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Operator training and development of performance metrics are simultaneously implemented by a novel program for microwave nondestructive testing (NDT) of composite ceramic armor. A Portable Automated Microwave Scanning System (PAMSS) and accompanying Hand-Held Tool (HHT) were developed for efficient condition assessment of composite ceramic armor, in-situ on vehicles. Operator training for the simpler, HHT will be based on a self-study course available on the tool's operator interface computer. The course includes a library of examination samples, created using the more operator-controllable PAMSS, and validated by digital x-ray NDT. Operators will be able to study examples from the library on their own, and take a performance test using the operator interface computer. Using analysis of variance gauge repeatability and reproducibility techniques, the overall performance and performance of individual operators can be characterized by use of Cohen's kappa coefficient. The microwave interference scanning technique can image the volume of most dielectric parts, including those with complex structure and complex materials. This work is supported by the US Army Tank-Automotive Research, Development and Engineering Center (TARDEC), the US Army Research Laboratory who provided test panels and Evisive, Inc. internal development. [ABSTRACT FROM AUTHOR]

As the main cause of visual function deficits in children and adolescents worldwide, amblyopia causes serious impairment of monocular visual acuity and stereopsis. The recovery of visual functions from amblyopia beyond the critical period is slow and incomplete due to the limited plasticity of the mature cortex; notably, visual stimulation training seems to be an effective therapeutic strategy in clinical practice. However, the precise neural basis and cellular mechanisms that underlie amblyopia and visual stimulation treatment remain to be elucidated. Using monocular deprivation in juvenile mice to model amblyopia, we employed two-photon calcium imaging and chemogenetic techniques to investigate the visual responses of individual excitatory neurons and parvalbumin (PV+) interneurons in the primary visual cortex (V1) of amblyopic mice. We demonstrate that amblyopic mice exhibit an excitation/inhibition (E/I) imbalance. Moreover, visual stimulation decreases the response of PV+ interneurons, reactivates the ocular dominance plasticity of excitatory neurons, and promotes vision recovery in adult amblyopic mice. Our results reveal a dynamic E/I balance between excitatory neurons and PV+ interneurons that may underlie the neural mechanisms of amblyopia during cortical development and visual stimulation-mediated functional recovery from adult amblyopia, providing evidence for therapeutic applications that rely on reactivating adult cortical plasticity. A dynamic excitation and inhibition (E/I) balance between excitatory neurons and PV+ interneurons in the primary visual cortex underlying the neural mechanisms of amblyopia during cortical development and visual stimulation-mediated functional recovery from adult amblyopia. [ABSTRACT FROM AUTHOR]

The growing interest in physically deposited model catalysts for uncovering complex structure‐activity relationships is spurred by the possibility of depositing nanoparticles of precise atomic structure and composition using cluster‐beam sources. However, the limitations accompanying these synthesis techniques, such as low deposition rates and flat sample geometry, present a challenge for in situ structural characterization using bulk‐sensitive methods, such as X‐ray absorption spectroscopy (XAS), especially at elevated pressures (1–100 bar). To overcome this challenge, we constructed an in situ XAS cell operating in a grazing incidence (GI) geometry. The GIXAS cell was used to investigate the structure of cluster‐beam‐generated Pd and Au0.3Ag0.7 nanoparticles under CO2‐to‐methanol hydrogenation conditions (230 °C, 20 bar, CO2:H2=1 : 3). These nanoparticles, with metal loading of 0.96–10 μg cm−2, demonstrated stability and resistance to sintering upon activation in H2 at 120 °C and catalytic conditions, revealed by in situ XAS. The promising results from our work will help bridge the gap in the investigation of model catalytic materials produced by gas‐phase cluster deposition at industrially relevant pressures and temperatures, which is vital for a mechanistic understanding of catalytic processes. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are vesicular structures comprised of a bilayer lipid membrane, released by living cells. There is a growing body of evidence for their functionality, indicating that small EVs (sEVs) can mediate specific forms of intercellular communication. The future applications of sEVs hold great promise, not only as diagnostic markers but also as therapeutic agents. However, the greatest difficulty in the clinical translation of sEVs is that they are currently poorly understood, especially concerning their in vivo behaviour. In this study, we provide a novel method for monitoring sEVs in blood circulation based on in vivo flow cytometry (IVFC). We have demonstrated that the height of the IVFC signal baseline is proportional to the concentration of sEVs. Moreover, we have found out that the peaks in the IVFC signal are generated by the aggregation or cellular uptake of sEVs. In vivo monitoring of sEVs clearance from the blood indicates that PEGylated sEVs have a longer residence time and exhibit less aggregation in circulation compared to non‐PEGylated sEVs. These studies reveal that IVFC enables real‐time in vivo monitoring of circulating sEVs, which can provide valuable insights into the pharmacokinetics and cellular targeting capabilities of sEVs. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are lipid nanoparticles and play an important role in cell‐cell communications, making them potential therapeutic agents and allowing to engineer for targeted drug delivery. The expanding applications of EVs in next generation medicine is still limited by existing tools for scaling standardized EV production, single EV tracing and analytics, and thus provide only a snapshot of tissue‐specific EV cargo information. Here, we present the Snorkel‐tag, for which we have genetically fused the EV surface marker protein CD81, to a series of tags with an additional transmembrane domain to be displayed on the EV surface, resembling a snorkel. This system enables the affinity purification of EVs from complex matrices in a non‐destructive form while maintaining EV characteristics in terms of surface protein profiles, associated miRNA patterns and uptake into a model cell line. Therefore, we consider the Snorkel‐tag to be a widely applicable tool in EV research, allowing for efficient preparation of EV standards and reference materials, or dissecting EVs with different surface markers when fusing to other tetraspanins in vitro or in vivo. [ABSTRACT FROM AUTHOR]

Background/Objectives: Rare diseases are a wide and heterogeneous group of multisystem life-threatening or chronically debilitating clinical conditions with reduced life expectancy and a relevant mortality rate in childhood. Some of these disorders have typical neurological symptoms, presenting from birth to adulthood. Dietary patterns and nutritional compounds play key roles in the onset and progression of neurological disorders, and the impact of alimentary needs must be enlightened especially in rare neurological diseases. This work aims to collect the in vitro, in vivo, and clinical evidence on the effects of diet and of nutrient intake on some rare neurological disorders, including some genetic diseases, and rare brain tumors. Herein, those aspects are critically linked to the genetic, biological, biochemical, and pathophysiological hallmarks typical of each disorder. Methods: By searching the major web-based databases (PubMed, Web of Science Core Collection, DynaMed, and Clinicaltrials.gov), we try to sum up and improve our understanding of the emerging role of nutrition as both first-line therapy and risk factors in rare neurological diseases. Results: In line with the increasing number of consensus opinions suggesting that nutrients should receive the same attention as pharmacological treatments, the results of this work pointed out that a standard dietary recommendation in a specific rare disease is often limited by the heterogeneity of occurrent genetic mutations and by the variability of pathophysiological manifestation. Conclusions: In conclusion, we hope that the knowledge gaps identified here may inspire further research for a better evaluation of molecular mechanisms and long-term effects. [ABSTRACT FROM AUTHOR]

In plants, development of all above-ground tissues relies on the shoot apical meristem (SAM) which balances cell proliferation and differentiation to allow life-long growth. To maximize fitness and survival, meristem activity is adjusted to the prevailing conditions through a poorly understood integration of developmental signals with environmental and nutritional information. Here, we show that sugar signals influence SAM function by altering the protein levels of SHOOT MERISTEMLESS (STM), a key regulator of meristem maintenance. STM is less abundant in inflorescence meristems with lower sugar content, resulting from plants being grown or treated under limiting light conditions. Additionally, sucrose but not light is sufficient to sustain STM accumulation in excised inflorescences. Plants overexpressing the α1-subunit of SUCROSE-NON-FERMENTING1-RELATED KINASE 1 (SnRK1) accumulate less STM protein under optimal light conditions, despite higher sugar accumulation in the meristem. Furthermore, SnRK1α1 interacts physically with STM and inhibits its activity in reporter assays, suggesting that SnRK1 represses STM protein function. Contrasting the absence of growth defects in SnRK1α1 overexpressors, silencing SnRK1α in the SAM leads to meristem dysfunction and severe developmental phenotypes. This is accompanied by reduced STM transcript levels, suggesting indirect effects on STM. Altogether, we demonstrate that sugars promote STM accumulation and that the SnRK1 sugar sensor plays a dual role in the SAM, limiting STM function under unfavorable conditions but being required for overall meristem organization and integrity under favorable conditions. This highlights the importance of sugars and SnRK1 signaling for the proper coordination of meristem activities. [ABSTRACT FROM AUTHOR]

Background: The efficacy of mesenchymal stem cells (MSCs) in treating liver fibrosis has been supported by various clinical studies. However, stem cell transplantation is limited in clinical application due to its low survival rate, low liver implantation rate, and possible carcinogenicity. Recently, there has been increasing interest in the use of MSC-exos due to their widespread availability, low immunogenicity, and non-carcinogenic properties. Numerous studies have demonstrated the potential of MSC-exos in treating liver fibrosis and preventing progression to end-stage liver disease. Objective: This study aimed to systematically investigate the efficacy of MSCexos single administration in the treatment of hepatic fibrosis and the combined advantages of MSC-exos in combination with drug therapy (MSC-exos-drugs). Methods: Data sources included PubMed, Web of Science, Embase, and the Cochrane Library, which were built up to January 2024. The population, intervention, comparison, outcomes, and study design (PICOS) principle was used to screen the literature, and the quality of the literature was evaluated to assess the risk of bias. Finally, the data from each study's outcome indicators were extracted for a combined analysis. Results: After screening, a total of 18 papers (19 studies) were included, of which 12 involved MSC-exos single administration for the treatment of liver fibrosis and 6 involved MSC-exos-drugs for the treatment of liver fibrosis. Pooled analysis revealed that MSC-exos significantly improved liver function, promoted the repair of damaged liver tissue, and slowed the progression of hepatic fibrosis and that MSC-exos-drugs were more efficacious than MSC-exos single administration. Subgroup analyses revealed that the use of AD-MSC-exos resulted in more consistent and significant efficacy when MSC-exos was used to treat hepatic fibrosis. For MSC-exos-drugs, a more stable end result is obtained by kit extraction. Similarly, infusion through the abdominal cavity is more effective. Conclusion: The results suggest that MSC-exos can effectively treat liver fibrosis and that MSC-exos-drugs are more effective than MSC-exos single administration. Although the results of the subgroup analyses provide recommendations for clinical treatment, a large number of high-quality experimental validations are still needed. [ABSTRACT FROM AUTHOR]

Recovery from sepsis is a key global health issue, impacting 38 million sepsis survivors worldwide per year. Sepsis survivors face a wide range of physical, cognitive, and psychosocial sequelae. Readmissions to hospital following sepsis are an important driver of global healthcare utilization and cost. Family members of sepsis survivors also experience significant stressors related to their role as informal caregivers. Increasing recognition of the burdens of sepsis survivorship has led to the development of postsepsis recovery programs to better support survivors and their families, although optimal models of care remain uncertain. The goal of this article is to perform a narrative review of recovery from sepsis from the perspective of patients, families, and health systems. [ABSTRACT FROM AUTHOR]

The existence of cortical columns, regarded as computational units underlying both lower and higher-order information processing, has long been associated with highly evolved brains, and previous studies suggested their absence in rodents. However, recent discoveries have unveiled the presence of ocular dominance columns (ODCs) in the primary visual cortex (V1) of Long-Evans rats. These domains exhibit continuity from layer 2 through layer 6, confirming their identity as genuine ODCs. Notably, ODCs are also observed in Brown Norway rats, a strain closely related to wild rats, suggesting the physiological relevance of ODCs in natural survival contexts, although they are lacking in albino rats. This discovery has enabled researchers to explore the development and plasticity of cortical columns using a multidisciplinary approach, leveraging studies involving hundreds of individuals--an endeavor challenging in carnivore and primate species. Notably, developmental trajectories differ depending on the aspect under examination: while the distribution of geniculo-cortical afferent terminals indicates matured ODCs even before eye-opening, consistent with prevailing theories in carnivore/primate studies, examination of cortical neuron spiking activities reveals immature ODCs until postnatal day 35, suggesting delayed maturation of functional synapses which is dependent on visual experience. This developmental gap might be recognized as 'critical period' for ocular dominance plasticity in previous studies. In this article, I summarize crossspecies differences in ODCs and geniculo-cortical network, followed by a discussion on the development, plasticity, and evolutionary significance of rat ODCs. I discuss classical and recent studies on critical period plasticity in the venue where critical period plasticity might be a component of experiencedependent development. Consequently, this series of studies prompts a paradigm shift in our understanding of species conservation of cortical columns and the nature of plasticity during the classical critical period. [ABSTRACT FROM AUTHOR]

Recent developments in the synthesis of hybrid organic-inorganic halide perovskite quantum dots (HP-QDs) through compositional adjustments have highlighted their potential applications in the fields of photovoltaics and light sources due to their unique optoelectronic properties. However, traditional methods to fine-tune their composition involve repetitive, labor-intensive, and costly processes. Herein, the utilization of a continuous flow chemistry approach is developed, in combination with a Proportional-Integral (PI) feedback control system as an effective method for producing on-demand methylammonium lead bromoiodide (MAPbBr x I 3-x ) HP-QDs. The PI feedback control allows for real-time optimization of the flow rates of halide precursor solutions (halide PSs), enabling the precise tuning of the emission wavelength of HP-QDs. HP-QDs having an emission wavelength of 550 and 650 nm are synthesized through a blue-shifted and red-shifted algorithm, respectively, from any arbitrary reaction condition within 400 s. The iterative process through the PI feedback control produces the target HP-QDs with short rise time and low overshoot. The proposed automatic flow chemistry system integrated with a universal and accessible control algorithm of PI can generate the target HP-QDs with high accuracy, stability, and robustness, demonstrating a significant advancement in constructing an autonomous flow chemistry synthetic system., (© 2024 Wiley‐VCH GmbH.)

Small extracellular vesicles (sEVs) are membranous vesicles released from cellular structures through plasma membrane budding. These vesicles contain cellular components such as proteins, lipids, mRNAs, microRNAs, long-noncoding RNA, circular RNA, and double-stranded DNA, originating from the cells they are shed from. Ranging in size from ≈25 to 300 nm and play critical roles in facilitating cell-to-cell communication by transporting signaling molecules. The discovery of sEVs in bodily fluids and their involvement in intercellular communication has revolutionized the fields of diagnosis, prognosis, and treatment, particularly in diseases like cancer. Conventional methods for isolating and analyzing sEVs, particularly their nucleic acid content face challenges including high costs, low purity, time-consuming processes, limited standardization, and inconsistent yield. The development of microfluidic devices, enables improved precision in sorting, isolating, and molecular-level separation using small sample volumes, and offers significant potential for the enhanced detection and monitoring of sEVs associated with cancer. These advanced techniques hold great promise for creating next-generation diagnostic and prognostic tools given their possibility of being cost-effective, simple to operate, etc. This comprehensive review explores the current state of research on microfluidic devices for the detection of sEV-derived nucleic acids as biomarkers and their translation into practical point-of-care and clinical applications., (© 2024 Wiley‐VCH GmbH.)

Green hydrogen (H 2 ) is an essential component of global plans to reduce carbon emissions from hard-to-abate industries and heavy transport. However, challenges remain in the highly efficient H 2 production from water electrolysis powered by renewable energies. The sluggish oxygen evolution restrains the H 2 production from water splitting. Rational electrocatalyst designs for highly efficient H 2 production and oxygen evolution are pivotal for water electrolysis. With the development of high-performance electrolyzers, the scale-up of H 2 production to an industrial-level related activity can be achieved. This review summarizes recent advances in water electrolysis such as the proton exchange membrane water electrolyzer (PEMWE) and anion exchange membrane water electrolyzer (AEMWE). The critical challenges for PEMWE and AEMWE are the high cost of noble-metal catalysts and their durability, respectively. This review highlights the anode and cathode designs for improving the catalytic performance of electrocatalysts, the electrolyte and membrane engineering for membrane electrode assembly (MEA) optimizations, and stack systems for the most promising electrolyzers in water electrolysis. Besides, the advantages of integrating water electrolyzers, fuel cells (FC), and regenerative fuel cells (RFC) into the hydrogen ecosystem are introduced. Finally, the perspective of electrolyzer designs with superior performance is presented., (© 2024 The Author(s). Small Methods published by Wiley‐VCH GmbH.)

During the first and second stages of postnatal development, neocortical neurons exhibit a wide range of spontaneous synchronous activity (SSA). Towards the end of the second postnatal week, the SSA is replaced by a more sparse and desynchronized firing pattern. The developmental desynchronization of neocortical spontaneous neuronal activity is thought to be intrinsically generated, since sensory deprivation from the periphery does not affect the time course of this transition. The extracellular protein reelin controls various aspects of neuronal development through multimodular signaling. However, so far it is unclear whether reelin contributes to the developmental desynchronization transition of neocortical neurons. The present study aims to investigate the role of reelin in postnatal cortical developmental desynchronization using a conditional reelin knockout (RelncKO) mouse model. Conditional reelin deficiency was induced during early postnatal development, and Ca2+ recordings were conducted from organotypic cultures (OTCs) of the somatosensory cortex. Our results show that both wild type (wt) and RelncKO exhibited an SSA pattern during the early postnatal week. However, at the end of the second postnatal week, wt OTCs underwent a transition to a desynchronized network activity pattern, while RelncKO activity remained synchronous. This changing activity pattern suggests that reelin is involved in regulating the developmental desynchronization of cortical neuronal network activity. Moreover, the developmental desynchronization impairment observed in RelncKO was rescued when RelncKO OTCs were co-cultured with wt OTCs. Finally, we show that the developmental transition to a desynchronized state at the end of the second postnatal week is not dependent on glutamatergic signaling. Instead, the transition is dependent on GABAAR and GABABR signaling. The results suggest that reelin controls developmental desynchronization through GABAAR and GABABR signaling. [ABSTRACT FROM AUTHOR]

Compared to well-developed catalytic 1,2-diazidation of alkenes to produce vicinal diazides, the corresponding catalytic 1,1-diazidation of alkenes to yield geminal diazides has not been realized. Here we report an efficient approach for catalytic 1,1-diazidation of alkenes by redox-active selenium catalysis. Under mild conditions, electron-rich aryl alkenes with Z or E or Z/E mixed configuration can undergo migratory 1,1-diazidation to give a series of functionalized monoalkyl or dialkyl geminal diazides that are difficult to access by other methods. The method is also effective for the construction of polydiazides. The formed diazides are relatively safe by TGA-DSC analysis and impact sensitivity tests, and can be easily converted into various valuable molecules. In addition, interesting reactivity that geminal diazides give valuable molecules via the geminal diazidomethyl moiety as a formal leaving group in the presence of Lewis acid is disclosed. Mechanistic studies revealed that a selenenylation-deselenenylation followed by 1,2-aryl migration process is involved in the reactions, which provides a basis for the design of new reactions. [ABSTRACT FROM AUTHOR]

Over the past two decades, advances in droplet-based microfluidics have facilitated new approaches to process and analyze samples with unprecedented levels of precision and throughput. A wide variety of applications has been inspired across multiple disciplines ranging from materials science to biology. Understanding the dynamics of droplets enables optimization of microfluidic operations and design of new techniques tailored to emerging demands. In this review, we discuss the underlying physics behind high-throughput generation and manipulation of droplets. We also summarize the applications in droplet-derived materials and droplet-based lab-on-a-chip biotechnology. In addition, we offer perspectives on future directions to realize wider use of droplet microfluidics in industrial production and biomedical analyses. [ABSTRACT FROM AUTHOR]

This investigation aims to synthesize, analyze the molecularity, and test the ability of bacterial inhibition capability of silver nanoparticles that have been synthesized by simply mixing silver nitrate and aqueous extracts of marine natural products with and without the addition of amylum as a stabilizing agent. This research, with and without the addition of amylum as a stabilizing agent, obtained 39.0 and 55.2 mg of solids of round-shaped morphology silver nanoparticles with diameters of 87.9 and 103.0 nm., respectively. In addition, the antibacterial testing assay against Staphylococcus aureus and Escherichia coli showed some considerably good results. S. aureus with the addition of amylum had inhibition zone diameters of 8.55 and 7.45 mm, whereas without the addition of amylum had inhibition zone diameters of 7.82 and 7.22 mm. E. coli with the addition of amylum had inhibition zone diameters of 7.0 and 7.65 mm, whereas E. coli without the addition of amylum had inhibition zone diameters of 7.82 and 7.22 mm. [ABSTRACT FROM AUTHOR]

Aims and objectives: To explore emotional, mental health and physical symptoms up to 3 months after discharge for adults hospitalized with COVID‐19. Background: 10%–30% of adults with COVID‐19 experience physical and psychological symptoms 3 months or more following infection. Knowing symptoms can help direct early intervention. Design: A longitudinal descriptive design to study COVID‐related symptoms 2 weeks, 6 weeks and 3 months after hospitalization. Methods: Sixty‐six patients were recruited from a hospital system in Midwestern US (October 2020–May 2021). Participants self‐reported demographics, hospital and post discharge symptoms, PROMIS measures (depression, anxiety, fatigue, cognitive function, satisfaction social roles, sleep disturbance) and Impact of Event Scale‐Revised (IES‐R). Hospital length of stay, comorbidities, lowest oxygen saturation, respiratory support and resources used were collected. Descriptive and nonparametric statistics described the sample and identified correlations between variables. The STROBE checklist was used. Results: Data from 1 (T1) and 3 months (T2) post discharge were analysed (N = 52). A majority were female, white and married; 96% experienced ≥1 COVID‐related symptoms at T1; 85% at T2. Fatigue was most prevalent, followed by shortness of breath, muscle weakness and foggy thinking. More physical symptoms during hospitalization correlated positively with number of symptoms at T1 and T2; a majority stated these impacted their normal routine 'somewhat' or 'a lot'. T1 depression highly correlated with all T2 PROMIS and IES‐R scores and number of physical symptoms. More symptoms at T1 were associated with worse fatigue, lower cognitive function and lower satisfaction with social roles at T2. Conclusion: This study adds to the growing knowledge of mental, physical and emotional symptoms and relationships between these early after hospitalization with COVID‐19. Relevance to clinical practice: Findings can help identify holistic nursing interventions to improve health and mitigate symptoms for people with long COVID. Patient or public contribution: Patients contributed via study participation. [ABSTRACT FROM AUTHOR]

Aims and Objectives: The aim of this study was to investigate the prevalence of post‐traumatic stress symptoms, and to identify possible predictive factors in Norwegian intensive care unit survivors, 6 months after admission to the intensive care unit with COVID‐19. Background: The SARS CoV‐2 virus causing COVID‐19 has spread worldwide since it was declared a pandemic in March 2020. The most severely ill patients have been treated in the intensive care due to acute respiratory failure and also acute respiratory distress syndrome. It is well documented that these severe conditions can lead to complex and long‐lasting symptoms, such as psychological distress, and was, therefore, investigated for the specific COVID‐19 population. Design: Prospective observational study. Methods: Clinical data and patient reported outcome measures were collected by the Norwegian Intensive Care and Pandemic Registry and by the study group 6 months after admission to an intensive care unit. Results: Among 222 COVID‐19 patients admitted to Norwegian intensive care units between 10 March and 6 July 2020, 175 survived. The study sample consisted of 131 patients who responded to at least one patient reported outcome measure at 6 months following admission. The primary outcome was self‐reported post‐traumatic stress symptoms, using the Impact of Event Scale‐6 (n = 89). Of those, 22.5% reported post‐traumatic stress symptoms 6 months after admission. Female gender, younger age and having a high respiratory rate at admission were statistically significant predictive factors for reporting post‐traumatic stress symptoms. Conclusions: The result is in accordance with previously published research with comparable populations, suggesting that for many COVID‐19 survivors psychological distress is a part of the post‐acute sequelae. Results from the present study should be replicated in larger datasets. Relevance to Clinical Practice: This project provides important insight to post‐acute sequelae after COVID‐19 that patients may experience after critical illness. [ABSTRACT FROM AUTHOR]

Mixing within micro- and millichannels is a pivotal element across various applications, ranging from chemical synthesis to biomedical diagnostics and environmental monitoring. The inherent low Reynolds number flow in these channels often results in a parabolic velocity profile, leading to a broad residence time distribution. Achieving efficient mixing at such small scales presents unique challenges and opportunities. This review encompasses various techniques and strategies to evaluate and enhance mixing efficiency in these confined environments. It explores the significance of mixing in micro- and millichannels, highlighting its relevance for enhanced reaction kinetics, homogeneity in mixed fluids, and analytical accuracy. We discuss various mixing methodologies that have been employed to get a narrower residence time distribution. The role of channel geometry, flow conditions, and mixing mechanisms in influencing the mixing performance are also discussed. Various emerging technologies and advancements in microfluidic devices and tools specifically designed to enhance mixing efficiency are highlighted. We emphasize the potential applications of micro- and millichannels in fields of nanoparticle synthesis, which can be utilized for biological applications. Additionally, the prospects of machine learning and artificial intelligence are offered toward incorporating better mixing to achieve precise control over nanoparticle synthesis, ultimately enhancing the potential for applications in these miniature fluidic systems. [ABSTRACT FROM AUTHOR]

Copper indium sulfide (CuInS2) is a ternary A(I)B(III)X (VI)2 -type semiconductor featuring a direct bandgap with a high absorption coefficient. In attempts to explore their practical applications, nanoscale CuInS2 has been synthesized with crystal sizes down to the quantum confinement regime. The merits of CuInS2 nanocrystals (NCs) include wide emission tunability, a large Stokes shift, long decay time, and eco-friendliness, making them promising candidates in photoelectronics and photovoltaics. Over the past two decades, advances in wet-chemistry synthesis have achieved rational control over cation–anion reactivity during the preparation of colloidal CuInS2 NCs and post-synthesis cation exchange. The precise nano-synthesis coupled with a series of hybridization strategies has given birth to a library of CuInS2 NCs with highly customizable photophysical properties. This review article focuses on the recent development of CuInS2 NCs enabled by advanced synthetic and hybridization techniques. We show that the state-of-the-art CuInS2 NCs play significant roles in optoelectronic and biomedical applications. [ABSTRACT FROM AUTHOR]

Purpose: To test the hypothesis that rod photoreceptor mitochondria function in vivo progressively declines over time. Methods: 2, 12, and 24 month-old dark- and light-adapted C57BL/6J (B6J) mice were examined by OCT. We measured (i) an index of mitochondrial configuration within photoreceptors measured from the profile shape aspect ratio (MCP/AR) of the hyperreflective band posterior to the external limiting membrane (ELM), (ii) a proxy for energy-dependent pH-triggered water removal, the thickness of the ELM-retinal pigment epithelium (ELM-RPE), and its correlate (iii) the hyporeflective band (HB) signal intensity at the photoreceptor tips. Visual performance was assessed by optokinetic tracking. Results: In 2 and 24 month-old mice, MCP/AR in both inferior and superior retina was smaller in light than in dark; no dark-light differences were noted in 12 month-old mice. Dark-adapted inferior and superior, and light-adapted superior, ELM-RPE thickness increased with age. The dark-light difference in ELM-RPE thickness remained constant across all ages. All ages showed a decreased HB signal intensity magnitude in dark relative to light. In 12 month-old mice, the dark-light difference in HB magnitude was greater than in younger and older mice. Anatomically, outer nuclear layer thickness decreased with age. Visual performance indices were reduced at 24 month-old compared to 2 month-old mice. Conclusion: While the working hypothesis was not supported herein, the results raise the possibility of a mid-life adaptation in rod mitochondrial function during healthy aging in B6J mice based on OCT biomarkers, a plasticity that occurred prior to declines in visual performance. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) can be loaded with therapeutic cargo and engineered for retention by specific body sites; therefore, they have great potential for targeted delivery of biomolecules to treat diseases. However, the pharmacokinetics and biodistribution of EVs in large animals remain relatively unknown, especially in primates. We recently reported that when cell culture‐derived EVs are administered intravenously to Macaca nemestrina (pig‐tailed macaques), they differentially associate with specific subsets of peripheral blood mononuclear cells (PBMCs). More than 60% of CD20+ B cells were observed to associate with EVs for up to 1 h post‐intravenous administration. To investigate these associations further, we developed an ex vivo model of whole blood collected from healthy pig‐tailed macaques. Using this ex vivo system, we found that labelled EVs preferentially associate with B cells in whole blood at levels similar to those detected in vivo. This study demonstrates that ex vivo blood can be used to study EV‐blood cell interactions. [ABSTRACT FROM AUTHOR]

Plant sterols are known for their hypocholesterolemic action, and the molecular mechanisms behind this within the gut have been extensively discussed and demonstrated to the point that there is a degree of consensus. However, recent studies show that these molecules exert an additional umbrella of therapeutic effects in other tissues, which are related to immune function, lipid metabolism, and glucose metabolism. A strong hypothesis to explain these effects is the structural relationship between plant sterols and the ligands of a group of nuclear receptors. This review delves into the molecular aspects of therapeutic effects related with lipid and energy metabolism that have been observed and demonstrated for plant sterols, and turns the perspective to explore the involvement of nuclear receptors as part of these mechanisms., (© 2024 AOCS.)

Synapse formation and stabilization are aided by several families of adhesion molecules, which are generally seen as specialized surface receptors. The function of most surface receptors, including adhesion molecules, is modulated in non-neuronal cells by the processes of endocytosis and recycling, which control the number of active receptors found on the cell surface. These processes have not been investigated extensively at the synapse. This review focuses on the current status of this topic, summarizing general findings on the membrane trafficking of the most prominent synaptic adhesion molecules. Remarkably, evidence for endocytosis processes has been obtained for many synaptic adhesion proteins, including dystroglycans, latrophilins, calsyntenins, netrins, teneurins, neurexins, neuroligins and neuronal pentraxins. Less evidence has been obtained on their recycling, possibly because of the lack of specific assays. We conclude that the trafficking of the synaptic adhesion molecules is an important topic, which should receive more attention in the future., (© 2024 The Author(s). The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Synthetic chemistry is built around the formation of carbon-carbon bonds. However, the development of methods for selective carbon-carbon bond cleavage is a largely unmet challenge 1-6 . Such methods will have promising applications in synthesis, coal liquefaction, petroleum cracking, polymer degradation and biomass conversion. For example, aromatic rings are ubiquitous skeletal features in inert chemical feedstocks, but are inert to many reaction conditions owing to their aromaticity and low polarity. Over the past century, only a few methods under harsh conditions have achieved direct arene-ring modifications involving the cleavage of inert aromatic carbon-carbon bonds 7,8 , and arene-ring-cleavage reactions using stoichiometric transition-metal complexes or enzymes in bacteria are still limited 9-11 . Here we report a copper-catalysed selective arene-ring-opening reaction strategy. Our aerobic oxidative copper catalyst converts anilines, arylboronic acids, aryl azides, aryl halides, aryl triflates, aryl trimethylsiloxanes, aryl hydroxamic acids and aryl diazonium salts into alkenyl nitriles through selective carbon-carbon bond cleavage of arene rings. This chemistry was applied to the modification of polycyclic aromatics and the preparation of industrially important hexamethylenediamine and adipic acid derivatives. Several examples of the late-stage modification of complex molecules and fused ring compounds further support the potential broad utility of this methodology., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Significant progress has been made in recent years in the development of liquid metal alloy catalysts. This article provides an overview of the state‐of‐the‐art research pertaining to liquid metal alloy catalysis, including alloy synthesis, reactor design, and theoretical calculations. Different alloy synthesis methods are discussed with a focus on strategies that can achieve colloidal intermetallic structures in liquid metal alloys. Current reactors for liquid metal‐based electrocatalytic and thermochemical processes are summarized. The application of theoretical tools, such as machine learning and computational chemistry to further liquid metal alloy design, is discussed. Finally, an outlook on the technological challenges and our perspective on future research opportunities for liquid metal alloy catalysis are presented. [ABSTRACT FROM AUTHOR]

Vision is our primary sense, and maintaining it throughout our lifespan is crucial for our well-being. However, the retina, which initiates vision, suffers from an age-related, irreversible functional decline. What causes this functional decline, and how it might be treated, is still unclear. Synapses are the functional hub for signal transmission between neurons, and studies have shown that aging is widely associated with synaptic dysfunction. In this study, we examined the first synapse of the visual system - the rod and cone photoreceptor ribbon synapse - in the mouse retina using light and electron microscopy at 2-3 months, ~1 year, and >2 years of age. We asked, whether age-related changes in key synaptic components might be a driver of synaptic dysfunction and ultimately age-related functional decline during normal aging. We found sprouting of horizontal and bipolar cells, formation of ectopic photoreceptor ribbon synapses, and a decrease in the number of rod photoreceptors and photoreceptor ribbon synapses in the aged retina. However, the majority of the photoreceptors did not show obvious changes in the structural components and protein composition of their ribbon synapses. Noteworthy is the increase in mitochondrial size in rod photoreceptor terminals in the aged retina. [ABSTRACT FROM AUTHOR]

Stroke is one of the most common causes of disability, and there are few treatments that can improve recovery after stroke. Therapeutic development has been hindered because of a lack of understanding of precisely how neural circuits are affected by stroke, and how these circuits change to mediate recovery. Indeed, some of the hypotheses for how the CNS changes to mediate recovery, including remapping, redundancy, and diaschisis, date to more than a century ago. Recent technological advances have enabled the interrogation of neural circuits with ever greater temporal and spatial resolution. These techniques are increasingly being applied across animal models of stroke and to human stroke survivors, and are shedding light on the molecular, structural, and functional changes that neural circuits undergo after stroke. Here we review these studies and highlight important mechanisms that underlie impairment and recovery after stroke. We begin by summarizing knowledge about changes in neural activity that occur in the peri-infarct cortex, specifically considering evidence for the functional remapping hypothesis of recovery. Next, we describe the importance of neural population dynamics, disruptions in these dynamics after stroke, and how allocation of neurons into spared circuits can restore functionality. On a more global scale, we then discuss how effects on long-range pathways, including interhemispheric interactions and corticospinal tract transmission, contribute to post-stroke impairments. Finally, we look forward and consider how a deeper understanding of neural circuit mechanisms of recovery may lead to novel treatments to reduce disability and improve recovery after stroke. [ABSTRACT FROM AUTHOR]

Synaptic density in the central nervous system can be measured in vivo using PET with [18F]SynVesT-1. While [18F]SynVesT-1 has been proven to be a powerful radiopharmaceutical for PET imaging of neurodegenerative disorders such as Parkinson's disease (PD), its currently validated acquisition and quantification protocols are invasive and technically challenging in these populations due to the arterial sampling and relatively long scanning times. The objectives of this work were to evaluate a noninvasive (reference tissue) quantification method for [18F]SynVesT-1 in PD patients and to determine the minimum scan time necessary for accurate quantification. [18F]SynVesT-1 PET scans were acquired in 5 patients with PD and 3 healthy control subjects for 120 min with arterial blood sampling. Quantification was performed using the one-tissue compartment model (1TCM) with arterial input function, as well as with the simplified reference tissue model (SRTM) to estimate binding potential (B P ND ) using centrum semiovale (CS) as a reference region. The SRTM2 method was used with k 2 ′ fixed to either a sample average value (0.037 min-1) or a value estimated first through coupled fitting across regions for each participant. Direct SRTM estimation and the Logan reference region graphical method were also evaluated. There were no significant group differences in CS volume, radiotracer uptake, or efflux (p s > 0.47). Each fitting method produced B P ND estimates in close agreement with those derived from the 1TCM (subject R 2 s > 0.98 , bias < 10 %), with no difference in bias between the control and PD groups. With SRTM2, B P ND estimates from truncated scan data as short as 80 min produced values in excellent agreement with the data from the full 120 min scans (bias < 6 %). While these are preliminary results from a small sample of patients with PD (n = 5), this work suggests that accurate synaptic density quantification may be performed without blood sampling and with scan time under 90 minutes. If further validated, these simplified procedures for [18F]SynVesT-1 PET quantification can facilitate its application as a clinical research imaging technology and allow for larger study samples and include a broader scope of patients including those with neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

An interlude of dark exposure for about 1 week is known to shift excitatory/inhibitory (E/I) balance of the mammalian visual cortex, promoting plasticity and accelerating visual recovery in animals that have experienced cortical lesions during development. However, the translational impact of our understanding of dark exposure from animal studies to humans remains elusive. Here, we used magnetic resonance spectroscopy as a probe for E/I balance in the primary visual cortex (V1) to determine the effect of 60 min of dark exposure, and measured binocular combination as a behavioural assay to assess visual plasticity in 14 normally sighted human adults. To induce neuroplastic changes in the observers, we introduced 60 min of monocular deprivation, which is known to temporarily shift sensory eye balance in favour of the previously deprived eye. We report that prior dark exposure for 60 min strengthens local excitability in V1 and boosts visual plasticity in normal adults. However, we show that it does not promote plasticity in amblyopic adults. Nevertheless, our findings are surprising, given the fact that the interlude is very brief. Interestingly, we find that the increased concentration of the excitatory neurotransmitter is not strongly correlated with the enhanced functional plasticity. Instead, the absolute degree of change in its concentration is related to the boost, suggesting that the dichotomy of cortical excitation and inhibition might not explain the physiological basis of plasticity in humans. We present the first evidence that an environmental manipulation that shifts cortical E/I balance can also act as a metaplastic facilitator for visual plasticity in humans. Key points: A brief interlude (60 min) of dark exposure increased the local concentration of glutamine/glutamate but not that of GABA in the visual cortex of adult humans.After dark exposure, the degree of the shift in sensory eye dominance in favour of the previously deprived eye from short‐term monocular deprivation was larger than that from only monocular deprivation.The neurochemical and behavioural measures were associated: the magnitude of the shift in the concentration of glutamine/glutamate was correlated with the boost in perceptual plasticity after dark exposure.Surprisingly, the increase in the concentration of glutamine/glutamate was not correlated with the perceptual boost after dark exposure, suggesting that the physiological mechanism of how E/I balance regulates plasticity is not deterministic. In other words, an increased excitation did not unilaterally promote plasticity. [ABSTRACT FROM AUTHOR]

Sepsis, defined as the life-threatening dysregulated host response to an infection leading to organ dysfunction, is considered as one of the leading causes of mortality worldwide, especially in intensive care units (ICU). Moreover, sepsis remains an enigmatic clinical syndrome, with complex pathophysiology incompletely understood and a great heterogeneity both in terms of clinical expression, patient response to currently available therapeutic interventions and outcomes. This heterogeneity proves to be a major obstacle in our quest to deliver improved treatment in septic critical care patients; thus, identification of clinical phenotypes is absolutely necessary. Although this might be seen as an extremely difficult task, nowadays, artificial intelligence and machine learning techniques can be recruited to quantify similarities between individuals within sepsis population and differentiate them into distinct phenotypes regarding not only temperature, hemodynamics or type of organ dysfunction, but also fluid status/responsiveness, trajectories in ICU and outcome. Hopefully, we will eventually manage to determine both the subgroup of septic patients that will benefit from a therapeutic intervention and the correct timing of applying the intervention during the disease process. [ABSTRACT FROM AUTHOR]

The remarkable control function over the functional material formation process enabled by droplet microfluidic emulsification approaches can lead to the efficient and one‐step encapsulation of active substances in microparticles, with the microparticle characteristics well regulated. In comparison to the conventional fabrication methods, droplet microfluidic technology can not only construct microparticles with various shapes, but also provide excellent templates, which enrich and expand the application fields of microparticles. For instance, intersection with disciplines in pharmacy, life sciences, and others, modifying the structure of microspheres and appending functional materials can be completed in the preparation of microparticles. The as‐prepared polymer particles have great potential in a wide range of applications for chemical analysis, heavy metal adsorption, and detection. This review systematically introduces the devices and basic principles of particle preparation using droplet microfluidic technology and discusses the research of functional microparticle formation with high monodispersity, involving a plethora of types including spherical, nonspherical, and Janus type, as well as core–shell, hole–shell, and controllable multicompartment particles. Moreover, this review paper also exhibits a critical analysis of the current status and existing challenges, and outlook of the future development in the emerging fields has been discussed. [ABSTRACT FROM AUTHOR]

Neurons decline in their functionality over time, and age‐related neuronal alterations are associated with phenotypes of neurodegenerative diseases. In nonneural tissues, an infolded nuclear shape has been proposed as a hallmark of aged cells and neurons with infolded nuclei have also been reported to be associated with neuronal activity. Here, we performed time‐lapse imaging in the visual cortex of Nex‐Cre;SUN1‐GFP mice. Nuclear infolding was observed within 10 min of stimulation in young nuclei, while the aged nuclei were already infolded pre‐stimulation and showed reduced dynamics of the morphology. In young nuclei, the depletion of the stimuli restored the nucleus to a spherical shape and reduced the dynamic behavior, suggesting that nuclear infolding is a reversible process. We also found the aged nucleus to be stiffer than the young one, further relating to the age‐associated loss of nuclear shape dynamics. We reveal temporal changes in the nuclear shape upon external stimulation and observe that these morphological dynamics decrease with age. [ABSTRACT FROM AUTHOR]

The retina and brain share similar neurochemistry and neurodevelopmental origins, with the retina, often viewed as a "window to the brain." With retinal measures of structure and function becoming easier to obtain in clinical populations there is a growing interest in using retinal findings as potential biomarkers for disorders affecting the central nervous system. Functional retinal biomarkers, such as the electroretinogram, show promise in neurological disorders, despite having limitations imposed by the existence of overlapping genetic markers, clinical traits or the effects of medications that may reduce their specificity in some conditions. This narrative review summarizes the principal functional retinal findings in central nervous system disorders and related mouse models and provides a background to the main excitatory and inhibitory retinal neurotransmitters that have been implicated to explain the visual electrophysiological findings. These changes in retinal neurochemistry may contribute to our understanding of these conditions based on the findings of retinal electrophysiological tests such as the flash, pattern, multifocal electroretinograms, and electro-oculogram. It is likely that future applications of signal analysis and machine learning algorithms will offer new insights into the pathophysiology, classification, and progression of these clinical disorders including autism, attention deficit/hyperactivity disorder, bipolar disorder, schizophrenia, depression, Parkinson's, and Alzheimer's disease. New clinical applications of visual electrophysiology to this field may lead to earlier, more accurate diagnoses and better targeted therapeutic interventions benefiting individual patients and clinicians managing these individuals and their families. [ABSTRACT FROM AUTHOR]

Sigma (σ) receptors are a class of unique proteins with two subtypes: the sigma-1 (σ1) receptor which is situated at the mitochondria-associated endoplasmic reticulum (ER) membrane (MAM), and the sigma-2 (σ2) receptor, located in the ER-resident membrane. Increasing evidence indicates the involvement of both σ1 and σ2 receptors in the pathogenesis of Alzheimer's disease (AD), and thus these receptors represent two potentially effective biomarkers for emerging AD therapies. The availability of optimal radioligands for positron emission tomography (PET) neuroimaging of the σ1 and σ2 receptors in humans will provide tools to monitor AD progression and treatment outcomes. In this review, we first summarize the significance of both receptors in the pathophysiology of AD and highlight AD therapeutic strategies related to the σ1 and σ2 receptors. We then survey the potential PET radioligands, with an emphasis on the requirements of optimal radioligands for imaging the σ1 or σ2 receptors in humans. Finally, we discuss current challenges in the development of PET radioligands for the σ1 or σ2 receptors, and the opportunities for neuroimaging to elucidate the σ1 and σ2 receptors as novel biomarkers for early AD diagnosis, and for monitoring of disease progression and AD drug efficacy. [ABSTRACT FROM AUTHOR]