In-depth Characterization Research Articles

Arterial stiffness characterization of patients with different ACS-causing plaque morphologies quantified by optical coherence tomography

Abstract Background Optical coherence tomography (OCT) has refined acute coronary syndrome (ACS)-management by enabling in-depth characterization of culprit lesions. Differentiating between plaques with ruptured (RFC) and intact fibrous cap (IFC) has shaped clinical decision making. However, the systemic vascular changes associated with different plaque morphologies remain unexplored. Purpose To investigate arterial stiffness among different ACS-causing plaque morphologies (RFC vs. IFC) and its prognostic value post-ACS. Methods We conducted a secondary analysis of a prospective registry study, including patients who underwent OCT-characterization of the ACS-causing culprit lesion and received arterial stiffness assessment 90 days post-index event. The association between arterial stiffness parameters, such as pulse wave velocity (PWV), aortic pulse pressure (APP), heart rate-corrected augmentation index (AIx@75) and plaque morphologies was assessed using logistic regression, adjusted for age, sex, hypertension, presence of diabetes mellitus, smoking status, LDL-C and discharge medications (ACE-inhibitors/ARBs, beta blockers, calcium-channel blockers and diuretics). A multiparameter model additionally included intima-media-thickness and all arterial stiffness metrics. Cox regression, further adjusted for stroke history, prior percutaneous coronary intervention or stable coronary artery disease and Killip class, evaluated the link between arterial stiffness parameters and major adverse cardiovascular events plus (MACE+). Results In total, 110 patients with arterial stiffness and OCT data were included. Of these, 78 (70.9%) patients had RFC- and 32 (29.1%) IFC-ACS. The median age was 61.5 years and 80.0% of patients were male. Patients with RFC- had significantly higher PWV (8.35 vs. 7.50 m/s, p=0.015) compared to IFC-ACS. Both groups received similar regimens of antihypertensive, diuretic and lipid-lowering pharmacological therapy at discharge (p>0.1). After multivariable adjustment, increased PWV (4th Quartile [Q4] vs. 1st Quartile [Q1] Adjusted Hazard Ratio [aHR]: 1.38 [95% Confidence Interval (CI) 1.02-1.88], p=0.043) was associated with RFC- while high APP was significantly associated with IFC-ACS as the underlying plaque morphology (Q4 vs. Q1 aHR: 0.65 [95% CI 0.48-0.87], p=0.005) (Figure 1). Furthermore, per one-unit increment in APP we observed a 10% increase in risk for MACE+ in patients with RFC-ACS (aHR: 1.10 [95% CI 1.02-1.19], p=0.016) but not IFC-ACS (aHR: 0.95 [95% CI 0.82-1.11], p=0.54). No risk modification with increases in PWV and AIx@75 were observed, regardless of underlying plaque pathology (p>0.05). Conclusion There are distinct differences in arterial stiffness between patients with RFC- and IFC-ACS. These results underscore the value of a patient-specific approach that integrates invasive and non-invasive vascular characterization for identifying high-risk individuals and guiding therapy to enhance clinical outcomes.

Atrial and ventricular mitral regurgitation in the general population

Abstract Background Functional mitral valve regurgitation (FMR) is the result of two concurrent pathomechanisms: (1) the dilatation of mitral valve annulus (atrial) or (2) remodelling of the left ventricle (ventricular) in the absence of relevant leaflet degeneration¹. Even though FMR has been reported to be the most common cause of relevant MR², there is no general accepted definition of the two subtypes, nor are there population-based data regarding their prevalence, distribution and risk profiles¹. Purpose We aimed to evaluate the prevalence of FMR and to provide an in-depth characterisation of the subtypes aFMR and vFMR in the general population. Methods The study included the first 10,000 participants of the population-based Hamburg City Health Study enrolled between 2016 and 2019. Of these, 8.543 echocardiographic samples were available for analysis. Mitral valve was assessed by two independent investigators. Isolated degenerative MRs as determined by valve mobility (prolapse or restrictive) were excluded. FMR was classified as ventricular when fulfilling one of the following criteria: history of myocardial infarction or coronary artery disease, left ventricular ejection fraction (LVEF) ≤ 40%, restrictive leaflet, tenting area ≥ 150 mm² or coaptation depth ≥ 10 mm. All FMR with LVEF > 55% were classified as atrial. Results After excluding the samples with an insufficient image quality or missing data and re-assessment by the second investigator, 216 of 282 participants with a relevant MR (i.e. moderate or severe) remained (2,6% of the total cohort, see figure 1). In the next step, 153 participants were classified as pure FMR (68.9%), the remaining were mainly functional with minor degenerative features. A total of 31 (14.4%) MRs were classified as vFMR, the remaining 185 participants had an aFMR. Female gender was significantly more common in the aFMR cohort. The remaining demographic variables (age, body mass index) as well as established cardiovascular risk factors (i.e., diabetes, smoking, hypertension) were comparable between the vFMR and aFMR cohort. However, vFMR patients had significantly higher levels of NT-proBNP or NHYA state and presented more frequently with an atrial fibrillation (see figure 2). LVEF and LV stroke volume, TAPSE, left atrial ejection fraction and E/A ratio as a parameter of diastolic dysfunction were lower in the vFMR cohort whereas tenting area and left atrial endsystolic volume was significantly increased. Conclusion In our population-based study, aFMR was found to be the predominant subtype of FMR. The established cardiovascular risk factors were comparable in the vFMR and aFMR cohort. Echocardiographic variables differed significantly and indicate more advanced heart failure and LV remodelling in the vFMR cohort. Further categorization of FMR, in particular regarding the prognostic impact and long-term outcomes, is strongly warranted to allow a clinically relevant definition of aFMR and vFMR.Figure 1:Overview of sample sizeFigure 2:Baseline characteristics

Heralded Generation of Correlated Photon Pairs from CdS/CdSe/CdS Quantum Shells.

Quantum information processing demands efficient quantum light sources (QLS) capable of producing high-fidelity single photons or entangled photon pairs. Single epitaxial quantum dots (QDs) have long been proven to be efficient sources of deterministic single photons; however, their production via molecular-beam epitaxy presents scalability challenges. Conversely, colloidal semiconductor QDs offer scalable solution processing and tunable photoluminescence, but suffer from broader linewidths and unstable emissions. This leads to spectrally inseparable emission from exciton (X) and biexciton (XX) states, complicating the production of single photons and triggered photon pairs. Here, we demonstrate that colloidal semiconductor quantum shells (QSs) achieve significant spectral separation (∼75-80 meV) and long temporal stability of X and XX emissive states, enabling the observation of exciton-biexciton bunching in colloidal QDs. Our low-temperature single-particle measurements show cascaded XX-X emission of single photon pairs for over 200 s, with minimal overlap between X and XX features. The X-XX distinguishability allows for an in-depth theoretical characterization of cross-correlation strength, placing it in perspective with photon pairs of epitaxial counterparts. These findings highlight a strong potential of semiconductor quantum shells for applications in quantum information processing.

Online Comprehensive Two-Dimensional Liquid Chromatography/Quadrupole Time-of-Flight Mass Spectrometry-Based Metabolic Profiling and Comparison Enabling the Characterization of 1146 Ginsenosides and More Explicit Differentiation of Ginseng.

This work was designed for the in-depth characterization and holistic comparison of up to 12 ginseng varieties, which can benefit the development of functional foods and ensure their authenticity in the food industry. An online comprehensive two-dimensional liquid chromatography/quadrupole time-of-flight mass spectrometry (2D-LC/QTOF-MS) approach was established by configurating the XCharge C18 and HSS Cyano columns. Under the optimal conditions, we characterized a total of 1146 ginsenosides (including 876 potentially new compounds) from 12 ginseng varieties by reference to an in-house library of 573 known ginsenosides and 70 reference compounds. The online 2D-LC/QTOF-MS-based untargeted metabolomics workflows were developed, by which 126 potential ginsenoside markers were unveiled and utilized to establish the key identification points for each ginseng species. Compared with the conventional liquid chromatography/mass spectrometry metabolomics, our multidimensional chromatography approach performed better in discriminating multiple ginseng varieties. This work demonstrates a potent and practical methodology to identify easily confused functional plants.

Brivaracetam and rufinamide combination increased seizure threshold and improved neurobehavioral deficits in corneal kindling model of epilepsy.

Besides seizures, a myriad of overlapping neuropsychiatric and cognitive comorbidities occur in patients with epilepsy, which further debilitates their quality of life. This study provides an in-depth characterization of the impact of brivaracetam and rufinamide individually and in combination at 10 and 20 mg/kg doses, respectively, on corneal kindling-induced generalized seizures and behavioral alterations. Furthermore, observed convulsive frequency and behavioral changes were correlated to post-kindling-induced changes in the activity of markers of oxidative stress. Adult C57BL/6 mice were kindled via twice-daily transcorneal 50-Hz electrical stimulations (3 mA) for 3 s for 12 days until animals reached a fully kindled state. After the kindling procedure, animals were tested using a set of behavioral tests, and neurochemical alterations were assessed. Corneal-kindled animals exhibited intense generalized convulsions, altered behavioral phenotypes typified by positive symptoms (hyperlocomotion), negative symptoms (anxiety and anhedonia), and deficits in semantic and working memory. BRV 10 + RFM 20 dual regime increased convulsive threshold and propensity toward the start of stage 4-5 seizures and improved phenotypical deficits, that is, anxiety, depression, and memory impairments. Moreover, this combination therapy mitigated kindling-induced redox impairments as evidenced by reduced malondialdehyde and acetylcholinesterase levels and increased glutathione antioxidant activity in the brain of animals subjected to repetitive brain insult. Based on our outcomes, this dual therapy provides supporting evidence in alleviating epilepsy-induced neurobehavioral comorbidities and changes in redox homeostasis.

Characterization of the Flavin-Dependent Monooxygenase Involved in the Biosynthesis of the Nocardiosis-Associated Polyketide†.

Some species of the Nocardia genus harbor a highly conserved biosynthetic gene cluster designated as the NOCardiosis-Associated Polyketide (NOCAP) synthase that produces a unique glycolipid natural product. The NOCAP glycolipid is composed of a fully substituted benzaldehyde headgroup linked to a polyfunctional alkyl tail and an O-linked disaccharide composed of 3-α-epimycarose and 2-O-methyl-α-rhamnose. Incorporation of the disaccharide unit is preceded by a critical step involving hydroxylation by NocapM, a flavin monooxygenase. In this study, we employed biochemical, spectroscopic, and kinetic analyses to explore the substrate scope of NocapM. Our findings indicate that NocapM catalyzes hydroxylation of diverse aromatic substrates, although the observed coupling between NADPH oxidation and substrate hydroxylation varies widely from substrate to substrate. Our in-depth biochemical characterization of NocapM provides a solid foundation for future mechanistic studies of this enzyme as well as its utilization as a practical biocatalyst.

In-Depth Characterization of Natural Clays from Southeast Albania

Clays have been exploited in the manufacture of diverse products from ceramics to paints, pharmaceuticals, plastics, cosmetics, and more. Thus, they can be used in many industrial applications, showing good adsorbent ability thanks to their lamellar structure, high cation exchange capacity, pore size distribution, and large surface area. For this reason, considerable attention has been paid to their in-depth characterization, for further integration in sectors such as biomedicine, construction, remediation, aerospace, and nanotechnology. For this aim, two samples of natural clays, ALO1 and PRE4, from the southeast part of Albania, were subject to a multi-methodological characterization, with the aim of addressing the use of such geomaterials in possible sensing applications. X-ray fluorescence analysis, morphological characterization of the samples, and energy-dispersive system spectroscopy pointed to an extreme mineralogical variety, with kaolinite in AL01 and montmorillonite in PRE4 as the most abundant phases. This fact was further confirmed by powder X-ray diffraction, showing a quartz content of 20%, a kaolinite content of 64%, and a muscovite content of 16% for ALO1; meanwhile, for PRE4, we found a content of quartz of 45%, a content of montmorillonite of 34.9%, and a content of clinochlore of 20%. Infrared spectroscopy and thermal analyses confirmed the presence of hydroxyl groups in both samples, suggesting a higher content in ALO1. Measurement of N2 adsorption isotherms on the clay samples yields specific surface areas of 87 m2/g for PRE4 and 32 m2/g for ALO1, pore volumes of 0.721 cm3/g for PRE4 and 0.637 cm3/g for ALO1, and similar pore sizes in the range of 6–12 nm. Electrochemical analysis highlighted a good conductivity of ALO1 and PRE4 when used for the modification of commercial carbon-based screen-printed electrodes. In detail, higher currents were registered by differential pulse voltammetry for the electrodes modified with the clays with respect to bare electrodes, as well as good repeatability of the measurements. In addition, a comparative study with nanomaterials, known for their good conductivity, was achieved, using carbon black and gold nanoparticles as a reference, showing that the conductivity of the clays was lower than but not so different from those of the reference materials.

The clinical and genetic spectrum of paediatric speech and language disorders.

Speech and language disorders are known to have a substantial genetic contribution. Although frequently examined as components of other conditions, research on the genetic basis of linguistic differences as separate phenotypic subgroups has been limited so far. Here, we performed an in-depth characterization of speech and language disorders in 52 143 individuals, reconstructing clinical histories using a large-scale data-mining approach of the electronic medical records from an entire large paediatric healthcare network. The reported frequency of these disorders was the highest between 2 and 5 years old and spanned a spectrum of 26 broad speech and language diagnoses. We used natural language processing to assess the degree to which clinical diagnoses in full-text notes were reflected in ICD-10 diagnosis codes. We found that aphasia and speech apraxia could be retrieved easily through ICD-10 diagnosis codes, whereas stuttering as a speech phenotype was coded in only 12% of individuals through appropriate ICD-10 codes. We found significant comorbidity of speech and language disorders in neurodevelopmental conditions (30.31%) and, to a lesser degree, with epilepsies (6.07%) and movement disorders (2.05%). The most common genetic disorders retrievable in our analysis of electronic medical records were STXBP1 (n = 21), PTEN (n = 20) and CACNA1A (n = 18). When assessing associations of genetic diagnoses with specific linguistic phenotypes, we observed associations of STXBP1 and aphasia (P = 8.57 × 10-7, 95% confidence interval = 18.62-130.39) and MYO7A with speech and language development delay attributable to hearing loss (P = 1.24 × 10-5, 95% confidence interval = 17.46-infinity). Finally, in a sub-cohort of 726 individuals with whole-exome sequencing data, we identified an enrichment of rare variants in neuronal receptor pathways, in addition to associations of UQCRC1 and KIF17 with expressive aphasia, MROH8 and BCHE with poor speech, and USP37, SLC22A9 and UMODL1 with aphasia. In summary, our study outlines the landscape of paediatric speech and language disorders, confirming the phenotypic complexity of linguistic traits and novel genotype-phenotype associations. Subgroups of paediatric speech and language disorders differ significantly with respect to the composition of monogenic aetiologies.

Nucleo-SAFARI: Automated Identification of Fragment Ions in Top-Down MS/MS Spectra of Nucleic Acids.

Recent progress in top-down mass spectrometry analysis of progressively larger nucleic acids has enabled in-depth characterization of intact, modified RNA molecules. Development of methods for desalting and MS/MS fragmentation allows rapid acquisition of high-quality top-down MS/MS spectra of nucleic acids up to 100 nt, which has spurred the need for development of software approaches to identify and validate nucleic acid fragment ions. We have implemented an R-based approach to aid in analysis of MS/MS spectra of nucleic acids based on fragment ions observed directly in the m/z domain. This program, entitled Shiny Application for Fragment Assignment by Relative Isotopes (Nucleo-SAFARI), utilizes the Shiny HTML framework for deployment of a user-friendly application for automated annotation of top-down MS/MS spectra of nucleic acids recorded on Orbitrap mass spectrometer platforms. This approach proceeds through in silico generation of fragment ions and their isotopic distributions, followed by algorithmic assessment of the experimental isotopic distributions. Nucleo-SAFARI is available for download at https://github.com/mblanzillotti/Nucleo-SAFARI.

In-depth characterization of food and environmental microbiomes across different meat processing plants

BackgroundProcessing environments can be an important source of pathogenic and spoilage microorganisms that cross contaminate meat and meat products. The aim of this study was to characterize the microbiome of raw materials, processing environments and end products from 19 facilities producing different meat products.ResultsThe taxonomic profiles of the microbial communities evolved along processing, from raw materials to end products, suggesting that food contact (FC) surfaces play an important role in modulating the microbiome of final products. Some species persisted with the highest relative abundance in raw materials, food processing environments and/or in the final product, including species from the genera Pseudomonas, Staphylococcus, Brochothrix, Acinetobacter and Psychrobacter. Processing environments showed a very diverse core microbiota, partially shared with the products. Pseudomonas fragi and Pseudomonas sp. Lz4W (in all sample and facility types) and Brochothrix thermosphacta, Psychrobacter sp. and Psychrobacter sp. P11F6 (in raw materials, FC surfaces and end products) were prominent members of the core microbiota for all facilities, while Latilactobacillus sakei was found as a dominant species exclusively in end products from the facilities producing fermented sausages. Processing environments showed a higher amount of antimicrobial resistance genes and virulence factors than raw materials and end products. One thousand four hundred twenty-one medium/high-quality metagenome-assembled genomes (MAGs) were reconstructed. Of these, 274 high-quality MAGs (completeness > 90%) corresponded to 210 putative new species, mostly found in processing environments. For two relevant taxa in meat curing and fermentation processes (S. equorum and L. sakei, respectively), phylogenetic variation was observed associated with the specific processing facility under study, which suggests that specific strains of these taxa may be selected in different meat processing plants, likely contributing to the peculiar sensorial traits of the end products produced in them.ConclusionsOverall, our findings provide the most detailed metagenomics-based perspective up to now of the microbes that thrive in meat, meat products and associated environments and open avenues for future research activities to better understand the microbiome functionality and potential contribution to meat quality and safety.BW5-yJYgBWXLb4-yN7W47nVideo

Quantum bit with telecom wave-length emission from a simple defect in Si

Defect-related spin-to-photon interfaces in silicon promise the realization of quantum repeaters by combining advanced semiconductor and photonics technologies. Recently, controlled creation/erasure of simple carbon interstitial defects have been successfully realised in silicon. This defect has a stable structure near room temperature and coherently emits in the wave-length where the signal loss is minimal in optical fibres used in communication technologies. Our in-depth theoretical characterization confirms the assignment of the observed emission to the neutral charge state of this defect, as arising due to the recombination of a bound exciton. We also identified a metastable triplet state that could be applied as a quantum memory. Based on the analysis of the electronic structure of the defect and its similarities to a known optically detected magnetic resonance centre in silicon, we propose that a carbon interstitial can act as a quantum bit and may realize a spin-to-photon interface in complementary metal-oxide semiconductor-compatible platforms.

In-Depth Characterization of the Volatile Aroma Profile and Other Characteristics of White Wine Produced by Sequential Inoculation with a Lachancea thermotolerans Starter Yeast Strain

In-Depth Characterization of the Volatile Aroma Profile and Other Characteristics of White Wine Produced by Sequential Inoculation with a Lachancea thermotolerans Starter Yeast Strain

In-Situ Anchoring of Co Single-Atom Synergistically with Cd Vacancy of Cadmium Sulfide for Boosting Asymmetric Charge Distribution and Photocatalytic Hydrogen Evolution.

In the context of reshaping the energy pattern, designing and synthesizing high-performance noble metal-free photocatalysts with ultra-high atomic utilization for hydrogen evolution reaction (HER) still remains achallenge. In a streamlined synthesis process, in-situ single atom anchoring is performed in parallel with HER by irradiating a precursory defect-state CdS/Co suspension (Co-DCdS-Ss) system under simulated sunlight and the in-situ synthesizing single-atom Co photocatalyst (Co5:DCdS) exhibits further improved catalytic performance (60.10 mmolg-1h-1) compared with Co-DCdS-Ss (18.09 mmolg-1h-1), reaching an apparent quantum yield of 57.6% at 500nm and a solar-chemical energy conversion efficiency (SCC) of 6.26% at AM 1.5G. In-depth characterization tests and density functional theory (DFT) calculations prove that the anchoring of Co single atom deepens the asymmetric charge distribution of the two-coordination S atom adjacent to the cadmium vacancy (VCd). The synergy between electron delocalization VCd and Co single atom on the catalyst surface is constructed, which bifunctional sites responsible for boosting water adsorption-dissociation and hydrogen evolution. This study advances the understanding of the underlying mechanisms of synergy between surface defects and metal single atoms and opens a new horizon for the development of advanced materials in the field of photocatalysis.

Multi-omics profiling of DNA methylation and gene expression alterations in human cocaine use disorder

Structural and functional changes of the brain are assumed to contribute to excessive cocaine intake, craving, and relapse in cocaine use disorder (CUD). Epigenetic and transcriptional changes were hypothesized as a molecular basis for CUD-associated brain alterations. Here we performed a multi-omics study of CUD by integrating epigenome-wide methylomic (N = 42) and transcriptomic (N = 25) data from the same individuals using postmortem brain tissue of Brodmann Area 9 (BA9). Of the N = 1 057 differentially expressed genes (p < 0.05), one gene, ZFAND2A, was significantly upregulated in CUD at transcriptome-wide significance (q < 0.05). Differential alternative splicing (AS) analysis revealed N = 98 alternatively spliced transcripts enriched in axon and dendrite extension pathways. Strong convergent overlap in CUD-associated expression deregulation was found between our BA9 cohort and independent replication datasets. Epigenomic, transcriptomic, and AS changes in BA9 converged at two genes, ZBTB4 and INPP5E. In pathway analyses, synaptic signaling, neuron morphogenesis, and fatty acid metabolism emerged as the most prominently deregulated biological processes. Drug repositioning analysis revealed glucocorticoid receptor targeting drugs as most potent in reversing the CUD expression profile. Our study highlights the value of multi-omics approaches for an in-depth molecular characterization and provides insights into the relationship between CUD-associated epigenomic and transcriptomic signatures in the human prefrontal cortex.

Investigating Exposure and Hazards of Micro- and Nanoplastics During Pregnancy and Early Life (AURORA Project): Protocol for an Interdisciplinary Study.

Micro- and nanoplastics (MNPs) are emerging pollutants of concern with ubiquitous presence in global ecosystems. MNPs pose potential implications for human health; however, the health impacts of MNP exposures are not yet understood. Recent evidence suggests that MNPs can cross the placental barrier, underlying the urgent need to understand their impact on reproductive health and development. The Actionable eUropean ROadmap for early-life health Risk Assessment of micro- and nanoplastics (AURORA) project will investigate MNP exposures and their biological and health effects during pregnancy and early life, which are critical periods due to heightened vulnerability to environmental stressors. The AURORA project will enhance exposure assessment capabilities for measuring MNPs, MNP-associated chemicals, and plastic additives in human tissues, including placenta and blood. In this interdisciplinary project, we will advance methods for in-depth characterization and scalable chemical analytical strategies, enabling high-resolution and large-scale toxicological, exposure assessment, and epidemiological studies. The AURORA project performs observational studies to investigate determinants and health impacts of MNPs by including 800 mother-child pairs from 2 existing birth cohorts and 110 women of reproductive age from a newly established cohort. This will be complemented by toxicological studies using a tiered-testing approach and epidemiological investigations to evaluate associations between maternal and prenatal MNP exposures and health perturbations, such as placental function, immune-inflammatory responses, oxidative stress, accelerated aging, endocrine disruption, and child growth and development. The ultimate goal of the AURORA project is to create an MNP risk assessment framework and identify the remaining knowledge gaps and priorities needed to comprehensively assess the impact of MNPs on early-life health. In the first 3 years of this 5-year project (2021-2026), progress was made toward all objectives. This includes completion of recruitment and data collection for new and existing cohorts, development of analytical methodological protocols, and initiation of the toxicological tiered assessments. As of September 2024, data analysis is ongoing and results are expected to be published starting in 2025. As plastic pollution increases globally, it is imperative to understand the impact of MNPs on human health, particularly during vulnerable developmental stages such as early life. The contributions of the AURORA project will inform future risk assessment. DERR1-10.2196/63176.

In-depth genome-wide characterization of MaNAC25 and MaNAC28 cold-responsive transcription factor binding sites in banana via DAP-Seq

Mapping transcription factor proteins' binding sites across the entire genome in banana is crucial for unveiling their transcriptional regulatory mechanisms and enhancing our understanding of their regulatory networks. Our study showed that DAP-Seq experiments identified MaNAC25 and MaNAC28 numerous binding peaks, mainly in the promoter regions, with strong signals near the transcription start site (TSS). Significantly, the discovery of new binding motifs for MaNAC28 excluding NAC core binding element CGTA/G indicates their potential as novel DNA binding motifs for NAC transcription factors in cold stress response. Moreover, MaNAC25 was found to chiefly influence biological processes and molecular functions, whereas MaNAC28 was more focused on molecular functions. Both MaNAC25 and MaNAC28 extended their regulatory networks by interacting with other transcription factors during cold stress. Therefore, DAP-Seq technology furnishes essential insights and a robust foundation for researching transcriptional regulatory mechanisms among diverse transcription factors and broadening their regulatory networks.

Determination of double bond positions in unsaturated fatty acids by pre-column derivatization with dimethyl and dipyridyl disulfide followed by LC-SWATH-MS analysis.

Comprehensive in-depth structural characterization of free mono-unsaturated and polyunsaturated fatty acids often requires the determination of carbon-carbondouble bond positions due to their impact on physiological properties and relevance in biological samples or during impurity profiling of pharmaceuticals. In this research, we report on the evaluation of disulfides as suitable derivatization reagents for the determination of carbon-carbondouble bond positions of unsaturated free fatty acids by UHPLC-ESI-QTOF-MS/MS analysis and SWATH (sequential windowed acquisition of all theoretical mass spectra) acquisition. Iodine-catalyzed derivatization of C = C double bonds with dimethyl disulfide (DMDS) enabled detection of characteristic carboxy-terminal MS2 fragments for various fatty acids in ESI negative mode. The determination of double bond positions of fatty acids with up to three double bonds, the transfer of the method to plasma samples, and its limitations have been shown. To achieve charge-switching for positive ion mode MS-detection, derivatization with 2,2'-dipyridyldisulfide (DPDS) was investigated. It enabled detection of both corresponding characteristic omega-end- and carboxy-end-fragments for fatty acids with up to two double bonds in positive ion mode. It provides a straightforward strategy for designing MRM transitions for targeted LC-MS/MS assays. Both derivatization techniques represent a simple and inexpensive way for the determination of double bond positions in fatty acids with low number of double bonds. No adaptation of MS hardware is required and the specific isotopic pattern of resulting sulfur-containing products provides additional structural confirmation. This reaction scheme opens up the avenue of structural tuning of disulfide reagents beyond DMDS and DPDS using reagents like cystine and analogs to achieve enhanced performance and sensitivity.

Characterizing smartphone capabilities for seismic and structural monitoring

As seismic events continue to pose significant threats to urban infrastructure, leveraging smartphones equipped with accelerometers for real-time monitoring has gained prominence. To ascertain the reliability and sensitivity of smartphone-based measurements, an in-depth characterization of their response is essential. This article presents a thorough characterization of the performance of typical accelerometers installed on three distinct smartphone models. For this, a novel experimental apparatus has been developed to conduct a comparative study involving three different smartphones against a reference accelerometer. We determine each accelerometer’s transfer functions for Fourier frequencies 0.1–40 Hz, evidencing main differences and demonstrating a higher sensitivity than expected. Possible implementation in future distributed networks of heterogeneous and synchronized sensors, capable of independently generating and validating timely alerts in particular seismic events, are also discussed.

Mechanism-Based Regiocontrol in SNAr: A Case Study of Ortho-Selective Etherification with Chloromagnesium Alkoxides.

Although nucleophilic aromatic substitution (SNAr) is routinely employed as a practical alternative to transition-metal-catalyzed cross-coupling, the mechanistic basis for reactivity and regioselectivity remains underexplored and is an active area of research. This article reports a SNAr-based etherification of 2,4-difluoroarylcarboxamides as a model system and shows that the ortho/para regioselectivity spans >500:1 to 1:∼20 simply by varying the reaction conditions via high-throughput experimentation (HTE). An in-depth characterization of the ortho-selective lead conditions is presented, and these insights are used to build a reactivity model that self-consistently accounts for the regioselectivity and reaction scope. This article discusses synthetic implications of condition-dependent magnesium coordination and Schlenk equilibria and demonstrates that consideration of molecular-level stoichiometry and isomerism is an essential prerequisite for rationalizing reactivity and regioselectivity in SNAr.

297P In-depth behavioral characterization of Duchenne muscular dystrophy mouse models lacking one, multiple or all dystrophin isoforms in the brain

297P In-depth behavioral characterization of Duchenne muscular dystrophy mouse models lacking one, multiple or all dystrophin isoforms in the brain