Circuit mechanism for suppression of frontal cortical ignition during NREM sleep.

Conscious perception is greatly diminished during sleep, but the underlying circuit mechanism is poorly understood. We show that cortical ignition-a brain process shown to be associated with conscious awareness in humans and non-human primates-is strongly suppressed during non-rapid-eye-movement (NREM) sleep in mice due to reduced cholinergic modulation and rapid inhibition of cortical responses. Brain-wide functional ultrasound imaging and cell-type-specific calcium imaging combined with optogenetics showed that activity propagation from visual to frontal cortex is markedly reduced during NREM sleep due to strong inhibition of frontal pyramidal neurons. Chemogenetic activation and inactivation of basal forebrain cholinergic neurons powerfully increased and decreased visual-to-frontal activity propagation, respectively. Furthermore, although multiple subtypes of dendrite-targeting GABAergic interneurons in the frontal cortex are more active during wakefulness, soma-targeting parvalbumin-expressing interneurons are more active during sleep. Chemogenetic manipulation of parvalbumin interneurons showed that sleep/wake-dependent cortical ignition is strongly modulated by perisomatic inhibition of pyramidal neurons.

Fe Single Atom Catalysts Promoting Polysulfide Redox Reduction in Quantum Dot Photovoltaics.

Developing cost-effective and highly efficient photocathodes toward polysulfide redox reduction is highly desirable for advanced quantum dot (QD) photovoltaics. Herein, we demonstrate nitrogen doped carbon (N-C) shell-supported iron single atom catalysts (Fe-SACs) capable of catalyzing polysulfide reduction in QD photovoltaics for the first time. Specifically, Fe-SACs with FeN4 active sites feature a power conversion efficiency of 13.7% for ZnCuInSe-QD photovoltaics (AM1.5G, 100 mW/cm2), which is the highest value for ZnCuInSe QD-based photovoltaics, outperforming those of Cu-SACs and N-C catalysts. Compared with N-C, Fe-SACs exhibit suitable energy level matching with polysulfide redox couples, revealed by the Kelvin probe force microscope, which accelerates the charge transferring at the interfaces of catalyst/polysulfide redox couple. Density functional theory calculations demonstrate that the outstanding catalytic activity of Fe-SACs originates from the preferable adsorption of S42- on the FeN4 active sites and the high activation degree of the S-S bonds in S42- initiated by the FeN4 active sites.

Inhibition of impulsive action by projection-defined prefrontal pyramidal neurons.

The prefrontal cortex (PFC) plays a critical role in curbing impulsive behavior, but the underlying circuit mechanism remains incompletely understood. Here we show that a subset of dorsomedial PFC (dmPFC) layer 5 pyramidal neurons, which project to the subthalamic nucleus (STN) of the basal ganglia, play a key role in inhibiting impulsive responses in a go/no-go task. Projection-specific labeling and calcium imaging showed that the great majority of STN-projecting neurons were preferentially active in no-go trials when the mouse successfully withheld licking responses, but lateral hypothalamus (LH)-projecting neurons were more active in go trials with licking; visual cortex (V1)-projecting neurons showed only weak task-related activity. Optogenetic activation and inactivation of STN-projecting neurons reduced and increased inappropriate licking, respectively, partly through their direct innervation of the STN, but manipulating LH-projecting neurons had the opposite effects. These results identify a projection-defined subtype of PFC pyramidal neurons as key mediators of impulse control.

Transient Solid-State Laser Activation of Indium for High-Performance Reduction of CO2 to Formate.

Deficiencies in understanding the local environment of active sites and limited synthetic skills challenge the delivery of industrially-relevant current densities with low overpotentials and high selectivity for CO2 reduction. Here, a transient laser induction of metal salts can stimulate extreme conditions and rapid kinetics to produce defect-rich indium nanoparticles (L-In) is reported. Atomic-resolution microscopy and X-ray absorption disclose the highly defective and undercoordinated local environment in L-In. In a flow cell, L-In shows a very small onset overpotential of ≈92 mV and delivers a current density of ≈360 mA cm-2 with a formate Faradaic efficiency of 98% at a low potential of -0.62 V versus RHE. The formation rate of formate reaches up to 6364.4 µmol h-1mgIn-1$mg_{{\rm{In}}}^{--1}$ , which is nearly 39 folds higher than that of commercial In (160.7 µmol h-1mgIn-1$mg_{{\rm{In}}}^{--1}$ ), outperforming most of the previous results that have been reported under KHCO3 environments. Density function theory calculations suggest that the defects facilitate the formation of *OCHO intermediate and stabilize the *HCOOH while inhibiting hydrogen adsorption. This study suggests that transient solid-state laser induction provides a facile and cost-effective approach to form ligand-free and defect-rich materials with tailored activities.

Speciation Evolution of Phosphorus and Sulfur Derived from Sewage Sludge Biochar in Soil: Ageing Effects.

Phosphorus (P) and sulfur (S) are usually involved simultaneously in the immobilization of heavy metals in sewage sludge during pyrolysis, and thus their speciation in sewage sludge-derived biochar (SSB) profoundly affects the recycling of the nutrients and the environmental risks of sewage sludge. Here, we investigated the speciation evolution of P and S in SSB induced by ageing processes in soil using X-ray absorption near edge structure spectroscopy. Results showed that Ca-bound compounds like hydroxyapatite dominated the P forms, while over 60% of S existed as reduced inorganic sulfides in the SSB. The stable Ca-associated P species in SSB tended to be transformed gradually into relatively soluble species during ageing in soil. The speciation composition of S in SSB remained almost unaffected when aged in pot soils, whereas about 33.6% of reduced sulfides were transformed into oxidized species after 1-year ageing in field soils. SSB significantly increased the proportion of sulfides and the contents of available P and S in the amended soil but showed relatively weak effects on the speciation distribution of P in the soil because of their similar compositions. These findings provide insights into biogeochemistry of nutrients and behaviors of heavy metals in SSB after its application to the soil environments.

SIRT1 suppresses self-renewal of adult hippocampal neural stem cells.

The balance between self-renewal and differentiation of adult neural stem cells (aNSCs) is essential for the maintenance of the aNSC reservoir and the continuous supply of new neurons, but how this balance is fine-tuned in the adult brain is not fully understood. Here, we investigate the role of SIRT1, an important metabolic sensor and epigenetic repressor, in regulating adult hippocampal neurogenesis in mice. We found that there was an increase in SIRT1 expression during aNSC differentiation. In Sirt1 knockout (KO) mice, as well as in brain-specific and inducible stem cell-specific conditional KO mice, the proliferation and self-renewal rates of aNSCs in vivo were elevated. Proliferation and self-renewal rates of aNSCs and adult neural progenitor cells (aNPCs) were also elevated in neurospheres derived from Sirt1 KO mice and were suppressed by the SIRT1 agonist resveratrol in neurospheres from wild-type mice. In cultured neurospheres, 2-deoxy-D-glucose-induced metabolic stress suppressed aNSC/aNPC proliferation, and this effect was mediated in part by elevating SIRT1 activity. Microarray and biochemical analysis of neurospheres suggested an inhibitory effect of SIRT1 on Notch signaling in aNSCs/aNPCs. Inhibition of Notch signaling by a γ-secretase inhibitor also largely abolished the increased aNSC/aNPC proliferation caused by Sirt1 deletion. Together, these findings indicate that SIRT1 is an important regulator of aNSC/aNPC self-renewal and a potential mediator of the effect of metabolic changes.

Characteristics of secondary inorganic aerosol and sulfate species in size-fractionated aerosol particles in Shanghai.

Sulfate, nitrate and ammonium (SNA) are the dominant species in secondary inorganic aerosol, and are considered an important factor in regional haze formation. Size-fractionated aerosol particles for a whole year were collected to study the size distribution of SNA as well as their chemical species in Shanghai. SNA mainly accumulated in fine particles and the highest average ratio of SNA to particulate matter (PM) was observed to be 47% in the fine size fraction (0.49-0.95 µm). Higher sulfur oxidation ratio and nitrogen oxidation ratio values were observed in PM of fine size less than 0.95 µm. Ion balance calculations indicated that more secondary sulfate and nitrate would be generated in PM of fine size (0.49-0.95 µm). Sulfur K-edge X-ray absorption near-edge structure (XANES) spectra of typical samples were analyzed. Results revealed that sulfur mainly existed as sulfate with a proportion (atomic basis) more than 73% in all size of PM and even higher at 90% in fine particles. Sulfate mainly existed as (NH4)2SO4 and gypsum in PM of Shanghai. Compared to non-haze days, a dramatic increase of (NH4)2SO4 content was found in fine particles on haze days only, which suggested the promoting impact of (NH4)2SO4 on haze formation. According to the result of air mass backward trajectory analysis, more (NH4)2SO4 would be generated during the periods of air mass stagnation. Based on XANES, analysis of sulfate species in size-fractionated aerosol particles can be an effective way to evaluate the impact of sulfate aerosols on regional haze formation.

Advances in Hydrogels of Drug Delivery Systems for the Local Treatment of Brain Tumors.

The management of brain tumors presents numerous challenges, despite the employment of multimodal therapies including surgical intervention, radiotherapy, chemotherapy, and immunotherapy. Owing to the distinct location of brain tumors and the presence of the blood-brain barrier (BBB), these tumors exhibit considerable heterogeneity and invasiveness at the histological level. Recent advancements in hydrogel research for the local treatment of brain tumors have sought to overcome the primary challenge of delivering therapeutics past the BBB, thereby ensuring efficient accumulation within brain tumor tissues. This article elaborates on various hydrogel-based delivery vectors, examining their efficacy in the local treatment of brain tumors. Additionally, it reviews the fundamental principles involved in designing intelligent hydrogels that can circumvent the BBB and penetrate larger tumor areas, thereby facilitating precise, controlled drug release. Hydrogel-based drug delivery systems (DDSs) are posited to offer a groundbreaking approach to addressing the challenges and limitations inherent in traditional oncological therapies, which are significantly impeded by the unique structural and pathological characteristics of brain tumors.

Activation of locus coeruleus noradrenergic neurons rapidly drives homeostatic sleep pressure.

Homeostatic sleep regulation is essential for optimizing the amount and timing of sleep, but the underlying mechanism remains unclear. Optogenetic activation of locus coeruleus noradrenergic neurons immediately increased sleep propensity following transient wakefulness. Fiber photometry showed that repeated optogenetic or sensory stimulation caused rapid declines of locus coeruleus calcium activity and noradrenaline release. This suggests that functional fatigue of noradrenergic neurons, which reduces their wake-promoting capacity, contributes to sleep pressure.

A rechargeable Ca/Cl2 battery.

Rechargeable calcium (Ca) metal batteries are promising candidates for sustainable energy storage due to the abundance of Ca in Earth's crust and the advantageous theoretical capacity and voltage of these batteries. However, the development of practical Ca metal batteries has been severely hampered by the current cathode chemistries, which limit the available energy and power densities, as well as their insufficient capacity retention and low-temperature capability. Here, we describe the rechargeable Ca/Cl2 battery based on a reversible cathode redox reaction between CaCl2 and Cl2, which is enabled by the use of lithium difluoro(oxalate)borate as a key electrolyte mediator to facilitate the dissociation and distribution of Cl-based species and Ca2+. Our rechargeable Ca/Cl2 battery can deliver discharge voltages of 3 V and exhibits remarkable specific capacity (1000 mAh g-1) and rate capability (500 mA g-1). In addition, the excellent capacity retention (96.5% after 30 days) and low-temperature capability (down to 0 °C) allow us to overcome the long-standing bottleneck of rechargeable Ca metal batteries.

Microglia regulate sleep through calcium-dependent modulation of norepinephrine transmission.

Sleep interacts reciprocally with immune system activity, but its specific relationship with microglia-the resident immune cells in the brain-remains poorly understood. Here, we show in mice that microglia can regulate sleep through a mechanism involving Gi-coupled GPCRs, intracellular Ca2+ signaling and suppression of norepinephrine transmission. Chemogenetic activation of microglia Gi signaling strongly promoted sleep, whereas pharmacological blockade of Gi-coupled P2Y12 receptors decreased sleep. Two-photon imaging in the cortex showed that P2Y12-Gi activation elevated microglia intracellular Ca2+, and blockade of this Ca2+ elevation largely abolished the Gi-induced sleep increase. Microglia Ca2+ level also increased at natural wake-to-sleep transitions, caused partly by reduced norepinephrine levels. Furthermore, imaging of norepinephrine with its biosensor in the cortex showed that microglia P2Y12-Gi activation significantly reduced norepinephrine levels, partly by increasing the adenosine concentration. These findings indicate that microglia can regulate sleep through reciprocal interactions with norepinephrine transmission.

Sulfur speciation and bioaccumulation in camphor tree leaves as atmospheric sulfur indicator analyzed by synchrotron radiation XRF and XANES.

Analyzing and understanding the effects of ambient pollution on plants is getting more and more attention as a topic of environmental biology. A method based on synchrotron radiation X-ray fluorescence and X-ray absorption near edge structure spectroscopy was established to analyze the sulfur concentration and speciation in mature camphor tree leaves (CTLs), which were sampled from 5 local fields in Shanghai, China. Annual SO2 concentration, SO4(2-) concentration in atmospheric particulate, SO4(2-) and sulfur concentration in soil were also analyzed to explore the relationship between ambient sulfur sources and the sulfur nutrient cycling in CTLs. Total sulfur concentration in mature camphor tree leaves was 766-1704 mg/kg. The mainly detected sulfur states and their corresponding compounds were +6 (sulfate, include inorganic sulfate and organic sulfate), +5.2 (sulfonate), +2.2 (suloxides), +0.6 (thiols and thiothers), +0.2 (organic sulfides). Total sulfur concentration was strongly correlated with sulfate proportion with a linear correlation coefficient up to 0.977, which suggested that sulfur accumulated in CTLs as sulfate form. Reduced sulfur compounds (organic sulfides, thiols, thioethers, sulfoxide and sulfonate) assimilation was sufficed to meet the nutrient requirement for growth at a balanced level around 526 mg/kg. The sulfate accumulation mainly caused by atmospheric sulfur pollution such as SO2 and airborne sulfate particulate instead of soil contamination. From urban to suburb place, sulfate in mature CTLs decreased as the atmospheric sulfur pollution reduced, but a dramatic increase presented near the seashore, where the marine sulfate emission and maritime activity pollution were significant. The sulfur concentration and speciation in mature CTLs effectively represented the long-term biological accumulation of atmospheric sulfur pollution in local environment.

Dopamine release and negative valence gated by inhibitory neurons in the laterodorsal tegmental nucleus.

GABAergic neurons in the laterodorsal tegmental nucleus (LDTGABA) encode aversion by directly inhibiting mesolimbic dopamine (DA). Yet, the detailed cellular and circuit mechanisms by which these cells relay unpleasant stimuli to DA neurons and regulate behavioral output remain largely unclear. Here, we show that LDTGABA neurons bidirectionally respond to rewarding and aversive stimuli in mice. Activation of LDTGABA neurons promotes aversion and reduces DA release in the lateral nucleus accumbens. Furthermore, we identified two molecularly distinct LDTGABA cell populations. Somatostatin-expressing (Sst+) LDTGABA neurons indirectly regulate the mesolimbic DA system by disinhibiting excitatory hypothalamic neurons. In contrast, Reelin-expressing LDTGABA neurons directly inhibit downstream DA neurons. The identification of separate GABAergic subpopulations in a single brainstem nucleus that relay unpleasant stimuli to the mesolimbic DA system through direct and indirect projections is critical for establishing a circuit-level understanding of how negative valence is encoded in the mammalian brain.

Cardiovascular baroreflex circuit moonlights in sleep control.

Sleep disturbances are strongly associated with cardiovascular diseases. Baroreflex, a basic cardiovascular regulation mechanism, is modulated by sleep-wake states. Here, we show that neurons at key stages of baroreflex pathways also promote sleep. Using activity-dependent genetic labeling, we tagged neurons in the nucleus of the solitary tract (NST) activated by blood pressure elevation and confirmed their barosensitivity with optrode recording and calcium imaging. Chemogenetic or optogenetic activation of these neurons promoted non-REM sleep in addition to decreasing blood pressure and heart rate. GABAergic neurons in the caudal ventrolateral medulla (CVLM)-a downstream target of the NST for vasomotor baroreflex-also promote non-REM sleep, partly by inhibiting the sympathoexcitatory and wake-promoting adrenergic neurons in the rostral ventrolateral medulla (RVLM). Cholinergic neurons in the nucleus ambiguous-a target of the NST for cardiac baroreflex-promoted non-REM sleep as well. Thus, key components of the cardiovascular baroreflex circuit are also integral to sleep-wake brain-state regulation.

A common hub for sleep and motor control in the substantia nigra.

The arousal state of the brain covaries with the motor state of the animal. How these state changes are coordinated remains unclear. We discovered that sleep-wake brain states and motor behaviors are coregulated by shared neurons in the substantia nigra pars reticulata (SNr). Analysis of mouse home-cage behavior identified four states with different levels of brain arousal and motor activity: locomotion, nonlocomotor movement, quiet wakefulness, and sleep; transitions occurred not randomly but primarily between neighboring states. The glutamic acid decarboxylase 2 but not the parvalbumin subset of SNr γ-aminobutyric acid (GABA)-releasing (GABAergic) neurons was preferentially active in states of low motor activity and arousal. Their activation or inactivation biased the direction of natural behavioral transitions and promoted or suppressed sleep, respectively. These GABAergic neurons integrate wide-ranging inputs and innervate multiple arousal-promoting and motor-control circuits through extensive collateral projections.

Investigation of elemental sulfur speciation transformation mediated by Acidithiobacillus ferrooxidans.

The speciation transformation of elemental sulfur mediated by the leaching bacterium Acidithiobacillus ferrooxidans was investigated using an integrated approach including scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, energy dispersive X-ray spectroscopy, and X-ray absorption near edge spectroscopy (XANES). Our results showed that when grown on elemental sulfur powder, At. ferrooxidans ATCC23270 cells were first attached to sulfur particles and modified the surface sulfur with some amphiphilic compounds. In addition, part of the elemental sulfur powder might be converted to polysulfides. Furthermore, sulfur globules were accumulated inside the cells. XANES spectra of these cells suggested that these globules consisted of elemental sulfur bound to thiol groups of protein.

Control of Non-REM Sleep by Midbrain Neurotensinergic Neurons.

The periaqueductal gray (PAG) in the midbrain is known to coordinate behavioral and autonomic responses to threat and injury through its descending projections to the brainstem. Here, we show that neurotensin (NTS)-expressing glutamatergic neurons in the ventrolateral PAG (vlPAG) powerfully promote non-rapid eye movement (NREM) sleep partly through their projection to the caudal medulla. Optogenetic and chemogenetic activation of vlPAG NTS neurons strongly enhanced NREM sleep, whereas their inactivation increased wakefulness. Calcium imaging and optrode recording showed that they are preferentially active during NREM sleep. The NREM-promoting effect of vlPAG NTS neurons is partly mediated by their projection to the caudal ventromedial medulla, where they excite GABAergic neurons. Bidirectional optogenetic and chemogenetic manipulations showed that the medullary GABAergic neurons also promote NREM sleep, and they innervate multiple monoaminergic populations. Together, these findings reveal a novel pathway for NREM sleep generation, in which glutamatergic neurons drive broad GABAergic inhibition of wake-promoting neuronal populations.

Sleep Regulation by Neurotensinergic Neurons in a Thalamo-Amygdala Circuit.

A crucial step in understanding the sleep-control mechanism is to identify sleep neurons. Through systematic anatomical screening followed by functional testing, we identified two sleep-promoting neuronal populations along a thalamo-amygdala pathway, both expressing neurotensin (NTS). Rabies-mediated monosynaptic retrograde tracing identified the central nucleus of amygdala (CeA) as a major source of GABAergic inputs to multiple wake-promoting populations; gene profiling revealed NTS as a prominent marker for these CeA neurons. Optogenetic activation and inactivation of NTS-expressing CeA neurons promoted and suppressed non-REM (NREM) sleep, respectively, and optrode recording showed they are sleep active. Further tracing showed that CeA GABAergic NTS neurons are innervated by glutamatergic NTS neurons in a posterior thalamic region, which also promote NREM sleep. CRISPR/Cas9-mediated NTS knockdown in either the thalamic or CeA neurons greatly reduced their sleep-promoting effect. These results reveal a novel thalamo-amygdala circuit for sleep generation in which NTS signaling is essential for both the upstream glutamatergic and downstream GABAergic neurons.

Transcriptome Analysis Highlights Defense and Signaling Pathways Mediated by Rice pi21 Gene with Partial Resistance to Magnaporthe oryzae.

Rice blast disease is one of the most destructive rice diseases worldwide. The pi21 gene confers partial and durable resistance to Magnaporthe oryzae. However, little is known regarding the molecular mechanisms of resistance mediated by the loss-of-function of Pi21. In this study, comparative transcriptome profiling of the Pi21-RNAi transgenic rice line and Nipponbare with M. oryzae infection at different time points (0, 12, 24, 48, and 72 hpi) were investigated using RNA sequencing. The results generated 43,222 unique genes mapped to the rice genome. In total, 1109 differentially expressed genes (DEGs) were identified between the Pi21-RNAi line and Nipponbare with M. oryzae infection, with 103, 281, 209, 69, and 678 DEGs at 0, 12, 24, 48, and 72 hpi, respectively. Functional analysis showed that most of the DEGs were involved in metabolism, transport, signaling, and defense. Among the genes assigned to plant-pathogen interaction, we identified 43 receptor kinase genes associated with pathogen-associated molecular pattern recognition and calcium ion influx. The expression levels of brassinolide-insensitive 1, flagellin sensitive 2, and elongation factor Tu receptor, ethylene (ET) biosynthesis and signaling genes, were higher in the Pi21-RNAi line than Nipponbare. This suggested that there was a more robust PTI response in Pi21-RNAi plants and that ET signaling was important to rice blast resistance. We also identified 53 transcription factor genes, including WRKY, NAC, DOF, and ERF families that show differential expression between the two genotypes. This study highlights possible candidate genes that may serve a function in the partial rice blast resistance mediated by the loss-of-function of Pi21 and increase our understanding of the molecular mechanisms involved in partial resistance against M. oryzae.

Organization of long-range inputs and outputs of frontal cortex for top-down control.

Long-range projections from the frontal cortex are known to modulate sensory processing in multiple modalities. Although the mouse has become an increasingly important animal model for studying the circuit basis of behavior, the functional organization of its frontal cortical long-range connectivity remains poorly characterized. Here we used virus-assisted circuit mapping to identify the brain networks for top-down modulation of visual, somatosensory and auditory processing. The visual cortex is reciprocally connected to the anterior cingulate area, whereas the somatosensory and auditory cortices are connected to the primary and secondary motor cortices. Anterograde and retrograde tracing identified the cortical and subcortical structures belonging to each network. Furthermore, using new viral techniques to target subpopulations of frontal neurons projecting to the visual cortex versus the superior colliculus, we identified two distinct subnetworks within the visual network. These findings provide an anatomical foundation for understanding the brain mechanisms underlying top-down control of behavior.