A Low Dose of Rapamycin Promotes Hair Cell Differentiation by Enriching SOX2+ Progenitors in the Neonatal Mouse Inner Ear Organoids.

PURPOSE: To investigate the impact of rapamycin on the differentiation of hair cells. METHODS: Murine cochlear organoids were derived from cochlear progenitor cells. Different concentrations of rapamycin were added into the culture medium at different proliferation and differentiation stages. RESULTS: Rapamycin exhibited a concentration-dependent reduction in the proliferation of these inner ear organoids. Nevertheless, organoids subjected to a 10-nM dose of rapamycin demonstrated a markedly increased proportion of hair cells. Furthermore, rapamycin significantly upregulated the expression of markers associated with both hair cells and supporting cells, including ATOH1, MYO7A, and SOX2. Mechanistic studies revealed that rapamycin preferentially suppressed cells without Sox2 expression during the initial proliferation stage, thereby augmenting and refining the population of SOX2+ progenitors. These enriched progenitors were predisposed to differentiate into hair cells during the later stages of organoid development. Conversely, the use of the mTOR activator MHY 1485 demonstrated opposing effects. CONCLUSION: Our findings underscore a practical strategy for enhancing the generation of inner ear organoids with a low dose of rapamycin, achieved by enriching SOX2+ progenitors in an in vitro setting.

Synergistic effect of hydrothermal sludge and food waste in the anaerobic co-digestion process: microbial shift and dewaterability.

While thermal hydrolysis technology is commonly employed for sewage sludge treatment in extensive wastewater treatment facilities, persistent challenges remain, including issues such as ammonia-induced digestive inhibition and reduced productivity stemming from nutrient deficiency within the hydrothermal sludge. In this study, the effects of hydrothermal sludge-to-food waste mixing ratios and fermentation temperatures on anaerobic co-digestion were systematically investigated through a semi-continuous experiment lasting approximately 100 days. The results indicated that anaerobic co-digestion of hydrothermal sludge and food waste proceeded synergistically at any mixing ratio, and the synergistic effect is mainly attributed to the improvement of carbohydrate removal and digestive system stability. However, thermophilic digestion did not improve the anaerobic performance and methane yield. On the contrary, mesophilic digestion performed better in terms of organic matter removal, especially in the utilization of soluble carbohydrates, soluble proteins, and VFAs. Microbial community analysis revealed that the transition from mesophilic to thermophilic anaerobic co-digestion prompts changes in the methane-producing pathways. Specifically, the transition entails a gradual shift from pathways involving acetoclastic and hydrogenotrophic methanogenesis to a singular hydrogenotrophic methanogenesis pathway. This shift is driven by thermodynamic tendencies, as reflected in Gibbs free energy, as well as environmental factors like ammonia nitrogen and volatile fatty acids. Lastly, it is worth noting that the introduction of food waste did lead to a reduction in cake solids following dewatering. Nevertheless, it was observed that thermophilic digestion had a positive impact on dewatering performance.

Hepatitis B virus-mediated sodium influx contributes to hepatic inflammation via synergism with intrahepatic danger signals.

The NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome has been involved in the pathogenesis of various chronic liver diseases. However, its role in hepatitis B virus (HBV)-associated hepatitis remains unknown. Here we demonstrate the synergistic effect of HBV with potential intrahepatic danger signals on NLRP3 inflammasome activation. HBV exposure at the appropriate temporal points enhances potassium efflux-dependent NLRP3 inflammasome activation in macrophages and also increases NLRP3 inflammasome-mediated inflammation in HBV-transgenic mouse model. HBV-mediated synergism with intrahepatic signals represented by ATP molecules on NLRP3 activation was observed via relevance analysis, confocal microscopy, and co-immunoprecipitation, and its effector cytokines exhibit positive associations with hepatic inflammation in patients with severe hepatitis B. Furthermore, the synergism of HBV on NLRP3 inflammasome activation owes to increased sodium influx into macrophages. Our data demonstrate that HBV contributes to hepatic inflammation via sodium influx-dependent synergistic activation of NLRP3 inflammasome, which provides a deeper understanding of immune pathogenesis in HBV-associated hepatitis.

A brain-tumor neural circuit controls breast cancer progression in mice.

Tumor burden, considered a common chronic stressor, can cause widespread anxiety. Evidence suggests that cancer-induced anxiety can promote tumor progression, but the underlying neural mechanism remains unclear. Here, we used neuroscience and cancer tools to investigate how the brain contributes to tumor progression via nerve-tumor crosstalk in a mouse model of breast cancer. We show that tumor-bearing mice exhibited significant anxiety-like behaviors and that corticotropin-releasing hormone (CRH) neurons in the central medial amygdala (CeM) were activated. Moreover, we detected newly formed sympathetic nerves in tumors, which established a polysynaptic connection to the brain. Pharmacogenetic or optogenetic inhibition of CeMCRH neurons and the CeMCRH→lateral paragigantocellular nucleus (LPGi) circuit significantly alleviated anxiety-like behaviors and slowed tumor growth. Conversely, artificial activation of CeMCRH neurons and the CeMCRH→LPGi circuit increased anxiety and tumor growth. Importantly, we found alprazolam, an antianxiety drug, to be a promising agent for slowing tumor progression. Furthermore, we show that manipulation of the CeMCRH→LPGi circuit directly regulated the activity of the intratumoral sympathetic nerves and peripheral nerve-derived norepinephrine, which affected tumor progression by modulating antitumor immunity. Together, these findings reveal a brain-tumor neural circuit that contributes to breast cancer progression and provide therapeutic insights for breast cancer.

Prelimbic area to lateral hypothalamus circuit drives social aggression.

Controlling aggression is a vital skill in social species such as rodents and humans and has been associated with the medial prefrontal cortex (mPFC). In this study, we showed that during aggressive behavior, the activity of GABAergic neurons in the prelimbic area (PL) of the mPFC was significantly suppressed. Specific activation of GABAergic PL neurons significantly curbed male-to-male aggression and inhibited conditioned place preference (CPP) for aggression-paired contexts, whereas specific inhibition of GABAergic PL neurons brought about the opposite effect. Moreover, GABAergic projections from PL neurons to the lateral hypothalamus (LH) orexinergic neurons mediated aggressive behavior. Finally, directly modulated LH-orexinergic neurons influence aggressive behavior. These results suggest that GABAergic PL-orexinergic LH projection is an important control circuit for intermale aggressive behavior, both of which could be targets for curbing aggression.

Optimal deployment of thermal hydrolysis and anaerobic digestion to maximize net energy output based on sewage sludge characteristics.

Thermal hydrolysis (TH) is widely employed in combination with anaerobic digestion (AD) to efficiently treat primary sludge and waste-activated sludge in municipal wastewater treatment plants. In this study, four different scenarios-conventional AD (S1), TH-AD (S2), AD-TH-AD (S3), and characteristics-based AD-TH-AD (S4, primary AD only for primary sludge)-were evaluated to determine the optimal deployment of TH and AD for treating primary sludge and waste-activated sludge to maximize net energy output. The maximum net energy output of 4899 MJ/t-TSfed (per ton total solids of sludge fed) was achieved in S4 when assuming the recovered heat was only used for AD heating and surplus heat was wasted, and the net energy output of S4 was 70.8 % higher than that of S1 and 48.6 % higher than that of S2. This remarkable improvement was attributed to a reduction of > 15.2 % in refractory compounds, resulting in a 17 % increase in methane yield. Importantly, this study provides the first comparison of refractory compounds between inter-thermal hydrolysis (inter-TH) and pre-thermal hydrolysis (pre-TH) using a simulated A2O process. Overall, this study provides innovative insights and strategies for enhancing the TH and AD process performance based on the specific characteristics of sewage sludge derived from wastewater treatment plants.

Enhanced Electrical Conductivity of (001) Oriented Sr0.9La0.1TiO3 Microplatelets for Thermoelectric Applications.

Two-dimensional perovskite microplatelets have played an important role in various applications, especially acting as a template to guide grains' epitaxial growth in the preparation of textured ceramics. The (001) oriented Sr0.9La0.1TiO3 microplatelets with a high aspect ratio of ∼20 were synthesized and obtained from Aurivillius Bi4Ti3O12 precursors. To reveal the mechanism of topochemical microcrystal conversion of Bi4Ti3O12 to Sr0.9La0.1TiO3, the reaction interface, morphology development, and phase composition evolution of the (001) oriented Sr0.9La0.1TiO3 microplatelets were investigated. When the temperature of the molten salt is above 753 °C, multiple Sr0.9La0.1TiO3 topological nucleation events took place. At 950 °C, the polycrystalline aggregate of (001)-oriented Sr0.9La0.1TiO3 crystallites grew in place of the original single crystal Bi4Ti3O12 platelets. When the temperature reached 1150 °C, the Sr0.9La0.1TiO3 platelets preserved the shape of a high aspect ratio and exhibited not only enhanced electrical conductivity with a carrier concentration of 3.518 × 1020 cm-3 and carrier mobility of 8.460 cm2·V-1·s-1 but also significantly decreased thermal conductivity ranging from 5.65 W·m-1·K-1 at 300 K to 2.54 W·m-1·K-1 at 1073 K. It can be widely applied in the field of template grain growth methods for preparing textured thermoelectric ceramics to improve their thermoelectric properties.

A Novel Unsupervised Video Anomaly Detection Framework Based on Optical Flow Reconstruction and Erased Frame Prediction.

Reconstruction-based and prediction-based approaches are widely used for video anomaly detection (VAD) in smart city surveillance applications. However, neither of these approaches can effectively utilize the rich contextual information that exists in videos, which makes it difficult to accurately perceive anomalous activities. In this paper, we exploit the idea of a training model based on the "Cloze Test" strategy in natural language processing (NLP) and introduce a novel unsupervised learning framework to encode both motion and appearance information at an object level. Specifically, to store the normal modes of video activity reconstructions, we first design an optical stream memory network with skip connections. Secondly, we build a space-time cube (STC) for use as the basic processing unit of the model and erase a patch in the STC to form the frame to be reconstructed. This enables a so-called "incomplete event (IE)" to be completed. On this basis, a conditional autoencoder is utilized to capture the high correspondence between optical flow and STC. The model predicts erased patches in IEs based on the context of the front and back frames. Finally, we employ a generating adversarial network (GAN)-based training method to improve the performance of VAD. By distinguishing the predicted erased optical flow and erased video frame, the anomaly detection results are shown to be more reliable with our proposed method which can help reconstruct the original video in IE. Comparative experiments conducted on the benchmark UCSD Ped2, CUHK Avenue, and ShanghaiTech datasets demonstrate AUROC scores reaching 97.7%, 89.7%, and 75.8%, respectively.

Hotspots and future trends of phosphorus recycling from livestock manure: A bibliometric review.

In recent decades, the importance of managing the earth's dwindling phosphorus (P) has grown exponentially, as have efforts to develop a circular economy. Livestock manure represents a P-rich waste product, so recycling P from livestock manure has garnered the attention of scholars worldwide. Based on a global database from 1978 to 2021, this study presents the current status of recycling P from livestock manure and proposes strategies for efficient P utilization. Unlike traditional review articles, this work establishes a visual collaborative network on P recycling from livestock manure of research areas, countries, institutions, and authors through a bibliometric analysis using Citespace and VOSviewer software. The co-citation analysis of literature revealed the development of the main research content in this field, and further clustering analysis illustrated the current key research directions. Keyword co-occurrence analysis identified the hotspots and new frontiers of research in this field. According to the results, the United States was the most influential and actively contributing nation, and China was the country with the tightest international ties. The most popular research area was environmental science, and the Bioresource Technology published the largest number of papers in this area. The research priority was the technologies development of P recycling from livestock manure, of which the most used method was struvite precipitation and biochar adsorption. Subsequently, evaluation is also essential, including the economic benefits and environmental impacts of the recycling process by life cycle assessment and substance flow analysis, as well as the agronomic efficiency of the recycled products. New directions for technological innovation in recycling P from livestock manure and potential risks in the recycling process are explored. The results of this study may provide a framework for understanding the mechanisms of P utilization in livestock manure, and support the overall popularization of P recycling technology from livestock manure.

Exploration and identification of six novel ferroptosis-related hub genes as potential gene signatures for peripheral nerve injury.

Specific biomarkers of ferroptosis after peripheral nerve injury (PNI) are still under debate. In this study, 52 differentially expressed ferroptosis-related genes (DE-FRGs) were retrieved from publicly accessible sequencing data of intact and injured samples of rats with sciatic nerve crush injury. Functional enrichment analyses revealed that adipogenesis, mitochondrial gene sets, and pathways of MAPK, p53, and CD28 family were predominantly engaged in ferroptosis after PNI. Next, Cdkn1a, Cdh1, Hif1a, Hmox1, Nfe2l2, and Tgfb1 were investigated as new ferroptosis-associated hub genes after PNI. Subsequently, clustering correlation heatmap shows six hub genes are linked to mitochondria. The immunofluorescence assay at 0, 1, 4, 7, and 14 days indicated the temporal expression patterns of Tgfb1, Hmox1, and Hif1a after PNI were consistent with ferroptosis validated by PI and ROS staining, while Cdh1, Cdkn1a, and Nfe2l2 were the opposite. In summary, this study identified six hub genes as possible ferroptosis-related biomarkers for PNI, which may offer therapeutic targets for peripheral nerve regeneration and provide a therapeutic window for ferroptosis.

A High-Temperature Accelerometer with Excellent Performance Based on the Improved Graphene Aerogel.

A high-temperature accelerometer plays an important role for ensuring normal operation of equipment in aerospace, such as monitoring and identifying abnormal vibrations of aircraft engines. Phase transitions of piezoelectric crystals, mechanical failure and current leakage of piezoresistive/capacitive materials are the prominent inherent limitations of present high-temperature accelerometers working continuously above 973 K. With the rapid development of aerospace, it is a great challenge to develop a new type of vibration sensor to meet the crucial demands at high temperature. Here we report a high-temperature accelerometer working with a contact resistance mechanism. Based on the improved graphene aerogel (GA) prepared by a modulated treatment process, the accelerometer can operate continuously and stably at 1073 K and intermittently at 1273 K. The developed sensor is lightweight (sensitive element <5 mg) and has high sensitivity (an order of magnitude higher than MEMS accelerometers) and wide frequency response range (up to 5 kHz at 1073 K) with marked stability, repeatability and low nonlinearity error (<1%). These merits are attributed to the excellent and stable mechanical properties of the improved GA in the range of 299-1073 K. The accelerometer could be a promising candidate for high-temperature vibration sensing in space stations, planetary rovers and others.

Two-step anaerobic digestion of rice straw with nanobubble water.

Lignocellulose usually requires pretreatment to improve biogas production. To enhance lignocellulose biodegradability and improve anaerobic digestion (AD) efficiency, different types (N2, CO2, and O2) of nanobubble water (NW) were applied in this study as soaking agent and AD accelerant to increase the biogas yield of rice straw. The results showed that the cumulative methane yields of treating with NW in two-step AD increased by 11.0%-21.4% compared with untreated straw. The maximum cumulative methane yield was 313.9±1.7 mL/gVS in straw treated with CO2-NW as soaking agent and AD accelerant (PCO2-MCO2). The application of CO2-NW and O2-NW as AD accelerants increased bacterial diversity and relative abundance of Methanosaeta. This study suggested that using NW could enhance soaking pretreatment and methane production of rice straw in two-step AD; however, combined treatment with inoculum and NW or microbubble water in the pretreatment needs to compare in future.

Protective Mechanism of Cordyceps sinensis Treatment on Acute Kidney Injury-Induced Acute Lung Injury through AMPK/mTOR Signaling Pathway.

OBJECTIVE: To investigate protective effect of Cordyceps sinensis (CS) through autophagy-associated adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway in acute kidney injury (AKI)-induced acute lung injury (ALI). METHODS: Forty-eight male Sprague-Dawley rats were divided into 4 groups according to a random number table, including the normal saline (NS)-treated sham group (sham group), NS-treated ischemia reperfusion injury (IRI) group (IRI group), and low- (5 g/kg·d) and high-dose (10 g/kg·d) CS-treated IRI groups (CS1 and CS2 groups), 12 rats in each group. Nephrectomy of the right kidney was performed on the IRI rat model that was subjected to 60 min of left renal pedicle occlusion followed by 12, 24, 48, and 72 h of reperfusion. The wet-to-dry (W/D) ratio of lung, levels of serum creatinine (Scr), blood urea nitrogen (BUN), inflammatory cytokines such as interleukin- ß and tumor necrosis factor- α, and biomarkers of oxidative stress such as superoxide dismutase, malonaldehyde (MDA) and myeloperoxidase (MPO), were assayed. Histological examinations were conducted to determine damage of tissues in the kidney and lung. The protein expressions of light chain 3 II/light chain 3 I (LC3-II/LC3-I), uncoordinated-51-like kinase 1 (ULK1), P62, AMPK and mTOR were measured by Western blot and immunohistochemistry, respectively. RESULTS: The renal IRI induced pulmonary injury following AKI, resulting in significant increases in W/D ratio of lung, and the levels of Scr, BUN, inflammatory cytokines, MDA and MPO (P<0.01); all of these were reduced in the CS groups (P<0.05 or P<0.01). Compared with the IRI groups, the expression levels of P62 and mTOR were significantly lower (P<0.05 or P<0.01), while those of LC3-II/LC3-I, ULK1, and AMPK were significantly higher in the CS2 group (P<0.05 or P<0.01). CONCLUSION: CS had a potential in treating lung injury following renal IRI through activation of the autophagy-related AMPK/mTOR signaling pathway in AKI-induced ALI.

Estradiol enhances T-type calcium channel activation in human myometrium telocytes.

Uterine peristalsis is essential for gamete transport and embryo implantation. It shares the characteristics of spontaneity, rhythmicity, and directivity with gastrointestinal peristalsis. Telocytes, the "interstitial Cajal-like cells" outside the digestive canal, are also located in the uterus and may act as pacemakers. To investigate the possible origin and regulatory mechanism of periodic uterine peristalsis in the human menstrual cycle, telocytes in the myometrium were studied to determine the effect of estradiol on T-type calcium channel regulation. In this study, biopsies of the human myometrium were obtained for cell culture, and double-labeling immunofluorescence screening was used to identify telocytes and T-type calcium channel expression. Intracellular calcium signal measurements and patch-clamp recordings were used to investigate the role of T-type calcium channels in regulating calcium currents with or without estradiol. Our study demonstrates that telocytes exist in the human uterus and express T-type calcium channels. The intracellular Ca2+ fluorescence intensity marked by Fluo-4AM was dramatically decreased by NNC 55-0396, a highly selective T-type calcium channel blocker, but enhanced by estradiol. T-type calcium current amplitude increased in telocytes incubated with estradiol in a dose-dependent manner compared to the control group. In conclusion, our study demonstrated that telocytes exist in the human myometrium, expressing T-type calcium channels and estradiol-enhanced T-type calcium currents, which may be a reasonable explanation for the origin of uterine peristalsis. The role of telocytes in the human uterus as pacemakers and message transfer stations in uterine peristalsis may be worth further investigation.

Corticostriatal Neurons in the Anterior Auditory Field Regulate Frequency Discrimination Behavior.

The anterior auditory field (AAF) is a core region of the auditory cortex and plays a vital role in discrimination tasks. However, the role of the AAF corticostriatal neurons in frequency discrimination remains unclear. Here, we used c-Fos staining, fiber photometry recording, and pharmacogenetic manipulation to investigate the function of the AAF corticostriatal neurons in a frequency discrimination task. c-Fos staining and fiber photometry recording revealed that the activity of AAF pyramidal neurons was significantly elevated during the frequency discrimination task. Pharmacogenetic inhibition of AAF pyramidal neurons significantly impaired frequency discrimination. In addition, histological results revealed that AAF pyramidal neurons send strong projections to the striatum. Moreover, pharmacogenetic suppression of the striatal projections from pyramidal neurons in the AAF significantly disrupted the frequency discrimination. Collectively, our findings show that AAF pyramidal neurons, particularly the AAF-striatum projections, play a crucial role in frequency discrimination behavior.

Regulation of the autophagy plays an important role in acute kidney injury induced acute lung injury.

AIM: This study aimed to investigate the regulatory role of autophagy in acute kidney injury (AKI) induced acute lung injury (ALI). METHODS: The male Sprague-Dawley rats were divided into four groups: normal saline-treated sham rats (sham group), normal saline-treated ischemia-reperfusion injury rats (IRI group), 3-methyladenine-treated IRI rats (3-MA group), and rapamycin-treated IRI rats (RA group). The rats in the IRI rat model received the nephrectomy of the right kidney and was subjected to 60 mins of left renal pedicle occlusion, followed by 12, 24, 48, and 72 h of reperfusion. The levels of Scr, BUN, wet-to-dry ratio of lung, inflammatory cytokines, and oxidative stress were determined. The damage to tissues was detected by histological examinations. The western blot and immunohistochemistry methods were conducted to determine the expression of indicated proteins. RESULTS: Renal IRI could induce the pulmonary injury after AKI, which caused significant increases in the function index of pulmonary and renal, the levels of inflammatory cytokines, and biomarkers of oxidative stress. In comparison to the IRI group, the RA group showed significantly decreased P62 and Caspase-3 expression and increased LC-II/LC3-I, Beclin-1, Bcl-2, and unc-51-like autophagy activating kinase 1 expression. Meanwhile, by suppressing the inflammation and oxidative stress, as well as inhibiting the pathological lesions in kidney and lung tissues, the autophagy could effectively ameliorate IRI-induced AKI and ALI. CONCLUSIONS: Autophagy plays an important role in AKI-induced ALI, which could be used as a new target for AKI therapy and reduce the mortality caused by the complication.

Pathological mechanisms of connexin26-related hearing loss: Potassium recycling, ATP-calcium signaling, or energy supply?

Hereditary deafness is one of the most common human birth defects. GJB2 gene mutation is the most genetic etiology. Gap junction protein 26 (connexin26, Cx26) encoded by the GJB2 gene, which is responsible for intercellular substance transfer and signal communication, plays a critical role in hearing acquisition and maintenance. The auditory character of different Connexin26 transgenic mice models can be classified into two types: profound congenital deafness and late-onset progressive hearing loss. Recent studies demonstrated that there are pathological changes including endocochlear potential reduction, active cochlear amplification impairment, cochlear developmental disorders, and so on, in connexin26 deficiency mice. Here, this review summarizes three main hypotheses to explain pathological mechanisms of connexin26-related hearing loss: potassium recycling disruption, adenosine-triphosphate-calcium signaling propagation disruption, and energy supply dysfunction. Elucidating pathological mechanisms underlying connexin26-related hearing loss can help develop new protective and therapeutic strategies for this common deafness. It is worthy of further study on the detailed cellular and molecular upstream mechanisms to modify connexin (channel) function.

Dietary intake of deuterium oxide decreases cochlear metabolism and oxidative stress levels in a mouse model of age-related hearing loss.

Age-related hearing loss (ARHL) is the most prevalent sensory disorder in the elderly. Currently, no treatment can effectively prevent or reverse ARHL. Aging auditory organs are often accompanied by exacerbated oxidative stress and metabolic deterioration. Here, we report the effect of deuterated oxygen (D2O), also known as "heavy water", mouse models of ARHL. Supplementing the normal mouse diet with 10% D2O from 4 to 9 weeks of age lowered hearing thresholds at selected frequencies in treated mice compared to untreated control group. Oxidative stress levels were significantly reduced and in the cochlear duct of treated vs. untreated mice. Through metabolic flux analysis, we found that D2O mainly slowed down catabolic reactions, and may delay metabolic deterioration related to aging to a certain extent. Experiments confirmed that the Nrf2/HO-1/glutathione axis was down-regulated in treated mice. Thus, D2O supplementation can hinder ARHL progression in mouse models by slowing the pace of metabolism and reducing endogenous oxidative stress production in the cochlea. These findings open new avenues for protecting the cochlea from oxidative stress and regulating metabolism to prevent ARHL.

Effect of Notch1 signaling on cellular proliferation and apoptosis in human laryngeal carcinoma.

BACKGROUND: The occurrence and development of malignancies include excessive proliferation and apoptosis resistance in tumor cells. This study aimed to identify the effects of Notch1 signaling on proliferation and apoptosis of laryngeal cancer cells in a hypoxic microenvironment. METHODS: Notch1 and Ki-67 expression in laryngeal squamous cell carcinoma (LSCC) tissues was detected by immunohistochemistry. The apoptotic index (AI) of LSCC was evaluated by the TUNEL method. Small interfering RNA (siRNA) was used to inhibit Notch1 expression in laryngeal cancer cells. Real-time PCR was used to measure Notch1, Hes1, and Hey1 mRNA expression, and Western blotting was used to measure Notch1 and Notch1 intracellular domain (N1ICD) protein expression. Annexin V-FITC/propidium iodide staining and Cell Counting Kit-8 assays were used to measure cell apoptosis and proliferation, respectively. RESULTS: Notch1 expression was significantly related to the proliferation index (PI) and AI in LSCC tissues. Hypoxia could induce proliferation and inhibit apoptosis in cancer cells. Notch1 expression and Notch1 signaling activity could be upregulated by hypoxia. Suppressing Notch1 signaling activity in hypoxic cells could decrease proliferation and increase apoptosis. CONCLUSIONS: Our study has demonstrated that hypoxia may promote proliferation and inhibit apoptosis of laryngeal cancer cells. Notch1 signaling may play a pivotal role in regulating the proliferation and apoptosis resistance of laryngeal cancer cells under hypoxic conditions.

Itch-specific neurons in the ventrolateral orbital cortex selectively modulate the itch processing.

Itch is a cutaneous sensation that is critical in driving scratching behavior. The long-standing question of whether there are specific neurons for itch modulation inside the brain remains unanswered. Here, we report a subpopulation of itch-specific neurons in the ventrolateral orbital cortex (VLO) that is distinct from the pain-related neurons. Using a Tet-Off cellular labeling system, we showed that local inhibition or activation of these itch-specific neurons in the VLO significantly suppressed or enhanced itch-induced scratching, respectively, whereas the intervention did not significantly affect pain. Conversely, suppression or activation of pain-specific neurons in the VLO significantly affected pain but not itch. Moreover, fiber photometry and immunofluorescence verified that these itch- and pain-specific neurons are distinct in their functional activity and histological location. In addition, the downstream targets of itch- and pain-specific neurons were different. Together, the present study uncovers an important subpopulation of neurons in the VLO that specifically modulates itch processing.