Electrical properties determine the liquid flow direction in plasma-liquid interactions.

During atmospheric pressure plasma impingement, plasma induced liquid flow will influence the transport and distribution of plasma generated charged and reactive species in liquids. We use particle image velocimetry and supplementary pH, conductivity and temperature measurements to investigate electrical properties of an AC kHz plasma jet interacting with water and electrolytes. We observe that the dominant driving mechanism in low conductive solutions are surface forces such as shear stresses and stagnation-pressure induced dimpling. These give upwards flows beneath the plasma-liquid interaction point. In highly conductive solutions, such as water with dissolved salts, the dominant driving mechanism is electro-hydrodynamic forces, with flows directed downwards underneath the plasma jet in our system. We therefore demonstrate that the direction of initial plasma induced liquid flows can be controlled through the addition of salt ions. In electrically grounded salt solutions, we also observe time resolved flow direction switching, possibly due to modification of salt solutions via electrolytic and plasma induced reactions changing the dominant flow mechanism over time.

Photoredox Activation of Fluorinated Organozinc Reagents: Hydrofluoroalkylation of Unactivated and Electron Deficient Alkenes.

Hydrofluoroalkylation of alkenes with organozinc reagents under photocatalytic conditions is described. The fluorinated alkyl radicals were generated from organozincs by the single electron oxidation of the carbon-zinc bond. The radical addition step is followed either by hydrogen atom transfer for unactivated olefins or by a reduction/protonation sequence for strongly accepting arylidenemalononitriles.

Detecting emergence of ruptures in individual layers of the stretched intestinal wall using optical coherence elastography: A pilot study.

We report a new application of compression optical coherence elastography (C-OCE) to monitor the emergence of ruptures in individual layers of longitudinally stretched small-intestine walls using tissue samples (n = 36) from nine minipigs. Before stretching, C-OCE successfully estimated stiffness for each intestine-wall layer: longitudinal muscular layer with serosa, circumferential muscular layer, submucosa and mucosa. In stretched samples, C-OCE clearly visualized initial stiffening in both muscular layers. By 25% elongation, a sharp stiffness decrease for the longitudinal muscular layer, indicated emergence of tears in all samples. With further stretching, for most samples, ruptures emerged in the circumferential muscular layer and submucosa, while mucosa remained undamaged. Histology confirmed the OCE-revealed damaging and absence of tissue damage for ~15% elongation. Thus, C-OCE has demonstrated a high potential for determining the safety tissue-stretching threshold which afterward may be used intraoperatively to prevent rupture risk in intestinal tissues stretched during various diagnostic/therapeutic procedures.

Catalyst- and solvent-free regiospecific SNHAr phosphinylation of pyridines with H-phosphinates mediated by benzoylphenylacetylene.

Pyridines undergo a facile SNHAr phosphinylation with H-phosphinates under catalyst- and solvent-free conditions (50-55 °C) in the presence of benzoylphenylacetylene to afford 4-phosphinylpyridines in up to 68% yield. In this reaction, benzoylphenylacetylene activates the pyridine ring by the formation of a 1,3(4)-dipolar complex, deprotonates H-phosphinates to generate P-centered anions and finally acts as an oxidizer, being eliminated from an intermediate ion pair. Terminal electron-deficient acetylenes (methyl propiolate and benzoylacetylene) are inefficient as mediators in the above SNHAr process.

Gold/cobalt ferrite nanocomposite as a potential agent for photothermal therapy.

The study encompasses an investigation of optical, photothermal and biocompatibility properties of a composite consisting of golden cores surrounded by superparamagnetic CoFe2O4 nanoparticles. Accompanied with the experiment, the computational modeling reveals that each adjusted magnetic nanoparticle redshifts the plasmon resonance frequency in gold and nonlinearly increases the extinction cross-section at ~800 nm. The concentration dependent photothermal study demonstrates a temperature increase of 8.2 K and the photothermal conversion efficiency of 51% for the 100 µg/mL aqueous solution of the composite nanoparticles, when subjected to a laser power of 0.5 W at 815 nm. During an in vitro photothermal therapy, a portion of the composite nanoparticles, initially seeded at this concentration, remained associated with the cells after washing. These retained nanoparticles effectively heated the cell culture medium, resulting in a 22% reduction in cell viability after 15 min of the treatment. The composite features a potential in multimodal magneto-plasmonic therapies.

Cancer fusion transcripts with human non-coding RNAs.

Cancer chimeric, or fusion, transcripts are thought to most frequently appear due to chromosomal aberrations that combine moieties of unrelated normal genes. When being expressed, this results in chimeric RNAs having upstream and downstream parts relatively to the breakpoint position for the 5'- and 3'-fusion components, respectively. As many other types of cancer mutations, fusion genes can be of either driver or passenger type. The driver fusions may have pivotal roles in malignisation by regulating survival, growth, and proliferation of tumor cells, whereas the passenger fusions most likely have no specific function in cancer. The majority of research on fusion gene formation events is concentrated on identifying fusion proteins through chimeric transcripts. However, contemporary studies evidence that fusion events involving non-coding RNA (ncRNA) genes may also have strong oncogenic potential. In this review we highlight most frequent classes of ncRNAs fusions and summarize current understanding of their functional roles. In many cases, cancer ncRNA fusion can result in altered concentration of the non-coding RNA itself, or it can promote protein expression from the protein-coding fusion moiety. Differential splicing, in turn, can enrich the repertoire of cancer chimeric transcripts, e.g. as observed for the fusions of circular RNAs and long non-coding RNAs. These and other ncRNA fusions are being increasingly recognized as cancer biomarkers and even potential therapeutic targets. Finally, we discuss the use of ncRNA fusion genes in the context of cancer detection and therapy.

Tissue Elasticity as a Diagnostic Marker of Molecular Mutations in Morphologically Heterogeneous Colorectal Cancer.

The presence of molecular mutations in colorectal cancer (CRC) is a decisive factor in selecting the most effective first-line therapy. However, molecular analysis is routinely performed only in a limited number of patients with remote metastases. We propose to use tissue stiffness as a marker of the presence of molecular mutations in CRC samples. For this purpose, we applied compression optical coherence elastography (C-OCE) to calculate stiffness values in regions corresponding to specific CRC morphological patterns (n = 54). In parallel to estimating stiffness, molecular analysis from the same zones was performed to establish their relationships. As a result, a high correlation between the presence of KRAS/NRAS/BRAF driver mutations and high stiffness values was revealed regardless of CRC morphological pattern type. Further, we proposed threshold stiffness values for label-free targeted detection of molecular alterations in CRC tissues: for KRAS, NRAS, or BRAF driver mutation-above 803 kPa (sensitivity-91%; specificity-80%; diagnostic accuracy-85%), and only for KRAS driver mutation-above 850 kPa (sensitivity-90%; specificity-88%; diagnostic accuracy-89%). To conclude, C-OCE estimation of tissue stiffness can be used as a clinical diagnostic tool for preliminary screening of genetic burden in CRC tissues.

Mutational dissection of a hole hopping route in a lytic polysaccharide monooxygenase (LPMO).

Oxidoreductases have evolved tyrosine/tryptophan pathways that channel highly oxidizing holes away from the active site to avoid damage. Here we dissect such a pathway in a bacterial LPMO, member of a widespread family of C-H bond activating enzymes with outstanding industrial potential. We show that a strictly conserved tryptophan is critical for radical formation and hole transference and that holes traverse the protein to reach a tyrosine-histidine pair in the protein's surface. Real-time monitoring of radical formation reveals a clear correlation between the efficiency of hole transference and enzyme performance under oxidative stress. Residues involved in this pathway vary considerably between natural LPMOs, which could reflect adaptation to different ecological niches. Importantly, we show that enzyme activity is increased in a variant with slower radical transference, providing experimental evidence for a previously postulated trade-off between activity and redox robustness.

Clinical and genetic factors involved in Porto-sinusoidal vascular disorder after oxaliplatin exposure.

BACKGROUND AND AIMS: Oxaliplatin (OX) has been described as a potential etiologic agent for porto-sinusoidal vascular disorder (PSVD). Our aim was to describe the natural history of PSVD due to OX in colon cancer (CRC) and identify risk factors for its development. METHODS: We made a multicenter retrospective case-control (ratio 1:3) study with patients diagnosed of PSVD-OX. Baseline data, end of treatment, years of follow-up and diagnosis of PSVD were collected and compared to controls (without PSVD). Besides, 16 different SNPs were selected from bibliography and analyzed by genotyping in the case group to identify potential genetic risk factors. RESULTS: 41 cases were identified, with a median time to PSVD diagnosis after the end of OX of 34 months. Spleen diameter was the strongest predictor of PSVD during treatment (OR 43.94 (14.48-133.336); p < 0.0001). Additionally, thrombocytopenia (<150 × 10^9) at one year was a significant disease risk marker (OR 9.35; 95% CI: 3.71-23.58; p = 0.001). We could not establish any significant association between the selected SNPs and PSVD diagnosis. CONCLUSION: The increase of spleen diameter is the strongest predictor of PSVD in patients treated with OX for CRC. These patients could be candidates for a specific follow-up of portal hypertension-related complications.

Radiosensitizing effects of heparinized magnetic iron oxide nanoparticles in colon cancer.

The combination of radiation treatment and chemotherapy is currently the standard for management of cancer patients. However, safe doses do not often provide effective therapy, then pre-treated patients are forced to repeat treatment with often already increased tumor resistance to drugs and irradiation. One of the solutions we suggest is to improve primary course of radiation treatment via enhancing radiosensitivity of tumors by magnetic-guided iron oxide nanoparticles (magnetite). We obtained spherical heparinized iron oxide nanoparticles (hIONPs, ∼20 nm), characterized it by TEM, Infrared spectroscopy and DLS. Then hIONPs cytotoxicity was assessed for colon cancer cells (XTT assay) and cellular uptake of nanoparticles was analyzed with X-ray fluorescence. Combination of ionizing radiation (IR) and hIONPs in vitro caused an increase of G2/M arrest of cell cycle, mitotic errors and decrease in survival (compared with samples exposed to IR and hIONPs separately). The promising results were shown for magnetic-guided hIONPs in CT26-grafted BALB/C mice: the combination of intravenously administrated hIONPs and IR showed 20,8% T/C ratio (related to non-treated mice), while single radiation had no shown significant decrease in tumor growth (72,4%). Non-guided by magnets hIONPs with IR showed 57,9% of T/C. This indicates that ultra-small size and biocompatible molecule are not the key to successful nano-drug design, in each case, delivery technologies need to be improved when transferred to in vivo model.

Ankle arthrodesis through minimally-invasive transfibular approach: a new surgical technique.

PURPOSE: The purpose of our work was to demonstrate the surgical technique of ankle arthrodesis using the minimally-invasive transfibular (MITF) approach, which minimizes soft tissue damage and is advantageous for high-risk patients. METHODS: In this prospective study, a total of 12 patients with end-stage varus ankle osteoarthritis, including high-risk individuals, underwent ankle arthrodesis using the MITF approach. The technique involves a unique osteotomy at the joint space level, minimizing soft tissue detachment from the fibula. The primary outcomes assessed included bony union, time to weight-bearing, correction of varus deformity, and functional outcomes measured by the American Orthopedic Foot and Ankle Society (AOFAS) hindfoot scale. However, the study's limitations encompass a small sample size and the absence of a control group. RESULTS: At 6 months post-operation, all patients achieved bony union, with a mean time to union of 13.7 ± 5.2 weeks. The average time to initiate weight-bearing without additional support was 11.2 ± 3.8 weeks. Preoperative varus deformity (17.08 ± 8.36 degrees) and talar tilt (8.75 ± 4.33 degrees) were successfully corrected, with postoperative alignment within 0-5 degrees of valgus. Functional outcomes showed a significant improvement in AOFAS scores from 37.83 ± 7.79 points preoperatively to 77.42 ± 5.63 points one year after surgery (p = 0.002). Minor complications occurred in two patients, both effectively treated with local therapy and antibiotics. CONCLUSIONS: The MITF approach for ankle arthrodesis demonstrates promising results in addressing end-stage varus ankle osteoarthritis, even in high-risk patients. However, the study's limitations highlight the need for a prospective comparative clinical trial with a larger sample size to ascertain the technique's effectiveness and safety definitively.

Exploring Embodied Intelligence in Soft Robotics: A Review.

Soft robotics is closely related to embodied intelligence in the joint exploration of the means to achieve more natural and effective robotic behaviors via physical forms and intelligent interactions. Embodied intelligence emphasizes that intelligence is affected by the synergy of the brain, body, and environment, focusing on the interaction between agents and the environment. Under this framework, the design and control strategies of soft robotics depend on their physical forms and material properties, as well as algorithms and data processing, which enable them to interact with the environment in a natural and adaptable manner. At present, embodied intelligence has comprehensively integrated related research results on the evolution, learning, perception, decision making in the field of intelligent algorithms, as well as on the behaviors and controls in the field of robotics. From this perspective, the relevant branches of the embodied intelligence in the context of soft robotics were studied, covering the computation of embodied morphology; the evolution of embodied AI; and the perception, control, and decision making of soft robotics. Moreover, on this basis, important research progress was summarized, and related scientific problems were discussed. This study can provide a reference for the research of embodied intelligence in the context of soft robotics.

Oxidative Transformation of 2-Furylanilines into Indolin-3-ones.

Oxidation of 2-furylaninlies with m-CPBA followed by treatment with a base provides access to functionalized indolin-3-ones. The designed oxidative transformation utilizes an underassessed chemical behavior of furyl-containing amines to form a C-N bond via engaging a ß-carbon atom of the furan core upon a ring-forming step, thereby providing an alternative disconnection toward nitrogen-containing heterocycles.

Tungsten Oxide Dispersed on Silica as Robust and Readily Available Oxo/Imido Heterometathesis Catalyst.

Continuing our investigation of catalytic oxo/imido heterometathesis as novel water-free method for C=N bond construction, we report here the application of classical transition metal oxides dispersed on silica (MOx/SiO2, M=V, Mo, W) as cheap, robust and readily available alternative to the catalysts prepared via Surface Organometallic Chemistry (SOMC). The oxide materials demonstrated activity in heterometathetical imidation of ketones, WO3/SiO2 being the most efficient. We also describe a new well-defined supported W imido complex (≡SiO)W(=NMes)2(Me2Pyr) (Mes=2,4,6-Me3C6H2, Me2Pyr=2,5-dimethylpyrrolyl) and characterize it with SOMC protocols, which allowed us to identify the position of W on the oxo/imido heterometathesis activity scale (Mo

Perineuronal Net Microscopy: From Brain Pathology to Artificial Intelligence.

Perineuronal nets (PNN) are a special highly structured type of extracellular matrix encapsulating synapses on large populations of CNS neurons. PNN undergo structural changes in schizophrenia, epilepsy, Alzheimer's disease, stroke, post-traumatic conditions, and some other brain disorders. The functional role of the PNN microstructure in brain pathologies has remained largely unstudied until recently. Here, we review recent research implicating PNN microstructural changes in schizophrenia and other disorders. We further concentrate on high-resolution studies of the PNN mesh units surrounding synaptic boutons to elucidate fine structural details behind the mutual functional regulation between the ECM and the synaptic terminal. We also review some updates regarding PNN as a potential pharmacological target. Artificial intelligence (AI)-based methods are now arriving as a new tool that may have the potential to grasp the brain's complexity through a wide range of organization levels-from synaptic molecular events to large scale tissue rearrangements and the whole-brain connectome function. This scope matches exactly the complex role of PNN in brain physiology and pathology processes, and the first AI-assisted PNN microscopy studies have been reported. To that end, we report here on a machine learning-assisted tool for PNN mesh contour tracing.

Exploration of Vitamin B6-Based Redox-Active Pyridinium Salts Towards the Application in Aqueous Organic Flow Batteries.

Pyridoxal hydrochloride, a vitamin B6 vitamer, was synthetically converted to a series of diverse redox-active benzoyl pyridinium salts. Cyclic voltammetry studies demonstrated redox reversibility under basic conditions, and two of the most promising salts were subjected to laboratory-scale flow battery tests involving galvanostatic cycling at 10 mM in 0.1 M NaOH. In these tests, the battery was charged completely, corresponding to the transfer of two electrons to the electrolyte, but no discharge was observed. Both CV analysis and electrochemical simulations confirmed that the redox wave observed in the experimental voltammograms corresponds to a two-electron process. To explain the irreversibility in the battery tests, we conducted bulk electrolysis with the benzoyl pyridinium salts, affording the corresponding benzylic secondary alcohols. Computational studies suggest that the reduction proceeds in three consecutive steps: first electron transfer (ET), then proton-coupled electron transfer (PCET) and finally proton transfer (PT) to give the secondary alcohol. 1H NMR deuterium exchange studies indicated that the last PT step is not reversible in 0.1 M NaOH, rendering the entire redox process irreversible. The apparent reversibility observed in CV at the basic media likely arises from the slow rate of the PT step at the timescale of the measurement.

Two-year retest reliability and predictive validity of the Self- and Informant-Personality Inventory for ICD-11 in older adults.

The International Classification of Diseases, 11th edition (ICD-11) adopted a fully dimensional model of personality disorder. The Personality Inventory for ICD-11 (PiCD) and Informant-Personality Inventory for ICD-11 (IPiC) were developed to assess the ICD-11 trait model, and the PiCD has since received significant validation support. However, there has only been one prior study of longitudinal predictive validity of the PiCD, two relatively short test-retest reliability studies of the PiCD, and no prior longitudinal tests of the IPiC. Longitudinal psychometric support for psychological assessment measures is essential. The present study provides a longer, larger, 2-year psychometric validation test of the PiCD and IPiC. Participants (N = 711) and their informants (N = 569) were recruited in the St. Louis Personality and Aging Network. The results demonstrated strong 2-year retest reliability for the PiCD and IPiC, as well as mean-level stability. Additionally, we explored the relationships between the PiCD and IPiC and important life outcome measures (depressive symptoms, satisfaction with life, and health status). The analysis revealed several significant associations between PiCD and IPiC scales and the outcome variables across time. Further, the PiCD Negative Affectivity and IPiC Detachment scales demonstrated incremental validity over each other and the outcome variables at Wave 1 in the prediction of depressive symptoms and satisfaction with life, respectively. The findings provide essential longitudinal test-retest reliability and predictive validity support for the PiCD and IPiC. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Application of the intramolecular Diels-Alder vinylarene (IMDAV) reaction for the synthesis of benzo-, carbocyclo-, thienothiopheneisoindolecarboxylic acids and its limitations.

Thienylallylamines, readily accessible from the corresponding thienyl aldehydes, react with maleic and trifluoromethylmaleic anhydrides leading to the formation of acids with a thieno[2,3-f]isoindole core. The reaction sequence involves two successive steps: acylation of the nitrogen atom of the initial allylamine and the intramolecular Diels-Alder vinylarene (IMDAV) reaction. The scope and limitations of the proposed method were thoroughly investigated. It has been revealed with the aid of X-ray analysis and DFT calculations that the key step, the IMDAV reaction, proceeds through an exo-transition state, giving rise to the exclusive formation of a single diastereomer of the target heterocycle. The obtained functionally substituted thieno[2,3-f]isoindole carboxylic acids are potentially useful substrates for further transformations and bioscreening. The antimicrobial evaluation of the obtained compounds revealed that 1-oxo-2-(3-(trifluoromethyl)phenyl)hexahydrobenzo[4,5]thieno[2,3-f]isoindole-10-carboxylic acid is the most active sample in the synthesized library. It exhibits antibacterial activity against sensitive strains of Gram-positive bacteria, including S. aureus, Enterococcus faecium, Bacillus cereus, and Micrococcus luteus, as well as the Gram-negative bacteria E. coli and Pseudomonas fluorescens, with MIC values ranging from 4 to 64 µg mL-1. 9-Oxo-8-phenyloctahydronaphtho[2,1-d]thieno[2,3-f]isoindole-10-carboxylic acid showed antifungal activity against yeast culture C. albicans with a MIC value of 32 µM.

Association of Altered Plasma Lipidome with Disease Severity in COVID-19 Patients.

The severity of COVID-19 is linked to an imbalanced immune response. The dysregulated metabolism of small molecules and bioactive lipids has also been associated with disease severity. To promote understanding of the disease biochemistry and provide targets for intervention, we applied a range of LC-MS platforms to analyze over 100 plasma samples from patients with varying COVID-19 severity and with detailed clinical information on inflammatory responses (>30 immune markers). This is the third publication in a series, and it reports the results of comprehensive lipidome profiling using targeted LC-MS/MS. We identified 1076 lipid features across 25 subclasses, including glycerophospholipids, sterols, glycerolipids, and sphingolipids, among which 531 lipid features were dramatically changed in the plasma of intensive care unit (ICU) patients compared to patients in the ward. Patients in the ICU showed 1.3-57-fold increases in ceramides, (lyso-)glycerophospholipids, diglycerides, triglycerides, and plasmagen phosphoethanolamines, and 1.3-2-fold lower levels of a cyclic lysophosphatidic acid, sphingosine-1-phosphates, sphingomyelins, arachidonic acid-containing phospholipids, lactosylceramide, and cholesterol esters compared to patients in the ward. Specifically, phosphatidylinositols (PIs) showed strong fatty acid saturation-dependent behavior, with saturated fatty acid (SFA)- and monosaturated fatty acid (MUFA)-derived PI decreasing and polystaturated (PUFA)-derived PI increasing. We also found ~4000 significant Spearman correlations between lipids and multiple clinical markers of immune response with |R| ≥ 0.35 and FDR corrected Q < 0.05. Except for lysophosphatidic acid, lysophospholipids were positively associated with the CD4 fraction of T cells, and the cytokines IL-8 and IL-18. In contrast, sphingosine-1-phosphates were negatively correlated with innate immune markers such as CRP and IL-6. Further indications of metabolic changes in moderate COVID-19 disease were demonstrated in recovering ward patients compared to those at the start of hospitalization, where 99 lipid species were altered (6 increased by 30-62%; 93 decreased by 1.3-2.8-fold). Overall, these findings support and expand on early reports that dysregulated lipid metabolism is involved in COVID-19.

Functionalized graphene-oxide grids enable high-resolution cryo-EM structures of the SNF2h-nucleosome complex without crosslinking.

Single-particle cryo-EM is widely used to determine enzyme-nucleosome complex structures. However, cryo-EM sample preparation remains challenging and inconsistent due to complex denaturation at the air-water interface (AWI). Here, to address this issue, we develop graphene-oxide-coated EM grids functionalized with either single-stranded DNA (ssDNA) or thiol-poly(acrylic acid-co-styrene) (TAASTY) co-polymer. These grids protect complexes between the chromatin remodeler SNF2h and nucleosomes from the AWI and facilitate collection of high-quality micrographs of intact SNF2h-nucleosome complexes in the absence of crosslinking. The data yields maps ranging from 2.3 to 3 Å in resolution. 3D variability analysis reveals nucleotide-state linked conformational changes in SNF2h bound to a nucleosome. In addition, the analysis provides structural evidence for asymmetric coordination between two SNF2h protomers acting on the same nucleosome. We envision these grids will enable similar detailed structural analyses for other enzyme-nucleosome complexes and possibly other protein-nucleic acid complexes in general.