General anesthesia (GA) can produce analgesia (loss of pain) independent of inducing loss of consciousness, but the underlying mechanisms remain unclear. We hypothesized that GA suppresses pain in ...part by activating supraspinal analgesic circuits. We discovered a distinct population of GABAergic neurons activated by GA in the mouse central amygdala (CeA
neurons). In vivo calcium imaging revealed that different GA drugs activate a shared ensemble of CeA
neurons. CeA
neurons also possess basal activity that mostly reflects animals' internal state rather than external stimuli. Optogenetic activation of CeA
potently suppressed both pain-elicited reflexive and self-recuperating behaviors across sensory modalities and abolished neuropathic pain-induced mechanical (hyper-)sensitivity. Conversely, inhibition of CeA
activity exacerbated pain, produced strong aversion and canceled the analgesic effect of low-dose ketamine. CeA
neurons have widespread inhibitory projections to many affective pain-processing centers. Our study points to CeA
as a potential powerful therapeutic target for alleviating chronic pain.
In vivo calcium imaging using a 1-photon-based miniscope and a microendoscopic lens enables studies of neural activities in freely behaving animals. However, the high and fluctuating background, the ...inevitable movements and distortions of imaging field, and the extensive spatial overlaps of fluorescent signals emitted from imaged neurons inherent in this 1-photon imaging method present major challenges for extracting neuronal signals reliably and automatically from the raw imaging data. Here, we develop a unifying algorithm called the miniscope 1-photon imaging pipeline (MIN1PIPE), which contains several stand-alone modules and can handle a wide range of imaging conditions and qualities with minimal parameter tuning and automatically and accurately isolate spatially localized neural signals. We have quantitatively compared MIN1PIPE with other existing partial methods using both synthetic and real datasets obtained from different animal models and show that MIN1PIPE has superior efficiency and precision in analyzing noisy miniscope calcium imaging data.
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•A generic end-to-end processing pipeline (MIN1PIPE) for 1-photon calcium imaging•A hierarchical motion correction module corrects all types of deformations•A seeds-cleansed signal extraction module automatically extracts shapes and traces•MIN1PIPE removes the parameters unknown a priori but central in other algorithms
Lu et al. develop an end-to-end pipeline (MIN1PIPE) for automatic processing of single-photon calcium imaging data that uses different algorithms for movement correction and signal extraction and outperforms existing methods.
Premotor circuits in the brainstem project to pools of orofacial motoneurons to execute essential motor action such as licking, chewing, breathing, and in rodent, whisking. Previous transsynaptic ...tracing studies only mapped orofacial premotor circuits in neonatal mice, but the adult circuits remain unknown as a consequence of technical difficulties. Here, we developed a three-step monosynaptic transsynaptic tracing strategy to identify premotor neurons controlling vibrissa, tongue protrusion, and jaw-closing muscles in the adult mouse. We registered these different groups of premotor neurons onto the Allen mouse brain common coordinate framework (CCF) and consequently generated a combined 3D orofacial premotor atlas, revealing unique spatial organizations of distinct premotor circuits. We further uncovered premotor neurons that simultaneously innervate multiple motor nuclei and, consequently, are likely to coordinate different muscles involved in the same orofacial motor actions. Our method for tracing adult premotor circuits and registering to Allen CCF is generally applicable and should facilitate the investigations of motor controls of diverse behaviors.
Combining plasmonic noble metals with semiconductor materials has been considered to be an effective way to improve catalyst performance. In the present paper, Au nanoparticles (NPs) were decorated ...onto CVD-grown
β
-Ga
2
O
3
nanowires (NWs) through a chemical reduction method. Different quantity of HAuCl
4
solution was used to control the size and density of Au NPs. The photocatalytic activity of the Au–Ga
2
O
3
NWs is evaluated by degrading rhodamine B (Rh B) under UV and visible light irradiation. It is found that the size and density of the Au NPs had a great influence on the photocatalytic efficiency of
β
-Ga
2
O
3
NWs. And Ga
2
O
3
NWs with Au NPs of ~ 5.7 nm size and ~ 420/μm
2
density shows the best catalytic efficiency. Moreover, Au NPs attachment on the Ga
2
O
3
could extend its photocatalytic activity towards the visible light irradiation, which is significant to efficient utilization more solar light. A jointly effect of both the interfacial Schottky potential field between Au NPs and
β
-Ga
2
O
3
NWs and local surface plasma resonance excitation is proposed to contribute the enhancement effects.
Ciprofloxacin (CFX) is a widely used second-generation fluoroquinolone, broad-spectrum antibiotic. Increasingly, it has been detected in water supplies and has been shown to be harmful to the ...environment. Antibiotic contamination in the aquatic environment has adverse effects on non-target organisms, including promoting bacterial resistance, inhibiting algae growth, affecting chloroplast replication, transcription and translation, and disrupting the N cycle involved in microorganisms. Here, a novel electrochemical sensor was developed based on simple nitrogen plasma modification; critically, this sensor effectively detected CFX in water. Collectively, X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), contact angle (CA) measurements, and electrochemical impedance spectroscopy (EIS) were used to characterize the physical and electrochemical properties of the electrode. The results showed that both the electrochemical activity and the electron transfer of the carbon electrode were significantly enhanced by the nitrogen plasma modification. This was likely due to an increase in nitrogen functional groups (
i.e.
, the nitrogens contained within the pyrrole and graphite groups) and it did not result in damage to the roughness of the electrode's surface. These results also indicated that our sensor selectively detected CFX in the presence of interference antibiotics and/or inorganic ions. Under optimal conditions (pH = 5, plasma power = 140 W, and modification time = 8 min), our sensor showed a broad linear concentration range (2.5 × 10
−7
-1.0 × 10
−4
M) with detection limits as low as 8 nM. The sensor was also successfully applied in the detection of CFX in different types of water sources, namely groundwater and tap water. The recoveries varied from 92.10 to 109.48% with a relative standard deviation (RSD) less than 4.07%. Taken together, these results show a simple and rapid modification method that provides a promising means for rapid,
in situ
sensor-based monitoring of aquatic environmental pollutants like antibiotics.
We developed a novel electrochemical sensor based on nitrogen plasma modification to effectively detect ciprofloxacin in water.
Pyroptosis is a newly discovered type of programmed cell death associated with inflammatory and fibrotic diseases. Macrophages play an important role in inducing early immune inflammation in systemic ...sclerosis (SSc).
To investigate the effect of macrophages pyroptosis on fibrosis of SSc.
Pyroptosis/inflammatory markers in serum and skin of SSc patients were detected. Bleomycin (BLM) was subcutaneously injected to establish SSc mouse model. The levels of pyroptosis markers, dermal thickness and collagen deposition in skin were assessed before and after the administration of pyroptosis inhibitors, including MCC950, Disulfiram and necrosulfonamide (NSA). Human-derived monocyte-macrophage cell line (THP-1) or mouse bone marrow-derived macrophages (BMDMs) were primed with lipopolysaccharide (LPS) and stimulated by silicon dioxide (SiO2) to induce cell pyroptosis. Fibroblasts from patients with SSc were co-cultured with pyroptotic THP-1 cells, and the collagen production was assessed.
Pyroptotic/inflammatory proteins, including NLRP3, cleaved-Caspase (CASP)1, GSDMD-N terminal and IL-18 were increased in the serum, and ASC aggregation and GSDMD were elevated in macrophages in the skin of SSc patients. SSc mice showed increased pyroptosis markers, dermal thickness and collagen deposition in skins, which were alleviated by MCC950, Disulfiram and NSA. Pyroptosis of THP-1 cells and BMDMs was induced by LPS/SiO2, and it was reduced by the inhibitors of Cathepsin B, NLRP3, CASP1 and GSDMD. Co-culture with pyroptotic THP-1 cells increased the fibrotic proteins in fibroblasts, which were alleviated by pyroptosis inhibitors.
SSc patients and BLM-induced mouse model presented increased pyroptosis. LPS/SiO2-induced macrophage pyroptosis promoted fibrosis of SSc through Cathepsin B/NLRP3/GSDMD pathway.
•Macrophage pyroptosis was increased in SSc patients and BLM-induced SSc mouse model.•Inhibition of pyroptosis reduced inflammation and fibrosis of SSc mouse model.•Inhibiting NLRP3/GSDMD-mediated macrophage pyroptosis inactivates fibroblasts.
•The overall gut microbial communities of alopecia areata (AA) are distinct from the healthy controls.•The gut microbiota plays a role in the pathogenesis of AA.•The gut microbial markers may ...potentially be used for earlier AA diagnosis.•The gut microbial markers may be used as therapeutic targets for AA.
The gut microbiota is known to play a key role in autoimmune diseases.
To identify and compare the characteristics in the gut microbial composition of patients with alopecia areata (AA) and healthy controls (HCs).
In a cross-sectional discovery cohort, we enrolled 33 patients with AA and 35 HCs from the same geographic location in Shanghai, China. The 16S rRNA gene sequencing and bioinformatic analyses were conducted to analyze DNA extracted from the subjects.
The α-diversity of the AA group demonstrated no statistically significant differences compared with the HC group (P > 0.05). However, the overall gut microbial communities in the AA group were distinct from the HCs (P = 0.0096). We also adopted a random forest model to select three AA-associated OTU biomarkers: OTU1237(Achromobacter), OTU257(Megasphaera), and OTU1784(Lachnospiraceae Incertae Sedis).
The overall gut microbial composition for AA was distinct from that of HCs. The gut microbial markers we identified may potentially be used for earlier diagnosis and as therapeutic targets.
Adsorbed metal atoms and metal doping onto TiO₂ can effectively enhance the optical and photocatalytic activity of photocatalytic efficiency of titanium dioxide (TiO₂), favoring the extension of its ...optical absorption spectrum and the efficiency of hydrogen generation. To investigate the possible mechanism causing potential improvement of photocatalytic activity, the electronic and optical properties of the anatase TiO₂(101) plane with different adsorbed metal atom have been theoretically calculated through density functional theory (DFT) method. Adsorption of Pd and Ru atoms increases the delocalization of the density of states, with an impurity state near the Fermi level. Moreover, the investigated adsorbed metal atoms (Mo, Pd, Ru, Rh) narrow the band gap of anatase TiO₂, thus enhancing the probability of photoactivation by visible light. The orbital hybridization of the d orbit from the adsorbed metal atom and the p orbit from the O of the defect site increases the Schottky barrier of the electronic structure.
Animals employ active touch to optimize the acuity of their tactile sensors. Prior experimental results and models lead to the hypothesis that sensory inputs are used in a recurrent manner to tune ...the position of the sensors. A combination of electrophysiology, intersectional genetic viral labeling and manipulation, and classical tracing allowed us to identify second-order sensorimotor loops that control vibrissa movements by rodents. Facial motoneurons that drive intrinsic muscles to protract the vibrissae receive a short latency inhibitory input, followed by synaptic excitation, from neurons located in the oralis division of the trigeminal sensory complex. In contrast, motoneurons that retract the mystacial pad and indirectly retract the vibrissae receive only excitatory input from interpolaris cells that further project to the thalamus. Silencing this feedback alters retraction. The observed pull-push circuit at the lowest-level sensorimotor loop provides a mechanism for the rapid modulation of vibrissa touch during exploration of peri-personal space.
•Vibrissa contact leads to brainstem-mediated feedback signals to facial motoneurons•Intrinsic (protraction) motoneurons receive prompt inhibitory and excitatory feedback•Extrinsic (retraction) motoneurons receive excitatory feedback•These disynaptic reflexes are a substrate for fast, top-down modulation of touch
Bellavance et al. have identified three parallel, disynaptic sensorimotor loops that control contact-induced reflexive motion of the vibrissae in rodents. These anatomically low-level reflex arcs can incorporate the current goals and attention-driven focus of the animal.
Programmed cell death protein-1 (PD-1) is primarily recognized as an inhibitory receptor involved in the regulation of immunological tolerance. However, recent studies have indicated that PD-1/PD-L1 ...signaling could also regulate the functions of nonimmune cells and may be involved in regulating hair biology. In this study, we showed in a mouse model of depilation-induced hair cycling that PD-1/PD-L1 are expressed in the murine epidermis and hair follicle (HF) in a hair cycle-dependent manner. During HF morphogenesis, PD-1 expression was strongly decreased during the anagen phase compared with the catagen and telogen phases. PD-L1 expression was enhanced during the catagen phase compared with the anagen and telogen phases. Moreover, direct blockade of PD-L1 not only accelerated hair anagen phase onset but also delayed catagen progression. In conclusion, our findings indicated that PD-1/PD-L1 signaling may act as a negative regulator of hair cycle transition. Anti-PD-1/PD-L1 therapy may thus be a promising strategy for treating anagen-reduced hair loss.
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