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Unbiased quantitative analysis of macroscopic biological samples demands fast imaging systems capable of maintaining high resolution across large volumes. Here we introduce RAPID (rapid autofocusing via pupil-split image phase detection), a real-time autofocus method applicable in every widefield-based microscope. RAPID-enabled light-sheet microscopy reliably reconstructs intact, cleared mouse brains with subcellular resolution, and allowed us to characterize the three-dimensional (3D) spatial clustering of somatostatin-positive neurons in the whole encephalon, including densely labeled areas. Furthermore, it enabled 3D morphological analysis of microglia across the entire brain. Beyond light-sheet microscopy, we demonstrate that RAPID maintains high image quality in various settings, from in vivo fluorescence imaging to 3D tracking of fast-moving organisms. RAPID thus provides a flexible autofocus solution that is suitable for traditional automated microscopy tasks as well as for quantitative analysis of large biological specimens.RAPID (rapid autofocusing via pupil-split image phase detection) is a sample-agnostic real-time autofocus method for widefield microscopy. RAPID removes most image degradation in large, cleared samples for enhanced quantitative analyses.

Neuroblastoma (NB) is an aggressive pediatric tumor, responsible for 15% of cancer-related deaths in childhood, lacking an effective treatment in its advanced stages. The P2X7 receptor for extracellular ATP was associated to NB cell proliferation and recently emerged as a promoter of tumor engraftment, growth and vascularization. In an effort to identify new therapeutic options for neuroblastoma, we studied the role of P2X7 receptor in NB biology. We first analyzed the effect of P2X7 activation or down-modulation of the main biochemical ways involved in NB progression: the PI3K/Akt/GSK3β/MYCN and the HIF1α/VEGF pathways. In ACN human NB cells, P2X7 stimulation enhanced PI3K/Akt, while decreasing GSK3β activity. In the same model, P2X7 silencing or antagonist administration reduced the activity of PI3K/Akt and increased that of GSK3β, leading to a decrease in cellular glycogen stores. Similarly, P2X7 downmodulation caused a reduction in HIF1α levels and vascular endothelial growth factor (VEGF) secretion. Systemic administration of two different P2X7 antagonists (AZ10606120 or A740003) in nude/nude mice reduced ACN-derived tumor growth. An even stronger effect of P2X7 blockade was obtained in a syngeneic immune-competent neuroblastoma model: Neuro2A cells injected in AlbinoJ mice. Together with tumor regression, treatment with P2X7 antagonists caused downmodulation of the Akt/HIF1α axis, leading to reduced VEGF content and decreased vessel formation. Interestingly, in both experimental models, P2X7 antagonists strongly reduced the expression of the probably best-accepted oncogene in NB: MYCN . Finally, we associated P2X7 overexpression with poor prognosis in advanced-stage NB patients. Taken together, our data suggest that P2X7 receptor is an upstream regulator of the main signaling pathways involved in NB growth, metabolic activity and angiogenesis, and a promising therapeutic target for neuroblastoma treatment.

There is a growing interest in monitoring muscle oxygen saturation (SmO2), which is a localized measure of muscle oxidative metabolism and can be acquired continuously and noninvasively using near‐infrared spectroscopy (NIRS) methods. Most NIRS systems are cumbersome, expensive, fiber coupled devices, with use limited to lab settings. A novel, low cost, wireless, wearable has been developed for use in athletic training. In this study, we evaluate the advantages and limitations of this new simple continuous‐wave (CW) NIRS device with respect to a benchtop, frequency‐domain near‐infrared spectroscopy (FDNIRS) system. Oxygen saturation and hemoglobin/myoglobin concentration in the exercising muscles of 17 athletic individuals were measured simultaneously with the two systems, while subjects performed an incremental test on a stationary cycle ergometer. In addition, blood lactate concentration was measured at the end of each increment with a lactate analyzer. During exercise, the correlation coefficients of the SmO2 and hemoglobin/myoglobin concentrations between the two systems were over 0.70. We also found both systems were insensitive to the presence of thin layers of varying absorption, mimicking different skin colors. Neither system was able to predict the athletes’ lactate threshold power accurately by simply using SmO2 thresholds. Instead, the proprietary software of the wearable device was able to predict the athletes’ lactate threshold power within half of one power increment of the cycling test. These results indicate this novel wearable device may provide a physiological indicator of athlete's exertion. In this work, we deployed a novel wearable optical technology to monitor oxygenation in exercising muscles of 17 athletes cycling on a stationary ergometer. The results validated the accuracy of a novel wearable sensor against a sophisticated benchtop frequency‐domain near‐infrared spectroscopy system. The wearable was able to predict the lactate threshold power of each athlete with high accuracy. This wearable device holds promise for optimizing athletes’ training regimens.

In this study, we have preformed simultaneous near-infrared spectroscopy (NIRS) along with BOLD (blood oxygen level dependent) and ASL (arterial spin labeling)-based fMRI during an event-related motor activity in human subjects in order to compare the temporal dynamics of the hemodynamic responses recorded in each method. These measurements have allowed us to examine the validity of the biophysical models underlying each modality and, as a result, gain greater insight into the hemodynamic responses to neuronal activation. Although prior studies have examined the relationships between these two methodologies through similar experiments, they have produced conflicting results in the literature for a variety of reasons. Here, by employing a short-duration, event-related motor task, we have been able to emphasize the subtle temporal differences between the hemodynamic parameters with a high contrast-to-noise ratio. As a result of this improved experimental design, we are able to report that the fMRI measured BOLD response is more correlated with the NIRS measure of deoxy-hemoglobin ( R = 0.98; P < 10 −20) than with oxy-hemoglobin ( R = 0.71), or total hemoglobin ( R = 0.53). This result was predicted from the theoretical grounds of the BOLD response and is in agreement with several previous works [Toronov, V.A.W., Choi, J.H., Wolf, M., Michalos, A., Gratton, E., Hueber, D., 2001. “Investigation of human brain hemodynamics by simultaneous near-infrared spectroscopy and functional magnetic resonance imaging.” Med. Phys. 28 (4) 521–527.; MacIntosh, B.J., Klassen, L.M., Menon, R.S., 2003. “Transient hemodynamics during a breath hold challenge in a two part functional imaging study with simultaneous near-infrared spectroscopy in adult humans”. NeuroImage 20 1246–1252.; Toronov, V.A.W., Walker, S., Gupta, R., Choi, J.H., Gratton, E., Hueber, D., Webb, A., 2003. “The roles of changes in deoxyhemoglobin concentration and regional cerebral blood volume in the fMRI BOLD signal“ Neuroimage 19 (4) 1521–1531]. These data have also allowed us to examine more detailed measurement models of the fMRI signal and comment on the roles of the oxygen saturation and blood volume contributions to the BOLD response. In addition, we found high correlation between the NIRS measured total hemoglobin and ASL measured cerebral blood flow ( R = 0.91; P < 10 −10) and oxy-hemoglobin with flow ( R = 0.83; P < 10 −05) as predicted by the biophysical models. Finally, we note a significant amount of cross-modality, correlated, inter-subject variability in amplitude change and time-to-peak of the hemodynamic response. The observed co-variance in these parameters between subjects is in agreement with hemodynamic models and provides further support that fMRI and NIRS have similar vascular sensitivity.

AbstractObjectiveTo assess the effects of food supplementation on improving working memory and additional measures including cerebral blood flow in children at risk of undernutrition.DesignRandomized controlled trial.Setting10 villages in Guinea-Bissau.Participants1059 children aged 15 months to 7 years; children younger than 4 were the primary population.InterventionsSupervised isocaloric servings (≈1300 kJ, five mornings each week, 23 weeks) of a new food supplement (NEWSUP, high in plant polyphenols and omega 3 fatty acids, within a wide variety and high fortification of micronutrients, and a high protein content), or a fortified blended food (FBF) used in nutrition programs, or a control meal (traditional rice breakfast).Main outcome measurementsThe primary outcome was working memory, a core executive function predicting long term academic achievement. Additional outcomes were hemoglobin concentration, growth, body composition, and index of cerebral blood flow (CBFi). In addition to an intention-to-treat analysis, a predefined per protocol analysis was conducted in children who consumed at least 75% of the supplement (820/925, 89%). The primary outcome was assessed by a multivariable Poisson model; other outcomes were assessed by multivariable linear mixed models.ResultsAmong children younger than 4, randomization to NEWSUP increased working memory compared with the control meal (rate ratio 1.20, 95% confidence interval 1.02 to 1.41, P=0.03), with a larger effect in the per protocol population (1.25, 1.06 to 1.47, P=0.009). NEWSUP also increased hemoglobin concentration among children with anemia (adjusted mean difference 0.65 g/dL, 95% confidence interval 0.23 to 1.07, P=0.003) compared with the control meal, decreased body mass index z score gain (−0.23, −0.43 to −0.02, P=0.03), and increased lean tissue accretion (2.98 cm2, 0.04 to 5.92, P=0.046) with less fat (−5.82 cm2, −11.28 to −0.36, P=0.04) compared with FBF. Additionally, NEWSUP increased CBFi compared with the control meal and FBF in both age groups combined (1.14 mm2/s×10−8, 0.10 to 2.23, P=0.04 for both comparisons). Among children aged 4 and older, NEWSUP had no significant effect on working memory or anemia, but increased lean tissue compared with FBF (4.31 cm2, 0.34 to 8.28, P=0.03).ConclusionsChildhood undernutrition is associated with long term impairment in cognition. Contrary to current understanding, supplementary feeding for 23 weeks could improve executive function, brain health, and nutritional status in vulnerable young children living in low income countries. Further research is needed to optimize nutritional prescriptions for regenerative improvements in cognitive function, and to test effectiveness in other vulnerable groups.Trial registrationClinicalTrials.gov NCT03017209.

The neonatal brain is extremely vulnerable to injury during periods of hypoxia and/or ischemia. Risk of brain injury is increased during neonatal cardiac surgery, where pre-existing hemodynamic instability and metabolic abnormalities are combined with long periods of low cerebral blood flow and/or circulatory arrest. Our understanding of events associated with cerebral hypoxia-ischemia during cardiopulmonary bypass (CPB) remains limited, largely due to inadequate tools to quantify cerebral oxygen delivery and consumption non-invasively and in real-time. This pilot study aims to evaluate cerebral blood flow (CBF) and oxygen metabolism (CMRO 2 ) intraoperatively in neonates by combining two novel non-invasive optical techniques: frequency-domain near-infrared spectroscopy (FD-NIRS) and diffuse correlation spectroscopy (DCS). CBF and CMRO 2 were quantified before, during and after deep hypothermic cardiopulmonary bypass (CPB) in nine neonates. Our results show significantly decreased CBF and CMRO 2 during hypothermic CPB. More interestingly, a change of coupling between both variables is observed during deep hypothermic CPB in all subjects. Our results are consistent with previous studies using invasive techniques, supporting the concept of FD-NIRS/DCS as a promising technology to monitor cerebral physiology in neonates providing the potential for individual optimization of surgical management.

Individuals often lack field-based tools to monitor exercise effectiveness. New sensing methods may allow for an improved measurement of the individualized response to exercise by monitoring oxygen kinetics directly in muscle tissue. This study aimed to validate a non-invasive wearable sensor capable of measuring muscle oxygen saturation (SmO2) using continuous-wave near-infrared spectroscopy (CW-NIRS) against a laboratory-validated frequency-domain NIRS (FDNIRS) device. Ten physically fit adults performed an incremental cycling test until voluntary exhaustion. Devices were placed on contralateral rectus femoris muscles. SmO2 was simultaneously measured continuously for the duration of the protocol. Time series alignment was performed using linear interpolation to enable direct comparison between devices at matched time points. Z-score normalization accounted for inter-individual differences in a group-level analysis. Individual subject validation showed strong correlations between the two devices (r = 0.792, range: 0.69–0.88, p < 0.001) with an RMSD < 5% for most subjects, a mean bias of 0.005 and low proportional bias (−0.199) between all paired measurements. Group-level analysis demonstrated a correlation of r = 0.788. Bland–Altman analysis revealed that 95% of all measurements fell between −8.1% and 7.6% SmO2. The CW-NIRS device delivered reliable performance compared to the FDNIRS device, offering potential applications for real-time physiological monitoring during exercise and performance assessment.

Observations at submillimetre and X-ray wavelengths show that rapid star formation was common in the host galaxies of active galactic nuclei when the Universe was 2–6 Gyr old, but that the most vigorous star formation is not observed around powerful black holes, thereby confirming a key prediction of models in which an active galactic nucleus expels the interstellar medium of its host galaxy. Star formation blocked by powerful black holes Radiation from active galactic nuclei (AGNs) outshines that produced by star formation at most wavelengths, but in the far-infrared to millimetre waveband AGNs emit comparatively little radiation in comparison with strongly star-forming galaxies. A combination of deep X-ray observations from the Chandra catalogue and submillimetre observations from the SPIRE instrument on the Herschel Space Observatory shows that rapid star formation was common in the host galaxies of AGNs when the Universe was between two billion and six billion years old, but that vigorous star formation is not seen around the more luminous black holes. This suppression of star formation in galaxies that host a powerful AGN is a key prediction of models in which the AGN expels the interstellar medium of its host galaxy when it becomes sufficiently powerful. The old, red stars that constitute the bulges of galaxies, and the massive black holes at their centres, are the relics of a period in cosmic history when galaxies formed stars at remarkable rates and active galactic nuclei (AGN) shone brightly as a result of accretion onto black holes. It is widely suspected, but unproved, that the tight correlation between the mass of the black hole and the mass of the stellar bulge 1 results from the AGN quenching the surrounding star formation as it approaches its peak luminosity 2 , 3 , 4 . X-rays trace emission from AGN unambiguously 5 , whereas powerful star-forming galaxies are usually dust-obscured and are brightest at infrared and submillimetre wavelengths 6 . Here we report submillimetre and X-ray observations that show that rapid star formation was common in the host galaxies of AGN when the Universe was 2–6 billion years old, but that the most vigorous star formation is not observed around black holes above an X-ray luminosity of 10 44 ergs per second. This suppression of star formation in the host galaxy of a powerful AGN is a key prediction of models in which the AGN drives an outflow 7 , 8 , 9 , expelling the interstellar medium of its host and transforming the galaxy’s properties in a brief period of cosmic time.

We present the Spitzer Extragalactic Representative Volume Survey (SERVS), an18 deg2 18     deg 2 medium-deep survey at 3.6 and 4.5 μm with the postcryogenicSpitzer Space Telescopeto≈2 μJy ≈ 2     μ Jy (AB = 23.1 AB = 23.1 ) depth of five highly observed astronomical fields (ELAIS-N1, ELAIS-S1, Lockman Hole, Chandra Deep Field South, and XMM-LSS). SERVS is designed to enable the study of galaxy evolution as a function of environment from z ∼ 5 z ∼ 5 to the present day and is the first extragalactic survey that is both large enough and deep enough to put rare objects such as luminous quasars and galaxy clusters at z ≳ 1 z ≳ 1 into their cosmological context. SERVS is designed to overlap with several key surveys at optical, near- through far-infrared, submillimeter, and radio wavelengths to provide an unprecedented view of the formation and evolution of massive galaxies. In this article, we discuss the SERVS survey design, the data processing flow from image reduction and mosaicking to catalogs, and coverage of ancillary data from other surveys in the SERVS fields. We also highlight a variety of early science results from the survey.

Nickel-based nanostructures are widely investigated as cost-effective alternatives to precious metal catalysts for hydrogen evolution reaction (HER) in alkaline electrolysis. However, controlling the growth of nickel nanoparticles (NiNPs) on conductive substrates remains a challenge for optimizing their catalytic performance. In this study, we explored the controlled growth of NiNPs on two distinct substrates: 316L stainless steel plated with nickel and 316L stainless steel coated with graphene oxide (GO). The NiNPs synthesis involved a simple chemical approach that entailed immersing the substrate plates in a solution containing nickel nitrate, sodium citrate, and sodium borohydride as a reducing agent. Various experimental parameters were examined, including variations in the concentration of Ni2⁺ ions, sequential NiNPs deposition on the surface, and temperature adjustments. Scanning electron microscopy (SEM) images revealed significant differences in the distribution and size of NiNPs. The NiWatts-coated substrate (Ni-SS) exhibited a higher nanoparticle coverage (72 ± 5% surface coverage) and more uniform distribution, while the GO-coated substrate (GO-Ni-SS) presented larger (average diameter: 85 ± 10 nm vs. 45 ± 8 nm for Ni-SS) and more widely dispersed nanoparticles. Preliminary alkaline electrolysis experiments demonstrated that both substrates exhibit excellent electrocatalytic activity for the hydrogen evolution reaction, with Ni-SS achieving a lower overpotential of − 270 ± 5 mV at 10 mA cm⁻2 compared to − 310 ± 7 mV for GO-Ni-SS.