Tunable superconductivity in electron- and hole-doped Bernal bilayer graphene.

Graphene-based, high-quality, two-dimensional electronic systems have emerged as a highly tunable platform for studying superconductivity1-21. Specifically, superconductivity has been observed in both electron- and hole-doped twisted graphene moiré systems1-17, whereas in crystalline graphene systems, superconductivity has so far been observed only in hole-doped rhombohedral trilayer graphene (RTG)18 and hole-doped Bernal bilayer graphene (BBG)19-21. Recently, enhanced superconductivity has been demonstrated20,21 in BBG because of the proximity to a monolayer WSe2. Here we report the observation of superconductivity and a series of flavour-symmetry-breaking phases in electron- and hole-doped BBG/WSe2 devices by electrostatic doping. The strength of the observed superconductivity is tunable by applied vertical electric fields. The maximum Berezinskii-Kosterlitz-Thouless transition temperature for the electron- and hole-doped superconductivity is about 210 mK and 400 mK, respectively. Superconductivities emerge only when the applied electric fields drive the BBG electron or hole wavefunctions towards the WSe2 layer, underscoring the importance of the WSe2 layer in the observed superconductivity. The hole-doped superconductivity violates the Pauli paramagnetic limit, consistent with an Ising-like superconductor. By contrast, the electron-doped superconductivity obeys the Pauli limit, although the proximity-induced Ising spin-orbit coupling is also notable in the conduction band. Our findings highlight the rich physics associated with the conduction band in BBG, paving the way for further studies into the superconducting mechanisms of crystalline graphene and the development of superconductor devices based on BBG.

Ago2/CAV1 interaction potentiates metastasis via controlling Ago2 localization and miRNA action.

Ago2 differentially regulates oncogenic and tumor-suppressive miRNAs in cancer cells. This discrepancy suggests a secondary event regulating Ago2/miRNA action in a context-dependent manner. We show here that a positive charge of Ago2 K212, that is preserved by SIR2-mediated Ago2 deacetylation in cancer cells, is responsible for the direct interaction between Ago2 and Caveolin-1 (CAV1). Through this interaction, CAV1 sequesters Ago2 on the plasma membranes and regulates miRNA-mediated translational repression in a compartment-dependent manner. Ago2/CAV1 interaction plays a role in miRNA-mediated mRNA suppression and in miRNA release via extracellular vesicles (EVs) from tumors into the circulation, which can be used as a biomarker of tumor progression. Increased Ago2/CAV1 interaction with tumor progression promotes aggressive cancer behaviors, including metastasis. Ago2/CAV1 interaction acts as a secondary event in miRNA-mediated suppression and increases the complexity of miRNA actions in cancer.

A Light-Responsive Neural Circuit Suppresses Feeding.

Light plays an essential role in a variety of physiological processes, including vision, mood, and glucose homeostasis. However, the intricate relationship between light and an animal's feeding behavior has remained elusive. Here, we found that light exposure suppresses food intake, whereas darkness amplifies it in male mice. Interestingly, this phenomenon extends its reach to diurnal male Nile grass rats and healthy humans. We further show that lateral habenula (LHb) neurons in mice respond to light exposure, which in turn activates 5-HT neurons in the dorsal Raphe nucleus (DRN). Activation of the LHb→5-HTDRN circuit in mice blunts darkness-induced hyperphagia, while inhibition of the circuit prevents light-induced anorexia. Together, we discovered a light-responsive neural circuit that relays the environmental light signals to regulate feeding behavior in mice.

Metabolomic and Proteomic Analysis of ApoE4-Carrying H4 Neuroglioma Cells in Alzheimer's Disease Using OrbiSIMS and LC-MS/MS.

Growing clinical evidence reveals that systematic molecular alterations in the brain occur 20 years before the onset of AD pathological features. Apolipoprotein E4 (ApoE4) is one of the most significant genetic risk factors for Alzheimer's disease (AD), which is not only associated with the AD pathological features such as amyloid-ß deposition, phosphorylation of tau proteins, and neuroinflammation but is also involved in metabolism, neuron growth, and synaptic plasticity. Multiomics, such as metabolomics and proteomics, are applied widely in identifying key disease-related molecular alterations and disease-progression-related changes. Despite recent advances in the development of analytical technologies, screening the entire profile of metabolites remains challenging due to the numerous classes of compounds with diverse chemical properties that require different extraction processes for mass spectrometry. In this study, we utilized Orbitrap Secondary Ion Mass Spectrometry (OrbiSIMS) as a chemical filtering screening tool to examine molecular alterations in ApoE4-carried neuroglioma cells compared to wild-type H4 cells. The findings were compared using liquid chromatography (LC)-MS/MS targeted metabolomics analysis for the confirmation of specific metabolite classes. Detected alterations in peptide fragments by OrbiSIMS provided preliminary indications of protein changes. These were extensively analyzed through proteomics to explore ApoE4's impact on proteins. Our metabolomics approach, combining OrbiSIMS and LC-MS/MS, revealed disruptions in lipid metabolism, including glycerophospholipids and sphingolipids, as well as amino acid metabolism, encompassing alanine, aspartate, and glutamate metabolism; aminoacyl-tRNA biosynthesis; glutamine metabolism; and taurine and hypotaurine metabolism. Further LC-MS/MS proteomics studies confirmed the dysfunction in amino acid and tRNA aminoacylation metabolic processes, and highlighted RNA splicing alterations influenced by ApoE4.

USP47 deficiency in mice modulates tumor infiltrating immune cells and enhances antitumor immune responses in prostate cancer.

This study investigates the role of USP47, a deubiquitinating enzyme, in the tumor microenvironment and its impact on antitumor immune responses. Analysis of TCGA database revealed distinct expression patterns of USP47 in various tumor tissues and normal tissues. Prostate adenocarcinoma showed significant downregulation of USP47 compared to normal tissue. Correlation analysis demonstrated a positive association between USP47 expression levels and infiltrating CD8+ T cells, neutrophils, and macrophages, while showing a negative correlation with NKT cells. Furthermore, using Usp47 knockout mice, we observed a slower tumor growth rate and reduced tumor burden. The absence of USP47 led to increased infiltration of immune cells, including neutrophils, macrophages, NK cells, NKT cells, and T cells. Additionally, USP47 deficiency resulted in enhanced activation of cytotoxic T lymphocytes (CTLs) and altered T cell subsets within the tumor microenvironment. These findings suggest that USP47 plays a critical role in modulating the tumor microenvironment and promoting antitumor immune responses, highlighting its potential as a therapeutic target in prostate cancer.

Matched Redox Kinetics on Triazine-Based Carbon Nitride/Ni(OH)2 for Stoichiometric Overall Photocatalytic CO2 Conversion.

Mismatched reaction kinetics of CO2 reduction and H2O oxidation is the main obstacle limiting the overall photocatalytic CO2 conversion. Here, a molten salt strategy is used to construct tubular triazine-based carbon nitride (TCN) with more adsorption sites and stronger activation capability. Ni(OH)2 nanosheets are then grown over the TCN to trigger a proton-coupled electron transfer for a stoichiometric overall photocatalytic CO2 conversion via "3CO2 + 2H2O = CH4 + 2CO + 3O2." TCN reduces the energy barrier of H2O dissociation to promote H2O oxidation to O2 and supply sufficient protons to Ni(OH)2, whereby the CO2 conversion is accelerated due to the enhanced proton-coupled electron transfer process enabled by the sufficient proton supply from TCN. This work highlights the importance of matching the reaction kinetics of CO2 reduction and H2O oxidation by proton-coupled electron transfer on stoichiometric overall photocatalytic CO2 conversion.

Monomeric Far-red and Near-infrared Fluorescent Biliproteins of Ultrahigh Brightness.

Far-red and near-infrared fluorescent proteins have regions of maximum transmission in most tissues and can be widely used as fluorescent biomarkers. We report that fluorescent phycobiliproteins originating from the phycobilisome core subunit ApcF2 can covalently bind biliverdin, named BDFPs. To further improve BDFPs, we conducted a series of studies. Firstly, we mutated K53Q and T144A of BDFPs to increase their effective brightness up to 190 % in vivo. Secondly, by homochromatic tandem fusion of high-brightness BDFPs to achieve monomerization, which increases the effective brightness by up to 180 % in vivo, and can effectively improve the labeling effect. By combining the above two approaches, the brightness of the tandem BDFPs was much improved compared with that of the previously reported fluorescent proteins in a similar spectral range. The tandem BDFPs were expressed stably while maintaining fluorescence in mammalian cells and Caenorhabditis elegans. They were also photostable and resistant to high temperature, low pH, and chemical denaturation. The tandem BDFPs advantages were proved in applications as biomarkers for imaging in super-resolution microscopy.

Deep learning framework for three-dimensional surface reconstruction of object of interest in photoacoustic tomography.

Photoacoustic tomography (PAT) is a non-ionizing hybrid imaging technology of clinical importance that combines the high contrast of optical imaging with the high penetration of ultrasonic imaging. Two-dimensional (2D) tomographic images can only provide the cross-sectional structure of the imaging target rather than its overall spatial morphology. This work proposes a deep learning framework for reconstructing three-dimensional (3D) surface of an object of interest from a series of 2D images. It achieves end-to-end mapping from a series of 2D images to a 3D image, visually displaying the overall morphology of the object. The framework consists of four modules: segmentation module, point cloud generation module, point cloud completion module, and mesh conversion module, which respectively implement the tasks of segmenting a region of interest, generating a sparse point cloud, completing sparse point cloud and reconstructing 3D surface. The network model is trained on simulation data sets and verified on simulation, phantom, and in vivo data sets. The results showed superior 3D reconstruction performance both visually and on the basis of quantitative evaluation metrics compared to the state-of-the-art non-learning and learning approaches. This method potentially enables high-precision 3D surface reconstruction from the tomographic images output by the preclinical PAT system without changing the imaging system. It provides a general deep learning scheme for 3D reconstruction from tomographic scanning data.

Bio-Inspired Underwater Superoleophobic Aramid Nanofiber-Based Aerogel Membranes for Highly Efficient Removal of Emulsified Oils and Organic Dyes.

Effective elimination of insoluble emulsified oils and soluble organic dyes has received extensively attention in wastewater treatment. In this work, a chitosan and polydopamine @ aramid nanofibers (CS&PDA@ANFs) aerogel membrane was fabricated through an integration methodology consisting of phase inversion and successive deposition of PDA and CS. The as-prepared aerogel membrane possessed a satisfactory three-dimensional interpenetrating network architecture with high porosity and desirable mechanical property. Furthermore, due to the synergistic effect of hydrophilic CS and PDA, the resultant membrane exhibited good superhydrophilicity and underwater superoleophobicity associated with favorable oil resistance/antioil fouling properties. The combination of the interconnected porous structures and super wettability endowed the aerogel membranes with desirable oil-in-water emulsion separation performance. Particularly, an extremely high permeation flux (3729 L/m2/h) and a rejection rate (99.3%) were achieved for the CS&PDA@ANFs membrane. Moreover, diverse dyes could be also adsorbed by the resultant membrane, and the equilibrium adsorption capacity of cationic dye malachite green could reach 36 mg/g, with a high rejection rate over 97%. This study indicated that the CS&PDA@ANFs aerogel membrane held great promise for practical applications in complex wastewater remediation.

miR-575/RIPK4 axis modulates cell cycle progression and proliferation by inactivating the Wnt/ß-catenin signaling pathway through inhibiting RUNX1 in colon cancer.

Receptor interacting protein serine/threonine kinase 4 (RIPK4) is widely involved in human cancer development. Nevertheless, its role in colon cancer (COAD) has not been elucidated till now. Our research aimed at exploring the function and underlying molecular mechanism of RIPK4 in COAD progression. Through bioinformatic analyses and RT-qPCR, RIPK4 was discovered to be increased in COAD cells and tissues, and its high level predicted poor prognosis. Loss-of-function assays revealed that RIPK4 silencing suppressed COAD cell growth, induced cell cycle arrest, and enhanced cell apoptosis. In vivo experiments also proved that tumor growth was inhibited by silencing of RIPK4. Luciferase reporter assay validated that RIPK4 was targeted and negatively regulated by miR-575. Western blotting demonstrated that Wnt3a, phosphorylated (p)-GSK-3ß, and cytoplasmic and nuclear ß-catenin protein levels, ß-catenin nuclear translocation, and Cyclin D1, CDK4, Cyclin E, and c-Myc protein levels were reduced by RIPK4 knockdown, which however was reversed by treatment with LiCl, the Wnt/ß-catenin pathway activator. LiCl also offset the influence of RIPK4 knockdown on COAD cell growth, cell cycle process, and apoptosis. Finally, RIPK4 downregulation reduced RUNX1 level, which was upregulated in COAD and its high level predicted poor prognosis. RIPK4 is positively associated with RUNX1 in COAD. Overexpressing RUNX1 antagonized the suppression of RIPK4 knockdown on RUNX1, Wnt3a, p-GSK-3ß, cytoplasmic ß-catenin, nuclear ß-catenin, Cyclin D1, CDK4, Cyclin E, and c-Myc levels. Collectively, miR-575/RIPK4 axis repressed COAD progression via inactivating the Wnt/ß-catenin pathway through downregulating RUNX1.

Gestational age-specific hematological features in preterm infants with necrotizing enterocolitis.

BACKGROUND: This study aimed to investigate gestational age-specific hematological features in preterm infants with necrotizing enterocolitis (NEC) and identify predictive hematological biomarkers for surgical NEC. METHODS: We conducted a retrospective study comparing gestational age (GA)-specific clinical data between medical NEC (m-NEC) and surgical NEC (s-NEC) subgroups, stratified by GA as <28 weeks, 28 ≤ GA < 32 weeks, and 32 ≤ GA < 37 weeks. Multivariate logistic analysis and receiver operating characteristic curve were used to identify the independent predictors of s-NEC. RESULTS: In comparison to m-NEC at NEC onset, s-NEC infants exhibited the following findings: In GA < 28 weeks, s-NEC infants had lower platelet counts. In 28 ≤ GA < 32 weeks, lower absolute lymphocyte counts, and significant percent drop in platelets, lymphocytes, and monocytes were observed. In 32 ≤ GA < 37 weeks, lower absolute lymphocyte counts and significant percent drop in lymphocytes were found. Independent predictors were able to distinguish s-NEC from m-NEC. The area under the curve (AUC) for platelet counts in GA < 28 weeks was 0.880, while C-reactive protein in 28 ≤ GA < 32 weeks had an AUC of 0.889. The AUC for lymphocyte counts in 32 ≤ GA < 37 weeks was 0.892. CONCLUSION: This study identified hematological abnormalities in the development of NEC based on gestational age. Independent predictors may help clinicians distinguish surgical NEC from medical NEC. IMPACT: Necrotizing enterocolitis (NEC) patients with different gestational ages (GA) exhibit different hematological features and independent predictors of surgical NEC differ among different GAs. Our research made the current studies about peripheral hematological features with NEC more complete by analyzing peripheral data collected within 24 h of birth, at day 5-7, day 3-4, day 1-2 before NEC onset, at the time of NEC onset, day 1, day 2, day 3, day 4-5, day 6-7 after NEC onset. Our study is helpful to clinicians in developing a more detailed diagnostic strategy based on GA for the early identification of surgical NEC.

Tracking changes in image-defined risk factors during neoadjuvant chemotherapy and their predictive value for surgical outcomes based on the International Neuroblastoma Surgical Report Form.

BACKGROUND: The capacity of presurgical image-defined risk factors (IDRFs) to predict secondary surgical outcomes in patients with neuroblastoma is controversial. METHODS: The International Neuroblastoma Surgical Report Form (INSRF) was employed to retrospectively collect the clinical data of 53 patients diagnosed with neuroblastoma at our hospital from April 2014 to April 2020. IDRFs were identified at the time of diagnosis and reassessed during the course of neoadjuvant chemotherapy. Various statistical tests were used to evaluate the correlation between IDRFs and secondary surgical outcomes. RESULTS: A total of 195 IDRFs were identified. Notably, by two courses of neoadjuvant chemotherapy, the number of "two body compartments," "intraspinal tumor extension," and "trachea-compressing" IDRFs decreased significantly (p = .001). The primary tumor volumes and the number of IDRFs decreased significantly by four courses of neoadjuvant chemotherapy, especially in "intraspinal tumor extension" IDRFs (p = .034). The median number of IDRF per patient was four (interquartile range [IQR]: 1-5) at diagnosis, which diminished to one (IQR: 1-3) subsequent to neoadjuvant chemotherapy. The presence of preoperative IDRFs was not associated with surgical complications (p = .286) or the extent of surgery (p = .188). However, the number of preoperative IDRFs linked to the extent of surgery (p = .002), not to operative complications (p = .669). Specifically, presurgery "renal vessel contact" IDRFs were predictive of surgical complications, while presurgery "infiltration of vital structures" IDRFs were associated with the extent of surgery. CONCLUSION: The number of IDRFs decreased significantly by four courses of neoadjuvant chemotherapy. The number and type of presurgery IDRFs may predict secondary surgical outcomes, surpassing the mere consideration of their presence or absence.

Gaining Insight into Updated MR Imaging for Quantitative Assessment of Cartilage Injury in Knee Osteoarthritis.

PURPOSE OF THE REVIEW: Knee Osteoarthritis (KOA) entails progressive cartilage degradation, reviewed via MRI for morphology, biochemical composition, and microtissue alterations, discussing clinical advantages, limitations, and research applicability. RECENT FINDINGS: Compositional MRI, like T2/T2* mapping, T1rho mapping, gagCEST, dGEMRIC, sodium imaging, diffusion-weighted imaging, and diffusion-tensor imaging, provide insights into cartilage injury in KOA. These methods quantitatively measure collagen, glycosaminoglycans, and water content, revealing important information about biochemical compositional and microstructural alterations. Innovative techniques like hybrid multi-dimensional MRI and diffusion-relaxation correlation spectrum imaging show potential in depicting initial cartilage changes at a sub-voxel level. Integration of automated image analysis tools addressed limitations in manual cartilage segmentation, ensuring robust and reproducible assessments of KOA cartilage. Compositional MRI techniques reveal microstructural changes in cartilage. Multi-dimensional MR imaging assesses biochemical alterations in KOA-afflicted cartilage, aiding early degeneration identification. Integrating artificial intelligence enhances cartilage analysis, optimal diagnostic accuracy for early KOA detection and monitoring.

A Halloysite Nanotubes-based Probe for Efficient Fluorescence Detection and Adsorption Removal of Pb2+ in Water.

The detection and removal of Pb2+ is of utmost importance for environmental protection and human health due to its toxicity, persistent pollution, and bioaccumulation effects. To address the limitations associated with organic small molecule-based fluorescence probes such as poor water solubility and single functionality in detecting Pb2+, a fluorescence probe based on halloysite nanotubes was developed. This probe not only enables specific, rapid, and reliable detection of Pb2+ but also facilitates efficient removal of it from water. The development of this bifunctional fluorescent probe provides a valuable insight for designing more advanced probes targeting heavy metal ions.

Absolute Configuration of Oxabornyl Polyenes Prugosenes A1-A3 and Structural Revision of Prugosene A2.

Oxabornyl polyenes represent a unique group of polyketides characterized by a central polyene core flanked by a conserved oxabornyl moiety and a structurally diverse oxygen heterocyclic ring. They are widely distributed in fungi and possess a variety of biological activities. Due to the significant spatial separation between the two stereogenic ring systems, it is difficult to establish their overall relative configurations. Here, we isolated three oxabornyl polyenes, prugosenes A1-A3 (1-3), from Talaromyces sp. JNU18266-01. Although these compounds were first reported from Penicillium rugulosum, their overall relative and absolute configurations remained unassigned. By employing ozonolysis in combination with ECD calculations, we were able to establish their absolute configurations, and additionally obtained seven new chemical derivatives (4-10). Notably, through NMR data analysis and quantum chemical calculations, we achieved the structural revision of prugosene A2. Furthermore, prugosenes A1-A3 exhibited potent antiviral activity against the respiratory syncytial virus, with compound 1 displaying an IC50 value of 6.3 µM. Our study thus provides a valuable reference for absolute configuration assignment of oxabornyl polyene compounds.

USP11 promotes renal tubular cell pyroptosis and fibrosis in UUO mice via inhibiting KLF4 ubiquitin degradation.

The pyroptosis of renal tubular epithelial cells leads to tubular loss and inflammation and then promotes renal fibrosis. The transcription factor Krüppel-like factor 4 (KLF4) can bidirectionally regulate the transcription of target genes. Our previous study revealed that sustained elevation of KLF4 is responsible for the transition of acute kidney injury (AKI) into chronic kidney disease (CKD) and renal fibrosis. In this study, we explored the upstream mechanisms of renal tubular epithelial cell pyroptosis from the perspective of posttranslational regulation and focused on the transcription factor KLF4. Mice were subjected to unilateral ureteral obstruction (UUO) surgery and euthanized on D7 or D14 for renal tissue harvesting. We showed that the pyroptosis of renal tubular epithelial cells mediated by both the Caspase-1/GSDMD and Caspase-3/GSDME pathways was time-dependently increased in UUO mouse kidneys. Furthermore, we found that the expression of the transcription factor KLF4 was also upregulated in a time-dependent manner in UUO mouse kidneys. Tubular epithelial cell-specific Klf4 knockout alleviated UUO-induced pyroptosis and renal fibrosis. In Ang II-treated mouse renal proximal tubular epithelial cells (MTECs), we demonstrated that KLF4 bound to the promoter regions of Caspase-3 and Caspase-1 and directly increased their transcription. In addition, we found that ubiquitin-specific protease 11 (USP11) was increased in UUO mouse kidneys. USP11 deubiquitinated KLF4. Knockout of Usp11 or pretreatment with the USP11 inhibitor mitoxantrone (3 mg/kg, i.p., twice a week for two weeks before UUO surgery) significantly alleviated the increases in KLF4 expression, pyroptosis and renal fibrosis. These results demonstrated that the increased expression of USP11 in renal tubular cells prevents the ubiquitin degradation of KLF4 and that elevated KLF4 promotes inflammation and renal fibrosis by initiating tubular cell pyroptosis.

Nonionic surfactant Tween 80-facilitated bacterial transport in porous media: A nonmonotonic concentration-dependent performance, mechanism, and machine learning prediction.

The surfactant-enhanced bioremediation (SEBR) of organic-contaminated soil is a promising soil remediation technology, in which surfactants not only mobilize pollutants, but also alter the mobility of bacteria. However, the bacterial response and underlying mechanisms remain unclear. In this study, the effects and mechanisms of action of a selected nonionic surfactant (Tween 80) on Pseudomonas aeruginosa transport in soil and quartz sand were investigated. The results showed that bacterial migration in both quartz sand and soil was significantly enhanced with increasing Tween 80 concentration, and the greatest migration occurred at a critical micelle concentration (CMC) of 4 for quartz sand and 30 for soil, with increases of 185.2% and 27.3%, respectively. The experimental results and theoretical analysis indicated that Tween 80-facilitated bacterial migration could be mainly attributed to competition for soil/sand surface sorption sites between Tween 80 and bacteria. The prior sorption of Tween 80 onto sand/soil could diminish the available sorption sites for P. aeruginosa, resulting in significant decreases in deposition parameters (70.8% and 33.3% decrease in KD in sand and soil systems, respectively), thereby increasing bacterial transport. In the bacterial post-sorption scenario, the subsequent injection of Tween 80 washed out 69.8% of the bacteria retained in the quartz sand owing to the competition of Tween 80 with pre-sorbed bacteria, as compared with almost no bacteria being eluted by NaCl solution. Several machine learning models have been employed to predict Tween 80-faciliated bacterial transport. The results showed that back-propagation neural network (BPNN)-based machine learning could predict the transport of P. aeruginosa through quartz sand with Tween 80 in-sample (2 CMC) and out-of-sample (10 CMC) with errors of 0.79% and 3.77%, respectively. This study sheds light on the full understanding of SEBR from the viewpoint of degrader facilitation.

Langerhans cell histiocytosis in children with refractory diarrhoea and hypoalbuminaemia as the initial presentation: two case reports and a literature review.

Langerhans cell histiocytosis (LCH) involving the gastrointestinal tract is a rare condition for which clinical experience is limited. We describe the cases of two patients who initially presented with chronic diarrhoea, hypoproteinaemia, and intermittent fever. These findings suggest that in cases of refractory diarrhoea accompanied by recurrent hypoalbuminaemia, especially with abdominal rash, LCH should be considered. Gastrointestinal endoscopy, biopsy, and imaging studies are essential for obtaining a definitive diagnosis. This approach might be helpful for the early recognition of gastrointestinal tract involvement in LCH.

Identification of ETH receptor and its possible roles in the mud crab Scylla paramamosain.

Ecdysis-triggering hormone (ETH) is a neuropeptide hormone characterized by a conserved KxxKxxPRx amide structure widely identified in arthropods. While its involvement in the regulation of molting and reproduction in insects is well-established, its role in crustaceans has been overlooked. This study aimed to de-orphanise a receptor for ETH in the mud crab Scylla paramamosain and explore its potential impact on ovarian development. A 513-amino-acid G protein-coupled receptor for ETH (SpETHR) was identified in S. paramamosain, exhibiting a dose-dependent activation by SpETH with an EC50 value of 75.18 nM. Tissue distribution analysis revealed SpETH was in the cerebral ganglion and thoracic ganglion, while SpETHR was specifically expressed in the ovary, hepatopancreas, and Y-organ of female crabs. In vitro experiments demonstrated that synthetic SpETH (at a concentration of 10-8 M) significantly increased the expression of SpVgR in the ovary and induced ecdysone biosynthesis in the Y-organ. In vivo experiments showed a significant upregulation of SpEcR in the ovary and Disembodied and Shadow in the Y-organ after 12 h of SpETH injection. Furthermore, a 16-day administration of SpETH significantly increased 20E titers in hemolymph, gonadosomatic index (GSI) and oocyte size of S. paramamosain. In conclusion, our findings suggest that SpETH may play stimulatory roles in ovarian development and ecdysone biosynthesis by the Y-organ.

School Bullying Victimization and Depression Symptoms in Adolescents: The Mediating Role of Internet Addiction and Moderating Role of Living Areas.

School bullying and depression are both serious social and public health problems among adolescents. Prior studies indicated a correlation between bullying and depression. However, the potential moderators remain largely unexplored. This study aimed to identify the mediating effect of Internet addiction and the moderating effect of living in urban or rural areas in the relationship between school bullying victimization and depression symptoms among Chinese adolescents. This cross-sectional study of adolescents was conducted using two-stage random cluster sampling of students in urban and rural public high schools in China. A moderated mediation model was constructed to uncover the underlying mechanism of school bullying victimization and depression symptoms. A total of 2,376 adolescents (52.65% females, mean age ± SD a 14.69 ± 1.76 years) were included in the study. The prevalence of clinical depression symptoms with a cut-off value of 16 on the Center for Epidemiological Studies Depression Scale (CES-D) was 21.76% (95% CI: 20.15, 23.46), and with a cut-off value of 20 on the CES-D was 13.85% (95% CI: 12.51, 15.30) for overall. Our findings indicated a significant positive association between school bullying victimization and depression symptoms (p < 0.01) and a significant mediating effect of Internet addiction in the association between school bullying victimization and depression symptoms (indirect effect = 1.143, 95% CI: 0.677, 1.609; percentage of mediation: 16.7%, 95% CI: 10.3, 23.1). This indirect relationship was partially moderated by the living in urban or rural areas in the mediation process. Specifically, the effect of school bullying victimization on Internet addiction was greater among urban adolescents (simple slope: 0.774, 95% CI: 0.524, 1.024, p < 0.01) than among rural adolescents (simple slope: 0.337, 95% CI: 0.132, 0.543, p < 0.01), but moderating effect of urban-rural areas was not significant on the relationship between Internet addiction and depression symptoms. These findings highlight the mediating role of Internet addiction and the moderating role of living areas in school bullying victimization and adolescents' depression symptoms, which provide evidence for social work, mental health services, and policy interventions for adolescents in China.