wavelengths from the spectra of complex real-world samples but also improved the stability and robustness of variable selection results.

Real-time in-line prediction of drug loading and release rate in the coating process of diclofenac sodium spheres based on near infrared spectroscopy.

The preparation of diclofenac sodium spheres by fluidized bed is a common production mode for the pharmaceutical preparations at present, but the critical material attributes in the production process is mostly analyzed off-line, which is time-consuming and laborious, and the analysis results lag behind. In this paper, the real-time in-line prediction of drug loading of diclofenac sodium and the release rate during the coating process was realized by using near infrared spectroscopy. For the best near infrared spectroscopy (NIRS) model of drug loading, R2cv, R2p, RMSECV, RMSEP were 0.9874, 0.9973, 0.002549 mg/g, 0.001515 mg/g respectively. For the best NIRS model of three release time points, the R2cv, R2p, RMSECV and RMSEP were 0.9755, 0.9823, 3.233%, 4.500%; 0.9358, 0.9965, 2.598%, 0.7939% and 0.9867, 0.9927, 0.4085%, 0.4726% respectively. And the analytical ability of these model was verified. The organic combination of these two parts of work constituted an important basis for ensuring the safety and effectiveness of diclofenac sodium spheres from the perspective of production process.

A rapid extraction process monitoring of Swertia mussotii Franch. With near infrared spectroscopy.

Swertia mussotii Franch. (SMF), a traditional Tibetan medicine, which has miraculous effect on treating hepatitis diseases. However, there is no research on its entire production process, and invisible production process has seriously hindered the SMF modern development. In this study, principal component analysis (PCA), subtractive spectroscopy, and two-dimensional correlation spectroscopy (2D-COS) were used to explain changes of characteristic groups in the extraction process. Four main characteristic peaks at 1884 nm, 1944 nm, 2246 nm and 2308 nm were identified to describe the changes of molecular structure information of total active components in SMF extraction process. In addition, multi critical quality attributes (CQAs) models were established by near-infrared spectroscopy (NIRS) combined with the total quantum statistical moment (TQSM). The coefficients of determination (R2eval and R2ival) were both greater than 0.99. The ratios of the standard deviation of validation to the standard error of the prediction (RPDe and RPDi) were greater than five. The quantitative model of AUCT could save time on primary data measurement by not requiring determination of indicator components compared with others. In conclusion, these results demonstrated that it was feasible to understand the SMF extraction process through AUCT and characteristic groups. These could realize the visual digital characterization and quality stability of the SMF extraction process.

Schiff base nanoarchitectonics for supramolecular assembly of dipeptide as drug carriers.

Development of peptide-based supramolecular materials with hierarchical morphology and tunable guest loading displays broad potential as drug carrier in view of biocompatibility and biodegradability. Herein, we report a facile Schiff base nanoarchitectonic for supramolecular assembly of diphenylalanine (FF) metastable gel. The addition of trace glutaraldehyde (GA)/H2O solution induces the Schiff base reaction between GA and FF accompanying by phase transition from gel to solution. FF nanoparticles and hierarchical beaded nanofibers with autofluorescence properties can be constructed by regulating the competitive assembly between FF-H2O and FF-GA oligomer. Moreover, various guest molecules with different hydrophilic and hydrophobic properties can be easily loaded into such assembled particles and its release can be triggered under weak alkaline conditions, which show the potential application of the assembled FF system as drug carriers.

CO2 Induces Symmetry Breaking in Layered Dipeptide Crystals.

Control of symmetry breaking of materials provides large opportunities to regulate their properties and functions. Herein, we report breaking the symmetry of layered dipeptide crystals by utilizing CO2 to induce the adjacent monomolecular layers to stack from the opposite to the same direction. The role of CO2 is to cover the interlayer interaction sites and force the dipeptides to adsorb at asymmetric positions. Further, the dipeptide crystals exhibit far superior piezoelectricity after symmetry breaking and the piezoelectric voltage generated from the dipeptide-based generators becomes more than 500 % higher than before. This work reveals a potential route to engineer structures and properties of layered materials and provides a deep insight into the control of non-covalent interactions.

Glycosaminoglycan-based injectable hydrogels with multi-functions in the alleviation of osteoarthritis.

Osteoarthritis (OA), as an "undead cancer", causes a serious burden for both individuals and society. In this study, a glycosaminoglycan-based injectable hydrogel was prepared with hyaluronic acid (HA), chondroitin sulfate E disaccharide (ΔUA-diSE) and thermosensitive Pluronic F127 (PF127) to provide a new strategy for OA alleviation. Both in vitro and in vivo biological evaluations were introduced to investigate the slow-release capacity, related mechanisms, and effectiveness of PF-HA-diSE on OA. The results demonstrated that PF-HA-diSE could alleviate OA effectively by regulating the complement system, especially the formation of C5b-9, and its downstream signals. Interestingly, we also found that PF127 was not only a drug carrier, but may have the potential on inhibiting C5b-9 formation. Altogether, these findings provided a more effective local drug delivery system for glycosaminoglycans in better treatment of OA and related diseases.

Co-assembled Supramolecular Gel of Dipeptide and Pyridine Derivatives with Controlled Chirality.

It is commonly considered that amyloid-ß (Aß) fibrils are heavily involved in the neurological diseases. Establishing an external model based on the core recognition motif (diphenylalanine, FF) of Aß would be of significance in understanding the assembly and disassembly of Aß fibrils in living system. Herein, supramolecular gels with structure transition from amyloid-like ß-sheet to different supramolecular helices were obtained through the co-assembly of a N-fluorenylmethoxycarbonyl-protected L-FF (L-FmocFF) with achiral pyridine derivatives. It is found that the different stacking modes (H- or J-aggregates) of additives and the microenvironment of chiral carbon play vital roles for the selectively chiral transfer or amplification of L-FmocFF. The dynamic process of helix formation was also captured. This work provides a convenient co-assembly way to explore the structure basis of Aß fibrils with a controlled chirality.

Self-Assembled Vesicles Formed by Positional Isomers of Sodium Dodecyl Benzene Sulfonate-Based Pseudogemini Surfactants.

The construction of pseudogemini surfactants based on noncovalent interactions (such as electrostatic interaction and π-π stacking) was a powerful method to assemble well-defined aggregates in aqueous solution. The mixtures of butane-1,4-bis(methylimidazolium bromide) ([mim-C4-mim]Br2) and positional isomers of sodium dodecyl benzene sulfonate (SDBS-0,11 or SDBS-3,8) in a molar ratio of 1:2 were studied to characterize the effect of straight and branched alkyl chains on the aggregation behavior of pseudogemini surfactants. Spontaneous phase transition from micelles to vesicles was formed by these two kinds of complexes. Interestingly, a densely stacked onion-like structure (multilamellar vesicles) with more than one dozen layers was fabricated. The micelle and vesicle phases were characterized in detail by cryogenic transmission electron microscopy, polarized optical microscopy, dynamic light scattering, and rheological measurements. It can be clearly demonstrated that the structure of alkyl chain can significantly influence the surface adsorption, solution self-assembly, and aqueous two-phase system of pseudogemini surfactants. Our work provided a convenient technique to achieve controlled self-assembly by introducing positional isomers of surfactants.

Photoluminescent polymer hydrogels with stimuli-responsiveness constructed from Eu-containing polyoxometalate and imidazolium zwitterions.

Inorganic-organic co-assembly of anionic polyoxometalates (POMs) with zwitterions provides a facile way to fabricate functional soft materials. In this paper, a translucent, photoluminescent polymer hydrogel was fabricated from Weakley-type POM Na9EuW10O36 (EuW10) and polymerizable imidazole-type zwitterion 3-(1-vinyl-3-imidazolio)propanesulfonate (VIPS) via a one-step synthesis method. Detailed characterization indicated that the polymerization of double bonds in VIPS and electrostatic interactions between EuW10 and VIPS play important roles in the formation of the hydrogels. Additionally, the introduction of non-polymerizable zwitterions 3-(1-methyl-3-imidazolio)propanesulfonate (MIPS) or 3-(1-decyl-3-imidazolio)propanesulfonate (C10IPS) can improve the mechanical and luminous performances of the hydrogels. Especially, C10IPS with a long alkyl chain would more significantly alter the coordination environment of EuW10, and consequently resulted in a more efficient energy transfer process. Further investigations revealed that the chemical environment around the Eu3+ can be highly influenced by organic solvents with stronger coordination abilities than water molecules, such as acetone. The translucency and luminescence intensity of the hydrogels can be reversibly transformed after alternately immersing in acetone or H2O for several minutes. Our results provided a useful strategy for the fabrication of luminescent hydrogels by regulating the noncovalent interactions between POMs and zwitterions.

Chirality transfer based on dynamic covalent chemistry: from small chiral molecules to supramolecules.

Single-tailed and gemini-type supra-gelators were facilely fabricated via the conjugation of the d- or l-enantiomeric dihydrazide TDH with single-tailed achiral aldehyde C12BAD through dynamic acylhydrazone bonding. Chirality transfer from small molecules to supramolecules was successfully achieved via the spontaneous assembly of the formed supra-gelators into supramolecular chiral hydrogels.

Interaction among Worm-like Micelles in Polyoxometalate-Based Supramolecular Hydrogel.

The co-assembly of zwitterionic amphiphile and polyoxometalate is a new and promising technique to construct a hierarchical and multifunctional supramolecular hydrogel. To comprehensively investigate the assemble mechanism, zwitterionic amphiphiles with different cations, namely, 3-(1-hexadecyl-3-imidazolio) propanesulfonate (C16IPS) and 3-(1-hexadecyl-2-methyl-3-imidazolio) propanesulfonate (C16bIPS), were designed to complex with silicotungstic acid (HSiW). Hydrogen bonding between the oxygen atoms of HSiW and the protons on C-2 of the imidazolium rings and the steric effect significantly influence the morphology and rheological property of the hydrogel. Interestingly, cross-linked worm-like micelles in parallel, vertical, and tilted distribution were observed using cryogenic transmission electron microscopy. In addition, these aggregates were further stacked into hexagonal phases on a large scale. Hence, deep insights into the relationship among the structure of zwitterionic amphiphile, self-assembled architecture, and the mechanical property of a polyoxometalate-based hydrogel were disclosed.

Polyoxometalate-Based Photochromic Supramolecular Hydrogels with Highly Ordered Spherical and Cylindrical Micellar Nanostructures.

Polyoxometalates (POMs) have attracted much attention in the field of photochromic materials. However, POM-based photochromic supramolecular hydrogels with high transparency and good photochromic properties are seldom reported. In this work, a homogenous, optically transparent, injectable, and photochromic supramolecular hydrogel was fabricated through the coassembly of ammonium heptamolybdate (Mo7 ) and an imidazolium-based zwitterionic amphiphile (3-(1-hexadecyl-3-imidazolio)propanesulfonate (C16 IPS)). The balance between electrostatic attraction and repulsion of Mo7 clusters and zwitterionic amphiphiles enables them to coassemble into a homogenous and transparent supramolecular hydrogel. By adjusting the molar ratio of C16 IPS/Mo7 , ordered spherical micelle-based hydrogels and aligned wormlike micelle-based hydrogels can be obtained. The incorporation of Mo7 into hydrogels endows these hydrogels with excellent photochromic properties. Specifically, after coassembly with C16 IPS, the photochromic ability of hydrogels is significantly enhanced compared with that of a pure aqueous solution of Mo7 . These hydrogels exhibit great potential applications as photochromic materials for the recording of rewritable information.

Supramolecular Thermotropic Ionic Liquid Crystals Formed via Self-Assembled Zwitterionic Ionic Liquids.

Supramolecular thermotropic ionic liquid crystals (ILCs) with hexagonal and lamellar phases were fabricated by the self-assembly of zwitterionic ionic liquids, which were formed by 3-(1-alkyl-3-imidazolio) propanesulfonate with different alkyl chain lengths C nIPS ( n = 12, 14, 16) and 3,4,5-tris(dodecyloxy)benzoic acid (TDBA) based on intermolecular electrostatic interactions. The phase behaviors of ILCs were investigated by differential scanning calorimetry (DSC), small-angle X-ray scattering (SAXS), and polarized optical microscopy (POM). The highly ordered and well-defined microstructure of ILCs can be considered to be proton pathways and to radically improve the ionic conductivity, suggesting the induction of proton conduction through a hopping mechanism.

Coassembly of a Polyoxometalate and a Zwitterionic Amphiphile into a Luminescent Hydrogel with Excellent Stimuli Responsiveness.

The co-existence of electrostatic attraction and repulsion between zwitterionic amphiphile and anionic polyoxometalate (POM) promotes the formation of aqueous inorganic-organic coassemblies. Injectable, luminescent supramolecular hydrogels have been fabricated by using this novel and versatile technique. Hydrogels with different characteristics can be flexibly manipulated by adjusting the molar ratios of compounds. Interestingly, a linear relationship between the luminescence intensity and temperature accompanying the sol-gel transition was observed. In addition, the emission properties of the hydrogels were sensitive to external acid and base gasses. Such multi-stimuli responsive luminescent hydrogels provide an attractive pathway to construct intelligent optical soft materials, especially for biological sensors for which stimuli responsiveness is necessary.

Smart low molecular weight hydrogels with dynamic covalent skeletons.

We report a new strategy for fabricating a smart low molecular weight hydrogel based on dynamic covalent chemistry from a bola-type supra-gelator, which was facilely fabricated in situ from two non-assembling building blocks, (3-(2-(4-formylphenoxy) ethyl)-1-methyl imidazolium bromide, MA) and (3,3'-dithiobis (propionohydrazide), DSPDZ), through dynamic acylhydrazone bonding. The obtained low molecular weight hydrogels exhibited redox-responsive and controllable self-healing properties. The role of dynamic covalent bonding in the formation of smart hydrogels is revealed in this study, which provides a simple and bottom-up method for constructing smart low molecular weight hydrogels.