Enantioselective liquid-liquid extraction of 2-cyclohexylmandelic acid enantiomers using chiral ionic liquids.

Obtaining optically pure compounds in an eco-friendly and cost-efficient manner plays an important role in human health and pharmaceutical industry. Racemic separation using multistage stereoselective liquid-liquid extraction has become one of the most practical and effective approach to access homochiral enantiomers. Currently, chiral ionic liquids (CILs) with structural designability have become a promising chiral additive and enable them as adjustable candidates for racemic separation. Herein, a high-effective stereoselective liquid-liquid extraction process composed of imidazolium cations and amino acid-derived anions as the chiral additive was established for racemic 2-cyclohexylmandelic acid (CHMA) separation. We have systematically investigated the choice of organic solvent, concentration of CIL, extraction temperature, and the pH of aqueous phase. For three-stage stereoselective extraction, the maximum enantiomeric excess (e.e.) for CHMA was reached up to 40.6%. Furthermore, the mechanism of steric effect and stereoselective capacity between the CILs and racemic CHMA was discussed and simulated. We envision that the work will facilitate the development of CILs in multistage liquid-liquid extraction and promote the large-scale production of optically pure enantiomers.

The sources, properties, extraction, biosynthesis, pharmacology, and application of lycopene.

Lycopene is an important pigment with an alkene skeleton from Lycopersicon esculentum, which is also obtained from some red fruits and vegetables. Lycopene is used in the food field with rich functions and serves in the medical field with multiple clinical values because it has dual functions of both medicine and food. It was found that lycopene was mainly isolated by solvent extraction, ultrasonic-assisted extraction, supercritical fluid extraction, high-intensity pulsed electric field-assisted extraction, enzymatic-assisted extraction, and microwave-assisted extraction. Meanwhile, it was also obtained via 2 synthetic pathways: chemical synthesis and biosynthesis. Pharmacological studies revealed that lycopene has anti-oxidant, hypolipidemic, anti-cancer, immunity-enhancing, hepatoprotective, hypoglycemic, cardiovascular-protective, anti-inflammatory, neuroprotective, and osteoporosis-inhibiting effects. The application of lycopene mainly includes food processing, animal breeding, and medical cosmetology fields. It is hoped that this review will provide some useful information and guidance for future study and exploitation of lycopene.

Synthesis of cell penetrating peptide sterol coupler and its liposome study on S-mRNA.

In order to overcome the current LNP-mRNA delivery system's weakness of poor stability and rapid degradation by nuclease, a novel chol-CGYKK molecule and then the new phospholipid liposome were designed and prepared. A solid phase approach synthesized CGYKK and connected it to cholesterol via a disulfide linker to form the desired chol-CGYKK. Four formulated samples with different proportions of excipients were prepared by freeze-drying cationic liposomes and packaged S-mRNA. The stability test shows that after six months at 4 °C, the encapsulation rate of this novel phospholipid liposome was still approximately 90%, which would significantly improve the storage and transportation requirement. Transmission electron microscopy, atomic force microscopy, and scanning electron microscopy indicated that the liposomes were spherical and uniformly dispersed. On comparing the levels of mRNA protein expression of the four formulated samples, the S protein vaccine expression of formulated sample 1 was the highest. Uptake by vector cells for formulated sample 1 showed that compared to Lipo2000, and the transfection efficiency was 66.7%. Furthermore, the safety evaluation of the CGYKK and mRNA vaccine liposomes revealed no toxic effects. The in vivo study demonstrated that this novel mRNA vaccine had an immune response. However, it was still not as good as the LNP group right now, but its excellent physicochemical properties, stability, in vitro biological activity, and in vivo efficacy against SARS-CoV-2 provided new strategies for developing the next generation of mRNA delivery system.

Lyophilization process optimization and molecular dynamics simulation of mRNA-LNPs for SARS-CoV-2 vaccine.

Some studies have shown that lyophilization significantly improves the stability of mRNA-LNPs and enables long-term storage at 2-8 °C. However, there is little research on the lyophilization process of mRNA-lipid nanoparticles (LNPs). Most previous studies have used empirical lyophilization with only a single lyoprotectant, resulting in low lyophilization efficiency, often requiring 40-100 h. In the present study, an efficient lyophilization method suitable for mRNA-LNPs was designed and optimized, shortening the total length of the lyophilization process to 8-18 h, which significantly reduced energy consumption and production costs. When the mixed lyoprotectant composed of sucrose, trehalose, and mannitol was added to mRNA-LNPs, the eutectic point and collapse temperature of the system were increased. The lyophilized product had a ginger root-shaped rigid structure with large porosity, which tolerated rapid temperature increases and efficiently removed water. In addition, the lyophilized mRNA-LNPs rapidly rehydrated and had good particle size distribution, encapsulation rate, and mRNA integrity. The lyophilized mRNA-LNPs were stable at 2-8 °C, and they did not reduce immunogenicity in vivo or in vitro. Molecular dynamics simulation was used to compare the phospholipid molecular layer with the lyoprotectant in aqueous and anhydrous environments to elucidate the mechanism of lyophilization to improve the stability of mRNA-LNPs. This efficient lyophilization platform significantly improves the accessibility of mRNA-LNPs.

Preparation of COF-coated nickel foam adsorbents for dispersive solid-phase extraction of 16 polycyclic aromatic hydrocarbons from Chinese herbal medicines.

Covalent organic framework coated nickel foam (NF@COF) was prepared as a sorbent for the dispersive solid phase extraction (DSPE) of polycyclic aromatic hydrocarbons (PAHs) from Chinese herbal medicines (CHMs) prior to their determination by gas chromatography-mass spectrometry (GC-MS). The structure and morphology of the as-synthesized NF@COF were characterized by different techniques. Various key parameters affecting the performance of the DSPE method, including the amount of sorbent, desorption solvent, desorption volume and time, extraction time, and sample volume, were investigated. Under the optimized conditions, NF@COF combined with GC-MS was successfully applied to the determination of 16 PAHs in CHMs. The method showed wide linearity (20-2000 ng mL-1), low limits of determination (0.3-2.7 ng mL-1), and high recoveries (78.0-124%). These results revealed that NF@COF has the potential for efficient extraction of PAHs from complex samples.

Fatty acid binding protein 1 and fatty acid synthetase over-expression have differential effects on collagen III synthesis and cross-linking in Zongdihua pig primary adipocytes.

The purpose of this study was to determine whether FABP1 and FAS regulate expression of collagen and its crosslinking via lysyl oxidase in isolated adipocytes from Zongdihua pigs. We aimed to identify biochemical processes affecting meat quality using molecular tools to provide a basis for breeding improvement of these animals. We measured expression levels of FABP1 and related genes using qRT-PCR in longissimus dorsi muscle and subcutaneous adipose tissues. Primary adipocytes from fat tissues were isolated and FABP1 and FAS were over-expressed from recombinant plasmids. Sequence analysis of the cloned genes indicated that FABP1 encodes a hydrophobic protein of 128 amino acids and contained 12 predicted phosphorylation sites and no transmembrane regions. The basal levels of FABP1 and FAS expression in pig tissues were 3-3.5-fold higher in subcutaneous fat compared with muscle (P < 0.01). Recombinant expression plasmids were successfully transfected into the cloned preadipocytes and (a) over-expression of FAS resulted in significantly increased expression of COL3A1 (P < 0.05) and significantly inhibited lysyl oxidase LOX expression (P < 0.01); (b) over-expression of FABP1 significantly increased COL3A1 expression (P < 0.01) and significantly inhibited LOX expression (P< 0.05) and significantly reduced lysyl oxidase activity (P < 0.01). Therefore, FAS enhanced FABP1 expression resulting in increased collagen accumulation and this preliminarily suggested that FAS and FABP1 can serve as fat-related candidate genes and provide a theoretical basis for the study of fat deposition in Zongdihua pigs.

Grad-MobileNet: A Gradient-Based Unsupervised Learning Method for Laser Welding Surface Defect Classification.

Deep learning technology has advanced rapidly and has started to be applied for the detection of welding defects. In the manufacturing process of power batteries for new energy vehicles, welding defects may occur due to the high directivity, convergence, and penetration of the laser beam. The accuracy of deep learning prediction relies heavily on big data, but balanced big data of welding defects is hard to acquire at the battery production site. In this paper, the authors construct a dataset named RIAM, which consists of images captured from an industrial environment for laser welding of power battery modules. RIAM contains four types of images: Normality, Lack of fusion, Surface porosity, and Scaled surface. The characteristics of RIAM are carefully considered in the application scenarios. Moreover, this paper proposes a gradient-based unsupervised model named Grad-MobileNet, which can be trained with only a few normal images and can extract the feature gradients of the input images. Welding defects can then be classified by the gradient distribution. This model is based on MobileNetV3, which is a lightweight convolutional neural network (CNN), and achieves 99% accuracy, which is higher than the accuracy expected from supervised learning.

Synthesis of CuxO/Ag nanoparticles on exfoliated graphene: application for enhanced electrochemical detection of H2O2 in milk.

In this paper, a novel composite is constructed as a non-enzymatic hydrogen peroxide (H2O2) sensor by liquid-phase exfoliation method, which is composed of copper oxide, cuprous oxide and silver nanoparticles doped few-layer-graphene (CuxO/Ag@FLG). Its surface morphology and composition were characterized by scanning electron microscopy (SEM) and X-ray photo spectroscopy (XPS), and its H2O2 sensing performances include catalytic reduction and quantitative detection were studied with electrochemical methods. Our sensor had a high sensitivity of 174.5 µA mM-1 cm-2 (R2 = 0.9978) in an extremely wide range of concentrations from 10 µM to 100 mM, a fast response (about 5 s) and a low limit of detection (S/N = 3) of 2.13 µM. The sensor exhibits outstanding selectivity in the presence of various biological interference, such as dopamine, ascorbic acid, uric acid, citric acid, etc. In addition, the constructed sensor continued 95% current responsiveness after 1 month of storage further points to its long-term stability. Last but not least, it has a good recovery rate (90.12-102.00%) in milk sold on the open market, indicating that it has broad application possibilities in the food industry and biological medicine.

Determination of polycyclic aromatic hydrocarbons in Chinese herbal medicines by gas chromatography-mass spectrometry with graphene-functionalized nickel foam.

Graphene-functionalized nickel foam (NF) sorbent materials were prepared and characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy and Thermogravimetric analysis. For the separation and detection of polycyclic aromatic hydrocarbons (PAHs) in five Chinese medicine samples, namely dandelion, fructus aurantii, peppermint, mulberry leaf and embryo chrysanthemum, a method combining dispersive micro-solid phase extraction and gas chromatography-mass spectrometry (GC-MS) was developed. Four conditions affecting the extraction efficiency, such as the type of desorption solvent, the amount of sorbent, the extraction time and the volume of water sample, were optimized. The results of the methodological validation showed that NF@SiO2@G was able to adsorb PAHs well and with good reproducibility. All analytes showed good linearity in the concentration range of 20-2000 ng/mL with coefficient of determination R2≥0.9956. The limit of detection was 0.98-13.34 ng/mL, and the limit of quantification ranged from 3.25 to 44.47 ng/mL. Both the intra-day and inter-day precision were lower than 15.46%, and the spiked recoveries were in the range of 75.5-118.4%. The total contents of the 16 PAHs contained in these five Chinese herbal medicines (CHMs) were varied from 450 to 1557 µg/kg. The results indicated that the graphene-functionalized NF sorbent combined with GC-MS can effectively detect PAHs in CHMs.

TIME-Net: Transformer-Integrated Multi-Encoder Network for limited-angle artifact removal in dual-energy CBCT.

Dual-energy cone-beam computed tomography (DE-CBCT) is a promising imaging technique with foreseeable clinical applications. DE-CBCT images acquired with two different spectra can provide material-specific information. Meanwhile, the anatomical consistency and energy-domain correlation result in significant information redundancy, which could be exploited to improve image quality. In this context, this paper develops the Transformer-Integrated Multi-Encoder Network (TIME-Net) for DE-CBCT to remove the limited-angle artifacts. TIME-Net comprises three encoders (image encoder, prior encoder, and transformer encoder), two decoders (low- and high-energy decoders), and one feature fusion module. Three encoders extract various features for image restoration. The feature fusion module compresses these features into more compact shared features and feeds them to the decoders. Two decoders perform differential learning for DE-CBCT images. By design, TIME-Net could obtain high-quality DE-CBCT images using two complementary quarter-scans, holding great potential to reduce radiation dose and shorten the acquisition time. Qualitative and quantitative analyses based on simulated data and real rat data have demonstrated the promising performance of TIME-Net in artifact removal, subtle structure restoration, and reconstruction accuracy preservation. Two clinical applications, virtual non-contrast (VNC) imaging and iodine quantification, have proved the potential utility of the DE-CBCT images provided by TIME-Net.

mRNA based vaccines provide broad protection against different SARS-CoV-2 variants of concern.

In order to overcome the pandemic of COVID-19, messenger RNA (mRNA)-based vaccine has been extensively researched as a rapid and versatile strategy. Herein, we described the immunogenicity of mRNA-based vaccines for Beta and the most recent Omicron variants. The homologous mRNA-Beta and mRNA-Omicron and heterologous Ad5-nCoV plus mRNA vaccine exhibited high-level cross-reactive neutralization for Beta, original, Delta, and Omicron variants. It indicated that the COVID-19 mRNA vaccines have great potential in the clinical use against different SARS-CoV-2 variants.

A highly selective and sensitive "on-off" fluorescent probe for detecting cadmium ions and l-cysteine based on nitrogen and boron co-doped carbon quantum dots.

Cadmium ions (Cd2+) have caused relatively serious pollution, threatening human health and ecosystems. l-Cysteine (l-Cys) is an essential amino acid in living organisms and concentration of l-Cys is closely related to some human diseases. In this work, we first introduced 2-amino-3-hydroxypyridine and sodium borohydride as the nitrogen source and boron source to fabricate boron and nitrogen co-doped carbon quantum dots (N,B-CQDs) with high fluorescence quantum yield (21.2%), which were synthesized through a simple, low-consumption and pollution-free one-pot hydrothermal method. The obtained N,B-CQDs are able to detect Cd2+ rapidly and sensitively through fluorescence enhancement, which may be ascribed to chelation enhanced fluorescence that is induced by the formation of the N,B-CQDs/Cd2+ complex. Simultaneously, N,B-CQDs can be used to detect l-cysteine because significant fluorescence quenching was observed when l-Cys was added into the N,B-CQDs/Cd2+ system. In the two fluorescence "turn-on" and "turn-off" processes, this fluorescent probe obtained a good linear relationship over Cd2+ concentration ranging from 2.5 µM to 22.5 µM with a detection limit of 0.45 µM, while the concentration of l-cysteine showed a linear relationship in the range of 2.5-17.5 µM with a detection limit of 0.28 µM. The sensor has been successfully used to detect Cd2+ and l-cysteine in real samples with satisfying results.

Synthesis of palm sheath derived-porous carbon for selective CO2 adsorption.

Biomass-derived porous carbons are regarded as the most preferential adsorbents for CO2 capture due to their well-developed textural properties, tunable porosity and low cost. Herein, novel porous carbons were facilely prepared by activation of palm sheath for the highly selective separation of CO2 from gas mixtures. The textural features of carbon materials were characterized by the analysis of surface morphology and N2 isotherms for textural characterization. The as-prepared carbon adsorbents possess an excellent CO2 adsorption capacity of 3.48 mmol g-1 (298 K) and 5.28 mmol g-1 (273 K) at 1 bar, and outstanding IAST selectivities of CO2/N2, CO2/CH4, and CH4/N2 up to 32.7, 7.1 and 4.6 at 298 K and 1 bar, respectively. Also, the adsorption evaluation criteria of the vacuum swing adsorption (VSA) process, the breakthrough experiments, and the cyclic experiments have comprehensively demonstrated the palm sheath derived porous carbons as efficient adsorbents for practical applications.

2D leaf-like ZIF-L decorated with multi-walled carbon nanotubes as electrochemical sensing platform for sensitively detecting thiabendazole pesticide residues in fruit samples.

Excessive use of pesticides in modern agriculture results in large amounts of pesticide residues in agricultural production, greatly threatening human health. Herein, novel two-dimensional leaf-like zeolitic imidazolate framework-L decorated with multi-walled carbon nanotubes (MWCNTs/ZIF-L) was prepared by a facile solvent way and exploited as electrode material for sensitive electrochemical sensing of thiabendazole (TBZ). Two-dimensional ZIF-L presents high surface area, large pore volume, and abundant active sites, which exhibits high enrichment ability towards TBZ molecules, while the MWCNTs interspersed on ZIF-L can prominently enhance the electron transport capability and improve the electrocatalytic activity for TBZ oxidation. Due to the intriguing synergy between the components, the MWCNTs/ZIF-L-based electrochemical sensor reveals a limit of detection (LOD) of 6.0 nmol·L-1, which is lower than that reported in most literatures. Additionally, satisfactory reproducibility and repeatability, long-term stability, and excellent selectivity are acquired. The proposed method was also applied for the detection of TBZ in apple and orange samples with acceptable recoveries.

Fast liquid chromatography method for separation of peptides using a sub-2 µm ground silica monolith packed column.

A stationary phase based on sub-2 µm ground silica monolith particles was fabricated by in situ polymerization and applied in micro-column for separation of peptides. The sub-2 µm silica particles were obtained from monolith using sol-gel process followed by grinding and sedimentation to remove the fines. Initially, the silica monolith particles were pretreated with 3-trimethoxysilyl propyl methacrylate to attach double-bonded ligands onto the surface, then a network structure was formed onto the surface of the particle using styrene, N-isopropylacrylamide, and ethylene glycoldimethacrylate. The effect of the flow rate of the mobile phase on the separation performance was investigated. The stationary phase was characterized by field emission scanning electron microscopy, thermogravimetry, particle size distribution, and element analysis. The resultant phase was packed in glass-lined stainless steel micro-columns (2.1 mm × 50 mm) and evaluated for fast separation. An average number of theoretical plates as high as 9800 plates/column (5.10 µm plate height) was achieved for five synthetic peptides under the optimized flow rate of 0.15 mL/min. The repeatabilities of column-to-column, intraday, and interday through relative standard deviation were found better than 4%, exhibiting satisfactory repeatability of the developed micro-column for fast separation of peptides.

Preparation of multicolor luminescence Schiff-base compound based on solvent control and its application in the detection of pentachloronitrobenzene.

Fluorescent materials with tunable optical properties are critical to their potential application. So far, the tuning of double-color luminescence has been easily achieved for many organic materials, but there are very few reports on multicolor luminescence materials. In this work, a multicolor emissions Schiff-base fluorescent compound 1,1'-{4,4'-Biphenyldiylbis[nitrilo(E)methylylidene]}di(2-naphthol) (BPDN) with an aggregation induced emission (AIE) characteristic was synthesized, and its luminescent characteristic was investigated. The BPDN molecules with low concentration in solution can emit faint light, but a new AIE phenomenon will appear when the BPDN molecules are aggregated in the solvent with low solubility or high concentration. The color and efficiency of the AIE of BPDN can be tuned by changing its aggregation state: the luminescence of the aggregate gradually redshifts (blue, green, to orange) as the solvent with poor solubility in the mixture increases or increasing the concentration of the BPDN. Based on the multicolor luminescence BPDN, a molecularly imprinted ratiometric fluorescent probe test strip (MIRF test strip) had been prepared and successfully applied to visual detection of pentachloronitrobenzene (PCNB). The color of test strip could change gradually from orange to yellow to green with the increase of the concentration of PCNB. This work shows the characteristic and application of multicolor luminescence BPDN.

Synthesis of Rottlerone Analogues and Evaluation of Their α-Glucosidase and DPP-4 Dual Inhibitory and Glucose Consumption-Promoting Activity.

Our previous study found that desmethylxanthohumol (1) inhibited α-glucosidase in vitro. Recently, further investigations revealed that dehydrocyclodesmethylxanthohumol (2) and its dimer analogue rottlerone (3) exhibited more potent α-glucosidase inhibitory activity than 1. The aim of this study was to synthesize a series of rottlerone analogues and evaluate their α-glucosidase and DPP-4 dual inhibitory activity. The results showed that compounds 4d and 5d irreversibly and potently inhibited α-glucosidase (IC50 = 0.22 and 0.12 µM) and moderately inhibited DPP-4 (IC50 = 23.59 and 26.19 µM), respectively. In addition, compounds 4d and 5d significantly promoted glucose consumption, with the activity of 5d at 0.2 µM being comparable to that of metformin at a concentration of 1 mM.

Application of artificial intelligence in COVID-19 medical area: a systematic review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has caused a large-scale global epidemic, impacting international politics and the economy. At present, there is no particularly effective medicine and treatment plan. Therefore, it is urgent and significant to find new technologies to diagnose early, isolate early, and treat early. Multimodal data drove artificial intelligence (AI) can potentially be the option. During the COVID-19 Pandemic, AI provided cutting-edge applications in disease, medicine, treatment, and target recognition. This paper reviewed the literature on the intersection of AI and medicine to analyze and compare different AI model applications in the COVID-19 Pandemic, evaluate their effectiveness, show their advantages and differences, and introduce the main models and their characteristics. METHODS: We searched PubMed, arXiv, medRxiv, and Google Scholar through February 2020 to identify studies on AI applications in the medical areas for the COVID-19 Pandemic. RESULTS: We summarize the main AI applications in six areas: (I) epidemiology, (II) diagnosis, (III) progression, (IV) treatment, (V) psychological health impact, and (VI) data security. The ongoing development in AI has significantly improved prediction, contact tracing, screening, diagnosis, treatment, medication, and vaccine development for the COVID-19 Pandemic and reducing human intervention in medical practice. DISCUSSION: This paper provides strong advice for using AI-based auxiliary tools for related applications of human diseases. We also discuss the clinicians' role in the further development of AI. They and AI researchers can integrate AI technology with current clinical processes and information systems into applications. In the future, AI personnel and medical workers will further cooperate closely.

Sulfhydryl functionalized carbon quantum dots as a turn-off fluorescent probe for sensitive detection of Hg2.

Mercury ion (Hg2+) is one of the most toxic heavy metal ions and lowering the detection limit of Hg2+ is always a challenge in analytical chemistry and environmental analysis. In this work, sulfhydryl functionalized carbon quantum dots (HS-CQDs) were synthesized through a one-pot hydrothermal method. The obtained HS-CQDs were able to detect mercury ions Hg2+ rapidly and sensitively through fluorescence quenching, which may be ascribed to the formation of nonfluorescent ground-state complexes and electron transfer reaction between HS-CQDs and Hg2+. A modification of the HS-CQD surface by -SH was confirmed using Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). The HS-CQDs sensing system obtained a good linear relationship over a Hg2+ concentration ranging from 0.45 µM to 2.1 µM with a detection limit of 12 nM. Delightfully, the sensor has been successfully used to detect Hg2+ in real samples with satisfactory results. This means that the sensor has the potential to be used for testing actual samples.