Hexakis(2-alkoxy-1,5-phenyleneimine) macrocycles were synthesized using a simple one−pot procedure through by precipitation−driven cyclization. The acetal−protected AB−type monomers, 2-alkoxy-5-aminobenzaldehyde diethyl acetals, underwent polycondensation in water or acid−containing tetrahydrofuran. The precipitation−driven cyclization based on imine dynamic covalent chemistry and π−stacked columnar aggregation played a decisive role in the one−pot synthesis. The progress of the reaction was analyzed by MALDI−TOF mass spectrometry. The macrocycles with alkoxy chains were soluble in specific organic solvents such as chloroform, allowing their structures to be analyzed by NMR. The shape−anisotropic, nearly planar, and persistent macrocycles aggregated into columnar assemblies in polymerization solvents, driven by aromatic π−stacking. The octyloxylated macrocycle OcO−Cm6 exhibited an enantiotropic columnar liquid crystal−like mesophase between 165°C and 197°C. In the SEM image of (S)-(−)-3,7-dimethyloctyloxylated macrocycle (−)BCO-Cm6, columnar substances with a diameter of 100−200 nm were observed. The polymerization solution for 2-(2-methoxyethoxy)ethoxy)ethoxylated macrocycle (TEGO−Cm6) gelled and showed thixotropic properties by forming a hydrogen bond network.

Abstract：Objective: To compare the effects of fermentation on the chemical composition of Gastrodia Tuder Halimasch Powder, and to provide a basis for the processing, processing and clinical application of this medicinal material. Methods: UHPLC-Q-Orbitrap HRMS was used to identify compound structure by comparing excimer ions, characteristic fragment ions and reference substances, and referring to relevant literature and database search. The main differential components were screened by orthogonal partial least squares-discriminant analysis (OPLS-DA), and the differential components were quantitatively studied by high performance liquid chromatography, and the differences in the types and contents of chemical components before and after fermentation were compared. Results: A total of 77 compounds were identified or preliminarily derived after fermentation, including 21 terpenes, 18 organic acids, 9 flavonoids, 7 nucleosides, 6 amides, 4 amino acids, 2 pyrrolidone derivatives, 2 sterols, 2 alkaloids and 6 others.Through high performance liquid chromatography, it was found that the content of daidzein genistein and ergosterol was significantly increased after fermentation, and a new component ergosterol was produced. Compared with Gastrodia Tuder Halimasch Powder before fermentation, the content of genistin and other components was significantly reduced, and there may be a process of genistin conversion to genistein.Conclusion: The fermentation process will have a certain influence on the types and contents of the chemical components of Gastrodia Tuder Halimasch Powder, and ergosterol, genistein and .daidzein may be the main pharmacodynamic components, which can provide a useful reference for the clinical rational application, quality control and mechanism of action of Gastrodia Tuder Halimasch Powder.

A facile and environmentally benign method for a single-phase barium titanate synthesis in water vapor medium was studied to reveal the mechanism of phase transformation of the initial simple oxides mixture and estimate the capability of the product to be used as a raw material for low-frequency dielectric ceramics. The composition and structure of the reaction mixture treated in vapor at 130…150 °C as well as 230 °C for various time were investigated by means of XRD, SEM, HRTEM, EDX, and FTIR methods. The kinetics of the occurring phase transformation was described by Johnson-Mehl-Avrami-Erofeev equation. The reaction between the initial oxides was considered as a topochemical process with an apparent activation energy of 74…80 kJ mol^-1. A crucial role in this process belonged to the water vapor medium, which facilitated the generation of the reaction zone and its spreading inward the solid particles. The synthesized tetragonal barium titanate powder (mean particle size of 135 ± 24 nm) was sintered by a conventional technique at 1250 °C to obtain ceramics with grains of about 2 μm. Capacitance measurements performed a dielectric constant and loss tangent of ceramics, which reached 3879 and 6.7 10^-3, respectively, at 1 kHz and room temperature.

A large body of evidence, replicated in many mouse models of Alzheimer Disease (AD), demonstrated the therapeutic efficacy of oral rapamycin. Administration of m-TOR inhibitors (mTOR-Is), early after the clinical onset, greatly diminished cognitive impairment, amyloid angiopathy, intracellular beta Amyloid and neurofibrillary tangles load. The daily intake of rapamycin has always been 2.24g/Kg/24h. In humans the maximal tolerated oral dose is a few milligrams/day, and at this dosage patients are severely immunosuppressed. Thanks to rapalogs’ scarce CNS-related side effects, we administered intracerebroventricularly (ICV) high doses of the mTOR-I everolimus in a mouse model of AD (3xTg-AD) without significant systemic effects. The instability of the liquid formulation at body temperature (BT) made the treatment very short. Nevertheless, the efficacy of the treatment was high and much longer lasting than expected. In order to set up a thermostable, translational liquid formulation of mTOR-Is, we loaded everolimus in distearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG2000) micelles by the thin layer method. The formulation we obtained maintained over 95% of activity after 14 days at BT. We can envision short, potentially periodic ICV treatments in AD patients which replicate results obtained on animal models. The treatment could benefit also Tuberous Sclerosis and Multiple Sclerosis patients.

Fanconi anemia (FA) patients display an exacerbated risk of oral squamous cell carcinoma (OSCC) and precursor lesions at young ages, mainly at the oral cavity. As patients have defects in DNA repair mechanisms, standard-of-care treatments to OSCC such as radiotherapy and chemotherapy give rise to severe toxicities. New methods for early diagnosis are urgently necessary to allow treatments in early disease stages and achieve better clinical outcomes. We have conducted a prospective, longitudinal study whereby liquid biopsies from sixteen lesion/tumor-free patients were analyzed for the presence of mutations in cancer genes. DNA from saliva and plasma were sequentially collected and deep-sequenced, and the clinical evolution followed during a median time of around 2 years. In 9/16 FA patients we detected mutations in cancer genes (mainly TP53) with molecular allele frequencies (MAF) down to 0.07 %. Importantly, all patients having mutations and clinical follow-up data after mutation detection (n=6) developed oral precursor lesions or OSCC. Lead-time between mutation detection and tumor diagnosis ranged from 23 to 630 days. Strikingly, FA patients without mutations display significantly lower risk of developing precursor lesions or OSCC. Therefore, our diagnostic approach could help to stratify FA patients into risk groups, which would allow closer surveillance for OSCC or precursor lesions.

Keywords: liquid alloys, microstratification, dispersed particles, spontaneous dispersion, criteria for true (entropic) spontaneous dispersion, mechanisms of quasi-spontaneous dispersion, methods and results for assessing size of dispersed particles.

The study of cell-free DNA (cfDNA) and other peripheral blood components (known as “liquid biopsies”) is promising and has been investigated especially in solid tumors. Nevertheless, it is increasingly showing greater utility in the diagnosis, prognosis, and response to treatment of hematological malignancies; in the future, it could prevent invasive techniques, such as bone marrow (BM) biopsy. Most of the studies about this topic have been focused on B cell lymphoid malignancies; some of them have shown that cfDNA can be used as a novel way for diagnosis and minimal residual monitoring in B cell lymphomas, using techniques such as next-generation sequencing (NGS). In myelodysplastic syndromes, multiple myeloma, or chronic lymphocytic leukemia, liquid biopsies may allow for an interesting genomic representation of the tumor clones affecting different lesions (spatial heterogeneity). In acute leukemias, it can be helpful in the monitoring of early treatment response and the prediction of treatment failure. In chronic lymphocytic leukemia, the evaluation of cfDNA permits the definition of clonal evolution and drug resistance in real-time. However, there are limitations such as the difficulty in obtaining sufficient circulating tumor DNA for achieving a high sensitivity to assess minimal residual disease or the lack of standardization of the method and clinical studies to confirm its prognostic impact. This review focuses on clinical applications of cfDNA on minimal residual disease in hematological malignancies.

A novel stationary phase for affinity separations is presented. This material is based on sintered borosilicate glass readily available as semi-finished filter plates with defined porosity and surface area. The material shows fast binding kinetics and excellent long-term stability under real application conditions due to lacking macropores and high mechanical rigidity. The glass surface can be easily modified with standard organosilane chemistry to immobilize selective binders or other molecules used for biointeraction. In this paper, the manufacturing of the columns and their respective column holders by 3D printing is shown in detail. The model system protein A/IgG was chosen as an example to examine the properties of such monolithic columns under realistic application conditions. Several specifications, such as (dynamic) IgG capacity, pressure stability, long-term performance, productivity, non-specific binding, and peak shape, are presented. It could be shown that due to the very high separation speed, 250 mg antibody per hour and column can be collected, which surpasses the productivity of most standard columns of the same size. The total IgG capacity of the shown columns is around 4 mg (5.5 mg/mL), which is sufficient for most tasks in research laboratories. The cycle time of an IgG separation can be less than 1 minute. Due to the glass material's excellent pressure resistance, these columns are compatible with standard HPLC systems. This is usually not the case with standard affinity columns, limited to manual use or application in low-pressure systems. The use of a standard HPLC system also improves the ability for automation, which enables the purification of hundreds of cell supernatants in one day. The sharp peak shape of the elution leads to an enrichment effect, which might increase the concentration of IgG by a factor of 3. The final concentration of IgG can be around 7.5 mg/mL without the need for an additional nanofiltration step. The purity of the IgG was > 95% in one step and nearly 99% with a second polishing run.

Chemotherapy for lung cancer has made remarkable progress, and its selection has been subdivided by genetic analysis. Although response evaluation criteria in solid tumors (RECIST) is a simple and highly objective evaluation method, it has been pointed out that it has the disadvantage of not being able to accurately evaluate the therapeutic effect of molecularly targeted drugs and immune checkpoint inhibitors. The purpose of this study is to determine whether quantitative evaluation of DWIBS is useful in determining the effectiveness of treatment for lung cancer. There were 31 patients with lung cancer and 56 patterns were obtained. First, the determination of treatment effect (PD, SD, PR) based on RECIST was performed on CT. Second, tDV and ADC (median) were measured using BD score from DWI images taken at the same time, and the rate of change was calculated. Then, we compared and examined the correlation between RECIST and the rate of change in tDV. There were correlations between RECIST and the rate of change in tDV in PD and PR cases respectively. Compared RECIST on CT, DWIBS using BD score would be more accurate for response evaluation of treatment. There was a tendency that tDV decreased with increasing ADC values, but some of the cases had a dissociated response with increasing ADC values and increasing tDV. Thus, since the color display of ADC values allows us to infer their contents, it would be useful for the evaluation of cases such as dissociated response and pseudoprogression, which are suspected to be atypical responses that are difficult to evaluate with RECIST and other methods.

Microsamples (collections usually less than 50 µL) have been introduced in pre-clinical, clinical, and research settings to overcome obstacles in sampling via traditional venipuncture. However, venipuncture remains the sampling gold standard for metabolic phenotyping of blood. This pre-sents several challenges in metabolic phenotyping workflows: accessibility for individuals in ru-ral and remote underserved areas (due to the need for trained personnel), the unamenable nature to frequent sampling protocols in longitudinal research (for its invasive nature), and sample col-lection difficulty in the young and elderly. Furthermore, venous sample stability may be compro-mised when temperate conditions necessary for cold-chain transport are beyond control. Alter-natively, research utilising microsamples extends phenotyping possibilities to inborn errors of metabolism, therapeutic drug monitoring, nutrition, as well as sport and anti-doping. Although the application of microsamples in metabolic phenotyping exists, it is still in its infancy, with whole blood being overwhelmingly the primary biofluid collected through the collection method of dried blood spots. Research into metabolic phenotyping of microsamples is limited; however, with advances in commercially available microsampling devices, common barriers such as volumetric inaccuracies and the ‘haematocrit effect’ in dried blood spot microsampling can be overcome. In this review, we provide an overview of the common uses and workflows for mi-crosampling in metabolic phenotyping research. We discuss the advancements in technologies, highlighting key considerations and remaining knowledge gaps for employment of microsamples in metabolic phenotyping research. Supporting the translation of research from the ‘bench to the community’.

Tea (Camellia sinensis) is one of the most popular beverages worldwide. Many types of tea prod-ucts continuously emerge in an endless stream; so, the classification or verification of tea be-comes more difficult. Aroma is a vital indicator of tea quality. The present study deals with the identification of aroma compounds in 18 different kinds of tea belonging to three typical tea va-rieties, including green tea, oolong tea, and black tea, using GC-IMS and GC×GC-O-MS. More-over, the clustering of all 18 tea samples and the in-depth correlation analysis between sensory evaluation and instrumental data were performed using the PCA and OPLS-DA. The results re-vealed that in all 18 kinds of tea, a total of 85 aroma compounds were detected by GC-IMS, whereas 318 were detected by GC×GC-O-MS. The PCA result revealed that green tea, oolong tea, and black tea could be clearly separated based on their peak areas. The OPLS-DA result showed that a total of 49 aroma compounds with VIP value > 1.0 could be considered as the potential in-dicators to quickly classify or verify tea types. This study not only compared the aroma differ-ences across different types of teas, but also provided ideas for the rapid monitoring of tea qual-ity and variety.

Oral squamous cell carcinoma (OSCC) is a highly prevalent and aggressive malignancy, with mortality rates that reach 60%, mainly due to an excessive diagnostic delay. MiRNAs, a class of crucial epigenetic gene-expression regulators, have emerged as potential diagnostic biomarkers, with >200 molecules reported to be dysregulated in OSCC. We had previously established an in silico methodology for the identification of the most disease-specific molecules by bridging genetics and epigenetics. Here, we identified the stage-specific miRNAs that govern the asymptomatic early stages of oral tumorigenesis by exploiting the reverse interplay between miRNA-levels and their target-genes’ expression. Incorporating gene expression data from our group’s experimental hamster model of sequential oral oncogenesis, we bioinformatically detected the miRNAs that simultaneously target/regulate >75% of the genes that are characteristically upregulated or downregulated in the consecutive stages of hyperplasia, dysplasia and early-invasion OSCC, while exhibiting the opposite expressional dysregulation in OSCC-derived tissue and/or saliva specimens. We found that all stages share the downregulation of miR-34a-5p, miR124-3p, and miR-125b-5p, while miR-1-3p is underexpressed in dysplasia and early-invasion. Malignant early-invasion stage is distinguished by the downregulation of miR-147a and the overexpression of miR-155-5p, miR-423-3p and miR-34a-5p. The identification of stage-specific miRNA molecules may facilitate their utilization as biomarkers for presymptomatic OSCC diagnosis.

Diseases caused by arboviruses are on the increase worldwide. In addition to arthropod bites, most arboviruses can be transmitted via accessory routes. Products of human origin (labile blood products, solid organs, hematopoietic stem cells, tissues) present a risk of contamination for the recipient if the donation is made when the donor is viremic. This narrative review describes the risks of acquiring certain arboviral diseases from human products, mainly solid organs and hematopoietic stem cells, in the French context. Mainland France and its overseas territories are exposed to a complex array of imported and endemic arboviruses, which differ according to their respective location. The main risks considered in this study are infections by West Nile virus, dengue virus and tick-borne encephalitis virus. The ancillary risks represented by Usutu virus infection, chikungunya and Zika are also addressed more briefly. For each disease, the guidelines issued by the French High Council of Public Health, which is responsible for issuing guidelines to mitigate the risks associated with products of human origin and for supporting public health policy decisions, are briefly outlined. The aim of this review is also to contribute to the standardization of recommendations at international level in areas with the same viral epidemiology.

Downwind odor characteristics can be very different depending upon the size of the upwind point-source, interim topography, and wind conditions. At one extreme, the downwind odor plume from a relatively large, confined animal feeding operation (CAFO), located on a flat open plain and under stable, near-straight-line wind conditions can be rather broad, sustained and predictable relative to a fixed receptor site downwind. In contrast, the plume from a small point-source (e.g., a roof vent stack) located on irregular topography and under rapidly shifting wind conditions can be intermittent and fleeting. These transient odor events can be surprisingly intense and offensive, in spite of their fleeting occurrence and perception. This work reports on efforts to optimize an environmental odor sampling strategy, which is optimized for the challenges of (1) sampling of such transient odor 'spikes' and (2) the prioritization of odors/odorants from multiple, closely co-located point-sources, under such transient event conditions. Protocol refinement has emerged by way of 2 environmental odor assessment projects which have been undertaken on behalf of the Missouri Department of Natural Resources. The challenge of transient odor events has been mitigated utilizing rapid, odor cued whole-air grab capture sampling into metalized-FEP gas sampling bags, followed by immediate adsorption transfer onto SPME fibers or sorbent tubes for stabilization during the shipment and storage interval between collection and final analysis. Initial results demonstrated approximately 11 fold increases in target odorant yields for 900 mL sorbent tube transfers from 2-3 second 'burst' odor event bag-captures, as compared to equivalent direct collections at the same downwind receptor location but during perceived (stable) odor 'lull' periods. Results-to-date targeting refinement and field trials of this integrated environmental odor assessment strategy are presented. Preliminary application targeting general odor sampling and point-source differentiation utilizing tracer gases is also presented.

Nonporous corundum powder, known as an abrasive material in the industry, was functionalized covalently with protein binders to isolate and enrich specific proteins from complex matrices. The materials based on corundum were characterized by TEM, ESEM, BET, DLS, and zeta potential measurements. The strong Al-O-P bonds between the corundum surface and amino phosphonic acids are used to introduce functional groups for further conjugations. The common crosslinker glutaraldehyde was compared with a hyperbranched polyglycerol (PG) of around 10 kDa. The latter is oxidized with periodate to generate aldehyde groups that can covalently react with the amines of the surface and the amino groups from the protein via a reductive amination process. The amount of bound protein was quantified via aromatic amino acid analysis (AAAA). This work shows that oxidized polyglycerol can be used as an alternative to glutaraldehyde. With polyglycerol, more of the model protein bovine serum albumin (BSA) could be attached to the surface under the same conditions, and lower nonspecific binding (NSB) was observed. As a proof of concept, IgG was extracted with protein A from crude human plasma. The purity of the product was examined by SDS-PAGE. A binding capacity of 1.8 mg IgG per g of corundum powder was achieved. The advantages of corundum are the very low price, extremely high physical and chemical stability, pressure resistance, favorable binding kinetics, and flexible application.

The local and global order in dense packings of linear, semi-flexible polymers of tangent hard spheres are studied by employing extensive Monte Carlo simulations at increasing volume fractions. Chain stiffness is controlled by a tunable harmonic potential for the bending angle whose intensity dictates the rigidity of the polymer backbone as a function of the bending constant and equilibrium angle. The studied angles range from acute to obtuse ones, reaching the limit of rod-like polymers. We analyze how packing density and chain stiffness affect the ability of chains to self-organize at the local and global levels. The former corresponds to crystallinity as quantified by the Characteristic Crystallographic Element (CCE) norm descriptor, while the latter is computed through the scalar orientational order parameter. In all cases, we identify the critical volume fraction for the phase transition and gauge the established crystal morphologies, developing a complete phase diagram as a function of packing density and equilibrium bending angle. A plethora of structures is obtained, ranging from random hexagonal closed packed morphologies of mixed character and almost perfect face centered cubic (FCC) and hexagonal close-packed (HCP) crystals at the level of monomers, to nematic mesophases, with prolate and oblate mesogens at the level of chains. For rod-like chains, hysteresis is observed between the establishment of long-range nematic order and crystallization, while for right-angle chains both transitions are synchronized. A comparison is also provided against the analogous packings of monomeric and fully flexible chains of hard spheres.

This article seeks to strengthen efforts in technological developments based on the classification of PET plastic that positively impacts sustainable development and contributes to suitable solutions in collection centers in Mexico. Three experiment designs and machine learning tools for data processing were developed. For the experimentation, three factors were considered: the bottle's size, the amount of liquids inside the bottle, and the label on the bottle. The first experiment was to identify the distance of the sensor from post-consumer PET bottles. The second experiment was to determine the detection ability of the sensor with different levels of liquids inside the bottles, and the third was to determine the detection ability on the bottle labels. A digital lux meter on a microcontroller was developed to monitor illuminance on post-consumer PET plastic when it contains liquid as it passes through a conveyor belt for processing at an average rate of three bottles per second. With the implemented methodology, liquids were satisfactorily detected inside the transparent PET bottles when they had beverages between 25% and 100% of their capacity. Finally, this paper highlights that it is possible to implement an affordable design to identify bottles with liquids for collection centers.

Immobilized metal affinity chromatography (IMAC) is a popular and valuable method for the affinity purification of polyhistidine-tagged recombinant proteins. However, it often shows practical limitations, which might require cumbersome optimizations, additional polishing, and enrichment steps. Here, we present functionalized corundum particles for the efficient, economical, and fast purification of recombinant proteins in a column-free format. The corundum surface is first derivatized with the amino silane APTES, then EDTA dianhydride, and subsequently loaded with nickel ions. The Kaiser test, well-known in solid-phase peptide synthesis, was used to monitor amino silanization and the reaction with EDTA dianhydride. In addition, ICP-MS was performed to quantify the metal-binding capacity. His-tagged protein A/G (PAG), mixed with bovine serum albumin (BSA), was used as a test system. The PAG binding capacity was around 3 mg protein per gram of corundum. Cytoplasm obtained from different E. coli strains was examined as an example of a complex matrix. The imidazole concentration was varied in the loading and washing buffers. As expected, higher imidazole concentrations during loading are usually beneficial when higher purities are desired. Even when higher sample volumes, such as one liter, were used, recombinant protein down to a concentration of 1 µg/mL could be isolated selectively. Comparing the corundum material with standard Ni-NTA agarose beads indicated higher purities of proteins isolated using corundum. His6-MBP-mSA2, a fusion protein consisting of monomeric streptavidin and maltose-binding protein in the cytoplasm of E. coli, was purified successfully. To show that this method is also suitable for mammalian cell culture supernatants, purification of the SARS-CoV-2-S-RBD His8 expressed in human Expi293F cells was performed. The material cost of the nickel-loaded corundum material (without regeneration) is estimated to be less than 30 cents for 1 gram of functionalized support or 10 cents per milligram of isolated protein. Another advantage of the novel system is the corundum particles' extremely high physical and chemical stability. The new material should be applicable in small laboratories and large-scale industrial applications. In summary, we could show that this new material is an efficient, robust, and cost-effective purification platform for the purification of His-tagged proteins, even in challenging, complex matrices and large sample volumes of low product concentration.

A new generation of nano-technologies is expanding solid propulsion capabilities and increasing their relevance for versatile and manoeuvrable micro-satellites with safe high-performance propulsion. We propose the innovative concept, connected with application of new synergistic effect of the energetic materials performance enhancement and reaction zones programming for the next generation small satellite multimode solid propulsion system. The main idea of suggested concept is manipulating by the self-organized wave patterns excitation phenomenon, by the properties of the energetic materials reaction zones and by localization of the energy release areas. This synergistic effect can be provided through application of the functionalized carbon-based nanostructured metamaterials as a nano-additives along with simultaneous manipulating by their properties through the electrostatic field. Mentioned effect will be controlled through predictive programming both by the spatial structure and physics-chemical properties of the functionalized carbon-based nano-additives and through the electromagnetic control of the self-organized wave pattern excitation and micro- and nano- scale oscillatory networks in the energetic material reaction zones. Suggested new concept makes it possible to increase the energetic material regression rate and increase the thrust of the solid propulsion system with minimal additional energy consumption.