Difluorenoheteroles: topological control of π conjugation in diradicaloids and mixed-valence radical ions.

Two families of difluorenoheterole diradicaloids were synthesized, featuring isomeric ring systems with distinct conjugation topologies. The two types of difluorenoheteroles contain, respectively, a Chichibabin-like motif (CH) and a newly introduced heteroatom-linked triphenylmethyl dyad (TD-X). Combined experimental and theoretical investigations show that the TD-X systems have reduced quinoidal character but the interaction between formal spin centers is sufficiently strong to ensure a singlet ground state. The singlet-triplet energy gaps in the TD-X difluorenoheteroles are strongly affected by the heterocyclic ring, with values of -4.3 and -0.7 kcal mol-1 determined for the pyrrole- and thiophene-containing analogues, respectively. In cyclic voltammetry experiments, the TD-X systems show diminished energy gaps and superior reversibility in comparison with their CH counterparts. The radical anions and cations obtained from these diradicaloids show extremely red-shifted bands, occasionally with λ max > 3500 nm. Computational studies show that some of these ions adopt distonic structures and may be characterized as class-II mixed-valence species.

A Metastable Semiquinone Molecular Switch Modulated by Ascorbate/O2: a Study from a System Far-From-Equilibrium to Biological Assays in Mitochondria.

A molecular switch based on the metastable radical anion derived from a substituted heteroaryl quinone is described. Pyrrolil quinone thiocyanate (PQ 5) showed an interaction with the fluoride anion that was visible to the naked eye and quantified by UV/vis and 1H and 13C NMR. The metastable quinoid species formed by the interaction with F- ("ON" state) showed a molecular switching effect autocontrolled by the presence of ascorbate ("OFF" state) and back to the "ON" state by an autooxidation process, measured by visible and UV/vis spectroscopy. Due to its out-of-equilibrium properties and the exchange of matter and energy, a dissipative structural behaviour is proposed. Considering its similarity to the mechanism of coenzyme Q in oxidative phosphophorylation, PQ 5 was evaluated on Saccharomyces cerevisiae mitochondrial function for inhibition of complexes II, III and IV, reactive oxygen species (ROS) production, catalase activity and lipid peroxidation. The results showed that PQ 5 inhibited complex III activity as well as the activity of all electron transport chain (ETC) complexes. In addition, PQ 5 reduced ROS production and catalase activity in yeast. The results suggest that PQ 5 may have potential applications as a new microbicidal compound by inducing ETC dysfunction.

Ultradense Array of On-Chip Sensors for High-Throughput Electrochemical Analyses.

High-throughput sensors are valuable tools for enabling massive, fast, and accurate diagnostics. To yield this type of electrochemical device in a simple and low-cost way, high-density arrays of vertical gold thin-film microelectrode-based sensors are demonstrated, leading to the rapid and serial interrogation of dozens of samples (10 µL droplets). Based on 16 working ultramicroelectrodes (UMEs) and 3 quasi-reference electrodes (QREs), a total of 48 sensors were engineered in a 3D crossbar arrangement that devised a low number of conductive lines. By exploiting this design, a compact chip (75 × 35 mm) can enable performing 16 sequential analyses without intersensor interferences by dropping one sample per UME finger. In practice, the electrical connection to the sensors was achieved by simply switching the contact among WE adjacent fingers. Importantly, a short analysis time was ensured by interrogating the UMEs with chronoamperometry or square wave voltammetry using a low-cost and hand-held one-channel potentiostat. As a proof of concept, the detection of Staphylococcus aureus in 15 samples was performed within 14 min (20 min incubation and 225 s reading). Additionally, the implementation of peptide-tethered immunosensors in these chips allowed the screening of COVID-19 from patient serum samples with 100% accuracy. Our experiments also revealed that dispensing additional droplets on the array (in certain patterns) results in the overestimation of the faradaic current signals, a phenomenon referred to as crosstalk. To address this interference, a set of analyses was conducted to design a corrective strategy that boosted the testing capacity by allowing using all on-chip sensors to address subsequent analyses (i.e., 48 samples simultaneously dispensed on the chip). This strategy only required grounding the unused rows of QRE and can be broadly adopted to develop high-throughput UME-based sensors. In practice, we could analyze 48 droplets (with [Fe(CN)6]4-) within ∼8 min using amperometry.

Healthcare Communication Experiences of Hispanic Caregivers of Childhood Cancer Survivors.

BACKGROUND: Interpersonal communication is a crucial component of the cancer experience that can contribute to managing cancer care and improving cancer survivors' and caregivers' quality of life. Cultural and contextual factors may impact Hispanic childhood cancer survivor (CCS) and parent caregiver relationships and communication. This study sought to describe the healthcare communication experiences of Hispanic parents with CCS, families, and medical providers. METHODS: We conducted 15 semi-structured interviews with Hispanic caregivers from a safety-net hospital in Los Angeles County. Interviews were conducted in English and Spanish, audio-recorded and professionally transcribed, and analyzed using a thematic approach. RESULTS: Caregivers shared the importance and impact of medical communication when exploring the "first big talk" of the diagnosis, uncertainty about treatment, navigating multiple providers, therapeutic communication (i.e., providing emotional reassurance), and current and lingering effects of cancer. All caregivers shared "good communication" experiences, while others shared various barriers to communication, including a lack of understanding of the cancer diagnosis and caregiver experience, psychological challenges impacting communication, cultural and language differences, physical factors that limit communication, and young age of child impacting communication with caregivers. CONCLUSIONS: Our findings suggest that a strong interpersonal communication skill set for clinicians can contribute to managing cancer care and improving caregivers' psychological adjustment.

Health Claims for Sports Drinks-Analytical Assessmentaccording to European Food Safety Authority's Scientific Opinion.

In Europe, sports food supplements (SSFs) are subject to specific laws and regulations. Up to 70% of athletes are highly influenced by the information on the label or the advertisement of the SSF, which often does not correspond to the scientific evidence, such as health claims. The aim is to analyze such claims relating to sports drinks (SDs) in commercial messages. To this end, an observational and cross-sectional study was conducted based on the analysis of the content and degree of adequacy of the health claims indicated on the labelling or technical data sheet of the SDs with those established by the European legislation in force according to the European Food Safety Authority (EFSA). The SSFs were searched for via Amazon and Google Shopping. A total of 114 health claims were evaluated. No claim fully conformed with the recommendations. A total of 14 claims (n = 13 products) almost conformed to the recommendations; they were "Maintain endurance level in exercises requiring prolonged endurance", "Improve water absorption during physical exercise", and "Improved physical performance during high intensity, high duration physical exercise in trained adults", representing 12.3% of the total (n = 114). The vast majority of the claims identified indicated an unproven cause-effect and should be modified or eliminated, which amounts to food fraud towards the consumer.

Concurrent response and action effect representations across the somatomotor cortices during novel task preparation.

Instructions allow us to fulfill novel and complex tasks on the first try. This skill has been linked to preparatory brain signals that encode upcoming demands in advance, facilitating novel performance. To deepen insight into these processes, we explored whether instructions pre-activated task-relevant motoric and perceptual neural states. Critically, we addressed whether these representations anticipated activity patterns guiding overt sensorimotor processing, which could reflect that internally simulating novel tasks facilitates the preparation. To do so, we collected functional magnetic resonance imaging data while female and male participants encoded and implemented novel stimulus-response associations. Participants also completed localizer tasks designed to isolate the neural representations of the mappings-relevant motor responses, perceptual consequences, and stimulus categories. Using canonical template tracking, we identified whether and where these sensorimotor representations were pre-activated. We found that response-related templates were encoded in advance in regions linked with action control, entailing not only the instructed responses but also their somatosensory consequences. This result was particularly robust in primary motor and somatosensory cortices. While, following our predictions, we found a systematic decrease in the irrelevant stimulus templates' representational strength compared to the relevant ones, this difference was due to below-zero estimates linked to the irrelevant category activity patterns. Overall, our findings reflect that instruction processing relies on the sensorimotor cortices to anticipate motoric and kinesthetic representations of prospective action plans, suggesting the engagement of motor imagery during novel task preparation. More generally, they stress that the somatomotor system could participate with higher-level frontoparietal regions during anticipatory task control.

Analysis of Concentric and Eccentric Power in Flywheel Exercises Depending on the Subjects' Strength Level and Body Mass.

ABSTRACT: Asencio, P, García-Valverde, A, Albaladejo-García, C, Beato, M, Moreno-Hernández, FJ, and Sabido, R. Analysis of concentric and eccentric power in flywheel exercises depending on the subjects' strength level and body mass. J Strength Cond Res XX(X): 000-000, 2024-The objective of this study is to describe how flywheel exercise mechanical outputs are affected by the athletes' body mass (BM) and strength level and by the exercise type. Forty-six recreational athletes came to a laboratory 3 times. On the first day, descriptive data, squat (1 repetition maximum: 1RM) and flywheel familiarization were performed. After a second day of familiarization, subjects performed a randomized flywheel exercise-testing protocol of squat and split squat exercises. The variables used for data analysis were peak concentric power and peak eccentric power, eccentric/concentric ratio, and their relationship with 1RM/BM. Subjects were assigned to a stronger or weaker group according to their 1RM/BM ratio. Group differences were found in absolute values of eccentric overload (EOL) (p < 0.01; effect size [ES] = 0.51) and EOL/BM (p < 0.01; ES = 0.46) only in the split squat. Absolute power values in the concentric phase showed differences between inertial load (p < 0.01; ES = 0.41). The stronger group did not present significant differences between inertial loads during squat (p < 0.01; ES = 0.46), but they showed different ratios with light inertias in comparison with the weaker group (p < 0.01; ES = 0.46). There were significant differences between groups with light inertias in split squat (nondominant) and squat exercises (p < 0.05; ES = 0.29) in the eccentric and concentric phases (p < 0.116; ES = 0.20). Squat and split squat exercises present different profiles depending on the training level. In conclusion, it is recommended that practitioners perform a test to understand the inertial load-power profile (concentric, eccentric, and their ratio) for each exercise and also consider the user's strength level for selection of the inertial load and for the exercise to use in training.

Unraveling the Impact of Six Pentacyclic Triterpenes Regulating Metabolic Pathways on Lung Carcinoma Cells.

Recently, there has been great interest in plant-derived compounds known as phytochemicals. The pentacyclic oleanane-, ursane-, and lupane-type triterpenes are phytochemicals that exert significant activity against diseases like cancer. Lung cancer is the leading cause of cancer-related death worldwide. Although chemotherapy is the treatment of choice for lung cancer, its effectiveness is hampered by the dose-limiting toxic effects and chemoresistance. Herein, we investigated six pentacyclic triterpenes, oleanolic acid, ursolic acid, asiatic acid, betulinic acid, betulin, and lupeol, on NSCLC A549 cells. These triterpenes have several structural variations that can influence the activation/inactivation of key cellular pathways. From our results, we determined that most of these triterpenes induced apoptosis, S-phase and G2/M-phase cycle arrest, the downregulation of ribonucleotide reductase (RR), reactive oxygen species, and caspase 3 activation. For chemoresistance markers, we found that most triterpenes downregulated the expression of MAPK/PI3K, STAT3, and PDL1. In contrast, UrA and AsA also induced DNA damage and autophagy. Then, we theoretically determined other possible molecular targets of these triterpenes using the online database ChEMBL. The results showed that even slight structural changes in these triterpenes can influence the cellular response. This study opens up promising perspectives for further research on the pharmaceutical role of phytochemical triterpenoids.

Atomic-Scale Description of the Magnetic TiN|FeCo Multilayers.

Motivated by the experimental findings of Wolff et al., we investigated the TiN|FeCo multilayers at the atomic scale. Four different models were employed to investigate the interface, considering both Fe and Co surface terminations of the FeCo compounds. The interface formation energy formalism was employed to study the thermodynamic stability of these models. The results show that an interface mediated by Co atoms is most likely to appear in the experiment. Also, the Fe surface termination is more viable than a Co surface termination. The magnetic moments of Co at the interface are 1.48 µB/atom, which denotes a decay compared to bulk (1.76 µB/atom). Besides, Ti acquires a very small induced magnetization of -0.05 µB/atom. Our proposed atomistic model of the TiN|FeCo multilayer system fits perfectly with the structure obtained in experiments, and it is a step forward in the theoretical-experimental design of wear-resistant coatings with outstanding magnetic and mechanical properties.

Triindenotriphenylenes: Spin-Frustrated Triskelion Triradicals with Excellent Ambient Stability.

A triskelion-shaped triradical triindeno[1,2-a:1',2'-g:1'',2''-m]triphenylen-7-yl (1) and its internally fused derivative obtained by oxidative cyclization (2) were prepared in a straightforward synthetic sequence. Both compounds were confirmed to be triradicals and to possess intramolecular antiferromagnetic exchange interactions between spins, displaying a spin-frustrated doublet ground state with doublet-quartet energy gaps of -0.14 kcal/mol for 1 and -0.06 kcal/mol for 2. Despite their open-shell character, they were sufficiently stable to be handled under ambient conditions on a timescale of days. Both compounds could be reversibly reduced to mono-, di-, and trianions and oxidized to 1+ and 22+, with strong NIR absorptions (1800 to over 3200 nm) observed for all open-shell ions.

A primal-dual data-driven method for computational optical imaging with a photonic lantern.

Optical fibers aim to image in vivo biological processes. In this context, high spatial resolution and stability to fiber movements are key to enable decision-making processes (e.g. for microendoscopy). Recently, a single-pixel imaging technique based on a multicore fiber photonic lantern has been designed, named computational optical imaging using a lantern (COIL). A proximal algorithm based on a sparsity prior, dubbed SARA-COIL, has been further proposed to solve the associated inverse problem, to enable image reconstructions for high resolution COIL microendoscopy. In this work, we develop a data-driven approach for COIL. We replace the sparsity prior in the proximal algorithm by a learned denoiser, leading to a plug-and-play (PnP) algorithm. The resulting PnP method, based on a proximal primal-dual algorithm, enables to solve the Morozov formulation of the inverse problem. We use recent results in learning theory to train a network with desirable Lipschitz properties, and we show that the resulting primal-dual PnP algorithm converges to a solution to a monotone inclusion problem. Our simulations highlight that the proposed data-driven approach improves the reconstruction quality over variational SARA-COIL method on both simulated and real data.

Intracranial thrombus composition is associated with occlusion location and endovascular treatment outcomes: results from ITACAT multicenter study.

BACKGROUND: The impact of thrombolytics directed towards different thrombus components regarding site of occlusion in combination with mechanical thrombectomy (MT) to achieve endovascular complete recanalization is unclear. METHODS: Retrospective analysis of a prospective database in two stroke centers. Intracranial thrombi retrieved by MT were analyzed using hematoxylin-eosin staining for fibrin and red blood cell proportions, and CD61 immunostaining for platelets proportion in thrombus (PLTPT) assessment. Thrombi composition, baseline variables, etiology, treatment features and occlusion location were analyzed. RESULTS: Overall, 221 patients completed the per protocol analysis and 110 cases achieved a final expanded Thrombolysis in Cerebral Infarction (eTICI) 3 (49%) of which 70 were MT (32%) by first pass effect (FPE). Thrombi from medium distal vessel occlusions had higher PLTPT compared with thrombi from proximal large vessel occlusions (68% vs 61%, P=0.026). In particular, middle cerebral artery M2-M3 segment thrombi had the highest PLTPT (70%), and basilar artery thrombi the lowest PLTPT (41%). After logistic regression analysis adjusted for occlusion location and intravenous fibrinolysis, lower baseline National Institutes of Health Stroke Scale score (adjusted OR (aOR) 0.95, 95% CI 0.913 to 0.998) and PLTPT (aOR 0.97, 95% CI 0.963 to 0.993) were independently associated with FPE. Fewer MT passes (aOR 0.67, 95% CI 0.538 to 0.842) and platelet poor thrombus (<62% PLTPT; aOR 2.39, 95% CI 1.288 to 4.440) were independently associated with final eTICI 3. CONCLUSIONS: Occlusion location might be a surrogate parameter for thrombus composition. Platelet poor clots and fewer MT passes were independently associated with complete endovascular recanalization. Clinical trials testing the benefits of combining selective intra-arterial platelet antagonists with MT to improve endovascular outcomes are warranted.

Robust Isolated Attosecond Pulse Generation with Self-Compressed Subcycle Drivers from Hollow Capillary Fibers.

High-order harmonic generation (HHG) arising from the nonperturbative interaction of intense light fields with matter constitutes a well-established tabletop source of coherent extreme-ultraviolet and soft X-ray radiation, which is typically emitted as attosecond pulse trains. However, ultrafast applications increasingly demand isolated attosecond pulses (IAPs), which offer great promise for advancing precision control of electron dynamics. Yet, the direct generation of IAPs typically requires the synthesis of near-single-cycle intense driving fields, which is technologically challenging. In this work, we theoretically demonstrate a novel scheme for the straightforward and compact generation of IAPs from multicycle infrared drivers using hollow capillary fibers (HCFs). Starting from a standard, intense multicycle infrared pulse, a light transient is generated by extreme soliton self-compression in a HCF with decreasing pressure and is subsequently used to drive HHG in a gas target. Owing to the subcycle confinement of the HHG process, high-contrast IAPs are continuously emitted almost independently of the carrier-envelope phase (CEP) of the optimally self-compressed drivers. This results in a CEP-robust scheme which is also stable under macroscopic propagation of the high harmonics in a gas target. Our results open the way to a new generation of integrated all-fiber IAP sources, overcoming the efficiency limitations of usual gating techniques for multicycle drivers.

Metamagnetism and canted antiferromagnetic ordering in two monomeric CoII complexes with 1-(2-pyrimidyl)piperazine. Hirshfeld surface analysis and theoretical studies.

Here we present the magnetic properties of two cobalt complexes formulated as: [Co(SCN)2(L)2] (1) and (H2L)2[Co(SCN)4]·H2O (2) (L = 1-(2-pyrimidyl)piperazine). The two compounds contain isolated tetrahedral CoII complexes with important intermolecular interactions that lead to the presence of a canted antiferromagnetic order below 11.5 and 10.0 K, with coercive fields at 2 K of 38 and 68 mT, respectively. Theoretical calculations have been used to explain this behaviour. Hirshfeld surface analysis shows the presence of strong intermolecular interactions in both compounds. The crystal geometries were used for geometry optimization using the DFT method. From the topological properties, electrostatic potential maps and molecular orbital analysis, information about the noncovalent interaction and chemical reactivity was obtained.

Meta-Analysis in Transgenic Alzheimer's Disease Mouse Models Reveals Opposite Brain Network Effects of Amyloid-ß and Phosphorylated Tau Proteins.

Background: Cognitive deficits observed in Alzheimer's disease (AD) patients have been correlated with altered hippocampal activity. Although the mechanism remains under extensive study, neurofibrillary tangles and amyloid plaques have been proposed as responsible for brain activity alterations. Aiming to unveil the mechanism, researchers have developed several transgenic models of AD. Nevertheless, the variability in hippocampal oscillatory alterations found in different genetic backgrounds and ages remains unclear. Objective: To assess the oscillatory alterations in relation to animal developmental age and protein inclusion, amyloid-ß (Aß) load, and abnormally phosphorylated tau (pTau), we reviewed and analyzed the published data on peak power, frequency, and quantification of theta-gamma cross-frequency coupling (modulation index values). Methods: To ensure that the search was as current as possible, a systematic review was conducted to locate and abstract all studies published from January 2000 to February 2023 that involved in vivo hippocampal local field potential recording in transgenic mouse models of AD. Results: The presence of Aß was associated with electrophysiological alterations that are mainly reflected in power increases, frequency decreases, and lower modulation index values. Concomitantly, pTau accumulation was associated with electrophysiological alterations that are mainly reflected in power decreases, frequency decreases, and no significant alterations in modulation index values. Conclusions: In this study, we showed that electrophysiological parameters are altered from prodromal stages to the late stages of pathology. Thus, we found that Aß deposition is associated with brain network hyperexcitability, whereas pTau deposition mainly leads to brain network hypoexcitability in transgenic models.

Simultaneous quantitative respirometry and fluorometric assays in dissected hippocampal tissue from mice.

Respirometry is a technique for studying mitochondrial function that has proven compatibility with ≥0.5 mg of brain tissue. Here, we present a protocol for assessing oxygen consumption and H2O2 production rates in hippocampal tissue using the Oroboros O2k system. We describe steps for brain harvesting, tissue preparation, hippocampal microdissection, and respirometry assays. This approach has been valuable to study the metabolism of dentate granule cells of the hippocampus and could be applicable to other brain subregions. For complete details on the use and execution of this protocol, please refer to Rose et al.1.

A Rare Case of Persistent Multifocal Cribriform-Morular Thyroid Carcinoma.

Background/Objective: Cribriform-morular thyroid carcinoma (CMTC) was considered a variant of papillary thyroid carcinoma (PTC) but is a separate entity in the 2022 World Health Organization classification. CMTC has an association with familial adenomatous polyposis (FAP). Our objective is to report a case of CMTC who was subsequently diagnosed with FAP, to highlight these associated entities and implications for management. Case Report: A 15-year-old female with a history of iron-deficiency anemia and alpha-gal syndrome presented with several years of goiter and dysphagia. She also noted unintentional weight loss, abdominal pain, melena and hematochezia, and symptomatic anemia. Physical examination was significant for multiple thyroid nodules. Laboratory results revealed normal thyroid function and iron deficiency. Multiple nodules were visualized on thyroid ultrasound, and fine needle aspiration biopsy was consistent with PTC. Total thyroidectomy was performed with a revised diagnosis of multifocal CMTC, with administration of adjuvant radioactive iodine due to persistent disease. Genetic testing confirmed FAP and she was referred for upper endoscopy, colonoscopy, and an evaluation for colectomy. Discussion: There are no best practice guidelines for management of CMTC. Management of CMTC is guided by FAP status; sporadic cases can be managed with hemithyroidectomy, while FAP-associated cases are better managed with total thyroidectomy. Recurrence is usually managed with surgical resection. The decision to treat with adjuvant radioactive iodine is often extrapolated from management of classic PTC. Conclusion: Thyroid carcinoma in the setting of extensive family history of colorectal carcinoma should arouse suspicion for CMTC. Patients with CMTC should receive a referral for colonoscopy and genetic testing for FAP.

Ultradense Electrochemical Chips with Arrays of Nanostructured Microelectrodes to Enable Sensitive Diffusion-Limited Bioassays.

Nanostructured microelectrodes (NMEs) are an attractive alternative to yield sensitive bioassays in unprocessed samples. However, although valuable for different applications, nanoporous NMEs usually cannot boost the sensitivity of diffusion-limited analyses because of the enlarged Debye length within the nanopores, which reduces their accessibility. To circumvent this limitation, nanopore-free gold NMEs were electrodeposited from 45 µm SU-8 apertures, featuring nanoridged microspikes on a recessed surface of gold thin film while carrying interconnected crown-like and spiky structures along the edge of a SU-8 passivation layer. These structures were grown onto ultradense, vertical array chips that offer a promising strategy for translating reproducible, high-resolution, and cost-effective sensors into real-world applications. The NMEs yielded reproducible analyses, while machine learning allowed us to predict the analytical responses from NME electrodeposition data. By taking advantage of the high surface area and accessible structure of the NMEs, these structures provided a sensitivity for [Fe(CN)6]3-/4- that was 5.5× higher than that of bare WEs while also delivering a moderate antibiofouling property in undiluted human plasma. As a proof of concept, these electrodes were applied toward the fast (22 min) and simple determination of Staphylococcus aureus by monitoring the oxidation of [Fe(CN)6]4-, which acted as a cellular respiration rate redox reporter. The sensors also showed a wide dynamic range, spanning 5 orders of magnitude, and a calculated limit of detection of 0.2 CFU mL-1.