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Abstract Cryogenic electron microscopy (cryo-EM), X-ray crystallography, and nuclear magnetic resonance (NMR) contribute structural data that are interchangeable, cross-verifiable, and visualizable on common platforms, making them powerful tools for our understanding of protein structures. Unfortunately, atomic force microscopy (AFM) has so far failed to interface with these structural biology methods, despite the recent development of localization AFM (LAFM) that allows extracting high-resolution structural information from AFM data. Here, we build on LAFM and develop a pipeline that transforms AFM data into 3D-density files (.afm) that are readable by programs commonly used to visualize, analyze, and interpret structural data. We show that 3D-LAFM densities can serve as force fields to steer molecular dynamics flexible fitting (MDFF) to obtain structural models of previously unresolved states based on AFM observations in close-to-native environment. Besides, the .afm format enables direct 3D or 2D visualization and analysis of conventional AFM images. We anticipate that the file format will find wide usage and embed AFM in the repertoire of methods routinely used by the structural biology community, allowing AFM researchers to deposit data in repositories in a format that allows comparison and cross-verification with data from other techniques.

Abstract Research on the association between dietary adherence and cancer risk is limited, particularly concerning overall cancer risk and its underlying mechanisms. Using the UK Biobank data, we prospectively investigate the associations between adherence to a Mediterranean diet (MedDiet) or a Mediterranean-Dietary Approaches to Stop Hypertension Diet Intervention for Neurodegenerative Delay diet (MINDDiet) and the risk of overall and 22 specific cancers, as well as the mediating effects of metabolites. Here we show significant negative associations of MedDiet and MINDDiet adherence with overall cancer risk. These associations remain robust across 14 and 13 specific cancers, respectively. Then, a sequential analysis, incorporating Cox regression, elastic net and gradient boost models, identify 10 metabolites associated with overall cancer risk. Mediation results indicate that these metabolites play a crucial role in the association between adherence to a MedDiet or a MINDDiet and cancer risk, independently and cumulatively. These findings deepen our understanding of the intricate connections between diet, metabolites, and cancer development.

Radon decay products attach to particulate matter (referred to as particle radioactivity, PR) has been shown to be potential to promote airway damage after inhalation. In this study, we investigated associations between PR with respiratory symptoms and health-related quality of life (HRQL) in patients with COPD. 141 male patients with COPD, former smokers, completed the St. George's Respiratory Questionnaire (SGRQ) after up to four 1-week seasonal assessments (N=474) of indoor (home) and ambient (central site) particulate matter ≤ 2.5 µm in diameter (PM2.5) and black carbon (BC). Indoor PR was measured as α-activity (radiation) on PM2.5 filter samples. The ratio of indoor/ambient sulfur in PM2.5 (a ventilation surrogate) was used to estimate α-PR from indoor radon decay. SGRQ responses assessed frequent cough, phlegm, shortness of breath, wheeze, and chest attacks in the past 3 months. Multivariable linear regression with generalized estimating equations accounting for repeated measures was used to explore associations, adjusting for potential confounders. Median (IQR) indoor α-PR was 1.22 (0.62) mBq/m3. We found that there were positive associations between α-PR with cough and phlegm. The strongest associations were with estimated α-PR of indoor origin for cough (31.1 % increase/IQR, 95 %CI: 8.8 %, 57.8 %), and was suggestive for phlegm (13.0 % increase/IQR, 95 %CI: −2.5 %, 31.0 %), similar adjusting for indoor BC or PM2.5. α-PR of indoor origin was positively associated with an increase in SGRQ Symptoms score [1.2 units/IQR; 95 %CI: −0.3, 2.6] that did not meet conventional levels of statistical significance. Our results suggested that exposure to indoor radon decay products measured as particle radioactivity, a common indoor exposure, is associated with cough, and suggestively associated with phlegm and worse HRQL symptoms score in patients with COPD.

Abstract Thermal protective textiles are crucial for safeguarding individuals, particularly firefighters and steelworkers, against extreme heat, and for preventing burn injuries. However, traditional firefighting gear suffers from statically fixed thermal insulation properties, potentially resulting in overheating and discomfort in moderate conditions, and insufficient protection in extreme fire events. Herein, an innovative soft robotic textile is developed for dynamically adaptive thermal management, providing superior personal protection and thermal comfort across a spectrum of environmental temperatures. This unique textile features a thermoplastic polyurethane (TPU)‐sealed actuation system, embedded with a low boiling point fluid for reversible phase transition, resembling an endoskeleton that triggers an expansion within the textile matrix for enhanced air gap and thermal insulation. The thermal resistance improves automatically from 0.23 to 0.48 Km2 W−1 by self‐actuating under intense heat, exceeding conventional textiles by maintaining over 10 °C cooler temperatures. Additionally, the knitted substrate incorporated into the soft actuators can substantially mitigate convective heat transfer, as evidenced by the thermal resistance tests and the temperature mapping derived from numerical simulations. Moreover, it boasts significantly increased moisture permeability. The thermoadaptation and breathability of this durable all‐fabric system signify considerable progress in the development of protective clothing with high comfort for dynamic and extreme temperature conditions.

Abstract A growing number of studies have implicated that gut microbiota abundance is associated with myasthenia gravis (MG). However, the causal relationship underlying the associations is still unclear. Here, we aim to investigate the causal effect of gut microbiota on MG using Mendelian randomization (MR) method. Publicly available Genome-wide association study (GWAS) summary-level data for gut microbiota and for MG were extracted. Inverse variance weighted was used as the main method to analyze causality. The robustness of the results was validated with sensitivity analyses. Our results indicated that genetically predicted increased phylum Lentisphaerae (OR = 1.319, p = 0.026), class Lentisphaerae (OR = 1.306, p = 0.044), order Victivallales (OR = 1.306, p = 0.044), order Mollicutes (OR = 1.424, p = 0.041), and genus Faecalibacterium (OR = 1.763, p = 0.002) were potentially associated with a higher risk of MG; while phylum Actinobacteria (OR = 0.602, p = 0.0124), class Gammaproteobacteria (OR = 0.587, p = 0.036), family Defluviitaleaceae (OR = 0.695, p = 0.047), family Peptococcaceae (OR = 0.698, p = 0.029), and family Family XIII (OR = 0.614, p = 0.017) were related to a lower risk of MG. The present study provides genetic evidence for the causal associations between gut microbiota and MG, thus suggesting novel insights into the gut microbiota-neuromuscular junction axis in the pathogenesis of MG.

BackgroundAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the degeneration of motor neurons in the brain and spinal cord with a poor prognosis. Previous studies have observed cognitive decline and changes in brain morphometry in ALS patients. However, it remains unclear whether the brain structural alterations contribute to the risk of ALS. In this study, we conducted a bidirectional two-sample Mendelian randomization (MR) and colocalization analysis to investigate this causal relationship.MethodsSummary data of genome-wide association study were obtained for ALS and the brain structures, including surface area (SA), thickness and volume of subcortical structures. Inverse-variance weighted (IVW) method was used as the main estimate approach. Sensitivity analysis was conducted detect heterogeneity and pleiotropy. Colocalization analysis was performed to calculate the posterior probability of causal variation and identify the common genes.ResultsIn the forward MR analysis, we found positive associations between the SA in four cortical regions (lingual, parahippocampal, pericalcarine, and middle temporal) and the risk of ALS. Additionally, decreased thickness in nine cortical regions (caudal anterior cingulate, frontal pole, fusiform, inferior temporal, lateral occipital, lateral orbitofrontal, pars orbitalis, pars triangularis, and pericalcarine) was significantly associated with a higher risk of ALS. In the reverse MR analysis, genetically predicted ALS was associated with reduced thickness in the bankssts and increased thickness in the caudal middle frontal, inferior parietal, medial orbitofrontal, and superior temporal regions. Colocalization analysis revealed the presence of shared causal variants between the two traits.ConclusionOur results suggest that altered brain morphometry in individuals with high ALS risk may be genetically mediated. The causal associations of widespread multifocal extra-motor atrophy in frontal and temporal lobes with ALS risk support the notion of a continuum between ALS and frontotemporal dementia. These findings enhance our understanding of the cortical structural patterns in ALS and shed light on potentially viable therapeutic targets.

Previous studies have shown significant associations between home environmental factors and childhood eczema. However, few studies have compared how associations differ in different regions. This study investigated associations between home environmental factors and childhood eczema ever, and related symptoms including itchy rash (IR) and being awakened by itchy rash at night (awake by IR) in 4 cities located in different regions of China, based on cross-sectional investigations during 2010–2012. We used two-step analysis to explore the associations between influencing factors and eczema/related symptoms: first, group Least Absolute Shrinkage and Selection Operator (LASSO) was conducted to identify important factors among a list of candidates; then, the associations in total study population and in each city were estimated using logistic regression. We found these home environmental factors to be risk factors for eczema or related symptoms: large residence size, shared room, air cleaner at home, abnormal smell, perceived dry air, visible mold or damp stains, cooking with coal or wood, painted wall, incense, mice, new furniture during pregnancy, abnormal smell at birth, window condensation at birth and environmental tobacco smoke at birth. Environmental protective factors were rural house location and window ventilation. Associations of factors with eczema/related symptoms differed across cities. For example, air conditioning was protective for eczema in Beijing and awakening by IR in Shanghai with ORs of 0.70 (95%CI: 0.52, 0.95) and 0.33 (95%CI: 0.14, 0.81) respectively, but not significant in other cities. Our results have implications for improving home environments to reduce the risk of childhood eczema/related symptoms in different regions of China.

In this study, large eddy simulation (LES) was used to investigate the dynamic characteristics of diffusion flames in a swirl combustion chamber at an oxygen content of 11–23 wt% and temperature of 770 K. The proper orthogonal decomposition (POD) method was employed to obtain flame dynamic modes. The results indicate that oxygen content has a significant impact on the downstream flow and flame combustion characteristics of the swirl combustion chamber. With oxygen content increasing, the size of the recirculation zone is reduced, and the flame field fluctuations are intensified. The pressure and heat release fluctuations under different oxygen contents were analyzed using frequency spectrum analysis. Finally, the flame modes were analyzed using the POD method, and it was found that the coherent structures are asymmetric relative to the local coordinate system. At an oxygen content of 11 wt%, they exhibit larger coherent structures, while at an oxygen content of 23 wt%, they exhibit numerous turbulent structures.

Loxoprofen sodium (LOX) is a propionic acid derivative non-steroidal anti-inflammatory drug (NSAID), existing in the form of four stereoisomers. The main metabolites of LOX in vivo were trans- and cis-alcohol, each consisting of four stereoisomers. The objectives of the present study were to examine the selective pharmacokinetic behavior of LOX stereoisomers and stereoselective formation of its alcohol metabolites in rats based on a chiral liquid chromatographytandem mass spectrometry (LC-MS/MS) method by using an FLM Chiral NQ-RH column, which was reported for the first time. The significant difference in pharmacokinetic parameters of four stereoisomers indicated that stereoselective behavior has occurred in rats after oral administration of LOX. (1′S,2S)-LOX showed the highest concentration among the four stereoisomers in both plasma and urine samples. Trans- and cis-alcohol metabolites of LOX were also detected in plasma and urine, and trans-alcohol was found to be primary and the stereoisomeric fractions (SFs) of its four stereoisomers at different times were calculated. Examination of the stereoisomeric composition indicated a stereo preference for (2S)-configuration with respect to trans-alcohol formation. The overall results of the present study revealed the enantioselective pharmacokinetic properties of LOX stereoisomers in rats, which provided a means to advance understanding of the complex pharmacokinetic of LOX.

BackgroundEssential and non-essential elements have an important impact on the development of the central nervous system during fetal development. Due to their less developed brain, preterm infants are more sensitive to element exposure, and are high-risk groups of neurodevelopmental abnormalities. However, it is not clear whether the effects of element exposure in utero on postpartum neurodevelopment are different between full-term infants and preterm infants. ObjectiveTo evaluate the effects of element exposure levels during pregnancy on neurodevelopment of children aged 6-24 months (of corrected age), and compare the effects between preterm and full-term children. MethodsA prospective study design was adopted and this study was conducted based on the Maoming Birth Cohort Study (MBCS) in Maoming City, Guangdong Province. Twenty elements in cord blood of 197 preterm infants and 297 full-term infants were measured, including 11 essential trace elements [vanadium (V), chromium (Cr), manganese (Mn), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), selenium (Se), strontium (Sr), tin (Sn), and iron (Fe)], and 9 non-essential trace elements [aluminum (Al), arsenic (As), thallium (Tl), lead (Pb), uranium (U), cerium (Ce), antimony (Sb), cadmium (Cd), and yttrium (Y)]. The neurodevelopment of the children at 6, 12, and 24 months were evaluated by the Ages and Stages Questionnaires-the Third Edition (ASQ-3). A generalized estimating equation (GEE) model was adopted to evaluate the associations between elements and neurodevelopment in full-term and preterm children separately. ResultsThe positive rates of 10 elements (Mn, Cu, Zn, Se, Sr, Fe, Sb, Tl, Pb, and As) in cord blood were greater than 80%. Among the preterm birth children, the results of GEE analysis showed that after adjusting for the covariates, for each increase of interquartile range (IQR) in ln-transformed concentration, As was associated with problems/delay in the communication and problem-solving sub-scales, with the adjusted odds ratios (OR) and 95% confidence intervals (CI) of 1.36 (1.03-1.80) and 1.55 (1.10-2.20), respectively; the adjusted OR (95%CI) of problems/delay in the fine motor and problem-solving sub-scales were 1.44 (1.00-2.07) and 1.76 (1.09-2.84) for Sb, respectively; the adjusted OR (95%CI) of problems/delay in the communication sub-scale was 1.37 (1.09-1.74) for Se. No statistically significant associations between umbilical cord blood element concentrations and neurodevelopment indicators were observed among full-term children. The results of stratified analysis by sex showed that the associations between umbilical cord blood element concentrations and neurodevelopment problems/delay were only significant among female preterm children. ConclusionExposures to As, Se, and Sb during pregnancy may increase the risk of neurodevelopment problems/delay in preterm children aged 6-24 months, and female seem to be more vulnerable.

As modern aeroengine combustors advance towards high temperatures, afterburners are inevitably affected by diminished oxygen content in incoming flows, thus affecting combustion efficiency, instability, and flammability limits. In this study, the dynamic combustion characteristics of V-shaped bluff body-stabilised diffusion flames were investigated using a large eddy simulation method with an oxygen mass fraction range of 14–23% and temperatures ranging from 900 to 1100 K. The results show the significant effects of oxygen content and inflow temperature on the flame/flow behaviours downstream of the bluff-body flame holder. In a separated shear layer, two distinct modes of flow/flame shedding are observed when varying the oxygen content and inflow temperature. The results show that BVK instability governs the far-field wake flow/flame features, whereas the oxygen concentration and temperature significantly affect their oscillation amplitudes. In addition, variations in the incoming oxygen content and temperature shift the axial position of the transition from KH instability to BVK instability. Finally, a spectral analysis is conducted to investigate the characteristics of pressure and heat release pulsations under different scenarios. This study highlights the importance of oxygen content on the combustion dynamics of bluff body-stabilised diffusion flames at various temperatures, which is essential for optimising combustion efficiency and stability in practical applications.

Maternal exposure to chemical elements, including essential and non-essential elements, have been found to be associated with preterm births (PTB). However, few studies have measured element concentrations in cord whole blood, which reflects activity at the maternal-fetal interface and may be biologically associated with PTBs. In this study, we determined concentrations of 21 elements in cord whole blood and explored the associations between element concentrations and PTB in a nested case-control study within a birth cohort in Guangdong, China. Finally, 515 preterm infants and 595 full-term infants were included. We performed single-element and multi-element logistic regressions to evaluate linear relationships between element concentrations and PTB. According to the results of single-element models, most essential elements (including K, Ca, Si, Zn, Se, Sr and Fe) were negatively associated with PTB, while Cu, V, Co and Sn were positively associated with PTB. Of the non-essential elements, Sb, Tl, and U were positively associated with PTB, while Pb was negatively associated with PTB. The multi-element model results for most elements were similar, except that the association between Mg and PTB was shown to be significantly positive, and the association for Cu became much larger. A possible explanation is that the effects of Mg and Cu may be influenced by other elements. We performed restricted cubic spline (RCS) regressions and found significantly non-linear exposure-response relationships for Mg, Se, Sr, K and Sb, indicating that the effects of these elements on PTB are not simply detrimental or beneficial. We also examined the joint effect using a Bayesian kernel machine regression (BKMR) model and found the risk of PTB decreased significantly with element mixture concentration when lnC was larger than the median. Bivariate interaction analysis suggested antagonistic effects of Sb on Zn and Sr, which may be attributed to Sb negating the antioxidant capacity of Zn and Sr. This study provides additional evidence for the effect of element exposures on PTB, and will have implications for the prevention of excessive exposures or inappropriate element supplementation during pregnancy.

Résumé Contexte Le bromodomaine contenant la protéine 7 (BRD7), un membre de la famille du bromodomaine contenant des protéines, joue des rôles importants dans la modification de la chromatine et la régulation transcriptionnelle. Un modèle récent de souris Brd7-knockout présentait une azoospermie et une infertilité mâle, ce qui implique un rôle potentiel de BRD7 dans l’altération de la spermatogenèse chez l’homme. Cette étude cas-témoins visait à explorer l’association du gène BRD7 avec l’efficacité de la spermatogenèse et le risque d’altérations spermatogéniques chez l’homme. Résultats Un total de six variants hétérozygotes ont été détectés dans les régions de codage et d’épissage du gène BRD7 chez les patients présentant une azoospermie. Pour chacun des quatre variants rares prédits pour potentiellement endommager la fonction BRD7, nous avons en outre identifié ces quatre variants dans l’oligozoospermie et la normozoospermie. Cependant, nous n’avons observé aucune différence dans les fréquences d’allèle et de génotype des variants rares entre les cas avec altérations de la spermatogenèse et les témoins avec normozoospermie ; les produits du sperme des porteurs de variants étaient semblables à ceux des non-porteurs. Par ailleurs, on a observé une distribution semblable des allèles, des génotypes et des haplotypes de sept polymorphismes simples de nucléotide de balise (tagSNPs) entre les cas avec azoospermie ou oligozoospermie et les témoins normozoospermiques; aucune association n’a pas été identifiée entre les allèles BRD7 tagSNP-distingués et des produits du sperme. Conclusion L’absence d’association des variants rares liés à BRD7 et des variants communs liés à BRD7 avec les altérations de la spermatogenèse implique une contribution limitée du gène BRD7 à l’efficacité spermatogénique et à la susceptibilité à l’infertilité masculine chez l’homme.

With the unprecedented development of green and renewable energy sources, the proportion of clean hydrogen (H2) applications grows rapidly. Since H2 has physicochemical properties of being highly permeable and combustible, high-performance H2 sensors to detect and monitor hydrogen concentration are essential. This review discusses a variety of fiber-optic-based H2 sensor technologies since the year 1984, including: interferometer technology, fiber grating technology, surface plasma resonance (SPR) technology, micro lens technology, evanescent field technology, integrated optical waveguide technology, direct transmission/reflection detection technology, etc. These technologies have been evolving from simply pursuing high sensitivity and low detection limits (LDL) to focusing on multiple performance parameters to match various application demands, such as: high temperature resistance, fast response speed, fast recovery speed, large concentration range, low cross sensitivity, excellent long-term stability, etc. On the basis of palladium (Pd)-sensitive material, alloy metals, catalysts, or nanoparticles are proposed to improve the performance of fiber-optic-based H2 sensors, including gold (Au), silver (Ag), platinum (Pt), zinc oxide (ZnO), titanium oxide (TiO2), tungsten oxide (WO3), Mg70Ti30, polydimethylsiloxane (PDMS), graphene oxide (GO), etc. Various microstructure processes of the side and end of optical fiber H2 sensors are also discussed in this review.

The non-axisymmetric exciting guided wave can detect the thinning section of the elbow, and the time domain energy value of the signal collected at the outer arch position of the receiving end displays a downward trend as the remaining thickness of the erosion area decreases. To address the difficulty in detecting the erosion degree of the elbow with high accuracy, this paper uses the linear frequency modulation (LFM) signal to excite a non-axisymmetric guided wave that propagates in the 90° elbow and collects signals through four PZT receivers. To predict the erosion degree, the corresponding relationship between the energy value of the four signals after fractional Fourier filtering and the degree of elbow erosion is established through the particle swarm optimization (PSO)–least squares support vector machine (LSSVM) algorithm. The results show that the method proposed has an average accuracy rate of 98.1864%, 94.7167%, 99.119%, and 99.9593% for predicting the erosion degree of four elbow samples, and 94.0039%. and 81.2976% for two new erosion degrees, which are higher than the nonlinear regression model, LSSVM algorithm, and BP neural network algorithm. This study has guiding significance for real-time monitoring of elbow erosion.

Achieving well-controlled directional steering of liquids is of great significance for both fundamental study and practical applications, such as microfluidics, biomedicine, and heat management. Recent advances allow liquids with different surface tensions to select their spreading directions on a same surface composed of macro ratchets with dual reentrant curvatures. Nevertheless, such intriguing directional steering function relies on 3D printed sophisticated structures and additional polishing process to eliminate the inevitable microgrooves-like surface deficiency generated from printing process, which increases the manufacturing complexity and severally hinders practical applications. Herein, we developed a simplified dual-scale structure that enables directional liquid steering via a straightforward 3D printing process without the need of any physical and chemical post-treatment. The dual-scale structure consists of macroscale tilt ratchet equipped with a reentrant tip and microscale grooves that decorated on the whole surface along a specific orientation. Distinct from conventional design requiring the elimination of microgrooves-like surface deficiency, we demonstrated that the microgrooves of dual-scale structure play a key role in delaying or promoting the local flow of liquids, tuning of which could even enable liquids select different spreading pathways. This study provides a new insight for developing surfaces with tunable multi-scale structures, and also advances our fundamental understanding of the interaction between liquid spreading dynamics and surface topography.

Hesperidin and narirutin are a class of flavanone glycosides, which are the main active constituents in Citrus reticulata Blanco. In the present study, a chiral HPLC-UV method with amylose tris(3,5-dimethylphenylcarbamate) as a stationary phase under a normal-phase mode was used to achieve the stereoselective separation of the C-2 diastereomers of hesperidin and narirutin simultaneously. The single epimer was then successfully prepared by applying semi-preparative chromatography, whose absolute configuration (R/S) was characterized by combining the experimental electronic circular dichroism (ECD) detection with time-dependent density functional theory (TDDFT) calculations. The epimer composition of these two chiral flavanone glycosides in Citrus reticulata Blanco was then determined, which was found to be slightly different in the herbs from different production regions. The anti-inflammatory activity of each prepared single epimer was further evaluated, and some differences between one pair of epimers of hesperidin and narirutin were observed, which suggested that the presence of different epimers should be considered in the quality evaluation and control of natural medicine.

Accumulating evidence suggests that circular RNAs (circRNAs)—miRNA–mRNA ceRNA regulatory network—may play an important role in neurological disorders, such as Alzheimer’s disease (AD). Interestingly, neuropathological changes that closely resemble AD have been found in nearly all Down syndrome (DS) cases > 35 years. However, few studies have reported circRNA transcriptional profiling in DS cases, which is caused by a chromosomal aberration of trisomy 21. Here, we characterized the expression profiles of circRNAs in the fetal hippocampus of DS patients (n = 8) and controls (n = 6) by using microarray. MiRNA, mRNA expression profiling of DS from our previous study and scRNA-seq data describing normal fetal hippocampus development (GEO) were also integrated into the analysis. The similarity between circRNAs/genes with traits/cell-types was calculated by weighted correlation network analysis (WGCNA). miRanda and miRWalk2 were used to predict ceRNA network interactions. We identified a total of 7,078 significantly differentially expressed (DE) circRNAs, including 2,637 upregulated and 4,441 downregulated genes, respectively. WGCNA obtained 15 hub circRNAs and 6 modules with cell type–specific expression patterns among scRNA-seq data. Finally, a core ceRNA network was constructed by 14 hub circRNAs, 17 DE miRNA targets and 245 DE mRNA targets with a cell type–specific expression pattern annotation. Known functional molecules in DS or neurodegeneration (e.g., miR-138, OLIG1, and TPM2) were also included in this network. Our findings are the first to delineate the landscape of circRNAs in DS and the first to effectively integrate ceRNA regulation with scRNA-seq data. These data may provide a valuable resource for further research on the molecular mechanisms or therapeutic targets underlying DS neuropathy.

Obtaining information on the amplitude, phase and polarization profile of optical beams is of huge interest. Here, the authors create a generalized Hartmann-Shack array with metalenses which measures phase and phase-gradient profiles of optical beams but also measures spatial polarization profiles at the same time.

A method for the separation of folinic acid diastereomers by capillary electrophoresis in chiral separation media was developed. Aiming to achieve a good separation of the anionic analytes, a newly synthesized cationic β-cyclodextrin derivative, mono-6-deoxy-6-piperdine-β-cyclodextrin, was applied as the chiral selector. The effect of background electrolyte pH, the concentration of the cyclodextrin additive, and organic modifier on the separation was investigated. A good separation of folinic acid diastereomers was obtained with 30 mmol/L phosphate buffer at pH 6.50 containing 6.0 mmol/L of mono-6-deoxy-6-piperdine-β-cyclodextrin in 10% acetonitrile. Based on the capillary electrophoresis data, the binding constants of each diastereomer with mono-6-deoxy-6-piperdine-β-cyclodextrin were determined. Moreover, a computational modeling study, using the semi-empirical PM3 method, was used to discuss the possible mechanism of separation of folinic acid with mono-6-deoxy-6-piperdine-β-cyclodextrin.