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Low rainfall rates are becoming increasingly frequent because of climate change, causing droughts and threatening world food security. For popcorn, drought is the most limiting abiotic factor for plant's growth and development. Thus, the water deficit directly impacts for crop productivity. Based on knowledge of the genetic basis of traits involved in stages of popcorn germination and seedling development under water stress, genotypes with potential for adaptation to adverse growing conditions can be selected early. Therefore, data on genetic effects and combining ability of 10 popcorn parents were compiled to propose breeding strategies for the development of cultivars with greater adaptation to water stress in the early stages. Forty-five diallel hybrids were evaluated under two different water regimes, that is, water stress and full irrigation. This corresponded to a water retention capacity of 25% and 70% of the germination paper. The plants were watered daily as needed for seven days. A range of factors were evaluated, that is, germination traits including the germination speed index and germination on the seventh day; shoot traits including length and dry weight; and root system including length, dry weight, root-to-shoot ratio, maximum root number, root network area, specific and root network length, and root volume. Breeding for drought adaption in the early stages of popcorn development can be successful when hybrids are used, because of the genetic effects of dominance (Φs). These control the traits evaluated at the seedling stage. The combinations L61 x P2 and L71 x P3 were recommended, in view of the more successful performance estimated for traits related to the shoot and root system. [ABSTRACT FROM AUTHOR]

Multiple molecular pathways and cellular processes have been implicated in the neurobiology of autism and other neurodevelopmental conditions. There is a current focus on synaptic gene conditions, or synaptopathies, which refer to clinical conditions associated with rare genetic variants disrupting genes involved in synaptic biology. Synaptopathies are commonly associated with autism and developmental delay and may be associated with a range of other neuropsychiatric outcomes. Altered synaptic biology is suggested by both preclinical and clinical studies in autism based on evidence of differences in early brain structural development and altered glutamatergic and GABAergic neurotransmission potentially perturbing excitatory and inhibitory balance. This review focusses on the NRXN-NLGN-SHANK pathway, which is implicated in the synaptic assembly, trans-synaptic signalling, and synaptic functioning. We provide an overview of the insights from preclinical molecular studies of the pathway. Concentrating on NRXN1 deletion and SHANK3 mutations, we discuss emerging understanding of cellular processes and electrophysiology from induced pluripotent stem cells (iPSC) models derived from individuals with synaptopathies, neuroimaging and behavioural findings in animal models of Nrxn1 and Shank3 synaptic gene conditions, and key findings regarding autism features, brain and behavioural phenotypes from human clinical studies of synaptopathies. The identification of molecular-based biomarkers from preclinical models aims to advance the development of targeted therapeutic treatments. However, it remains challenging to translate preclinical animal models and iPSC studies to interpret human brain development and autism features. We discuss the existing challenges in preclinical and clinical synaptopathy research, and potential solutions to align methodologies across preclinical and clinical research. Bridging the translational gap between preclinical and clinical studies will be necessary to understand biological mechanisms, to identify targeted therapies, and ultimately to progress towards personalised approaches for complex neurodevelopmental conditions such as autism. [ABSTRACT FROM AUTHOR]

White matter deficits are a common neuropathologic finding in neurologic disorders, including HIV‐associated neurocognitive disorders (HAND). In HAND, the persistence of white matter alterations despite suppressive antiretroviral (ARV) therapy suggests that ARVs may be directly contributing to these impairments. Here, we report that a frontline ARV, bictegravir (BIC), significantly attenuates remyelination following cuprizone‐mediated demyelination, a model that recapitulates acute demyelination, but has no impact on already formed mature myelin. Mechanistic studies utilizing primary rat oligodendrocyte precursor cells (OPCs) revealed that treatment with BIC leads to significant decrease in mature oligodendrocytes accompanied by lysosomal deacidification and impairment of lysosomal degradative capacity with no alterations in lysosomal membrane permeability or total lysosome number. Activation of the endolysosomal cation channel TRPML1 prevents both lysosomal deacidification and impairment of oligodendrocyte differentiation by BIC. Lastly, we show that deacidification of lysosomes by compounds that raise lysosomal pH is sufficient to prevent maturation of oligodendrocytes. Overall, this study has uncovered a critical role for lysosomal acidification in modulating oligodendrocyte function and has implications for neurologic diseases characterized by lysosomal dysfunction and white matter abnormalities. [ABSTRACT FROM AUTHOR]

There is a recent resurgence of interest in phage therapy (the therapeutic use of bacterial viruses) as an approach to eliminating difficult-to-treat infections. However, existing approaches for therapeutic phage selection and virulence testing are time-consuming, host-dependent, and facing reproducibility issues. Here, this study presents an innovative approach wherein integrated resonant photonic crystal (PhC) cavities in silicon are used as optical nanotweezers for probing and manipulating single bacteria and single virions with low optical power. This study demonstrates that these nanocavities differentiate between a bacterium and a phage without labeling or specific surface bioreceptors. Furthermore, by tailoring the spatial extent of the resonant optical mode in the low-index medium, phage distinction across phenotypically distinct phage families is demonstrated. The work paves the road to the implementation of optical nanotweezers in phage therapy protocols., (© 2024 The Authors. Small published by Wiley‐VCH GmbH.)

To effectively diagnose and treat subjective cognitive symptoms in post-acute sequalae of COVID-19 (PASC), it is important to understand objective cognitive impairment across the range of acute COVID-19 severity. Despite the importance of this area of research, to our knowledge, there are no current meta-analyses of objective cognitive functioning following non-severe initial SARS-CoV-2 infection. The aim of this meta-analysis is to describe objective cognitive impairment in individuals with non-severe (mild or moderate) SARS-CoV-2 cases in the post-acute stage of infection. This meta-analysis was pre-registered with Prospero (CRD42021293124) and utilized the PRISMA checklist for reporting guidelines, with screening conducted by at least two independent reviewers for all aspects of the screening and data extraction process. Fifty-nine articles (total participants = 22,060) with three types of study designs met our full criteria. Individuals with non-severe (mild/moderate) initial SARS-CoV-2 infection demonstrated worse objective cognitive performance compared to healthy comparison participants. However, those with mild (nonhospitalized) initial SARS-CoV-2 infections had better objective cognitive performance than those with moderate (hospitalized but not requiring ICU care) or severe (hospitalized with ICU care) initial SARS-CoV-2 infections. For studies that used normative data comparisons instead of healthy comparison participants, there was a small and nearly significant effect when compared to normative data. There were high levels of heterogeneity (88.6 to 97.3%), likely reflecting small sample sizes and variations in primary study methodology. Individuals who have recovered from non-severe cases of SARS-CoV-2 infections may be at risk for cognitive decline or impairment and may benefit from cognitive health interventions., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The functional topography of the human primary somatosensory cortex hand area is a widely studied model system to understand sensory organization and plasticity. It is so far unclear whether the underlying 3D structural architecture also shows a topographic organization. We used 7 Tesla (7T) magnetic resonance imaging (MRI) data to quantify layer-specific myelin, iron, and mineralization in relation to population receptive field maps of individual finger representations in Brodman area 3b (BA 3b) of human S1 in female and male younger adults. This 3D description allowed us to identify a characteristic profile of layer-specific myelin and iron deposition in the BA 3b hand area, but revealed an absence of structural differences, an absence of low-myelin borders, and high similarity of 3D microstructure profiles between individual fingers. However, structural differences and borders were detected between the hand and face areas. We conclude that the 3D structural architecture of the human hand area is nontopographic, unlike in some monkey species, which suggests a high degree of flexibility for functional finger organization and a new perspective on human topographic plasticity. [ABSTRACT FROM AUTHOR]

Over the past decades, there has been an escalating rise in the need for chemicals and catalytic materials to keep up with global demands. Addressing those issues by conventional methods often becomes inefficient, with myriad operational risks. Process intensification methods through procedural and equipment‐based modifications have been considered greener, have higher heat and mass transfer rates, and operate with lower costs. In this review, research using ultrasonic reactors and microreactors, along with developments through an integrated external energy source, for synthesizing acrylic microspheres is covered extensively. Acrylic microspheres have garnered much interest for their biocompatibility, affinity toward functionalization, and wide range of applications. Core–shell, composite, functional‐group modified, and porous acrylic microspheres are used for enzyme immobilization and as catalyst carriers. The use of acrylic support has provided huge improvements in catalytic activity, reusability, recyclability, and overall stability. Finally, various other process intensification methods and alternate support materials are covered to help enhance future developments in the field of catalysis. [ABSTRACT FROM AUTHOR]

The cytomatrix at the active zone-associated structural protein (CAST) and its homologue, named ELKS, being rich in glutamate (E), leucine (L), lysine (K), and serine (S), belong to a family of proteins that organize presynaptic active zones at nerve terminals. These proteins interact with other active zone proteins, including RIMs, Munc13s, Bassoon, and the β subunit of Ca2+ channels, and have various roles in neurotransmitter release. A previous study showed that depletion of CAST/ELKS in the retina causes morphological changes and functional impairment of this structure. In this study, we investigated the roles of CAST and ELKS in ectopic synapse localization. We found that the involvement of these proteins in ribbon synapse distribution is complex. Unexpectedly, CAST and ELKS, in photoreceptors or in horizontal cells, did not play a major role in ribbon synapse ectopic localization. However, depletion of CAST and ELKS in the mature retina resulted in degeneration of the photoreceptors. These findings suggest that CAST and ELKS play critical roles in maintaining neural signal transduction in the retina, but the regulation of photoreceptor triad synapse distribution is not solely dependent on their actions within photoreceptors and horizontal cells. [ABSTRACT FROM AUTHOR]

Visible‐light photocatalysis provides numerous useful methodologies for synthetic organic chemistry. However, the mechanisms of these reactions are often not fully understood. Common mechanistic experiments mainly aim to characterize excited state properties of photocatalysts and their interaction with other species. Recently, in situ reaction monitoring using dedicated techniques was shown to be well‐suited for the identification of intermediates and to obtain kinetic insights, thereby providing more holistic pictures of the reactions of interest. This minireview surveys these technologies and discusses selected examples where reaction monitoring was used to elucidate the mechanism of photocatalytic reactions. [ABSTRACT FROM AUTHOR]

Biodiesel is produced on a large scale as an eco‐friendly substitute and additive to fossil fuels. Catalytic homogeneous processes using strong acids, alkalis, and natural oils have been realized in industry. However, these traditional methods have several disadvantages, such as the generation of large volumes of waste, high water and reagent needs, use of hazardous reagents, high operation costs, and utilization of valuable feedstocks and catalysis, respectively. Different solutions have subsequently been investigated, such as cheap alternative feedstocks, co‐solvents and catalysts, sustainable operational conditions, advanced reactor designs and scales, and advantageous pre‐ and post‐reaction treatments. This review explores and analyzes the main aspects of current biodiesel technologies and opportunities. It also describes some advanced improvement strategies. [ABSTRACT FROM AUTHOR]

Muscle deconditioning and impaired vascular function in the lower extremities (LE) are among the long‐term symptoms experienced by COVID‐19 patients with a history of severe illness. These symptoms are part of the post‐acute sequelae of Sars‐CoV‐2 (PASC) and currently lack evidence‐based treatment. To investigate the efficacy of lower extremity electrical stimulation (E‐Stim) in addressing PASC‐related muscle deconditioning, we conducted a double‐blinded randomized controlled trial. Eighteen (n = 18) patients with LE muscle deconditioning were randomly assigned to either the intervention (IG) or the control (CG) group, resulting in 36 LE being assessed. Both groups received daily 1 h E‐Stim on both gastrocnemius muscles for 4 weeks, with the device functional in the IG and nonfunctional in the CG. Changes in plantar oxyhemoglobin (OxyHb) and gastrocnemius muscle endurance (GNMe) in response to 4 weeks of daily 1 h E‐Stim were assessed. At each study visit, outcomes were measured at onset (t0), 60 min (t60), and 10 min after E‐Stim therapy (t70) by recording ΔOxyHb with near‐infrared spectroscopy. ΔGNMe was measured with surface electromyography at two time intervals: 0–5 min (Intv1) and: 55–60 min (Intv2). Baseline OxyHb decreased in both groups at t60 (IG: p = 0.046; CG: p = 0.026) and t70 (IG = p = 0.021; CG: p = 0.060) from t0. At 4 weeks, the IG's OxyHb increased from t60 to t70 (p < 0.001), while the CG's decreased (p = 0.003). The IG had higher ΔOxyHb values than the CG at t70 (p = 0.004). Baseline GNMe did not increase in either group from Intv1 to Intv2. At 4 weeks, the IG's GNMe increased (p = 0.031), whereas the CG did not change. There was a significant association between ΔOxyHb and ΔGNMe (r = 0.628, p = 0.003) at 4 weeks in the IG. In conclusion, E‐Stim can improve muscle perfusion and muscle endurance in individuals with PASC experiencing LE muscle deconditioning. [ABSTRACT FROM AUTHOR]

A Teflon AF‐2400 based tube‐in‐tube device was used to generate flow streams of CO2 in acetonitrile and a computer‐vision based 'bubble counting' technique was used to estimate the amount of CO2 that had passed into solution whilst in the tube‐in‐tube device by quantifying the amount of CO2 that left solution (forming separate gas‐phase segments) downstream of the back‐pressure regulator. For both CO2 pressures used, there appeared to be a minimum residence time below which no CO2 was observed to leave solution. This was assumed to be due to residual CO2 below (or close to) the saturation concentration at atmospheric pressure and, by taking this into account, we were able to fit curves corresponding to simple gradient‐driven diffusion and which closely matched previously obtained colorimetric titration data for the same system. The estimated value for the residual concentration of CO2 (0.37 M) is higher than, but in reasonable general correspondence with, saturation concentrations previously reported for CO2 in acetonitrile (0.27 M). [ABSTRACT FROM AUTHOR]

Pd membranes can play an important role in H2 separation and purification for the development of sustainable and renewable energies. By supporting on porous substrates, Pd layer thickness can be reduced to several micrometers, thus improving the H2 permeance by several orders of magnitude. However, the supported thin Pd membranes are concomitant with pinhole formation due to either fabrication (e.g., electroless-plating) or thermal treatment, which exist as a remarkable challenge for its widespread applications. This study presents a novel and facile approach for self-repair of Pd membrane defects by immersing the stainless-steel supported Pd membranes in PdCl2 solution. Three membranes were deliberately selected with a low selectivity of 152–1687 (400 ​°C, 0.1Mpa), for which disproportionation reactions between Pd2+ and Fe/Cr/Ni at the defect sites spontaneously occur leading to the formation of Pd particles at the exact point of defects. This self-repair process can be enhanced when applying a high pressure of 30–50 ​bar in the PdCl2 solution for 30 ​min, by overcoming the capillary resistance and penetrating through the pinholes. Interestingly, densely distributed hillocks were observed on the membrane surface probably due to reduction of PdCl2 under following H2 treatment, thus increasing the H2 permeance with a higher effective surface area. The H2/N2 selectivity can be improved by more than one order of magnitude (in the best case from 1687 to 8768) and a long-term stability test of 300 ​h was achieved for the repaired membranes, corroborating the application potential of this approach. [ABSTRACT FROM AUTHOR]

Abnormal brain structural and functional properties were demonstrated in patients with infantile esotropia (IE). However, few studies have investigated the interaction between structural and functional connectivity (SC-FC) in patients with IE. Structural network was generated with diffusion tensor imaging and functional network was constructed with resting-state functional magnetic resonance imaging for 18 patients with IE as well as 20 ageand gender-matched healthy subjects. The SC-FC coupling for global connectome, short connectome and long connectome were examined in IE patients and compared with those of healthy subjects. A linear mixed effects model was employed to examine the group-age interaction in terms of the coupling metrics. The Pearson correlation between coupling measures and strabismus degree was evaluated in IE patients, on which the regulatory effect of age was also investigated through hierarchical regression analysis. Significantly decreased SC-FC coupling score for short connections was observed in left caudate nucleus (CAU) in IE patients, whereas no brain regions exhibited altered coupling metrics for global connections or long connections. The group-age interaction was also evident in local coupling metrics of left CAU. The age-related regulatory effect on coupling-degree association was distinguishing between brain regions implicated in visual processing and cognition-related brain areas in IE patients. Local SC-FC decoupling in CAU was evident in patients with IE and was initiated in their early postnatal period, possibly interfering the visual cortico-striatal loop and subcortical optokinetic pathway subserving visual processing and nasalward optokinesis during neurodevelopment, which provides new insight into underlying neuropathological mechanism of IE. [ABSTRACT FROM AUTHOR]

A novel class of diazonium salts is introduced for the photochemical aryl-aryl coupling to produce (substituted) biphenyls. As common diazonium tetrafluoroborate salts fail, soluble and safe aryl diazonium trifluoroacetates are applied. In this mild synthesis route no catalysts are required to generate an aryl-radical by irradiation with UV-A light (365 nm). This reactive species undergoes direct C-H arylation at an arene, forming the product in reasonable reaction times. With the implementation of a continuous flow setup in a capillary photoreactor 13 different biphenyl derivatives are successfully synthesized. By integrating an inline 19 F-NMR benchtop spectrometer, samples are reliably quantified as the fluorine-substituents act as a probe. Here, real-time NMR spectroscopy is a perfect tool to monitor the continuously operated system, which produces fine chemicals of industrial relevance even in a multigram scale., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Synaptic dysfunction and altered synaptic pruning are present in people with Parkinsonian disorders. Dopamine loss and alpha-synuclein accumulation, two hallmarks of Parkinson's disease (PD) pathology, contribute to synaptic dysfunction and reduced synaptic density in PD. Atypical Parkinsonian disorders are likely to have unique spatiotemporal patterns of synaptic density, differentiating them from PD. Therefore, quantification of synaptic density has the potential to support diagnoses, monitor disease progression, and treatment efficacy. Novel radiotracers for positron emission tomography which target the presynaptic vesicle protein SV2A have been developed to quantify presynaptic density. The radiotracers have successfully investigated synaptic density in preclinical models of PD and people with Parkinsonian disorders. Therefore, this review will summarize the preclinical and clinical utilization of SV2A radiotracers in people with Parkinsonian disorders. We will evaluate how SV2A abundance is associated with other imaging modalities and the considerations for interpreting SV2A in Parkinsonian pathology., (© 2023 The Authors. Journal of Neuroscience Research published by Wiley Periodicals LLC.)

Extensive studies showed increased subjective pain sensitivity in Parkinson's disease (PD), which appeared to be partially reversed by dopaminergic (DA) treatment. Although cell replacement represents an attractive therapeutic strategy, its potential for PD-related hyperalgesia remains unclear. We investigated re-establishment of DA function via allografting exogenic DA cells on pain hypersensitivity in a rat model of PD. We evaluated the antinociceptive effects of fetal ventral mesencephalic (rVM) tissue allografts in PD rats after unilateral 6-OHDA-induced toxicity in the medial forebrain bundle. The drug -induced rotation test was used to validate the severity of the nigrostriatal lesion; von Frey and thermal pain tests were employed to evaluate nociceptive function. Nociception-induced cerebral blood volume (CBV) response was measured using a 4.7-T MR system. Finally, the immunohistochemical (IHC) studies were performed and the results were compared with the imaging findings from functional magnetic resonance imaging (fMRI). The grafts significantly improved drug-induced rotation behavior and increased mechanical and thermal nociceptive thresholds in PD rats. The elevation of CBV signals significantly recovered on the grafted striatum, whereas this effect was inhibited by the D2R antagonist eticlopride in each striatum. Quantitative IHC analysis revealed the transplantation markedly increased the numbers of tyrosine hydroxylase immunoreactive cells. Therefore, we concluded transplantation of rVM tissue results in anti-nociceptive effects and improves motor function. Moreover, in vivo CBV response confirmed the key role of D2R-mediated pain modulation. Therefore, we demonstrate fMRI as a reliable imaging index in evaluating the anti-nociceptive therapeutic effects of fetal rVM transplantation in the rat model of PD. [ABSTRACT FROM AUTHOR]

Epilepsy is a common symptom of many neurological disorders and can lead to neuronal damage that plays a major role in seizure-related disability. The peptidyl-prolyl isomerase Pin1 has wide-ranging influences on the occurrence and development of neurological diseases. It has also been suggested that Pin1 acts on epileptic inhibition, and the molecular mechanism has recently been reported. In this review, we primarily focus on research concerning the mechanisms and functions of Pin1 in neurons. In addition, we highlight the significance and potential applications of Pin1 in neuronal diseases, especially epilepsy. We also discuss the molecular mechanisms by which Pin1 controls synapses, ion channels and neuronal signaling pathways to modulate epileptic susceptibility. Since neurotransmitters and some neuronal signaling pathways, such as Notch1 and PI3K/Akt, are vital to the nervous system, the role of Pin1 in epilepsy is discussed in the context of the CaMKII-AMPA receptor axis, PSD-95-NMDA receptor axis, NL2/gephyrin-GABA receptor signaling, and Notch1 and PI3K/Akt pathways. The effect of Pin1 on the progression of epilepsy in animal models is discussed as well. This information will lead to a better understanding of Pin1 signaling pathways in epilepsy and may facilitate development of new therapeutic strategies. [ABSTRACT FROM AUTHOR]

The transition from batch catalytic processes to continuous flow processes requires highly active and stable catalysts that still need to be developed. The preparation and characterization of catalysts where palladium single atoms and nanoparticles are simultaneously present on carbon nanotubes were recently reported by us. These catalysts are considerably more active than commercial or previously described catalysts for the liquid phase hydrogenation of terpenes. Herein is shown that under solvent‐free conditions, squalene (SQE) could be converted into squalane (SQA,>98 %) using only 300 ppm of Pd in less than 1.4 h at 20 bar H2 and 120 °C. Catalyst stability was assessed in a lab‐scale flow reactor, and long‐term experiments led to turnover number (TON) higher than 300000 without any detectable loss in the activity. Then, the implementation of this catalyst in a commercial intensified continuous‐flow milli‐reactor pilot was achieved. High purity SQA (>98 %) could be obtained by continuous hydrogenation of solvent‐free SQE at 180 °C and 30 bar H2 with a contact time below 15 min. A production capacity of 3.6 kg per day of SQA could be obtained with an effective reactor volume (VR) of 43.2 mL for this complex 3 phase reaction. Large‐scale production can now be foreseen thanks to seamless scale‐up provided by the continuous flow pilot supplier. [ABSTRACT FROM AUTHOR]

Purpose: To investigate cortical differences, age-related cortical differences, and structural covariance differences between children with intermittent exotropia (IXT) and healthy controls (HCs) using high-resolution magnetic resonance imaging (MRI). Methods: Sixteen IXT patients and 16 HCs underwent MRI using a 3-T MR scanner. FreeSurfer software was used to obtain measures of cortical volume, thickness, and surface area. Group differences in cortical thickness, volume and surface area were examined using a general linear model with intracranial volume (ICV), age and sex as covariates. Then, the age-related cortical differences between the two groups and structural covariance in abnormal morphometric changes were examined. Results: Compared to HCs, IXT patients demonstrated significantly decreased surface area in the left primary visual cortex (PVC), and increased surface area in the left inferior temporal cortex (ITC). We also found increased cortical thickness in the left orbitofrontal cortex (OFC), right middle temporal cortex (MT), and right inferior frontal cortex (IFC). No significant differences were found in cortical volume between the two groups. There were several negative correlations between neuroanatomic measurements and age in the HC group that were not observed in the IXT group. In addition, we identified altered patterns of structural correlations across brain regions in patients with IXT. Conclusion: To our knowledge, this study is the first to characterize the cortical morphometry of the children and adolescents with IXT. Based on our results, children and adolescents with IXT exhibited significant alterations in the PVC and association cortices, different cortical morphometric development patterns, and disrupted structural covariance across brain regions. [ABSTRACT FROM AUTHOR]

Novel nanocarriers such as multifunctional nanoparticles (NPs) have recently attracted attention due to their various applications, specifically in medicine and treatment. However, it is vital that these particles be synthesized with meticulous control of different structural, chemical, and physical properties. In response to this demand, microfluidic (MF) technology as a reliable procedure can provide promising results in the development of desired NPs and efficient drug delivery systems. By controlling the flow rates of multiphase fluids and conditions of chemical reactions, MF technology enables the fabrication of uniform and highly stable particles with enhanced surfaces, higher encapsulation efficiency, and controlled release of therapeutic agents compared with conventional bulk methods. This review article investigates the MF‐based methods utilized in the synthesis of NPs and their advantages in developing novel drug delivery systems. It also provides a comprehensive comparison with conventional methods from a different point of view, emphasizing a novel category of nanocarriers' critical characteristics. In addition, a summary of the most recent representative works on NPs fabrication by MF procedures is presented, and their potential and applications in drug delivery are discussed. [ABSTRACT FROM AUTHOR]

Aims: In minimally invasive surgery (MIS), intraoperative guidance has been limited to verbal communication without direct visual guidance. Communication issues and mistaken instructions in training procedures can hinder correct identification of anatomical structures on the MIS screen. The iSurgeon system was developed to provide visual guidance in the operating room by telestration with augmented reality (AR). Methods: Laparoscopic novices (n = 60) were randomized in two groups in a cross-over design: group 1 trained only with verbal guidance first and then with additional telestration with AR on the operative screen and vice versa for group 2. Training consisted of laparoscopic basic training and subsequently a specifically designed training course, including a porcine laparoscopic cholecystectomy (LC). Outcome included time needed for training, performance with Global Operative Assessment of Laparoscopic Skills (GOALS), and Objective Structured Assessment of Technical Skills (OSATS) score for LC, complications, and subjective workload (NASA-TLX questionnaire). Results: Telestration with AR led to significantly faster total training time (1163 ± 275 vs. 1658 ± 375 s, p < 0.001) and reduced error rates. LC on a porcine liver was performed significantly better (GOALS 21 ± 5 vs. 18 ± 4, p < 0.007 and OSATS 67 ± 11 vs. 61 ± 8, p < 0.015) and with less complications (13.3% vs. 40%, p < 0.020) with AR. Subjective workload and stress were significantly reduced during training with AR (33.6 ± 12.0 vs. 30.6 ± 12.9, p < 0.022). Conclusion: Telestration with AR improves training success and safety in MIS. The next step will be the clinical application of telestration with AR and the development of a mobile version for remote guidance. [ABSTRACT FROM AUTHOR]

In recent years, the clinical decision support system (CDSS) has been gradually improved, which effectively reduces the probability of doctors' misdiagnosis or missed diagnosis. Therefore, the clinical decision support system has always been a research hotspot, deep learning and collaborative filtering technologies are developing rapidly, and more and more are applied to different fields. Based on the deep learning technology, this paper conducts in-depth research on the methods of assisted diagnosis of clinical diseases and prediction of clinical high-risk diseases in the field of CDSS. Aiming at the problem of clinical decision support system, this article analyzes the deep learning identification method in depth and is committed to applying machine deep learning to clinical decision-making, changing the lack of information and its challenges to clinical decision-making. Based on previous studies, two unsupervised learning methods based on machine learning are proposed, namely user collaborative filtering and RBM, to improve CDSS. The experimental results show that the overall performance of the RBM-based method is the best. When the missing degree of the two data sets is 30.6%, the classification accuracy rate is still more than 92.8%. [ABSTRACT FROM AUTHOR]

Glycogen synthase kinase 3 (GSK3) is a key regulator of many cellular signaling processes and performs a wide range of biological functions in the nervous system. Due to its central role in numerous cellular processes involved in cell degeneration, a rising number of studies have highlighted the interest in developing therapeutics targeting GSK3 to treat neurodegenerative diseases. Although recent works strongly suggest that inhibiting GSK3 might also be a promising therapeutic approach for retinal degenerative diseases, its full potential is still under-evaluated. In this review, we summarize the literature on the role of GSK3 on the main cellular functions reported as deregulated during retinal degeneration, such as glucose homeostasis which is critical for photoreceptor survival, or oxidative stress, a major component of retinal degeneration. We also discuss the interest in targeting GSK3 for its beneficial effects on inflammation, for reducing neovascularization that occurs in some retinal dystrophies, or for cell-based therapy by enhancing Müller glia cell proliferation in diseased retina. Together, although GSK3 inhibitors hold promise as therapeutic agents, we highlight the complexity of targeting such a multitasked kinase and the need to increase our knowledge of the impact of reducing GSK3 activity on these multiple cellular pathways and biological processes. [ABSTRACT FROM AUTHOR]

Purpose. [18F]F-AraG is a radiolabeled nucleoside analog that shows relative specificity for activated T cells. The aim of this study was to investigate the biodistribution of [18F]F-AraG in healthy volunteers and assess the preliminary safety and radiation dosimetry. Methods. Six healthy subjects (three female and three male) between the ages of 24 and 60 participated in the study. Each subject received a bolus venous injection of [18F]F-AraG (dose range: 244.2–329.3 MBq) prior to four consecutive PET/MR whole-body scans. Blood samples were collected at regular intervals and vital signs monitored before and after tracer administration. Regions of interest were delineated for multiple organs, and the area under the time-activity curves was calculated for each organ and used to derive time-integrated activity coefficient (TIAC). TIACs were input for absorbed dose and effective dose calculations using OLINDA. Results. PET/MR examination was well tolerated, and no adverse effects to the administration of [18F]F-AraG were noted by the study participants. The biodistribution was generally reflective of the expression and activity profiles of the enzymes involved in [18F]F-AraG's cellular accumulation, mitochondrial kinase dGK, and SAMHD1. The highest uptake was observed in the kidneys and liver, while the brain, lung, bone marrow, and muscle showed low tracer uptake. The estimated effective dose for [18F]F-AraG was 0.0162 mSv/MBq (0.0167 mSv/MBq for females and 0.0157 mSv/MBq for males). Conclusion. Biodistribution of [18F]F-AraG in healthy volunteers was consistent with its association with mitochondrial metabolism. PET/MR [18F]F-AraG imaging was well tolerated, with a radiation dosimetry profile similar to other commonly used [18F]-labeled tracers. [18F]F-AraG's connection with mitochondrial biogenesis and favorable biodistribution characteristics make it an attractive tracer with a variety of potential applications. [ABSTRACT FROM AUTHOR]

Pelizaeus–Merzbacher Disease (PMD) is an inherited leukodystrophy affecting the central nervous system (CNS)—a rare disorder that especially concerns males. Its estimated prevalence is 1.45–1.9 per 100,000 individuals in the general population. Patients affected by PMD exhibit a drastic reduction or absence of myelin sheaths in the white matter areas of the CNS. The Proteolipid Protein 1 (PLP1) gene encodes a transmembrane proteolipid protein. PLP1 is the major protein of myelin, and it plays a key role in the compaction, stabilization, and maintenance of myelin sheaths. Its function is predominant in oligodendrocyte development and axonal survival. Mutations in the PLP1 gene cause the development of a wide continuum spectrum of leukopathies from the most severe form of PMD for whom patients exhibit severe CNS hypomyelination to the relatively mild late-onset type 2 spastic paraplegia, leading to the concept of PLP1-related disorders. The genetic diversity and the biochemical complexity, along with other aspects of PMD, are discussed to reveal the obstacles that hinder the development of treatments. This review aims to provide a clinical and mechanistic overview of this spectrum of rare diseases. [ABSTRACT FROM AUTHOR]

Cuscuta chinensis Lam. (CCL) is a medicinal herb widely used in traditional Chinese medicine for the treatment of ophthalmic diseases, including age-dependent vision-threatening retinal degenerative disorders that involve irreversible loss of the first-order retinal neurons, photoreceptors. However, evidence is lacking if CCL is pharmacologically active at protecting against loss of photoreceptors and photoreceptor degeneration-associated retinal structural and functional impairment. The current study thus evaluates the potential photoreceptor protective effects of CCL to better support its clinical applications in the prevention and treatment of photoreceptor degenerative diseases. Non-invasive full-retinal optical coherence tomography, electroretinography, histological examination, immunohistochemistry and real-time qPCR analysis were performed to assess the retinal protective effects of CCL in light-exposed BALB/c mice characterized by photooxidative stress-mediated photoreceptor loss and associated retinal morphological and functional impairment. The results showed that CCL treatment protected against light-induced degeneration of the photoreceptor structure and deterioration of the retinal function. Furthermore, CCL treatment increased the retinal expression of rhodopsin, S-opsin and M-opsin, supporting the protective effects of CCL in both rod and cone photoreceptors. CCL treatment suppressed photoreceptor cell death in the light-exposed retinas. The morphological integrity of the second-order retinal neurons was also preserved as a result of CCL treatment. In addition, CCL treatment attenuated light-induced reactive müller gliosis, microglial activation and inflammation in the retina. In conclusion, the current work demonstrates for the first time that CCL protects against photooxidative stress-mediated degeneration of photoreceptors and associated disturbance of structural, functional and immune homeostasis of the retina. The findings here thus provide novel experimental evidence supporting the clinical application of CCL in the prevention and treatment photoreceptor degenerative diseases. [ABSTRACT FROM AUTHOR]

Heterogeneous reactions are considered the heart of chemical synthesis with numerous industrial applications due to their high conversion rates and low reaction time. On the other hand, the performance of heterogeneous reactions suffers from several drawbacks such as lower product selectivity and high mass transfer resistance that, in many cases, reduce the reaction rate. The efficiency of various conventional mixing techniques in heterogeneous reactors is believed to play a critical role in controlling the product quality and mass transfer rates besides other essential factors. Microfluidics technology provides a unique opportunity to revisit many established heterogeneous reaction processes to optimize and understand the reaction mechanisms. The unique flow conditions in microflow systems provide an excellent platform for exploring the effect of high‐precision micromixing techniques on reaction rates and productivities. Recent advances in microreactor technology in general and specifically heterogeneous reactions in microflow systems with an insight on the enzymatic reactions in microreactors are reviewed. [ABSTRACT FROM AUTHOR]

We developed a procedure to measure diffusion coefficients using microfluidic devices that contributes to the transport analysis of high molecular weight solutes with low diffusion coefficient. This procedure allows a quick determination of diffusion coefficients and a precise evaluation of measurement errors. Making use of color variation of a pH indicator, we determined its diffusion coefficient in its own solvent (water). The value obtained was compared with previously published ones and was found to be similar to those cited. The microfluidic device has a serpentine-shaped channel that allows monitoring the solution evolution in different regions of the path in a single visual field without the need to move the camera or the microchip. This kind of device also allows the spatial and temporal tracking of the diffusion process. The solution color intensity is used to determine solute concentration; therefore, this method presents an advantage compared to those based on fluorescence detection. A complete analysis of the diffusive behavior along the channel path was performed in order to test the accuracy of these kinds of methodologies. This analysis can be used with similar devices, and the techniques employed for diffusion analysis can be applied to a µTAS-type microfluidic platform, allowing obtain variations of the diffusion coefficient as a function of time due to variations in external factors, e.g., temperature, etc. [ABSTRACT FROM AUTHOR]

Recent thermodynamic modelling indicates that maintaining the brain tissue ratio of O 2 to CO 2 (abbreviated tissue O 2 /CO 2 ) is critical for preserving the entropy increase available from oxidative metabolism of glucose, with a fall of that available entropy leading to a reduction of the phosphorylation potential and impairment of brain energy metabolism. This provides a novel perspective for understanding physiological responses under different conditions in terms of preserving tissue O 2 /CO 2 . To enable estimation of tissue O 2 /CO 2 in the human brain, a detailed mathematical model of O 2 and CO 2 transport was developed, and applied to reported physiological responses to different challenges, asking: how well is tissue O 2 /CO 2 preserved? Reported experimental results for increased neural activity, hypercapnia and hypoxia due to high altitude are consistent with preserving tissue O 2 /CO 2 . The results highlight two physiological mechanisms that control tissue O 2 /CO 2 : cerebral blood flow, which modulates tissue O 2 ; and ventilation rate, which modulates tissue CO 2 . The hypoxia modelling focused on humans at high altitude, including acclimatized lowlanders and Tibetan and Andean adapted populations, with a primary finding that decreasing CO 2 by increasing ventilation rate is more effective for preserving tissue O 2 /CO 2 than increasing blood haemoglobin content to maintain O 2 delivery to tissue. This work focused on the function served by particular physiological responses, and the underlying mechanisms require further investigation. The modelling provides a new framework and perspective for understanding how blood flow and other physiological factors support energy metabolism in the brain under a wide range of conditions. KEY POINTS: Thermodynamic modelling indicates that preserving the O 2 /CO 2 ratio in brain tissue is critical for preserving the entropy change available from oxidative metabolism of glucose and the phosphorylation potential underlying energy metabolism. A detailed model of O 2 and CO 2 transport was developed to allow estimation of the tissue O 2 /CO 2 ratio in the human brain in different physiological states. Reported experimental results during hypoxia, hypercapnia and increased oxygen metabolic rate in response to increased neural activity are consistent with maintaining brain tissue O 2 /CO 2 ratio. The hypoxia modelling of high-altitude acclimatization and adaptation in humans demonstrates the critical role of reducing CO 2 with increased ventilation for preserving tissue O 2 /CO 2 . Preservation of tissue O 2 /CO 2 provides a novel perspective for understanding the function of observed physiological responses under different conditions in terms of preserving brain energy metabolism, although the mechanisms underlying these functions are not well understood., (© 2024 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Neuronal homeostasis prevents hyperactivity and hypoactivity. Age-related hyperactivity suggests homeostasis may be dysregulated in later life. However, plasticity mechanisms preventing age-related hyperactivity and their efficacy in later life are unclear. We identify the adult cortical plasticity response to elevated activity driven by sensory overstimulation, then test how plasticity changes with age. We use in vivo two-photon imaging of calcium-mediated cellular/synaptic activity, electrophysiology and c-Fos-activity tagging to show control of neuronal activity is dysregulated in the visual cortex in late adulthood. Specifically, in young adult cortex, mGluR5-dependent population-wide excitatory synaptic weakening and inhibitory synaptogenesis reduce cortical activity following overstimulation. In later life, these mechanisms are downregulated, so that overstimulation results in synaptic strengthening and elevated activity. We also find overstimulation disrupts cognition in older but not younger animals. We propose that specific plasticity mechanisms fail in later life dysregulating neuronal microcircuit homeostasis and that the age-related response to overstimulation can impact cognitive performance., (© 2023. The Author(s).)

1,4,2-Dioxazol-5-ones are known to undergo decarboxylation under thermal conditions followed by Lossen's rearrangement to give isocyanates. Described herein is the in situ trapping of the isocyanates by indoles to give indole-3-carboxamides in good to excellent yields. [ABSTRACT FROM AUTHOR]

Red blood cell velocity (RBCv), cerebral blood flow (CBF), and volume (CBV) are three key parameters when describing brain hemodynamics. Functional ultrasound imaging is a Doppler-based method allowing for real-time measurement of relative CBV at high spatiotemporal resolution (100 × 110 × 300 μm3, up to 10 Hz) and large scale. Nevertheless, the measure of RBCv and CBF in small cortical vessels with functional ultrasound imaging remains challenging because of their orientation and size, which impairs the ability to perform precise measurements. We designed a directional flow filter to overpass these limitations allowing us to measure RBCv in single vessels using a standard functional ultrasound imaging system without contrast agents (e.g., microbubbles). This method allows to quickly extract the number of vessels in the cortex that was estimated to be approximately 650/cm3 in adult rats, with a 55–45% ratio for penetrating arterioles versus ascending venules. Then, we analyzed the changes in RBCv in these vessels during forepaw stimulation. We observed that ∼40 vessels located in the primary somatosensory forelimb cortex display a significant increase of the RBCv (median ΔRBCv ∼15%, maximal ΔRBCv ∼60%). As expected, we show that RBCv was higher for penetrating arterioles located in the center than in the periphery of the activated area. The proposed approach extends the capabilities of functional ultrasound imaging, which may contribute to a better understanding of the neurovascular coupling at the brain-wide scale. [ABSTRACT FROM AUTHOR]

More and more studies showed that strabismus is not simply an ocular disease, but a neuro-ophthalmology disease. To analyze potential changes in brain activity and their relationship to behavioral performance in comitant strabismus patients and healthy controls. Our study recruited 28 patients with comitant strabismus and 28 people with matched weight, age range, and sex ratio as healthy controls. Using resting-state functional magnetic resonance imaging, we evaluated fALFF to compare spontaneous brain activity between comitant strabismus and healthy controls. We did hospital anxiety and depression scale questionnaires for these patients. We found significantly lower fALFF value in comitant strabismus patients compared with controls in the left frontal superior medial gyrus and the right middle cingulum. In the latter region, fALFF was significantly negatively correlated with the hospital anxiety and depression scale, as well as the duration of disease. Receiver operating characteristic curve analysis indicated that the fALFF method has clear potential for the diagnosis of comitant strabismus patients. These results revealed abnormal spontaneous activity in two brain regions of comitant strabismus patients, which may indicate underlying pathologic mechanisms and may help to advance clinical treatment. [ABSTRACT FROM AUTHOR]

The effects of electron beam (EB) radiation in thermoplastic elastomers based on SEBS/TPU and SEBS‐g‐MA/TPU are evaluated. 60/40 blend of both the systems were subjected to EB using an ILU type industrial accelerator. Radiation dose was varied from 0 to 100 kGy, and the sol–gel content evaluation along with detailed analysis of mechanical, thermal, rheological, and morphological implications was conducted. The interplay between crosslinking and chain scission was quantified using the Charlesby‐Pinner equation. Both the blends showed the presence of a three‐dimensional cross‐linked network in them after the irradiation. The tensile strength of SEBS/TPU was found to deteriorate with an increase in radiation dose, but an opposite trend was observed in SEBS‐g‐MA/TPU. Improvement in interfacial adhesion between SEBS‐g‐MA and TPU was confirmed. The morphological analysis through atomic force microscopy and scanning electron microscopy clearly showed the appearance of rough ridges and pits due to irradiation along with the cross‐linked networks. From differential scanning calorimetry analysis, the changes in glass transitions and melting endotherm were assessed. Thermogravimetric analysis results indicated an improvement in the thermal stability of the blends. The storage modulus and complex viscosity of the samples enhanced as perceived from the rheological measurements. X‐ray diffraction patterns of the blends also showed considerable variation after irradiation. [ABSTRACT FROM AUTHOR]

Oxide nanoparticles (oxide NPs) are advanced materials with a wide variety of applications in different fields. The use of continuous flow methods is particularly appealing for their synthesis due to the high control achieved over the reaction conditions and the easy process scalability. The present review focuses on the preparation of oxide NPs using microfluidic setups at low temperature (≤80 °C), since the employment of mild reaction conditions is crucial for developing sustainable and cost‐effective processes. A particular emphasis will be put on the improvement over the final product features (e. g. size, shape, and size distribution) given by flow methods with respect to conventional batch procedures. The main issues that arise by treating NPs suspensions in microfluidic systems are product deposition or channel clogging; mitigation strategies to overcome these drawbacks will also be presented and discussed. [ABSTRACT FROM AUTHOR]